Xoft - Carpeta de Producto by deleccientifica

CONTENIDO XOFT XOFT® AXXENT®

BENEFICIOS ASOCIADOS A ESTE SISTEMA

DELEC CIENTÍFICA

A B O C A D O S A L A I N N O VA C I Ó N

C O N S U LT O R Í A E S P E C I A L I Z A D A

SOBRE XOFT DE ICAD INC. XOFT AXXENT®

COMPONENTES DEL SISTEMA

S EG U R I DA D R A D I O LÓ G I C A

B A S E I N S TA L A D A

Esta carpeta fue generada por el equipo de consultores de DeLeC Científica. 2020. DeLeC Científica Uruguaya - Representante Regional Exclusivo Fco. García Corina 2357 – Piso 1. Montevideo - Uruguay DeLeC Científica Argentina – Agente Comercial Local Aráoz 821 -C1414DPQ - Buenos Aires – Argentina. Tel: (+54-11) 4775 5844

as mejoras de las distintas técnicas de tratamiento para patologías oncológicas han sido por muchos años tema de investigación y el

objetivo principal de los grandes avances tecnológicos en equipos y sistemas emisores de radiación. En DeLeC vamos de la mano con estos avances y nos preocupamos por ofrecer equipos de última tecnología, que garanticen tratamientos óptimos y eficaces de las diferentes patologías oncológicas. Una de las modalidades de tratamiento radioterapéutico es la braquiterapia, la cual consiste en colocar la fuente de radiación dentro del tumor o en la zona adyacente mediante aplicadores especialmente diseñados. De esta forma, es posible administrar una dosis de radiación personalizada a la zona de destino con un elevado nivel de precisión, a la vez que se minimiza la dosis no deseada en los tejidos y órganos sanos circundantes. La braquiterapia se utiliza en todo el mundo para el tratamiento de una amplia variedad de patologías, logrando combinar de forma eficiente dos objetivos fundamentales del tratamiento radiante: una dosis efectiva para el tumor y la conservación del tejido sano que lo rodea. Actualmente, representa una parte importante del tratamiento estándar para cánceres de tipo ginecológico. El versátil sistema Xoft® Axxent® utiliza tecnología de braquiterapia electrónica de vanguardia. Se basa en una fuente de rayos X miniaturizada (con capacidad de encendido y apagado) libre de isótopos radioactivos. Proporciona fotones de baja energía con una tasa de dosis alta (similar a la del radioisótopo Ir-192), siendo posible la entrega de tratamientos radiantes altamente focalizados en el volumen blanco en salas con mínimos requerimientos de blindaje. El sistema Xoft® Axxent® se caracteriza por ser móvil y portátil, permitiendo el tratamiento en una amplia gama de entornos clínicos. Su plataforma de radioterapia avanzada permite optimizar los flujos de trabajo y acelerar los tiempos de instalación, capacitación y tratamiento; constituyendo, por lo tanto, un método efectivo para reducir costos y hacer un uso más eficiente de los recursos. Estas son solo algunas de las razones por las que en DeLeC confiamos en que el sistema Xoft® Axxent® es el equipo más eficiente y versátil para braquiterapia disponible en el mercado. Nos enfocamos en ofrecer la mejor tecnología en las distintas modalidades de radioterapia, siempre en beneficio del paciente. Invitamos a que lo conozcan y consulten las publicaciones científicas anexas que respaldan sus resultados.

Sistema de braquiterapia portátil,

no utiliza fuentes radiactivas, garantiza una menor dosis a tejidos sanos y exige mínimos requisitos de blindaje. que

La braquiterapia electrónica cumple todos los objetivos de la radioterapia moderna actual: • perfil de alta eficacia y baja toxicidad • tecnología de vanguardia • alto nivel de aceptación por parte de los pacientes y usuarios • rentabilidad y opciones de tratamiento personalizadas

XOFT®

¿Qué es Xoft® Axxent®?

Es un versátil sistema diseñado y fabricado para procedimientos eficientes de braquiterapia. Xoft® no hace uso de isotopos radiactivos para la administración del tratamiento radiante, evitando -por lo tanto- las numerosas desventajas asociadas con el uso de material radiactivo. Posee una exclusiva fuente de radiación formada por un micro tubo de rayos X que se activa sólo en las posiciones predeterminadas para el tratamiento, emitiendo radiación de forma isotrópica. Esto, sin lugar a dudas, representa un importante desarrollo tecnológico en el campo de la braquiterapia, revolucionando esta práctica clínica y mejorando la experiencia de los pacientes y usuarios. La fuente de rayos X miniaturizada de alta tasa de dosis (HDR) funciona a 50 kV, proporcionando un haz de baja energía. La micro fuente incrustada en la punta de un catéter se coloca dentro de aplicadores especialmente diseñados y compatibles con imágenes tomográficas (TC). Debido a la baja energía de la radiación empleada, es posible la entrega de tratamientos en salas con mínimos requerimientos de blindaje, por lo que la entrega del tratamiento se puede llevar a cabo incluso en la misma sala donde se le realiza la imagen al paciente. El sistema de braquiterapia Xoft se considera electrónico debido a que el movimiento de la fuente de rayos X en pasos definidos dentro del aplicador es controlado electrónicamente. Constituye un sistema realmente portátil debido a su diseño compacto y a su tamaño reducido (pesa aproximadamente 90 Kg), lo que permite una alta movilidad del equipo. Posee, además, un scanner de código de barras que agiliza la entrada precisa de los datos del tratamiento del paciente al sistema. El sistema Xoft para el uso general de braquiterapia está aprobado por la FDA, marcado CE y autorizado en un número creciente de países para el tratamiento del cáncer. Consideramos que el sistema de braquiterapia electrónica Xoft® puede ser incorporado en cualquier institución sin la necesidad de requerimientos complejos, garantizando procedimientos eficaces y seguros, con un nivel de complejidad mínimo y flujos de trabajo optimizados. Así mismo, su incorporación lleva consigo una reducción de costos significativos.

AXXENT®

Beneficios del Sistema de Braquiterapia de Xoft

• La importación es mucho más fácil ya que no utiliza ningún tipo de material radioactivo. • La protección radiológica está garantizada y la exposición a la radiación está controlada, minimizando los riesgos de incidentes asociados a la radiación y eliminando la logística de procedimientos de emergencias para el control de exposiciones accidentales. • El recambio de la fuente de rayos X se realiza en un tiempo muy corto, aproximadamente en 5 minutos, sin que esto conlleve a la generación de residuos radiactivos. • No necesita Búnker para operar, haciendo posible la entrega de tratamientos incluso en la sala de adquisición de imágenes. • Es portátil, debido a su peso ligero y a su diseño compacto resulta un equipo de muy fácil traslado. • No existe el decaimiento radiactivo por lo que los tiempos de tratamientos son siempre constantes. • El mantenimiento es muy simple y el servicio está garantizado (esto incluye la cantidad de fuentes de rayos X necesarias para asegurar la continuidad de los tratamientos). • Incluye sistema de planificación y equipamiento de dosimetría para control de calidad.

Las capacidades integrales del sistema Xoft ofrecen una opción atractiva para médicos y pacientes para mejorar la flexibilidad, precisión y personalización en el tratamiento específico del cáncer.

DELEC CIENTÍFICA

ABOCADOS A LA

¿Quiénes somos?

INNOVACIÓN

DeLeC Científica es una empresa exitosa, en constante crecimiento, líder en innovación tecnológica aplicada a la medicina que fue fundada en el año 2003 por un grupo empresario de capitales nacionales, con vocación de servicio y alto grado de Responsabilidad Social.

“Si en el futuro somos lo que proyectamos, en el presente somos lo que hacemos en virtud de aquella decisión y proyecto”. José Ortega y Gasset

¿Cuál es nuestra misión y concepto de negocio? Nuestra misión es impulsar la mejora continua de nuestro sistema de salud regional, ofreciendo para ello los mejores productos de la revolución tecnológica del siglo XXI. A tal fin, nos hemos propuesto hacer foco en lo especial y proveer soluciones a problemas de los que nadie se ha ocupado, teniendo en cuenta que hay muchas empresas de electromedicina, de todo tipo y tamaño, que se dedican a atender el mercado de volumen con soluciones estandarizadas que dejan afuera a mucha gente.

¿A quiénes servimos y con qué tipo de productos? Servimos a las comunidades científicas y médicas proveyéndoles productos y servicios de última generación y alto valor agregado. Nos concentramos exclusivamente en aquellos que son seguros y están debidamente certificados y aprobados por los organismos internacionales de control - FDA y CE - y también los nacionales - ANMAT y ARN –; todo en el marco de un soporte pre y post venta de excelencia.

¿En qué nos especializamos? Somos consultores altamente especializados en el desarrollo e implementación de programas médicos de excelencia soportados por equipos y sistemas de real innovación tecnológica.

¿Cómo estamos organizados? La firma cuenta con seis áreas de trabajo con roles bien definidos. • División de Sistemas Médicos: Se distingue por proveer la mejor tecnología de punta disponible, a partir de la revolución tecnológica del siglo XXI, para cubrir necesidades de equipamiento de diagnóstico y también de tratamiento. Busca optimizar resultados clínicos y al mismo tiempo mejorar la calidad de la experiencia vivida por los pacientes antes, durante y después del proceso de tratamiento. • División de Cirugía Robótica y Simulación: pone a disposición de la comunidad médica la posibilidad inigualable de asistencia robótica a la cirugía mínimamente invasiva y también los únicos simuladores quirúrgicos verdaderamente realísticos; considerados los mejores del mundo en cirugía virtual. • División de Radioterapia y Radiocirugía: Ofrece el conjunto ideal de equipos para tratamiento de tumores malignos y benignos. Incluye, además, diferentes sistemas que representan alternativas complementarias para cubrir todas las necesidades requeridas por un centro de radioterapia. • División de Ingeniería, Soporte Técnico y Aplicaciones Clínicas: Asegura el correcto funcionamiento de la base de equipos de innovación tecnológica instalada, incluyendo su actualización continua, y brinda servicio docente a los usuarios para asegurar su correcta utilización y las buenas prácticas. • División de Comunicación y Marketing: Área en constante crecimiento que busca llegar estratégicamente a los públicos de relevancia para la empresa y trasmitir un mensaje claro sobre su misión y objetivos. Para que “las cosas sean” es necesario comunicar que existen. “No se desea lo que no se conoce”. • División de Administración, Personal y Finanzas: Optimiza los resultados económicos de la empresa, cuidando que haya una distribución equitativa de los recursos entre los seis grupos de interés: proveedores, clientes, personal, accionistas, bancos/inversores y el fisco. Su objetivo principal es velar por una gestión eficiente y ecuánime al momento de crear valor económico produciendo, al mismo tiempo, valor social.

Precisión submilimétrica e innovación en tratamientos de radioterapia y radiocirugía.

Radioterapia intraoperatoria, pequeño, ligero, móvil, autoblindado y efectivo.

Tomógrafo de mamas con imágenes 3D realmente isotrópicas.

Hospitales móviles diseñados a la necesidad del cliente.

Tomógrafos móviles autoblindados de uso en clínicas y ambulancias.

Adquisición continua de imagen en bipedestación 2D y 3D con baja dosis.

Simuladores de alta y mediana fidelidad y sistema audiovisual con herramientas de gestión.

Cabezas para intubación, torso para trauma y monitor multiparamétrico simulado.

Tecnología no invasiva que ayuda a visualizar venas no visibles a simple vista.

Sistema de adquisición de señales biológicas y software para educación e investigación.

Braquiterapia sin fuentes radiactivas. Eficiente, portátil y seguro.

Plataforma para la planificación inteligente de tratamiento radioterapéutico.

¿Cuál es nuestra filosofía? Nuestro lema es ganar cuando el cliente también gana, cumplir con lo prometido y hacerlo a tiempo.

¿Qué nos diferencia del resto de las empresas del rubro? Nuestro diferencial es que no sólo proveemos equipos, sino que desarrollamos programas médicos de excelencia, acompañando al cliente desde la etapa embrionaria del proyecto hasta su optimización operativa. • Seleccionamos el equipamiento necesario y lo instalamos. • Brindamos soporte técnico con garantía oficial. • Nos encargamos del entrenamiento de los médicos y del personal de la institución local. • Una vez que llegamos a una institución, nunca nos vamos.

¿Cuál es nuestra modalidad de trabajo? Trabajamos en equipo con proveedores y clientes a través de una continua actividad de docencia. No tenemos vendedores, pero nos atenemos al perfil y la descripción habitual de las tareas de un vendedor técnico. Nuestro equipo se compone de profesionales universitarios, frecuentemente con posgrado que, a poco de ingresar a la compañía, son enviados a las distintas fábricas representadas para capacitarse de la mejor forma para ofrecer cada producto con solvencia técnica y científica.

¿Contra quiénes competimos? No poseemos competidores, ya que vamos en una dirección distinta al resto, usualmente: cambiando paradigmas.

¿Dónde comercializamos y soportamos nuestros productos? La firma comercializa la mayoría de sus productos en Argentina, Uruguay, Paraguay y Bolivia. Sin embargo, muchas veces, a pedido de distintos fabricantes, extendemos nuestro radio de acción llegando a otros países de América del Sur. En el 2010 introdujimos la cirugía robótica en Colombia, preparando el terreno para que luego se nombrara un distribuidor local. Antes, en el 2008, habíamos instalado las dos primeras unidades da Vinci que hubo en Brasil. Lo hicimos en el Hospital Albert Einstein y en el Sirio Libanes, ambos de Sao Paulo. Cabe destacar que también en este país existe actualmente un distribuidor local para esta tecnología.

¿Cuál es nuestra visión de futuro? En el mediano plazo esperamos ser líderes regionales y referentes indiscutidos en innovación tecnológica aplicada a la medicina. Esto lo lograremos gracias a nuestro comportamiento empresarial, calidad de relaciones que establezcamos, eficiencia y efectividad de nuestros productos y servicios. Apostamos a ser una organización de renombre y prestigio regional, comprometiéndonos con la comunidad y ayudando para la construcción de un mundo mejor a través de la mejora continua del servicio de salud.

Oficinas de DeLeC Científica

C O N S U LT O R Í A Nuestra experiencia en el ámbito de la innovación tecnológica en salud nos dice que el mejor equipo no hace una intervención de calidad por sí mismo. Tan importante como la herramienta son la formación, la comprensión de la tecnología, el buen uso, el asesoramiento y los objetivos que orientan la práctica. Por eso en DeLeC Científica acompañamos a las instituciones desde el desarrollo de los proyectos, el diseño de nuevas áreas o servicios de salud, el asesoramiento en la adquisición de nuevas tecnologías, los requerimientos normativos y legales, la diagramación logística, el mantenimiento y el monitoreo del uso.

Un asesoramiento adecuado es clave para: • obtener planificaciones que permitan optimizar el tiempo de los proyectos, • prever los riesgos potenciales para garantizar la viabilidad en el mediano y largo plazo, • identificar todos los stakeholders alrededor del proyecto y prever cuál será el impacto en ellos, • conseguir una mirada profunda sobre la inversión, el retorno y reconocer oportunidades que no están a la vista.

Con el fin de asesorar tomando como referencia los máximos estándares de calidad, los consultores de DeLeC nos actualizamos de acuerdo a los programas de formación de las firmas que representamos y participamos de forma activa en la agenda más relevante de la innovación tecnológica médica en Occidente.

ESPECIALIZADA

SERVICIO TÉCNICO Ofrecer un servicio técnico de alta performance, alineado tanto a las exigencias y estándares de las marcas con las que trabajamos, como a los requerimientos de nuestros clientes es un punto destacado en nuestra empresa. El equipo técnico asiste en la interpretación de los requerimientos previos (condiciones eléctricas, infraestructura, etc.), se ocupa de la instalación, cuando el equipo lo requiere, y luego monitorea el funcionamiento y el uso para garantizar el desempeño óptimo de la tecnología. Nuestros técnicos deben cumplir con un cronograma de formación y capacitación anual, en las casas matrices de las firmas que representamos. Por lo tanto, desde DeLeC Científica ofrecemos una asistencia de instalación y posventa certificada por fábrica.

EXPERTO

SOBRE XOFT DE iCAD INC.

Xoft Microtube se fundó en 1998 con el objetivo de desarrollar una fuente de rayos X miniaturizada. La intención inicial era utilizar dicha fuente en cardiología para tratar la restenosis intravascular. Más tarde, esta empresa aposto a los beneficios que podría generar su tecnología en el tratamiento del cáncer, específicamente en aplicaciones de radioterapia intraoperatoria, logrando su aprobación por FDA en el año 2005. Posteriormente, desarrollaron su aplicación en el tratamiento de braquiterapia ginecológica y superficial, obteniendo su certificación por FDA en el 2008. En la actualidad, esta tecnología patentada, combinada con las capacidades integrales del sistema Xoft, ha impulsado el tratamiento de braquiterapia en miles de pacientes con cáncer en todo el mundo. Cada componente de este sistema avanzado ha mejorado la calidad de la atención, el flujo de trabajo operativo y ha aumentado el acceso a la radioterapia de vanguardia. Xoft Microtube fue adquirida por iCAD Inc. en diciembre de 2010. iCAD es una empresa que se especializa en el desarrollo de software para el diagnóstico de cáncer de mama. Brinda soluciones de atención médica precisa, diseñadas por expertos para optimizar la eficiencia operativa, la confianza del médico y los resultados de los pacientes. La sede corporativa de iCAD se encuentra en Nashua, New Hampshire; mientras que las instalaciones de fabricación y oficinas de Xoft se encuentran en San José, California. Misión de Xoft iCAD:

ampliar el acceso a una radioterapia altamente

conformada para mejorar el tratamiento de una amplia gama de cánceres.

“El sistema Xoft es capaz de apuntar con precisión a las células cancerosas y preservar el tejido sano circundante, lo que resulta en una reducción significativa de la dosis de radiación que llega a los órganos en riesgo. Nuestros primeros resultados con esta tecnología dirigida son muy prometedores, y nos complace ofrecer esta valiosa opción de tratamiento a pacientes adecuadamente seleccionadas con cáncer de endometrio y cuello uterino.” Agustina Mendez Villamon, MD Radiation Oncologist Miguel Servet University Hospital, Zaragoza, Spain

XOFT AXXENT®

El versátil sistema de braquiterapia Xoft® Axxent® (eBx®) utiliza tecnología de braquiterapia electrónica (libre de isotopos radiactivos) de vanguardia para administrar tratamientos radiantes altamente focalizados en el volumen blanco, en salas con mínimos requerimientos de blindaje. Constituye un sistema realmente portátil debido a su diseño compacto y a su tamaño reducido (pesa aproximadamente 90 Kg), lo que permite una alta movilidad del equipo y, por lo tanto, su adaptación en una amplia gama de entornos clínicos. El sistema está compuesto principalmente por: • Controlador Axxent® • Fuente de rayos X HDR Axxent® • Juego de tubos y bomba de refrigeración Axxent® • Brazo de tratamiento Axxent® • Aplicadores Axxent® • El kit de accesorios de física de Axxent® • Sistema de Planificación. • FlexiShield Axxent® o barreras de protección contra la radiación.

Controlador Axxent® El controlador Axxent® suministra energía a la fuente de rayos X y hace circular agua para el enfriamiento de la misma. Se encarga también de controlar el movimiento de la fuente en pasos definidos dentro del aplicador, los cuales son asignados por el operador durante de planificación de tratamiento.

Brazo flexible: Permite un posicionamiento de la fuente de manera precisa

Scanner de código de barras: Agiliza la entrada de datos del tratamiento del paciente de manera precisa

Protección radiológica garantizada: Permite tratamientos en salas con mínimos requerimientos de blindaje debido a la baja energía de la radiación

Panel de pantalla táctil: Ofrece instrucciones paso a paso fáciles de leer e información sobre el tratamiento en tiempo real

Conector USB: Comunica planes de tratamientos individualizados

Portátil: Pesa 90 kg y su tamaño reducido permiten que el sistema sea móvil

A través del controlador se puede pausar o detener el tratamiento en cualquier momento, interrumpiendo instantáneamente la producción de rayos X.

Parada de emergencia

Brazo de tratamiento

Nido de extracción de la fuente

Cámara de pozo blindada con inserto personalizado

Fuente de rayos X HDR Axxent® La fuente corresponde a un tubo de rayos X miniaturizado (2,2 mm de diámetro), desechable, sellado al vacío y diseñado para administrar radiación con emisión isotrópica. Funciona con un potencial acelerador de hasta 50 kV y una corriente máxima de 300 μA. El tubo de rayos X se encuentra integrado en la punta de un catéter flexible refrigerado por agua, el cual en su versión estándar mide 250 mm de longitud y 5 mm de diámetro (500 mm de longitud en su versión extendida).

Conexión de HV

Conexión de tubos de refrigeración

El controlador está programado para limitar el uso de la fuente de rayos X a 750 minutos. Si esta es usada por más de 750 minutos el material del catéter puede degradarse y tener fugas. Los usuarios suelen adquirir fuentes en virtud de un contrato anual basado en el volumen de pacientes tratados, de modo que puedan utilizar múltiples fuentes a lo largo del año según sea necesario. Las fuentes pueden ser reemplazadas rápida y fácilmente por el usuario en unos pocos minutos; no es necesario que el personal de servicio técnico esté en el lugar para realizar el procedimiento de reemplazo de la fuente.

Diagrama esquemático de la composición del tubo de rayos X.

Circuito HV

Ánodo cónico

X-ray Tube

Refrigeración

La fuente se calibra antes de la administración de cada fracción de radiación utilizando una cámara de pozo incorporada en el controlador y un electrómetro de uso exclusivo. Durante el funcionamiento de la fuente, la energía media del haz es de aproximadamente 26,7 keV (similar a la del 125Ir) con una energía máxima de 50 keV, proporcionando un haz de baja energía y alta tasa de dosis (1 Gy/min a 1 cm en tejido). La energía media del sistema Xoft es menor a la de los rayos gamma de 192Ir (380 keV) y de 60Co (alrededor de 1250 keV), por lo que ofrece una ventaja significativa en cuanto a la reducción de la dosis en órganos a riesgo.

Cualquier mal funcionamiento en el circuito de alto voltaje (HV), incluido el tubo de rayos X, dará como resultado que el tratamiento se detenga, registrándose los parámetros del tratamiento administrados hasta ese momento. El controlador posee una pantalla en la que se podrá observar el tiempo transcurrido, el tiempo total planificado, el tiempo restante en la posición de parada actual y la posición de la fuente de forma esquemática.

Juego de tubos y bomba de refrigeración Axxent® La bomba de refrigeración, en conjunto con el juego de tubos de refrigeración, hace circular agua a través del catéter donde va insertada la fuente durante el tratamiento. Cualquier interrupción en el flujo de agua es detectada por un sensor de flujo, que indicará al controlador que deje de producir rayos X hasta que se solucione la restricción de flujo de agua. El juego de tubos de enfriamiento y la bolsa de agua esterilizada (de medio litro), deben reemplazarse periódicamente, según los patrones de uso en cada instalación.

Parada de emergencia

Bomba de agua Bolsa refrigerante

Tubos de refrigeración

Brazo de tratamiento Axxent®

El controlador cuenta con un brazo con amplios grados de libertad y alta capacidad de articulación. Dicho brazo posee sensores que verifican si el aplicador y la fuente están bien posicionados para la administración de tratamiento. También cuenta con un dispositivo, denominado “nido de extracción de la fuente”, que se encarga de controlar el movimiento de la fuente en pasos definidos dentro del aplicador de acuerdo con la planificación del tratamiento.

Conexión de alto voltaje para la fuente Palanca de ajuste de altura de brazo de tracción

Nido de extracción de la fuente

(con el catéter de la fuente conectado)

Perilla para fijar el brazo de tracción

Conexión del aplicador

Aplicadores Axxent® El sistema Xoft cuenta con una gama de aplicadores diseñados por expertos y testeados con más de 200 ciclos de radiación para el tratamiento de cáncer de endometrio, cuello uterino y vagina, todos los aplicadores compatibles con TC.

Aplicador cervical Axxent® El aplicador cervical Axxent® está indicado para su uso con el sistema electrónico de braquiterapia Xoft para administrar braquiterapia de HDR en el tratamiento intracavitario de cuello uterino. Es un diseño tipo Henschke, construido con tubería de titanio de pared delgada (0,4 mm) que se conecta al sistema Xoft a través de tubos de transferencia. El aplicador es esterilizable y reutilizable. Hay cuatro geometrías de tándem, todos con alrededor de 8 mm de diámetro: un tándem recto y tres tándems en ángulos de 15°, 30° y 45°. Los colpostatos tienen tapas en forma de ovoide de diámetro variable (20, 25 y 30 mm). Se utiliza un soporte para mantener los tres tubos juntos mientras se coloca el aplicador en el paciente. El aplicador cervical Axxent® recibió la aprobación de la FDA en 2013.

Aplicador cervical Xoft compuesto por tándem y dos colpostatos. El tándem de 45 grados con tapón cervical y ovoides de 25 mm se muestran aquí con el soporte estabilizador.

Aplicador vaginal Axxent® El aplicador vaginal Axxent® de tipo cilindro está indicado para su uso con el sistema electrónico de braquiterapia Xoft para administrar braquiterapia intracavitaria en la vagina. El juego incluye aplicadores de cuatro diámetros diferentes, que van desde 20 hasta 35 mm. Los aplicadores son esterilizables y reutilizables.

Contenido del juego de aplicador vaginal Axxent®, de izquierda a derecha: 4 canales de origen idénticos, 4 aplicadores vaginales con diámetros de: 35 mm, 30 mm, 25 mm y 20 mm.

Cilindro colocado en soporte estabilizador para tratamiento.

La siguiente figura muestra la imagen por TC de un aplicador vaginal con un catéter marcador insertado, se observa también el tapón del canal en la punta del aplicador.

Imagen por TC del aplicador vaginal con tapón. En la imagen se observa el contraste generado por la presencia de sulfato de bario en la pared exterior del aplicador.

Los aplicadores vaginales Axxent® se diseñaron de manera que la dosis de radiación administrada se atenúa en un 6%. Para compensar esta atenuación, resultante de la presencia de sulfato de bario en la pared exterior del aplicador, se seleccionó el material que compone el cuerpo principal de los aplicadores vaginales tal que atenúe menos radiación que el agua. Los aplicadores vaginales para la administración de braquiterapia intracavitaria en la vagina recibieron la aprobación de la FDA en 2008. *Actualmente se están desarrollando otros aplicadores, dentro de los cuales destaca el de recto y uno para próstata.

Kit de accesorios de física de Axxent® El kit de accesorios de física de Axxent® permite a los físicos realizar pruebas de control de calidad para verificar que el sistema está funcionando correctamente. Antes del tratamiento, se puede utilizar el kit de accesorios, con sus manómetros y catéteres especializados, para confirmar parámetros operativos claves y especificaciones de los componentes.

Sistema de Planificación de Tratamiento El software de planificación que se utiliza con el sistema Xoft permite al médico y al físico médico personalizar la administración del tratamiento, considerando el sitio del tumor, la prescripción y la protección de los órganos sanos circundantes. Una vez realizada la planificación, el plan de tratamiento se transfiere al controlador para su administración. El controlador entrega el tratamiento al paciente moviendo la fuente de rayos X a través del aplicador según los tiempos de espera y las posiciones de paradas establecidas durante la planificación. La administración localizada de braquiterapia con el sistema Xoft minimiza la dosis recibida por el tejido sano y, así mismo, minimiza la exposición del personal, lo que permite a los médicos y profesionales tratantes permanecer en la sala de tratamiento con el paciente.

Planificación del tratamiento de braquiterapia ginecológica con Xoft

La preparación y planificación de un plan de tratamiento ginecológico con el sistema Xoft es similar a un plan creado para cualquier otro sistema de braquiterapia HDR. Las curvas de isodosis mostradas en las distintas publicaciones científicas respaldan el uso del Xoft, demostrando que la fuente de 50 kV tiene una cobertura del PTV (por sus siglas en inglés “Planning Target Volume”) comparable a la de Ir pero con una dosis más baja para los órganos a riesgo.

192

Ir -192 HDR

Xoft 50 kV

Vejiga V50% - 48.50%

Vejiga V50% - 22.50

Recto V50% - 21.70%

Recto V50% - 13.70

Vejiga V35 % - 80.0%

Vejiga V35% - 42.1%

Recto V35% - 47.0%

Recto V35% - 27.7%

Implante de cuello uterino; figura tomada de: PM Mobit et al “Comparison of Axxent-Xoft, 192Ir and 60 Co high-dose-rate brachytherapy sources for image-guided brachytherapy treatment planning for cervical cancer”. Published by the British Institute of Radiology 2015.

Ir -192 HDR

Xoft 50 kV

V95% - 99.7%

V95% - 99.6%

Vejiga V35% - 47.7%

Vejiga V35% - 27.4%

Recto V35% - 48.3%

Recto V35% - 28.3%

Implante vaginal; figura tomada de: Adam Dickler et al “A dosimetric comparison of Xoft Axxent Electronic Brachytherapy and 192iridium high-dose-rate brachytherapy in the treatment of endometrial cancer”. Published by ELSEVIER 2008.

La siguiente imagen representa un Histograma de Dosis-Volumen (DVH) para la vejiga, recto, intestino delgado y sigmoide de tres planes de tratamientos creados de forma estandarizada para un implante ginecológico de cuello uterino típico con Xoft, 192Ir y 60Co.

Figura tomada de: PM Mobit et al “Comparison of Axxent-Xoft, 192Ir and 60Co high-dose-rate brachytherapy sources for image-guided brachytherapy treatment planning for cervical cancer”. Published by the British Institute of Radiology 2015.

Comparado con las fuentes

Ir o

192

Co, Xoft proporciona una mejor

conservación de los órganos a riesgo pélvicos asociados (vejiga, recto, sigmoides e intestino delgado), generalmente, en todo el rango de dosis. No parece haber diferencias significativas entre los planes generados con fuentes radioactivas de 192Ir o 60Co. Por todo esto, podemos decir que la fuente de 50 kV usada en braquiterapia es ideal para tratar patologías ginecológicas, ofreciendo una opción atractiva para mejorar la flexibilidad, precisión y personalización del tratamiento.

FlexiShield Axxent® Aunque no se necesitan mayores requerimientos de protección radiológica, el sistema viene con un escudo protector -FlexiShield Axxent®-, el cual está diseñado para proteger al operador de la radiación injustificada durante el tratamiento. El FlexiShield no es estéril y es reutilizable. En caso de que se considere necesario, el operador podría optar por utilizar otros tipos de escudos de radiación fijos o portátiles.

Seguridad Radiológica La baja energía de la fuente de rayos X de Xoft permite que los tratamientos puedan ser administrados en salas con mínimos requerimientos de blindaje La primera capa hemirreductora (HVL) de la fuente de braquiterapia Xoft varía de 1,39 a 1,56 mm de aluminio, mientras que el HVL para 192Ir es de 3 mm de plomo y para 60Co es de 11 mm de plomo. Por lo tanto, no es necesario trasladar al paciente de la sala de imágenes a un búnker de braquiterapia HDR. El blindaje requerido en una sala de imágenes por rayos X suele ser suficiente para el uso del sistema Xoft. El sistema podría ser trasladado fácilmente de una habitación a otra o incluso entre instalaciones, lo que permite una alta flexibilidad en la programación de los pacientes, aumentándoles la accesibilidad a este tipo de tratamientos.

El siguiente gráfico proporciona un ejemplo de tasas de exposición en la sala donde se administre el tratamiento. Sin embargo, cada instalación debería realizar sus propias mediciones y establecer su propio plan de seguridad radiológica.

Tasas de exposición: paciente con FlexiShield, todas las mediciones están dentro de 2 metros

Xoft se diferencia de otros sistemas por su versatilidad y ventaja operativa. En la siguiente tabla, se resumen algunas características importantes de la braquiterapia realizada con Xoft que destacan sobre otros sistemas de braquiterapia.

XOFT AXXENT

VARIAN GAMMAMED

BEBIG M U LT I S O U R C E

92 KG

250 KG

300 KG

Micro tubo de rayos X con capacidad de encendido y apagado.

Fuente de 192Ir.

Fuente de 60Co.

Tasa de dosis constante de 1 Gy/min a 1 cm en tejido.

Requiere corrección por decaimiento para cada tratamiento.

Sin concepto de vida media. La fuente tiene un límite de uso de 750 minutos. Las fuentes pueden ser reemplazadas rápida y fácilmente por el usuario.

Vida media de unos 74 días. El vendedor recomienda reemplazar las fuentes radiactivas 4 veces al año.

Vida media de 5,3 años. El proveedor recomienda reemplazar la fuente cada 3 a 4 años.

0,0267 MeV

0,38 MeV

1,25 MeV

1,39 - 1,56 mm (Al)

3 mm (Pb)

11 mm (Pb)

Incluye cámara de pozos y electrómetro Standard Imaging.

Cámara de pozo y electrómetro no integrado.

Sistema de dosimetría integrado.

PROCEDIMIENTOS LO G Í S T I CO S PA R A L A I M P O R TAC I Ó N D E FUENTES RADIAC TIVAS

MANIPULACIÓN H O S P I TA L A R I A DE FUENTES RADIAC TIVAS

RIESGO DE EXPOSICIÓN

RESIDUOS DE M AT E R I A L E S RADIACTIVOS

CARACTERÍSTICA

PESO

TIPO DE FUENTE

EMISIÓN ISOTRÓPICA

TA S A D E D O S I S

VIDA MEDIA

ENERGÍA MEDIA DE LA FUENTE

HVL

NECESIDAD DE BÚNKER EXCLUSIVO

CALIBRACIÓN DE LA FUENTE

No. El tratamiento se puede administrar incluso en salas de TC.

*El sistema Bebig MultiSource de Eckert & Ziegler ofrece la posibilidad de fuentes de 60C o de 192Ir, pero para efectos de comparaciones en la tabla se indica solo la fuente de 60Co.

Base instalada

B A S E I N S TA L A DA

USA

AUSTRALIA

CHINA

CANTIDAD

86 1

IRÁN

ESPAÑA

PORTUGAL

SUIZA

TURQUÍA

RUSIA

BANGLADES

TRINIDAD Y TOBAGO

INDIA

MALASIA

Instituciones referentes en el uso de la tecnología: Kaiser Permanente, California - Estados Unidos

TA I WÁ N

BULGARIA

REINO UNIDO

COREA

UC Health, Colorado - Estados Unidos Hospital Miguel Servet, Zaragoza - España Hospital de Cáceres, Cáceres - España ICO Girona, Girona - España Hospital de Bellinzona, Bellinzona - Suiza Grupo Omega, Guntur - India

PAPERS

CONTENIDO A dosimetric comparison of Xoft Axxent Electronic Brachytherapy and iridium-192 high-dose-rate brachytherapy in the treatment of endometrial cancer

Comparison of Axxent-Xoft,192 Irand60 Co high-dose-rate brachytherapy Sources for image-guide dbrachytherapy treatment planning for cervical cancer

Prospective multi-center trial utilizing electronic brachytherapy for the treatment of endometrial cancer

Treatment of cervical cancer with electronic brachytherapy

Use of electronic brachytherapy to deliver postsurgical adjuvant radiation therapy or endometrial cancer: a retrospective multicenter study

Calculated and measured brachytherapy dosimetry parameters in wรกter for the Xoft Axxent X-Ray Source: An electronic brachytherapy sourcea)

A dosimetric comparison of Xoft Axxent Electronic Brachytherapy and iridium-192 high-dose-rate brachytherapy in the treatment of endometrial cancer

Calculation of relative biological effectiveness of a low-energy electronic brachytherapy source

Electronic brachytherapy for postsurgical adjuvant vaginal cuff irradiation therapy in endometrial and cervical cancer: A retrospective study

A comparison of the biological effective dose of 50-kV electronic brachytherapy with 192Ir high-dose-rate brachytherapy for vaginal cuff irradiation

102

A continuación se pone a disposición una selección de publicaciones científicas que avalan las características y beneficios del sistema Xoft, de iCAD Inc. En la selección de estos papers se dio prioridad a los contenidos más recientes y pertinentes, confeccionada por DeLeC Científica. Si el lector desea ampliar la información científica sobre los usos del sistema Xoft puede consultar a los sitios www.delec.com.ar, o bien al correo: comunicaciones@delec.com.ar

ARTICLE IN PRESS

Brachytherapy

(2008)

Regular Article

A dosimetric comparison of Xoft Axxent Electronic Brachytherapy and iridium-192 high-dose-rate brachytherapy in the treatment of endometrial cancer Adam Dickler1,*, Michael C. Kirk2, Alan Coon2, Damian Bernard2, Tom Zusag2, Jacob Rotmensch3, David E. Wazer4 1

Department of Radiation Oncology, Little Company of Mary Hospital, Evergreen Park, IL 2 Department of Radiation Oncology, Rush University Medical Center, Chicago, IL 3 Department of Obstetrics and Gynecology, Rush University Medical Center, Chicago, IL 4 Department of Radiation Oncology, Brown University School of Medicine, Providence, RI

ABSTRACT

PURPOSE: This analysis was undertaken to dosimetrically compare iridium-192 high-dose-rate brachytherapy (IB) and Xoft Axxent Electronic Brachytherapy (XB; Xoft Inc., Sunnyvale, CA) in the treatment of endometrial cancer. METHODS AND MATERIALS: The planning CT scans from 11 patients previously treated with IB were used to construct hypothetical treatment plans using the source characteristics of the XB device. The mean V95, V100, and V150 (percent of the planning target volume that received 95%, 100%, and 150% of the prescription dose) were calculated. For both the bladder and rectum, the V35 (percent of the organ that received 35% of the prescription dose) and V50 (percent of the organ that received 50% of the prescription dose) were calculated for each patient using both methods of vaginal brachytherapy. RESULTS: The mean %V95 was 99.7% vs. 99.6% ( p 5 ns) and the mean %V100 was 99.0% vs. 99.1% ( p 5 ns) for the IB and XB methods, respectively. The mean %V150 was 35.8% vs. 58.9% ( p!0.05) for the IB and XB methods, respectively. The mean bladder %V35 was 47.7% vs. 27.4% ( p!0.05) and the mean bladder %V50 was 26.5% vs. 15.9% ( p!0.05) for the IB and XB methods, respectively. The mean rectal %V35 was 48.3% vs. 28.3% ( p!0.05) and the mean rectal %V50 was 27.8% vs. 17.0% ( p!0.05) for the IB and XB methods, respectively. CONCLUSIONS: The IB and XB methods of vaginal brachytherapy offer equivalent target volume coverage; however, the XB method allows increased sparing of the bladder and rectum. 2008 American Brachytherapy Society. All rights reserved.

Keywords:

Xoft electronic brachytherapy; Brachytherapy; Endometrial cancer

Received 20 December 2007; accepted 28 May 2008. * Corresponding author. Department of Radiation Oncology, Little Company of Mary Hospital, 2800 West 95th Street, Evergreen Park, IL 60805. Tel.: Ăž1-708-229-5560; fax: Ăž1-708-229-5378. E-mail address: atd22_99@yahoo.com (A. Dickler).

High-dose-rate (HDR) vaginal brachytherapy using iridium-192 (IB) is being increasingly used as an adjuvant radiation treatment for selected patients with endometrial cancer, either as monotherapy or as a boost to the vaginal cuff after external beam radiation (EBRT). IB has several advantages over low-dose-rate brachytherapy. It does not require hospitalization for the procedure, minimizes the radiation exposure to the hospital staff, and decreases the risk of thromboembolic events. Unfortunately, IB is not feasible for all patients who are eligible for this form of treatment. IB requires expensive equipment, including a HDR afterloader unit and a shielded room, which is not available at all radiation facilities. In addition, scheduling of IB patients can lead to logistic difficulties for busy radiation centers that have a single-shielded

ARTICLE IN PRESS 2

A. Dickler et al. / Brachytherapy

vault used for treatment of both their EBRT and brachytherapy patients. Xoft Axxent Electronic Brachytherapy (XB; Xoft Inc., Sunnyvale, CA) was developed to overcome these barriers to treatment associated with IB. XB uses a 50 kV X-ray source and thus does not require a shielded radiation vault or a HDR afterloader unit. Consequently, a kilovoltage approach could lead to vaginal brachytherapy being more accessible to many patients, particularly those who do not live near a radiation facility with a HDR afterloader unit. Two previous reports described a dosimetric comparison between XB and IB in the treatment of partial breast irradiation (2, 3). To date, no data have been published comparing these two brachytherapy techniques in the treatment of endometrial cancer. This study was conducted to retrospectively compare both the target coverage and normal tissue radiation doses with IB and XB.

(2008)

associated with increased dose in the high-dose region. The mean %V95 was 99.7% vs. 99.6% ( p 5 ns) and the mean %V100 was 99.0% vs. 99.1% ( p 5 ns) for the IB and XB methods, respectively. The mean %V150 was 35.8% vs. 58.9% ( p! 0.05) for the IB and XB methods, respectively (see Table 1). XB was able to achieve increased bladder and rectal sparing compared to IB. The mean bladder %V35 was 47.7% vs. 27.4% ( p ! 0.05) and the mean bladder %V50 was 26.5% vs. 15.9% ( p! 0.05) for the IB and XB methods, respectively. The mean rectal %V35 was 48.3% vs. 28.3% ( p !0.05) and the mean rectal %V50 was 27.8% vs. 17.0% ( p! 0.05) for the IB and XB methods, respectively (see Table 2).

Discussion Methods and materials The study population consisted of 11 patients previously treated with IB. Patients received IB either as monotherapy or as a boost to the vaginal cuff after 45 Gy of EBRT. Vaginal cylinder diameters ranged from 2.5 to 3.5 cm in the study population. The CT scans used in radiation planning for the IB treatment for these 11 patients were used to construct hypothetical treatment plans using the source characteristics of the XB device. In this study, a prescription dose of 7 Gy in three fractions prescribed to 0.5 cm depth was used for both methods of brachytherapy for all 11 patients. Treatment planning and plan optimization were performed with PLATO treatment planning software, version 14.3.2 (Nucletron, B.V., Veenendaal, the Netherlands). The physics parameters for the iridium-192 and XB sources were entered in TG-43 format. The planning target volume (PTV) was defined as the first 5 cm of vaginal cuff. The PTV, bladder, and rectum were contoured. The mean %V95 (percent of the PTV that received 95% of the prescription dose), %V100 (percent of the PTV that received 100% of the prescription dose), %V150 (percent of the PTV that received 150% of the prescription dose), bladder %V35 (percent of the bladder that received 35% of the prescription dose), bladder %V50 (percent of the bladder that received 50% of the prescription dose), rectal %V35 (percent of the rectum that received 35% of the prescription dose), and rectal %V50 (percent of the rectum that received 50% of the prescription dose) were then determined for each patient using the two methods of vaginal brachytherapy. The results were compared using the nonparametric Wilcoxon signed ranks test. Results The XB and IB methods of vaginal brachytherapy offered equivalent target volume coverage, but XB was

XB was developed to make brachytherapy more accessible to patients, especially those who live a significant distance from a center with a HDR afterloader unit. This enhanced accessibility has the potential to increase the number of women who receive adjuvant radiation therapy after surgery. In addition, this technology may allow improved quality of life for selected endometrial cancer patients who could be treated with vaginal brachytherapy alone, allowing them to receive a shorter course of radiation compared to the typical 5-week course of EBRT. Previous reports have evaluated the dosimetric properties of XB in the treatment of breast cancer (2, 3). The current series is the first report evaluating this device in the potential treatment of endometrial cancer. Table 1 PTV coverage IB

%V95

%V100

%V150

Patient

6.65 Gy per fx

7.0 Gy per fx

10.5 Gy per fx

1 2 3 4 5 6 7 8 9 10 11

99.78 99.54 99.93 99.55 99.72 99.85 99.56 99.75 99.69 99.58 99.86

99.27 99.49 99.61 99.27 99.60 99.84 99.61 99.95 99.66 99.72 99.81

98.89 98.55 99.81 98.67 99.02 99.37 98.42 99.13 99.09 98.86 98.80

98.10 98.79 99.16 98.53 99.13 99.50 99.07 99.78 99.26 99.34 98.93

22.07 25.98 42.17 33.41 36.91 41.82 38.61 49.99 40.68 41.13 21.16

42.16 48.32 59.68 53.77 56.55 67.29 60.35 75.69 72.52 67.40 44.38

Mean p Value

99.7 ns

99.6

99.0 ns

99.1

35.8 !0.05

58.9

IB 5 Iridium-192 high-dose-rate brachytherapy; XB 5 Xoft electronic brachytherapy; PTV 5 planning target volume; fx 5 radiation fraction; %V95 5 percent of the PTV that received 95% of the prescription dose; %V100 5 percent of the PTV that received 100% of the prescription dose; %V150 5 percent of the PTV that received 150% of the prescription dose.

ARTICLE IN PRESS A. Dickler et al. / Brachytherapy

(2008)

Table 2 Normal tissue doses IB

Bladder %V35

Bladder %V50

Rectal %V35

Rectal %V50

Patient

2.45 Gy per fx

3.50 Gy per fx

2.45 Gy per fx

3.50 Gy per fx

1 2 3 4 5 6 7 8 9 10 11

54.29 68.43 82.37 46.66 50.58 59.75 35.53 56.62 23.07 13.07 33.90

30.86 36.70 55.02 23.43 26.42 33.85 18.49 36.79 12.87 8.80 18.16

31.51 35.03 56.07 23.79 27.18 29.08 18.68 34.08 10.67 8.05 17.07

17.53 18.67 37.91 11.75 14.52 18.76 9.99 24.47 6.36 5.51 9.59

57.65 40.98 68.36 36.18 56.58 50.07 42.39 67.96 37.04 28.48 45.37

34.91 24.26 39.30 15.94 30.46 33.49 24.40 38.61 23.28 22.30 23.88

35.65 24.13 41.63 16.35 31.38 32.12 25.31 34.67 21.12 21.27 22.60

21.54 14.47 23.68 7.69 17.07 21.87 16.12 21.29 14.70 15.65 12.45

47.7 !0.05

27.4

26.5 !0.05

15.9

48.3 !0.05

28.3

27.8 !0.05

17.0

Mean p Value

IB 5 Iridium-192 high-dose-rate brachytherapy; XB 5 Xoft electronic brachytherapy; PTV 5 planning target volume; fx 5 radiation fraction; bladder %V35 5 percent of the bladder that received 35% of the prescription dose; bladder %V50 5 percent of the bladder that received 50% of the prescription dose; rectal %V35 5 percent of the rectum that received 35% of the prescription dose; and rectal %V50 5 percent of the rectum that received 50% of the prescription dose.

Our results showed that XB offers equivalent target volume coverage to IB; however, it was associated with increased ‘‘hot spots’’ in the target volume. The mean %V150 was 35.8% vs. 58.9% ( p! 0.05) for the IB and XB methods, respectively. With the XB method a mean of almost 60% of the upper vaginal cuff received 10.5 Gy per fraction, when the prescription dose was 7 Gy per fraction. Based upon reported clinical results, it is unlikely that this increased volume of vaginal cuff in the high-dose region will lead to clinically significant side effects. The American Brachytherapy Society lists a fractionation schedule of 10.5 Gy in three fractions prescribed to the vaginal surface as a suggested dosing schedule (4). In addition, Noyes and investigators from University of Wisconsin reported their results using two fractions of 16.2 Gy prescribed to the ovoid surface in 63 patients. With this relatively large fraction size, there were no Grade III/IV complications reported, and only 4 patients reported symptomatic vaginal apex fibrosis (5). XB was associated with increased normal tissue sparing compared to IB. The mean bladder %V35 was 47.7% vs. 27.4% ( p !0.05) and the mean bladder %V50 was 26.5% vs. 15.9% ( p! 0.05) for the IB and XB methods, respectively. The mean rectal %V35 was 48.3% vs. 28.3% ( p ! 0.05) and the mean rectal %V50 was 27.8% vs. 17.0% ( p! 0.05) for the IB and XB methods, respectively. Because kilovoltage irradiation is attenuated in tissue more quickly than radiation from the higher-energy iridium-192 source, the dose received by the bladder and rectum was reduced (see Fig. 1). Vaginal brachytherapy is generally a well-tolerated procedure, but serious adverse bladder and rectal side effects have been reported. Fayed et al. conducted a retrospective review of 1179 patients treated with vaginal brachytherapy at the Mallinckrodt Institute Radiation Oncology Center

Fig. 1. Dose distributions for IB (top) and XB (bottom) vaginal brachytherapy. 25% IDL 5 25% Isodose line, 50% IDL 5 50% Isodose line.

ARTICLE IN PRESS 4

A. Dickler et al. / Brachytherapy

between November 1960 and December 2004. The authors of this study observed Grade III or IV gastrointestinal and genitourinary complications in 2% of patients treated with low dose rate and 4% of patients treated with HDR ( p 5 ns). The rates of Grades III and IV complications were greater if patients received EBRT before vaginal brachytherapy (6). Hansgen et al. reported on 541 patients who were treated either with vaginal brachytherapy alone or combined with EBRT. Severe late complications consisting of fistulas of the bladder or bowel occurred in 2.8% of patients in the combined radiotherapy group, and 0.7% of patients in the HDR brachytherapy alone group (7). Clinical results will be needed to determine whether a reduction in radiation dose to the bladder and rectum achievable with XB will further reduce the risk of treatment-related toxicity in patients treated with combined EBRT and vaginal brachytherapy or vaginal brachytherapy alone.

Conclusion XB has the potential to make vaginal brachytherapy more accessible to patients and to decrease their risk of side

(2008)

effects. Clinical studies are needed to validate these promising dosimetric results. References [1] Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2007. CA Cancer J Clin 2007;57:43e66. [2] Dickler A, Kirk MC, Seif N, et al. A dosimetric comparison of MammoSite high-dose-rate brachytherapy and Xoft Axxent electronic brachytherapy. Brachytherapy 2007;6:164e168. [3] Smitt MC, Kirby R. Dose-volume characteristics of a 50-kV electronic brachytherapy source for intracavitary accelerated partial breast irradiation. Brachytherapy 2007;6:207e211. [4] Nag S, Erickson B, Parikh S, et al. The American Brachytherapy Society recommendations for high-dose-rate brachytherapy for carcinoma of the endometrium. Int J Radiat Oncol Biol Phys 2000;48: 779e790. [5] Noyes WR, Bastin K, Edwards SA, et al. Postoperative vaginal cuff irradiation using high dose rate remote afterloading: a phase II clinical protocol. Int J Radiat Oncol Biol Phys 1995;32:1439e1443. [6] Fayed A, Mutch DG, Rader JS, et al. Comparison of high-dose-rate and low-dose-rate brachytherapy in the treatment of endometrial carcinoma. Int J Radiat Oncol Biol Phys 2007;67:480e484. [7] Hansgen G, Nagel M, Dunst J, et al. Postoperative radiotherapy in endometrial carcinoma. A retrospective analysis of 541 cases. Strahlenther Onkol 1999;175:548e553.

BJR Received: 29 December 2014

Accepted: 20 May 2015

doi: 10.1259/bjr.20150010

Cite this article as: 60 Mobit PN, Packianathan S, He R, Yang CC. Comparison of Axxent-Xoft, 192Ir and Co high-dose-rate brachytherapy sources for image-guided brachytherapy treatment planning for cervical cancer. Br J Radiol 2015; 88: 20150010.

FULL PAPER

Comparison of Axxent-Xoft, 192Ir and 60Co high-dose-rate brachytherapy sources for image-guided brachytherapy treatment planning for cervical cancer 1,2

P N MOBIT, PhD, 1S PACKIANATHAN, MD, PhD, 1R HE, MS and 1C C YANG, PhD

Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, MS, USA Cameroon Oncology Center, PO Box 1870, Douala, Cameroon

Address correspondence to: Dr Paul N Mobit E-mail: mobit_paul@yahoo.ca

Objective: To evaluate the dosimetric differences and similarities between treatment plans generated with Axxent-Xoft electronic brachytherapy source (XoftEBS), 192 Ir and 60 Co for tandem and ovoids (T&O) applicators. Methods: In this retrospective study, we replanned 10 patients previously treated with 192Ir high-dose-rate brachytherapy. Prescription was 7 Gy 3 4 fractions to Point A. For each original plan, we created two additional plans with Xoft-EBS and 60Co. The dose to each organ at risk (OAR) was evaluated in terms of V35% and V50%, the percentage volume receiving 35% and 50% of the prescription dose, respectively, and D2cc, highest dose to a 2 cm3 volume of an OAR. Results: There was no difference between plans generated by 192Ir and 60Co, but the plans generated using

Xoft-EBS showed a reduction of up to 50% in V35%, V50% and D2cc. The volumes of the 200% and 150% isodose lines, however, were 74% and 34% greater than the comparable volumes generated with the 192Ir source. Point B dose was on average only 16% of the Point A dose for plans generated with Xoft-EBS compared with 30% for plans generated with 192Ir or 60Co. Conclusion: The Xoft-EBS can potentially replace either 192 Ir or 60Co in T&O treatments. Xoft-EBS offers either better sparing of the OARs compared with 192Ir or 60Co or at least similar sparing. Xoft-EBS-generated plans had higher doses within the target volume than 192Ir- or 60Cogenerated ones. Advances in knowledge: This work presents newer knowledge in dosimetric comparison between Xoft-EBS, 192Ir or 60 Co sources for T&O implants.

Cervical cancer is the most common cancer for females in the developing world, accounting for over 230,000 deaths per year.1 In developing countries, most cancers are diagnosed in the later stages, which makes them difﬁcult to treat, and cervical cancer is no exception. According to the American Brachytherapy Society Task Group Report,2 cervical cancer with clinical Stages IB2—IVA should be treated primarily with concurrent chemoradiation treatment followed by brachytherapy. Many clinical studies have shown that high-dose-rate (HDR) brachytherapy is of comparable efﬁcacy with low-dose-rate brachytherapy for patients with early- to advanced-stage cervical cancers.3,4 Many cancer centres in the developed world have thus adopted HDR brachytherapy treatments for patients with cervical and endometrial cancer.

may need to be constructed if for some reason the afterloader cannot be located in one of the pre-existing teletherapy bunkers. 192Ir has been the radioactive source of choice for most HDR brachytherapy devices, but the 192Ir source needs to be changed at least 3–4 times per year because the half-life of 192Ir is 73.8 days. In a resourcelimited setting such as in developing countries, this ongoing cost may be prohibitive. Afterloaders have recently been developed to house the miniaturized 60Co radioactive source, and the use of this source reduces the number of source exchanges from 3–4 times a year to once every 5–7 years owing to its much longer half-life of 5.26 years.5,6 This certainly reduces the ongoing cost of source exchanges, but one still needs a shielded bunker to use a 60Co radioactive source.

The main limitation to the widespread adoption of HDR brachytherapy in developing countries is the high cost of the afterloader, and the fact that a new shielded bunker

In the past few years, however, promising new technologies, mainly with electronic brachytherapy systems, have been developed that have eliminated the need for

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administrating brachytherapy in a shielded bunker. The AxxentiCad Xoft® electronic brachytherapy system (iCad, Inc., Nashua, NH) is based on a miniaturized 50 kVp X-ray source of 2.2 mm in length. The Bremsstrahlung photon spectrum ranges from 26.7 to 34.5 keV, which is similar to 125I (27.2–35.5 keV; mean, 28.4 keV). The ﬁrst half-value layer (HVL) of Xoft-electronic brachytherapy source (EBS) ranges from 1.39 to 1.56 mm (Al). The average energy of the Xoft-EBS is about 30 keV, which is ,10% of that of 192Ir (380 keV) or 60Co g-rays (1170 and 1330 keV). The HVL for 192Ir is 2.5 mm of lead while that for 60 Co is 11 mm of lead. Because of the low energy of Xoft-EBS, treatments using this source can be delivered in rooms shielded for CT or in regular operating rooms with minimal portable shielding.7 This electronic brachytherapy system has been investigated by numerous authors for brachytherapy applications such as accelerated partial breast irradiation, surface treatments for skin cancers and endometrial cancer brachytherapy treatments but not for tandem and ovoids (T&O) applicators.7–10 The objective of this study was to evaluate the dosimetry of T&O treatment plans generated using the Axxent-Xoft EBS. These plans were then compared with plans generated with the 192Ir and 60Co HDR radioactive sources.

METHODS AND MATERIALS All patients treated for cervical cancer in our facility with HDR brachytherapy received an individually customized plan based on the CT scan that was performed after the insertion of the applicator into the patient on the day of treatment. All the patients reported in this series were previously treated in our clinic with an 192Ir HDR source. They all received 25 fractions of 1.8 Gy each in external beam treatment to the whole pelvis followed by three fractions of the same dose to the sidewall as a boost delivered with a midline block. This was then followed by four fractions of T&O HDR brachytherapy of 7 Gy prescribed to Point A. The following organs at risk (OARs) were contoured on the CT scans: rectum, bladder, sigmoid and small bowel. The contours were based on GEC-ESTRO contouring guidelines.11 The CT scan had a slice thickness of 2 mm. The planning objectives were to keep the highest dose to 2 cm3 of the OARs, D2cc, ,80% of the prescription dose. This is a retrospective study in which we created CT-based plans on 10 patients who were previously planned and treated in our facility with T&O applicators using an 192Ir HDR brachytherapy source. Each patient originally had four different

Figure 1. Coronal view of the dose distribution. On the left is 192Ir and on the right the Xoft electronic brachytherapy source. L, left; R, right; F, foot; H, head; P, posterior.

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Table 1. Evaluation of volumes of 200%, 150%, 100% and 50% isodose volume for Xoft electronic brachytherapy source-, 60 Co-generated plans for a tandem and ovoids applicator with tandem length of 6 cm

Source type 192

Volume of 150% isodose line (cm3)

Volume of 100% isodose line (cm3)

Volume of 50% isodose line (cm3)

35.6

64.0

125.1

350.4

36.4

65.1

128.0

356.3

Xoft-EBS

61.9

87.1

134.8

270.2

CT scans and four different treatment plans (one new plan is generated for each fraction of HDR T&O insertion and treatment). For each HDR plan generated with the 192Ir radioactive source, we generated two additional plans using Xoft-EBS and 60Co, for a total of 12 plans per patient. Thus, for this study, we evaluated 120 CT-based plans in total. Treatment planning was performed using the Varian BrachyVisionTM treatment planning system v. 8.9 (Varian® Medical Systems, Palo Alto, CA). We had previously commissioned the 192 Ir HDR source that we routinely use for our HDR programme. We also had commissioned the Xoft-EBS as well as the BeBigTM 60Co HDR source manufactured by Eckert & Ziegler into the Varian BrachyVision treatment planning system using AAPM-TG43 format for the two sources.12–14 For the work reported in this article, we entered the American Association of Physicists in Medicine Task Group 43 data into the planning system and did a hand calculation of the dose predictions at several points for both the 60Co and the Xoft-EBS sources. During the clinical commissioning of the Xoft-EBS source in the planning system, we did extensive measurements in manufacturer supplied phantoms and compared the dose prediction using the radiochromic film. The results were in good agreement and consistent with what has been published in the literature for the Xoft-EBS source.7,8 OARs including rectum, bladder, sigmoid and small bowel were all individually contoured. The Foley catheter balloon with the contrast media was also contoured to represent the bladder. The corresponding data from the three radiation sources (Xoft-EBS, 192Ir and 60Co) are compared in one-way analysis of variance using IBM SPSS® Statistics for Windows v. 22 (IBM Corporation, Armonk, NY) at a confidence level of 95%, and an initial p-value was derived. If the initial p-value is .0.05, it indicates no significant difference between any two data groups. If the initial p-value is ,0.05, further tests between any two groups from the three groups of data are performed using the least significant difference, and p-values will be derived to determine which two groups of data are significantly different in the means. RESULTS Figure 1 shows the coronal view of two plans from our database that was generated with the Xoft-EBS and the 192Ir source. We observed that the pear-shaped dose distribution of the prescription isodose line appeared similar for both sources, and we did not discern any obvious significant differences between the two sources in terms of the prescription isodose line. This suggested that sharp dose gradients could be achieved using

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Ir- and

Volume of 200% isodose line (cm3)

192

a T&O applicator with the appropriate arrangement of sources (or dwell positions) using either of these sources. Furthermore, Figure 1 also shows that there were significant differences in the 200% isodose (yellow) and 150% isodose lines (pink) between the Xoft-EBS and 192Ir generated plans. For instance, the 150% isodose line for the Xoft-EBS-generated plan is continuous throughout the plane of view and the 200% isodose is mostly continuous. This contrasted sharply with the corresponding lines in the plan generated with the 192Ir source where there are significant breaks in the continuity of both isodose lines (150% and 200%). This finding indicated that near the applicator, the Xoft-EBS created a more extensive “highdose” volume than that of a comparable plan generated with 192 Ir. By contrast, it is not very apparent from Figure 1, but the width of the 50% isodose line (blue) measured through the reference point for the EBS-generated plan is smaller than the 50% isodose width generated with the 192Ir source. In order to further compare the volumetric dose distribution, we converted the 200%, 150%, 100% and 50% isodose lines into volume structures for three plans using a tandem length of 6.0 cm. All calculated isodose volumes include the applicator volume. The results are displayed in Table 1, which shows the volume of the converted structures with the 200%, 150%, 100% and 50% isodose lines. We again noted from Table 1 that the volume of the 200% isodose line with Xoft-EBS is approximately 74% greater than the comparable volume generated with either 192 Ir or 60Co. For the 150% and the 100% isodose lines, these volumes were still about 34% and 7% higher, respectively. However, this trend is reversed for the 50% isodose line where the volume of the isodose line for the Xoft source is only 77% of the isodose volume generated by either 192Ir or 60Co. Table 2 shows the comparison of the average doses to Point B for the 10 patients in our study. Once again, we saw small differences between the Point B doses for 192Ir and 60Co sources, which averaged about 210 and 203 cGy, respectively. However, the mean Point B dose is only 112 cGy for the Xoft-EBS-generated plans, i.e. about 45% less than the Point B dose for plans generated with either 192Ir or 60Co sources. We summarized from Figure 1 and Tables 1 and 2 that: (a) the prescription isodose line appears to be similar regardless of the radioactive source used (b) there seems to be no significant differences between plans generated by either 192Ir or 60Co radioactive HDR sources (c) there are significant differences in the volumes encompassing the 200%, 150% and 50% isodose lines between Xoft-EBSgenerated plans and either of the 192Ir- or 60Co-based plans

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Table 2. Comparison of average dose to Point B for Xoft electronic brachytherapy source, 192Ir and 60Co sources with tandem length of 6 cm

Source type 192

Point B (cGy)

Prescription dose (%)

210 6 27

203 6 31

Xoft-EBS

111 6 35

(d) there are signiﬁcant differences between the Point B doses for plans with either 192Ir or 60Co and that for plans generated with Xoft-EBS, which is only amounting to about 16% of Point A dose compared with an average of 30% in 192 Ir or 60Co plans. Figure 2 shows the dose distributions in all three orthogonal planes and the dose–volume histogram (DVH) for the bladder, rectum, small bowel and sigmoid for one of our T&O plans. The plans were generated in a standardized fashion with the Xoft-EBS source, 192Ir and 60Co. It seems apparent that the plan generated using the Xoft-EBS source may offer a signiﬁcant organ dosesparing advantage especially in the lower dose region since the DVH curve for the 192Ir-generated plan lies above that of the

Xoft-EBS-generated plans for all the OARs. Although this looks intuitive, we quantified the differences by determining the V50%, V35% and D2cc for the OARs for all the three radiation sources. The D2cc represents a measure of the highest dose to the OARs. Table 3 shows the D2cc for the rectum and bladder for all the patients in our study; each data point is the average of the values from four different fraction plans. The mean value for all 10 patients would show that there appears to be no significant differences between the values for Xoft-EBS, 192Ir and 60Co, as the p-value is 0.314. For the bladder, the average D2cc was 3.07 Gy for the XoftEBS plans compared with approximately 4.11 Gy for 192Ir or 60Co, a reduction of about 25%. A statistical analysis shows that p 5 0.036 ,a 5 0.05, concluding that there is a significant

Figure 2. Dose distribution and dose–volume histogram for organs at risk.

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Table 3. Evaluation of D2cc (highest dose to a 2-cm3 volume of the organ at risk) for rectum and bladder

Patient

Rectum (Gy) 192

Bladder (Gy) Xoft

192

Xoft

4.88

5.02

4.76

2.26

2.21

2.42

3.48

3.52

2.87

5.28

5.38

4.01

4.65

4.93

4.21

3.94

3.99

3.06

3.82

3.93

3.21

3.76

2.39

3.77

3.84

3.28

4.67

4.62

3.51

3.66

3.70

3.50

3.40

3.11

1.89

3.63

3.74

3.09

3.97

3.91

2.80

5.07

5.15

4.70

3.51

3.46

2.28

5.86

5.91

5.33

5.51

5.53

4.38

3.75

4.06

3.42

4.79

5.08

4.02

4.26 6 0.81

4.38 6 0.81

3.84 6 0.85

4.11 6 0.95

4.10 6 1.05

3.07 6 0.86

Average 6 standard deviation p (three groups) (a , 0.05) pIr-Xoft or pCo-Xoft (a , 0.05)

0.314 NA

difference between the three groups. There are significant differences between Xoft-EBS and 192Ir (p 5 0.024), and Xoft and 60Co (p 5 0.025), but not between 192Ir and 60Co (p . 0.05, not given in Table 3, which applies also in Tables 4–6) for D2cc to the bladder. The results for the sigmoid colon and small bowel are displayed in Table 4 for all the sources. There was a small difference for the D2cc for the sigmoid between the Xoft-EBS and 192Ir or 60Co (p 5 0.157). There was no significant difference for the small bowel doses except that the Xoft-EBS average value was marginally smaller but without statistical significance (p 5 0.865). Assessment of the V35% and V50% provides a measure of the planned dose in the low-dose regions of the DVH. Table 5 shows the

0.036 NA

0.024

0.025

comparison of the V50% for the rectum and bladder using all three sources, while Table 6 shows the data for V35%. As shown in Tables 5 and 6, for both rectum and bladder, the normalized volume of tissue receiving 35% and 50% of the prescription dose is smaller for the Xoft-EBS plans compared with plans generated with 192Ir or 60Co (p-values are given to indicate the level of signiﬁcance). DISCUSSION The results obtained in our study, which is based on data from 40 patient plans that were previously generated and treated with the 192Ir HDR source, show that the Xoft EBS can potentially serve as a replacement for 192Ir or 60Co radioactive sources. Similarly, the 60Co source appears to be adequate as an alternative to 192Ir for brachytherapy use in cervical cancer; indeed, it

Table 4. Evaluation of D2cc (highest dose to a 2-cm3 volume of the organ at risk) for sigmoid colon and small bowel

Patient number

Sigmoid 192

Small bowel Xoft

192

Xoft

2.63

2.62

1.64

1.39

1.42

1.10

5.17

5.13

4.51

5.32

5.31

5.14

3.09

3.11

2.36

3.76

3.83

3.60

4.76

4.14

6.53

6.55

6.72

3.89

3.95

3.12

5.08

5.10

4.65

4.89

4.90

4.18

4.61

4.55

4.23

4.16

4.12

3.55

3.36

3.31

2.97

3.14

3.10

2.56

4.85

4.80

4.40

5.03

5.21

4.34

4.39

4.32

3.94

3.92

3.72

3.09

3.93

3.61

3.35

4.07 6 0.90

4.06 6 0.93

3.35 6 0.96

4.32 6 1.37

4.28 6 1.38

4.01 6 1.47

Average 6 standard deviation p (three groups) (a , 0.05)

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0.157

0.865

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appears to have dose characteristics similar to that of the iridium source. There are, however, a number of caveats that must be taken into consideration by both the Medical Physicist and the Radiation Oncologist during the planning process for Xoft-EBS HDR brachytherapy treatment. Firstly, lower energy X-rays and g-rays have a higher relative biological effectiveness (RBE) than higher energy X-rays or g-rays such as those from 192Ir sources or 60Co.15,16 Thus, the “biologically equivalent dose” (BED) around the applicator itself could be exceedingly high and consequently lead to undesirable short- and long-term side effects on the tissues approximated closest to the applicators. One alternative approach to potentially mitigate the BED-related effect on the cervix and endometrium is to use a lower dose per fraction and higher number of fractions when utilizing the Xoft-EBS. Secondly, the volumes of the 200% and 150% isodose lines are signiﬁcantly greater when the plan is generated with the XoftEBS compared with plans generated with 192Ir or 60Co sources. This means that a larger central volume around the applicator itself is potentially receiving a higher dose and with a higher biological equivalent dose. To minimize toxicity, the midline block that is traditionally used in external beam radiation therapy at doses above about 45 Gy may need to be implemented at a lower external beam dose so as to limit the external beam dose to the

central region of the pelvis. Using a lower dose per fraction and a higher number of fractions for the brachytherapy portion can also help to reduce the BED to levels somewhat more comparable with those generated by 192Ir or 60Co. Thirdly, Point B, which is located 5 cm lateral of patient midline at the level of Point A in inferior to superior direction, typically receives approximately 25–30% of the prescription dose, representing approximately 7 Gy over the course of traditional HDR brachytherapy. Plans generated with Xoft-EBS only receive about 16% of the Point A dose. Because any attempt to throw the dose more laterally during brachytherapy will likely result in much higher midline doses, an alternative means of achieving adequate dose to Point B may be to supplement it during the external beam portion of the therapy. Fourthly, we have demonstrated that in this study the Xoft-EBS appears to provide better sparing of the associated pelvic OARs (bladder, rectum, sigmoid and small bowel) than either 192Ir or 60 Co sources, generally over the entire dose range as shown in Figure 3, which shows the DVH comparison for a typical implant generated with all three sources. There was only one patient for whom the dose to the small bowel was greater than that seen in plans generated with either 192Ir or 60Co sources. Since the XoftEBS has a higher RBE compared with the other two sources, increasing the number of fractions and reducing the fractional

Table 5. Percentage of rectum and bladder receiving 50% of prescription dose (V50%)

Patient number 1 2 3 4 5 6 7 8 9 10 Average 6 standard deviation

Rectum (V50%) 192

19.7

20.2

19.7

20.1

61.5

64.9

10.1

16.7

29.1

32.0

10.5

11.3

11.8

13.0

11.6

12.8

13.2

13.7

29.9

30.9

21.7 6 15.8

23.5 6 16.2

p (three groups) (a , 0.05) pIr-Xoft or pCo-Xoft (a , 0.05)

Bladder (V50%) Xoft-EBS

192

11.9

9.4

8.9

2.1

11.6

9.6

8.9

11.6

38.9

77.6

76.6

37.8

8.7

61.9

67.2

31.6

20.7

41.9

42.0

18.7

4.9

33.5

32.1

10.0

9.3

51.6

48.6

22.7

5.8

39.4

37.7

17.2

8.6

87.9

86.6

41.6

16.8

72.4

70.0

31.5

13.7 6 10.1

48.5 6 27

47.9 6 27.1

0.019

0.022

0.280 NA

Xoft-EBS

22.5 6 12.9

0.029 NA

NA, not applicable.

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Table 6. Percentage of rectum and bladder receiving 35% of prescription dose (V35%)

Patient number

Rectum 192

39.5

40.9

Bladder Xoft

192

41.2

23.1

40.7

38.6

5.9

41.3

23.1

40.6

38.6

6.4

86.0

88.0

61.3

99.9

99.5

67.7

35.9

43.5

20.6

96.5

97.2

59.6

65.3

68.0

48.4

76.6

76.9

42.2

39.2

40.1

16.8

74.4

73.2

25.6

42.1

43.4

14.1

92.1

90.4

40.2

Xoft

29.0

30.6

14.0

79.0

76.8

38.2

37.1

37.2

19.3

100.0

72.5

55.2

55.9

36.3

100.0

62.9

Average 6 standard deviation

47.0 6 17.2

p (three groups) (a , 0.05) pIr-Xoft or pCo-Xoft (a , 0.05)

48.9 6 17.2

27.7 6 15.9

80.0 6 23.0

0.015 0.016

0.009

79.1 6 23.7

42.1 6 24.0

0.001 NA

0.001

0.002

NA, not applicable.

dose as previously suggested could mitigate the effect of a higher physical dose, if, for some reason, the Xoft-EBS-generated plans increased the dose to any of the OARs of radiation damage. It is also important to note that analysing the data in terms of D0.01cc, D2cc and D5cc did not change the conclusions. CONCLUSIONS All three sources appear to be suitable for use in cervical cancer HDR brachytherapy, but the use of Xoft-EBS may reduce the doses to the OARs while achieving a comparable dose coverage to the target. The V35% and V50% may be useful as indicators of

the quality of the plan as they appear to characterize the lower dose region of the DVH curves more adequately. There were no noticeable differences between the 192Ir and 60Co T&O plans, but the plans generated using the Xoft-EBS offered better sparing of OARs when evaluating the V35% and V50%, which represent the lower dose in the DVH curve. However, when the D2cc was used to evaluate the dose to the OARs, there was no signiďŹ cant dose difference in the D2cc value for the rectum, which represents doses closer to the prescription dose. There was a reduction of up to 50% of the dose between Xoft-EBS and the other two sources when calculating the dose to Point B.

Figure 3. Comparison of doseâ&#x20AC;&#x201C;volume histogram for a tandem and ovoids implant for plans generated with 192Ir, 60Co and Xoft-EBS sources.

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Sankaranarayanan R. Overview of cervical cancer in the developing world. FIGO 26th Annual Report on the Results of Treatment in Gynecological Cancer. Int J Gynaecol Obstet 2006; 95(Suppl. 1): 205–10. doi: 10.1016/ S0020-7292(06)60035-0 Viswanathan AN, Thomadsen B; American Brachytherapy Society Cervical Cancer Recommendations Committee; American Brachytherapy Society. American Brachytherapy Society consensus guidelines for locally advanced carcinoma of the cervix. Part I: general principles. Brachytherapy 2012; 11: 33–46. doi: 10.1016/j.brachy.2011.07.003 Falkenberg E, Kim RY, Meleth S, De Los Santos J, Spencer S. Low-dose-rate vs. highdose-rate intracavitary brachytherapy for carcinoma of the cervix: the University of Alabama at Birmingham (UAB) experience. Brachytherapy 2006; 5: 49–55. doi: 10.1016/j. brachy.2005.12.001 Saitoh J, Ohno T, Sakurai H, Katoh H, Wakatsuki M, Noda SE, et al. High-dose-rate interstitial brachytherapy with computed tomography-based treatment planning for patients with locally advanced uterine cervical carcinoma. J Radiat Res 2011; 52: 490–5. doi: 10.1269/jrr.10189 Ntekim A, Adenipekun A, Akinlade B, Campbell O. High dose rate brachytherapy in the treatment of cervical cancer: preliminary experience with cobalt 60 Radionuclide source-A Prospective Study. Clin Med Insights Oncol 2010; 19: 89–94.

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Richter J, Baier K, Flentje M. Comparison of 60 cobalt and 192 iridium sources in high dose rate afterloading brachytherapy. Strahlenther Onkol 2008; 184: 187–92. doi: 10.1007/s00066-008-1684-y 7. Mobit PN, Rajaguru P, Brewer M, Baird M, Packianathan S, Yang CC. Radiation safety consideration during intraoperative radiation therapy. Radiat Prot Dosimetry 2015; 164: 376–82. doi: 10.1093/rpd/ncu292 8. Dickler A, Kirk MC, Coon A, Bernard D, Zusag T, Rotmensch J, et al. A dosimetric comparison of Xoft Axxent Electronic Brachytherapy and iridium-192 high-dose-rate brachytherapy in the treatment of endometrial cancer. Brachytherapy 2008; 7: 351–4. doi: 10.1016/j.brachy.2008.05.003 9. Dickler A, Kirk MC, Seif N, Griem K, Dowlatshahi K, Francescatti D, et al. A dosimetric comparison of MammoSite highdose-rate brachytherapy and Xoft Axxent electronic brachytherapy. Brachytherapy 2007; 6: 164–8. doi: 10.1016/j. brachy.2007.01.005 10. Smitt MC, Kirby R. Dose-volume characteristics of a 50-kV electronic brachytherapy source for intracavitary accelerated partial breast irradiation. Brachytherapy 2007; 6: 207–11. doi: 10.1016/ j.brachy.2007.03.002 11. Pötter R, Haie-Meder C, Van Limbergen E, Barillot I, De Brabandere M, Dimopoulos J, et al; GEC ESTRO Working Group. Recommendations from gynecological (GYN) GEC

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Dickler et al. Radiation Oncology 2010, 5:67 http://www.ro-journal.com/content/5/1/67

Open Access

RESEARCH

Prospective multi-center trial utilizing electronic brachytherapy for the treatment of endometrial cancer Research

Adam Dickler*1, Mohamed Y Puthawala2, John P Thropay3, Ajay Bhatnagar4 and Gary Schreiber5

Abstract Background: A modified form of high dose rate (HDR) brachytherapy has been developed called Axxent Electronic Brachytherapy (EBT). EBT uses a kilovolt X-ray source and does not require treatment in a shielded vault or a HDR afterloader unit. A multi-center clinical study was carried out to evaluate the success of treatment delivery, safety and toxicity of EBT in patients with endometrial cancer. Methods: A total of 15 patients with stage I or II endometrial cancer were enrolled at 5 sites. Patients were treated with vaginal EBT alone or in combination with external beam radiation. Results: The prescribed doses of EBT were successfully delivered in all 15 patients. From the first fraction through 3 months follow-up, there were 4 CTC Grade 1 adverse events and 2 CTC Grade II adverse events reported that were EBT related. The mild events reported were dysuria, vaginal dryness, mucosal atrophy, and rectal bleeding. The moderate treatment related adverse events included dysuria, and vaginal pain. No Grade III or IV adverse events were reported. The EBT system performed well and was associated with limited acute toxicities. Conclusions: EBT shows acute results similar to HDR brachytherapy. Additional research is needed to further assess the clinical efficacy and safety of EBT in the treatment of endometrial cancer. Introduction Endometrial cancer is the most common gynecologic cancer, and an estimated 42,160 new cases of endometrial cancer were diagnosed in 2009 [1]. The standard management for endometrial cancer is a total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH-BSO) with or without lymph node sampling. The vagina is the most common site of recurrence, and whole pelvic radiotherapy, vaginal cuff brachytherapy, or both types of radiation therapy may follow surgical treatment. Radiation therapy significantly decreases the risk of local regional recurrence and has been associated with improved survival in patients with stage IC disease [2-4]. Vaginal brachytherapy is often employed in the treatment of endometrial cancer, either alone or in combination with external beam radiation. Vaginal brachytherapy has typically been delivered using a vaginal cylinder and a

high dose rate (HDR) Iridium-192 radiation source. A modified form of HDR brachytherapy has been developed called Axxent Electronic Brachytherapy (EBT). The EBT device uses a 50 kilovoltage (kV) electronic X-ray source, which does not require a shielded vault for treatment or an HDR afterloader unit. The dosimetric properties of the EBT and Ir-192 sources were compared in the treatment of endometrial cancer [5]. Both sources provided equivalent target volume coverage, and EBT was associated with increased bladder and rectum sparing compared to Ir-192. A prospective, multi-center clinical study was carried out to evaluate the success of treatment delivery, safety and toxicity of EBT as post-surgical adjuvant radiation therapy in patients with early-stage endometrial cancer. The results of this trial represent the first clinical report of EBT in the treatment of endometrial cancer.

* Correspondence: atd22_99@yahoo.com 1

Little Company of Mary Hospital, Evergreen Park, IL USA

Full list of author information is available at the end of the article ÂŠ 2010 Dickler et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Dickler et al. Radiation Oncology 2010, 5:67 http://www.ro-journal.com/content/5/1/67

Methods The study was approved at the institutional review boards at each of the five participating sites. Each patient was consented prior to enrollment in the trial. Patients

This trial utilized the FIGO staging system for endometrial cancer developed in 1988. Eligibility for the trial included patients with Stage I & II endometrial cancer, excluding Stage IA Grade 1, who had undergone a TAHBSO. Exclusion criteria included patients with collagen vascular disease, scleroderma, or active lupus. Materials

The EBT system consists of the disposable X-ray source, vaginal applicators, the controller unit, and the base plate and clamp. The miniature X-ray source produces 50 kilovolt X-rays at its tip and can be translated within the applicator to provide a predictable dose of radiation to the tissue surrounding the cylinder. The vaginal applicators are cylinders made of medical-grade polymers and provide transmission characteristics specifically for the low energy X-rays emitted by the EBT source. A vaginal cylinder size was selected for each patient, and 25 mm, 30 mm, 35 mm cylinders were utilized in the study. The applicator was inserted just prior to treatment and removed following treatment on each treatment visit. The base plate and clamp provide stabilization of the applicator during radiation treatment. The mobile controller unit provides power to the X-ray source and contains the user interface. Treatment

If vaginal brachytherapy was to be administered as the sole radiation treatment modality, sites were given the option of treating with a prescription dose 7.0 Gy x 3 to 0.5-cm depth or 5.5 Gy x 4 to 0.5-cm depth. If vaginal brachytherapy was to be delivered in conjunction with external beam radiation therapy (EBRT), sites first delivered 45 Gy EBRT in 25 fractions to the pelvis. At the completion of EBRT, sites were given the option of treating with an EBT prescription dose of 6.0 Gy x 3 to the vaginal surface or 8.0 Gy x 2 to the vaginal surface. Treatment planning was performed according to the standard of care at the treating institution and typically with BrachyVisionâ&#x201E;˘ treatment planning software (Varian Medical Systems, Palo Alto, CA) or Platoâ&#x201E;˘ treatment planning software (Nucletron, Columbia, MD).Three dimensional treatment planning was completed for each patient prior to the first brachytherapy fraction. Both 2D and 3D treatment planning were permitted prior to each fraction according to the physician's standard of care, but a 3D treatment plan based on computed tomography (CT) was required so that normal tissue doses could be calculated. CT images were recorded prior to each frac-

Page 2 of 6

tion on all patients to verify correct applicator placement. A CT scan was performed with the vaginal applicator in place and the patient in a supine position. The CT scan encompassed a superior border of L5/S1 and an inferior border of the ischial tuberosities. TG-43 parameters specific to EBT were used to compute the delivered dose [5,6]. Patients were followed at 1 month and 3 months post-treatment. Endpoints

The primary endpoints of the study were the successful delivery of the prescribed radiation dose and treatmentrelated adverse events. Adverse events and severity were recorded during treatment and at the 1- and 3-month follow-up visits. Adverse events were graded according to the common terminology criteria (CTC) version 3.0. The n (number of observations) and proportion is reported for each endpoint. For continuous variables, the mean, standard deviation, and range is presented. Categorical variables are described using proportions and frequencies.

Results

Patient Population

A total of 15 patients were enrolled in the study. The first patient was enrolled in September 2008, and enrollment was completed in October 2009. Patient and disease characteristics are listed in Table 1. The mean age of the patients was 63.2 years of age (range 41.6-72.7). Nearly half (46.7%) had FIGO Stage IB cancer; 5 (33.3%) had Stage IC, and 3 (20.0%) had Stage IIA. All patients were followed for 3 months. Treatment

The EBT vaginal brachytherapy was successfully delivered for all 48 treatments in the 15 patients. In the 10 patients who received EBT alone, the prescription dose was 7.0 Gy x 3 fractions to a 0.5 cm depth in 7 patients and 5.5 Gy x 4 fractions to a 0.5 cm depth in 3 patients (Table 2). In the 5 patients who received EBRT before EBT, the EBRT dose was 45 Gy in 25 fractions in 4 patients delivered by IMRT in 3 and three dimensional conformal radiation therapy (3D-CRT) in 1, and 50.4 Gy in 28 fractions in 1 patient delivered by 3D-CRT. Following EBRT, the EBT prescription dose was 6.0 Gy x 3 fractions to the vaginal surface in 3 patients, 5.0 Gy x 4 to the vaginal surface in 1 patient, and 8.0 Gy x 2 to the vaginal surface in 1 patient. The mean treatment time was 4.9 minutes. The brachytherapy treatment summary and applicator size used for each patient is listed in Table 1. CT scans were used to evaluate the dose to normal tissues and volume of treatment after applicator insertion and prior to the first fraction of brachytherapy. The length of vagina treated ranged from 4.0 to 7.0 cm with a

Dickler et al. Radiation Oncology 2010, 5:67 http://www.ro-journal.com/content/5/1/67

Page 3 of 6

Table 1: Patient Characteristics Mean Age (Range) Years

63.2 (41.6-72.7)

loose clamp assembly. This issue was easily rectified, and treatment was completed as scheduled. Adverse Events

Race

An independent data safety monitor adjudicated the adverse events. Six patients reported adverse events possibly or probably related to the EBT treatment including 4 CTC Grade I toxicities and 2 CTC Grade II toxicities (Table 4). There were no treatment related adverse events reported at the time of treatment and there were no serious adverse events reported in the study. One patient developed Grade I dysuria at her 1-month follow-up visit. Additional Grade I adverse events reported by one patient each included mild mucosal atrophy, vaginal drying, and rectal bleeding. A patient reported both Grade II dysuria and pelvic pain at her 1-month follow-up visit. Nine of 15 patients reported no treatment related adverse events during treatment through the 3-month follow-up visits.

n (%)

Caucasian

11 (73.3%)

Hispanic

1 (6.7%)

Asian

2 (13.3%)

Other

1 (6.7%)

FIGO Cancer Stage IB

7 (46.7%)

5 (33.3%)

IIA

3 (20.0%)

Tumor Grade Grade 1

3 (20.0%)

Grade 2

8 (53.3%)

Grade 3

4 (26.7%)

Depth of Myometrial Invasion â&#x2030;¤1/3

8 (53.3%)

> 1/3 and â&#x2030;¤ 2/3

5 (33.3%)

> 2/3

2 (13.3%)

Mean Time from Hysterectomy to 1st EBT Treatment

113.1 Days

(Range)

(37-787) Days

Applicator Sizes

n (%)

25 mm

7 (46.7%)

30 mm

7 (46.7%)

35 mm

1 (6.7%)

mean length of 5.28 cm. The dosimetric data is summarized in Table 3. The EBT system performed without major malfunction. No technical issues occurred with the controller or the applicators. At one site there was a source issue related to the electrical connection, which was traced to a

Discussion Post-operative vaginal brachytherapy was compared with external beam radiation therapy (EBRT) in 427 patients with stage I or IIA endometrial cancer in a report of the PORTEC-2 trial [7]. The rates of overall survival, disease free survival, and vaginal relapse were not significantly different between the two treatment modalities. However, the rates of Grade I-II gastrointestinal toxicity were significantly lower in the vaginal brachytherapy arm (27/ 215 patients or 12.6%) as compared with the EBRT arm (112/208 patients or 53.8%). The authors of this study concluded that vaginal brachytherapy alone should be the adjuvant treatment of choice for patients with high-intermediate risk endometrial cancer [7]. Those results may lead to more patients being treated with post-surgical vaginal brachytherapy alone for early stage endometrial cancer. This combined with patients who receive both EBRT and vaginal brachytherapy likely will lead to an increasing utilization of HDR vaginal brachytherapy. Currently, the most common method of delivering vaginal brachytherapy relies on a radioactive isotope, Iridium-192, which is not feasible for all centers. Many centers do not have an HDR afterloader device, which is

Table 2: Total Prescribed Dose (Gy) of EBT in patients categorized by whether they received EBRT in addition to EBT EBT Alone

EBT + EBRT Prescription

Dose (Gy)

5.5Gy x 4Fx to 0.5 cm

7Gy x 3Fx to 0.5 cm

8Gy x 2Fx to Vaginal Surface

6Gy x 3Fx to Vaginal Surface

5Gy x 4Fx to 0.5 cm

# of patients (%)

3 (20.0%)

7 (46.7%)

1 (6.7%)

3 (20.0%)

1 (6.7%)

Gy = gray, EBRT= external beam radiation therapy, Fx = Fraction, cm = centimeter

Dickler et al. Radiation Oncology 2010, 5:67 http://www.ro-journal.com/content/5/1/67

Page 4 of 6

Table 3: Dosimetry Analysis: The percent of the planned target volume (PTV) or organ receiving 50, 95, 100, or 150% of the prescribed dose at depth followed by the maximum point dose in cGy to the indicated organ Mean % ± SD

Range

%V95

91.0 ± 13.6

49.0 - 103.0

%V100

87.6 ± 13.7

48.0 - 98.0

%V150

34.1 ± 15.6

3.3 - 69.7

Bladder %V50

11.5 ± 9.7

0 - 40.2

Rectal %V50

17.4 ± 10.9

0 - 36.0

Max Point Dose to Bladder

701.2 ± 169.3 cGy

467 - 1087 cGy

Max Point Dose to Rectum

775.0 ± 355.4 cGy

100 - 1584 cGy

Max Point Dose to Small Bowel

421.3 ± 391.1 cGy

0 - 1188 cGy

required with an Ir-192 source. In addition, many centers have a single shielded radiation vault for both their EBRT and HDR patients. This can lead to logistical difficulties in scheduling patients at a busy radiation center. Electronic brachytherapy (EBT) was developed to make brachytherapy more accessible for patients. EBT treatment does not require a shielded radiation bunker and thus increases the settings in which brachytherapy treatments can be performed. This report describes the first prospective clinical trial of vaginal EBT for the treatment of endometrial cancer.

EBT treatment was delivered successfully for all 48 fractions of treatment in this study. The EBT device performed as expected with minimal technical issues. EBT was well tolerated with no serious adverse events. Six patients reported Grade 1-2 adverse events. Previous reports of EBT for accelerated partial breast irradiation (APBI) demonstrated an acceptable safety profile similar to that seen with Ir-192 based APBI [8]. Previous reports with Ir-192 based vaginal brachytherapy have shown it to be a very well tolerated procedure. Fayed, et al., reported only a 4% risk of Grade III/IV toxicity in 175 patients treated with HDR. The authors also noticed that the complication risk was higher if the patients also received EBRT [9]. Weiss et al and MacLoed et al have both reported on studies with over 100 patients treated with HDR brachytherapy alone and described no Grade III/IV toxicity [10,11]. It should be noted that these studies utilizing Ir-192 have larger patient numbers and longer follow-up than the current series. The EBT radiation fractionation schedules utilized in this study were derived from the American Brachytherapy Society Recommendations for the suggested doses of Ir-192 HDR alone or in combination with EBRT [12]. It has previously been shown by Dickler, et al., in a dosimetric comparison that EBT offers similar target volume coverage and increased bladder and rectum sparing compared to Ir-192 based vaginal brachytherapy [5]. As a result, using the same radiation fractionation as used for Ir-192 treatment, it is reasonable to expect similar or possibly less bladder and rectal toxicity with EBT treatment. In the current study at 3 months follow-up, there have

Table 4: Number (%) of patients with adverse events reported at the one-month (1 mo) or three-month (3 mo) follow-up visit that are possibly related or probably related to the EBT treatment 1 Month Visit Pt #

Adverse Event

Grade

N (%)

Visit

Relationship to EBT Treatment

Visit Resolved

EBT & EBRT

Dysuria

1 mo

Possibly related

Unresolved at 3 mo. visit

EBT & EBRT

Dysuria

1 mo

Possibly related

Resolved at 3 mo. visit

EBT & EBRT

Vaginal pain

1 mo

Probably related

Resolved at 6 wk. visit

3 Month Visit Pt #

Adverse Event

Grade

N (%)

Visit

Relationship to EBT Treatment

Visit Resolved

EBT

Mucosal atrophy

3 mo

Probably Related

Reported at 3 mo. visit

EBT

Rectal bleeding

3 mo

Probably Related

Reported at 3 mo. visit

EBT & EBRT

Vaginal Drying

3 mo

Possibly Related

Reported at 3 mo. visit

EBT = Electronic Brachytherapy, EBRT = External Beam Radiation Therapy RT = radiation therapy treatment, mo = month, wk = week

Dickler et al. Radiation Oncology 2010, 5:67 http://www.ro-journal.com/content/5/1/67

been no reports of Grade III/IV toxicity, and 9 of 15 patients have reported no toxicity at all. This is consistent with previous published reports using Ir-192 brachytherapy [7,10,11]. Although the study by Dickler, et al., showed similar target coverage between EBT and Ir-192 HDR treatment, EBT was associated with increased "hot spots" in the vaginal canal [5]. Specifically, the %V150 (percent of the target volume receiving 150% of the prescription dose) was 58.9% vs. 35.8% for the EBT and Ir-192 treatments, respectively. It is not known whether an increased volume of the vaginal canal being exposed to higher radiation doses will put patients at an increased risk for vaginal side effects such as stenosis or vaginal shortening. At 3 months follow-up, there were no incidences of vaginal stenosis or shortening in the current study. Of note, Noyes and investigators from University of Wisconsin have reported their results treating 63 patients with HDR and vaginal ovoids with vaginal surface doses of 16.2 Gy. The authors reported no incidence of Grade III/IV side effects using much higher vaginal surface doses than used in the current study [13]. Further follow-up will be needed to determine if late vaginal side effects occur at an increased rate with EBT treatment.

Conclusions The EBT system performed well and was associated with limited acute adverse events. The prescribed dose was successfully delivered in all 15 patients. Acute results are similar to those using HDR brachytherapy. Further research with EBT will be needed to establish its clinical efficacy and long-term toxicity in the treatment of patients with endometrial cancer. List of Abbreviations AE: Adverse events; CT: Computerized tomography; CTC: Common Terminology Criteria; EBRT: External Beam Radiation Therapy; EBT: Electronic Brachytherapy; Gy: Gray; HDR: High Dose Rate; Ir- 192: Iridium 192; kV: kilovoltage; QID: Four times per day, TAH-BSO: total abdominal hysterectomy and bilateral salpingooophorectomy Author's Information AD has completed dosimetric comparisons of electronic brachytherapy and iridium-192 and requested to proceed with a small study on the initial experience using electronic brachytherapy for the treatment endometrial cancer following TAH-BSO. Competing interests We disclose to Radiation Oncology the following potential conflicts of interest: Author Disclosures: Dr. Dickler is on the scientific advisory board for Xoft, Inc.

Page 5 of 6

Authors' contributions All five authors contributed significantly to this manuscript by contributing to the study data collection, reviewing the data analyses, revising, and approving the final manuscript. All authors contributed to the study design of this first experience. Acknowledgements The authors wish to thank all site participants and investigators who supported this research, and the patients for participating in this study. A medical writer, Leslie Todd, assisted with preparation of this manuscript, and Xoft, Inc, compensated her time. Funding for this study was provided by Xoft, Inc. Author Details 1Little Company of Mary Hospital, Evergreen Park, IL USA, 2Rhode Island Hospital, Providence, RI USA, 3Beverly Oncology and Imaging Centers, Montebello, CA USA, 4Cancer Treatment Services Arizona, Casa Grande, AZ USA and 5Swedish Covenant Hospital, Chicago, IL USA Received: 13 May 2010 Accepted: 20 July 2010 Published: 20 July 2010 Radiation ÂŠ 2010 This article is an Dickler Open Oncology is available et Access al;2010, licensee from: article 5:67 http://www.ro-journal.com/content/5/1/67 BioMed distributed Central under Ltd.the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

References 1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ: Cancer statistics 2009. CA Cancer J Clin. 2009, 59(4):225-49. 2. Scholten AN, van Putten WL, Beerman H, Smit VT, Koper PC, Lybeert ML, Jobsen JJ, Warlam-Rodenhuis CC, De Winter KA, Lutgens LC, van Lent M, Creutzberg CL: Postoperative radiotherapy for stage I endometrial carcinoma: long-term outcome of the randomized PORTEC trial with central pathology review. Int J Radiat Oncol Biol Phys 2005, 63:834-38. 3. Keys HM, Roberts JA, Brunetto VL, Zaino RJ, Spirtos NM, Bloss JD, Pearlman A, Maiman MA, Bell JG: A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a gynecologic oncology group study. Gynecol Oncol 2004, 92:744-51. 4. Lee CM, Szabo A, Shrieve DC, Macdonald OK, Gaffney DK: Frequency and Effect of Adjuvant Radiation Therapy Among Women with Stage I Endometrial Adenocarcinoma. JAMA 2009, 295:389-97. 5. Dickler A, Kirk MC, Coon A, Bernard D, Zusag T, Rotmensch J, Wazer DE: A dosimetric comparison of xoft axxent electronic brachytherapy and Ir192 hdr brachytherapy in the treatment of endometrial cancer. Brachytherapy 2008, 7(4):351-4. 6. Rivard MJ, Davis SD, DeWerd LA, Rusch TW, Axelrod S: Calculated and measured brachytherapy dosimetry parameters in water for the Xoft Axxent X-Ray Source: An electronic brachytherapy. Med Phys 2006, 33:4020-32. 7. Nout RA, Smit VT, Putter H, Jurgenliemk-Schulz IM, Jobsen JJ, Lutgens LC, van der Steen-Banasik EM, Mens JW, Slot A, Kroese MC, van Bunningen BN, Ansink AC, van Putten WL, Creutzberg CL: Vaginal brachytherapy versus pelvic external beam radiotherapy for patients with endometrial cancer of high-intermediate risk (PORTEC-2): an open label non-inferiority, randomized trial. Lancet 2010, 375:816-23. 8. Mehta VK, Algan O, Griem KL, Haile K, Wazer DE, Stevens RE, Chadha M, Kurtzman S, Modin SD, Dowlatshahi K, Elliott KW, Rusch TW: Experience with an electronic brachytherapy technique for intracavitary accelerated partial breast irradiation. Am J Clin Oncol 2010. published online April 9. Fayed A, Mutch DG, Rader JS, Rader JS, Gibb RK, Powell MA, Wright JD, Elnaga I, Zoberi I, Grigsby PW: Comparison of high-dose-rate and lowdose-rate brachytherapy in the treatment of endometrial cancer. Int J Radiat Oncol Biol Phys 2007, 67(2):480-4. 10. Weiss E, Hirnle P, Arnold-Bofinger H, Hess CF, Bamberg M: Adjuvant vaginal high-dose-rate afterloading alone in endometrial carcinoma: patterns of relapse and side effects following low-dose therapy. Gynecol Oncol 1998, 71:72-6. 11. MacLeod C, Fowler A, Duval P, D'costa I, Dalrymple C, Elliott P, Atkinson K, Firth I, Carter J: High-dose-rate brachytherapy alone post-hysterectomy for endometrial cancer. Int J Radiat Oncol Biol Phys 1998, 42:1033-9. 12. Nag S, Erickson B, Parikh S, Gupta N, Varia M, Glasgow G: The American brachytherapy society recommendations for high-dose-rate brachytherapy for carcinoma of the endometrium. Int J Radiat Oncol Biol Physics 2000, 48(3):779-90.

Dickler et al. Radiation Oncology 2010, 5:67 http://www.ro-journal.com/content/5/1/67

13. Noyes WR, Bastin K, Edwards SR, Buchler DA, Stitt JA, Thomadsen BR, Fowler JF, Kinsella TJ: Postoperative vaginal cuff irradiation using high dose rate remote afterloading: a phase II clinical protocol. Int J Radiat Oncol Biol Phys 1995, 32:1439-43. doi: 10.1186/1748-717X-5-67 Cite this article as: Dickler et al., Prospective multi-center trial utilizing electronic brachytherapy for the treatment of endometrial cancer Radiation Oncology 2010, 5:67

Page 6 of 6

Received: 27 November 2018

Revised: 9 May 2019

Accepted: 20 May 2019

DOI: 10.1002/acm2.12657

RADIATION ONCOLOGY PHYSICS

Treatment of cervical cancer with electronic brachytherapy Sergio Lozares-Cordero1 | José Antonio Font-Gómez1 | Almudena Gandía‐Martínez1 | Anabela Miranda‐Burgos2 | Agustina Méndez‐Villamón2 | David Villa‐Gazulla1 | Verónica Alba‐Escorihuela1 | Sara Jiménez‐Puertas1 | Víctor González‐Pérez3 1 Department of Physics and Radiation Protection, Miguel Servet University Hospital, Zaragoza, Spain 2

Department of Radiation Oncology, Miguel Servet University Hospital, Zaragoza, Spain 3 Department of Physics and Radiation Protection, Fundación IVO, Valencia, Spain

Author to whom correspondence should be addressed. Lozares‐Cordero Sergio E‐mail: slozares@salud.aragon.es.

Abstract Purpose: We report the ﬁrst cervical cancer cases treated with interstitial electronic brachytherapy (eBT) at our hospital and compare them with plans made with high‐ dose‐rate interstitial brachytherapy based on Ir192 (HDR‐BT). Materials and methods: Eight patients with cervical cancer were treated with the Axxent eBT device (Xoft, Inc.). Planning was with magnetic resonance imaging and computed tomography following the recommendations of the EMBRACE protocol. The dosimetry parameters of organs at risk (OAR) were evaluated for the bladder, rectum, and sigmoid colon (D2cc, D1cc, and D0.1cc). In addition, the V150 and V200 of irradiated tissue were compared for both eBT and HDR‐BT. All patients received intensity‐modulated external beam radiation therapy with a regimen of 23 sessions of 2 Gy followed by four sessions of 7 Gy of eBT performed over 2 weeks (two sessions followed by another two sessions a week later) following the EMBRACE recommendations. Each of the eight patients was followed to assess acute toxicity associated with treatment. Results: The doses reaching OAR for eBT plans were lower than for HDR‐BT plans. As for acute toxicity associated with eBT, very few cases of mucositis were detected. No cases of rectal toxicity and one case with grade 1 urinary toxicity were detected. The results at 1 month are equally good, and no relapses have occurred to date. Conclusions: The ﬁrst results of treatment with the Axxent eBT device are promising, as no recurrences have been observed and toxicity is very low. eBT is a good alternative for treating cervical cancer in centers without access to conventional HDR. KEY WORDS

cervical cancer, electronic brachytherapy, HDR, image‐guided brachytherapy

1 | INTRODUCTION

most frequent type of cancer in developing countries, with more than 500,000 new cases diagnosed every year.1

Cervical cancer is the second most frequent type of cancer in

The initial approach in patients with stage IA1‐IA2 cervical cancer

women, with a mean age at onset of 45 yr worldwide. It is also the

is generally surgery, if possible, and radiotherapy or brachytherapy

---------------------------------------------------------------------------------------------------------------------------------------------------------------------This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2019 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine. J Appl Clin Med Phys 2019; 1–9

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SERGIO

ET AL.

(BT) if not. Patients with advanced cancer (IB2‐IIA bulky‐IIB‐III‐IVA)

The unit is constructed of a disposable mini‐x‐ray tube inserted

receive chemotherapy and radiotherapy concomitantly, as well as BT,

into a ﬂexible plastic sheath approximately 5.5 mm in diameter. Water

irrespective of whether they can undergo surgery.2

is pumped around the source to reduce heating from the target. The

The use of BT as a key component in the treatment of cervical cancer is the main prognostic factor in local control of the disease.3

electrons (20–50 keV) are emitted from a ﬁlament nearly 1 cm from the anode. The anode is made mainly of a microlayer of tungsten on

As with cancer at other sites, the response of gynecological can-

an yttrium substrate that acts as a buffering layer and a small amount

cer to radiation is dose‐dependent, with improved local control at

of silver that acts as a constituent of the brazing alloy. The anode tran-

higher doses.4 Better knowledge of tumor extension at diagnosis

sitions are from a spherical tip to a conical‐hemisphere section and

and the response to the treatment received has led to more realistic

ﬁnally to a cylinder. The source is mounted on a mechanical robot arm

local treatment of cervical carcinoma, with adapted BT that is tai-

that is attached to a movable treatment control console.19

lored depending on the ﬁndings at different points during the course

The unit can be used to treat nonmelanoma skin tumors, intraop-

of the disease. Therefore, BT has proven to be efﬁcacious as a com-

erative radiotherapy in breast cancer, and postoperative treatment

ponent of radiation therapy. The dose released by BT in contact

of endometrial and cervical cancer.

with the tumor (4 fractions in 2 weeks) is at least equivalent to the

The case of skin tumors is problematic. High doses can reach

dose administered during external beam radiation therapy (EBRT) on

bone (high atomic number), owing to the predominant photoelectric

the pelvis for 5 or 6 weeks.5

effect at low energies.20 Such a situation could arise in cases of cer-

Any nonsurgical treatment of gynecologic cancer with curative intent should combine EBRT and BT.6 The traditional approach has 7

vical cancer, although, to date, we have had no reports of this problem at our center.

been low‐dose rate BT. For the last few years, the type of BT

It can also be used to treat cervical cancer in protocols that

applied has been high‐dose rate BT (HDR‐BT) with Ir192,8 which

require treatment with HDR‐BT after chemotherapy and EBRT with

makes it possible to optimize both the dose and patient comfort,

a dedicated applicator (Fig. 1).

since it can be administered on an outpatient basis, even though more sessions are necessary. Technical advances in imaging and dosimetry have led to the use

The eBT system at our center was acquired in May 2015 for treatment of skin cancer and intraoperative radiotherapy for breast cancer after tumor removal.

of computed tomography (CT) and magnetic resonance imaging

Postoperative treatment of endometrial cancer with the Axxent

(MRI) to locate the tumor and organs at risk (OAR) and to plan treat-

eBT unit was started in 2015, and in May 2016, we treated the ﬁrst

ment based on real anatomy.9

case of cervical cancer.

A working group from GEC‐ESTRO published recommendations

This therapeutic approach was traditionally applied in many cen-

on contouring the target tumor and OAR, as well as on the dose vol-

ters throughout the world with HDR devices based on Iridium‐192

ume parameters to be reported for image‐guided BT in deﬁnitive

(Ir192, half‐life of 73.8 days and mean energy of 0.355 MeV) and

radiotherapy for locally advanced cervical cancer.10 The major advan-

different types of applicator, of which Fletcher applicators were the

tage of this technique is the possibility of conforming the dose to

most common. In the current century, others have appeared and

both volume (3D) and time (4D). Thus, repetitive imaging performed

may help in treatment based on interstitial needles placed in various

before each BT implant makes it possible to adapt the BT dose to

conﬁgurations.21

the anatomy of the individual patient, taking into account not only

Retrospective studies on patients treated with Ir192 have com-

the position of the OAR but also tumor regression, which is often

pared endometrial cancer,22,23 cervical cancer,24 and breast cancer.25

achieved with previous EBRT and chemotherapy.

A lower dose was always found in the OAR in patients whose planning

The EMBRACE study,11 which was developed some time after

was based on eBT, although the patients in those studies were treated

publication of the GEC‐ESTRO recommendations, attempted to unify

with Ir192. Another study comparing patients with endometrial cancer

all of the processes involved in the management of cervical cancer

treated with eBT has reported favorable preliminary results.26

by providing guidelines for the participating centers. A key feature is

The objective of treatmenting with eBT is to provide an alternative

the use of MRI to better deﬁne the tumor and the OAR volumes. It

with a portable device, thus conferring the advantage of mobility and

allows to prescribe higher doses to the region of interest thus

obviating the need for a shielded room: with the energy used by the

increasing the tumor control as shown in the Retro EMBRACE

device, screening equivalent to 0.5 mm of lead on walls and doors is

study.12 All of the participating centers used HDR‐BT with Ir192 in

sufﬁcient. Transport is no longer a factor since it does not involve

their treatments.

radioactive sources. In addition, the device facilitates quality control

Electronic brachytherapy (eBT) has been evolving since the start

and preparation and implementation of the treatment.27

of the 21st century13 and has become a treatment option for various tumor sites in different settings.14–18 The Axxent eBT unit (Xoft, Inc., subsidiary of iCAD, San José,

2 | MATERIALS AND METHODS

CA, USA) provides treatment to patients with a miniature 50‐kVp x‐ ray source that irradiates the tumor directly in skin cancer and with

At our center, patients diagnosed with cervical cancer who are can-

different applicators in the case of breast or gynecologic cancer.

didates for eBT after EBRT are selected from among those who, at

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ET AL.

FIG. 1.

Cervical applicator.

T A B L E 1 Characteristics of electronic brachytherapy sources. 750 minutes of clinical use

Working life of eBT sources

T A B L E 3 EMBRACE protocol dosimetric requirements based on ESTRO‐ABS recommendations for CTVs and OARs in EQD2. Target

D90 HR‐CTV EQD210

D98 HR‐CTV EQD210

D98 IR‐CTV EQD210

planning aims

>90 Gy < 95 Gy

>75 Gy

>60 Gy

Deviation allowed with respect to calibration certiﬁcate

<10%

Deviation allowed with respect to ﬁrst measure

<5%

Limits for prescribed dose

>85 Gy

Maximum energy

50 kVp

OAR

Average energy

29.6 keV

Bladder D2cc EQD23

Rectum D2cc EQD23

Sigmoid D2cc EQD23

Treatment time for cervical treatment

15–25 min

Planning aims

<80 Gy

<65 Gy

<70 Gy

Limits for prescribed dose

<90 Gy

<75 Gy

T A B L E 2 Patients and treatments characteristics.

T A B L E 4 EMBRACE protocol dosimetric requirements for BT (4 fractions of 7 Gy) after 46 Gy of EBRT in EQD2, %PD and dose per BT fraction.

Patients

Age + Range (years)

59.7 (27–72)

FIGO Stage

D90 HR‐CTV

IB1

12.5% (1)

%PD

1 fraction

%PD

1 fraction

IB2

12.5% (1)

>107%

>7.5 Gy

>80%

>5.6 Gy

IIA2

25% (2)

<117%

<8.2 Gy

IIB

37.5% (3)

D98 IR‐CTV

IIIB

12.5% (1)

%PD

1 fraction

Uterine probe inclination

15° (8)

>46%

>3.2 Gy

Ovoids 3 cm

50% (4)

Ovoids 2.5 cm

25% (2)

Ovoids 2 cm

25% (2)

Bladder: D2cc ≤ 90 Gy, D0.1cc ≤ 110‐115 GyBladder: D2cc ≤ 75– 87%, D0.1 cc ≤ 107–113%Bladder: D2cc ≤ 5.3–6.1 Gy, D0.1cc ≤ 7.5–7.9 Gy

Time IMRT to eBT

10.6 (7–15) days

OTT

52.5 (49–58) days

Treatment time in tandem per fraction

14.6 (8.8–19.5) min

Treatment time in ovoids per fraction

3.5 (0.8–7.5) min

Proportions are given with number of total and median range. FIGO stage is given in percentage of the total number of patients. Time IMRT to eBT: time between the end IMRT treatment and the start of eBT. OTT, Overall treatment time.

D98 HR‐CTV

Rectum: D2cc ≤ 75 Gy, D0.1 cc ≤ 80–85 GyRectum: D2cc ≤ 51–67%, D0.1 cc ≤ 75–81%Rectum: D2cc ≤ 3.6–4.7 Gy, D0.1 cc ≤ 5.3–5.7 Gy Sigmoid: D2cc ≤ 75 Gy, D0.1 cc ≤ 80–85 GySigmoid: D2cc ≤ 60– 67%, D0.1 cc ≤ 75–81%Sigmoid: D2cc ≤ 4.2–4.7 Gy, D0.1 cc ≤ 5.3– 5.7 Gy Prescribed dose of BT treatment: 4 fractions of 7 Gy. EQD2n, Dosage equivalent to 2 Gy per session for α/β = n according to the quadratic linear model. The limit value is the result of adding EBRT + BT; HR‐CTV, High‐risk clinical target volume; IR‐CTV, Intermediate‐risk clinical target volume; %PD, Percentage of prescribed dose.

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ET AL.

F I G . 2 . Isodose lines in Axial, Coronal, and Sagittal views for eBT and Ir192. (a) Axial view: Distances to 25% of the prescribed dose: 5.1 cm (eBT) and 5.7 cm (Ir192). (b) Coronal view: Distances to 25% of the prescribed dose: 5.9 cm (eBT) cm and 6.2 cm (Ir192). (c) Sagittal view: Distances to 25% of the prescribed dose: 5.2 cm (eBT) cm and 5.7 cm (Ir192). Red line: HR‐CTV contour. Prescribed Dose: 7 Gy per fraction.

their ﬁrst evaluation for radiotherapy, are expected to have a resid-

excluding quality control time, each eBT source has a useful average

ual tumor ≤3 cm with no parametrial involvement after EBRT. They

clinical life of 750 min. If a source is not stable, it is withdrawn and

are re‐evaluated after EBRT to determine whether the diagnostic

replaced (Table 1). Each session lasted between 15 and 25 min.

parameters remain unchanged (see above).

Mean age was 59.8 yr (27–70 yr), with different tumor stages

In this study eight patients were treated using the Axxent (Xoft)

(Table 2). The eight patients received chemotherapy without surgery

device between May 2016 and June 2018 with the Axxent cervical

and adjuvant EBRT in the form of intensity modulated radiation

applicator (Modiﬁed Henschke HDR Cervix Applicator‐Fig. 1),

therapy (IMRT) with a regimen comprising 23 sessions of 2 Gy each

intrauterine probes angled at 15°, and ovoids of 2–3 cm. After

all over the pelvis, followed by eBT (28 Gy in four sessions). The

SERGIO

ET AL.

sessions were administered twice weekly (Thursday and Friday) after radiation therapy. Planning was with MRI and CT scans acquired

CT images are used to reconstruct the applicators appropriately; MRI is used to contour the target volumes and the OAR.

before the ﬁrst session. The patient was then admitted for the sec-

The high‐risk clinical target volume (HR‐CTV) and the intermedi-

ond session the following day, after a new CT check‐up. The proce-

ate‐risk clinical target volume (IR‐CTV) are contoured, and the blad-

dure is repeated the following week for the third and fourth

der,

sessions, with new MRI and CT images. OAR and target volumes are

rectum,

and

sigmoid

colon

OAR

following

the

recommendations of GEC‐ESTRO.

contoured in accordance with the EMBRACE protocol. The treat-

After the medical physicist reconstructs the applicators and pre-

ment planning system (TPS) used is Brachyvision‐Eclipse (Varian

pares the plan according to the dosimetric requirements of the

Medical System Inc., Palo Alto, CA, USA). The mean time from initia-

EMBRACE protocol10 (Tables 3 and 4), the radiation oncologist

tion of IMRT to the end of eBT was 52.5 days (49–58 days), and the

approves it, and if appropriate, the patient is treated. Subsequently,

time between the end of IMRT and the end of eBT was 10.6 days

an additional plan is drawn up for treatment with Ir192 source in

(7–15 days) (Table 2). The calculations are compared retrospectively

order to compare both plans. The processing unit deﬁned in the TPS

with those for Ir192 sources and for each of the eight patients, with

for this purpose is Gammamed Plus with GammaMed Plus HDR

two plans per patient, giving a total of 32 different plans (16 for eBT

source 0.9 mm (Varian Medical System Inc., Palo Alto, CA, USA). The calculation algorithm is TG‐43, with speciﬁc parameters for

and 16 for Ir192). Planning was performed after a CT study (3‐mm slice thickness) and T2‐weighted MRI study (5‐mm slice thickness). Both sets of

the Axxent device.29 As for HR‐CTV and IR‐CTV, the values of the dose were determined to 90% (D90) and 98% (D98). HR‐CTV values are the same in

images were registered.

T A B L E 5 Comparison of dosimetric parameters for Axxent eBx and Ir‐192 HDR. EBRT (IMRT) Dose per fraction:

2 Gy

No fractions

Total dose:

46 Gy

BT (eBx or Ir‐192) Dose per fraction:

7 Gy

No fractions

Total dose:

28 Gy Dose per fraction (Gy)

Vol HR‐CTV: 16.6cc (10.1–38.7)

Axxent‐eBx

Ir‐192

Mean (Gy)

SD (Gy)

%PD

Range (Gy)

D98

0.7

100%

6.3–7.8

D90

8.5

0.9

121%

7.6–10.0

D98

0.9

57%

3.0–5.4

D90

4.9

1.0

70%

3.7–6.5

D2cc

4.4

0.8

63%

3.9–6.1

D1cc

4.9

0.8

70%

D0.1cc

5.9

0.9

84%

Range(%PD)

Mean (Gy)

SD (Gy)

%PD

Range (Gy)

Range(%PD)

89–111%

7.1

0.8

101%

6.3–8.3

89–119%

108–142%

8.4

0.8

120%

7.6–10

108–143%

42–76%

4.1

0.8

59%

3.4–5.3

48–76%

53–93%

0.9

71%

4.1–6.4

58–91%

55–87%

4.6

0.8

66%

4.1–6.3

59–90%

4.3–6.7

61–96%

5.1

0.8

73%

4.5–6.9

64–99%

5.4–8.1

77–115%

0.9

86%

5.5–8.2

79–117%

Target HR‐CTV

IR‐CTV

Organs at risk Bladder

Rectum

Sigmoid

D2cc

2.1

0.7

30%

1.3–3.5

19–49%

2.6

0.7

37%

1.9–3.9

26–56%

D1cc

2.5

0.8

36%

1.5–3.8

21–54%

0.8

43%

2.1–4.1

30–59%

D0.1cc

3.5

1.0

50%

1.9–4.4

26–63%

3.9

1.0

56%

2.5–4.9

36–70%

D2cc

3.8

0.7

54%

3.1–5.2

44–74%

0.7

57%

3.3–5.3

47–76%

D1cc

4.4

0.9

63%

3.7–6.2

52–88%

4.6

0.9

66%

3.9–6.4

55–91%

D0.1cc

1.4

86%

4.6–8.5

65–121%

6.2

1.4

89%

4.8–8.7

69–124%

D98, D90: Dose to the 98% or 90% of the HR‐CTV or IR‐CTV volume in Gy. D2cc, D1cc, D0.1cc: Doses to the volume of 2 cc, 1 cc, or 0.1 cc in Gy and in %PD (percentage of prescribed dose). SD, standard deviation; Vol HR‐CTV, Volume of HR‐CTV, average, and range; HR‐CTV, high‐risk clinical target volume; IR‐CTV, intermediate‐risk clinical target volume.

SERGIO

ET AL.

the two treatment plans in each case, since the same normalization is applied throughout planning. We also determined V150 and V200, both of the HR‐CTV and of total tissue (sum of tumor tissue and healthy tissue), which receive 150% and 200% of the prescribed dose. As for the OAR, the parameters are the same as those recommended in the EMBRACE protocol, and they are determined for all OAR of interest in the study, namely, bladder, rectum, and sigmoid colon. The parameters compared are D2cc (maximum dose, 2 cc), D1cc, and D0.1cc; toxicity is evaluated according to the parameters of the Radiation Therapy Oncology Group (RTOG).30

3 | RESULTS Patients were followed up for a median of 13.4 months (2– 28 months). Patients planned with eBT received a lower dose in the OARs than those planned with Ir192. The differences in the energy of both irradiation methods constitute the isodose lines that lead to the dose differences in the OARs (Fig. 2). In the bladder, the average dose parameters for all the treatments compared (eBT vs Ir192) were 63% of the prescribed dose vs 66% for D2cc, 70% vs 73% for D1cc, and 84% vs 86% for D0.1cc. The differences were more remarkable in the rectum (30% vs 37% for D2cc, 32.9% vs 36% for D1cc, and 50% vs 56% for D0.1cc) and in the sigmoid colon (D2cc, 54% vs 57%; D1cc, 63% vs 66%; and D0.1cc, 86% vs 89%) with an average HR‐CTV volume of 16.6 cc (Table 5). By applying these data and the t test, we see that the difference is signiﬁcant for cases of D2cc and D1cc of the rectum (P < 0.05) (Fig. 3).

FIG. 3.

Box and Whisker Plot: D1cc and D2cc of rectum.

Although D90 and D98 for HR‐CTV were the values used to standardize the plans, we did observe a small difference in the cov-

4 | DISCUSSION

erage of IR‐CTV—57% of the prescribed dose for eBT vs 59% for HDR‐BT—although both were above the objective set by EMBRACE

We obtained acceptable results after the ﬁrst 28 months (mean fol-

(>46%, Tables 3 and 4). In addition to the differences in the IR‐CTV

low‐up, 13.4; range, 2–28 months) using the Axxent eBT device for

coverage percentage, it is useful to observe the differences in dose

treatment of cervical cancer with EBRT and chemotherapy, thus indi-

equivalent to 2 Gy (EQD2), taking into account the contribution of

cating that this option is a good alternative in BT.

EBRT and the part of eBT or Ir192 in each case (Table 6). V150 and

The dose prescribed in each eBT treatment was administered

V200 for HR‐CTV were greater for the cases calculated with Axxent

without taking into account the fact that the mean beam energy

than for those calculated with Ir192, although the difference was

was much lower than in Ir192 (26 keV vs 355 keV) and, therefore,

very small owing to the volume of the tumors treated. In addition,

without taking into account the differences in the relative radiobio-

even though tissue volumes that received 150% and 200% of the

logical effectiveness (RBE) expected for low‐energy radiation.31,32

dose prescribed were included (Table 7), given the low energy of

One clinical study showed that reducing the dose prescribed for

eBT compared to Ir192 also observed an increase in the dose in the

treatment of nodular and superﬁcial basal cell carcinoma using eBT

vaginal wall in contact with the surface of the ovoids of 13% on

and based on a different RBE reduced control of the tumor from

average, although no cases of acute mucositis were observed. Of

95% to 90%, thus demonstrating better control for the standard pre-

the eight patients treated at our center, only one had grade 2 acute

scription.33

toxicity (RTOG) (Table 8). One month after treatment, vaginal toxic-

In our study, we did not modify treatment owing to differences

ity had disappeared. Rectal toxicity and urinal toxicity were minimal

in RBE with respect to Ir192 because of the good results achieved

(Table 8). To date, no patients have experienced recurrence of their

with treatment administered to the endometrium26 and the contra-

disease.

dictory results reported in several published studies. Modiﬁcation of

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ET AL.

T A B L E 6 EQD2 for Axxent and Ir‐192. BT and EBRT (IMRT) obtained adding doses according to linear quadratic model. AXXENT

Ir‐192

EQD2(Gy)

BT + IMRT

%PD

%SD

BT + IMRT

%PD

Prescription dose.

39.7

85.7

100%

D98

39.7

85.7

100%

D90

52.4

98.4

121%

D98

18.7

68.7

57%

D90

24.3

70.3

D2cc

26.6

D1cc

30.0

D0.1cc

%SD

39.7

85.7

100%

40.5

86.5

101%

14%

13%

51.5

97.5

120%

17%

13%

19.3

65.3

59%

70%

14%

25.0

71.0

71%

10%

72.6

64%

28.0

74.0

66%

76.0

69%

10%

33.0

79.0

73%

10%

41.4

87.4

84%

12%

43.2

89.2

86%

12%

6.1

52.1

23%

11.6

57.6

37%

α/β = 10Gy Target HR‐CTV

IR‐CTV

α/β = 3Gy Organs at risk Bladder

Rectum

D2cc D1cc

Sigmoid

9.0

55.0

31%

14.4

60.4

43%

D0.1cc

14.6

60.6

43%

21.5

67.5

56%

D2cc

19.8

65.8

53%

22.4

68.4

57%

D1cc

23.8

69.8

59%

28.0

74.0

66%

D0.1cc

38.1

84.1

79%

12%

45.6

91.6

89%

13%

α/β = 10 Gy for target and 3 Gy for OAR according to EMBRACE. EQD2, Equivalent dose to 2 Gy per fraction in EBRT; %PD, Percentage of Prescribed Dose; %SD, Standard Deviation of %PD; IMRT, intensity modulated radiation therapy; BT, brachytherapy; HR‐CTV, high‐risk clinical target volume; IR‐CTV, intermediate‐risk clinical target volume.

the prescribed dose continues to be controversial in low‐energy cases.34

The sample of patients selected only included tumors with no parametrial extension so as not to require insertion of interstitial

We can achieve the same coverage of the cervix as during plan-

needles during treatment. Since this modality is not yet available in

ning when Ir192 is used in all of the cases presented and the dose

the Axxent model, patients requiring interstitial needles were

to OAR can be reduced, even though V150 and V200 of the plan-

referred to another center.

ning target volume increase very slightly. This could have led to an

Results for the healthy tissue volume that received high doses

increase in the number of cases of acute mucositis in the study pop-

are slightly higher in the case of eBT, where the tissue irradiated

ulation; however, the toxicity results, together with the reduced

with 150% of the prescribed dose corresponds to 132% of the HR‐

dose administered to OAR, lead us to conclude that eBT is a good

CTV volume, compared with 124% in cases planned with Ir192. For

alternative to treatment with Ir192 in cases of cervical cancer.

tissue irradiated with 200%, these values are 67% vs 63% (Table 7).

In their study of 10 patients, Mobit et al.24 evaluated dosimetric

The differences do not represent an excessive volume in each indi-

differences and similarities between treatment plans generated with

vidual case and, more importantly, do not correspond to an increase

the eBT source of Axxent and Ir92 for tandem applicators and

in the number of cases of mucositis.

ovoids. The authors reported a difference between the two approaches (eBT vs Ir192) for D2cc in the bladder (43.9% vs 58.7%

The dose in OAR is slightly lower in the case of eBT, and cases of toxicity associated with doses in OAR are minimal (Table 8).

of the prescribed dose), in the rectum (54.9% vs 60.9%), and in the

We did not encounter problems of overdosing in bone, because

sigmoid colon (44.1% vs 56%). However, in this case, patients were

we used low energies.20 However, overdosing should be avoided in

treated with Ir192, and the eBT plans were calculated prospectively.

order to reduce the number of fractions and thus prevent this prob-

As for the calculation method used, it is recommended to consider tissue composition and to perform the calculations based on 35

lem from arising. We believe that the scheme proposed by EMBRACE is adequate in this respect.

Our calculations were based on TG‐43, which

Both dosimetry requirements of the EMBRACE protocol were

was modiﬁed for eBT,29,36 with no correction for heterogeneity,

fulﬁlled for both types of treatment, although D0.1cc in the sigmoid

since this was the algorithm used in our TPS and in many other hos-

colon would be above tolerance for Ir192. However, as stated

pitals, for which our results will prove useful.

above, this does not lead to more cases of mucositis. These results,

Monte Carlo models.

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ET AL.

T A B L E 7 V150 and V200 for HR‐CTV and for soft tissue. Axxent‐eBx (%HR‐CTV Volume) Mean (%)

Ir‐192 (%HR‐CTV Volume)

SD (%)

Range (%)

Mean (%)

SD (%)

Range (%)

V150

73%

62–90%

73%

10%

57–91%

V200

51%

11%

36–71%

51%

12%

26–72%

Soft tissue 150%

132%

42%

95–246%

124%

26%

96–169%

Soft tissue 200%

67%

29%

34–153%

63%

12%

49–87%

Mean, standard deviation and range of V150, V200: Volume of HR‐CTV and Soft tissue with 150% and 200% of the prescribed dose in percentage of the HR‐CTV volume. HR‐CTV, high‐risk clinical target volume.

T A B L E 8 Acute and 1 month toxicity of patients. Grade 0

Grade 1

The eBT device is a useful addition in centers with an HDR Grade 2

device. Its mobility and versatility mean that it can be used as a %

radiotherapy in breast cancer, in skin cancer, and in postoperative

N=8 Acute vaginal mucositis

complementary facility to treat cervical cancer and for intraoperative

50%

37.5%

12.5%

treatment of endometrial cancer.26 based HDR devices, eBT could be a good alternative for patients who

In areas with a high incidence of cervical cancer and few Ir192‐

Acute rectal toxicity

87.5%

12.5%

Acute urinary toxicity

75%

25%

live far from a major hospital. In addition, given that treatment does not require a bunker for administration and the device is easily transported, this option is much more economically viable than others.

Toxicity (1 month) Vaginal toxicity

87.5%

12.5%

Rectal toxicity

100%

Urinary toxicity

100%

Grade 0,1,2: Int J Radiat Oncol Biol Phys. 1995 Mar 30;31(5):1341‐6. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). N, number of patients.

together with the absence of relapses to date, allow us to be optimistic with respect to determining a good eBT‐based alternative to this treatment approach, although longer follow‐up is necessary

ACKNOWLEDGMENTS We thank all the colleagues in the physics and radiation protection service, as well as in radiation oncology, for their support in the preparation of this work and their great daily work, as well as the work of the editor‐in‐chief of the journal and the reviewers who have participated in the correction of the article.

CONFLICT OF INTEREST No conﬂict of interest.

before we can confirm our findings. In addition, we must await the findings of other groups.

5 | CONCLUSION Treatment with eBT represents a huge advantage in centers with no HDR device, although more clinical results, results for local control, and results based on a longer follow‐up are necessary. Our data are based on only eight patients, thus reducing the importance of the conclusion. Nevertheless, they are a promising beginning for treatment of cervical cancer with electronic brachytherapy. The doses in the OARs are lower with eBT, although the difference is not signiﬁcant in the bladder or sigmoid colon. They are signiﬁcant, however, for the D2cc and D1cc parameters in the rectum. The broad experience accumulated over the years with Ir192 treatments makes it the reference for cervical cancer, eBT could be an alternative in cases where treatment with Ir 192 is not available, as long as the results obtained continue to be satisfactory.

REFERENCES 1. World Health Organization. A guide to essential practice. Comprehensive cervical cancer control: a guide to essential practice – 2nd ed. WHO Library Cataloguing-in-Publication Data. World Health Organization 2014. ISBN 978 92 4 154895 3. 2. National Comprehensive Cancer Network Inc. NCCN Guidelines. Version 2 2015. Cervical cancer. 2018. 3. Gerbaulet A, Pötter R, Mazeron JJ, Meertens H, VanLimbergen EThe GEC‐ESTRO handbook of Brachytherapy. ESTRO, Brussels. 2002: 365–403. 4. Rovirosa A, Samper P, Villafranca E. Braquiterapia 3D guiada por la imagen. SEOR (Sociedad Española de Oncología Radioterápica). Edition 2017. SL Edikamed, Barcelona, Spain. 5. Tanderup K, Fokdal LU, Sturdza A, et al. Effect of tumor dose, volume and overall treatment time on local control after radiochemotherapy including MRI guided brachytherapy of locally advanced cervical cancer. Radiother Oncol. 2016;120:441–446. 6. Tanderup K, Eifel PJ, Yashar CM, Pötter R, Grigsby PW. Curative radiation therapy for locally advanced cervical cancer: brachytherapy is NOT optional. Int J Radiat Oncol Biol Phys. 2014;88:537–539.

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7. Nag S, Chao C, Erickson B, et al. The American Brachytherapy Society recommendations for low‐dose‐rate brachytherapy for carcinoma of the cervix. Int J Radiat Oncol Biol Phys. 2002;52:33–48. 8. Viswanathan A, Beriwal S, De Los Santos JF, et al. American Brachytherapy Society consensus guidelines for locally advanced carcinoma of the cervix. Part II: High‐dose‐rate brachytherapy. Brachytherapy. 2012;11:47–52. 9. Pötter R, Georg P, Dimopoulos JCA, et al. Clinical outcome of protocol based image (MRI) guided adaptive brachytherapy combined with 3D conformal radiotherapy with or without chemotherapy in patients with locally advanced cervical cancer. Radiother Oncol. 2011;100:116–123. 10. Dimopoulos JCA, Petrow P, Tanderup K, et al. Recommendations from Gynaecological (GYN) GEC‐ESTRO Working Group (IV): basic principles and parameters for MR imaging within the frame of image based adaptive cervix cancer brachytherapy. Radiother Oncol. 2012;103:113–122. 11. Pötter R, Tanderup K, Kirisits C et al., The EMBRACE II study: The outcome and prospect of two decades of evolution within the GECESTRO GYN working group and the EMBRACE studies. Clinical and Translational Radiation Oncology. 2018;9:48–60. 12. Sturdza A, Pötter R, Fokdal LU, et al. Image guided brachytherapy in locally advanced cervical cancer: Improved pelvic control and survival in RetroEMBRACE, a multicenter cohort study. Radiother Oncol. 2016;120:428–433. 13. Dickler A, Dowlatshahi K. Xoft Axxent electronic brachytherapy. Expert Rev Med Devices. 2009;6:27–31. 14. Vaidya JS, Baum M, Tobias JS, Morgan S, De Souza D. The novel technique of delivering targeted intraoperative radiotherapy‐ target_for early breast cancer. Eur J Surg Oncol. 2002;28:447– 454. 15. Dinsmore M, Harte KJ, Sliski AP, et al. A new miniature x‐ray source for interstitial radiosurgery: Device description. Med Phys. 1996;23:45–52. 16. Dickler A, Ivanov O, Francescatti D. Intraoperative radiation therapy in the treatment of early‐stage breast cancer utilizing Xoft Axxent electronic brachytherapy. World J Surg Oncol. 2009;7:24–26. 17. Kasper ME, Chaudhary AA. Novel treatment options for nonmelanoma skin cancer: focus on electronic brachytherapy.Med. Devices. 2015;8:493–502. 18. Richardson S, García‐Ramírez J, Lu W, et al. Design and dosimetric characteristics of a new endocavitary contact radiotherapy system using an electronic brachytherapy source. Med Phys. 2012;39:6838– 6846. 19. Saﬁgholi H, Faghihi R, Jashni SK, Meigooni AS. Characteristics of miniature electronic brachytherapy x‐ray sources based on TG‐43U1 formalism using Monte Carlo simulation techniques. Med Phys. 2012;39:1971–1979. 20. Saﬁgholi H, Song WY, Meigooni AS. Optimum radiation source for radiation therapy of skin cancer. J Appl Clin Med Phys. 2015;16:219– 227. 21. Hellebust TP, Kirisits C, Berger D, et al. Recommendations from Gynaecological (GYN) GEC‐ESTRO Working Group: considerations and pitfalls in commissioning and applicator reconstruction in 3D

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Use of electronic brachytherapy to deliver postsurgical adjuvant radiation therapy for endometrial cancer: a retrospective multicenter study This article was published in the following Dove Press journal: OncoTargets and Therapy 17 September 2010 Number of times this article has been viewed

William c Dooley 1 John P Thropay 2 gary J schreiber 3 Mohamed Y Puthawala 4 steven c Lane 5 James c Wurzer 6 charles e stewart 7 gordon L grado 8 harish g Ahuja 9 gary M Proulx 10 University of Oklahoma health sciences center, Oklahoma city, OK; 2Beverly Oncology and imaging center, Montebello, cA; 3swedish covenant Medical center, chicago, iL; 4 rhode island hospital, Providence, ri; 5signature healthcare Brockton hospital, Brockton, MA; 6Atlanticare regional Medical center, egg harbor Township, nJ; 7st Francis Medical center, Tulsa, OK; 8southwest Oncology centers, scottsdale, AZ; 9 Aspirus regional Medical center, Wausau, Wi; 10exeter hospital, exeter, nh, UsA 1

correspondence: William c Dooley The University Oklahoma health sciences center, Oklahoma city, OK, 73104, UsA Tel +1 405 271 7867 Fax +1 405 271 4443 email william-dooley@ouhsc.edu

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Dovepress DOI: 10.2147/OTT.S13593

Background: This retrospective, multicenter study evaluated the feasibility and safety of high-dose rate electronic brachytherapy (EBT) as a postsurgical adjuvant radiation therapy for endometrial cancer. Methods: Medical records were reviewed from 41 patients (age 40–89 years) with endometrial cancer (Federation of International Gynecology and Obstetrics stages IA–IIIC) treated at nine centers between April 2008 and October 2009. Treatment included intracavitary vaginal EBT alone (n = l6) at doses of 18.0–24.0 Gy in 3–4 fractions and EBT in combination with external beam radiation therapy (EBRT, n = 25) at a total radiation dose range of 40.0–80.4 Gy. Doses were prescribed to a depth of 5 mm from the applicator surface and to the upper third (n = 15) and the upper half (n = 26) of the vagina. Results: Median follow-up was 3.8 (range 0.5–12.0) months. All 41 patients received the intended dose of radiation as prescribed. Adverse events occurred in 13 of 41 patients and were mild to moderate (Grade 1–2), consisting primarily of vaginal mucositis, rectal mucosal irritation and discomfort, and temporary dysuria and diarrhea. There were no Grade 3 adverse events in the EBT-only treatment group. One patient, who was being treated with the combination of EBT and EBRT for recurrent endometrial cancer, had a Grade 3 adverse event. No recurrences have been reported to date. Conclusion: Electronic brachytherapy provides a feasible treatment option for postoperative adjuvant vaginal brachytherapy as sole radiation therapy and in combination with EBRT for primary endometrial cancer. Early and late toxicities were mild to moderate. Keywords: endometrial cancer, electronic brachytherapy, radiation therapy

Introduction Endometrial cancer is the most common gynecologic cancer and the fourth most common type of cancer in women in the Western world.1 An estimated 42,160 women were diagnosed with endometrial cancer in 2009 in the US,1 with a majority of cases having early-stage disease.2 Early-stage endometrial cancer has a good prognosis, and five-year survival rates have recently increased to 80–90% in women who were treated with total abdominal hysterectomy, bilateral salpingo-oophorectomy (TAH-BSO), and adjuvant radiation therapy for Stage I disease. In a survey of over 21,000 patients with Stage I endometrial cancer, adjuvant radiation therapy was found to be significantly associated with improved survival.3 However, external beam radiation therapy (EBRT) in early-stage endometrial cancer has become less common due to the time and

OncoTargets and Therapy 2010:3 197–203 197 © 2010 Dooley et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.

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morbidity associated with this form of low-dose rate radiation. High-dose rate (HDR) intracavitary brachytherapy, which provides dose rates greater than 100 centigray per hour, can be completed in a shorter time on an outpatient basis, with decreased radiation exposure to nontarget organs and tissue. With the increased trend to stage endometrial cancer patients surgically, vaginal brachytherapy as sole radiation therapy or combined with other modalities has become an essential part of adjuvant treatment for endometrial cancer. Numerous studies of the use of vaginal brachytherapy have demonstrated good control rates with minimal morbidity.4â&#x20AC;&#x201C;13 HDR vaginal brachytherapy has typically relied on an 192 iridium source. However, this form of radiation requires an HDR afterloader unit and a shielded radiation vault, which is not financially feasible in smaller institutions or clinics and can present scheduling challenges at higher-volume centers. Electronic brachytherapy (EBT) utilizes a miniaturized 50 kilovoltage (kV) X-ray source that does not require a vault or an HDR afterloader unit. Minimal shielding, in the form of a rolling shield for staff and a half-apron over the lower abdomen of the patient, allows the therapist to be present in the treatment room, which significantly increases patient comfort. The device, once state registration, health physics, and regulatory requirements are met, can be moved from one procedure room to the next. EBT does not require storage and handling of isotopes.14,15 The AxxentÂŽ EBT system (Xoft, Inc, Sunnyvale, CA) has been utilized in the US for the treatment of breast cancer since 2005.15 In 2008, the US Food and Drug Administration provided clearance for the use of this EBT system with specifically designed applicators for the treatment of endometrial cancer. The objective of this retrospective multicenter study was to assess treatment feasibility and acute adverse events as documented in the records of patients treated with EBT as an adjuvant therapy for endometrial cancer.

Methods Medical records were reviewed from 41 patients at nine institutions (Beverly Oncology and Imaging Center, Montebello, CA; Swedish Covenant Medical Center, Chicago, IL; Rhode Island Hospital, Providence, RI; Signature Healthcare Brockton Hospital, Brockton, MA; AtlantiCare Regional Medical Center, Egg Harbor Township, NJ; St Francis Medical Center, Tulsa, OK; Southwest Oncology Centers, Scottsdale, AZ; Aspirus Regional Medical Center, Wausau, WI; and Exeter Hospital, Exeter, NH. The protocol was approved by the institutional review boards at the nine participating centers.

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Patients The medical records were reviewed for 41 patients with endometrial cancer who were treated with vaginal EBT between April 2008 and October 2009; follow-up visits took place between November 2008 and December 2009. Records of patients treated with EBT alone or EBT in combination with EBRT were included. Records of patients currently enrolled in any other EBT study were excluded. No other exclusion criteria were established. The staging of endometrial cancer for each patient was done according to the Federation of International Gynecology and Obstetrics (FIGO) staging criteria (1988). The histopathologic grade was defined as G1 (well differentiated), G2 (moderately differentiated), and G3 (poorly differentiated).

Data collection The data were collected retrospectively, with the centers sequentially numbered, and with patients sequentially numbered using three-digit numbers within each center. Adverse events were collected using Common Terminology Criteria for Adverse Events version 3.0. Adverse events were rated based on the Common Terminology Criteria for Adverse Events version 3, and included grades 1 = mild, 2 = moderate, 3 = severe/undesirable, 4 = life-threatening/ disabling, 5 = death related to adverse event.

Materials Vaginal EBT was delivered using the Axxent EBT system. The EBT system consists of the X-ray source, the vaginal cylinder applicator, and the controller. The X-ray source comprises a miniaturized 50 kV X-ray tube in a multilumen catheter that allows cooling fluid to circulate over the tube. The vaginal cylinder applicators were designed to provide transmission characteristics specifically for the low energy X-rays emitted by the electronic X-ray source. The cylinders are composed of common medical-grade polymers, and have a 94% Âą 5% X-ray transmission with respect to water. The X-ray tube is approximately 2.25 mm in diameter and 15 mm long, attached to a high-voltage cable, and encapsulated within an electrical ground. The controller provides power to the X-ray source and allows the X-ray source to be translated within the applicator. The translation or pullback movement of the X-ray source within the applicator is designed to provide a desired dose of radiation in the tissue surrounding the cylinder.

Treatment The prescription dose and brachytherapy treatment plans were prepared individually for each patient, typically based

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on CT scans. BrachyVision™ treatment planning software (Varian Medical Systems, Palo Alto, CA) or Plato™ treatment planning software (Nucletron, Columbia, MD) were used at most centers. A vaginal cylinder applicator was selected for each patient from the four sizes available (20 mm, 25 mm, 30 mm, 35 mm). The applicator was inserted just prior to treatment and removed following treatment on each treatment visit. Follow-up visits occurred periodically based on the standard practice at each study site.

statistics Case report forms were submitted to a data coordinating center where data were entered into a Access® (Microsoft, Redmond, WA) database by an independent data manager. Analysis of the data was performed using SAS statistical analysis software (Version 9.1.3; Sas Institute, Cary, NC). The number of observations (n) and proportion are reported for both the treatment success and acute outcome endpoints.

Results Patients Records from 41 female patients were reviewed, most of whom (93%) were aged 50 years or older, with 31% being aged 70 years or older. Patient characteristics are listed in Table 1. A majority (68%) had early-stage endometrial cancer (stages IA–IIA) according to the FIGO gynecologic staging system (1988). The remaining patients had cancer stages IIB–IIIC, including one patient with recurrent cancer. The median follow-up was 3.8 (range 0.5–12.0) months.

Treatment

Patients with primary endometrial cancer (n = 40) and recurrent endometrial cancer (n = 1) were treated with vaginal EBT alone (n = 16) or EBT in combination with EBRT (n = 25). All 41 patients received the intended dose of radiation as prescribed. When EBT was used alone, the mean prescription dose was 21.3 Gy (standard deviation, SD = 1.2 Gy) and was independent of FIGO stage as shown in Table 2. When EBT was combined with EBRT (n = 24), excluding the patient treated for recurrence, the total radiation dose of the two therapies combined ranged from 40 Gy to 70.4 Gy with a mean value of 60.7 Gy (SD = 5.8 Gy). Again, the total dose was independent of FIGO stage for these patients as indicated in Table 3. EBT dose was prescribed to a depth of 0.5 cm from the surface of the applicator, and the upper third to the upper half of the vagina was treated. The most commonly used vaginal cylinder diameter was 30 mm from a range of 20 mm to 35 mm (Table 4).

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Table 1 Patient characteristics n (%) Patients (n)

41 (100%)

Age range (years) 40–49 50–59 60–69 70–79 80–89

3 (7.3%) 12 (29.3%) 13 (31.7%) 10 (24.4%) 3 (7.3%)

FigO cancer stagea IAG unspecified iBg1 iBg2 iBg3 IBG unspecified icg1 icg2 icg3 ICG unspecified iiAg1 iiAg2 iiAg3 iiBg1 iiBg2 iiBg3 iiiAg3 IIIAG unspecified iiicg2 iiicg3b Unspecified (high-grade)c

1 (2.4%) 3 (7.3% ) 4 (9.8%) 8 (19.5%) 1 (2.4%) 2 (4.9%) 3 (7.3%) 1 (2.4%) 2 (4.9%) 1 (2.4%) 1 (2.4%) 1 (2.4%) 1 (2.4%) 2 (4.9%) 2 (4.9%) 2 (4.9%) 1 (2.4%) 2 (4.9%) 3 (7.3%) 1 (2.4%)d

grading g1 g2 g3 G unspecified

7 (17.1%) 12 (29.3%) 16 (39%) 6 (14.6%)

Time (days) from hysterectomy to first EBTe Mean ± sD Median range

96.2 ± 60.1 80.0 20–255

Notes: aFederation international gynecology and Obstetrics (FigO) gynecologic cancer staging system; bone patient in this group was treated for recurrent endometrial cancer; cthe “unspecified (high-grade)” cancer was a primary endometrial cancer; ddue to rounding, numbers do not total exactly 100%; eincludes only patients with primary endometrial cancer in this study. Abbreviations: eBT, electronic brachytherapy, sD, standard deviation.

Adverse events Of 41 patients, 13 (31.7%) had adverse events. Adverse events were mild to moderate (Grade 1–2) in 12 of the 13 patients, and there was one occurrence of a Grade 3 adverse event in one patient. Adverse events consisted primarily of temporary diarrhea and dysuria, vaginal mucositis, and rectal mucosal irritation and discomfort. The majority of patients (68.3%) experienced no gastrointestinal or genitourinary side effects. All adverse events are listed in Table 5, and the severity grade is shown if it was recorded in the medical record.

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Table 2 summary of prescription doses for patients receiving electronic brachytherapy only categorized by FigO stage FIGO stage

Patients (n)

EBT dose (Gy)

Fractions (n)

Mean total dose (Gy)

iA iB ic iiA iiB iiiA iiic Unknown Total

– 9 4 2 – 1 – – 16

– 18–24 21–22 21 – 22 – – –

– 3,4 3,4 3 – 4 – – –

– 21.3 21.3 21 – 22 – – 21.3 ± 1.2

Abbreviations: gy, gray; eBT, electronic brachytherapy; FigO, Federation international gynecology and Obstetrics.

Of the 16 patients treated with EBT alone 12 (75.0%) were followed for more than three months and six (37.5%) for more than six months. There were no early adverse events occurring in the first three months post-treatment in these patients. Late adverse events first reported at least three months after the last EBT fraction included four adverse events in three patients. One patient with blood tinged stool (day 119) and rectal bleeding (day 210) was diagnosed with a superficial rectal ulcer with Grade 2 toxicity during colonoscopy; the last follow-up visit (day 328) indicated that the events were less frequent with no alteration of gastrointestinal function. One patient (day 125) had anal discomfort, which resolved completely, and discomfort with intercourse, which did not require intervention. One patient had Grade 1 vaginal mucositis at day 115, and subsequent follow-up has not yet occurred. The single recorded Grade 3 adverse event in the study was vaginal mucosa toxicity, with chronic moist

desquamation recorded in the medical record at day 79 following the last brachytherapy fraction. No further mention of this finding was found in this patient’s medical record at the next follow-up visit (day 128). At that point, the record did show vaginal discomfort, irritation, and occasional serosanguinous discharge following the use of a dilator. This patient was the one patient in the study with recurrent endometrial cancer. The primary cancer was diagnosed in mid-2005 with poorly differentiated Stage III endometrial carcinoma and treated with TAH-BSO, segmental colonic resection, and six cycles of chemotherapy (carboplatin and paclitaxel). The cancer recurred with distant metastases and friable exophytic vaginal lesions from the previously diagnosed endometrial cancer. She received an additional six cycles of chemotherapy (carboplatin and gemcitabine) prior to the study treatment, which was a combined radiation treatment with 55.4 Gy EBRT and 25 Gy EBT, administered in five fractions using a 30 mm applicator.

Discussion This retrospective multicenter study evaluated treatment outcomes in patients treated with vaginal EBT as postsurgical adjuvant therapy for endometrial cancer. The study included patients with stages IA–IIIC endometrial cancer, according to the FIGO gynecologic staging system, and included one patient with recurrent Stage IIIC endometrial cancer. As a retrospective study, there is greater variation in the treatment protocols between patients than would have been treated in a prospective study with specific patient selection criteria and a treatment protocol. In this study, the prescribed dose range of vaginal EBT ranged from 8.0 to 30.0 Gy, and was successfully delivered as prescribed in all 41 patients. The treated area of

Table 3 summary of prescription doses for patients receiving electronic brachytherapy plus external beam radiation therapy categorized by FigO stage FIGO stage

Patients (n = 24)

EBT dose (Gy)

Fractions (n)

EBRT dose (Gy)

Combined dose range (Gy)

Mean combined dose (Gy)

iA iB ic iiA iiB iiiA iiic Unknown (high-grade) Mean ± sDa recurrence iiic

1 7 4 1 5 1 4 1

20 12–21 10–18 15 12–21 20 8–18 12

4 3,4 2,3,4 3 3 5 2,3 2

50.4 20–50.4 45–59.4 45 45–46.8 45 41.4–50.4 44

70.4 40–66 61–69.4 60 57–66 65 57–60 56

70.4 58.5 64.1 60.0 60.7 65.0 58.7 56

15.3 ± 3.7 25

45.4 ± 6.4 55.4

80.4

60.7 ± 5.8 80.4

Notes: aThe mean dose and standard deviation calculations do not include the patient with recurrent cancer. Abbreviations: gy, gray; eBrT, external beam radiation therapy; eBT, electronic brachytherapy; sD, standard deviation; FigO, Federation international gynecology and Obstetrics.

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Table 4 electronic brachytherapy treatment summary Treated area

n (%)

Upper half Upper third

26 (63) 15 (37)

Applicator size (diameter) 20 mm 25 mm 30 mm 35 mm

6 (14) 8 (20) 24 (59) 3 (7)

the upper third to upper half of the vagina, treatment depth, and selected cylinder diameters are consistent with reported practice patterns.16 Treatment times were not collected in this study, but would be expected to be consistent with the mean treatment time of 4.9 minutes reported by Dickler et al in a prospective study of 15 patients with endometrial cancer treated with mean EBT doses of 20.2 Gy, which is comparable with our mean dose of 20.0 Gy.15 No recurrences have been reported to date in these patients; however, the duration of follow-up is less than one year in nearly all patients. Numerous studies of the use of vaginal brachytherapy have demonstrated good control rates with minimal morbidity.4â&#x20AC;&#x201C;13 Recently, a large multicenter

study showed that vaginal brachytherapy treatment alone compared with EBRT provides a better quality of life over EBRT and should be the preferred treatment from a quality of life perspective, when appropriate, as the sole treatment for endometrial cancer.17 In this study, the majority of patients (28/41) had no adverse events, and 12 patients, who were treated for primary endometrial cancer, had only low-grade adverse events (Grade 1 or 2) following treatment. These results are consistent with those reported by Dickler et al in which 15 patients were treated with EBT alone or in combination with EBRT for endometrial cancer.18 In the present study, one patient, who was treated for a recurrence in the combined radiation group, exhibited a Grade 3 adverse event. Adverse events were numerically more common in the combined radiation group (36.0%) compared with the EBT alone group (18.8%); however, the small sample size does not warrant statistical testing. Interestingly, the EBT alone group had no acute adverse events during the first three months following the last fraction. The four events that occurred in this group were first recorded at 3.8 months post-treatment or later (Table 5). In contrast, 16 of 20 events that occurred

Table 5 Adverse events by patient following treatment with electronic brachytherapy alone or in combination with external beam radiation therapy as recorded at follow-up visits Patient number

AEs for patients treated with EBT and EBRT

Days post EBT (n)

CTC Gradea

1-1 1-2 2-1 3-1 3-2 4-1

Diarrhea Diarrhea Diarrhea, fatigue erythema at introitus Diarrhea Dysuria, abdominal discomfort hemorrhoid, abdominal discomfort Dysuria related to external beam therapy Fungal skin rash related to external beam therapy Burning/flushing sensation at tumor site related to external beam Diarrhea related to external beam therapy Dysuria Diverticulosis, hepatomegaly related to eBT renal stone (small right) Dysuria (end micturition) Bladder spasms, occasional chronic moist desquamation of vaginal mucosa Vaginal discomfort/irritation serosanguinous discharge with use of dilator (occasional) Urgency (occasional)

5 10 43 14 36 2 99 14 14 13 13, 111 13 111 111 38, 79 38, 79 79 38, 128 128 85

1 1 1, 2 1 1 1 2, 1 2 2 2 1, 2 2 1, 1 nA nA nA 3 nA nA nA

119 210, 266, 328 125 115

nA 2 nA 1

4-2

4-3

4-4

4-5

Aes for patients treated with eBT only 5-1 Blood-tinged mucous stool Superficial rectal ulcer with bleeding 6-1 Anal discomfort, discomfort with intercourse 7-1 Vaginal mucositis

Note: aThe Ae common Terminology criteria (cTc) grade is shown if provided in the patient record. Abbreviations: Ae, adverse event; eBT, electronic brachytherapy; eBrT, external beam radiation therapy; nA, not available.

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in the combined radiation group were recorded in the first three months following the last radiation treatment. The one patient with a Grade 3 adverse event (moist desquamation of vaginal mucosa) was treated for recurrent disease in the form of exophytic lesions in the vagina. She had received chemotherapy (two courses of six cycles each) following TAH-BSO for primary endometrial cancer, and subsequently was found to have exophytic lesions in the vagina and left lower pelvis recurrence in October 2008. She was then treated with a high total dose of 80.4 Gy with combined radiation therapy, of which the vaginal brachytherapy dose consisted of five fractions of 5 Gy each. Two factors may have contributed to the Grade 3 adverse event. First, the 12 cycles of chemotherapy might have lowered the tissue tolerance of the vaginal mucosa, leaving the tissue more susceptible to radiation effects. Second, in standard vaginal brachytherapy, occult cells are treated at a 5 mm depth and the normally intact superficial mucosa must tolerate the surface dose of vaginal brachytherapy. With the exophytic tumor lesions, the vaginal surface was damaged and not continuously intact while receiving the surface dose equivalent of the 5 Gy prescribed dose to 5 mm depth. The adverse event resolved completely; however, a combination of prior chemotherapy and superficial lesions at the contact points may predispose such patients to a greater risk of higher-grade adverse events. Dickler et al compared the dosimetry of an EBT source with that of a 192iridium source in patients treated for endometrial cancer. The results showed a higher surface dose but generally decreased exposure to nearby tissues with the EBT source.15 Dosimetric results from the EBT source may offer certain advantages and disadvantages that must be carefully weighed against those of the 192iridium source for each patient. A retrospective study cannot provide a perspective on patient selection for the study intervention because patients who did not receive the treatment are by definition not part of the study. This study is also somewhat limited by the inconsistencies inherent in a multicenter study because treatment planning, delivery, and standards of care vary from site to site. The benefits of a retrospective, multicenter study lie in providing an observation of treatment of a broad patient population in a real world setting.

Conclusion This retrospective multicenter study showed that EBT with vaginal cylinders is feasible and well tolerated as a postsurgical adjuvant radiation therapy for primary endometrial cancer. Additional studies are warranted to assess late toxicity and local control further.

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Acknowledgment The authors wish to thank all site investigators and research staff who supported this study. The authors acknowledge Heike Hausen MD for assistance with medical writing.

Disclosure GG has received honoraria within the past two years for speaking at radiation oncology conferences on his experience using electronic brachytherapy as an adjuvant treatment for cancer. Xoft Inc. funded the retrospective data collection study. KW provided statistics support, and Xoft Inc. compensated her time. Xoft Inc. provided funding for this study.

References

1. Endometrial cancer. National Cancer Institute. Available from: http:// www.cancer.gov/cancertopics/types/endometrial. Accessed 2010 Jun 30. 2. Lu KH. Management of early-stage endometrial cancer. Semin Oncol. 2009;36:137–144. 3. Lee CM, Szabo A, Shrieve DC, Macdonald OK, Gaffney DK. Frequency and effect of adjuvant radiation therapy among women with stage I endometrial adenocarcinoma. JAMA. 2009;295:389–397. 4. Chadha M, Nanavati PJ, Liu P, Fanning J, Jacobs A. Patterns of failure in endometrial carcinoma stage IB grade 3 and IC patients treated with postoperative vaginal vault brachytherapy. Gynecol Oncol. 1999;75: 103–107. 5. Pearcy R, Petereit D. Post-operative high dose rate brachytherapy in patients with low to intermediate risk endometrial cancer. Radiother Oncol. 2000;56:17–22. 6. Anderson JM, Stea B, Hallum AV, Rogoff E, Childers J. High dose rate postoperative vaginal cuff irradiation alone for stage IB and IC endometrial cancer. Int J Radiat Oncol Biol Phys. 2000;46:417–425. 7. Eltabbakh GH, Piver MS, Hempling RE, Shin KH. Excellent long-term survival and absence of vaginal recurrences in 332 patients with lowrisk stage I endometrial adenocarcinoma treated with hysterectomy and vaginal brachytherapy without formal staging lymph node sampling: Report of a prospective trial. Int J Radiat Oncol Biol Phys. 1997;38: 373–380. 8. Nori D, Merimsky O, Batata M, Caputo T. Postoperative high dose rate intravaginal brachytherapy combined with external irradiation for early stage endometrial cancer: A long term follow-up. Int J Radiat Oncol Biol Phys. 1994;30:831–837. 9. Jolly S, Vargas C, Kumar T, et al. Vaginal brachytherapy alone: An alternative to whole pelvis radiation for early stage endometrial cancer. Gynecol Oncol. 2005;97:887–892. 10. Solhjem MC, Petersen IA, Haddock MG. Vaginal brachytherapy alone is sufficient adjuvant treatment for patients with surgical stage I endometrial cancer. Int J Radiat Oncol Biol Phys. 2005;62:1379–1384. 11. Small W Jr, Zeytinoglu M, Keh R, et al. Endometrial adenocarcinoma invasive to 1/2 the myometrial thickness: Analysis of prognostic variables for recurrence and survival. Int J Radiat Oncol Biol Phys. 2001; 51 Suppl 2:S35–S36. 12. Petereit DG, Tannehill SP, Grosen EA, Hartenbach EM, Schink JC. Outpatient vaginal cuff brachytherapy for endometrial cancer. Int J Gynecol Cancer. 1999;9:456–462. 13. McCloskey SA, Tchabo NE, Malhotra HK, et al. Adjuvant vaginal brachytherapy alone for high risk localized endometrial cancer as defined by the three major randomized trials of adjuvant pelvic radiation. Gynecol Oncol. 2010;116:404–407.

OncoTargets and Therapy 2010:3

Dovepress 14. Mehta VK, Algan O, Griem KL, et al. Experience with an electronic brachytherapy technique for intracavitary accelerated partial breast irradiation. Am J Clin Oncol. 2010;33:327–335. 15. Dickler A, Kirk MC, Coon A, et al. A dosimetric comparison of Xoft Axxent Electronic Brachytherapy and iridium-192 high-dose-rate brachytherapy in the treatment of endometrial cancer. Brachytherapy. 2008;7:351–354. 16. Small W, Erickson B, Kwakwa F. American Brachytherapy Society survey regarding practice patterns of postoperative irradiation for endometrial cancer: Current status of vaginal brachytherapy. Int J Radiat Oncol Biol Phys. 2005;63:1502–1507.

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electronic brachytherapy for endometrial cancer 17. Nout RA, Putter H, Jürgenliemk-Schulz IM, et al. Quality of life after pelvic radiotherapy or vaginal brachytherapy for endometrial cancer: First results of the randomized PORTEC-2 trial. J Clin Oncol. 2009;27: 3547–3556. 18. Dickler A, Puthawala MY, Thropay JP, Bhatnagar A, Schreiber G. Prospective multi-center trial utilizing electronic brachytherapy for the treatment of endometrial cancer. Radiat Oncol. 2010;20:67.

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Calculated and measured brachytherapy dosimetry parameters in water for the Xoft Axxent X-Ray Source: An electronic brachytherapy sourcea… Mark J. Rivardb

Department of Radiation Oncology, Tufts-New England Medical Center, Boston, Massachusetts 02111

Stephen D. Davis and Larry A. DeWerd

Medical Radiation Research Center, University of Wisconsin, Madison, Wisconsin 53706

Thomas W. Rusch and Steve Axelrod Xoft, Inc., Fremont, California 94538

Received 17 March 2005; revised 23 August 2006; accepted for publication 23 August 2006; published 12 October 2006 A new x-ray source, the model S700 Axxent™ X-Ray Source Source , has been developed by Xoft Inc. for electronic brachytherapy. Unlike brachytherapy sources containing radionuclides, this Source may be turned on and off at will and may be operated at variable currents and voltages to change the dose rate and penetration properties. The in-water dosimetry parameters for this electronic brachytherapy source have been determined from measurements and calculations at 40, 45, and 50 kV settings. Monte Carlo simulations of radiation transport utilized the MCNP5 code and the EPDL97-based mcplib04 cross-section library. Inter-tube consistency was assessed for 20 different Sources, measured with a PTW 34013 ionization chamber. As the Source is intended to be used for a maximum of ten treatment fractions, tube stability was also assessed. Photon spectra were measured using a high-purity germanium HPGe detector, and calculated using MCNP. Parameters used in the two-dimensional 2D brachytherapy dosimetry formalism were determined. While the Source was characterized as a point due to the small anode size, 1 mm, use of the onedimensional 1D brachytherapy dosimetry formalism is not recommended due to polar anisotropy. Consequently, 1D brachytherapy dosimetry parameters were not sought. Calculated point-source model radial dose functions at g P 5 were 0.20, 0.24, and 0.29 for the 40, 45, and 50 kV voltage settings, respectively. For 1 r 7 cm, measured point-source model radial dose functions were typically within 4% of calculated results. Calculated values for F r , for all operating voltages were within 15% of unity along the distal end = 0 ° , and ranged from F 1 cm, 160° = 0.2 to F 15 cm, 175° = 0.4 towards the catheter proximal end. For all three operating voltages using the PTW chamber, measured dependence of output as a function of azimuthal angle, , was typically on average ±3% for 0 ° 360°. Excluding an energy response function, measurements of normalized photon energy spectra were made for three operating voltages, and were typically within 2% agreement with the normalized Monte Carlo calculated spectra. In general, the model S700 Source exhibited depth dose behavior similar to low-energy photon-emitting low dose rate sources 125I and 103Pd, yet with capability for variable and much higher dose rates and subsequently adjustable penetration capabilities. This paper presents the calculated and measured in-water brachytherapy dosimetry parameters for the model S700 Source at the aforementioned three operating voltages. © 2006 American Association of Physicists in Medicine. DOI: 10.1118/1.2357021 Key words: electronic brachytherapy, TG-43, brachytherapy dosimetry I. INTRODUCTION Recently, small x-ray tubes have been developed that offer the prospect of electronic brachytherapy. Xoft Inc. has developed a miniature x-ray brachytherapy source called the Xoft Axxent™ X-Ray Source Source .1–5 The model S700 Source consists of a disposable, microminiature x-ray tube Fig. 1 integrated into a cooled, flexible, disposable sheath which is directly attached to a treatment control console Fig. 2 . Water circulating within the cooling sheath having intimate contact with the anode allows a higher power dissipation and higher dose rate, without thermal damage to the 4020

Med. Phys. 33 „11…, November 2006

Source, surrounding probe structures, or the patient. If the cooling water supply is interrupted, the treatment control console will immediately shut off the operating voltage. Furthermore, if the tube should overheat, the Source will electronically short and terminate the operating voltage and radiation output. The Source is capable of operating voltages ranging from 20 to 50 kV. This range provides photons with energies 50 keV which negates shielding concerns required by a 192 Ir source used for high dose rate HDR brachytherapy. The Source current and photon beam intensity may be modu-

0094-2405/2006/33„11…/4020/13/$23.00

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Rivard et al.: Dosimetry parameters for the Xoft Axxent X-Ray Source

FIG. 1. Photographs and schematic diagram of the model S700 Xoft Axxent™ X-Ray Source. The left hand side image shows the model S700 Source in operation. The bottom illustration shows the Source enclosed by a gray water cooling sheath. The sheath outer diameter is 5.3 mm, and is flexible beyond the distal 15 mm.

lated to approximate the penetration and/or dose rate characteristics of clinically suitable radionuclides such as HDR 192 Ir, low dose rate LDR 125I, and LDR 103Pd. Therefore, an increased level of dose conformity is possible. At an operating voltage of 50 kV, the Source can produce air kerma strengths ranging from 1400 Gy cm2 h−1 with a tube current of 300 A approximately thrice that of a 10 Ci HDR 192Ir source down to 4.7 Gy cm2 h−1 at 1 A. Like conventional HDR remote afterloading brachytherapy sources using radionuclides attached to delivery drive wires, the Source can be positioned within the patient at multiple dwell positions for providing highly conformal radiotherapy delivery. This method of operation was approved by the FDA in December 2005. Initial clinical applications will operate at fixed voltage and current, 50 kV and 300 A for 15 W of power, with a tube design lifetime of 2.5 h for multi-fraction treatments of an entire therapy course. Another miniature x-ray source has been used for interstitial and intracavitary radiation therapy, the photon radiosurgery system PRS or INTRABEAM™ System developed by the Photoelectron Corporation, and now owned and mar-

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keted by Carl Zeiss, Inc. in North America. This device has been used intraoperatively for the irradiation of intracranial metastases and irradiation of the tumor bed following breastconserving surgery.6–8 X rays are generated in the PRS by a 50 keV electron beam focused from a conventional miniature electron gun onto the tip of a 3-mm-diam rigid drift tube.9–11 The tip of the drift tube comprises a beryllium tube with hemispherical x-ray window coated on the inside with a thin Au target and on the outside with thin nickel and titanium nitride films for biocompatibility. The electron beam is positioned in the center of the hemispherical Be window using a static magnetic deflection system. The Zeiss device has a dose distribution that is approximately spherically symmetrical but drops off in the proximal direction. Depth-dose data for a 25 min treatment time using the INTRABEAM™ System at 40 A and 50 kV were reported as 20, 5, and 1 Gy at 0.1, 1.0, and 2.7 cm, respectively, from the outer surface of a 3.5-cm diam spherical applicator.7 As will be shown later, the Xoft Axxent™ Source has a near-field dose rate that is at least six times higher beyond the catheter, and a more slowly decreasing depth-dose curve in comparison to the INTRABEAM™ System. This latter feature is due in part to the higher average photon energy from the Xoft Axxent™ Source through tube filtration of the low-energy x rays. This study presents in-water brachytherapy dosimetry parameters and data, calculated and measured at 40, 45, and 50 kV at 300 A, needed for clinical implementation of the Source with treatment planning systems.12–14 While not a LDR brachytherapy seed, this publication aims to provide data to satisfy, in part, the AAPM recommendations for dosimetric prerequisites and clinical implementation for posting on the joint AAPM/RPC Brachytherapy Source Registry.15 II. MATERIALS AND METHODS Certain commercial equipment, instruments, materials, and software are identified in this publication in order to adequately specify the experimental and calculative procedures. Such identification does not imply recommendation or endorsement by either the authors or their respective institutions, nor does it imply that the hardware or software identified is necessarily the best available for these purposes. A. Axxent™ x-ray source

FIG. 2. Schematic diagram of the entire model S700 Source probe illustrating the relationship of the Source to the water coolant inlet/outlet and HV connector. Though depicted as a straight, needle-like device, in reality the probe is flexible. The right hand side image shows the treatment control console adjacent to a radiotherapy stretcher bed. Medical Physics, Vol. 33, No. 11, November 2006

Calculations and experiments were performed to determine Source dose rate distributions in water. These dose rates were then manipulated to determine the requisite AAPM brachytherapy dosimetry parameters for subsequent use in treatment planning systems. The coordinate system was arbitrarily oriented such that = 0° points along the Source distal direction z axis , and asymmetry about the transverse plane x-y plane requires treatment planning from 0 ° 180°. This orientation is the same as for the Nucletron PLATO™ treatment planning system, yet = 0° points along the Source proximal direction for the Varian BrachyVision™ treatment planning system.

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B. Radiation transport calculations

C. Experimental measurements

Section V.E of the AAPM TG-43U1 report provides “Good Practice” recommendations for investigators performing Monte Carlo calculations, and that certain aspects of the calculation setup be described.12 We aim to follow these recommendations. Unlike radionuclides where there are recommended photon energy spectra such as for 125I and 103Pd, the Source photon energy spectra were initially unknown. In this study, Source spectra were calculated using mono-energetic electrons striking the anode surface to generate x rays. The electrons had kinetic energies of 40, 45, and 50 keV, and Monte Carlo calculations were used for determining the radiological physics interactions of photons and electrons in various media. While this brachytherapy application has not been previously studied using MCNP, the code has been benchmarked with measurements for photon production due to electron bremsstrahlung on similar high-Z materials.16–24 Photon energy spectra were calculated using the Monte Carlo N-Particle radiation transport code version MCNP5 using the EPDL97-based cross-section libraries, particle fluence F4 tally estimator with photon energy binned at 100 eV intervals, and the mass-attenuation coefficients of Seltzer used in the MCNP5 F6 tally.25–30 Unlike version 4C of MCNP which is subject to dosimetric errors due to inaccuracies in the default cross-section libraries, MCNP5 uses the latest set of libraries, EPDL97-based mcplib04.31–33 Calculations typically required 109 histories to achieve sufficient statistics to discern the effects studied. This number of histories produced k = 1 statistical uncertainties of 0.05% and 0.2% at 1 and 5 cm on the transverse plane, and 0.3% and 0.8% at 1 and 5 cm near the long axes, respectively. The Source geometry was simulated as shown in Fig. 1, assuming symmetry about the long axis. Components included in the model S700 simulation were the x-ray anode and substrate, wall materials, and water cooling sheath 5.3 mm outer diameter . While the internal dimensions and compositions are proprietary, the primary element producing x rays in the anode is tungsten. The coordinate system origin was positioned at the center of the x-ray anode cone. Details of the cooling sheath were included in all calculations presented herein. Calculations were performed at Tufts University, the University of Wisconsin, and Xoft. Generally, these were done in a 20 cm radius spherical liquid water phantom with an atomic ratio of 2:1 for H:O and = 0.998 g / cm3. Data were calculated for all three operating voltages at 0 ° 179° with 1° increments, and for 0.4 r 15.0 cm with 0.1 cm increments. The AAPM recommends at least 5 cm of backscattering material to approximate infinite scatter conditions when determining dose rate distributions within 10 cm of low-energy photon-emitting radionuclides such as 125I and 103Pd.13 This guidance has recently been substantiated over a wide range of radii and photon energies for a variety of radionuclides and monoenergetic photonemitting sources.34,35 More specifics on the geometry and voxel size used for calculating each set of brachytherapy dosimetry parameters are provided in the following sections.

Dose rate measurements were performed at Xoft using a PTW parallel plate ionization chamber model 34013, from Freiburg, Germany that was specifically designed for characterization of the INTRABEAM™ System. Due to its acrylic construction, radiological similarity to water at these photon energies, and small collecting volume 1.7 mm diam., 0.45-mm-thick air gap , this chamber is suitable for high dose rate measurements in water. The PTW ion chamber was calibrated at PTW with traceability to the German National Laboratory PTB in Braunschweig, Germany over voltage range 15 to 70 kVp which bounded those examined herein for the source at 40– 50 kV. An uncertainty k = 2 of ±2% is reported for this voltage range. The ionization chamber was within current calibration, as was the electrometer, a PTW UniDos E model. A computer running custom LABVIEW™ data acquisition and analysis software National Instruments, Austin, TX communicated with the electrometer via a serial port. Data were exchanged by ASCII strings, eliminating the possibility of inaccurate communications. The computer also controlled the high voltage power supply HVPS through National Instruments analog data acquisition cards on the peripheral component interface PCI bus. The power supply was separately calibrated with respect to front panel displays. The LABVIEW software was then checked against the HVPS displays for accuracy. Individual readings from the electrometer were sampled at 0.5 s intervals. Typically ten such readings were combined to yield an individual data point. Statistics were recorded, including the standard deviation of the readings, as a measure of system stability. Typically, standard deviations of the 0.5 s readings were on the order of 0.25% of the signal, even for signals as small as 0.25 pA. Depth dose for radial dose function , polar, and azimuthal dose rate data were acquired with a specially constructed fixture operating in a water tank. The measurement apparatus was mounted atop a steel water tank 11.0 cm high 29.2 cm long 29.2 cm wide designed to be opaque to source radiation and is shown as a computer-aided design rendering in Fig. 3. A Solid Water™ case, front thickness of 1.0 mm, enclosed the PTW chamber in a water tight configuration while permitting atmospheric pressure equilibration via a thin snorkel tube extending out of the water. The Source catheter entered the tank either vertically through the top or horizontally through thin-walled stainless steel tubes that ended at least 2 cm from the anode. For depth-dose measurements the Source entered the tank vertically, the chamber was positioned 90° relative to the Source long axis, then the linear stage stepped it from 1.0 to 7.0 cm in 0.2 cm increments. Azimuthal readings also used vertical source orientation; the detector distance was set using the linear stage, then the rotary stage moved the detector from 0° to 360° in 15° steps. Polar angle measurements were made with the Source horizontal; once again the detector distance was set via the linear stage, with the rotary stage locating the detector along an arc with the Source in the center. Due to interference between detector and catheter, the extremes of the arc depended on the detector distance; at larger distances a larger

Medical Physics, Vol. 33, No. 11, November 2006

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Rivard et al.: Dosimetry parameters for the Xoft Axxent X-Ray Source

FIG. 3. Spatial measurement apparatus in water tank, surrounding radiation shielding not shown. The structure at the top contains both rotary and linear stepper motors. Source catheters can enter from above for azimuthal, or through the front, for polar angle anisotropy function measurements. Radial dose function measurements can be made in either orientation. The ion chamber is encased in a sealed Solid Water™ box with a snorkel to allow equilibration with atmospheric pressure.

angular range was possible. A two axis micrometer stage not shown controlled the location of the horizontal entry tube to allow for precise Source alignment to the axis of rotation. The Source:detector distance was varied by a computercontrolled long-throw linear stage. The linear stage was mounted to a computer-interfaced rotary stage, providing angular control while maintaining the proper orientation of the detector entrance window to the Source. Stainless steel mounting fixtures, chosen for mechanical precision and compatibility with the water tank environment, were designed to be far enough from the Source and detector so as not to introduce detectable measurement errors. An identically constructed copy of the apparatus was subjected to a detailed inspection process, to validate accuracy of mechanical movement and positions. Location of the anode, which is the true source of the x rays, depends to an extent on the cooling catheter it resides within. The cooling catheter is designed with a plastic insert at its inner end that locates the anode longitudinally and centers it, while allowing for adequate flow of water over the anode surface. Location of the cooling catheter lengthwise within the stainless steel tube establishes the anode position in the plane of the detector in azimuthal measurements, and must be accurate to within 1 mm. For polar measurements, the cooling catheter position is critical since it sets the anode position within the arc traversed by the detector. In order to mitigate effects based on the intrinsically high sensitivity of results to Source:detector positioning, a spotting telescope with graticule was built into the side of the radiation tank. In combination with crosshair marks etched onto the Solid Water™ detector enclosure, longitudinal alignment is estimated to have an accuracy of 0.2 mm or better. Concentricity of detector rotation around the tube which guides the catheter and Source was adjusted on a lathe during assembly, and measured at time of use to be consisMedical Physics, Vol. 33, No. 11, November 2006

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tent at 0°, 90°, 180°, 270°, and 360° within a measurement uncertainty of ±0.1 mm. Absolute determination of Source:detector distance involved three direct measurements, plus use of the PTW-supplied 0.30 mm offset of the model 34013 chamber front window from the front locating surface. Distance values derived in this way were consistent with expected values, producing a localization uncertainty of ±0.2 mm. At r = 1, 2, and 3 cm, this level of localization uncertainty would be associated with dose rate uncertainties of ±4%, 2%, and 1%, respectively. To improve measurement statistics and evaluate consistency, all experimental results were obtained from 20 separate Sources at 50 kV n = 3 for 40 and 45 kV , and results from two complete rotations were averaged to improve measurement uncertainties of the angular distributions. Since some of the measurements were lengthy and the Sources have a finite beam life, approximately 110 Sources were used to perform the experiments described herein. The intent is for manufacturer quality control to negate the need for medical physicists to measure and validate brachytherapy dosimetry parameters, requiring only a measure of source strength preceding each treatment fraction. This approach has been approved by the U.S. FDA, and a separate publication is being prepared to evaluate the dose rate constant and provide an air kerma strength calibration procedure. D. Photon energy spectra

Calculated and measured photon energy spectra were determined in air. Calculations were performed using MCNP5 and 100 eV energy bins. Measurements were performed using a CdTe solid-state detector at Xoft, a high-purity germanium HPGe detector at the University of Wisconsin, and a HPGe detector during a research trip to the National Institute of Standards and Technology NIST . Due to significant artifacts of K-edge photoescape peaks from cadmium and tellurium, results from the CdTe detector are not presented. Because of improvements to the Source design since inception of this study, only recently obtained results at NIST are presented. Photon spectra were measured as a function of beam current, operating voltage, aperture, and filtration for a single Source. For consistency, only unfiltered spectra are presented. A 0.25-mm-diam tungsten aperture was used to collimate the Source photons which were measured in air with 60 eV energy bins at a distance of 178 cm to minimize HPGe detector dead time. Calculated and measured counts were normalized over the 23.0–26.0 keV range to minimize impact of characteristic x-ray peaks at the low-energy end and decreasing photon yield at the high-energy end. Note that photons of 10, 20, and 30 keV are attenuated by approximately 67%, 15%, and 7% in air at 178 cm, respectively. E. Brachytherapy dosimetry parameters

1. Point-source two-dimensional dosimetry formalism The appropriate combination of the brachytherapy dosimetry parameters in a treatment planning system should pro-

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Rivard et al.: Dosimetry parameters for the Xoft Axxent X-Ray Source

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TABLE I. Measured and calculated dose rates to water at the reference position r0 , 0 for the Axxentâ&#x201E;˘ Source at operating voltages of 40, 45, and 50 kV. Measurements were taken using a PTW 34013 ionization chamber in 11 29 29 cm3 liquid water bath, and calculations used MCNP5 in a 20 cm radius spherical liquid water phantom. The average measured readings were used to derive the ratio in the last row. P r0 , 0 water dose rate cGy hâ&#x2C6;&#x2019;1 Aâ&#x2C6;&#x2019;1 Source

40 kV

45 kV

50 kV

Measured maximum Measured average Calculated MCNP5 Measured/calculated

241 129 254 0.54

304 196 325 0.64

357 265 382 0.74

tively use Leff = 0.1 cm, the geometry function for r 0.5 cm using a line-source approximation would not differ from that using a point-source approximation by more than 1%. Therefore, we set Leff 0 and used the point-source approximation with GP r , = 1 / r2 throughout this work. However, the two-dimensional 2D formalism is still applicable due to polar anisotropy as will be shown later. Since recommendations in the TG-43U1 report do not explicitly include a 2D dosimetry formalism to account for point sources, the following equation, Eq. 1 , is presented to depict the formalism that was used for calculating the 2D dose rate distributions: DĚ&#x2021; r, = SK Âˇ Âˇ

r0 r

Âˇ g P r Âˇ F r, .

2. Radial dose function

FIG. 4. Measured and calculated relative photon energy spectra at 40, 45, and 50 kV for the model S700 Source along the transverse plane. Measurements were obtained at NIST using a high-purity germanium HPGe detector and 60 eV bin widths for the multichannel analyzer. Calculations were performed using MCNP5 with 100 eV bin widths. Relative photon spectra are shown at: a 40, b 45, and c 50 kV.

vide the correct dose rate distributions to the clinical user. All of these parameters require specification of either an active length, L, or an effective length, Leff. By design, the Source anode size results in Leff 0.1 cm. If one were to conservaMedical Physics, Vol. 33, No. 11, November 2006

Using a 1 / r2 geometry function, dose rate data normalized to dĚ&#x2021; r0 , 0 permitted calculation of g P r for all three operating voltages. These data are referred to as MCg P r 40, 45 50 for the 40, 45, and 50 kV voltage MCg P r , and MCg P r settings, respectively. For measurements of PTWg P r 40, 45 50 PTWg P r , and PTWg P r , the PTW 34013 chamber was moved by the stage from 1.0 r 7.0 cm in 0.2 cm increments for all three operating voltages. At 40, 45, and 50 kV, measurements were made with 3, 3, and 20 Sources, respectively. Because the Solid Waterâ&#x201E;˘ detector enclosure was thin and measurements were performed in liquid water, no medium correction factors were used for reporting radial dose function results. At r0, the standard deviation of measured dose rates for a given Source was 0.3% at all three operating voltages. For all three operating voltages, the average standard deviations of measured g 3 , g 5 , and g 7 were 4.5%, 5.3%, and 6.3%, respectively, and did not trend as a function of operating voltage.

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TABLE II. Calculated and measured radial dose function values using the point-source model for the 40, 45, and 50 kV voltage settings for the model S700 Axxentâ&#x201E;˘ Source. Measured results were for n = 3, n = 3, and n = 20 tubes for 40, 45, and 50 kV, respectively. Calculated and measured results were obtained with 1 and 2 mm precision, respectively. While ratios of measured-to-calculated g P r 50 approach 1.15 for large r, all differences are smaller than the measured uncertainties. Log-linear interpolation of measured results are presented in boldface, and result in errors 1% which are much less than the uncertainties. Calculated r cm 0.4 0.5 0.6 0.7 0.8 0.9 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10.0 10.5 11.0 11.5 12.0 12.5 13.0 13.5 14.0 14.5 15.0

MCg P r

1.678 1.511 1.373 1.257 1.159 1.074 1.000 0.935 0.877 0.825 0.778 0.736 0.698 0.662 0.630 0.600 0.573 0.462 0.381 0.318 0.269 0.229 0.196 0.168 0.145 0.126 0.109 0.0943 0.0818 0.0712 0.0620 0.0542 0.0472 0.0413 0.0361 0.0315 0.0276 0.0241 0.0211 0.0185 0.0162 0.0141 0.0124

MCg P r

1.603 1.455 1.332 1.230 1.142 1.066 1.000 0.941 0.889 0.842 0.799 0.761 0.726 0.694 0.664 0.637 0.612 0.507 0.430 0.369 0.320 0.278 0.244 0.214 0.189 0.167 0.148 0.131 0.116 0.103 0.0917 0.0812 0.0723 0.0643 0.0574 0.0510 0.0455 0.0405 0.0361 0.0321 0.0287 0.0255 0.0227

Measured MCg P r

1.551 1.418 1.305 1.211 1.131 1.061 1.000 0.946 0.898 0.855 0.816 0.780 0.748 0.718 0.690 0.665 0.641 0.544 0.470 0.411 0.362 0.322 0.286 0.256 0.229 0.206 0.185 0.166 0.150 0.135 0.122 0.110 0.0989 0.0890 0.0804 0.0725 0.0655 0.0591 0.0534 0.0481 0.0434 0.0392 0.0352

PTWg P r

1.000 0.942 0.887 0.838 0.792 0.751 0.711 0.677 0.644 0.614 0.585 0.473 0.389 0.326 0.275 0.234 0.200 0.174 0.150 0.131 0.112

3. Polar angle dependence The radial and angular ranges for calculated F r , values are given in Sec. II B. F r , values were measured at 2, 3, 5, and 7 cm for â&#x2C6;&#x2019;150Â° + 150Â° in 10Â° increments. These measurements were performed for all three operating voltages, for 20 different Sources, and then repeated. Thus, a total of 14 880 separate F r , measurements were obtained Medical Physics, Vol. 33, No. 11, November 2006

PTWg P r

1.000 0.948 0.899 0.853 0.809 0.771 0.735 0.703 0.673 0.645 0.619 0.513 0.434 0.372 0.323 0.281 0.246 0.216 0.192 0.170 0.151

Measured calculated PTWg P r

1.000 0.960 0.920 0.884 0.848 0.817 0.786 0.759 0.732 0.707 0.683 0.588 0.511 0.450 0.399 0.355 0.317 0.284 0.256 0.232 0.213

g P r 40

g P r 45

g P r 50

0.000 0.007 0.010 0.013 0.014 0.015 0.013 0.015 0.014 0.014 0.012 0.011 0.008 0.008 0.006 0.005 0.004 0.006 0.005 0.005 0.003

0.000 0.007 0.010 0.011 0.010 0.010 0.009 0.009 0.009 0.008 0.007 0.006 0.004 0.003 0.003 0.003 0.002 0.002 0.003 0.003 0.003

0.000 0.014 0.022 0.029 0.032 0.037 0.038 0.041 0.042 0.042 0.042 0.044 0.041 0.039 0.037 0.033 0.031 0.028 0.027 0.026 0.028

at Xoft. Data were not collected at the proximal end at 150Â° due to interference between the detector and coolant sheath. This constraint was distance dependent. As the origin of radiation from the Source was approximated as a point source, readings normalized to the 0 reading resulted in direct measurements of F r , . Reproducibility of measurements at a fixed distance and voltage was examined by com-

4026

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4026

paring results at the same angle, e.g., −30° and +30° obtained during two different rotations. F r , variability among the 20 Sources was also examined. 4. Azimuthal angle dependence Since the manufacturing process, and subsequently the Monte Carlo model, did not intentionally include asymmetry about the Source long axis, no dependence of output as a function of azimuthal angle, , is expected. Constancy of output as a function of azimuthal angle, , was measured in 15° increments from 0° to 360°, and at radial distances of 2, 4, and 6 cm for 20 different Sources at all operating voltages. The average variation as a function of azimuthal angle was obtained. Measurement reproducibility was examined by comparing rotationally symmetric results, i.e., results at 0° were compared with results at 360°. III. RESULTS AND DISCUSSION

FIG. 5. Radial dose functions for HDR 192Ir, LDR 125I, and LDR 103Pd brachytherapy sources in comparison to those for the model S700 Source at 40, 45, and 50 kV operating voltages. Improved penetration of the model S700 Source as a function of increasing depth is attributed to beam hardening.

A. Photon energy spectra

Figure 4 shows the pulse-height distributions measured with the HPGe detector for a Source operating at 40, 45, and 50 kV. Note that no corrections have been made for the detector response function, including the energy-dependent detector efficiency; only the normalized counts within a given energy bin are shown. From Fig. 4, it is evident that the maximum photon energies, keV, match the applied operating voltage, kV. The 8, 10, and 11 keV peaks result from tungsten L-edge characteristic x rays tungsten is used for the anode film ; the 15 and 17 keV peaks result from yttrium K-edge characteristic x rays yttrium is a constituent of the anode substrate ; and the 22 keV peak results from silver K-edge characteristic x rays silver is a constituent of the brazing alloy . Average calculated photon energies for the Source operating in air at 40, 45, and 50 kV were 22.8, 24.7, and 26.6 keV, with average measured photon energies of 23.1, 24.9, and 26.7 keV, respectively. Agreement among all operating voltages and energy bins was generally within 2%; bin-to-bin measurement noise was typically 4% near 25 keV, and the MCNP statistical error was typically 1%. Differences between measurements and calculations exceeded 20% at energies less than 12 keV, and were primarily due to the omission of multiple L-line generation by MCNP and unavailability of HPGe energy-dependent response functions correlating counts with photon energy fluence at the time of measurements. Upon comparing the 40 kV Source spectra with 40 kV INTRABEAM™ spectra published in Fig. 3 by Yanch and Harte,11 it is evident that the higher-energy photon distributions are similar. Differences in lower-energy photon distributions arise from differences in the target materials. B. Dose rates in water at the reference position

Table I presents the measured and calculated dose rates to water at the reference position at all three operating voltages. Increases in dose rates to water for a fixed beam current as a function of operating voltage are attributed to increased conversion efficiency for increasing applied potential as is typiMedical Physics, Vol. 33, No. 11, November 2006

cal of bremsstrahlung radiation emission. Measurement variability among Sources was attributed to differing tube efficiencies resultant from variables in the manufacturing process. Also, the maximum and average measured values for dose rates to water at the reference position were typically 17% and 40% less than the Monte Carlo results. This implied that the MCNP model may have overestimated the photon production efficiency; that the maximum tube efficiency to produce photons was 78%, 80%, and 91% of that produced by the MCNP model at 40, 45, and 50 kV, respectively; or that there was some combination of these reasons. C. Radial dose function

Calculated and measured g P r for all three operating voltages are presented in Table II. For distances greater than r0, g P r exhibited greater penetration ability as operating voltage increased. As distance increased, agreement between the two methods monotonically decreased. The disagreement could be based on artifacts of the simulations such as small differences between the actual and simulated in-water photon spectra since MCNP physics currently does not produce multiple tungsten L-edge characteristic x rays arising from electron impact ionization. Variations in calculated g r results due to statistical uncertainties were typically 0.1% for all operating voltages for r 7 cm. This disagreement could also be attributed to measurements using the PTW ionization chamber: i a 0.2 mm positioning offset would place calculated results within the standard deviation of measured results, ii a slight change in the response of the PTW ionization chamber because of varying photon energy at depth, or iii nonuniform angular sensitivity to an increasing amount of scattered radiation which increases as depth increases. For measured PTWg P r 50 results at 2, 3, 5, and 7 cm with 20 Sources, the standard deviation k = 2 was ±7.3%, ±9.1%, ±11.7%, and ±14.2%, respectively. Regardless, the observed differences between calculated and measured g r results were relatively small given other differences observed in the

4027

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4027

TABLE III. Calculated 2D anisotropy function data, F r , 40, for the Axxent™ Source at 40 kV. NA indicates the position is located within the model S700 Axxent™ Source and the dosimetry formalism is not applicable. Radial distance, r cm

Degrees

0.5

1.0

1.5

2.0

3.0

4.0

5.0

6.0

7.0

8.0

10.0

12.0

15.0

0° 5° 10° 15° 20° 25° 30° 35° 40° 45° 50° 55° 60° 65° 70° 75° 80° 85° 90° 95° 100° 105° 110° 115° 120° 125° 130° 135° 140° 145° 150° 155° 160° 165° 170° 175°

0.903 0.898 0.889 0.892 0.898 0.894 0.922 0.971 1.012 1.051 1.073 1.085 1.091 1.090 1.084 1.072 1.052 1.028 1.000 0.965 0.932 0.896 0.853 0.807 0.756 0.695 0.615 0.495 0.363 0.211 NA NA NA NA NA NA

0.945 0.945 0.942 0.946 0.949 0.947 0.953 1.000 1.037 1.064 1.081 1.091 1.095 1.091 1.084 1.069 1.050 1.028 1.000 0.970 0.937 0.900 0.858 0.812 0.759 0.691 0.604 0.508 0.411 0.318 0.248 0.164 0.168 0.194 NA NA

0.977 0.972 0.973 0.976 0.979 0.977 0.975 1.019 1.052 1.073 1.087 1.094 1.097 1.091 1.082 1.068 1.048 1.027 1.000 0.972 0.940 0.905 0.866 0.822 0.770 0.702 0.622 0.536 0.449 0.362 0.298 0.213 0.205 0.217 0.199 NA

0.994 0.993 0.997 0.996 0.999 0.996 0.991 1.030 1.061 1.079 1.091 1.096 1.097 1.092 1.081 1.067 1.047 1.026 1.000 0.973 0.942 0.909 0.871 0.830 0.780 0.713 0.639 0.560 0.478 0.396 0.333 0.254 0.237 0.242 0.218 NA

1.023 1.018 1.023 1.022 1.023 1.022 1.013 1.049 1.072 1.088 1.096 1.101 1.097 1.091 1.080 1.065 1.046 1.027 1.000 0.974 0.945 0.914 0.879 0.838 0.790 0.730 0.663 0.593 0.519 0.444 0.384 0.309 0.286 0.281 0.258 0.211

1.033 1.036 1.039 1.039 1.040 1.039 1.031 1.060 1.080 1.095 1.100 1.103 1.098 1.092 1.079 1.065 1.045 1.026 1.000 0.975 0.945 0.916 0.881 0.844 0.798 0.743 0.680 0.615 0.547 0.475 0.418 0.349 0.317 0.309 0.285 0.243

1.049 1.050 1.051 1.050 1.052 1.048 1.046 1.068 1.085 1.097 1.102 1.102 1.099 1.090 1.079 1.065 1.044 1.024 1.000 0.974 0.946 0.916 0.883 0.846 0.801 0.749 0.690 0.627 0.564 0.496 0.440 0.376 0.343 0.329 0.309 0.268

1.054 1.059 1.063 1.064 1.061 1.058 1.054 1.075 1.089 1.103 1.105 1.103 1.101 1.093 1.079 1.064 1.044 1.024 1.000 0.974 0.945 0.917 0.884 0.846 0.802 0.753 0.698 0.638 0.576 0.514 0.455 0.394 0.360 0.344 0.324 0.292

1.061 1.062 1.065 1.072 1.066 1.066 1.061 1.081 1.096 1.105 1.107 1.105 1.102 1.091 1.079 1.066 1.042 1.021 1.000 0.973 0.945 0.915 0.882 0.846 0.804 0.756 0.701 0.642 0.584 0.524 0.469 0.409 0.373 0.356 0.339 0.304

1.070 1.069 1.071 1.072 1.074 1.073 1.069 1.089 1.102 1.110 1.112 1.109 1.105 1.093 1.081 1.066 1.047 1.023 1.000 0.977 0.947 0.916 0.881 0.850 0.805 0.757 0.706 0.650 0.592 0.534 0.480 0.419 0.383 0.367 0.342 0.317

1.082 1.079 1.086 1.084 1.084 1.080 1.080 1.096 1.108 1.119 1.118 1.112 1.108 1.098 1.084 1.065 1.047 1.021 1.000 0.976 0.943 0.916 0.883 0.846 0.801 0.759 0.709 0.653 0.598 0.543 0.489 0.436 0.400 0.376 0.356 0.330

1.086 1.085 1.092 1.093 1.089 1.085 1.087 1.103 1.118 1.118 1.123 1.117 1.113 1.099 1.084 1.067 1.047 1.025 1.000 0.969 0.943 0.915 0.880 0.847 0.801 0.756 0.706 0.655 0.603 0.550 0.498 0.447 0.405 0.381 0.368 0.349

1.098 1.102 1.100 1.105 1.094 1.102 1.100 1.116 1.129 1.128 1.128 1.123 1.112 1.099 1.089 1.072 1.050 1.024 1.000 0.969 0.943 0.916 0.869 0.841 0.797 0.757 0.701 0.656 0.600 0.550 0.503 0.452 0.410 0.381 0.372 0.352

literature for low-energy photon-emitting brachytherapy source dosimetry.13 In Fig. 5, g r data for the Source are compared to data for conventional radionuclides such as HDR 192Ir,36 and 125I model 6711 and 103Pd model 200 from the 2004 AAPM TG-43U1 report.13 D. Two-dimensional anisotropy function

The calculated F r , data for the three operating voltages are presented in Tables III–V, and the measured F r , data are presented in Table VI. As expected due to increased average photon energy, it is evident that the anisotropy decreases with increasing operating voltage. Anisotropy is higher towards the proximal direction due to attenuation within the Source. The last three columns in Table VI provide comparisons of the measured and calculated F r , data at select distances and angles. As the solid-angle weighted Medical Physics, Vol. 33, No. 11, November 2006

results at each distance illustrate, there was very good agreement between calculated and measured F r , results at all distances and for all three operating voltages. This agreement further substantiates both methodologies. Summarizing all the results in this publication, it seems that Monte Carlo methods are capable of accurately predicting the photon energy spectra and the relative dosimetry parameters, F r , and g r , but not the absolute in-water dose rate Table I . E. Azimuthal angular dependence

For 20 Sources at 50 kV, the change in output relative to average output as a function of azimuthal angle had a range of 15.0%, 8.4%, and 6.1% at 2, 4, and 6 cm, respectively. Standard deviations k = 1 of these results at the same distances were 3.4%, 2.1%, and 1.5%, respectively. Consequently, a quality control procedure has been established at

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4028

TABLE IV. Calculated 2D anisotropy function data, F r , 45, for the Axxent™ Source at 45 kV. NA indicates the position is located within the model S700 Axxent™ Source and the dosimetry formalism is not applicable. Radial distance, r cm

Degrees

0.5

1.0

1.5

2.0

3.0

4.0

5.0

6.0

7.0

8.0

10.0

12.0

15.0

0° 5° 10° 15° 20° 25° 30° 35° 40° 45° 50° 55° 60° 65° 70° 75° 80° 85° 90° 95° 100° 105° 110° 115° 120° 125° 130° 135° 140° 145° 150° 155° 160° 165° 170° 175°

0.910 0.908 0.899 0.901 0.905 0.905 0.930 0.975 1.014 1.051 1.073 1.084 1.087 1.088 1.080 1.069 1.050 1.028 1.000 0.968 0.937 0.902 0.863 0.818 0.767 0.707 0.627 0.507 0.375 0.220 NA NA NA NA NA NA

0.961 0.956 0.955 0.956 0.962 0.962 0.963 1.007 1.041 1.066 1.082 1.090 1.092 1.089 1.080 1.066 1.049 1.026 1.000 0.970 0.940 0.905 0.866 0.821 0.769 0.702 0.618 0.522 0.425 0.331 0.261 0.177 0.179 0.206 NA NA

0.998 0.985 0.989 0.989 0.994 0.993 0.987 1.028 1.058 1.077 1.090 1.095 1.095 1.090 1.080 1.066 1.048 1.026 1.000 0.973 0.944 0.910 0.874 0.830 0.782 0.715 0.638 0.553 0.466 0.380 0.314 0.231 0.220 0.230 0.213 NA

1.015 1.005 1.009 1.011 1.013 1.011 1.004 1.039 1.065 1.082 1.093 1.096 1.095 1.088 1.078 1.064 1.045 1.024 1.000 0.974 0.945 0.913 0.878 0.837 0.791 0.726 0.654 0.578 0.498 0.416 0.352 0.273 0.254 0.256 0.232 NA

1.039 1.030 1.037 1.036 1.037 1.038 1.028 1.057 1.078 1.091 1.099 1.099 1.095 1.088 1.078 1.061 1.044 1.023 1.000 0.974 0.948 0.917 0.884 0.847 0.802 0.745 0.681 0.613 0.541 0.468 0.406 0.335 0.307 0.300 0.277 0.234

1.047 1.050 1.051 1.055 1.052 1.053 1.044 1.069 1.087 1.095 1.101 1.101 1.096 1.087 1.077 1.061 1.042 1.023 1.000 0.976 0.950 0.921 0.889 0.852 0.810 0.756 0.698 0.637 0.571 0.501 0.442 0.376 0.345 0.333 0.310 0.267

1.065 1.063 1.066 1.068 1.065 1.066 1.057 1.078 1.092 1.100 1.105 1.103 1.097 1.088 1.076 1.060 1.041 1.023 1.000 0.977 0.950 0.921 0.890 0.857 0.815 0.765 0.710 0.651 0.590 0.526 0.468 0.408 0.372 0.358 0.337 0.298

1.069 1.071 1.077 1.076 1.074 1.073 1.066 1.085 1.096 1.102 1.106 1.104 1.097 1.087 1.075 1.060 1.042 1.021 1.000 0.975 0.949 0.921 0.892 0.858 0.818 0.771 0.718 0.662 0.605 0.543 0.488 0.430 0.393 0.377 0.356 0.322

1.064 1.080 1.078 1.081 1.084 1.079 1.073 1.088 1.100 1.106 1.107 1.104 1.098 1.088 1.075 1.058 1.042 1.022 1.000 0.976 0.949 0.920 0.892 0.858 0.820 0.774 0.722 0.670 0.613 0.554 0.502 0.444 0.408 0.391 0.369 0.338

1.085 1.086 1.088 1.088 1.089 1.090 1.083 1.095 1.104 1.110 1.110 1.108 1.102 1.089 1.078 1.061 1.043 1.022 1.000 0.976 0.949 0.921 0.892 0.859 0.822 0.776 0.729 0.678 0.620 0.564 0.512 0.459 0.422 0.403 0.385 0.351

1.096 1.097 1.096 1.099 1.099 1.100 1.097 1.106 1.114 1.117 1.117 1.112 1.105 1.092 1.080 1.062 1.043 1.025 1.000 0.976 0.951 0.921 0.892 0.860 0.822 0.782 0.730 0.684 0.633 0.579 0.529 0.478 0.440 0.420 0.401 0.372

1.111 1.112 1.109 1.104 1.106 1.103 1.103 1.119 1.119 1.122 1.120 1.113 1.107 1.096 1.082 1.062 1.044 1.024 1.000 0.974 0.947 0.924 0.889 0.857 0.820 0.779 0.733 0.686 0.636 0.584 0.537 0.490 0.452 0.427 0.411 0.386

1.114 1.103 1.119 1.116 1.112 1.116 1.112 1.120 1.127 1.128 1.127 1.115 1.105 1.099 1.081 1.060 1.045 1.022 1.000 0.970 0.947 0.918 0.889 0.854 0.818 0.777 0.732 0.685 0.637 0.592 0.545 0.502 0.462 0.436 0.417 0.397

Xoft to measure Sources preceding shipment to ensure that those provided for clinical use will not have large output variations as a function of azimuthal angle. An indication of stability of the entire system was obtained from the measured reproducibility of the same Source upon rotation through 360°. Here, changes of 0.2% were observed. Similar results were obtained for the other two operating voltages. One may compare these changes in output as a function of azimuthal angle with those exhibited by radionuclides. Rivard et al. modeled a hypothetical 103Pd source, and obtained an azimuthal angle dependence of air kerma strength having a range of 2% for 0 ° 360°.37 This value is about half the typical range of measured azimuthal angle dependence for the 20 Sources at 2 cm, and approximately equal to the measured result at 4 cm. While the origin of the 103Pd azimuthal anisotropy is due to physical effects of shielding by Medical Physics, Vol. 33, No. 11, November 2006

internal components, azimuthal anisotropy for the model S700 Source is due to asymmetric photon production within the tube.

F. In-water dosimetry parameters

Based on the larger radial range and improved spatial resolution of the Monte Carlo results, and the relatively small differences between Monte Carlo results and measured results, we recommend use of the Monte Carlo-derived datasets for g P r at all operating voltages. For the 2D anisotropy function, the Monte Carlo-derived datasets are also recommended for F r , at all three operating voltages for similar reasons to the g P r choice, plus the improved angular resolution and range. While the dose rate at the reference

4029

Rivard et al.: Dosimetry parameters for the Xoft Axxent X-Ray Source

4029

TABLE V. Calculated 2D anisotropy function data, F r , 50, for the Axxent™ Source at 50 kV. NA indicates the position is located within the model S700 Axxent™ Source and the dosimetry formalism is not applicable. Radial distance, r cm

Degrees

0.5

1.0

1.5

2.0

3.0

4.0

5.0

6.0

7.0

8.0

10.0

12.0

15.0

0° 5° 10° 15° 20° 25° 30° 35° 40° 45° 50° 55° 60° 65° 70° 75° 80° 85° 90° 95° 100° 105° 110° 115° 120° 125° 130° 135° 140° 145° 150° 155° 160° 165° 170° 175°

0.908 0.905 0.902 0.903 0.910 0.908 0.933 0.974 1.012 1.048 1.067 1.077 1.081 1.081 1.074 1.063 1.047 1.025 1.000 0.970 0.941 0.908 0.871 0.828 0.777 0.718 0.638 0.519 0.388 0.230 NA NA NA NA NA NA

0.962 0.961 0.960 0.964 0.969 0.968 0.969 1.011 1.043 1.065 1.081 1.087 1.089 1.085 1.076 1.063 1.046 1.024 1.000 0.973 0.944 0.910 0.872 0.828 0.780 0.713 0.629 0.537 0.441 0.347 0.275 0.193 0.193 0.220 NA NA

0.991 0.989 0.993 0.997 1.001 0.999 0.994 1.031 1.058 1.076 1.087 1.092 1.091 1.085 1.075 1.062 1.044 1.024 1.000 0.975 0.946 0.914 0.878 0.837 0.791 0.725 0.650 0.568 0.484 0.397 0.330 0.250 0.236 0.244 0.226 NA

1.016 1.012 1.014 1.018 1.022 1.020 1.012 1.044 1.068 1.083 1.091 1.094 1.092 1.085 1.074 1.060 1.043 1.022 1.000 0.976 0.949 0.918 0.883 0.845 0.800 0.739 0.669 0.594 0.515 0.435 0.370 0.294 0.272 0.271 0.248 NA

1.038 1.042 1.042 1.043 1.047 1.044 1.035 1.061 1.078 1.090 1.095 1.096 1.091 1.084 1.072 1.058 1.041 1.020 1.000 0.977 0.950 0.923 0.890 0.855 0.812 0.758 0.697 0.630 0.561 0.488 0.428 0.359 0.329 0.320 0.297 0.251

1.059 1.058 1.062 1.061 1.063 1.061 1.051 1.072 1.087 1.095 1.098 1.097 1.092 1.083 1.072 1.057 1.041 1.021 1.000 0.977 0.953 0.925 0.895 0.860 0.820 0.771 0.716 0.656 0.592 0.525 0.467 0.404 0.370 0.356 0.334 0.290

1.072 1.071 1.072 1.073 1.074 1.073 1.064 1.081 1.091 1.098 1.102 1.098 1.093 1.083 1.072 1.058 1.041 1.021 1.000 0.977 0.954 0.928 0.897 0.865 0.825 0.781 0.729 0.673 0.614 0.550 0.495 0.437 0.401 0.384 0.362 0.320

1.081 1.078 1.083 1.082 1.082 1.080 1.073 1.088 1.098 1.102 1.103 1.100 1.094 1.085 1.072 1.057 1.041 1.020 1.000 0.979 0.955 0.929 0.898 0.869 0.830 0.787 0.739 0.685 0.630 0.572 0.518 0.462 0.425 0.407 0.385 0.346

1.091 1.085 1.090 1.089 1.088 1.089 1.083 1.092 1.101 1.105 1.106 1.100 1.094 1.085 1.072 1.057 1.040 1.021 1.000 0.978 0.954 0.929 0.899 0.869 0.833 0.792 0.744 0.693 0.640 0.585 0.533 0.481 0.443 0.423 0.403 0.369

1.092 1.093 1.095 1.093 1.095 1.093 1.086 1.099 1.105 1.107 1.107 1.104 1.095 1.085 1.072 1.057 1.040 1.022 1.000 0.978 0.953 0.927 0.899 0.868 0.834 0.795 0.748 0.699 0.648 0.595 0.545 0.495 0.458 0.438 0.416 0.386

1.102 1.105 1.103 1.102 1.102 1.101 1.098 1.106 1.111 1.111 1.111 1.105 1.096 1.087 1.072 1.056 1.041 1.021 1.000 0.977 0.952 0.927 0.899 0.869 0.835 0.798 0.754 0.708 0.662 0.610 0.562 0.515 0.479 0.455 0.436 0.410

1.107 1.114 1.113 1.110 1.111 1.110 1.105 1.114 1.115 1.116 1.114 1.108 1.102 1.086 1.074 1.057 1.041 1.020 1.000 0.976 0.952 0.926 0.898 0.869 0.834 0.799 0.758 0.713 0.668 0.619 0.573 0.530 0.495 0.470 0.449 0.424

1.122 1.117 1.123 1.120 1.119 1.119 1.113 1.122 1.123 1.124 1.121 1.115 1.106 1.092 1.077 1.058 1.041 1.022 1.000 0.976 0.951 0.925 0.896 0.868 0.834 0.799 0.759 0.716 0.672 0.628 0.582 0.540 0.507 0.483 0.461 0.443

position was determined, values of the dose rate constant are not provided since air kerma strength results were not available. G. Uncertainty analysis

An uncertainty analysis is presented for the measurements and calculations performed in water as recommended by the 2004 AAPM TG-43U1 report. 1. Measurement uncertainties Double uncertainties k = 2 in the PTW model 34013 ionization chamber energy correction and exposure calibration coefficients were ±1% and 2%, respectively. Precision of Source:detector positioning and anode motion within the sheath was ±0.2 mm. Combined in quadrature, these uncerMedical Physics, Vol. 33, No. 11, November 2006

tainties in positioning caused dosimetric uncertainties of 4.6% at r0. No measurement-medium correction factor was ascribed since transverse-plane measurements of g r with the ion chamber were directly performed in water. Variations in current and power supply voltage were much less than 1%. The quadrature sum of these Type B uncertainties is 4.6%. Taking the quadrature sum of this value with a Type A uncertainty of 3%, based on repetitive measurements of dose rate using the chamber for all Sources at all three operating voltages, gave a total k = 2 uncertainty of 5.5% for measurement of Ḋ r0 , 0 . 2. Calculation uncertainties On average, the Monte Carlo statistical uncertainties k = 2 in calculations of dose to water at 1 and 5 cm on the

Medical Physics, Vol. 33, No. 11, November 2006

0.976 0.986 1.000 1.011 1.052 1.077 1.082 1.069 1.042 0.943 0.874 0.789 0.667 0.512

0° 10° 20° 30° 40° 50° 60° 70° 80° 100° 110° 120° 130° 140° 150° 160°

1.024 1.029 1.041 1.054 1.072 1.082 1.080 1.067 1.043 0.942 0.875 0.812 0.705 0.564 0.413 0.313

degrees F 5 , 40

0° 10° 20° 30° 40° 50° 60° 70° 80° 100° 110° 120° 130° 140°

degrees F 2 , 0 40

0.993 1.001 1.013 1.024 1.052 1.072 1.075 1.063 1.037 0.953 0.895 0.820 0.709 0.564

F 2 , 50

1.050 1.054 1.059 1.065 1.075 1.080 1.075 1.062 1.036 0.950 0.894 0.825 0.731 0.616 0.473 0.364

F 5 , 50

Solid-angle weighted average ratio

1.050 1.056 1.066 1.075 1.087 1.093 1.087 1.070 1.041 0.941 0.891 0.810 0.711 0.585 0.443 0.336

F 5 , 45

Solid-angle weighted average ratio

0.997 1.008 1.022 1.031 1.066 1.087 1.087 1.072 1.044 0.946 0.879 0.798 0.679 0.530

Measured F 2 , 45

0.99

0.99 0.98 0.99 1.01 0.99 0.98 0.98 0.99 1.00 1.00 0.99 1.01 1.02 1.00 0.94 0.91

PTW 40 MCNPF 5 ,

1.01

0.98 0.99 1.00 1.01 1.00 0.99 0.99 0.99 0.99 1.00 1.00 1.02 1.05 1.07

0.99

0.99 0.99 1.00 1.01 1.00 0.99 0.99 0.99 1.00 0.99 1.00 0.99 1.00 0.99 0.95 0.90

PTW 45 MCNPF 5 ,

1.01

0.98 1.00 1.01 1.02 1.00 1.00 0.99 1.00 1.00 1.00 1.00 1.01 1.04 1.07

0.99

0.97 0.98 0.99 1.00 0.98 0.98 0.98 0.99 1.00 1.00 1.00 1.00 1.00 1.00 0.96 0.91

PTW 50 MCNPF 5 ,

1.01

0.98 0.99 0.99 1.00 0.99 0.98 0.98 0.99 0.99 1.00 1.01 1.03 1.06 1.09

0.997 1.012 1.025 1.033 1.068 1.085 1.085 1.071 1.042 0.945 0.877 0.796 0.681 0.539 0.383

5° 15° 25° 35° 45° 55° 65° 75° 85° 95° 105° 115° 125° 135° 145° 155° 165°

1.052 1.057 1.066 1.075 1.085 1.085 1.081 1.062 1.024 0.976 0.914 0.840 0.746 0.631 0.510 0.404 0.335

degrees F 7 , 40

0° 10° 20° 30° 40° 50° 60° 70° 80° 100° 110° 120° 130° 140° 150°

Measured/calculated PTW 45 PTW 50 degrees F 3 , 40 MCNPF 2 , MCNPF 2 ,

PTW 40 MCNPF 2 ,

TABLE VI. Measured F r , and comparisons to calculated results for the model S700 Axxent™ Source.

1.018 1.027 1.037 1.042 1.065 1.080 1.079 1.065 1.038 0.954 0.896 0.824 0.721 0.590 0.426

F 3 , 50

1.073 1.076 1.080 1.083 1.086 1.086 1.076 1.056 1.021 0.979 0.929 0.866 0.794 0.692 0.579 0.429 0.383

F 7 , 50

Solid-angle weighted average ratio

1.065 1.071 1.077 1.087 1.093 1.093 1.084 1.063 1.023 0.977 0.920 0.849 0.758 0.650 0.529 0.428 0.354

F 7 , 45

Solid-angle weighted average ratio

1.021 1.036 1.048 1.053 1.083 1.095 1.092 1.074 1.044 0.947 0.882 0.803 0.695 0.558 0.402

Measured F 3 , 45

0.99

0.99 0.99 1.00 0.99 0.98 0.98 0.99 1.00 1.00 1.00 1.00 0.99 0.99 0.98 0.97 0.99 0.94

PTW 40 MCNPF 7 ,

1.00

0.98 0.99 1.00 1.01 1.00 0.99 0.99 0.99 1.00 1.00 1.00 1.01 1.03 1.04 1.01

0.99

0.99 0.99 1.00 1.00 0.99 0.99 1.00 1.01 1.00 1.00 1.00 0.99 0.98 0.97 0.95 0.96 0.91

PTW 45 MCNPF 7 ,

1.00

0.98 1.00 1.01 1.02 1.01 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.02 1.03 0.99

0.99

0.99 0.99 0.99 0.99 0.98 0.99 0.99 1.00 1.00 1.00 1.00 1.00 1.00 1.00 0.99 0.89 0.91

PTW 50 MCNPF 7 ,

1.00

0.98 0.99 0.99 1.00 0.99 0.99 0.99 0.99 1.00 1.00 1.01 1.02 1.04 1.05 1.00

Measured/calculated PTW 45 PTW 50 MCNPF 3 , MCNPF 3 ,

PTW 40 MCNPF 3 ,

4030 Rivard et al.: Dosimetry parameters for the Xoft Axxent X-Ray Source 4030

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Rivard et al.: Dosimetry parameters for the Xoft Axxent X-Ray Source

transverse plane = 90° were 0.2% and 0.4%, respectively. The photoionization cross sections used were those recommended in the 2004 AAPM TG-43U1 report, with k = 2 uncertainties of 2.4% as reported by Rivard et al.37 Averaged over the energy spectra for the three operating voltages, the impact of the photoionization cross-section uncertainty on the transverse-plane dose rate at 1 and 5 cm is 0.2% and 0.9%, respectively. These are less than those reported by Rivard et al. for the 103Pd source because of the higher average photon energy of the Source. The estimated dosimetric impact of Source geometry uncertainties due to variation in anode thickness is 1.5%, and internal positioning ±0.2 mm within the sheath are 4% and 0.8% at 1 and 5 cm, respectively. Estimates of uncertainties in photon energy spectra on the transverse plane, based on a Monte Carlo parametric study varying material thicknesses, indicate that the dosimetric impact of Source spectrum uncertainties could be as high as 2% and 8% at 1 and 5 cm, respectively. In total, the quadrature sum of these k = 2 uncertainties on ḋ r = 1 cm, 0 and ḋ r = 5 cm, 0 are 4.7% and 8.2%, respectively. These uncertainties are comparable to those reported for other low-energy, photon-emitting sources. IV. SUMMARY This seminal report of the Xoft Axxent™ X-Ray Source, an electronic brachytherapy source, presents the in-water brachytherapy dosimetry parameters, Ḋ r0 , 0 , g P r , and F r , . These parameters were obtained using both measurements and calculations for three operating voltages. These data demonstrate customized depth-dose capabilities through varying the operating voltage. Furthermore, photon-energy spectra and azimuthal-angle dependence of in-water dose rate are presented. Additional research is in process at the University of Wisconsin to confirm results presented herein using different measurement techniques and Monte Carlo calculations. Finally, preparations are under way to perform a multi-institutional postmarket trial for breast cancer using accelerated partial breast irradiation and a balloon-based catheter system. ACKNOWLEDGMENTS Research support for some of the authors M.J.R., S.D.D., and L.A.D. was provided by Xoft, Inc. Tim Bohm of UW reviewed the Axxent™ Monte Carlo Source model, Robert R. Burnside of Xoft, Inc. assisted with some of the experimental measurements, and Sou-Tung Chiu-Tsao provided enlightening discussions on the compatibility of these datasets with various treatment planning systems such as BrachyVision™ and PLATO™. Finally, Michael Mitch, Stephen Seltzer, and Michelle O’Brien of the National Institute of Standards and Technology are gratefully acknowledged for providing the preliminary HPGe photon-energy spectra measurements and for efforts towards establishing traceable reference-quality measurements. a

This work was presented in part at the 27th annual meeting of the American Brachytherapy Society on May 15, 2004, and at the 46th annual

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meeting of the American Association of Physicists in Medicine on July 28, 2004. b Author to whom correspondence should be addressed; electronic mail: mrivard@tufts-nemc.org 1 T. W. Rusch and M. J. Rivard, “Application of the TG-43 dosimetry protocol to electronic brachytherapy sources,” Radiother. Oncol. 71(S2), S84 abstract 2004 . 2 S. Chiu-Tsao, T. Rusch, S. Axelrod, H. Tsao, and L. Harrison, “Dose response of GafChromic XR-T film to a new electronic brachytherapy source,” Radiother. Oncol. 71(S2), S84 abstract 2004 . 3 T. Rusch, S. Davis, L. DeWerd, R. Burnside, S. Axelrod, and M. Rivard, “Characterization of a new miniature x-ray source for electronic brachytherapy,” Med. Phys. 31, 1807 abstract 2004 . 4 S. Chiu-Tsao, T. Rusch, S. Axelrod, H. Tsao, and L. Harrison, “Radiochromic film dosimetry for a new electronic brachytherapy source,” Med. Phys. 31, 1913 abstract 2004 . 5 J. Fowler, R. Dale, and T. Rusch, “Variation of RBE with dose and dose rate for a miniature electronic brachytherapy source,” Med. Phys. 31, 1927 abstract 2004 . 6 R. M. Douglas, J. Beatty, K. Gall, R. F. Valenzuela, P. Biggs, P. Okunieff, and F. S. Pardo, “Dosimetric results from a feasibility study of a novel radiosurgical source for irradiation of intracranial metastases,” Int. J. Radiat. Oncol., Biol., Phys. 36, 443–450 1996 . 7 J. S. Vaidya, M. Baum, J. S. Tobias, D. D’Souza, S. V. Naidu, S. Morgan, M. Metaxas, K. J. Harte, A. P. Sliski, and E. Thomson, “Targeted intraoperative Radiotherapy Targit : An innovative method of treatment for early breast cancer,” Ann. Oncol. 12, 1075–1080 2001 . 8 J. S. Vaidya, M. Baum, J. S. Tobias, S. Morgan, and D. D’Souza, “The novel technique of delivering targeted intraoperative radiotherapy Targit for early breast cancer,” Eur. J. Surg. Oncol. 28, 447–454 2002 . 9 M. Dinsmore, K. J. Harte, A. P. Sliski, D. O. Smith, P. M. Nomikos, M. J. Dalterio, A. J. Boom, W. F. Leonard, P. E. Oettinger, and J. C. Yanch, “A new miniature x-ray source for interstitial radiosurgery: Device description,” Med. Phys. 23, 45–52 1996 . 10 J. Beatty, P. J. Biggs, K. Gall, P. Okunieff, F. S. Pardo, K. J. Harte, M. J. Dalterio, and A. P. Sliski, “A new miniature x-ray source for interstitial radiosurgery: Dosimetry,” Med. Phys. 23, 53–62 1996 . 11 J. C. Yanch and K. J. Harte, “Monte Carlo simulation of a miniature, radiosurgery x-ray tube using the ITS 3.0 coupled electron-photon transport code,” Med. Phys. 23, 1551–1558 1996 . 12 R. Nath, L. L. Anderson, G. Luxton, K. A. Weaver, J. F. Williamson, and A. S. Meigooni, “Dosimetry of interstitial brachytherapy sources: Recommendations of the AAPM Radiation Therapy Committee Task Group No. 43,” Med. Phys. 22, 209–234 1995 . 13 M. J. Rivard, B. M. Coursey, L. A. DeWerd, W. F. Hanson, M. S. Huq, G. S. Ibbott, M. G. Mitch, R. Nath, and J. F. Williamson, “Update of AAPM Task Group No. 43 Report: A revised AAPM protocol for brachytherapy dose calculations AAPM Report No. 84 ,” Med. Phys. 31, 633–674 2004 . 14 B. Fraass, K. Doppke, M. Hunt, G. Kutcher, G. Starkschall, R. Stern, and J. Van Dyke, “American Association of Physicists in Medicine Radiation Therapy Committee Task Group 53: Quality assurance for clinical radiotherapy treatment planning,” Med. Phys. 25, 1773–1829 1998 . 15 J. F. Williamson, B. M. Coursey, L. A. DeWerd, W. F. Hanson, and R. Nath, “Dosimetric prerequisites for routine clinical use of new low energy photon interstitial brachytherapy sources,” Med. Phys. 25, 2269–2270 1998 . http://rpc.mdanderson.org/rpc/htm/Home htm/Low-energy.htm last accessed August 20, 2006 . 16 J. W. Motz and R. C. Placious, “Bremsstrahlung cross-section measurements for 50 keV electrons,” Phys. Rev. 109 235–242 1958 . 17 M. J. Berger and S. M. Seltzer, “Bremsstrahlung and photoneutrons from thick tungsten targets,” Phys. Rev. C 2 621–631 1970 . 18 J. J. DeMarco, T. D. Solberg, R. E. Wallace, and J. B. Smathers, “A verification of the Monte Carlo code MCNP for thick target bremsstrahlung calculations,” Med. Phys. 22, 11–16 1995 . 19 J. R. Mercier, D. T. Kopp, W. D. McDavid, S. B. Dove, J. L. Lancaster, and D. M. Tucker, “Modification and benchmarking of MCNP for lowenergy tungsten spectra,” Med. Phys. 27 2680–2687 2000 . 20 S. Gallardo, J. Rodenas, and G. Verdu, “Monte Carlo simulation of the Compton scattering technique applied to characterize diagnostic x-ray spectra,” Med. Phys. 31, 2082–2090 2004 . 21 B. Wang, C.-H. Kim, and X. G. Xu, “Monte Carlo modeling of a highsensitivity MOSFET dosimeter for low- and medium energy photon

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Brachytherapy 7 (2008) 351e354

ABSTRACT

Keywords:

Xoft electronic brachytherapy; Brachytherapy; Endometrial cancer

Introduction Endometrial cancer is the most common gynecologic malignancy in the United States. An estimated 39,080 new patients will be diagnosed with endometrial cancer in 2007 (1). A standard treatment for endometrial cancer consists of a total abdominal hysterectomy with bilateral salpingo-oophorectomy followed by adjuvant radiation therapy. Received 20 December 2007; accepted 28 May 2008. Dr. Dickler discloses that he is on the Scientific Advisory Board of Xoft, Inc. * Corresponding author. Department of Radiation Oncology, Little Company of Mary Hospital, 2800 West 95th Street, Evergreen Park, IL 60805. Tel.: Ăž1-708-229-5560; fax: Ăž1-708-229-5378. E-mail address: atd22_99@yahoo.com (A. Dickler).

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A. Dickler et al. / Brachytherapy 7 (2008) 351e354

%V95

%V100

%V150

Patient

6.65 Gy per fx

7.0 Gy per fx

10.5 Gy per fx

1 2 3 4 5 6 7 8 9 10 11

99.78 99.54 99.93 99.55 99.72 99.85 99.56 99.75 99.69 99.58 99.86

99.27 99.49 99.61 99.27 99.60 99.84 99.61 99.95 99.66 99.72 99.81

98.89 98.55 99.81 98.67 99.02 99.37 98.42 99.13 99.09 98.86 98.80

98.10 98.79 99.16 98.53 99.13 99.50 99.07 99.78 99.26 99.34 98.93

22.07 25.98 42.17 33.41 36.91 41.82 38.61 49.99 40.68 41.13 21.16

42.16 48.32 59.68 53.77 56.55 67.29 60.35 75.69 72.52 67.40 44.38

Mean p Value

99.7 ns

99.6

99.0 ns

99.1

35.8 !0.05

58.9

A. Dickler et al. / Brachytherapy 7 (2008) 351e354

353

Table 2 Normal tissue doses IB

XB Rectal %V50