Functional imaging in radiotherapy by BIR Publishing

10 JULY 2015

FUNCTIONAL IMAGING IN RADIOTHERAPY Venue: Charles Darwin House, London CPD: 6 CREDITS

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BIR ANNUAL CONGRESS 2015 4–5 NOVEMBER LONDON • Room 1

Primers for the non-specialists

Day 1

Day 2 Clinical hybrid imaging in oncology • Room 1

Session organised by Dr David Wilson, Consultant Interventional MSK Radiologist, Oxford University Hospitals NHS Trust

Session organised by Dr Gopinath Gnanasegaran, Consultant Physician in Nuclear Medicine, St Thomas’ Hospital

• Room 2

Session organised by Mr Andy Rogers, Head of Radiation Physics, Nottingham University Hospitals NHS Trust

Session organised by Dr Hardi

Radiation protection — current issues in molecular imaging and radiotherapy

View the full programme and register: www.bir.org.uk

Emergency radiology — advances in trauma imaging and Essentials for the radiology trainee Madani, Radiology Registrar, Royal Free London Hospital and Dr Ausami Abbas, Cardiothoracic Radiology Post CCT

Welcome and thank you for coming to “Functional imaging in radiotherapy” organised by The British Institute of Radiology. We wish you a very enjoyable and educational experience. Certificate of attendance This meeting has been awarded 6 RCR category I CPD credits. Your certificate of attendance will be emailed to you within the next 2 weeks once you have completed the online event survey at: https://www.surveymonkey.com/s/Functionalimaginginradiotherapy

BIR Annual Congress 2015: 4–5 November, London

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Programme

09:00 Registration and refreshments 09:30 Welcome and introduction Mr Jamie Dean, PhD Student, The Institute of Cancer Research 09:45

An introduction to functional imaging modalities and what they can tell us Dr Simon Hughes, Consultant in Radiology and Nuclear Medicine, Nottingham University Hospital

10:15 An introduction to radiotherapy Mr Chris Bowen, Therapy Radiographer, Plymouth Hospitals NHS Trust 10:45 Refreshments 11:15 Radiobiology for radiotherapy Professor Kevin Prise, Professor of Radiation Biology, Queen’s University Belfast 11:45 Functional MRI and its application to radiotherapy treatment planning Dr Rafal Panek, MRI Physicist, Royal Marsden NHS Foundation Trust and Institute of Cancer Research 12:15 MRI and quality assurance Dr Peter Wright, Principal MR Physicist, Sheffield Teaching Hospitals NHS Foundation Trust 12:45 Lunch 13:45 PET-CT and its application to radiotherapy treatment planning Dr Robin Prestwich, Consultant Oncologist, Leeds Teaching Hospitals 14:15 PET-CT quality assurance Miss Lucy Pike, Clinical Scientist, King’s College London and Guy’s and St Thomas’ PET Centre 14:45 Radiobiological basis for dose painting Dr Chris South, Radiotherapy Physicist, Royal Surrey County Hospital 15:15 Refreshments 15:45 Radiotherapy trials utilising functional imaging Dr Liam Welsh, Consultant Clinical Oncologist, The Royal Marsden NHS Foundation Trust

16:15

The role of functional imaging and image registration for assessment of normal lung in thoracic radiotherapy Dr Rob Ireland, Lecturer in Image Guided Radiotherapy, Western Park Hospital and The University of Sheffield

16:45 Functional imaging for response assessment Dr Mike Partridge, Senior Group Leader for Radiotherapy Physics, CRUK/MRC Oxford Institute for Radiation Oncology 17:15 Close of event

Certificate of attendance This meeting has been awarded 6 RCR category I CPD credits. Your certificate of attendance will be emailed to you within the next 2 weeks once you have completed the online event survey at: https://www.surveymonkey.com/s/Functionalimaginginradiotherapy BIR Annual Congress 2015: 4â&#x20AC;&#x201C;5 November, London

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Speaker profiles (where supplied) Mr Chris Bowen Therapy Radiographer, Plymouth Hospitals NHS Trust Christopher Bowen is a Therapy Radiographer currently working at the Plymouth Oncology Centre as a Treatment Delivery Team Lead Radiographer. Since graduating from the South Wales School of Radiography in 1994 he spent many years as a rotational Radiographer but has specialised in treatment delivery since 2002. Currently he undertakes specialised treatments such as Stereotactic Ablative Radiotherapy (SABR) for lung cancers, Cranial Stereotactic, Volumetric Modulated Arc Therapy (VMAT) and Deep Inspiration Breath Hold (DIBH). Additionally he has experience in different imaging modalities such as megavoltage, kilovoltage, cone beam CT and implanted marker matching techniques. He also performs and facilitates training for junior staff in imaging and treatment delivery and is the Lead radiographer for the truebeam linear accelerator and Treatment Floor Radiation Protection Supervisor. He has a passion for innovation and implementation of new techniques and delivering high quality world class radiotherapy within a small but highly motivated and committed multidisciplinary team. Dr Rob Ireland Lecturer in Image Guided Radiotherapy, Western Park Hospital and The University of Sheffield Rob Ireland is an academic medical physicist with expertise in oncology image processing and clinical trials. Rob has been conducting radiotherapy imaging research and development at Weston Park Hospital in Sheffield since 2001 and is currently a Lecturer on Image Guided Radiotherapy at the University of Sheffield. Rob has published 20 academic papers, over 90 abstracts and has received numerous grants, including funding from CRUK and NIHR. The main themes of Robâ&#x20AC;&#x2122;s research focus on radiotherapy applications of image registration, validation of ventilation CT, and an investigation of the role of gas and proton MRI in lung cancer treatment planning and post-treatment evaluation. Dr Rafal Panek MRI Physicist, Royal Marsden NHS Foundation Trust and The Institute of Cancer Research Rafal Panek is an MRI Physicist conducting research in the field of functional MRI at the Royal Marsden NHS Foundation Trust and The Institute of Cancer Research. His current research focus is an evaluation of parameters defined by dynamic contrast enhanced MRI, blood oxygen level dependent MRI and diffusion weighted MRI as predictive biomarkers of poor outcome in head and neck patients and preclinical in vivo studies. Dr Panek collaborates with the MRI team within the Cancer Research UK 4

Cancer Imaging Centre at the Institute of Cancer Research and the Head and Neck clinical team at the Royal Marsden Hospital, which provides a unique opportunity to investigate techniques that can be effectively translated for the management of patients. Dr Mike Partridge Senior Group Leader for Radiotherapy Physics, CRUK/MRC Oxford Institute for Radiation Oncology Mike Partridge has been working in medical imaging and radiotherapy research for nearly 20 years. He studied natural sciences at Cambridge University and obtained a PhD in imaging at Cranfield University before working as a postdoctoral scientist at the Institute of Cancer Research, The Royal Marsden Hospital and the German Cancer Research Centre in Heidelberg. He moved to Oxford University in 2012 to start a new research group in radiotherapy physics. His current research focuses on functional imaging in radiotherapy with a particular focus on understanding the potential role of hypoxia imaging. This ranges from characterising heterogeneity at a cellular level and developing mathematical models that link hypoxia, imaging and radiation response to clinical studies investigating functional imaging to predict early response to therapy. When not at work he enjoys bird watching and walking. Miss Lucy Pike Clinical Scientist, King’s College London and Guy’s and St Thomas’ PET Centre Lucy Pike is a Clinical Scientist at the King’s College London and Guy’s and St Thomas’ PET Centre, London. Her current role involves providing support for clinical and research applications of PET-CT including the use of novel PET tracers and complex imaging techniques. In addition to this she manages the National Cancer Research Institute PET Core Lab, which provides technical support and develops standards for PET imaging in multicentre clinical trials. As part of the requirement for standardisation in multicentre clinical trials involving PET, she has been involved in developing a quality assurance program for inclusion of PET into radiotherapy treatment planning. Dr Robin Prestwich Consultant Oncologist, Leeds Teaching Hospitals Robin Prestwich trained in medicine at Oxford University graduating in 1998. His training in Clinical Oncology was based in Leeds and he gained his FRCR in 2006. He completed a PhD as a CRUK Clinical Training Fellow in 2009 exploring the role of the immune response in oncolytic virotherapy. Following completion of his training in Clinical Oncology in 2011, he completed a 1 year fellowship in the Department of Nuclear Medicine with his research primarily relating to the role of PET for radiotherapy planning. He has been a Consultant in Clinical Oncology since 2012 and is the chief investigator of three local studies exploring multimodality imaging for radiotherapy planning in head and neck cancer and lymphoma. 5

Professor Kevin Prise Professor of Radiation Biology, Queen’s University Belfast Kevin Prise is Professor of Radiation Biology and Deputy Director at the Centre for Cancer Research and Cell Biology, Queen’s University Belfast, where he has been since 2007. Prior to this he was Head of the Cell and Molecular Radiation Biology Group at the Gray Cancer Institute in Northwood, London. A biochemistry graduate of Aberdeen University, he has wide ranging interests in radiation biology including low dose, radiation quality and cell signalling mechanisms. His recent studies have been focused on developing new biological-based models for optimising advanced radiotherapies such as intensity modulated radiotherapy and particle therapies. He has over 250 publications. Dr Chris South Radiotherapy Physicist, Royal Surrey County Hospital Chris South has recently taken up the role of head of radiotherapy dosimetry at St Luke’s Cancer Centre, Guildford. From August 2012 to June 2015 he was deputy head of treatment planning at St Luke’s, prior to which he spent over a decade as a clinical radiotherapy physicist at the Royal Marsden Hospital in Sutton. In 2005 he began a part-time PhD at the Institute of Cancer Research on “The Use of Functional Imaging to Design Optimal Radiotherapy Dose Distributions”, graduating in 2011. He has been a registered Clinical Scientist since 2005 and has an MSc in Medical Physics from the University of Surrey (2001) and an MPhys from Oxford University (1998). Publications include “A theoretical framework for prescribing radiotherapy dose distributions using patient-specific biological information” (South et al, Med. Phys. 2008) and “Dose prescription complexity versus tumour control probability in biologically conformal radiotherapy” (South et al, Med. Phys. 2009). Dr Liam Welsh Consultant Clinical Oncologist, The Royal Marsden NHS Foundation Trust Liam Welsh read physics at the University of Cambridge and stayed on to research a PhD in structural biophysics with Richard Perham and Don Marvin in the Biochemistry Department. After a period as a Wellcome Trust post-doc in Richard Perham’s lab, Liam left academia to train in medicine at Guy’s, King’s and St Thomas’ Medical School, graduating with honours in 2004. After general medical training at St Bart’s and the Royal Free Hospital, Liam moved to the Royal Marsden Hospital to train in Clinical Oncology. During his SpR training Liam spent two years as a clinical research fellow within the Head and Neck Unit at the Royal Marsden working on functional MRI in head and neck cancer. Liam was appointed as a Consultant Clinical Oncologist in Neuro-oncology at the Royal Marsden in 2015, and retains a research interest in functional imaging.

Dr Peter Wright Principal MR Physicist, Sheffield Teaching Hospitals NHS Foundation Trust Peter Wright is the Principal MR Physicist at Sheffield Teaching Hospitals NHS Foundation Trust after previously being at the University Hospital of North Midlands where he supported the commissioning of three new Siemens MR systems and subsequent protocol setup and image quality improvement. Prior to the University Hospitals of North Midlands, Peter spent 3 years as the in-house physicist at Leeds Musculoskeletal and Biomedical Research Unit (LMBRU), a National Institute for Health Research funded unit at Leeds NHS Trust. This role included his clinical medical physics training. Prior to this he obtained his PhD at the University of Nottingham in functional MRI and related parameters using 7 T and 3 T MRI systems.

Abstracts (where supplied) An introduction to radiotherapy Mr Chris Bowen Radiotherapy is a highly specialised, and effective treatment for treating cancer, however it can cause serious acute and chronic side effects including inducing second malignancies. Owing to this risk the use of ionising radiation is stringently monitored to be as safe as possible allowing delivery of optimised high doses to target volumes while sparing normal healthy tissue. In order to do this radiotherapy treatments need to be extremely accurate to reduce risk to patients. Radiotherapy planning relies on the use of different imaging modalities to provide as accurate a picture as possible of the target volume requiring treatment. In turn Radiotherapy treatment has to be delivered precisely and consistently. Patient positioning and monitoring is key to the reproducibility of treatments. Many factors can influence the accuracy of treatment delivery but there are practical ways to minimise the impact of these factors. This talk aims to provide a basic introduction to Radiotherapy for audience members who are not conversant with the discipline of Radiotherapy. Educational aims: • To deliver an introduction to radiotherapy and patient pathway • Present the advantages, disadvantages and benefits of radiotherapy • Outline the radiotherapy patient pathway and different delivery methods of radiotherapy • Define volumes used to delineate treatment target areas • Highlight importance for consistency and accuracy in radiotherapy planning and treatment • Provide insight into how daily positional accuracy is assessed and monitored by different imaging methods • Highlight some of the major issues affecting patient position • Discuss potential innovative developments in radiotherapy Learning objectives: • To provide the audience with a brief and basic introduction to the nature of radiotherapy treatments • Demonstrate the necessity for accurate and reproducible positioning for radiotherapy patients • Demonstrate the need for good imaging interpretation and protocols Radiobiology for radiotherapy Professor Kevin Prise Radiation biology contributes to radiotherapy by providing the conceptual basis for its use and providing rationale for the development of new approaches and the scheduling choices that need to be made for its delivery. Underpinning this 8

are the “5Rs” of radiation biology which include intrinsic radiosensistivity, repair, repopulation, reassortment and reoxygenation. Cancer is defined by a series of hallmarks that differentiate tumours from the controlled growth and metabolism of normal tissues. Many of these hallmarks lead to differences in tumours that impact on radiobiological mechanisms and can be accessed by functional imaging for targeted radiotherapies for both clinical and preclinical studies. This overview lecture will give an understanding of some of the relevant concepts from radiobiology. Educational aims: • Review the basic radiobiological principles underpinning radiotherapy • Review the role of functional imaging from a radiobiological perspective Learning objectives: • Understand the key hallmarks of cancer • Understand the “5Rs” of radiobiology Further reading: • Hanahan D and Weinberg R.A, (2011), Hallmarks of cancer: the next generation. Cell 144, 646-74 • Boss MK1, Bristow R, Dewhirst MW. (2014), Linking the history of radiation biology to the hallmarks of cancer. Radiat Res. 181, 561-77. • Basic Clinical Radiobiology 4th Edition, (Eds M.C. Joiner and A. Van der Kogel) Arnold Hodder 2009 Functional MRI and its application to radiotherapy treatment planning Dr Rafal Panek In addition to high-resolution morphological images providing excellent soft tissue contrast, MRI can also be used to obtain information on the functional properties of tissues. These techniques exploit pathophysiological changes occurring within tumours as their contrast mechanism, such as altered perfusion, cellularity or blood oxygenation level. Therefore, functional techniques are increasingly being used for tumour detection, monitoring of treatment response, and detection of relapsed disease. Functional MRI methods such as diffusion weighted imaging (DWI) and blood oxygen level dependent MRI (BOLD) are functional techniques based on the endogenous contrast in the tissue, while others such as dynamic contrast enhanced (DCE) or dynamic susceptibility contrast (DSC) are based on exogenous gadolinium based contrast agents. In the radiotherapy context the ultimate goal of functional imaging is to identify radio-resistant disease and thus provide a biological target volume for dose boosting or alternative treatment. It can also be used to visualize organs at risk and is widely used to identify nerve fibres, which can be useful for regional sparing. Geometric accuracy is therefore essential to allow correct registration of functional MR images with anatomical MRI and CT datasets. The need for patient imaging in the radiotherapy treatment position poses additional challenges and requires development of MRI-compatible immobilization setups and RF coil configurations.

This presentation will cover an introduction to functional MRI methods, examples of method implementation in the context of RT planning (clinical trials) and challenges in functional MRI. Learning objectives: • To understand what functional information can be obtained using MRI • To understand main limitation of method implementation for RT planning Further reading: • Padhani AR, Liu G, Koh DM, Chenevert TL, Thoeny HC, Takahara T, DzikJurasz A, Ross BD et al. Diffusion-Weighted Magnetic Resonance Imaging as a Cancer Biomarker: Consensus and Recommendations, Neoplasia 2009; 11(2):102-125. • Galbán CJ, Chenevert TL, Meyer CR, Tsien C, Lawrence TS, Hamstra DA, Junck L et al. The parametric response map is an imaging biomarker for early cancer treatment outcome. Nature medicine, 2009;15(5): pp.572-6. • O’Connor J P B, Jackson A , Parker G J M, Jayson G C. DCE-MRI biomarkers in the clinical evaluation of antiangiogenic and vascular disrupting agents. British Journal of Cancer 2007; 96: 189–195. • Nuyts S. Defining the target for radio-therapy of head and neck cancer. Cancer Imaging 2007; 7:S50–S55. • Newbold K, Partridge M, Cook G, Sohaib SA, Charles-Edwards E, Rhys-Evans P, et al. Advanced imaging applied to radiotherapy planning in head and neck cancer: a clinical review. Br J Radiol. 2006 Jul 1;79(943):554–61. • Welsh L, Panek R, McQuaid D, Dunlop A, Schmidt M, Riddell A, Koh DM et al. Prospective, longitudinal, multi-modal functional imaging for radical chemoIMRT treatment of locally advanced head and neck cancer: the INSIGHT study. Radiat Oncol. 2015 May 15;10(1):112. • Wang D, Doddrell DM. Geometric distortion in structural magnetic resonance imaging. Current Medical Imaging Reviews 2005; 1: 49-60. • Metcalfe P, Liney GP, Holloway L, Walker A, Barton M, Delaney GP, Vinod S, Tome W. The potential for an enhanced role for MRI in radiation-therapy treatment planning. Technol Cancer Res Treat. 2013 Oct;12(5):429-46. • van der Heide UA, Houweling AC, Groenendaal G, Beets-Tan RGH, Lambin P. Functional MRI for radiotherapy dose painting. Magnetic resonance imaging. Elsevier Inc; 2012 Nov 1;30(9):1216–23. MRI and quality assurance Dr Peter Wright The MRI scanner is in its very a nature a complex machine, which means that when gremlins do get into the system it can be very hard to pin point the exact problem quickly and return the equipment to clinical use. By setting up and running a robust quality assurance scheme, any issues with the MR system will be highlighted at an early stage and potentially aid the manufacturer engineers in identifying the specific issue and allow a speedy resolution. 10

This talk will aim to highlight what determines image quality in MR and how these parameters are measured through quality assurance using the most commonly available phantoms. Finally, a few of the most common artefacts will be presented. Of those artefacts produced by physiological effects, we will discuss how these artefacts can be reduced. Educational aims: • Examine the components of an MR system • Discuss contributors to image quality • Examine parameters measured as part of a QA procedure and available phantoms • Review of artefacts seen in MRI and their cause PET-CT and its application to radiotherapy treatment planning Dr Robin Prestwich There has been an explosion of interest in the potential use of PET-CT for radiotherapy planning. The majority of work has focussed on 18 F-fluoro-2 deoxy D-glucose (FDG) although there is interest in imaging multiple biological processes with novel PET tracers. PET-CT may have a role in 3 key areas of radiotherapy planning: target selection, tumour delineation, treatment individualisation and adaptation. In terms of target selection, PET has a complimentary role to anatomical imaging for some tumour types although for some tumour sites no superiority of PET has been demonstrated; it is necessary to be aware of the possibility of false positive and negative results. With regard to the use of PET for contouring, the question of whether it is possible to use a qualitative diagnostic imaging modality for quantitative tumour edge delineation remains controversial. Multiple manual and automated algorithms for contouring areas of PET avidity have been proposed. Pathological validation is only available in a limited number of reported series. The ability of functional imaging with PET to evaluate tumour heterogeneity/biology both spatially and temporally has led to interest in the use of PET imaging as an imaging biomarker to guide approaches to treatment individualisation/adaptation. Significant challenges remain prior to adoption into clinical practice. Educational aims: • To learn about the potential role of PET in radiotherapy planning for target selection • To learn about the potential role of PET in radiotherapy planning for tumour contouring • To learn about the potential role of PET as an imaging biomarker to allow the individualisation of treatment/on-treatment adaptation

PET-CT quality assurance Miss Lucy Pike PET is increasingly used for disease staging, therapy monitoring and follow up for a range of tumour types in routine clinical management. In many tumour types PET can provide greater sensitivity and specificity for nodal staging than CT or MR and can detect functional changes much earlier than anatomical changes. The additional functional information from PET can complement the anatomical data provided by CT and there is much interest in incorporating this into radiotherapy planning to help more accurately define treatment volumes and potentially reduce radiation doses to healthy tissue. There is an increasing case to support the inclusion of FDG-PET in radiotherapy planning for some tumour types, but inappropriate use of PET to reduce treatment volumes could impair rather than improve patient outcomes. It is important therefore that a solid evidence base is established through clinical trials to determine how PET imaging is best utilised in radiotherapy planning. Evaluation of volume delineation techniques incorporating PET versus conventional contouring techniques in radiotherapy should be carefully planned and executed through clinical trials incorporating rigorous and consistent quality control and imaging protocols. This talk aims to outline the processes involved in incorporating PET into radiotherapy planning and discusses some of the technical challenges that may be encountered. In particular this draws on our own experience of developing PET-CT protocols and the patient pathway for a phase I FDG-guided dose escalation study. Educational aims: • To provide an overview of the technical requirements for incorporating PET-CT into radiotherapy planning • To discuss the practical issues of incorporating PET-CT into radiotherapy planning Learning objectives: • Identify the steps involved in setting up a quality assurance program for use of PET in radiotherapy • Identify the potential sources of error and how to minimise them through rigorous QC tests References and citations: • Somer EJ, Pike LC, Marsden PK. Recommendations for the use of PET and PET-CT for radiotherapy planning in research projects. Brit J Radiol. 2012;85(1016): e544-8. • Thomas CM, Pike LC, Hartill CE, Baker S, Woods E, Convery DJ, et al. Specific recommendations for accurate and direct use of PET-CT in PET guided radiotherapy for head and neck sites. Med Phys. 2014;41(4):041710. • Boellaard R, Delgado-Bolton R, Oyen WJ, Giammarile F, Tatsch K, Eschner W, et al. FDG PET/CT: EANM procedure guidelines for tumour imaging: version 12

2.0. Eur J Nucl Med Mol Imaging. 2015;42(2):328-54. Further reading: • Sattler B, Lee JA, Lonsdale M, Coche E. PET/CT (and CT) instrumentation, image reconstruction and data transfer for radiotherapy planning. Radiother Oncol. 2010;96(3):288-97. • Thorwarth D, Beyer T, Boellaard R, De Ruysscher D, Grgic A, Lee JA, et al. Integration of FDG-PET/CT into external beam radiation therapy planning Technical aspects and recommendations on methodological approaches. Nuklearmedizin-Nuclear Medicine. 2012;51(4):140-53 Radiobiological basis for dose painting Dr Chris South Traditionally a key aim in radiotherapy treatment planning has been to deliver a uniform high dose to a tumour. However, tumours are known to be biologically heterogeneous, with variations in a number of factors known to influence radiation response. Modern medical imaging techniques can provide information on the spatial distribution of many of these biological parameters. Technological advances in radiotherapy allow complex dose distributions to be calculated and delivered with unprecedented precision. It is therefore possible to design nonuniform dose prescriptions based on functional images, preferentially targeting higher doses to tumour regions at highest risk of recurrence, a process known as dose painting. A variety of methods have been proposed for linking local target dose to image intensity. In general, a model describing the radiobiological significance of the image data is used to optimise a non-uniform target dose distribution. The efficacy of such methods will depend on the accuracy of the interpretation and quantification of images as well as the correctness of the radiobiological model. Dose painting is technically feasible using a wide range of imaging modalities and planning techniques. Uncertainties in image interpretation and radiobiological modelling should be taken into account when predicting the efficacy of a given method. Educational aims: • To outline the principles of and rationale for dose painting • To describe the relative importance of various biological and radiobiological parameters • To compare and contrast a range of different approaches to dose painting Learning objectives: • Gain an appreciation of the range of imaging modalities and markers which may be used in dose painting • Gain an awareness of the strengths and weaknesses of a variety of methods for generating target dose distributions from functional images

The role of functional imaging and image registration for assessment of normal lung in thoracic radiotherapy Dr Rob Ireland Educational aims: • To review functional imaging of normal lung tissue in patients with lung cancer • To introduce examples of image registration applications for lung analysis Learning objectives: • To learn about novel applications of SPECT, MRI and CT that provide ventilation and perfusion information to assist with the planning and evaluation of radiotherapy Aims of imaging the ‘normal’ lung: • Radiotherapy planning: reduce the dose to normal lung tissue • Evaluation of treatment: assess radiation induced damage to normal lung Methods: • SPECT: e.g. papers by Lawrence Marks, Mike Partridge and Konstantin Lavrenkov • Hyperpolarised gas MRI: Papers by Rob Ireland and Jim Wild • Ventilation CT: Papers by Thomas Guerrero, Richard Castillo, Tokihiro Yamamoto • Ventilation MRI? Several papers by Grzegorz Bauman Results/findings: • Potential reduction of dose to normal lung tissue demonstrated in several papers • Potential identification of radiation induced lung damage also demonstrated Key points/conclusions: • Reduction of dose and identification of radiation damage in lung cancer patients has been investigated with a variety of imaging modalities. Challenges still exist before such techniques can be used routinely References and citations: • Ireland RH, et al. 2007 Feasibility of image registration and intensitymodulated radiotherapy planning with hyperpolarized helium-3 magnetic resonance imaging for non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 68 273-81 • Marks LB et al. 1997 Physical and biological predictors of changes in wholelung function following thoracic irradiation. Int J Radiation Oncology Biol Phys 39 563-570 • Munley MT, Marks LB et al. 1999 Multimodality nuclear medicine imaging in three-dimensional radiation treatment planning for lung cancer: challenges and prospects. Lung Cancer 23 105–114 14

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Simon BA 2000 Non-invasive imaging of regional lung function using x-ray computed tomography. J Clin Monit Comput 2000 16 433-42 Vinogradskiy YY, et al. 2012 Use of weekly 4DCT-based ventilation maps to quantify changes in lung function for patients undergoing radiation therapy Med Phys 39 289-98

Further reading: • Partridge M, et al. 2010 Imaging of normal lung, liver and parotid gland function for radiotherapy Acta Oncol 49 997-1011 • Simon BA, et al. 2012 What can computed tomography and magnetic resonance imaging tell us about ventilation? J Appl Physiol 113 647-57 Functional imaging for response assessment Dr Mike Partridge Medical imaging has for a long time played an absolutely central role in radiotherapy, with x-Ray CT being used to accurately optimise treatments employing patient-specific anatomy. However, magnetic resonance imaging (MRI) and positron emission tomography (PET) enable us to map not just patient anatomy but also physiological function, giving important information about the biochemistry of tumours in addition to their physical characteristics (size and location). For example, we know that regions of tumours that have low oxygen levels (hypoxic) offer resistance to both radiotherapy and chemotherapy. By imaging hypoxic tumour regions we can monitor response to therapy and, for patients who do not appear to be responding to a treatment, either escalate radiation dose or add a hypoxia-modifying drug (or both). Dynamic contrast-enhanced (DCE) and diffusion-weighted (DW) MRI can be used to map blood flow and perfusion and/or diffusion properties in tissue, telling us about oxygen supply. PET can be used to map glucose metabolism using fluorine-18 labelled fluorodeoxyglusoce (18F-FDG) and hypoxia using fluoromisonidazole (18F-FMISO). There is growing evidence that imaging changes in early functional response may enable more accurate prediction of outcome in a specific patient than just their pre-treatment images. However, we do not yet know what the best imaging modality to use is, what the optimum time-point to observer response is, or whether imaging with more than one modality will add additional information. In this lecture we will review some of the recently published work showing the use of dw MRI and FMISO PET for early response prediction and discuss how this information might be used in biologically-adaptive radiotherapy workflows. Educational aims: • To give a brief overview of current published work demonstrating the use of functional imaging to assess response to treatment • To illustrate how early response assessment might be incorporated into strategies for biologically-adaptive treatment 15

Learning objectives • To learn about current published work demonstrating the use of functional imaging to assess response to treatment • To learn about how early response assessment might be incorporated into strategies for biologically-adaptive treatment References and citations: • Lambrecht, M., et al. (2010). “Role and value of diffusion-weighted MRI in the radiotherapeutic management of head and neck cancer.” Expert Rev Anticancer Ther 10(9): 1451-1459. • Hoeben, B. A., et al. (2013). “18F-FLT PET during radiotherapy or chemoradiotherapy in head and neck squamous cell carcinoma is an early predictor of outcome.” J Nucl Med 54(4): 532-540. • Zips, D., et al. (2012). “Exploratory prospective trial of hypoxia-specific PET imaging during radiochemotherapy in patients with locally advanced headand-neck cancer.” Radiother Oncol 105(1): 21-28. • Tran, L. B., et al. (2015). “Predictive value of (18)F-FAZA PET imaging for guiding the association of radiotherapy with nimorazole: A preclinical study.” Radiother Oncol 114(2): 189-194. Further reading: • Jaffray, D. A. (2012). “Image-guided radiotherapy: from current concept to future perspectives.” Nat Rev Clin Oncol 9(12): 688-699.

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