March/April 2018
www.OncologyNurseAdvisor.com A F O R U M F O R P H YS I C I A N A S S I S TA N T S
FEATURE
SIDE-EFFECT MANAGEMENT Dietary PUFAs: Are All Food Sources Equally Beneficial?
FEATURE
Managing Cognitive Deficits in Survivors of Childhood Cancer
ASK THE EXPERTS
When Phlebotomy Is Not Enough: Cytoreductive Strategies for PV
FROM CANCERCARE
Sitting With Silence in End-of-Life Cancer Care
RADIATION & YOUR PATIENT
The Controversy Over Proton Beam Therapy
ISSUES IN CANCER SURVIVORSHIP
Incidence of PTSD High Among Patients With Cancer
ASK A PHARMACIST
FDA, ASHP Act to Manage, Prevent Drug Shortages
Prevention and Treatment of Adverse Skin Effects: RT-Associated Dermatitis More than half of patients undergoing radiation therapy develop radiodermatitis, a type of burn injury.
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Oncology Nurse Advisor (ISSN 2154-350X), March/April 2018, Volume 9, Number 2. Published 6 times annually by Haymarket Media Inc, 275 7th Avenue, 10th Floor, New York, NY 10001. For Advertising Sales & Editorial, call (646) 638-6000 (M-F, 9am-5pm, ET). Postmaster: Send changes of address to Oncology Nurse Advisor, P.O. Box 316, Congers, NY 10920. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without permission in writing from the publisher.
EDITORIAL BOARD Eucharia Borden, MSW, LCSW, OSW-C Lankenau Medical Center Wynnewood, Pennsylvania Ann J. Brady, MSN, RN-BC Huntington Cancer Center Pasadena, California Jiajoyce R. Conway, DNP, CRNP, AOCNP Cancer Care Associates of York York, Pennsylvania Marianne Davies, DNP, ACNP, AOCNP Smilow Cancer Center @ Yale New Haven New Haven, Connecticut Frank dela Rama, RN, MS, AOCNS Palo Alto Medical Foundation Palo Alto, California Donald R. Fleming, MD Cancer Care Center, Davis Memorial Hospital Elkins, West Virginia Leah A. Scaramuzzo, MSN, RN-BC, AOCN Kalispell Regional Healthcare Kalispell, Montana Lisa A. Thompson, PharmD, BCOP Kaiser Permanente Colorado Rosemarie A. Tucci, RN, MSN, AOCN Lankenau Hospital Wynnewood, Pennsylvania Kara M. L. Yannotti, MMH, BSN, RN, CCRP John Theurer Cancer Center at Hackensack University Medical Center Hackensack, New Jersey
4 ONCOLOGY NURSE ADVISOR • MARCH/APRIL 2018 • www.OncologyNurseAdvisor.com
CONTENTS 7
24
March/April 2018
7
IN THE NEWS • Breast Cancer Therapies Associated With Increased Risk for Cardiovascular Disease • Chemotherapy Toxicity Risk Score Use Improved Treatment Choice for Elderly • Second-line Nilotinib May Lead to Treatment-Free Remission in Chronic Phase CML … and more
15
ONCOLOGY NURSE ADVISOR FORUM • USP Standards for Handling Hazardous Drugs • Monitoring CLL Treated With Venetoclax
18
FEATURES How to Manage Adverse Skin Effects of Radiation Therapy Megan Garlapow, PhD
40
belly
no food or drink
abdomen
npo
22
Bette Weinstein Kaplan
24
FIND US ON
Managing Cognitive Deficits in Survivors of Childhood Cancer Lauren Chatalian
26
42
Dietary PUFAs: Are All Food Sources Equally Beneficial?
ASK THE EXPERTS When Phlebotomy Is Not Enough: Cytoreductive Strategies for PV
Continues on page 6
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FEATURE ARTICLE New Hypertension Threshold Guides Blood Pressure Management During Cancer Treatment
CONTENTS
March/April 2018
Publication of the JNC 8 introduces a lower threshold for initiating hypertension treatment during cancer therapy. Shannon Aymes, MD
JOURNAL REVIEW 35
STAT CONSULT Palbociclib (Ibrance)
40
RADIATION & YOUR PATIENT The Emerging Controversy Over Proton Beam Therapy Bryant Furlow
42
COMMUNICATION CHALLENGES Wait … What Do You Mean? Ann J. Brady, MSN, RN-BC
44
THE TOTAL PATIENT Patient Support Program Provides Diversions During Chemotherapy Infusions Bette Weinstein Kaplan
45
FROM CANCERCARE Sitting With Silence in End-of-Life Cancer Care Glenn Meuche, LCSW
47
ISSUES IN CANCER SURVIVORSHIP Incidence of Posttraumatic Stress Disorder High Among Patients With Cancer Bette Weinstein Kaplan
48
ASK A PHARMACIST FDA and ASHP Actions That Manage or Prevent Drug Shortages Lisa A. Thompson, PharmD, BCOP
6 ONCOLOGY NURSE ADVISOR • MARCH/APRIL 2018 • www.OncologyNurseAdvisor.com
Lung Cancer Screening: Risk-Targeting Approach vs NLST Eligibility Criteria
A risk-targeting approach was more efficient in selecting high-risk patients for lung cancer screening. John Schieszer, MA
Hodgkin Lymphoma Treatment in EU vs US: Similarities Would Enable Worldwide Studies
A review of management approaches to Hodgkin lymphoma in Europe vs the United States/North America. John Schieszer, MA
REFLECTIONS A Witness to Letting Go: Nursing Care at the End of Life
A new oncology nurse reflects on the first time she provided comfort care for a patient and her family at the end of life. Danielle Gillaspie, RN, BSN
PUBLISHERS’ ALLIANCE: DOVE PRESS Approach and Management of Checkpoint Inhibitor-related Immune Hepatitis
A review of diagnostic parameters and management modalities for checkpoint inhibitor-induced hepatic toxicity is presented. Journal of Gastrointestinal Oncology
ON THE
WEB
IN THE NEWS Breast Cancer Therapies Associated With Increased Risk for Cardiovascular Disease Certain anticancer therapies may increase the risk of cardiovascular disease (CVD) for patients with breast cancer, a study published in Circulation has shown. The likelihood of cancer survivors dying from CVD vs cancer recurrence is increasing due to the improved efficacy of breast cancer therapies, making effective management and prevention of CVD a priority for this patient population as they age. Chemotherapeutic agents, endocrine therapies, HER2-targeted therapies, novel emerging therapies, and radiotherapy are associated with increased incidence of many cardiovascular diseases including left ventricular dysfunction (LVD), arrhythmias, conduction abnormalities, heart failure, thrombosis, and cardiomyopathy. Identifying at-risk patients is crucial. Myocardial strain imaging with speckle-tracking echocardiography is an effective predictor of cardiac dysfunction in patients receiving chemotherapy for breast cancer. Biomarkers such as brain natriuretic peptide (BNP) and troponin I are indicators of chemotherapy-induced cardiac disease and may accurately reflect radiotherapy-induced cardiotoxicity occurrence as well. Changes in clinical practice may also reduce the risk of CVD for patients with breast cancer. Previous studies have shown that the administration of dexrazoxane to patients receiving chemotherapy may decrease the incidence of heart failure and cardiac events. Delivery methods, such as doxorubicin as an intravenous infusion instead of a bolus dose, or liposomal formulations of doxorubicin compared to standard preparations, may preserve the efficacy of therapy while reducing the incidence of cardiotoxicity. Pharmacotherapy may also be an effective strategy for reducing the risk of CVD and breast cancer. Previous studies have suggested that prophylactic therapy with β-blockers, ACE-inhibitors, ARBs, statins, and aspirin may improve long-term outcomes for patients with breast cancer. Exercise and survivorship programs may also improve CVD risk among survivors. The authors concluded that “with the evolving intersection of the cardiovascular and oncologic fields, comprehensive care is an essential element in the management of cancer patients to maximize gains in cancer treatment while minimizing the potential deleterious impact on cardiovascular health.”
© ARNO MASSEE / SCIENCE SOURCE
Read more at http://bit.ly/2phX8SD.
Antenatal Cancer Therapy Associated With Specific Neonatal Complications The incidence of antenatal cancer treatment has increased over the past 2 decades, and although studies have been conducted to assess the effects of therapy on maternal,
neonatal, and obstetric outcomes, the small sample sizes have produced less than robust data. For this descriptive cohort study, researchers retrospectively and prospectively registered 1170 patients with cancer diagnosed during pregnancy who were entered into the International Network on Cancer, Infertility, and Pregnancy
www.OncologyNurseAdvisor.com • MARCH/APRIL 2018 • ONCOLOGY NURSE ADVISOR 7
IN THE NEWS
Read more at http://bit.ly/2pf9uuJ.
Study Links Opioid Use to Cancer Survival and Health Care Utilization Opioids are the standard of care for the treatment of cancer-related pain and preservation of quality of life, but these drugs lead to a high rate of adverse effects and potential overdoses. Therefore, the association between health care utilization, survival, and HO defined as 5 mg opioid use requires further investigation. OME/day or more. For this retrospective study, researchers identified 1386 patients with newly diagnosed stage IV solid tumors and analyzed opioid usage records within 90 days of initiating anticancer therapies. Patients were stratified by use: low opioid (LO) use was defined as less than 5 mg oral morphine equivalents (OME)/day, and high opioid (HO) use was defined as 5 mg or more OME/day. Health care utilization was defined as the number of urgent care, inpatient, and emergency room visits. Baseline demographic characteristics were similar between patients in the HO use and LO use groups. Results showed that patients with HO use were significantly associated with greater health care utilization compared with those with LO use. Approximately 33% of patients in the HO use group had 2 or more healthcare visits compared with 22% of patients in the LO use group by 6 months, and increased health care utilization was sustained throughout the first year.
Median survival was shorter in the HO use group (5.5 months) than in the LO use group (12.4 months). Further analysis with multivariate models adjusting for age, gender, and prognostic group confirmed that median survival was lower among patients in the HO use group. Read more at http://bit.ly/2FTW4xT.
Chemotherapy Toxicity Risk Score Use Improved Treatment Choice for Elderly Elderly patients with advanced cancer who have a high chemotherapy toxicity risk score (CTRS) may experience significant toxicity and increased rates of hospitalization when treated with combination chemotherapy. The current criteria determining anticancer therapy for elderly patients — such as physician’s evaluation of fitness, geriatric assessment (GA) — often fail to take into consideration the entire clinical picture, leading to difficulties in choosing standard therapy (ST) or reduced therapy (RT) for this patient population. For this prospective observational study, researchers enrolled 58 elderly patients with advanced cancer who were scheduled to receive first-line combination chemotherapy. Patients were categorized into 2 groups: high-risk patients with a CTRS of 10 or greater for whom reduced dose combination or single-agent chemotherapy was the appropriate treatment choice, and patients with a CTRS of less than 10 for whom standard-dose therapy was appropriate. Of the 38 patients who received standard therapy, 21 patients had a CTRS of less than 10 and 17 had a CTRS of 10 or greater. Of the 20 patients who received reduced therapy, 12 had a CTRS of 10 or greater and 8 had a CTRS of less than 10. Among the patients in the ST group, 88% whose CTRS was 10 or greater had a significantly higher rate of toxicity compared with 40% of those whose CRTS was less than 10. Patients with a high CTRS score also had higher rates of hospitalization vs patients with low CTRS scores (50% vs 15%). Read more at http://bit.ly/2tN6Gda.
Cooling Therapy Demonstrates Effectiveness Against Hand-Foot Syndrome Although pegylated liposomal doxorubicin (PLD) is an effective treatment for various cancers, it is associated with hand-foot syndrome (HFS), a specific toxicity that greatly
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© JGI / JAMIE GRILL / GETTY IMAGES
(INCIP). Patients were assigned to 3 subgroups stratified by year of diagnosis: 1996 to 2004, 2005 to 2009, and 2010 to 2016. The long-term results of patients were analyzed, including changes to patient characteristics, outcomes, and treatment methods, as well as complications such as preterm, prelabor rupture of membranes (PPROM)/preterm contractions, small for gestational age, and admission to the neonatal intensive care unit (NICU). Associations between small-for-gestational age and platinum-based chemotherapy, and between NICU admission and taxane chemotherapy, were observed. Gastrointestinal cancers were associated with the high risk of NICU admission whereas thyroid cancers had the lowest risk compared with breast cancer, the most frequently reported malignancy during this study. Abdominal and cervical surgery led to a decreased likelihood of NICU admission.
reduces quality of life for patients. Previous studies demonstrated the efficacy of applying ice packs around the wrist and ankles but faced challenges in preparation. In this retrospective study, researchers evaluated the effect of frozen gloves and socks (FGS) therapy on 96 patients with advanced ovarian cancer who presented with PLD-induced or PLD+carboplatin (CBDCA)-induced hand-foot syndrome. The patients put the garments on 15 minutes prior to infusion and kept them on until 15 minutes after infusions, putting on fresh pairs after 45 minutes. FGS therapy was applied during all chemotherapy cycles unless refused. Incidence of HFS in the study population was 51% in patients treated with PLD and 38% in patients treated with PLD+CBDCA. Dose reductions were made in 41% and 5% of patients, respectively. PLD or PLD+CBDCA were discontinued in 31 and 17 patients, respectively, with only 2 discontinuations in the PLD group and none in the PLD+CBDCA group attributed to hand-foot syndrome. Ninety-six percent of patients completed FGS therapy, and only 3 patients discontinued FGS therapy due to associated pain from cooling. Read more at http://bit.ly/2Dvjapg.
© THODONAL / GETTY IMAGES
Fatigue Linked to Levothyroxine Use in Breast Cancer Studies have shown that 15% to 25% of patients with breast cancer undergoing adjuvant chemotherapy concurrently receive levothyroxine, a potential contributory factor for hormone dysregulation that may cause fatigue. For this secondary analysis of the BEATE and INVEST study — clinical trials assessing the effect of exercise during chemotherapy on fatigue — researchers analyzed the outcomes of 111 women and divided them into 3 groups. Group 1 consisted of women with breast cancer undergoing chemotherapy without exercise intervention, group 2 was women with breast cancer who were randomized to the exercise arm of the BEATE study, and group 3 was comprised of healthy patients from the INVEST study who had the same exercise intervention as patients in group 2. Levothyroxine therapy was significantly associated with lowered thyroid-stimulating hormone levels (TSH); TSH levels in patients not taking levothyroxine were comparable with those in healthy women. L-triiodothyronine (T3) levels were significantly reduced in women taking levothyroxine concurrently with chemotherapy but not in patients not taking levothyroxine.
Among patients not undergoing any exercise intervention, levothyroxine use was significantly associated with increased physical fatigue during chemotherapy. This association may have been affected by TSH levels, which also appeared to affect fatigue by increasing cortisol levels. The authors concluded that “breast cancer patients on [levothyroxine] treatment may need special monitoring of their thyroid levels and of fatigue during chemotherapy and should be supported to perform resistance exercise.” Read more at http://bit.ly/2DvctDP.
Melanoma Outcomes Improved for Some With Targeted and Immunotherapy Obesity has been associated with worse survival in various cancers, but its impact on mortality among patients with melanoma is unknown. Results of a recently published study showed that being obese may lead to improved survival outcomes among Obesity and therapy male patients with metastatic melanotype benefited men. ma treated with targeted or immune therapies compared with patients with a normal body mass index (BMI). For this retrospective study, investigators selected 6 cohort studies that included a total of 1918 patients to analyze the relationship of BMI (normal, overweight, or obese) with survival outcomes among patients with metastatic melanoma who underwent targeted therapy, immunotherapy, or chemotherapy. Of the study population, 36% of patients were determined to have a normal BMI, 37% were overweight, and 27% were obese. Analysis revealed that obese patients had improved survival, but only among those who received targeted therapy or immunotherapy. Furthermore, the survival benefit was observed only among obese men; no such associations were observed among women. No improvements in PFS or OS were observed among patients who received chemotherapy, regardless of BMI. Read more at http://bit.ly/2ItQGzY.
Second-line Nilotinib May Lead to TreatmentFree Remission in Chronic Phase CML Long-term treatment-free remission (TFR) is achievable for patients with chronic myeloid leukemia (CML) who had
www.OncologyNurseAdvisor.com • MARCH/APRIL 2018 • ONCOLOGY NURSE ADVISOR 13
IN THE NEWS
Read more at http://bit.ly/2HBsURc.
Bisphosphonate Therapy Underutilized in Multiple Myeloma Bone Disease Management Current treatment recommendations suggest initiating IV bisphosphonates for patients with multiple myeloma, not only for bone disease but also, as previous studies have demonstrated, possible benefit to overall survival and progressionfree survival. The direction of treatment upon response to primary myeloma therapy and real-world use in this patient population, however, requires further investigation. For this retrospective study, researchers collected data from 11,112 patients with multiple myeloma and evaluated the timing, frequency, schedule, change in dosing schedule, and discontinuation of zoledronic acid or pamidronate. Secondary outcomes included identifying predictors of bisphosphonate treatment initiation and to further analyze data once patients were stratified by chronic kidney disease stage. After a median follow-up of 687 days, results showed that 63% of patients received at least 1 dose of bisphosphonate therapy; patients received first dose of bisphosphonates after a mean time of 106 days after multiple myeloma diagnosis. Therapy was initiated within the first year of diagnosis in approximately 58% of patients, but slightly more than 50% had a change in dosing or discontinued treatment.
Patients who had poor renal function as measured by eGFR were less likely to receive bisphosphonate therapy and experienced a greater delay in therapy initiation. Therapy was initiated in 72% of patients at eGFR stage 1 vs 24% at eGFR stage 5, and treatment was initiated 25 days after diagnosis vs 70 days after diagnosis, respectively. Read more at http://bit.ly/2tS1SDk.
Recognizing Reduced Dietary Intake in Hospitalized Patients With Colorectal Cancer A common challenge faced by patients with colorectal cancer (CRC) is disease-related symptoms such as malnutrition and weight loss that often lead to prolonged hospitalization, poor clinical/surgical outcomes, and reduced survival and tolerance for Disease symptoms therapy. also increase risk. For this study, researchers analyzed the results of 1131 hospitalized patients with CRC who completed the nutritionDay survey, a 1-day cross-sectional audit that assesses patient nutritional status, food intake, characteristics, disease profiles, and symptoms. Investigators studied multiple patient- and disease-related variables that could potentially affect dietary intake (eg, age, sex, cancer stage, therapy situation, therapy goals). A univariate analysis revealed that female gender, advanced cancer stage, lower self-reported performance scores, longer duration of hospitalization, unintentional weight loss during the last 3 months, lower body mass index (BMI), therapy situation, palliative therapy, and higher number of drugs ingested daily were significantly associated with reduced dietary intake. Symptoms such as pain, depression, weakness, lack of appetite, and tiredness were also associated with reduced intake. The researchers suggested that management of related symptoms should be included in dietary assessments to achieve an optimal nutritional intake. Read more at http://bit.ly/2FUk4AP.
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© CAROLEGOMEZ / GETTY IMAGES
deep molecular response (DMR) after second-line nilotinib, according to a recently published study. BCR-ABL1 tyrosine kinase inhibitors (TKIs) have improved survival outcomes for CML dramatically, increasing the focus of TFR as a therapeutic outcome. For the ENESTop phase 2 study, researchers enrolled 163 patients with CML who received TKI therapy for at least 3 years, and achieved DMR (MR4.5) after switching to nilotinib for 2 years or longer after first-line imatinib; these patients underwent consolidation for 1 year on nilotinib. Of the 163 patients, 77% (126) were eligible to discontinue nilotinib and enter the TFR phase. After 48 weeks, 58% (73) of patients remained in TFR and by week 96 53% (67) of patients remained in TFR. Fifty-six patients were unable to maintain TFR and reinitiated nilotinib therapy, but 52 regained MR4 and MR4.5 by the 96-week cutoff date; 50% of patients regained MR4 or MR4.5 by week 12.0 and 13.1, respectively. No patients progressed to the accelerated or blast crisis phases of CML.
ONCOLOGY NURSE ADVISOR FORUM QUESTIONS & ANSWERS
Our Consultants
USP STANDARDS FOR HANDLING HAZARDOUS DRUGS What is the USP <800> and what do I need to know about it as an oncology nurse? — Name withheld upon request
Ann J. Brady, MSN, RN-BC, symptom management care coordinator at the Cancer Center, Huntington Hospital, Pasadena, California.
Jiajoyce R. Conway, DNP, FNP-C, AOCNP, NP-C, oncology nurse practitioner at Cancer Care Associates of York in York, Pennsylvania. Abimbola Farinde, PharmD, MS, BCPP, CGP, LCDC, PM/ PRC, FASCP, FACA, FNAP, Rsci, ARSPharmS, clinical pharmacist specialist, Clear Lake Regional Medical Center, Webster, Texas. Donald R. Fleming, MD, hematologist/oncologist, Cancer Care Center, Davis Memorial Hospital, Elkins, West Virginia.
USP <800> is the current chapter regarding standards for hazardous drugs issued by the US Pharmacopeial Convention. This is a nonprofit organization whose mission is to improve global health through public standards and programs that assist in ensuring the quality, safety, and benefit of medicines and foods. These standards were developed to increase awareness, standardize practice, and reduce the risk of exposure to hazardous drugs. Although NIOSH defines criteria and identifies hazardous drugs, USP developed standards for handling hazardous drugs to minimize the risk to public health. General Chapter <800> includes the requirements of personnel handling hazardous drugs; facility and engineering controls; procedures for deactivating, decontaminating, and cleaning; spill control; documentation; and medical surveillance. These standards apply to all healthcare personnel who receive, prepare, administer, transport, or otherwise come in contact with hazardous drugs. USP <800> will be enforced by each state’s board of pharmacy or their delegated agency effective December 1, 2019. — Leah Scaramuzzo, MSN, RN-BC, AOCN
MONITORING CLL TREATED WITH VENETOCLAX What are key monitoring guidelines when chronic lymphocytic leukemia (CLL) is treated with venetoclax (Venclexta)? — Name withheld on request
Kerstin L. Lappen, RN, MS, ACNS, ACHPN, clinical nurse specialist, palliative care consult service, Abbott Northwestern Hospital, Allina Health System, Minneapolis, Minnesota.
Chronic lymphocytic leukemia is one of the most common leukemic diagnoses in the United States. Treatment is based on the presence of cytochrome abnormalities specific to deletion of 17p [del(17p)]. del(17p) is a reflection of the loss of TP53 gene expression and is a prognostic indicator of response to chemotherapy and disease control.1 Venetoclax, a BCL-2 inhibitor, is the first drug granted FDA approval for the treatment of del(17p) CLL in patients who have received at least one prior therapy. The drug is given in a ramp-up dose administration. With this administration method, patients are subject to a significant and rapid reduction in tumor burden that can result in tumor lysis syndrome (TLS). Therefore, TLS prophylaxis with close monitoring of blood chemistries and CBC is crucial to managing the care of these patients. Other supportive measures can include aggressive hydration and hyperuricemic management. — Jiajoyce R. Conway, DNP, CRNP, AOCNP
K. Lynne Quinn, RN, MSN, CRNP, AOCNP, director of oncology, Bryn Mawr Hospital and Bryn Mawr Health Center, Bryn Mawr, Pennsylvania.
Lisa A. Thompson, PharmD, BCOP, clinical pharmacy specialist in oncology, Kaiser Permanente, Colorado.
REFERENCE 1. Borg MA, Clemmons A. Venetoclax: a novel treatment for patients with del(17p) chronic
Rosemarie A. Tucci, RN, MSN, AOCN, manager for oncology research & data services, Lankenau Hospital, Wynnewood, Pennsylvania.
lymphocytic leukemia. J Adv Pract Oncol. 2017;8:647-652.
DO YOU HAVE A QUESTION FOR OUR CONSULTANTS? Send it to editor.ona@haymarketmedia.com.
www.OncologyNurseAdvisor.com • MARCH/APRIL 2018 • ONCOLOGY NURSE ADVISOR 15
FEATURE | Side-Effect Management
How to Manage Adverse Skin Effects of Radiation Therapy This review of radiodermatitis discusses preventive and treatment options available that reduce and/or minimize symptoms of the condition. MEGAN GARLAPOW, PhD
R
adiodermatitis occurs in more than 50% of patients who undergo radiation therapy (RT) for cancer with or without chemotherapy, with some estimates of the rate of radiodermatitis as high as 95%.1, 2 Early radiodermatitis occurs within 2 months of RT. Late RD occurs more than 2 months after RT, sometimes not occurring until years later.1
© BSIP / MEDICAL IMAGES
DEVELOPMENT AND CLINICAL SYMPTOMS
Red patches indicating acute radiodermatitis on mastectomy scar
Acute radiodermatitis, which is a type of burn injury, varies in severity and how it responds to therapy. It forms after the delivery of an erythema dose of ionizing radiation to the skin, usually at a dose of 2 Gy or more. Factors inherent in the patient can affect the severity and response to therapy. In fact, researchers recently revealed an association between a single nucleotide polymorphism in the X-ray repair cross-complementing gene 1 (XRCC1) gene and the development of acute radiodermatitis in patients who underwent RT to treat nasopharyngeal carcinoma (odds ratio [OR] =2.860; P = .006; 95% CI, 1.354-6.043).3 Clinical symptoms usually appear within a few weeks of initiating radiation therapy. Acute radiodermatitis is characterized by the manifestation of red patches, sometimes with desquamation or blistering. Although most cases heal after several weeks, persistent reactions can cause complications. Chronic radiodermatitis occurs from the administration of suberythema doses of ionizing
18 ONCOLOGY NURSE ADVISOR • MARCH/APRIL 2018 • www.OncologyNurseAdvisor.com
radiation over a longer stretch of time, such as what would occur in radiologists prior to the implementation of x-ray filters. Telangiectasia on atrophic and fragile skin characterizes late-onset radiodermatitis. More commonly known as spider veins, telangiectases are widened, tiny blood vessels that form gradually. They typically form in clusters and gradually. Telangiectasia can significantly affect therapeutic regimens and a patient’s quality of life. LASER TREATMENT OPTIONS “Today, there is insufficient evidence available to form recommendations that would prevent or reduce radiodermatitis. However, several multidisciplinary groups have proposed guidelines that suggest management strategies with the objective to avoid or reduce the severity of radiodermatitis reactions,” wrote the authors of a recent review.1 Although evidence-based recommendations on the prevention or reduction of radiodermatitis are lacking, some early advances in its treatment are promising. For example, low level light therapy (LLLT) or vascular lasers can manage symptoms. Results from preclinical and clinical research suggest LLLT could have bio-stimulating properties, thereby promoting the regeneration of tissues for quicker healing, less inflammation, and fibrosis prevention. In the hospital-sponsored TRANSDERMIS trial in Belgium (ClinicalTrial.gov Identifier: NCT02443493), 120 patients with breast cancer who received identical RT regimens after Light micrograph of a skin section showing normal dermis tissue has been replaced with connective tissue (pale pink).
Results from 10 trials indicated use of topical corticosteroids led to reduced occurrence of the wet desquamation of radiodermatitis. lumpectomy were equally randomized to undergo LLLT or placebo 2 days per week, immediately after radiation therapy.2 LLLT was delivered via a class IV MLS® M6 laser combining 2 synchronized laser diodes in the infrared range (808 to 905 nm) with a fixed energy density (4 J/cm 2).2 Researchers used the Radiation Therapy Oncology Group (RTOG) and the Radiation-Induced Skin Reaction Assessment Scale (RISRAS) to score skin reactions. Patients responded to the Skindex-16 questionnaire to assess quality of life. Researchers collected measurements on the first day with an RT dose of 40 Gy and again at the end of therapy, with a total dose of 66 Gy.2 At the initial RT administration, no significant differences in distribution of RTOG grades occurred between the 2 groups. By the end of RT, however, significantly more patients in the placebo group (30%) experienced RTOG grade 2 or greater than in the LLLT group (6.7%; P =.004).2 This RISRAS score, which is objective, supported these results. Both the RISRAS score and the results from Skindex-16 indicated better quality of life in the LLLT group than the placebo group.2 These results suggest that LLLT can both prevent the development of radiodermatitis and manage the symptoms of the condition.2 Pulsed dye laser treatment can resolve telangiectasia that characterizes late-onset radiodermatitis. Therapy with pulsed dye laser has been used to treat hypertrophic scars, warts, hemangiomas, port wine stains, telangiectasias, and fibrosis.
© CNRI / SCIENCE SOURCE
TOPICAL TREATMENT OPTIONS
In a meta-analysis of randomized clinical trials on the use of topical corticosteroids in the treatment and prevention of radiodermatitis in patients who underwent RT for breast cancer, results from 845 patients across 10 trials indicated use of topical corticosteroids led to reduced occurrence of the wet desquamation of radiodermatitis (OR, 0.29; 95% CI, 0.19-0.45; P <.0001) and lower average radiodermatitis score (standardized mean difference, –0.47; 95% CI, –0.61 to 0.33; P <.00001).4 Another topical treatment that shows promise is a norepinephrine adrenergic vasoconstrictor cream (NG12-1) applied prior to the administration of RT. A preclinical model using www.OncologyNurseAdvisor.com • MARCH/APRIL 2018 • ONCOLOGY NURSE ADVISOR 19
FEATURE | Side-Effect Management rats indicated a 100% prevention of radiodermatitis with this approach.5 “Current best clinical practices for the prevention and treatment of acute radiation dermatitis are limited to agents that minimize discomfort, promote healing, or prevent infection,” wrote the authors.5 “No interventions to date have been shown to be clinically effective, and none address the core problem of preventing or minimizing acute radiation damage to the skin.”5 However, results from a phase 2A clinical trial (ClinicalTrial. gov Identifier: NCT01263366) showed significantly reduced radiodermatitis at the site of NG12-1 administration vs control areas within the same radiotherapy field. The average score for dermatitis was 0.47 in the area pretreated with NG12-1 and 0.72 in the untreated control area (P =.022). All 9 patients experienced reduced severity of radiodermatitis in the treatment areas, and no serious adverse events occurred.5 “The limitations of the present pilot phase 2a study include the small number of treated subjects, the lack of blinding between drug-treated and placebo-treated topical sites, and a 50-cm2 SDAS within a much larger chest and axilla radiation field,” noted the authors.5
To prevent acute radiodermatitis, daily dermocosmetic use is useful from the beginning of radiotherapy,” concluded the authors of one review. “There is evidence for the efficacy of PBM [LLLT] to both prevent and cure acute radiodermatitis. In chronic radiodermatitis, treatment with vascular lasers, especially pulsed dye laser, using short pulse durations, has been shown to be effective with an excellent tolerance, inducing a better quality of life for the patients.”1 ■
CONCLUSIONS
4. Haruna F, Lipsett A, Marignol L. Topical management of acute radiation
Megan Garlapow is a medical writer based in Tempe, Arizona. REFERENCES 1. Seité S, Bensadoun RJ, Mazer JM. Prevention and treatment of acute and chronic radiodermatitis. Breast Cancer (Dove Med Press). 2017;9:551-557. 2. Robijns J, Censabella S, Claes S, et al. Prevention of acute radiodermatitis by photobiomodulation: a randomized, placebo-controlled trial in breast cancer patients (TRANSDERMIS trial) [published online February 10, 2018]. Lasers Surg Med. doi: 10.1002/lsm.22804 3. Chen H, Wu M, Li G, Hua L, Chen S, Huang H. Association between XRCC1 single-nucleotide polymorphism and acute radiation reaction in patients with nasopharyngeal carcinoma: a cohort study. Medicine. 2017;96(44):e8202.
These results seem to indicate an early but changing tide in the treatment of radiodermatitis. As evidence mounts, clinicians can choose preventive and therapeutic options for their patients. “Today, there is increasing evidence to support various strategies to limit and treat cutaneous reactions to radiotherapy.
dermatitis in breast cancer patients: a systematic review and metaanalysis. Anticancer Res. 2017;37(10):5343-5353. 5. Cleary JF, Anderson BM, Eickhoff JC, Khuntia D, Fahl WE. Significant suppression of radiation dermatitis in breast cancer patients using a topically applied adrenergic vasoconstrictor. Radiat Oncol. 2017;12(1):201.
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FEATURE | Breast Cancer Prevention
Dietary PUFAs: Are All Food Sources Equally Beneficial? Researchers compared the association between diets high in plant-based vs marine-based polyunsaturated fatty acids and the risk for breast cancer. BETTE WEINSTEIN KAPLAN
B
© LISOVSKAYA / GETTY IMAGES
y now the health benefits of consuming foods and supplements containing omega3 polyunsaturated fatty acids (PUFAs) are known. Recent research, however, demonstrates that not all PUFAs function the same way. Three types of omega-3 fatty acids are involved in human physiology: alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). ALA, derived from plants, is found in walnuts and other nuts, flaxseed and other edible seeds, and in oils (eg, canola, soy, hemp). EPA and DHA are marine-based and sourced from salmon, tuna, trout, and other fatty fish, as well as phytoplankton and algae.
Seafood is high in EPA and DHA, which are better PUFA sources, but higher intake of plant ALA PUFAs can equalize the benefits.
OMEGA-3 PUFAS AND BREAST CANCER In a recent study, David Ma, PhD, and colleagues in the Department of Human Health and Nutritional Sciences at the University of Guelph, Canada, found that eating a diet rich in omega-3 fatty acids has a significant inhibitory effect on breast cancer. “There is certainly evidence that plant based omega-3s are beneficial for cancer prevention and treatment. Similarly, there is evidence for fish oil as well. One of the goals of our study was to define what the relative difference is,” explained Dr Ma. This is the first study to compare the potential of plant-based vs marine-based omega-3 fatty acids in inhibiting the development of mammary tumors. Its significance lies in that plants are the primary source of omega-3 fatty acids in the Western diet. Dr Ma’s team worked with mice used in studies on prevention and treatment of
22 ONCOLOGY NURSE ADVISOR • MARCH/APRIL 2018 • www.OncologyNurseAdvisor.com
HER-2 positive breast cancer. HER-2 positive cancer, which occurs in 25% to 30% of breast cancer cases, is highly aggressive and has a poor prognosis. The Guelph group compared the effects of diets containing the different types of omega-3s on this type of cancer. Their findings showed that marine-based fatty acids are more effective at inhibiting tumor development and growth than are plant-based ALA (D Ma, oral communication, January 2018). LIFELONG USE, LONG-TERM BENEFITS The researchers began their study by observing how these tumors develop. To do this, they first exposed the mice to omega-3 diets in utero via maternal diet consumption. This allowed the group to compare how well the different fatty acids prevented tumors from developing over the mice’s lifetimes. Study findings showed that over the course of lifelong exposure both plant-derived and marine-based omega-3 fatty acids are incorporated into mammary tumor tissue, thus allowing them to change the composition of the tissue. In addition, all types of omegas act to prevent and combat tumors by activating genes in the body’s immune system to block the pathways tumors use to grow. Lifelong exposure to fatty acids derived from marine sources was 8 times more effective at preventing and controlling HER-2 positive breast cancer than plant-derived fatty acids. Compared with plant-based ALA, consumption of marinebased DHA and EPA reduced the size of the tumors by 60% to 70% and reduced the development of tumors by one-third. Dr Ma said that plant-derived ALA was beneficial, but higher doses were necessary to achieve the same benefits. However, he noted, consuming higher doses of plant-based ALA will work well for people who do not like fish or fish oil. IMPLICATIONS FOR NURSING When asked how Oncology Nurse Advisor’s readers can interpret his study results, Dr Ma said, “Extrapolating from mouse studies is always challenging. A best guess is a minimum of 2 to 3 servings of fish per week, which is the current recommendation for prevention of heart disease.” Patients who wish to use fish oil or krill supplements should take several capsules
Food Sources for Omega-3 Fatty Acids This chart lists the 12 foods that offer the highest amounts of omega-3 fatty acids. Recommended daily intake is 250-500 mg for healthy adults. Food
Omega-3 Content
Serving Size
Anchovies
951 mg
1 can
Caviar
1086 mg
1 tbsp
Chia seeds
4915 mg
1 oz
Cod liver oil
2664 mg
1 tbsp
Flaxseeds
2338 mg
1 tbsp seeds
Herring
3181 mg
1 fillet
Mackerel
4107 mg
1 piece
Oysters
565 mg
6 oysters
Salmon
4023 mg
½ fillet
Sardines
2205 mg
1 cup
Soybeans
1241 mg
½ cup
Walnuts
2542 mg
1 oz (≈ 7 walnuts)
Type of Omega-3 ALA
• •
• •
EPA
DHA
•
•
• • • • •
• • • • •
• •
• •
KEY: ALA, α-linolenic acid; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid. SOURCE: Hjalmarsdottir F. 12 foods that are very high in omega-3. Healthline website. https://www.healthline.com/nutrition/12-omega-3-rich-foods. Published June 3, 2017. Accessed March 14, 2018.
per day depending on the level of purity. A simple calculation is: if the capsule is 50% EPA+DHA per 1 g-capsule, then 7 capsules are needed per day. However, patients who choose to use a high-concentration formulation would significantly reduce the number of capsules they take. Dr Ma stressed that the main take-away is the importance of getting more omega3s in our diets from plant or seafood. “Not only will there be benefits for cancer prevention but omega-3s are also good for the health of heart, brain, vision, etc.” ■ Bette Weinstein Kaplan is a medical writer based in Tenafly, New Jersey.
All types of omegas prevent and combat tumors by activating genes in the immune system to block the pathways tumors use to grow.
REFERENCE Liu J, Abdelmagid SA, Pinelli CJ, et al. Marine fish oil is more potent than plant based n-3 polyunsaturated fatty acids in the prevention of mammary tumours [published online December 27, 2017]. J Nutr Biochem. doi: 10.1016/j.jnutbio.2017.12.011
www.OncologyNurseAdvisor.com • MARCH/APRIL 2018 • ONCOLOGY NURSE ADVISOR 23
FEATURE | Pediatric Oncology
Managing Cognitive Deficits in Survivors of Childhood Cancer This review discusses how adverse effects such as “chemo brain” may present extra challenges and what can be done to ease these patients’ anxiety.
© BAPTISTE LIGNEL / SCIENCE SOURCE
Puzzles, word games, and integrative activities are critical for preventing cognitive deficits in children with cancer.
LAUREN CHATALIAN, LMSW
C
ancer-associated cognitive impairment, commonly known as chemo brain, is an adverse effect of cancer and its treatment that survivors experience to varying degrees. Symptoms generally include attention and concentration difficulties, reduced processing speed and executive function, and compromised shortterm memory.1 Chemo brain affects more than one-third of all survivors of childhood cancers. Cognitive dysfunction may arise at or soon after a cancer diagnosis; however, deficits may also arise several years later. Chemotherapy was thought to be the only cause of chemo brain, but research suggests that several types of cancer treatment, and even the cancer diagnosis itself, can cause these impairments.1 Children with cancer diagnosed at a young age appear to experience more chemo brain complications than any other patient group. As the childhood cancer survivor population increases, awareness of the potential long-term effects of cancer and its treatments is important.2 SUPPORT Childhood cancer poses many challenges for everyone affected. Each phase of a cancer diagnosis poses its own difficulties, and children and their families need to feel supported throughout. While a child is undergoing treatment or is in the hospital, support is readily available in the form of hospital-based emotional support and interventions.2 Unfortunately, many childhood cancer survivors and their families describe additional challenges that appear once treatment is over
24 ONCOLOGY NURSE ADVISOR • MARCH/APRIL 2018 • www.OncologyNurseAdvisor.com
or when the survivor is in remission.2 Experiencing adverse effects after treatment can be distressing, as they may be unexpected, occurring when families believe that their cancer journey has come to an end. Acknowledging that “this is real” and not imagined provides a child with additional support and reassurance.1 When a child experiences chemo brain or other cognitive deficits, keeping the mind active can help. When it comes time to introduce — or re-introduce —the child to school, slowly implementing learning can help the child feel less overwhelmed during reintegration to the school environment, as it can be a very anxiety-provoking time.3 A meeting with administration, teachers, and counselors prior to a classroom visit can be extremely helpful to create a plan for moving forward. Making these people aware of potential long-term adverse effects of the diagnosis and treatment is very important. A one-on-one aid or assistant for a child may be essential, and an individualized education plan (IEP) and classroom/ testing accommodations (504 plan) are 2 significant requests to make. Psychological testing may also be imperative.3 Once reintegration into the school environment begins, the child’s progress should be continuously monitored by parents and teachers. This allows for making necessary adjustments to accommodate changes in the child’s learning capabilities, as chemo brain may not become apparent immediately. Knowing who to contact and connect with throughout each stage can reduce uncertainty and miscommunication.2 Family members can build further trust with the hospital or school and feel less alone if they have a contact person at the institution. Addressing families’ feelings of being alone is important as this can cause additional stress and pressure for each family member. Hospital-based programs can help connect families with others that are going through similar experiences. Individual support, as well as support groups, can minimize the stressors that arise.1 Encouraging open communication about one’s experience can ensure
Keeping survivors’ brains active with activities and games is a fun, integrative way for children to better manage potential adverse effects. that necessary accommodations are available for the child. Reading material and resources related to a child’s diagnosis and treatment are also helpful for parents’ reference if any changes do develop.3 ADDITIONAL TECHNIQUES
There are many useful techniques for helping children experiencing symptoms of chemo brain. Keeping survivors’ brain active with activities and games is a fun, integrative way for children to better manage potential adverse effects. Puzzles, crosswords, and word games can help keep a child’s mind sharp during and after cancer treatment. Depending on the specific long-term effect that arises, many behavioral, pharmacologic, physical, and cognitive therapies are available to help survivors of childhood cancers.1 In addition, ongoing communication with the child’s healthcare team, as well as continuing a healthy diet and sleep schedule, are also beneficial.2 ■ Lauren Chatalian is an oncology social worker with CancerCare. REFERENCES 1. Höhn G. Talk on chemo-brain. Oral presentation at: CancerCare Staff Development Training; January 26, 2018; New York, NY. 2. Castellino SM, Ullrich NJ, Whelen MJ, Lange BJ. Developing interventions for cancer-related cognitive dysfunction in childhood cancer survivors. J Natl Cancer Inst. 2014;106(8):dju186. 3. Learning problems during or after treatment. CureSearch for Children’s Cancer website. https://curesearch.org/Learning-Problems-During-orAfter-Treatment. Accessed March 7, 2018.
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ASK THE EXPERTS | Polycythemia Vera
When Phlebotomy Is Not Enough: Cytoreductive Strategies for PV Our panel of experts discusses managing the treatment of polycythemia vera, including the role of phlebotomy and available options for patients who need further treatment. What is the role of phlebotomy in the treatment of patients with polycythemia vera (PV)?
Sandra Kurtin, PhDc, ANP-C, AOCN Assistant Professor of Clinical Medicine and Assistant Professor of Nursing, The University of Arizona Cancer Center, Tucson, Arizona
Lindsey Lyle, MS, PA-C Blood Cancers and Bone Marrow Transplant Program, University of Colorado Anschutz Medical Campus, Aurora, Colorado
Maureen E. Thyne, PA-C Weill Cornell Leukemia Program at Weill Cornell Medicine and New York-Presbyterian, New York, New York
KURTIN: PV is a disease that is primarily characterized by erythrocytosis. This increase in blood volume, together with the inflammatory nature of PV, places the patient at an increased risk for thrombosis. Phlebotomy, together with low-dose aspirin, is the treatment of choice in newly diagnosed patients. The goal is to maintain the hematocrit below 45%. The frequency and duration of phlebotomy will depend on the individual patient’s response and tolerance. LYLE: Phlebotomy, along with lowdose aspirin, is often the first therapeutic intervention performed in patients with polycythemia vera. While PV may be characterized by an increase in all 3 cell lines (white blood cells, red blood cells, and platelets), presentation is heterogeneous. The hallmark of PV is an increase in red blood cell production, resulting in elevated hematocrit levels. Patients with a hematocrit level greater than 45% are at higher risk for developing blood clots in the arteries or veins. Phlebotomy is the most rapid way to reduce the amount of red blood cells in a patient’s blood. Phlebotomy involves venipuncture and typically removal of a unit of blood, exact volumes may vary at different institutions or blood banks. By
26 ONCOLOGY NURSE ADVISOR • MARCH/APRIL 2018 • www.OncologyNurseAdvisor.com
reducing the amount of blood cells, blood flows easier through the vessels reducing the risk for blood clotting. Patients with PV are categorized as either high risk or low risk based on age and prior thrombosis. Low risk patients (younger than age 60 and no history of blood clot) can be treated with phlebotomy and aspirin alone. In high risk patients (older than age 60 or history of thrombotic event) phlebotomy may be used initially and intermittently as needed while trying to maintain hematocrit control with cytoreductive therapy. Results from a large multicenter study that evaluated patients with PV with strict hematocrit control (Hct < 45%) compared with loose control (Hct 45%-50%) showed that patients under strict hematocrit control had a significantly lower rate of cardiovascular death and major thrombosis.1 There may be situations where a lower hematocrit goal is appropriate and therapy should be individualized. This data highlights the importance of hematocrit with phlebotomy and/or additional therapy. THYNE: Polycythemia vera is a condition where the bone marrow makes too many cells — this extra production typically involves the red blood cells, but may also involve the white blood cells and/or platelets. One of the ways to treat patients with PV is to use phlebotomy (drawing blood, similar to a blood donation) to remove some of
the excess cells from circulation. This is particularly useful when a patient is first diagnosed (when the blood counts would be expected to be high) and sometimes periodically throughout the year. This helps remove the extra cells from circulation, but ultimately doesn’t change what’s being produced in the bone marrow. Often, an additional treatment (usually medication) is used to try to lower the blood counts and make the need for phlebotomy minimal. What options are available if phlebotomy does not provide adequate hematocrit control? KURTIN: Some of it will depend on the patient. The most common presentation is a high hemoglobin and hematocrit (erythrocytosis), but some patients may have elevated white blood cells (lymphocytosis) and elevated platelets (thrombocytosis). Phlebotomy does not effectively control lymphocytosis or thrombocytosis, both of which contribute to the risk of bleeding or clotting. If phlebotomy is not adequate in controlling the hematocrit or if the patient has significantly elevated white blood cells or platelets, cytoreductive therapy is recommended. In the United States, hydroxyurea is the most common cytoreductive therapy used. Interferon may also be used as cytoreductive therapy but is less common in the United States. LYLE: Cytoreductive therapy to control blood cell production is important in patients with high-risk disease (older than age 60 or those who have a thrombotic event history) regardless of adequate hematocrit control and aim to eliminate the need for phlebotomy. The goals of treatment in general are to reduce risk for blood clots,
the development of cardiovascular and cerebrovascular disease, bleeding, and management of disease-related symptoms. It is important to monitor patients with low-risk PV on a frequent basis for the need of cytoreductive therapy. Reasons to start additional therapy may be the need for frequent phlebotomy, poor tolerance of phlebotomy, progression of symptoms, development of symptomatic splenomegaly, progressive leukocytosis, or certainly the development of a thrombotic event or disease-related major bleed. The National Comprehensive Cancer Network (NCCN) guidelines recommend the use of hydroxyurea (an oral antimetabolite that inhibits DNA synthesis) or interferons (injectable biological agent) as front-line cytoreductive therapy for high-risk PV or patients with otherwise poor disease control. Additionally, anagrelide is available as an alternative therapy if clinically significant high platelets are the main issue, as this is a platelet-lowering agent. Ruxolitinib (JAK 1-2 inhibitor) is the only U.S. Food and Drug Administration (FDA) approved therapy for PV, but is indicated in patients with an inadequate response to or who are intolerant of hydroxyurea. THYNE: If the patient is needing more than an occasional phlebotomy to manage the blood counts, medication options are usually discussed. At this time, the two most common treatments are hydroxyurea or interferon. The goal
of these therapies is to lower the blood counts so that the patient no longer needs phlebotomy. These medications work differently, and there are different potential side effects, so patients should discuss what’s best for them with their health care team. What are the signs and/or symptoms that indicate the patient may have disease that is intolerant to treatment? What are your tactics for monitoring patients from diagnosis and throughout treatment? KURTIN: The JAK-STAT pathway is associated with hematopoiesis and inflammatory cytokines. Mutations in this pathway cause upregulation of the hematopoiesis and an increase of the inflammatory cytokines resulting in the elevated blood counts and the disabling symptoms patients with PV may experience. The most common disease-related symptoms include fatigue, pruritic, bone pain, fevers, early satiety (due to splenomegaly), and abdominal pain. Reducing these symptoms, along with reducing the elevated blood counts, is the primary goal of therapy in PV. First, we typically start patients on phlebotomy and aspirin to reduce the clotting potential. Again, the goal is to maintain the hematocrit below 45%. We also want to maintain the WBC below 10,000 and the platelets below 400,000. If a patient has splenomegaly, we expect that to decrease by at least 50%. We start
Phlebotomy, together with low-dose aspirin, is the treatment of choice in newly diagnosed patients. The goal is to maintain the hematocrit below 45%. Sandra Kurtin, PhDc, ANP-C, AOCN www.OncologyNurseAdvisor.com • MARCH/APRIL 2018 • ONCOLOGY NURSE ADVISOR 27
ASK THE EXPERTS | Polycythemia Vera hydroxyurea, together with aspirin, based on the patient’s counts and how many cell lines are involved. We will gradually increase the dose of hydroxyurea if we find that the treatment is not effective in reaching the milestones. If the patient continues to require phlebotomy despite cytoreductive therapy at the maximum dose (> hydroxyurea 2gm/day) or does not reach the milestones after 3 months at that dose, we will consider a change in therapy like ruxolitinib, a JAK2 inhibitor. We know that 95% of people with PV are JAK2-positive. In some patients, the hydroxyurea may cause the WBC or platelet count to go too low, placing the patient at an increased risk of infection or bleeding. Other patients may have difficulty tolerating the hydroxyurea, or in some cases may develop leg ulcers that are painful and are difficult to heal. Patients receiving interferon often experience profound fatigue and may have psychological changes or hyperglycemia. In both cases, the patient would be intolerant to cytoreductive therapy. Monitoring depends on the type of treatment that a patient is receiving. If a patient is on hydroxyurea and is well controlled the strategy would just be to follow them. In some patients, this approach can be used for many years. The frequency of visits will depend on their response (meeting milestones) and the presence or absence of symptoms of clinical findings. In patients with wellcontrolled disease, visits might be every 6 months after they have reached their milestones. For patients whose disease is less well controlled it is necessary to schedule follow up visits more frequently. We work closely with the patient to provide them with the information needed to contact us for any changes in their symptoms. If major changes occur, we may need to schedule a bone marrow biopsy to make sure that their disease isn’t moving toward myelofibrosis.
Medication dose adjustments and developing a plan for therapeutic phlebotomy frequency are important for optimal control/care of the patient. Lindsey Lyle, MS, PA-C LYLE: Establishing frequent time points for laboratory and symptom assessment is critical in the management of patients with PV. The frequency of visits is more often when a patient is first diagnosed or when initiating or changing therapy. In a newly diagnosed patient, I will see them once a week to ensure hematocrit control is obtained. Medication dose adjustments and developing a plan for therapeutic phlebotomy frequency are important for optimal control/care of the patient. As this disease is heterogenous, there is not a “one size fits all” dose of hydroxyurea or interferon that will be effective for all patients. Once a patient is established on a therapy with evidence of blood cell and symptom control, the visits can be spaced out and eventually even be as spaced out as every 3 months. The signs and symptoms that may indicate persistent disease or intolerance to treatment are similar to patients who may require cytoreductive therapy in addition to phlebotomy and low-dose aspirin alone. These include the need for frequent phlebotomy, poor tolerance of phlebotomy, progression of symptoms, development of symptomatic splenomegaly, progressive leukocytosis, or certainly the development of a thrombotic event or disease-related major bleed. Symptoms that are important to ask patients include the presence of pruritis (especially after a hot shower), erythromelalgia (burning pain in the hands or feet), paresthesias (numbness/tingling in the extremities), fatigue, headaches, or any changes in vision.
28 ONCOLOGY NURSE ADVISOR • MARCH/APRIL 2018 • www.OncologyNurseAdvisor.com
THYNE: Sometimes the blood counts remain poorly controlled even with medication, and the patient continues to require phlebotomy. Other times, some of the symptoms of the disease may not improve, such as itching, night sweats, or an enlarged spleen. These scenarios may indicate that the disease is resistant to the chosen medication. Sometimes the medication is almost “too successful” in reducing the blood counts, meaning it might lower the red blood cells perfectly and eliminate the need for phlebotomy, but might lower one of the other blood counts (white blood cells or platelets) too much, leaving the patient at risk for complications. In other cases, the medication may cause side effects making it difficult or impossible to continue taking. These are examples of a patient being intolerant to the medication. In both of these situations (disease that is resistant to the first choice medication, or an issue of intolerance to that medication) a change in medication therapy might be indicated. Again, this should be discussed with the patient and their health care team. Regardless of what type of treatment plan a patient is on, it’s important to closely monitor the lab work. Depending on the patient, this may be as often as weekly, or may only be every few months. It’s also important to establish good communication between the patient and the provider, so they can regularly review and discuss any new or changing symptoms, whether they are related to the disease or the treatment. Other health maintenance
should be reviewed and kept up to date as well, such a screening tests like mammogram and colonoscopy, dermatology skin exams, and vaccines like flu and pneumonia. Patients with chronic diseases can be at different risk than the general population, and it’s important to review and discuss these recommendations. What are the risks for patients with persistent/intolerant PV? KURTIN: The biggest risks of not controlling the disease are clotting and bleeding. Quality of life (QOL) is also very important. If we are not able to control the symptoms associated with PV, this will have a negative impact on QOL. Patients who develop neutropenia or thrombocytopenia due to cytoreductive therapy or progressive bone marrow failure will be at risk for infection or bleeding. The patients that develop hydroxyurea-associated ulcers are also at an increased risk of infection and often experience ulcer-related pain that is difficult to treat. LYLE: Patients who are refractory to first-line therapy are at higher risk for disease-related complications and reduced overall survival. Without therapy, patients with PV are estimated to have a 1.6-fold increase risk of death compared with the general population. The most common causes of disease-related mortality in the general PV population include cardiovascular complications, thrombosis, and progression to myelofibrosis or acute myeloid leukemia. Risk factors for transformation to acute leukemia include leukocytosis, advanced age, abnormal karyotype, and adverse molecular mutations. Reported rates of transformation to myelofibrosis and acute myeloid leukemia at 10 years are 4% to 6% and 2.3% to 14.4% respectively.
Once a patient has developed resistance or intolerance to therapy, their risk for these complications increase. Specif ically, resistance or intolerance to hydroxyurea is associated with increased symptom burden and decreased quality of life, increased thrombotic and cardiovascular complications, and a higher rate of leukemic transformation. A group in the United Kingdom recently published findings from an analysis of over 800 PV patients which identified that risk of progression to myelofibrosis was higher in patients who developed cytopenias or massive splenomegaly while on the dose of hydroxyurea necessary to control hematocrit levels.2 Additionally, cytopenias at the lowest dose of hydroxyurea to achieve response was an independent risk factor for transformation to acute leukemia.2 THYNE: PV is part of a group of diseases of the bone marrow called myeloproliferative neoplasms (MPNs). The extra blood cell production that characterizes these diseases can lead to more serious conditions, like myelofibrosis or even acute myeloid leukemia. There are also risks of secondary issues, like blood clots, which may be higher if the blood counts are not well controlled. Although each of these examples are rare, it’s important to have long-term, careful monitoring and to understand the risks.
What are the criteria for initiating treatment with ruxolitinib in patients with PV? Do you follow
a particular protocol to identify appropriate patients? KURTIN: The National Comprehensive
Cancer Network (NCCN) guidelines have been recently updated and provide specific criteria for determining if the patient is resistant or intolerant to hydroxyurea. I mentioned many of these previously. Criteria for defining resistance include the continuing need for phlebotomy despite cytoreductive therapy, meaning a patient’s hematocrit levels can’t be kept below 45%, and not controlling disease-related symptoms, including those associated with splenomegaly. Criteria for defining intolerance include the development of cytopenias due to cytoreductive therapy (ANC < 1000, platelets < 100,000), and treatment-related adverse events including hydroxyurea-associated leg ulcers. Patients that meet any of these criteria should be considered for treatment with ruxolitinib. LYLE: Ruxolitinib is approved by the
FDA for PV as a second line agent for patients who are resistant or intolerant to hydroxyurea. It is estimated that 15% to 25% of patients with PV will develop resistance or intolerance to hydroxyurea. European LeukemiaNet has developed and established a unified definition/standard criteria used in clinical practice to identify these patients.3 Since the ruxolitinib FDA indication, this definition has been used to identify patients who may benefit from treatment with ruxolitinib. Resistance is defined as meeting one of the following
The extra blood cell production that characterizes [MPNs] can lead to more serious conditions, like myelofibrosis or even acute leukemia. Maureen Thyne, PA-C www.OncologyNurseAdvisor.com • MARCH/APRIL 2018 • ONCOLOGY NURSE ADVISOR 29
ASK THE EXPERTS | Polycythemia Vera criteria after 3 months of hydroxyurea at a total dose of 2g/day or more. 1) Need for phlebotomy to maintain hematocrit levels > 45% 2) Platelet count > 400 × 109/L and WBC count > 10 × 109/L 3) ≤ 50% reduction in splenomegaly or failure to completely relieve splenomegaly symptoms Intolerance is defined by either the development of unacceptable hydroxyurea-related nonhematologic toxicites at any dose or clinically significant cytopenias at the lowest dose of hydroxyurea required to achieve a complete or partial response. Nonhematologic toxicities may include: development of leg ulcers, mucocutaneous manifestations, gastrointestinal symptoms, or pneumonitis. Significant cytopenias are defined as ANC less than 1.0 × 109/L or platelet count less than 100 × 109/L or hemoglobin less than 10 g/dL. In addition to control of symptoms related to polycythemia vera, as a clinician my goal is to eliminate the need for phlebotomy and to achieve a complete hematologic response (CHR). CHR is defined as WBC less than 10,000, Hct less than 45%, and platelets less than 400,000. Frequently meeting with my patients to evaluate hematologic and
In addition to control of symptoms related to [PV], as a clinician my goal is to eliminate the need for phlebotomy and to achieve CHR. Lindsey Lyle, MS, PA-C symptomatic response to therapy is key in helping me to identify patients who should have a change in therapy and necessary to optimize their quality of life and long-term outcomes.
decisions, the patient should thoroughly review the potential risks and benefits associated with this and all other therapeutic options and make an informed decision with their health care team. ■
THYNE: Currently, for PV patients, ruxolitinib is approved by the U.S. Food and Drug Administration as second-line therapy for those who have resistance or intolerance to hydroxyurea. This means if the patient is having well-controlled blood counts and well-managed disease symptoms and no ill effects while taking hydroxyurea, they should continue this treatment plan. However, if the hydroxyurea is not sufficient at controlling the blood counts and the patient is still requiring phlebotomy; or if the patient is having intolerable side effects of hydroxyurea; or if the hydroxyurea has controlled the red blood cells but caused other blood counts to become unnecessarily low, these patients would be eligible to consider treatment with ruxolitinib. As with all treatment
REFERENCES 1. Marchioli R, Finazzi G, Specchia G, et al. Cardiovascular events and intensity of treatment in polycythemia vera. N Engl J Med. 2013;368(1):22-33. doi: 10.1056/ NEJMoa1208500. 2. Alvarez-Larran A, Kerguelen A, HernandezBoluda JC, et al. Frequency and prognostic value of resistance/intolerance to hydroxycarbamide in 890 patients with polycythemia vera. Br J Haematol. 2016; 172(5):786-93. doi: 10.1111/bjh.13886 3. Barosi G, Birgegard G, Finazzi G, et al. A unified definition of clinical resistance and intolerance to hydroxycarbamide in polycythaemia vera and primary myelofibrosis: results of a European LeukemiaNet (ELN) consensus process. Br J Haematol. 2010;148(6):961-3. doi: 10.1111/j.1365-2141.2009.08019.x
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STAT CONSULT Palbociclib (Ibrance) Drug type
• Kinase inhibitor
Indication
• Hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2–) advanced or metastatic breast cancer in combination with ——An aromatase inhibitor as initial endocrine-based therapy in postmenopausal women, or ——Fulvestrant in women with disease progression following endocrine therapy Mechanism of Action
• Palbociclib is an inhibitor of cyclin-dependent kinases (CDK) 4 and 6 ——Cyclin D1 and CDK4/6 are downstream of signaling pathways that lead to cellular proliferation • In vitro studies have shown that palbociclib reduced cellular proliferation of estrogen receptor-positive breast cancer cell lines by blocking progression of the cell from G1 into S phase of the cell cycle Dosage and Administration
• 125 mg orally once daily • One capsule daily in a 28-day cycle consisting of 21 consecutive days of treatment followed by 7 days off • Swallow whole with food • Do not crush, chew, or open • If dose is missed or vomited, do not take an additional dose; take next prescribed dose at usual time • When an aromatase inhibitor is administered with palbociclib, refer to full prescribing information for the aromatase inhibitor used for recommended dose • When given with palbociclib, recommended dose of
fulvestrant is 500 mg on days 1, 15, 29, and once monthly thereafter ——Pre- and perimenopausal patients treated with palbociclib/fulvestrant should be treated with luteinizing hormone-releasing hormone (LHRH) agonists according to current clinical practice standards • Recommended dose modification for adverse events ——Starting dose: 125 mg/day ——First dose reduction: 100 mg/day ——Second dose reduction: 75 mg/day ——Discontinue if dose reductions cause dose to be less than 75 mg/day • Recommended dose modification for hematologic toxicity ——Grade 1 or 2 ■■ No dose adjustment required ——Grade 3 ■■ Day 1 of cycle: Withhold, repeat CBC monitoring within 1 week. When recovered to grade 2 or less, start next cycle at same dose ■■ Day 15 of first 2 cycles: If grade 3 on day 15, continue at current dose to complete cycle and repeat CBC on day 22. ■■ If grade 4 on Day 22, see grade 4 dose modifications ——Consider dose reduction if >1 week recovery from grade 3 neutropenia or recurrent grade 3 neutropenia on day 1 of subsequent cycles ——Grade 3 neutropenia with fever ≥38.5°C and/or infection ■■ Withhold until recovery to grade 2 or less. Resume at the next lower dose Continues on page 36
www.OncologyNurseAdvisor.com • MARCH/APRIL 2018 • ONCOLOGY NURSE ADVISOR 35
STAT CONSULT — Grade 4 ■ Withhold until recovery to grade 2 or less. Resume at the next lower dose — Monitor CBC before initiation, at the start of each cycle, on day 15 of the first 2 cycles, and as necessary — For patients who experience max Grade 1 or 2 neutropenia in the first 6 cycles, monitor CBC every 3 months, prior to the initiation of a cycle, and as necessary • Recommended dose modification for nonhematologic toxicity — Grade 1 or 2 ■ No dose adjustment required — Grade 3 or greater (if persisting despite optimal medical treatment) ■ Withhold until recovery of symptoms to » Grade 1 or lower » Grade 2 or lower, if not considered a safety risk for the patient ■ Resume at the next lower dose • Dose modification for use with strong CYP3A inhibitors — Avoid concomitant use — If necessary, reduce palbociclib dose to 75 mg once daily — Once CYP3A inhibitor is discontinued, increase palbociclib dose to dose used prior to initiation of inhibitor (after 3 to 5 half-lives of inhibitor) • Dose modification for hepatic impairment — No adjustment for mild-to-moderate impairment required (Child-Pugh classes A and B) — For severe impairment (Child-Pugh class C), recommended dose is 75 mg once daily for 21 days followed by 7 days off Specific Populations
• Pregnancy — No available data in pregnant women — May cause fetal harm based on findings in animal studies • Nursing mothers — Do not breastfeed during treatment and for 3 weeks after final dose • Patients of reproductive potential — Female: Use effective contraception during treatment and for at least 3 weeks after final dose — Male: Use effective contraception during treatment and for 3 months after final dose • Pediatric — Safety and efficacy not established
• Geriatric — No clinically relevant differences in safety of efficacy were observed between younger and older patients • Renal impairment — No adjustment required • Hepatic impairment — For severe impairment, reduce to 75 mg once daily — No adjustment required for mild-to-moderate impairment Boxed Warnings
• None Contraindications
• None Cautions
• Embryo-fetal toxicity — May cause fetal harm based on findings in animal studies • Male patients of reproductive potential — May cause infertility • Neutropenia — Monitor CBC prior to initiation, at start of each cycle, and on day 15 of the first 2 cycles, then as needed — Interrupt, reduce, or delay for patients who develop grade 3 to 4 neutropenia Adverse Effects
• Most common adverse reactions (≥10%) include: — Alopecia, anemia, asthenia, decreased appetite, diarrhea, fatigue, infections, leukopenia, nausea, neutropenia, pyrexia, rash, stomatitis, thrombocytopenia, vomiting Drug Interactions
• Strong CYP3A inhibitors — Avoid; if cannot be avoided, reduce palbociclib dose • Strong CYP3A inducers — Avoid • CYP3A substrates — Sensitive CYP3A substrates with narrow therapeutic indices may require dose reductions What to Tell Your Patient
• Palbociclib is a tyrosine kinase inhibitor. This is a type of anticancer medication, used to treat hormone receptorpositive, HER2-negative metastatic breast cancer in combination with
36 ONCOLOGY NURSE ADVISOR • MARCH/APRIL 2018 • www.OncologyNurseAdvisor.com
— An aromatase inhibitor as the first hormonal based therapy in women who have gone through menopause — Fulvestrant in women whose disease has progressed after hormonal therapy • Take palbociclib once daily with food — Swallow whole; do not chew, crush, or open capsules — Avoid drinking grapefruit juice or eating grapefruits — Do not take any capsules that are broken, cracked, or look damaged — If you vomit or miss or a dose, do not take an additional dose; take the next dose at its usual time • Tell your doctor and nurse if you — Have fever, chills, or any other signs or symptoms of infection — Have liver or kidney problems — Have any medical conditions — Are taking any current prescription or over-thecounter medications • Men of reproductive potential — Palbociclib may cause fertility problems, affecting your ability to father a child
— If you have a female partner of reproductive potential ■ Use effective contraception during treatment and for 3 months after your last dose • Women of reproductive potential — Tell your doctor or nurse if you are pregnant or think you may be pregnant — Use effective birth control during treatment and for at least 3 weeks after your last dose • You should not breastfeed during treatment and for 3 weeks after your last dose • You may experience side effects while taking palbociclib. Call your nurse or doctor if you experience any of these side effects or any side effects are severe and cannot be tolerated — Abnormalities in liver blood tests, bleeding or bruising easily, dizziness, hair thinning or loss, infections, loss of appetite, nausea/vomiting/diarrhea, nosebleeds, rash, shortness of breath, sore mouth, tiredness, weakness Prepared by James Nam, PharmD.
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RADIATION & YOUR PATIENT
The Emerging Controversy Over Proton Beam Therapy Bryant Furlow
© BSIP / AMELIE-BENOIST / MEDICAL IMAGES
P
roton beam therapy systems are now available at more than 2 dozen sites across the United States — including, most recently, the Miami Cancer Institute’s new Proton Therapy Center (scheduled to be unveiled March 15, 2018). These facilities are very expensive. Depending on the number of rooms and other factors, these facilities can cost more than $225 million each and have been called the single most expensive medical device ever built.1 Perhaps not surprisingly, treatment costs exceed those of traditional photon external-beam radiotherapy (EBRT) modalities.1 Most proton beam facilities costs less, $20 million to $150 million for singleand multiroom facilities, according to
Scott Warwick, executive director of the National Association of Proton Therapy. But proton therapy’s allure is strong despite its costs. Imprecise radiation beam targeting, skin surface dose, and in-path irradiation of nontarget internal-organ tissue are the main causes of dose-limiting radiotherapy toxicities.2 The large mass of protons reduces beam broadening and scatter seen with photon EBRT modalities, and most proton beam energy is deposited in target tumor tissue without significant irradiation of nontarget tissue along the beam path behind the target volume.1,2 It stands to reason that proton therapy is most promising for tumors close to the body surface. Proton therapy’s dosimetric depth-precision (its sharp lateral penumbra and distal fall-off ) have fueled interest in its use against ocular melanomas, tumors of the spine and skull-base, and childhood brain cancers — as well as its potential for reducing cardiovascular toxicity during breast tumor or esophageal tumor radiotherapy.3-5 Authors of a recent systematic review of 13 studies of proton therapy for breast cancer concluded that mean radiation doses to the heart and lungs were reduced with proton therapy compared with conventional photon EBRT modalities, including intensity-modulated radiotherapy (IMRT).4 However, large, well-designed comparative clinical studies are needed to confirm those potential clinical benefits, the authors cautioned.4 “There are many advantages of proton therapy,” said Minesh Mehta, MD, deputy director and chief of radiation oncology at Miami Cancer Institute. “Proton therapy delivers radiation with pinpoint accuracy, with little to no dose to tissues beyond the tumor, making treatment very effective and much gentler. Patients experience fewer
40 ONCOLOGY NURSE ADVISOR • MARCH/APRIL 2018 • www.OncologyNurseAdvisor.com
side effects and in certain cases have less chance of recurrence due to the opportunity to deliver higher tumor dose. One of the many open questions patients have with regard to proton therapy is who is a good candidate for this type of treatment. Though every case differs, typically, the best candidates for proton therapy are children with various cancers, and adults with skull-based tumors, tumors in and around the spine, orbital and eye tumors, as well as cancers of the head and neck, esophagus, pancreas and hepatobiliary system, sarcomas, as well as those with left-sided breast cancer.” Similarly, authors of a recent cohort study of 727 patients with esophageal cancer who underwent either IMRT or proton beam therapy at the University of Texas MD Anderson Cancer Center in Houston reported that proton therapy was associated with less irradiation of the heart and cardiac substructures compared with IMRT in patients with mid- to distal esophageal tumors.5 Critics have voiced concern, however, that the significant cost of building proton radiotherapy centers will encourage overuse, unnecessarily increasing the cost of treatment for more common cancers for which the evidence base for proton therapy remains unclear.1,6 EXPLORING ITS POTENTIAL Because it is a new and not yet widely used modality, the empirical evidence base for proton therapy has been slow to mature.3 Little is known about overall survival rates associated with proton therapy, for example. The relative biological effectiveness of proton therapy is still under study and factors such as beam angle, dose, and tissue type may affect results.7 The American Society for Radiation Oncology (ASTRO) recently issued a
model policy on proton beam therapy, noting that proton beam therapy “may offer dosimetric advantages as well as added complexity over conventional radiotherapy, 3D conformal radiation therapy (3D CRT) or intensity modulated radiation therapy (IMRT)” under some circumstances. The model policy notes the need for continued development of the clinical evidence base and the need for comparative effectiveness analyses to determine when it is appropriate to use PBT for different cancer sites. “Before applying PBT techniques, a comprehensive understanding of the benefits and consequences is required,” the ASTRO model policy states. A recent prospective cohort assessment of proton beam therapy, involving 204 evaluable men with intermediate- and high-risk prostate cancer at the Medipolis Proton Therapy and Research Center in Japan, found similar proton beam therapy monotherapy can maintain quality of life, with only 3.9% of patients experiencing grade 2 gastrointestinal toxicities within 6 months of treatment.8 A separate singleinstitution analysis of outcomes among 81 patients with prostate cancer found that proton beam therapy (79.2 Gy) was associated with good urinary and gastrointestinal function and quality of life, regardless of prostate size.9 However, as with studies of proton therapy in breast cancer, well-designed, randomized headto-head comparative trials are still needed to justify its use — and its significant excess cost — over traditional radiotherapy modalities such as IMRT.1,9
FIND US ON
There are at least 122 ongoing clinical studies of proton beam radiotherapy, according to a recent review, 21% of which address gastrointestinal tract cancers; 15%, central nervous system (CNS) tumors; and 12%, prostate cancers.6 Five are randomized clinical trials (enrolling patients with cancers of the lung, esophagus, oropharynx, prostate, and breast) designed to compare proton therapy outcomes against traditional photon EBRT.6
cancer: a systematic review of the literature. Cancer Treat Rev. 2018;63:19-27. 5. Shiraishi Y, Xu C, Yang J, Komaki R, Lin SH. Dosimetric comparison to the heart and cardiac substructure in a large cohort of esophageal cancer patients treated with proton beam therapy or intensity-modulated radiation therapy. Radiother Oncol. 2017;125(1):48-54. 6. Mishra MV, Aggarwal S, Bentzen SM, Knight N, Mehta MP, Regine WF. Establishing evidence-based indications for proton
NEUTRON RADIATION RISKS
therapy: an overview of current clinical
One continuing theoretical concern with the technology is that tungstenalloy multileaf collimators (MLCs) for dose-escalated delivery of proton therapy, an approach that is undergoing clinical study, could interact with proton beams to yield out-of-field secondary and residual neutron radiation exposures for radiotherapy staff and patients.10 Efforts are under way to develop detectors and tracking systems to study and monitor neutron scatter risks.11 ■
trials. Int J Radiat Oncol Biol Phys. 2016;97(2): 228-235. 7. Lühr A, von Neubeck C, Krause M, Troost EGC. Relative biological effectiveness in proton beam therapy — current knowledge and future challenges. Clin Transl Radiat Oncol. 2018;9:35-41. 8. Arimura T, Kondo N, Matsukawa K, et al. The role of proton beam therapy for patients with intermediate- and high-risk prostate cancer. Poster presentation at: 2018 Genitourinary Cancers Symposium; February 8-10, 2018; San Francisco, CA.
REFERENCES
Abstract 97.
1. Furlow B. Dosimetric promise versus cost:
9. Goenka A, Newman NB, Fontanilla H, et al.
critics question proton therapy. Lancet Oncol.
Patient-reported quality of life after pro-
2013;14(9):805-806.
ton beam therapy for prostate cancer: the
2. Doyen J, Falk AT, Floquet V, Hérault J, Hannoun-Levi JM. Proton beams in cancer treatments: clinical outcomes and dosimetric
effect of prostate size. Clin Genitourin Cancer. 2017;15(6):704-710. 10. Stokkevåg CH, Schneider U, Muren LP,
comparisons with photon therapy. Cancer
Newhauser W. Radiation-induced cancer risk
Treat Rev. 2016;43:104-112.
predictions in proton and heavy ion radio-
3. Mohan R, Grosshans D. Proton therapy — present and future. Adv Drug Deliv Rev. 2017;109:26-44.
therapy. Phys Med. 2017;42:259-262. 11. Valle SM, Battistoni G, Patera V, et al. The MONDO project: a secondary neutron track-
4. Kammerer E, Le Guevelou J, Chaikh A, et al. Proton therapy for locally advanced breast
er detector for particle therapy. Nucl Instrum Methods Phys Res A. 2017;845:556-559.
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www.OncologyNurseAdvisor.com • MARCH/APRIL 2018 • ONCOLOGY NURSE ADVISOR 41
COMMUNICATION CHALLENGES
Wait . . . What do you mean? Ann J. Brady, MSN, RN-BC
belly
npo
© DRAFTER123 / GETTY IMAGES
no food or drink
abdomen
Confusion can set in on both sides. How do we address possible confusion and provide clarity?
O
ne of the first things we learn in nursing school is medical terminology, what we often refer to as medicalese. We take that knowledge into our practice as we interpret information for our patients and their families. Yet each patient and family has innumerable points of contact with other healthcare providers. Even as we focus on being as clear as we can be, we can’t know how other healthcare providers explained things and how those explanations may differ from our own way of explaining and educating. To complicate things further, almost every medical term seems to be different from common-use terms; for example, abdomen instead of belly or tummy, NPO instead of no food or drink. Not to mention the confusing dual names for drugs: acetaminophen vs Tylenol. And then there is inconsistency in terms: one person says narcotics and someone else speaks of the opioid epidemic. In other words (pun intended), the language
of medicine is itself confusing. All of which makes patient communication a challenge. CASE Recently I was in the hospital room with Sylvia and her husband Rick. She had newly diagnosed ovarian cancer and then before she even started treatment, she was admitted through the emergency department with severe abdominal pain. Sylvia and Rick were eagerly waiting for the doctor to come in to review the results of her latest scan. When he did arrive, their anticipation and anxiety was palpable. Before he had a chance to speak, Rick asked about the scan, “Did you have a chance to look at it?” The doctor said, “The scan shows that the mass is basically unchanged in size.” Rick furrowed his brow. “Wait, what do you mean? It’s a mass and not cancer?” Because we know the language so well, we can forget the nuances. Cancer, tumor, mass — we may use those interchangeably, and for us they mean the same thing: Sylvia has ovarian cancer. Sylvia has a mass growing on her ovary. Sylvia has a tumor. Others, less adept at the strange language we use, may not understand that we are referring to the same thing. In this case, Rick thought of the word mass as being something less threatening than the word cancer, and he zeroed in on that single word, which to him momentarily was a relief: Sylvia had a mass and not cancer. Confusion can set in on both sides. How do we address possible confusion and provide clarity? DISCUSSION Often, in an effort to address misunderstandings, we ask, “Do you have any questions?”
42 ONCOLOGY NURSE ADVISOR • MARCH/APRIL 2018 • www.OncologyNurseAdvisor.com
as a way of determining whether a patient and family understood information. And yet a reasonable response, “I don’t have any questions,” is not a guarantee that they understood what they were told, for it requires a certain level of knowledge itself to know whether you have missed anything. It is a conundrum of sorts: How do you know if you do not know something when you do not know the information at all? There is no guarantee that our best effort at communication will be effective. How do we make sure we did a good job of explaining? In medicine, we have Goals of Care; how about the Goals of Communication? How do we achieve those goals? We may have an assumption that the patients and caregivers understand what is going on, or when we do inquire, it may look like we don’t know. If I ask a patient, “Tell me why you are here,” the response may be, “Haven’t you read my chart?” or, “I’d think you would know.” In nurse-to-nurse report or in reading the history and physical, there may be a reference to what the patient has been told. Yet what patients and caregivers have been told is not a guarantee of understanding. In a 2013 article published in Oncology Nursing Forum, Debra Jenkins, MSN, RN, and colleagues attribute the gap in understanding as arising from information that was not provided “in a way that led to understanding.”1 Our own grasp of the language of medicine may get in the way. It makes me think of idioms, expressions that are understood by those whose first language is English yet are not always understood by those who are nonnative speakers; for example, I understand what the saying “it’s raining cats and dogs” means, but it isn’t automatically understood by others. In an effort to ensure good patient education, nurses are taught the teach-back method. After we provide education, we ask patients to say back to us what they understood, and then we clarify any errors. But straight out asking someone to repeat back
what we just said puts them on the spot. It feels like a test of them, rather than a test of our teaching, which is awkward at a time when patients and their families are already uncomfortable. I like to add a kind of disclaimer that puts the burden back on me: “Let me check how well I explained things. Can you tell me what I said/go over with me what I said? That way if I didn’t do a good job, I can fix it.” It seems like a small distinction, but it puts any mistake back on me. If they get the information wrong, instead of it being their fault, it is mine. Taking the pressure away makes it easier for them to explain back and for me to clarify any errors in understanding. Yet how do we account for incorrect information we were not part of relaying? How do we assess whether they are confused, especially in a situation as with Sylvia and Rick, where they seemed to have a clear understanding? There is no correct answer to these questions. Overexplaining can be a problem because, once again, it is burdensome. Yet assuming a level of knowledge can also be problematic. Another part of nursing practice is assessment and reassessment, everything from vitals and response to medications to wounds and dressings and so forth. Our assessment can include questions that reveal knowledge: “Why are you here? I want to be sure you understand things. Tell me your story. What brought you to the hospital?” We aren’t going to catch all of the misinformation, but it is surprising what is revealed when we ask. How will we know otherwise? ■
There is no correct answer to these questions. Overexplaining can be a problem. Yet assuming a level of knowledge can also be problematic.
Ann Brady is the symptom management care coordinator at the Cancer Center, Huntington Hospital, Pasadena, California. REFERENCE 1. Cohen MZ, Jenkins D, Holston EC, Carlson ED. Understanding health literacy in patients receiving hematopoietic stem cell transplantation. Oncol Nurs Forum. 2013;40(5):508-515.
www.OncologyNurseAdvisor.com • MARCH/APRIL 2018 • ONCOLOGY NURSE ADVISOR 43
THE TOTAL PATIENT Patient Support Program Provides Diversions During Chemotherapy Infusions Bette Weinstein Kaplan
© PHOTO COURTESY OF CANCER WELLNESS CONNECTIONS
T
he idea is so clever: Caring people offering diversions of all types to patients while they are receiving their chemotherapy. That is what Cancer Wellness Connections is all about. Based in Rochester, New York, the organization is the innovation of Eileen Grossman, who thought of it while she was visiting friends during their chemotherapy infusions. Ms Grossman wanted to help her friends pass the time during their treatments, so she brought a card table and cards, snacks, another friend, and of course, chocolate. With all that, she certainly created a diversion in the infusion room. So much so that other patients asked to join the group. Ms Grossman realized that extending her card games to other patients — and even other hospitals — would be a good project. So she discussed her idea with oncologists Cynthia Angel, MD, and Brent DuBeshter, MD, at Lattimore Medical Center. Together, they founded Cancer Wellness Connections in 2006. The program currently supports patients undergoing treatment at 6 hospital locations throughout Rochester, and helps up to 20,000 patients each year. AGE-APPROPRIATE PROGRAMS In addition to its activities for adult patients during their infusions, Cancer Wellness Connections also developed a program for younger patients. Better
Day Buddies, launched in 2008, bring crafts, books, games, and pizza for patients aged 2 to 20 years. Better Day Buddies volunteers do not just come in and pass out the pizza (the cost of which is covered by a grant); they also hand out bags of goodies and toys. The volunteers interact with the parents as well, providing a much-needed release for both parents and children. Volunteers would pick up meals from local restaurants. As a result, Cancer Wellness Connections established relationships with more than 20 restaurants
Anything that can ensure patients stay on top of treatment is an asset. in Rochester that donate anything from a tray of cookies and pastries to a wonderful hearty soup or a pasta plate. CARE PARTNERS Program volunteers help patients pass the time or just give them an opportunity to have someone to talk to. In addition to the lay volunteers, Cancer Wellness Connections offers diversions provided by professional care partners with specific skill sets.
44 ONCOLOGY NURSE ADVISOR • MARCH/APRIL 2018 • www.OncologyNurseAdvisor.com
A personal trainer, for example, may give a talk about fitness and instruct patients in some gentle movement exercises they can do while sitting in the infusion chair that can help circulate the medication in the body. A manicurist is scheduled for some days in the month. “Women in treatment lose their hair, they lose their eyebrows … it’s hard to feel feminine. So we have people come in and give them manicures with formaldehydefree products. The women are able to feel pampered and cared for,” said Betsy Twohig-Barrett, president and executive director of Cancer Wellness Connections. The professional care partners receive a stipend and must complete each hospital’s rigorous volunteer and employee clearance process. EXPANDING SERVICES Over the last few years the organization has expanded its activities, incorporating some types of massage therapy. Although the effect massage might have on medication administration is a concern, unless there is a direct contraindication with a medication, the staff finds that most patients do well with massage. The type of massage offered is different from other massage techniques for cancer patients as these are performed right in the infusion chair while the patients Continues on page 46
FROM
© CAIAIMAGE / ROBERT DALY / GETTY IMAGES
T
he capacity to bear witness and respond empathically to a dying person’s suffering is inherent in end-of-life care. Holistic, relationship-centered, compassionate care is the hallmark of palliative end-oflife care.1 Yet, simultaneously, researchers have found medical training sometimes ill-equipped in preparing clinicians for the range of concerns and emotions expressed by dying patients and their families. Healthcare professionals report lacking skills in psychosocial and spiritual care of dying people, resulting in high levels of moral distress, grief, and burnout.1 Similarly, Tornoe and colleagues found “western society’s fastpaced healthcare environment conditions us to view death as a physiological event and a failure rather than a natural part of the human lifecycle and a second passage of a life.”2 Modern medicine with its emphasis on cure frequently discovers itself struggling with an array of challenges in end-of-life care. Studies on the influence of compassionate silence in end-of-life care have indicated that clinicians’ focus solely on “doing” may actually be inappropriate at times and inhibit their ability to effectively address and meet the needs of the person who is terminally ill. A prominent theme was that the “do, fix, and hopefully cure” mandate in modern medicine may not be appropriate at the end of life and, in fact, may need to be balanced with the quality of being present with those who are suffering.1 Being “present” to patients who are nearing death therefore entails
Sitting With Silence in End-of-Life Cancer Care Glenn Meuche, LCSW
that clinicians possess a certain comfort level in terms of “sitting with the silence” and offering the “gift of presence.” THE LANDSCAPE OF SILENCES The research of Back and colleagues outlined 3 types of silence that can manifest between patients and clinicians in the clinical encounter: awkward, invitational, and compassionate.3
In regard to awkward silences, they write, “silence most often feels like it is dragging on too long when a well-meaning clinician thinks he should be ‘using silence.’ While we recognize that new skills have a learning curve before they can be performed smoothly, we also think that the problem with a directive to stop doing something is unlikely to produce the quality of silence that is actually therapeutic.”3 Invitational silences are often intentional and used to evoke certain thoughts or feelings from the patient in an attempt to engender further dialogue and reflection. “The clinician deliberately creates a silence meant to convey empathy, allow a patient time to think or feel, or to invite the patient into the conversation in some way. While we recognize that these silences are tremendously valuable, we also note that these silences are often described as a kind of holding, which has a stagesetting, expectant quality,” explained Back.3 Invitational silence mentored by mindfulness can be effective in heightening patients’ awareness of the moment and help them observe their feelings and thoughts in noncritical or nonjudgmental ways. Conversely, mindfulness and the clinician’s ability to “quiet the mind” may also help to free one from distractions that might preclude attentiveness to the present moment. The clinician has to shift his or her thought from a narrative mode to one a patient perceives as more empathic or compassionate.3 A lthough minor attention has been given to compassionate silences, researchers recently have taken note
Back and colleagues outline 3 types of silence that can manifest in the clinical encounter: awkward, invitational, and compassionate. www.OncologyNurseAdvisor.com • MARCH/APRIL 2018 • ONCOLOGY NURSE ADVISOR 45
FROM and underscored its significance in end-of-life care. Rooted in contemplative practices, compassionate silences encompass a way of being in the world and with the dying that cannot be contrived or forced by clinicians. “Compassion in contemplative traditions is transmitted through a quality of mind … and is not a tool to be used with a specific set of indications and meanings,” Back explains.3 In another study conducted with hospice nurses and pertinent to the practice of consoling presence, Tornoe and colleagues found that embracing the silence demanded a mental shift from a focus on doing something for the patient to being with the patient.2 Compassionate silences, therefore, should never be understood as a means or device in which to create therapeutic relationships. The clinician’s ability to empathize and “ join with” the suffering of the dying fosters rapport. Being present in the moment elicits openness in allowing our humanity
to speak. Compassion for the other emerges naturally and freely from within. The ability to abide compassionately, amidst silence in end-of-life care and simply be, provides depth and soul to the patient-clinician encounter. Clinicians who developed the ability to maintain stable attention and emotional balance, and are naturally comfortable expressing empathy and compassion can spontaneously achieve compassionate silences.3
Total Patient
group can do to ensure patients stay on top of their treatment is an asset. Nurses will inquire about when a care partner such as a Reiki therapist will be in because it calms an anxious patient. The patient’s appointments are then set up to coincide with the times the Reiki therapist will be at the infusion center.
Continued from page 44
are receiving treatment. Patients are offered a foot massage, a scalp massage, or to have their shoulders loosened up. Children participating in Better Day Buddies activities are not offered massage, but their parents can get a mini massage. Ms Twohig-Barrett explains that when one person in the family is seriously ill the entire family feels the impact. So they try to emphasize to the parents the need for self-care. Reiki is another newly introduced diversion. It is so popular that the oncology staff will try to schedule a patient’s infusion to accommodate the Reiki master’s visit. A nurse manager at one facility said that anything the
suggests that meditation has a positive effect on factors known to influence empathic mental processes.4 ■ Glenn Meuche is the social work internship program coordinator at CancerCare. REFERENCES 1. Rushton CH, Sellers DE, Heller KS, Spring B, Dossey BM, Halifax J. Impact of a contemplative end-of-life training program: being with dying. Palliat Support Care. 2009;7(4):405-414.
CONCLUSION
Mindfulness meditation, contemplative practices, and centering prayer are proven to help clinicians cultivate empathy and develop “consoling presence.” Although further research is needed, studies have clearly demonstrated the positive influence of these techniques in promoting a way of being and quality of mind that is crucial to end-of-life care. Whether meditative practices enhance empathic behavior is not known; however, evidence
KEEPING PATIENTS’ HOURS Cancer Wellness Connections holds its activities from 10:00 am until 12:00 or 1:00 pm, Monday through Friday. If the volunteers and/or care partners arrive earlier, they find themselves in the way of patient setup. Likewise, much after 1:00 pm, the patients are tired or sleepy from medication. There are usually 13 to 15 chairs and a volunteer or care partner will target 2 activities a day.
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2. Tornoe KA, Danbolt LJ, Kvigne K, Sorlie V. The power of consoling presence – hospice nurses’ lived experience with spiritual and existential care for the dying. BMC Nurs. 2014;13:25. 3. Back AL, Bauer-Wu SM, Rushton CH, Halifax J. Compassionate silence in the patient-clinician encounter: a contemplative approach. J Palliat Med. 2009;12(12):1113-1117. 4. Mascaro JS, Rilling JK, Tenzin Negi L, Raison CL. Compassion meditation enhances empathic accuracy and related neural activity. Soc Cogn Affect Neurosci. 2013;8(1):48-55.
A care partner goes to each cubicle and asks if the patient is interested in the activity, or perhaps she would just like to talk. Meanwhile, at another end of the room, a personal trainer or manicurist might be with a patient, or a volunteer is leading a group activity. WANT MORE INFORMATION?
Cancer Wellness Connections has a video on their website (cancerwellness connections.org) that describes the benefits of the program for both facilities and patients. Ms Twohig-Barrett is happy to share the organization’s experience; she can be reached at bbarrett@rochester.rr.com. ■ Bette Weinstein Kaplan is a medical writer based in Tenafly, New Jersey.
ISSUES IN CANCER SURVIVORSHIP © EVA KATALIN KONDOROS / GETTY IMAGES
Incidence of Posttraumatic Stress Disorder High Among Patients With Cancer Bette Weinstein Kaplan
T
he shock of a cancer diagnosis is a life-changing, frightening experience, and not surprisingly, researchers report symptoms of posttraumatic stress disorder (PTSD) in as many as 20% of patients with cancer. Researchers at the National University of Malaysia and at Harvard Medical School and Dana-Farber Cancer Institute investigated the phenomenon. They sought to evaluate the course of PTSD in patients with cancer over 4 years starting at diagnosis via follow-up assessments. Their hypothesis was that signs of psychological distress at diagnosis and in the posttreatment period indicate the presence of PTSD, and it would endure over the long term in some patients, possibly affecting their treatment. All the participants were treated at one academic medical center and were recruited within 1 month of their cancer diagnosis. Inclusion criteria were a diagnosis of any type of cancer and ability to complete the required interviews and questionnaires, understand the study objective, and give informed consent.
Patients with cancer are at risk for PTSD, even a number of years after diagnosis.
ASSESSMENT RESULTS A total of 469 patients older than 18 years were enrolled. The investigators used 2 techniques for their evaluations: the Hospital Anxiety and Depression Scale (HADS) and structured clinical interviews based on the DSM-IVTR criteria for PTSD, with a cancer diagnosis as the potentially traumatic event. Assessments were administered at baseline (4 to 6 weeks after the initial diagnosis), at 6 months, at 1 year, and at 4 years. Participants who could not attend or complete their sessions were interviewed by telephone. PTSD was classified as: full, subsyndromal, no, or nonprobable. Those with no PTSD were patients whose PTSD did not fit any other classification. Participants with elevated HADS scores (n = 203) sat for the structured clinical interview at the 6-month follow-up. The researchers determined that 27 patients had full PTSD; 17, subsyndromal; 159, no PTSD; and 236, nonprobable. The combined incidence of full and subsyndromal PTSD was 21% at 6 months. Of 245 patients at the 4-year follow-up, 10 (4%) had full PTSD and 5 (2%) had subsyndromal PTSD. Overall incidence of PTSD diminished over time; however, approximately one-third of the participants whose diagnosis was full or subsyndromal PTSD at 6 months had full PTSD at 4 years, whereas none of the participants
with no PTSD at 6 months went on to develop PTSD after 4 years. The researchers found no significant differences across the PTSD groups in terms of age at diagnosis, gender, marital status, or ethnicity. There were significant differences, however, with regard to type and stage of cancer. For example, women who had breast cancer were less likely to develop PTSD by the 6-month assessment. The thought is that because breast cancer occurs frequently readily available support services help guard against PTSD in those patients. LONG-TERM RISKS The researchers caution that patients with cancer are at risk for developing PTSD, even a number of years after diagnosis and treatment. Clinicians should always monitor survivors for signs of PTSD, especially those who are long-term survivors because symptoms such as psychological distress, avoidance, and cognitive difficulties could affect treatment adherence. ■ Bette Weinstein Kaplan is a medical writer based in Tenafly, New Jersey. REFERENCE Chan CMH, Ng CG, Taib NA, Wee LH, Krupat E, Meyer F. Course and predictors of post-traumatic stress disorder in a cohort of psychologically distressed patients with cancer: a 4-year followup study. Cancer. 2018;124(2):406-416.
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ASK A PHARMACIST
FDA and ASHP Actions That Manage or Prevent Drug Shortages Every other week it seems like another chemotherapy drug is unavailable due to a shortage. What is being done about these?
© TEAM STATIC / GETTY IMAGES
— Name withheld on request
The frequency of drug shortages can be frustrating, and especially concerning when chemotherapy agents are involved. A 2017 survey conducted by the Institute for Safe Medication Practices (ISMP) indicated that 66% of respondents were affected by drug shortages on a daily basis, with 55% reporting a shortage of 21 or more drugs within the previous 6 months.1 The American Society of HealthSystem Pharmacists (ASHP), in
collaboration with the University of Utah Drug Information Service, maintains an ongoing list of medications on shortage and also tracks statistics on this. In 2017, 146 medications experienced a new shortage.2 Some of the medications most frequently affected are intravenous products such as electrolytes, antibiotics, CNS medications, and chemotherapy. The reasons for medication shortages vary. Some, such as the recent IV fluid shortage, are the result of natural disasters in Puerto Rico, where many of these products are manufactured. More frequently, shortages are due to manufacturing issues affecting medication quality, supply/demand imbalances, or shortages of raw materials needed to manufacture the medication. The Food and Drug Administration (FDA) and ASHP both maintain information on ongoing medication shortages. The FDA website maintains a list of medications on shortage with a focus on medically necessary drugs with the potential to affect public health, while the ASHP website lists every shortage reported to them as soon as it is confirmed. Both sites contain information about expected duration of the shortage as well as information on alternate suppliers, when available. Management strategies depend on the medication or product that is unavailable as well as the severity and duration of the shortage. If an appropriate alternate medication is available, patients may have their therapy changed until the
original medication is available again. In cases where the product on shortage has an alternate formulation, use of the other formulation may also be considered. In some instances, the FDA may permit the import of product from new sources in order to ease a shortage or may encourage other manufacturers to increase production of that product. In regard to long-term solutions, the FDA has developed multiple strategies to mitigate and prevent drug shortages.3 These include incentivizing manufacturers to improve quality practices to prevent shortages due to these issues, identifying early warning signals for manufacturing problems to prevent supply disruptions, and working with key stakeholders to identify new strategies. ■ REFERENCES 1. Drug shortage roundtable: minimizing impact on patient care. Bethesda, MD: American Society of Health-System Pharmacists; November 6, 2017. https://www. ashp.org/-/media/assets/drug-shortages/ docs/drug-shortages-nov-2017-shortagemeeting-report.ashx. Accessed March 7, 2018. 2. Drug shortages statistics. ASHP website. https://www.ashp.org/Drug-Shortages/ Shortage-Resources/Drug-ShortagesStatistics. Accessed March 7, 2018. 3. Strategic Plan for Preventing and Mitigating Drug Shortages. Silver Spring, MD: Food and Drug Administration; 2013. https://www. fda.gov/downloads/Drugs/DrugSafety/ DrugShortages/UCM372566.pdf. Accessed March 7, 2018.
Lisa A. Thompson, PharmD, BCOP Clinical Pharmacy Specialist in Oncology Kaiser Permanente, Colorado
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