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Survivorship, Version 2.2018, NCCN Clinical Practice 1216 NCCN Jeffrey Peppercorn, MD, MPH; William Pirl, MD; M. Alma Rodriguez, MD; Kathryn J. Ruddy, MD, MPH; Paula Silverman, MD; Sophia Smith, PhD, MSW; Survivorship, Karen L. Syrjala, PhD; Amye Tevaarwerk, MD; Susan G. Urba, MD; Mark T. Wakabayashi, MD, MPH; Version 2.2018 Phyllis Zee, MD, PhD; Nicole R. McMillian, MS; and Clinical Practice Guidelines in Oncology Deborah A. Freedman-Cass, PhD Crystal S. Denlinger, MD; Tara Sanft, MD; K. Scott Baker, MD, MS; Gregory Broderick, MD; Anthracycline-Induced Cardiac Toxicity Wendy Demark-Wahnefried, PhD, RD; Debra L. Friedman, MD, MS; Mindy Goldman, MD; Many cancer treatments, including chemotherapeu- Melissa Hudson, MD; Nazanin Khakpour, MD; tics, targeted agents, hormonal therapies, and radia- Allison King, MD; Divya Koura, MD; tion, are associated with cardiovascular toxicities.1–7 Robin M. Lally, PhD, RN, MS; Terry S. Langbaum, MAS; Cardiovascular sequelae can include arrhythmias, Allison L. McDonough, MD; Michelle Melisko, MD; Jose G. Montoya, MD; Kathi Mooney, RN, PhD; pericardial disease, hypertension, thrombosis, car- Javid J. Moslehi, MD; Tracey O’Connor, MD; diomyopathy/heart failure, and vascular and meta- Linda Overholser, MD, MPH; Electra D. Paskett, PhD; bolic issues. Survivors of some cancer types have a Abstract Please Note The NCCN Guidelines for Survivorship provide screening, evalua- The NCCN Clinical Practice Guidelines in Oncology tion, and treatment recommendations for common physical and (NCCN Guidelines®) are a statement of consensus of the psychosocial consequences of cancer and cancer treatment to authors regarding their views of currently accepted ap- help healthcare professionals who work with survivors of adult- proaches to treatment. Any clinician seeking to apply or onset cancer in the posttreatment period. This portion of the consult the NCCN Guidelines® is expected to use inde- guidelines describes recommendations regarding the manage- ment of anthracycline-induced cardiotoxicity and lymphedema. pendent medical judgment in the context of individual In addition, recommendations regarding immunizations and the clinical circumstances to determine any patient’s care or prevention of infections in cancer survivors are included. treatment. The National Comprehensive Cancer Net- ® ® J Natl Compr Canc Netw 2018;16(10):1216–1247 work (NCCN ) makes no representation or warranties doi: 10.6004/jnccn.2018.0078 of any kind regarding their content, use, or application and disclaims any responsibility for their applications or use in any way. The full NCCN Guidelines for Survivor- NCCN Categories of Evidence and Consensus ship are not printed in this issue of JNCCN but can be Category 1: Based upon high-level evidence, there is uniform accessed online at NCCN.org. NCCN consensus that the intervention is appropriate. © National Comprehensive Cancer Network, Inc. Category 2A: Based upon lower-level evidence, there is uni- 2018, All rights reserved. The NCCN Guidelines and the form NCCN consensus that the intervention is appropriate. illustrations herein may not be reproduced in any form Category 2B: Based upon lower-level evidence, there is without the express written permission of NCCN. NCCN consensus that the intervention is appropriate. Category 3: Based upon any level of evidence, there is ma- Disclosures for the NCCN Survivorship Panel jor NCCN disagreement that the intervention is appropriate. At the beginning of each NCCN Guidelines panel meeting, panel All recommendations are category 2A unless otherwise noted. members review all potential conflicts of interest. NCCN, in keep- ing with its commitment to public transparency, publishes these Clinical trials: NCCN believes that the best management for disclosures for panel members, staff, and NCCN itself. any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. Individual disclosures for the NCCN Survivorship Panel members can be found on page 1247. (The most recent version of these guidelines and accompanying disclosures are available on the NCCN Web site at NCCN.org.) These guidelines are also available on the Internet. For the latest update, visit NCCN.org. ©© JNCCN—JournalJNCCN—Journal ofof thethe NationalNational ComprehensiveComprehensive CancerCancer NetworkNetwork || VolumeVolume 16 15 Number Number 10 10 || OctoberOctober 2018 2018 1217 NCCN Guidelines® Journal of the National Comprehensive Cancer Network Survivorship markedly increased risk of developing cardiovascular Studies suggest that the incidence of clinical disease compared with noncancer populations.8 As a congestive heart failure after anthracycline-based result, a new field called “cardio-oncology,” focused on therapy for adult-onset cancer is <5%.16–19 For in- the cardiovascular health of patients with cancer and stance, in the NSABP B-31 trial of patients with survivors, has become established.9,10 breast cancer, the rates of symptomatic heart fail- Anthracyclines (eg, doxorubicin, epirubicin, dauno- ure after 7 years were 4% in patients treated with rubicin) are used to treat many cancer types, including anthracycline-based chemotherapy and trastu- lymphoma, sarcoma, and breast cancer, and are among zumab and 1.3% in those treated with anthra- the best studied and most common causes of cancer cycline-based chemotherapy alone.18 However, a treatment-induced cardiac injury.11–13 The mechanism significantly higher percentage of patients have by which anthracyclines cause cardiomyopathy is not evidence of subclinical heart failure, with reports fully understood, but likely involves the formation of of asymptomatic left ventricular ejection frac- reactive oxygen species, oxidative injury, and the subse- tion (LVEF) decline being 9% to 50% in various quent induction of apoptosis in cardiac cells.14 A role for studies.16,20–22 topoisomerase-IIβ in cardiomyocytes in the production The panel has focused specifically on anthra- of reactive oxygen species in response to anthracyclines cycline-induced cardiac toxicity in these guide- has been suggested.15 lines. Other systemic therapies (eg, HER2-target- Text cont. on page 1234. NCCN Survivorship Panel Members Linda Overholser, MD, MPHÞ University of Colorado Cancer Center *Crystal S. Denlinger, MD/Chair† *Electra D. Paskett, PhDε Fox Chase Cancer Center The Ohio State University Comprehensive Cancer Center – Tara Sanft, MD/Vice-Chair†Þ James Cancer Hospital and Solove Research Institute Yale Cancer Center/Smilow Cancer Hospital Jeffrey Peppercorn, MD, MPH† K. Scott Baker, MD, MS€ξ Massachusetts General Hospital Cancer Center Fred Hutchinson Cancer Research Center/ William Pirl, MDq Seattle Cancer Care Alliance Dana-Farber/Brigham and Women’s Cancer Center *Gregory Broderick, MDw M. Alma Rodriguez, MD‡†Þ Mayo Clinic Cancer Center The University of Texas MD Anderson Cancer Center Wendy Demark-Wahnefried, PhD, RD@ Kathryn J. Ruddy, MD, MPH‡† University of Alabama at Birmingham Comprehensive Cancer Mayo Clinic Cancer Center Center Paula Silverman, MD† Debra L. Friedman, MD, MS€‡† Case Comprehensive Cancer Center/ Vanderbilt-Ingram Cancer Center University Hospitals Seidman Cancer Center and *Mindy Goldman, MDΩ Cleveland Clinic Taussig Cancer Institute UCSF Helen Diller Family Comprehensive Cancer Center Sophia Smith, PhD, MSW£ Melissa Hudson, MD€‡† Duke Cancer Institute St. Jude Children’s Research Hospital/ *Karen L. Syrjala, PhDq£ The University of Tennessee Health Science Center Fred Hutchinson Cancer Research Center/ Nazanin Khakpour, MD¶ Seattle Cancer Care Alliance Moffitt Cancer Center Amye Tevaarwerk, MD‡ Allison King, MD€ψ‡† University of Wisconsin Carbone Cancer Center Siteman Cancer Center at Barnes-Jewish Hospital and *Susan G. Urba, MD†£ Washington University School of Medicine University of Michigan Rogel Cancer Center Divya Koura, MD‡ Mark T. Wakabayashi, MD, MPHΩ UC San Diego Moores Cancer Center City of Hope National Medical Center Robin M. Lally, PhD, RN, MS# Phyllis Zee, MD, PhDψ Fred & Pamela Buffett Cancer Center Robert H. Lurie Comprehensive Cancer Center of Terry S. Langbaum, MAS¥ Northwestern University The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins NCCN Staff: Deborah A. Freedman-Cass, PhD, Allison L. McDonough, MD and Nicole R. McMillian, MS Massachusetts General Hospital Cancer Center KEY: Michelle Melisko, MD†£ UCSF Helen Diller Family Comprehensive Cancer Center *Discussion Section Writing Committee *Jose G. Montoya, MDF Specialties: †Medical Oncology; ÞInternal Medicine; €Pediatric Stanford Cancer Institute Oncology; ξBone Marrow Transplantation; wUrology; @Nutrition Kathi Mooney, RN, PhD#† Science/Dietitian; ‡Hematology/Hematology Oncology; ΩGynecology/ Huntsman Cancer Institute at the University of Utah Gynecologic Oncology; ¶Surgery/Surgical Oncology; ψNeurology/ *Javid J. Moslehi, MDλÞ Neuro-Oncology; #Nursing; ¥Patient Advocacy; £Supportive Care Vanderbilt-Ingram Cancer Center Including Palliative, Pain Management, Pastoral Care, and Oncology Tracey O’Connor, MD† Social Work; FInfectious Diseases; λCardiology; εEpidemiology; Roswell Park Comprehensive Cancer Center qPsychiatry, Psychology, Including Health Behavior. © JNCCN—Journal of the National Comprehensive Cancer Network | Volume 16 Number 10 | October 2018 1218 ANTHRACYCLINE-INDUCED CARDIAC TOXICITY Survivorship, Version 2.2018 PRINCIPLES OF ANTHRACYCLINE-INDUCED CARDIAC TOXICITY INITIAL CLINICAL ASSESSMENT FOR PATIENTS WHO HAVE RECEIVED PREVIOUS ANTHRACYCLINE THERAPY • Cancer treatments can result in diverse cardiovascular issues. These guidelines
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