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Ilana M. Braun, Donna B. Greenberg and William F. Pirl

Although some cancer survivors report persistent fatigue years after treatment, little is known about the prevalence of the symptom in this population as compared with the general population. This article examines current evidence for the occurrence of fatigue in long-term cancer survivors by reviewing published population-based studies that incorporated controls from the general population. Using the search criteria “fatigue AND cancer survivors” in PubMed, the authors identified 16 articles (based on 15 cross-sectional datasets) comparing fatigue severities in survivors of adult cancers with those in the general population. When data allowed, Hedges' g effect size calculations were generated. A total of 8096 cancer survivors were examined across datasets. Cancer survivor sample sizes ranged from 15 to 1933 per dataset. Most datasets focused on either breast cancer (7) or Hodgkin's disease survivors (6). Four studies did not clearly exclude patients undergoing active treatment. Nine articles (based on 8 datasets) showed statistically significant (P < .05) differences among groups; 4 articles showed negative results; and 3 showed both positive and negative results depending on fatigue dimension measured. Among the studies that reported scores for the fatigue subscale of the European Organization for Research and Treatment of Cancer Core Questionnaire for Quality of Life (most studies), mean fatigue levels in cancer survivors ranged from 28.7 to 36.5 out of an overall score of 100, and mean fatigue levels in matched general population controls ranged from 20 to 30 out of 100. No associations between instruments and results were apparent. Although the small numbers of studies prevented comparisons among cancer subtypes, equal positive and negative studies were seen in breast cancer survivors and, notably, no negative studies were seen involving Hodgkin's disease survivors. Most effect sizes calculated were small. Fatigue was a burden to both cancer survivors and members of the general population. While evidence for greater fatigue severity in cancer survivors was mixed, most studies reported greater fatigue in cancer survivors as compared with controls. The magnitude of this effect was generally small. Inferences from the data were limited by variability in both the definition of survivor and the fatigue assessments used, as well as by the cross-sectional design of the studies. Prospective longitudinal studies are needed to determine causal relationships between excessive fatigue and surviving cancer.

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Jamie M. Jacobs, Molly E. Ream, Nicole Pensak, Lauren E. Nisotel, Joel N. Fishbein, James J. MacDonald, Joanne Buzaglo, Inga T. Lennes, Steven A. Safren, William F. Pirl, Jennifer S. Temel and Joseph A. Greer

Background: Oral therapies are increasingly common in oncology care. However, data are lacking regarding the physical and psychologic symptoms patients experience, or how these factors relate to medication adherence and quality of life (QoL). Materials and Methods: From December 2014 through August 2016, a total of 181 adult patients who were prescribed oral targeted therapy or chemotherapy enrolled in a randomized study of adherence and symptom management at Massachusetts General Hospital Cancer Center. Patients completed baseline assessments of adherence with electronic pill cap, QoL, symptom severity, mood, social support, fatigue, and satisfaction with clinicians and treatment. Relationships among these factors were examined using Pearson product-moment correlations and multivariable linear regression. Results: At baseline, the mean electronic pill cap adherence rate showed that patients took 85.57% of their oral therapy. The most commonly reported cancer-related symptoms were fatigue (88.60%), drowsiness (76.50%), disturbed sleep (68.20%), memory problems (63.10%), and emotional distress (60.80%). Patients who reported greater cancer-related symptom severity had lower adherence (r= −0.20). In a multivariable regression, greater depressive and anxiety symptoms, worse fatigue, less social support, lower satisfaction with clinicians and treatment, and higher symptom burden were associated with worse QoL (F[10, 146]=50.53; adjusted R 2=0.77). Anxiety symptoms were most strongly associated with clinically meaningful decrements in QoL (β= −7.10; SE=0.22). Conclusions: Patients prescribed oral therapies struggle with adherence, and cancer-related symptom burden is high and related to worse adherence and QoL. Given perceptions that oral therapies are less impairing, these data underscore the strong need to address adherence issues, symptom burden, and QoL for these patients.

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Ann M. Berger, Amy Pickar Abernethy, Ashley Atkinson, Andrea M. Barsevick, William S. Breitbart, David Cella, Bernadine Cimprich, Charles Cleeland, Mario A. Eisenberger, Carmen P. Escalante, Paul B. Jacobsen, Phyllis Kaldor, Jennifer A. Ligibel, Barbara A. Murphy, Tracey O'Connor, William F. Pirl, Eve Rodler, Hope S. Rugo, Jay Thomas and Lynne I. Wagner

Overview Fatigue is a common symptom in patients with cancer and is nearly universal in those undergoing cytotoxic chemotherapy, radiation therapy, bone marrow transplantation, or treatment with biologic response modifiers.1–10 The symptom is experienced by 70% to 100% of patients with cancer who undergo multi-modal treatments and dose–dense, dose-intense protocols.11 In patients with metastatic disease, the prevalence of cancer-related fatigue exceeds 75%. Cancer survivors report that fatigue is a disruptive symptom months or even years after treatment ends.12–21 The distinction between tiredness, fatigue, and exhaustion has not been made, despite conceptual differences.22,23 Patients perceive fatigue to be the most distressing symptom associated with cancer and its treatment, more distressing even than pain or nausea and vomiting, which, for most patients, can generally be managed with medications.24,25 Fatigue in patients with cancer has been underreported, underdiagnosed, and undertreated. Persistent cancer-related fatigue affects quality of life (QOL), because patients become too tired to fully participate in the roles and activities that make their lives meaningful.16,26–28 Health care professionals have been challenged in their efforts to help patients manage this distressful symptom and remain as fully engaged in life as possible. Because of the successes in cancer treatment, health care professionals are now likely to see patients with prolonged states of fatigue related to the late effects of treatment. Disability-related issues are relevant and often challenging, especially for patients who are cured of their malignancy but experience continued fatigue.29 Despite biomedical literature documenting this entity, patients with cancer-related fatigue often have difficulty obtaining...
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Ann M. Berger, Kathi Mooney, Amy Alvarez-Perez, William S. Breitbart, Kristen M. Carpenter, David Cella, Charles Cleeland, Efrat Dotan, Mario A. Eisenberger, Carmen P. Escalante, Paul B. Jacobsen, Catherine Jankowski, Thomas LeBlanc, Jennifer A. Ligibel, Elizabeth Trice Loggers, Belinda Mandrell, Barbara A. Murphy, Oxana Palesh, William F. Pirl, Steven C. Plaxe, Michelle B. Riba, Hope S. Rugo, Carolina Salvador, Lynne I. Wagner, Nina D. Wagner-Johnston, Finly J. Zachariah, Mary Anne Bergman and Courtney Smith

Cancer-related fatigue is defined as a distressing, persistent, subjective sense of physical, emotional, and/or cognitive tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and interferes with usual functioning. It is one of the most common side effects in patients with cancer. Fatigue has been shown to be a consequence of active treatment, but it may also persist into posttreatment periods. Furthermore, difficulties in end-of-life care can be compounded by fatigue. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Cancer-Related Fatigue provide guidance on screening for fatigue and recommendations for interventions based on the stage of treatment. Interventions may include education and counseling, general strategies for the management of fatigue, and specific nonpharmacologic and pharmacologic interventions. Fatigue is a frequently underreported complication in patients with cancer and, when reported, is responsible for reduced quality of life. Therefore, routine screening to identify fatigue is an important component in improving the quality of life for patients living with cancer.

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Crystal S. Denlinger, Tara Sanft, K. Scott Baker, Gregory Broderick, Wendy Demark-Wahnefried, Debra L. Friedman, Mindy Goldman, Melissa Hudson, Nazanin Khakpour, Allison King, Divya Koura, Robin M. Lally, Terry S. Langbaum, Allison L. McDonough, Michelle Melisko, Jose G. Montoya, Kathi Mooney, Javid J. Moslehi, Tracey O'Connor, Linda Overholser, Electra D. Paskett, Jeffrey Peppercorn, William Pirl, M. Alma Rodriguez, Kathryn J. Ruddy, Paula Silverman, Sophia Smith, Karen L. Syrjala, Amye Tevaarwerk, Susan G. Urba, Mark T. Wakabayashi, Phyllis Zee, Nicole R. McMillian and Deborah A. Freedman-Cass

The NCCN Guidelines for Survivorship provide screening, evaluation, and treatment recommendations for common physical and psychosocial consequences of cancer and cancer treatment to help healthcare professionals who work with survivors of adult-onset cancer in the posttreatment period. This portion of the guidelines describes recommendations regarding the management of anthracycline-induced cardiotoxicity and lymphedema. In addition, recommendations regarding immunizations and the prevention of infections in cancer survivors are included.

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NCCN Guidelines Insights: Survivorship, Version 2.2019

Featured Updates to the NCCN Guidelines

Tara Sanft, Crystal S. Denlinger, Saro Armenian, K. Scott Baker, Gregory Broderick, Wendy Demark-Wahnefried, Debra L. Friedman, Mindy Goldman, Melissa Hudson, Nazanin Khakpour, Divya Koura, Robin M. Lally, Terry S. Langbaum, Allison L. McDonough, Michelle Melisko, Kathi Mooney, Halle C.F. Moore, Javid J. Moslehi, Tracey O’Connor, Linda Overholser, Electra D. Paskett, Lindsay Peterson, William Pirl, M. Alma Rodriguez, Kathryn J. Ruddy, Sophia Smith, Karen L. Syrjala, Amye Tevaarwerk, Susan G. Urba, Phyllis Zee, Nicole R. McMillian and Deborah A. Freedman-Cass

The NCCN Guidelines for Survivorship provide screening, evaluation, and treatment recommendations for consequences of cancer and cancer treatment to aid healthcare professionals who work with survivors of adult-onset cancer. Guidance is also provided to help promote physical activity, weight management, and proper immunizations in survivors and to facilitate care coordination to ensure that all needs are addressed. These NCCN Insights summarize some of the topics discussed by the NCCN Survivorship Panel during the 2019 update of the guidelines, including the survivorship population addressed, ways to improve care coordination, and pain management.