Purpose To provide guidance regarding the practical assessment and management of vulnerabilities in older patients undergoing chemotherapy. Methods An Expert Panel was convened to develop clinical practice guideline recommendations based on a systematic review of the medical literature. Results A total of 68 studies met eligibility criteria and form the evidentiary basis for the recommendations. Recommendations In patients ≥ 65 years receiving chemotherapy, geriatric assessment (GA) should be used to identify vulnerabilities that are not routinely captured in oncology assessments. Evidence supports, at a minimum, assessment of function, comorbidity, falls, depression, cognition, and nutrition. The Panel recommends instrumental activities of daily living to assess for function, a thorough history or validated tool to assess comorbidity, a single question for falls, the Geriatric Depression Scale to screen for depression, the Mini-Cog or the Blessed Orientation-Memory-Concentration test to screen for cognitive impairment, and an assessment of unintentional weight loss to evaluate nutrition. Either the CARG (Cancer and Aging Research Group) or CRASH (Chemotherapy Risk Assessment Scale for High-Age Patients) tools are recommended to obtain estimates of chemotherapy toxicity risk; the Geriatric-8 or Vulnerable Elders Survey-13 can help to predict mortality. Clinicians should use a validated tool listed at ePrognosis to estimate noncancer-based life expectancy ≥ 4 years. GA results should be applied to develop an integrated and individualized plan that informs cancer management and to identify nononcologic problems amenable to intervention. Collaborating with caregivers is essential to implementing GA-guided interventions. The Panel suggests that clinicians take into account GA results when recommending chemotherapy and that the information be provided to patients and caregivers to guide treatment decision making. Clinicians should implement targeted, GA-guided interventions to manage nononcologic problems. Additional information is available at www.asco.org/supportive-care-guidelines .

IMPORTANCE Cancer-related fatigue (CRF) remains one of the most prevalent and troublesome adverse events experienced by patients with cancer during and after therapy. OBJECTIVE To perform a meta-analysis to establish and compare the mean weighted effect sizes (WESs) of the 4 most commonly recommended treatments for CRF—exercise, psychological, combined exercise and psychological, and pharmaceutical—and to identify independent variables associated with treatment effectiveness. DATA SOURCES PubMed, PsycINFO, CINAHL, EMBASE, and the Cochrane Library were searched from the inception of each database to May 31, 2016. STUDY SELECTION Randomized clinical trials in adults with cancer were selected. Inclusion criteria consisted of CRF severity as an outcome and testing of exercise, psychological, exercise plus psychological, or pharmaceutical interventions. DATA EXTRACTION AND SYNTHESIS Studies were independently reviewed by 12 raters in 3 groups using a systematic and blinded process for reconciling disagreement. Effect sizes (Cohen d) were calculated and inversely weighted by SE. MAIN OUTCOMES AND MEASURES Severity of CRF was the primary outcome. Study quality was assessed using a modified 12-item version of the Physiotherapy Evidence-Based Database scale (range, 0–12, with 12 indicating best quality). RESULTS From 17 033 references, 113 unique studies articles (11525 unique participants; 78% female; mean age, 54 [range, 35–72] years) published from January 1, 1999, through May 31, 2016, had sufficient data. Studies were of good quality (mean Physiotherapy Evidence-Based Database scale score, 8.2; range, 5–12) with no evidence of publication bias. Exercise (WES, 0.30; 95% CI, 0.25–0.36; P < .001), psychological (WES, 0.27; 95% CI, 0.21–0.33; P < .001), and exercise plus psychological interventions (WES, 0.26; 95% CI, 0.13–0.38; P < .001) improved CRF during and after primary treatment, whereas pharmaceutical interventions did not (WES, 0.09; 95% CI, 0.00–0.19; P = .05). Results also suggest that CRF treatment effectiveness was associated with cancer stage, baseline treatment status, experimental treatment format, experimental treatment delivery mode, psychological mode, type of control condition, use of intention-to-treat analysis, and fatigue measures (WES range, −0.91 to 0.99). Results suggest that the effectiveness of behavioral interventions, specifically exercise and psychological interventions, is not attributable to time, attention, and education, and specific intervention modes may be more effective for treating CRF at different points in the cancer treatment trajectory (WES range, 0.09–0.22). CONCLUSIONS AND RELEVANCE Exercise and psychological interventions are effective for reducing CRF during and after cancer treatment, and they are significantly better than the available pharmaceutical options. Clinicians should prescribe exercise or psychological interventions as first-line treatments for CRF.

Cancer-related fatigue (CRF) is one of the most prevalent symptoms patients with cancer experience, both during and after treatment. CRF is pervasive and affects patients' quality of life considerably. It is important, therefore, to understand the underlying pathophysiology of CRF in order to develop useful strategies for prevention and treatment. At present, the etiology of CRF is poorly understood and the relative contributions of the neoplastic disease, various forms of cancer therapy, and comorbid conditions (e.g., anemia, cachexia, sleep disorders, depression) remain unclear. In any individual, the etiology of CRF probably involves the dysregulation of several physiological and biochemical systems. Mechanisms proposed as underlying CRF include 5-HT neurotransmitter dysregulation, vagal afferent activation, alterations in muscle and ATP metabolism, hypothalamic-pituitary-adrenal axis dysfunction, circadian rhythm disruption, and cytokine dysregulation. Currently, these hypotheses are largely based on evidence from other conditions in which fatigue is a characteristic, in particular chronic fatigue syndrome and exercise-induced fatigue. The mechanisms that lead to fatigue in these conditions provide a theoretical basis for future research into the complex etiology of this distressing and debilitating symptom. An understanding of relevant mechanisms may offer potential routes for its prevention and treatment in patients with cancer.

A B S T R A C T PurposeSleep disruption is prevalent in patients with cancer and survivors, but the prevalence of insomnia, a distressing sleep disorder, in these populations has yet to be determined in large-scale studies. Patients and MethodsA total of 823 patients with cancer receiving chemotherapy (mean age, 58 years; 597 female patients) reported on sleep difficulties in a prospective study. ResultsDuring day 7 of cycle 1 of chemotherapy, 36.6% (n ϭ 301) of the patients with cancer reported insomnia symptoms, and 43% (n ϭ 362) met the diagnostic criteria for insomnia syndrome. Patients with cancer younger than 58 years were significantly more likely to experience either symptoms of insomnia or insomnia syndrome ( 2 ϭ 13.6; P ϭ .0002). Patients with breast cancer had the highest number of overall insomnia complaints. A significant positive association was found between symptoms of insomnia during cycles 1 and 2 of chemotherapy ( ϭ .62, P Ͻ .0001), showing persistence of insomnia during the first two cycles of chemotherapy. Sixty percent of the patient sample reported that their insomnia symptoms remained unchanged from cycle 1 to cycle 2. Those with insomnia complaints had significantly more depression and fatigue than good sleepers (all P Ͻ .0001). ConclusionThe proportions of patients with cancer in this sample reporting symptoms of insomnia and meeting diagnostic criteria for insomnia syndrome during chemotherapy are approximately three times higher than the proportions reported in the general population. Insomnia complaints persist throughout the second chemotherapy cycle for the majority of patients with cancer in this study. Insomnia is prevalent, underrecognized, undermanaged, and understudied among patients with cancer receiving chemotherapy.