Fatigue is a distressing and persistent symptom for patients with gynecological cancer and for survivors. Debilitating cancer-related fatigue (CRF) is produced by both the disease and its treatment. Although awareness and study of CRF have grown in recent years, consistent assessment has not been a priority in routine medical practice. The pathophysiological mechanisms that induce CRF remain unclear, and effective pharmacological interventions have yet to be established. Based on the literature and our own research results, this review focuses on recent progress toward understanding the nature and causes of CRF and on several promising treatment modalities. Given the prevalence and severity of CRF in the gynecological cancer patient population, establishing standardized fatigue measurement and management methods in routine clinical oncology care is of utmost importance. Whether CRF has an underlying inflammatory cause is still hypothetical, however, and no mechanism-driven symptom intervention is currently in clinical use, even though the development of such interventions would provide patients with greater symptom control. Advancing translational and clinical fatigue research will require anatomical pathway studies and well-designed clinical investigations that focus on the development of mechanism-driven interventions based on physiological–behavioral fatigue research, implementation of guidelines for experimental designs, and discovery of biomarkers identifying individuals at high risk for CRF. Validated patient-reported outcomes measures are an essential component of such clinical studies. Because numerous subscales, unidimensional measures, and multidimensional measures exist, clinicians and researchers should consider individual circumstances, good clinical practice, and research goals as guides for choosing the most appropriate fatigue measurement tool. Additionally, education about CRF should be made available to all patients and their caregivers, as accurate and age-appropriate information about conditions like CRF can alleviate much of the stress and anxiety brought on by poor communication about this distressing condition.

Although evidence of inflammation and fatigue has been noted in cancer survivors, whether inflammation is linked to the expression of fatigue and other symptoms arising from concurrent chemoradiation therapy (CXRT) has not been well studied. Patients undergoing CXRT for locally advanced colorectal or esophageal cancer (n = 103) reported multiple symptoms weekly via the M. D. Anderson Symptom Inventory (MDASI) from start of therapy. Serum samples were collected weekly to examine changes in inflammatory markers (interleukin [IL]-6, IL-8, IL-10, IL-1 receptor antagonist [IL-1RA], vascular endothelial growth factor [VEGF], and soluble receptor 1 for tumor necrosis factor [sTNF-R1]) via enzyme-linked immunosorbent assay. Relationships between symptom severity and inflammatory-marker concentration levels were estimated using mixed-effect regression analysis, controlled for week of therapy, age, sex, body mass index, pre-CXRT tumor stage, pre-CXRT chemotherapy, pre-CXRT statin use, and type of cancer. Fatigue was the most severe symptom over time, its development profile shared with pain, distress, drowsiness, poor appetite, and disturbed sleep. sTNF-R1 and IL-6 shared a similar pattern of symptom development, with significant increase during CXRT and decrease after completion of CXRT. Serum concentrations of sTNF-R1 were positively associated over time with the severity of fatigue (p = .00097), while sTNF-R1 and IL-6 were positively related to the severity of a component score of the six most severe symptoms (both p < .0001). This longitudinal study suggests a role for over-expressed sTNF-R1 and IL-6 in the development of fatigue and other severe sickness symptoms during CXRT in patients with colorectal or esophageal cancer.

A B S T R A C T PurposeWe compared risk factors for high disease-and treatment-related symptom burden over 15 weeks of therapy in medically underserved patients with advanced non-small-cell lung cancer and in patients treated at a tertiary cancer center. Patients and MethodsWe monitored symptom severity weekly during chemotherapy. Patients were recruited from a tertiary cancer center (n ϭ 101) and three public hospitals treating the medically underserved (n ϭ 80). We used a composite symptom-severity score and group-based trajectory analysis to form two groups: one with consistently more severe symptoms and another with less severe symptoms. We examined predictors of group membership. ResultsSeventy percent of the sample (n ϭ 126) reported low symptom-severity levels that decreased during therapy; 30% (n ϭ 55) had consistently severe symptoms throughout the study. In multivariate analysis, patients with good performance status being treated in public hospitals were significantly more likely than patients treated at the tertiary cancer center to be in the highsymptom group (odds ratio, 5.6; 95% CI, 2.1 to 14.6; P ϭ .001) and to report significantly higher symptom interference (P ϭ .001). Other univariate predictors of high-symptom group membership included variables associated with being medically underserved (eg, having less education, being single, and being nonwhite). No group differences by ethnicity were observed in the public hospitals. Medically underserved patients were less likely to receive adequate pain management. ConclusionPatients with advanced lung cancer and good performance status treated at public hospitals were more likely than those treated at a tertiary cancer center to experience substantial symptoms during chemotherapy.

The multiple symptoms arising from cancer and its treatment impose significant distress for patients. However, in clinical research, there is no agreed-upon way of assessing and presenting the effects of treatment on multiple symptoms, as either individual scores or a composite score. The ASCPRO (Assessing the Symptoms of Cancer Using Patient-Reported Outcomes) Multisymptom Task Force was established to make recommendations about measuring multiple symptoms as outcomes in cancer clinical trials. The Multisymptom Task Force addressed how to choose the symptoms to be assessed and how multiple individual symptom scores or composite scores of several symptoms might be used as clinical trial outcomes. Consensus was reached on a definition of a multisymptom outcome, the problem of source attribution, and the need for a hypothesis-driven conceptual framework to measure multisymptom outcomes. Validated single-item and multi-item measures currently available or that can be easily generated for oncology use were deemed sufficient for measuring multiple symptoms. The relative value of a composite score versus a set of individual symptom scores was discussed, along with issues in developing and deploying such a composite measure. The results indicated that more research on combining scores of different symptoms is needed. Symptom data should be a required component of cancer clinical trials. Patient-reported symptoms provide a unique patient perspective on treatment benefit and risk that goes beyond clinician-reported adverse events. A representation of changes in multiple symptoms would clarify the impact of treatment and enhance the interpretation of cancer clinical trials for clinicians, patients, and those who make health care policy.

Various sensory and motor effects are associated with cancer treatment-induced peripheral neuropathy. The current method for capturing the multifaceted nature of neuropathy includes a combination of objective tests, clinician evaluation, and subjective patient report—an approach that is often not logistically feasible, especially for multisite trials. We report the performance of a brief-yet-comprehensive, easily administered measure, the Treatment-induced Neuropathy Assessment Scale (TNAS), for assessing the severity and course of neuropathy across various cancer treatments. Data were derived from 4 longitudinal or cross-sectional patient cohorts (n=573). Patients with multiple myeloma treated primarily with bortezomib and patients with colorectal cancer receiving oxaliplatin evaluated candidate items. Cognitive debriefing showed that all items were easy to understand, and this preliminary TNAS demonstrated reliability, validity, and sensitivity. Numbness/tingling was the most-severe item, regardless of therapeutic agent. Although numbness and general pain were moderately correlated, patients perceived them as distinct. Most TNAS items were more severe at follow-up, demonstrating the instrument’s sensitivity to accumulating dose. The TNAS will be refined with further patient input, with final psychometric evaluation conducted in a new patient sample receiving treatments known to be associated with peripheral neuropathy. The nonpainful component of neuropathy may be more disabling than the pain component.