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Oral treatment (targeted or chemotherapy) for cancer is being increasingly used. While fatigue is a known side effect of intravenous chemotherapy, the rate of fatigue and the impact of fatigue on other patient-reported outcomes are not well described.
At Massachusetts General Hospital Cancer Center, 180 adult patients prescribed oral targeted or chemotherapy for various malignancies enrolled in a randomized controlled trial of adherence and symptom management. Patients completed baseline self-reported measures of fatigue (Brief Fatigue Inventory; BFI), anxiety and depressive symptoms (Hospital Anxiety and Depression Scale; HADS), and quality of life, including subscales for physical, social, emotional, and functional well-being ([QOL] Functional Assessment of Cancer Therapy — General; FACT-G). We examined clinically relevant fatigue using a validated cut-off score for moderate-severe fatigue (BFI global fatigue ≥4) and tested the associations with anxiety symptoms, depressive symptoms, and QOL with independent samples t-tests.
At baseline, 45 of 180 participants (25.0%) reported moderate-severe fatigue. Fatigued patients experienced more anxiety symptoms (mean diff. 3.73, P < 0.001), more depressive symptoms (mean diff. 4.14, P < 0.001), and worse QOL on the total FACT-G score (mean diff. −19.58, P < 0.001) and all subscales of the FACT-G compared to patients without moderate-severe fatigue.
Significance of results
One in four patients on oral treatment for cancer experienced clinically relevant fatigue that is associated with greater anxiety and depressive symptoms and worse QOL.
Wearable devices such as a wrist actigraph may have a potential to objectively estimate patients’ functioning and may supplement performance status (PS). This proof-of-concept study aimed to evaluate whether actigraphy data are significantly associated with patients’ functioning and are predictive of their survival in patients with metastatic non-small cell lung cancer.
We collected actigraphy data for a three-day period in ambulatory patients with stage IV non-small cell lung cancer. We computed correlations between actigraphy data (specifically, proportion of time spent immobile while awake) and clinician-rated PS, subjective report of physical activities, quality of life (the Functional Assessment of Cancer Therapy – Trial Outcome Index), and survival.
Actigraphy data (the proportion of time awake spent immobile) were significantly correlated with Functional Assessment of Cancer Therapy – Trial Outcome Index (r = −0.53, p < 0.001) and with the Eastern Cooperative Oncology Group PS (ECOG PS) (r = 0.37, p < 0.001). The proportion of time awake spent immobile was significantly associated with worse survival. For each 10% increase in this measure, the hazard ratio (HR) was 1.48 (95% confidence interval [CI95%] = 1.06, 2.06) for overall mortality, and odds ratio was 2.99 (CI95% = 1.27, 7.05) for six-month mortality. ECOG PS was also associated with worse survival (HR = 2.80, CI95% = 1.34, 5.86). Among patients with ECOG PS 0-1, the percentage of time awake spent immobile was significantly associated with worse survival, HR = 1.93 (CI95% = 1.10, 3.42), whereas ECOG PS did not predict survival.
Significance of Results
Actigraphy may have potential to predict important clinical outcomes, such as quality of life and survival, and may serve to supplement PS. Further validation study is warranted.
Early career investigators have few opportunities for targeted training in supportive oncology research. To address this need, we developed, implemented, and evaluated an intensive, six-day workshop on methods in supportive oncology research for trainees and junior faculty across multiple disciplines.
A multidisciplinary team of supportive oncology researchers developed a workshop patterned after the clinical trials workshop offered jointly by the American Society of Clinical Oncology and American Association of Cancer Research. The curriculum included lectures and a mentored experience of writing a research protocol. Each year since 2015, the workshop has accepted and trained 36 early career investigators. Over the course of the workshop, participants present sections of their research protocols daily in small groups led by senior researchers, and have dedicated time to write and revise these sections. Primary outcomes for the workshop included the frequency of completed protocols by the end of the workshop, a pre- and posttest assessing participant knowledge, and follow-up surveys of the participants and their primary mentors.
Over three years, the workshop received 195 applications; 109 early career researchers were competitively selected to participate. All participants (109/109, 100%) completed writing a protocol by the end of their workshop. Participants and their primary mentors reported significant improvements in their research knowledge and skills. Each year, participants rated the workshop highly in terms of satisfaction, value, and likelihood of recommending it to a colleague. One year after the first workshop, most respondents (29/30, 96.7%) had either submitted their protocol or written at least one other protocol.
Significance of results
We developed a workshop on research methods in supportive oncology. More early career investigators applied for the workshop than capacity, and the workshop was fully attended each year. Both the workshop participants and their primary mentors reported improvement in research skills and knowledge.
Although depression appears to be associated with worse survival from cancer, the underlying mechanisms of this association are unknown. Tumor epidermal growth factor receptor (EGFR) genotype is a known predictor of survival in metastatic non-small cell lung cancer (NSCLC) and appears to be associated with depression. We hypothesized that tumor EGFR genotype may account for a relationship between depression and survival in this population. We investigated this possible relationship in a cohort of patients with metastatic NSCLC, in which we had previously demonstrated an association between depression and worse survival.
A cohort of 151 patients with newly diagnosed metastatic NSCLC were enrolled and followed in a randomized controlled trial of early palliative care. At enrollment, 150 had depression assessed with the Patient Health Questionnaire-9 (PHQ-9), and categorical scoring for major depressive syndrome (MDS) was used for analyses. Patients with tumor tissue available underwent EGFR genotyping. Associations with survival were tested using Cox proportional hazards models, adjusting for potential confounders.
Twenty-one patients (14.0%) met criteria for MDS. Forty-four patients (29.3%) had EGFR genotyping, and 17 (38.6%) of these harbored EGFR mutations. Patients with EGFR mutations had significantly lower PHQ-9 scores (p = 0.03), and none met criteria for depression. EGFR mutations were significantly associated with superior survival (p = 0.02). When both depression and EGFR genotype were simultaneously entered into the model, only EGFR mutations remained significantly associated with survival (p = 0.02), and the effect of depression was attenuated.
Significance of results:
Depression is associated with worse survival in metastatic NSCLC, and this relationship may be at least partially explained by tumor EGFR genotype. Further study into whether depression could be associated with specific biologic properties of cancer that vary by genotype is warranted.
Fatigue is currently recognized as an undertreated symptom in cancer. To date the association between fatigue and inflammatory activation has not been examined in patients with advanced cancer. Our exploratory investigation considered whether variations in routinely available hematological parameters relate to the severity of fatigue reports.
Fatigue, white blood cell differential, and hemoglobin concentration were assessed in 44 Stage IIIb and IV non-small-cell lung cancer (NSCLC) patients. Days of survival and the relative timing of treatment discontinuation were also recorded. Relationships between fatigue intensity and length of survival and between fatigue and hematological variables were examined using binomial and linear regressions respectively.
When we controlled for effects related to age, gender, and time until treatment termination, more intense fatigue was associated with shorter survival (β = −.34, p = .03). Lower hemoglobin concentrations were associated with more intense fatigue (β = −.36, p = .04). When we controlled for the effect attributable to hemoglobin, higher neutrophil (β = .43, p = .01) and monocyte (β = .31, p = .05) concentrations were associated with reports of more severe fatigue.
Significance of results:
This exploratory study provides empiric data showing that the severity of fatigue reported by advanced-stage NSCLC patients is significantly associated with length of survival. Consistent with existing data, linear regression identified a negative association between fatigue intensity and hemoglobin concentration. When we controlled for this effect, further linear regressions identified significant relationships between fatigue and blood concentrations of neutrophils and monocytes. Further, the magnitude of relationship between myeloid cell concentrations and fatigue was similar to the effect size identified for the relationship between hemoglobin and fatigue. Thus, the indirect measure of inflammatory state provided by routinely assessed myeloid cell counts appears to play as strong a role as the established variable, hemoglobin, in accounting for the fatigue reported by this sample of advanced-stage lung cancer patients.
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