FIT: Functional and imaging testing for patients with metastatic cancer.

BACKGROUND: Selecting study endpoints in prospective cancer cachexia trials remains poorly defined. The aim of this study was to further evaluate associations in changes in weight, body composition, functional outcomes, and patient-reported outcomes (PROs) in patients with metastatic cancer. METHODS: We completed a 2-year (2016-2018) observational study in patients with metastatic solid cancer and ECOG performance status 0 to 2 while receiving chemotherapy and/or immunotherapy. We completed assessments at study enrollment and 3 months from enrollment. We analyzed longitudinal changes in weight and body composition using validated methods. Functional assessments included the 6-Min Walk Test, Timed Up and Go Test, and Short Physical Performance Battery. PROs included the Functional Assessment of Anorexia/Cachexia Therapy and Functional Assessment of Cancer Therapy Fatigue. We analyzed changes in body composition and functional assessment using paired t tests. Additionally, we utilized linear regression models to assess relationships between changes in body composition and function outcomes and PROs, adjusting for age and sex. RESULTS: A total of 57 patients completed baseline assessments, but 19 patients did not complete 3-month assessments (5 died, 1 hospice, 13 withdrew). Of the 38 patients with complete data, the mean age was 61.8 years and 47% were female. Metastatic cancer types included 71% gastrointestinal, 13% lung, and 8% gynecologic. Half received chemotherapy, 16% immunotherapy, and 34% a combination. From enrollment to 3 months, we did not observe a change in weight or skeletal muscle but did find an increase in total adipose tissue (16.9 ± 52.4 cm2, 95% CI - 33.79-0.63; p = 0.059; ~ 1.5 pounds). We did not observe any association with changes in weight with any functional outcomes or PROs. However, greater losses in skeletal muscle were associated with greater declines in physical function (6-Min Walk Test [B = 0.04, p = 0.01], Short Physical Performance Battery [B = 2.44, p < 0.01]). CONCLUSIONS: Patients with metastatic cancer receiving cancer-directed therapy may not experience a change in body weight. However, we found an association between losses in skeletal muscle and greater declines in physical function. Therefore, when selecting study endpoints, prospective cancer cachexia studies may consider selecting changes in body composition over weight.

Differential effects of an electronic symptom monitoring intervention based on the age of patients with advanced cancer.

BACKGROUND: Symptom monitoring interventions enhance patient outcomes, including quality of life (QoL), health care utilization, and survival, but it remains unclear whether older and younger patients with cancer derive similar benefits. We explored whether age moderates the improved outcomes seen with an outpatient electronic symptom monitoring intervention. PATIENTS AND METHODS: We carried out a secondary analysis of data from a randomized trial of 766 patients receiving chemotherapy for metastatic solid tumors. Patients received an electronic symptom monitoring intervention integrated with oncology care or usual oncology care alone. The intervention consisted of patients reporting their symptoms, which were provided to their physicians at clinic visits, and nurses receiving alerts for severe/worsening symptoms. We used regression models to determine whether age (older or younger than 70 years) moderated the effects of the intervention on QoL (EuroQol EQ-5D), emergency room (ER) visits, hospitalizations, and survival outcomes. RESULTS: Enrollment rates for younger (589/777 = 75.8%) and older (177/230 = 77.0%) patients did not differ. Older patients (median age = 75 years, range 70-91 years) were more likely to have an education level of high school or less (26.6% versus 20.9%, P = 0.029) and to be computer inexperienced (50.3% versus 23.4%, P < 0.001) compared with younger patients (median age = 58 years, range 26-69 years). Younger patients receiving the symptom monitoring intervention experienced lower risk of ER visits [hazard ratio (HR) = 0.74, P = 0.011] and improved survival (HR = 0.76, P = 0.011) compared with younger patients receiving usual care. However, older patients did not experience significantly lower risk of ER visits (HR = 0.90, P = 0.613) or improved survival (HR = 1.06, P = 0.753) with the intervention. We found no moderation effects based on age for QoL and risk of hospitalizations. CONCLUSIONS: Among patients with advanced cancer, age moderated the effects of an electronic symptom monitoring intervention on the risk of ER visits and survival, but not QoL. Symptom monitoring interventions may need to be tailored to the unique needs of older adults with cancer.

Pilot randomized trial of an electronic symptom monitoring intervention for hospitalized patients with cancer.

BACKGROUND: Hospitalized patients with cancer experience a high symptom burden, which is associated with poor health outcomes and increased health care utilization. However, studies investigating symptom monitoring interventions in this population are lacking. We conducted a pilot randomized trial to assess the feasibility and preliminary efficacy of a symptom monitoring intervention to improve symptom management in hospitalized patients with advanced cancer. PATIENTS AND METHODS: We randomly assigned patients with advanced cancer who were admitted to the inpatient oncology service to a symptom monitoring intervention or usual care. Patients in both arms self-reported their symptoms daily (Edmonton Symptom Assessment System and Patient Health Questionnaire-4). Patients assigned to the intervention had their symptom reports presented graphically with alerts for moderate/severe symptoms during daily team rounds. The primary end point of the study was feasibility. We defined the intervention as feasible if >75% of participants hospitalized >2 days completed >2 symptom reports. We observed daily rounds to determine whether clinicians discussed and developed a plan to address patients' symptoms. We used regression models to assess intervention effects on patients' symptoms throughout their hospitalization, readmission risk, and hospital length of stay (LOS). RESULTS: Among 150 enrolled patients (81.1% enrollment), 94.2% completed >2 symptom reports. Clinicians discussed 60.4% of the symptom reports and developed a plan to address the symptoms highlighted by the symptom reports 20.8% of the time. Compared with usual care, intervention patients had a greater proportion of days with lower psychological distress (B = 0.12, P = 0.008), but no significant difference in the proportion of days with improved Edmonton Symptom Assessment System-physical symptoms (B = 0.07, P = 0.138). Intervention patients had lower readmission risk (hazard ratio = 0.68, P = 0.224), although this difference was not significant. We found no significant intervention effects on hospital LOS (B = 0.16, P = 0.862). CONCLUSIONS: This symptom monitoring intervention is feasible and demonstrates encouraging preliminary efficacy for improving patients' symptoms and readmission risk.ClinicalTrials.gov identifier NCT02891993.

Factors associated with depression and anxiety symptoms in family caregivers of patients with incurable cancer.

BACKGROUND: Family caregivers (FCs) are critically important for patients with cancer, yet they may experience psychological distress related to caregiving demands. We sought to describe rates of depression and anxiety in FCs of patients with incurable cancer and identify factors associated with these symptoms to determine those at greatest risk for psychological distress. PATIENTS AND METHODS: We performed a cross-sectional analysis of baseline data from a randomized trial of early palliative care. We assessed depression and anxiety using the Hospital Anxiety and Depression Scale in patients within 8 weeks of diagnosis of incurable lung or gastrointestinal cancer and their FCs. We also assessed patients' quality of life (Functional Assessment of Cancer Therapy-General), coping strategies (Brief COPE), and their report of the primary goal of their cancer treatment. We used linear regression with purposeful selection of covariates to identify factors associated with FC depression and anxiety symptoms. RESULTS: We enrolled 78.6% (n = 275) of potentially eligible FCs. The majority were female (69.1%) and married to the patient (66.2%). While the proportion of FCs and patients reporting depression did not differ (16.4% versus 21.5%, P = 0.13), FCs were more likely to report anxiety compared with patients (42.2% versus 28.4%, P < 0.001). Patients' use of acceptance coping was associated with lower FC depression (B = -0.42, P < 0.001), while emotional support coping was associated with higher FC depression (B = 0.69, P = 0.001) and lower FC anxiety (B = -0.70, P < 0.001). Patient report that their primary goal of their treatment was to 'cure my cancer' was associated with higher FC depression (B = 0.72, P = 0.03). CONCLUSIONS: Patients with incurable cancer and their FCs report high levels of depression and anxiety symptoms. We demonstrated that patients' coping strategies and prognostic understanding were associated with FC depression and anxiety symptoms, underscoring the importance of targeting these risk factors when seeking to address the psychological distress experienced by FCs.

Best supportive care in clinical trials: review of the inconsistency in control arm design.

BACKGROUND: Best supportive care (BSC) as a control arm in clinical trials is poorly defined. We conducted a review to evaluate clinical trials' concordance with published, consensus-based framework for BSC delivery in trials. METHODS: A consensus-based Delphi panel previously identified four key domains of BSC delivery in trials: multidisciplinary care; supportive care documentation; symptom assessment; and symptom management. We reviewed trials including BSC control arms from 2002 to 2014 to assess concordance to BSC standards and to selected items from the CONSORT 2010 guidelines. RESULTS: Of 408 articles retrieved, we retained 18 after applying exclusion criteria. Overall, trials conformed to the CONSORT guidelines better than the BSC standards (28% vs 16%). One-third of articles offered a detailed description of BSC, 61% reported regular symptom assessment, and 44% reported using validated symptom assessment measures. One-third reported symptom assessment at identical intervals in both arms. None documented evidence-based symptom management. No studies reported educating patients about symptom management or goals of therapy. No studies reported offering access to palliative care specialists. CONCLUSIONS: Reporting of BSC in trials is incomplete, resulting in uncertain internal and external validity. Such studies risk systematically over-estimating the net clinical effect of the comparator arms.