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Functional Impairment, Symptom Burden, and Clinical Outcomes Among Hospitalized Patients With Advanced Cancer

Daniel E. Lage, Areej El-Jawahri, Charn-Xin Fuh, Richard A. Newcomb, Vicki A. Jackson, David P. Ryan, Joseph A. Greer, Jennifer S. Temel, and Ryan D. Nipp

Background: National guidelines recommend regular measurement of functional status among patients with cancer, particularly those who are elderly or high-risk, but little is known about how functional status relates to clinical outcomes among hospitalized patients with advanced cancer. The goal of this study was to investigate how functional impairment is associated with symptom burden and healthcare utilization and clinical outcomes. Patients and Methods: We conducted a prospective observational study of patients with advanced cancer with unplanned hospitalizations at Massachusetts General Hospital from September 2014 through March 2016. Upon admission, nurses assessed patients’ activities of daily living (ADLs; mobility, feeding, bathing, dressing, and grooming). Patients with any ADL impairment on admission were classified as having functional impairment. We used the revised Edmonton Symptom Assessment System (ESAS-r) and Patient Health Questionnaire-4 to assess physical and psychological symptoms, respectively. Multivariable regression models were used to assess the relationships between functional impairment, hospital length of stay, and survival. Results: Among 971 patients, 390 (40.2%) had functional impairment. Those with functional impairment were older (mean age, 67.18 vs 60.81 years; P<.001) and had a higher physical symptom burden (mean ESAS physical score, 35.29 vs 30.85; P<.001) compared with those with no functional impairment. They were also more likely to report moderate-to-severe pain (74.9% vs 63.1%; P<.001) and symptoms of depression (38.3% vs 23.6%; P<.001) and anxiety (35.9% vs 22.4%; P<.001). Functional impairment was associated with longer hospital length of stay (β = 1.29; P<.001) and worse survival (hazard ratio, 1.73; P<.001). Conclusions: Hospitalized patients with advanced cancer who had functional impairment experienced a significantly higher symptom burden and worse clinical outcomes compared with those without functional impairment. These findings provide evidence supporting the routine assessment of functional status on hospital admission and using this to inform discharge planning, discussions about prognosis, and the development of interventions addressing patients’ symptoms and physical function.

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Pilot Randomized Controlled Trial of an Educational Video for CAR T-Cell Therapy Recipients

P. Connor Johnson, Tejaswini Dhawale, Richard A. Newcomb, Ana Barata, Kyle Karpinski, Mitchell W. Lavoie, Dagny Vaughn, Kathleen Hennessey, David Schneider, Hermioni L. Amonoo, Angelo Volandes, and Areej El-Jawahri

Background: CAR T-cell therapy has transformed the treatment of hematologic malignancies, but it is complex and challenging to convey to patients. Educational video interventions are efficacious for improving patient knowledge about cancer therapeutics and informing their care preferences, yet no educational videos have been evaluated in CAR T-cell therapy. Methods: We conducted a randomized controlled trial comparing an educational video versus usual care in adults (age ≥18 years) with hematologic malignancies receiving CAR T-cell therapy at Massachusetts General Hospital. Intervention participants watched a 13-minute video depicting how CAR T-cell therapy works, logistics, toxicities, prognosis, recovery, and approaches for dealing with prognostic uncertainty. The primary outcome was feasibility (≥60% enrollment rate). Secondary outcomes included acceptability (≥80% reporting comfort with the video), patients’ knowledge about CAR T-cell therapy (10-item test), and self-efficacy (Communication and Attitudinal Self-Efficacy Scale–Cancer), decision satisfaction (Decision Conflict Scale), psychological distress (Hospital Anxiety and Depression Scale), and preference for CAR T-cell therapy. Results: We enrolled 79% (80/101) of eligible patients. Of that group, 91% (30/33) reported being very or somewhat comfortable watching the video, and 94% (31/33) would definitely or probably recommend the video. At 1 month, participants in the video arm reported higher self-efficacy (mean difference [MD], 9.2 [95% CI, –4.0 to 22.3]; Cohen’s d, 0.32), decision satisfaction (MD, 2.5 [95% CI, 0.7–4.2]; Cohen’s d, 0.67), and lower anxiety (MD, –0.8 [95% CI, –2.5 to 0.7]; Cohen’s d, 0.26) compared with participants in the usual care arm. At 1 week, both arms reported high preferences for CAR T-cell therapy (video arm, 94% [33/35]; usual care, 84% [27/32]). Conclusions: We found that an educational video for patients receiving CAR T-cell therapy was feasible and acceptable. The educational video demonstrated promising preliminary effects on patient self-efficacy and decision satisfaction and warrants further study.

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Relationship Between Longitudinal Coping Strategies and Outcomes in Patients With Acute Myeloid Leukemia

Hermioni L. Amonoo, Elizabeth Daskalakis, Emma C. Deary, Monica H. Bodd, Matthew J. Reynolds, Ashley M. Nelson, Richard Newcomb, Tejaswini M. Dhawale, Daniel Yang, Selina M. Luger, Jillian L. Gustin, Andrew Brunner, Amir T. Fathi, Thomas W. LeBlanc, and Areej El-Jawahri

Background: Patients with acute myeloid leukemia (AML) face an abrupt life-threatening illness and experience immense physical and psychological symptoms. However, no data describe how patients with AML cope longitudinally with their illness or the relationship between longitudinal coping and outcomes. Methods: We conducted a secondary analysis of longitudinal data from 160 patients with high-risk AML enrolled in a supportive care intervention trial to describe coping strategies longitudinally across the illness course. We used the Brief COPE questionnaire, the Hospital Anxiety and Depression Scale, the Post-Traumatic Stress Disorder (PTSD) Checklist-Civilian Version, and the Functional Assessment of Cancer Therapy-Leukemia to measure coping strategies, psychological distress, and quality of life (QoL) at baseline and at weeks 2, 4, 12, and 24 after diagnosis. Electronic health records were used to assess healthcare utilization and end-of-life (EoL) outcomes, and multivariate analyses were used to assess the relationship between coping and outcomes. Results: Longitudinal utilization of approach-oriented coping strategies was significantly associated with less distress (anxiety: β, –0.18; P<.001; depression symptoms: β, –0.42; P<.001; PTSD symptoms: β, –0.60; P<.001) and better QoL (β, 2.00; P<.001). Longitudinal utilization of avoidant coping strategies was significantly associated with greater distress (anxiety: β, 0.64; depression symptoms: β, 0.54; PTSD symptoms: β, 2.13; P<.001 for all) and worse QoL (β, –4.27; P<.001). Although the use of approach-oriented and avoidant coping strategies was not significantly associated with hospitalization, chemotherapy administration, or hospice use in the last 30 days of life, approach-oriented coping was associated with lower odds of ICU admissions (odds ratio, 0.92; P=.049). Conclusions: Longitudinal use of approach-oriented coping strategies was associated with less psychological distress, better QoL, and a lower likelihood of ICU admission, suggesting a possible target for supportive oncology interventions. Coping strategies did not impact EoL outcomes, and further research is needed to elucidate which patient factors impact EoL decision-making.

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Associations of Skeletal Muscle With Symptom Burden and Clinical Outcomes in Hospitalized Patients With Advanced Cancer

Emily van Seventer, J. Peter Marquardt, Amelie S. Troschel, Till D. Best, Nora Horick, Chinenye Azoba, Richard Newcomb, Eric J. Roeland, Michael Rosenthal, Christopher P. Bridge, Joseph A. Greer, Areej El-Jawahri, Jennifer Temel, Florian J. Fintelmann, and Ryan D. Nipp

Background: Low muscle mass (quantity) is common in patients with advanced cancer, but little is known about muscle radiodensity (quality). We sought to describe the associations of muscle mass and radiodensity with symptom burden, healthcare use, and survival in hospitalized patients with advanced cancer. Methods: We prospectively enrolled hospitalized patients with advanced cancer from September 2014 through May 2016. Upon admission, patients reported their physical (Edmonton Symptom Assessment System [ESAS]) and psychological (Patient Health Questionnaire-4 [PHQ-4]) symptoms. We used CT scans performed per routine care within 45 days before enrollment to evaluate muscle mass and radiodensity. We used regression models to examine associations of muscle mass and radiodensity with patients’ symptom burden, healthcare use (hospital length of stay and readmissions), and survival. Results: Of 1,121 patients enrolled, 677 had evaluable muscle data on CT (mean age, 62.86 ± 12.95 years; 51.1% female). Older age and female sex were associated with lower muscle mass (age: B, –0.16; P<.001; female: B, –6.89; P<.001) and radiodensity (age: B, –0.33; P<.001; female: B, –1.66; P=.014), and higher BMI was associated with higher muscle mass (B, 0.58; P<.001) and lower radiodensity (B, –0.61; P<.001). Higher muscle mass was significantly associated with improved survival (hazard ratio, 0.97; P<.001). Notably, higher muscle radiodensity was significantly associated with lower ESAS-Physical (B, –0.17; P=.016), ESAS-Total (B, –0.29; P=.002), PHQ-4-Depression (B, –0.03; P=.006), and PHQ-4-Anxiety (B, –0.03; P=.008) symptoms, as well as decreased hospital length of stay (B, –0.07; P=.005), risk of readmission or death in 90 days (odds ratio, 0.97; P<.001), and improved survival (hazard ratio, 0.97; P<.001). Conclusions: Although muscle mass (quantity) only correlated with survival, we found that muscle radiodensity (quality) was associated with patients’ symptoms, healthcare use, and survival. These findings underscore the added importance of assessing muscle quality when seeking to address adverse muscle changes in oncology.

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Group Coping Intervention in Patients With Chronic Graft-Versus-Host Disease: A Pilot Randomized Clinical Trial

Ashley M. Nelson, Daniel Yang, Annemarie D. Jagielo, Jennifer D’Alotto, Cathleen Poliquin, Dustin J. Rabideau, Katherine G. Cronin, Richard A. Newcomb, Yi-Bin Chen, Zachariah DeFilipp, Joseph A. Greer, Areej El-Jawahri, and Lara Traeger

Background: More than half the long-term survivors of allogeneic hematopoietic cell transplantation develop chronic graft-versus-host disease (GVHD), a debilitating inflammatory syndrome. Supportive interventions to assist survivors in coping with chronic GVHD are critically needed. Patients and Methods: We conducted a pilot randomized clinical trial of a multidisciplinary group intervention (Horizons Program; n=39) versus minimally enhanced usual care (n=41) for patients with moderate or severe chronic GVHD. Horizons participants received 8 weekly sessions about GVHD and coping co-led by a transplant clinician and a behavioral health expert via a secure videoconferencing platform. Participants completed the following surveys before randomization, at 10 weeks, and at 18 weeks: Functional Assessment of Cancer Therapy–Bone Marrow Transplant Scale (FACT-BMT) for quality of life (QoL), Lee Symptom Scale for symptom burden, and Hospital Anxiety and Depression Scale–Depression Symptoms (HADS) for mood. The primary endpoint was feasibility (≥50% enrollment, ≥80% attendance in half the sessions for the Horizons arm only, and ≥80% retention). We also explored preliminary efficacy of the Horizons intervention on changes in patient-reported outcomes with linear mixed effects models and estimates of effect size at 10 weeks. Results: We enrolled and registered 80 (67.2%) of 119 eligible patients (mean age, 62 years; 48.8% female). Of the participants in the Horizons Program, 84.6% attended at least half the sessions. Of registered participants, 91.3% completed assessment follow-ups (Horizons, 35/39 [89.7%]; minimally enhanced usual care, 38/41 [92.7%]). Horizons participants reported improvements in QoL (b = 2.24; d=0.53), anxiety symptoms (b = –0.10; d=0.34), and depression symptoms (b = –0.71; d=0.44) compared with participants who received minimally enhanced usual care. Conclusions: Participation in a multidisciplinary group intervention study was feasible for patients with chronic GVHD, with promising signals for improving QoL and mood. A full-scale efficacy trial is needed to confirm effects on patient-reported outcomes.