Reducing Anxiety and Dyspnea via Device-Guided Breathing (RELAX): A Multi-Site Feasibility Study in Post-Treatment Lung Cancer Survivors at Community Cancer Clinics (WF-01213).

INTRODUCTION: Anxiety and dyspnea are 2 common symptoms for lung cancer survivors. Although research suggests decreasing respiration rate can reduce anxiety in several populations, potential benefits of device-guided breathing have not been studied in lung cancer survivors. This feasibility study (WF-01213) provides estimates of accrual, adherence, retention, and preliminary efficacy of 2 doses of a device-guided breathing intervention versus a usual breathing control group for improving self-reported anxiety and dyspnea in post-treatment lung cancer survivors. METHODS: Stage I-IV lung cancer survivors were recruited through the NCI Community Oncology Research Program (NCORP) and randomized to 12 weeks of a device-guided breathing intervention (high dose vs. low dose) or control device. Self-reported outcomes (anxiety, depression, dyspnea, cancer-related worry, fatigue) were assessed at baseline, mid-intervention (Week-6), and post-intervention (Week-12). RESULTS: Forty-six participants (ages 41-77, median = 65; 78% White) were randomized to the high-dose intervention (n = 14), low-dose intervention (n = 14), or control (n = 18) groups between July 2015 and September 2019. Study accrual rate was 0.92 per month for 50 months (projected accrual was 6.3/month). Fourteen participants (30%) withdrew early from the study, with almost half of those discontinuing at or immediately following baseline assessment. No participants were adherent with the intervention per protocol specifications. The proportion minimally adherent (using device at least 1x/week) was 43% (6/14), 64% (9/14), and 61% (11/18) for high-dose, low-dose, and control groups, respectively. Anxiety significantly decreased from baseline for all groups at Week 12. Adherence to the intervention was low across all treatment groups. CONCLUSIONS: This study did not establish feasibility of a community-based randomized trial of 2 doses of device-guided breathing and a control group using an identical-looking device for lung cancer survivors. In both the high-dose and control groups, there were significant improvements from baseline for anxiety and dyspnea. In the low-dose group, there were significant improvements from baseline for anxiety and depression. Ratings and feedback on the intervention were mixed (although leaned in a positive direction). Participants reported liking the feeling of relaxation/calm, helping others, breathing awareness, and music. Participants reporting liking least finding/making time to use the device, frustration with the device, and completing study forms. TRIAL REGISTRATION: CLINICAL TRIALS ID: NCT02063828, clinicaltrials.gov.

Team-Based Hospice Referrals: A Potential Quality Metric for Lung Cancer in the Immunotherapy Era.

BACKGROUND: Immune checkpoint inhibitors (ICIs) can lead to durable responses in patients with lung cancer but may delay transitions to hospice at the end of life (EOL). We aimed to test the association of continuity of care with EOL outcomes in the ICI era. METHODS: We collected retrospective data on all patients with lung cancer who started ICI treatment at a single comprehensive cancer center in the United States (1/1/14-5/1/18) and subsequently died. We defined a hospice referral as having continuity of care if placed by a provider from the patient's multidisciplinary cancer team (e.g., a medical oncologist, palliative care specialist, intensivist, and hospitalist). RESULTS: In this cohort of 143 patients, 58% had a team-based hospice referral which was associated with a lower risk of death in the hospital. The most common reason patients declined hospice at EOL was an unwillingness to discontinue cancer-directed therapy. As compared to a similar historical cohort of patients treated with chemotherapy alone (2008-2010), there was a similar rate of hospice referral (68% vs 74%) but higher rates of new systemic therapy initiated within 30 days of death (17% vs 6%, p .001) and last dose within 14 days of death (13% vs 5%, p .005). CONCLUSIONS: Future studies should test the continuity of care at EOL as a new quality metric for advanced NSCLC.

SMARCA4 mutations in KRAS-mutant lung adenocarcinoma: a multi-cohort analysis.

KRAS is a key oncogenic driver in lung adenocarcinoma (LUAD). Chromatin-remodeling gene SMARCA4 is comutated with KRAS in LUAD; however, the impact of SMARCA4 mutations on clinical outcome has not been adequately established. This study sought to shed light on the clinical significance of SMARCA4 mutations in LUAD. The association of SMARCA4 mutations with survival outcomes was interrogated in four independent cohorts totaling 564 patients: KRAS-mutant patients with LUAD who received nonimmunotherapy treatment from (a) The Cancer Genome Atlas (TCGA) and (b) the MSK-IMPACT Clinical Sequencing (MSK-CT) cohorts; and KRAS-mutant patients with LUAD who received immune checkpoint inhibitor-based immunotherapy treatment from (c) the MSK-IMPACT (MSK-IO) and (d) the Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) immunotherapy cohorts. Of the patients receiving nonimmunotherapy treatment, in the TCGA cohort (n = 155), KRAS-mutant patients harboring SMARCA4 mutations (KS) showed poorer clinical outcome [P = 6e-04 for disease-free survival (DFS) and 0.031 for overall survival (OS), respectively], compared to KRAS-TP53 comutant (KP) and KRAS-only mutant (K) patients; in the MSK-CT cohort (n = 314), KS patients also exhibited shorter OS than KP (P = 0.03) or K (P = 0.022) patients. Of patients receiving immunotherapy, KS patients consistently exhibited the shortest progression-free survival (PFS; P = 0.0091) in the MSK-IO (n = 77), and the shortest PFS (P = 0.0026) and OS (P = 0.0014) in the WFBCCC (n = 18) cohorts, respectively. Therefore, mutations of SMARCA4 represent a genetic factor leading to adverse clinical outcome in lung adenocarcinoma treated by either nonimmunotherapy or immunotherapy.