Predictors of attendance during an exercise program for cancer survivors.

PURPOSE: Exercise programs delivered in community- or clinic-based settings improve physical and psychosocial outcomes among cancer survivors; however, adherence is essential to achieve such benefits. This study examined predictors of attendance to an exercise program in a large, diverse sample of cancer survivors. METHODS: Participants (n = 302) were enrolled in BfitBwell, an exercise program for adults diagnosed with cancer, and currently receiving or within 6 months of completing chemotherapy or radiation therapy. Participants were offered two supervised aerobic and resistance exercise sessions per week for 3 months. Predictors of attendance included demographics, cancer-related information, quality of life (QOL), fatigue, physical fitness, activity level, and importance of making various changes (e.g., improving fitness). Univariate linear regression first explored associations between predictor variables and adherence, and any important variables (p < .10) were included in a multivariate linear regression model. RESULTS: Participants were M = 54.9 ± 13.9 years old, mostly female (67.3%), white (83.6%), and most commonly diagnosed with breast cancer (34.8%). Average attendance was 16.2 ± 6.6 exercise sessions. Six-minute walk test distance, QOL, and fatigue were associated with exercise session attendance (p < .05). The multivariable model revealed that higher QOL predicted higher attendance (ß = .351, p = .005), and working full- or part-time significantly predicted lower attendance (ß =- .221, p =.021). CONCLUSIONS: Higher pre-program QOL and not working full- or part-time predicted higher exercise program attendance. Existing and future exercise programs for cancer survivors should consider ways to adapt program delivery to provide support to survivors who start with low QOL, and accommodate those who may face barriers to attending due to work schedule/conflict.

Resistance Mechanisms to Targeted Therapies in ROS1+ and ALK+ Non-small Cell Lung Cancer.

Purpose: Despite initial benefit from tyrosine kinase inhibitors (TKIs), patients with advanced non-small cell lung cancer (NSCLC) harboring ALK (ALK+) and ROS1 (ROS1+) gene fusions ultimately progress. Here, we report on the potential resistance mechanisms in a series of patients with ALK+ and ROS1+ NSCLC progressing on different types and/or lines of ROS1/ALK-targeted therapy.Experimental Design: We used a combination of next-generation sequencing (NGS), multiplex mutation assay, direct DNA sequencing, RT-PCR, and FISH to identify fusion variants/partners and copy-number gain (CNG), kinase domain mutations (KDM), and copy-number variations (CNVs) in other cancer-related genes. We performed testing on 12 ROS1+ and 43 ALK+ patients.Results: One of 12 ROS1+ (8%) and 15 of 43 (35%) ALK + patients harbored KDM. In the ROS1+ cohort, we identified KIT and ß-catenin mutations and HER2-mediated bypass signaling as non-ROS1-dominant resistance mechanisms. In the ALK+ cohort, we identified a novel NRG1 gene fusion, a RET fusion, 2 EGFR, and 3 KRAS mutations, as well as mutations in IDH1, RIT1, NOTCH, and NF1 In addition, we identified CNV in multiple proto-oncogenes genes including PDGFRA, KIT, KDR, GNAS, K/HRAS, RET, NTRK1, MAP2K1, and others.Conclusions: We identified a putative TKI resistance mechanism in six of 12 (50%) ROS1 + patients and 37 of 43 (86%) ALK+ patients. Our data suggest that a focus on KDMs will miss most resistance mechanisms; broader gene testing strategies and functional validation is warranted to devise new therapeutic strategies for drug resistance. Clin Cancer Res; 24(14); 3334-47. ©2018 AACR.