Online-delivered resistance exercise intervention among racially diverse breast cancer survivors: Feasibility, acceptability, and exploratory outcomes of B-REP.

PURPOSE: The aims are to determine the feasibility of an online-delivered resistance exercise program among racially diverse breast cancer survivors and to conduct an exploratory analysis of the intervention on muscular strength, physical activity levels, health-related quality of life, and self-efficacy. METHODS: A 2-arm randomized controlled trial study design with assessments at pre- and post-intervention was used. Participants (n = 52) were recruited from clinics at the host institution and randomized to either intervention (n = 28) or minimal contact control (MCC) conditions (n = 24). All participants received a 12-week individualized resistance exercise prescription based on their baseline functional strength assessment. Intervention participants exercised one-on-one once per week over Zoom with an exercise trainer. MCC participants received no supervision. Descriptive statistics were used to determine feasibility and acceptability (primary outcomes). Repeated measures ANOVAs were used to examine exploratory outcomes. RESULTS: The intervention demonstrated high rates for feasibility outcomes of enrollment (80.0%) and post-intervention assessment completion (92.9%). Acceptability outcomes were high for session attendance (98.0%) and satisfaction (Mscore = 4.87 out of 5, SD = .18). The intervention group increased upper- (p < .01) and lower- (p < .02) body strength compared to MCC condition. CONCLUSIONS: The intervention was feasible, acceptable, and demonstrated increases in muscular strength. Limitations include a small sample recruited from one cancer center. Future research is needed to determine longitudinal impacts of resistance exercise on survivorship outcomes. Online-delivered resistance exercise shows promising efficacy among racially diverse breast cancer survivors. CLINICALTRIALS: gov registration: NCT04562233 on September 18, 2020.

Nasal resistance and inflammation: mechanisms for obstructive sleep apnea from chronic rhinosinusitis.

STUDY OBJECTIVES: We have previously estimated that the prevalence of obstructive sleep apnea (OSA) among World Trade Center (WTC) rescue and recovery workers is 75% and identified that having symptoms of chronic rhinosinusitis (CRS) is an independent risk factor for OSA in this population. Nasal inflammation and/or elevated awake nasal resistance that carried over into sleep could explain this association. To understand the mechanism(s) for the elevated risk of OSA observed in WTC responders with chronic rhinosinusitis (CRS) symptoms we examined if elevated awake supine nasal resistance was associated with OSA, CRS and/or nasal inflammatory biomarkers. METHODS: 601 individuals (83% male, average age 53 years, BMI=29.9 ± 5.5 kg/m2) enrolled in the WTC Health Program and without significant pre-9/11 snoring, underwent two nights of home sleep apnea testing, measurements of anterior rhinomanometry in the supine position, and nasal lavage. RESULTS: Awake supine nasal resistance was not associated with OSA; 74.8% and 74.4% of the participants with low and high nasal resistance respectively, had OSA (P=NS). Patients with CRS had elevated nasal inflammatory markers (IL6, IL8, ECP and Neut) but did not have high nasal resistance. Nasal inflammatory markers were not correlated with nasal resistance. CONCLUSIONS: As awake nasal resistance did not explain the relationship of CRS to OSA in this large and well characterized dataset, our findings suggest that either "sleep" nasal resistance or other factors such as increased supraglottic inflammation, perhaps through impairing upper airway reflex mechanisms, or systemic inflammation are involved in the pathophysiology of OSA in the WTC population.

Lack of association of impaired upper airway sensation with the presence or absence of obstructive sleep apnoea or chronic rhinosinusitis in World Trade Center responders.

OBJECTIVE: Examine sensory function of the upper airway in four groups of subjects recruited from the World Trade Centre General Responder Cohort (WTCGRC), with/without obstructive sleep apnoea (OSA), and with/without chronic rhinosinusitis (CRS). METHODS: Upper airway sensory function was determined using 2-point discrimination (2-PD) and vibration threshold (VT) in 163 WTCGRC subjects with both OSA and CRS (cases), OSA or CRS alone and without OSA or CRS (controls). Presence of OSA was determined from clinical sleep studies or home sleep testing. Presence of CRS was determined by nasal symptom questionnaire. The relationship between the presence of OSA and CRS and upper airway sensory impairment was assessed using linear regression analysis with each of 2PD and VT sensory threshold values as the dependent variable; OSA, CRS and their interaction were the independent variables. Age, gender and body mass index were covariates in the statistical model. The primary analysis was comparison of OSA+CRS versus controls (no OSA and no CRS) evaluated by linear contrasts. RESULTS: There were no differences in 2-PD or VT in those with OSA+CRS, OSA and CRS alone or controls. However, both 2-PD and VT were significantly higher in the WTCGRC controls compared with values seen in historical controls using the same methodology (median 2-PD 13.0; CI (11.0 to 13.5) vs 10.5; CI (8 to 11); VT: mean±SEM (9.3±0.6 vs 2.2±0.1)). CONCLUSION: While no differences were found in upper airway sensation between cases of OSA and CRS versus controls in the WTGRC population, there was evidence of impaired upper airway sensation in the WTGRC overall.

Two-stage stratified designs with survival outcomes and adjustment for misclassification in predictive biomarkers.

Biomarker stratified clinical trial designs are versatile tools to assess biomarker clinical utility and address its relationship with clinical endpoints. Due to imperfect assays and/or classification rules, biomarker status is prone to errors. To account for biomarker misclassification, we consider a two-stage stratified design for survival outcomes with an adjustment for misclassification in predictive biomarkers. Compared to continuous and/or binary outcomes, the test statistics for survival outcomes with an adjustment for biomarker misclassification is much more complicated and needs to take special care. We propose to use the information from the observed biomarker status strata to construct adjusted log-rank statistics for true biomarker status strata. These adjusted log-rank statistics are then used to develop sequential tests for the global (composite) hypothesis and component-wise hypothesis. We discuss the power analysis with the control of the type-I error rate by using the correlations between the adjusted log-rank statistics within and between the design stages. Our method is illustrated with examples of the recent successful development of immunotherapy in nonsmall-cell lung cancer.

Randomized trial promoting cancer genetic risk assessment when genetic counseling cost removed: 1-year follow-up.

PURPOSE: Cancer genetic risk assessment (CGRA) is recommended for women with ovarian and high-risk breast cancer. However, the underutilization of CGRA has long been documented, and cost has been a major barrier. In this randomized controlled trial, a tailored counseling and navigation (TCN) intervention significantly improved CGRA uptake at 6-month follow-up, compared with targeted print (TP) and usual care (UC). We aimed to examine the effect of removing genetic counseling costs on CGRA uptake by 12 months. METHODS: We recruited racially and geographically diverse women with breast and ovarian cancer from cancer registries in Colorado, New Jersey, and New Mexico. Participants assigned to TCN received telephone-based psychoeducation and navigation. After 6 months, the trial provided free genetic counseling to participants in all arms. RESULTS: At 12 months, more women in TCN obtained CGRA (26.6%) than those in TP (11.0%; odds ratio [OR] = 2.77, 95% confidence interval [CI] = 1.56 to 4.89) and UC (12.2%; OR = 2.46, 95% CI = 1.41 to 4.29). There were no significant differences in CGRA uptake between TP and UC. The Kaplan-Meier curve shows that the divergence of cumulative incidence slopes (TCN vs UC, TCN vs TP) appears primarily within the initial 6 months. CONCLUSION: TCN significantly increased CGRA uptake at the 12-month follow-up. Directly removing the costs of genetic counseling attenuated the effects of TCN, highlighting the critical enabling role played by cost coverage. Future policies and interventions should address multilevel cost-related barriers to expand patients' access to CGRA. TRIAL REGISTRATION: This trial was registered with the NIH clinical trial registry, clinicaltrials.gov, NCT03326713. https://clinicaltrials.gov/ct2/show/NCT03326713.

Adaptive Lung Radiation Therapy in the Era of Immunotherapy: A Single-Center Retrospective Study.

Purpose: Treatment for locally advanced non-small cell lung cancer consists of concurrent chemoradiation followed by immunotherapy. Though this combination has been shown to have a benefit in both progression-free survival and overall survival, treatment is often limited by the development of pneumonitis. One way to mitigate toxicity is through adaptive radiation therapy, which does not currently have a standardized implementation in clinical practice. Methods and Materials: A single-center retrospective review of patients with locally advanced stage III or oligometastatic stage IV non-small cell lung cancer who were treated with chemoradiation with concurrent or subsequent immunotherapy from 2015 to 2020 was performed. Patients were stratified based on having 1 or more offline adapted plan. The aim of this study was to evaluate the association between dose-volume histogram values and common toxicities experienced during this treatment, including pneumonitis and esophagitis. Results: Twenty-five patients were included in the final analysis: 10 with adapted plans (AP), and 15 with nonadapted plans (NAP). Mean age at onset was 74 years. The most common histology was adenocarcinoma (N = 13). Five patients experienced pneumonitis: 2 in AP and 3 in NAP. Mann-Whitney U test of gross tumor volume sizes between AP (346.2 ± 269.7 cm3) and NAP (153.1 ± 99.6 cm3) was significant (P = .019). Multiple linear regression analysis with adjustment for covariates of pneumonitis versus plan adaptation (P = .106) and esophagitis versus plan adaptation (P = .59) did not demonstrate a significant difference in toxicity between the adapted and nonadaptive patients. Conclusions: Despite similar toxicities in both groups, the gross tumor volume size in the AP was more than double compared with NAP, suggesting that adaptive techniques provide a method for patients with larger target volumes to be treated without an observed difference in pneumonitis rates. These results suggest adaptive radiation therapy may have a role in mitigating toxicity experience from chemoradiation and immunotherapy and warrants further investigation.

Fixed and random effect selections in generalized linear mixed models.

Generalized linear mixed models are commonly used to describe relationships between correlated responses and covariates in medical research. In this paper, we propose a simple and easily implementable regularized estimation approach to select both fixed and random effects in generalized linear mixed model. Specifically, we propose to construct and optimize the objective functions using the confidence distributions of model parameters, as opposed to using the observed data likelihood functions, to perform effect selections. Two estimation methods are developed. The first one is to use the joint confidence distribution of model parameters to perform simultaneous fixed and random effect selections. The second method is to use the marginal confidence distributions of model parameters to perform the selections of fixed and random effects separately. With a proper choice of regularization parameters in the adaptive LASSO framework, we show the consistency and oracle properties of the proposed regularized estimators. Simulation studies have been conducted to assess the performance of the proposed estimators and demonstrate computational efficiency. Our method has also been applied to two longitudinal cancer studies to identify demographic and clinical factors associated with patient health outcomes after cancer therapies.