Background In this study, we provide the largest analysis to date of a US-based cancer cohort to characterize death from COVID-19. Methods A total of 4 020 669 patients across 15 subtypes living with cancer in 2020 and included in the National Cancer Institute’s Surveillance, Epidemiology, and End Results database were abstracted. We investigated prognostic factors for death due to COVID-19 using a Cox proportional hazards model and calculated hazard ratios (HRs). Standardized mortality ratios were calculated using observed mortality counts from Surveillance, Epidemiology, and End Results and expected mortality based on US mortality rates. Results A total of 291 323 patients died, with 14 821 (5.1%) deaths attributed to COVID-19 infection. The COVID-19 disease-specific mortality rate was 11.81/10 000-persons years, and the standardized mortality ratio of COVID-19 was 2.30 (95% confidence interval [CI] = 2.26 to 2.34; P < .0001). COVID-19 ranked as the second leading cause of death following ischemic heart disease (5.2%) among 26 noncancer causes of death. Patients who are older (80 years and older vs 49 years and younger: HR = 21.47, 95% CI = 19.34 to 23.83), male (vs female: HR = 1.46, 95% CI = 1.40 to 1.51), unmarried (vs married: HR = 1.47, 95% CI = 1.42 to 1.53), and Hispanic or non-Hispanic African American (vs non-Hispanic White: HR = 2.04, 95% CI = 1.94 to 2.14 and HR = 2.03, 95% CI = 1.94 to 2.14, respectively) were at greatest risk of COVID-19 mortality. Conclusions We observed that people living with cancer are at 2 times greater risk of dying from COVID-19 compared with the general US population. This work may be used by physicians and public health officials in the creation of survivorship programs that mitigate the risk of COVID-19 mortality.

Purpose We determined whether patients with peripheral artery disease (PAD) who walked at least 7 000 steps/day had better microvascular function, assessed by calf muscle oxygen saturation (StO2), and more favorable vascular biomarkers than patients who walked less than 7,000 steps/day. Methods Five hundred sixteen patients were assessed on daily ambulatory activity for one week with a step activity monitor and were grouped according to whether they walked fewer than 7,000 steps/day (Group 1; n = 306) or for 7 000 steps/day or greater (Group 2; n = 210). Results Exercise time to reach the minimum calf muscle StO2 was longer (p = 0.025) in Group 2 ([297 ± 339] s) than in Group 1 ([210 ± 232] s). Additionally, high-sensitivity C-reactive protein (HsCRP) was lower (p < 0.001) in Group 2 ([4.0 ± 4.5] mg/L) than in Group 1 ([6.8 ± 10.7] mg/L). In multivariable linear regression models, exercise time to minimum calf muscle StO2 was associated with physical activity group status after adjusting for ankle/brachial index (Model 1) (p = 0.032), and after adjusting for age, race, sex, education, and body mass index (Model 2) (p = 0.044). HsCRP was associated with physical activity group status after adjusting for Model 1 (p < 0.001), Model 2 (p < 0.001), and the two models combined (Model 3) (p < 0.001). Conclusions Walking at least 7 000 steps/day was associated with better microvascular function in the calf muscle during exercise and with lower vascular inflammation in patients with symptomatic PAD. The clinical significance is that community-based walking for at least 7 000 steps/day is a simple goal that is associated with more favorable vascular outcomes in patients with symptomatic PAD.

The identification of prognostic and predictive biomarker signatures is crucial for drug development and providing personalized treatment to cancer patients. However, the discovery process often involves high-dimensional candidate biomarkers, leading to inflated family-wise error rates (FWERs) due to multiple hypothesis testing. This is an understudied area, particularly under the survival framework. To address this issue, we propose a novel three-stage approach for identifying significant biomarker signatures, including prognostic biomarkers (main effects) and predictive biomarkers (biomarker-by-treatment interactions), using Cox proportional hazard regression with high-dimensional covariates. To control the FWER, we adopt an adaptive group LASSO for variable screening and selection. We then derive adjusted p-values through multi-splitting and bootstrapping to overcome invalid p values caused by the penalized approach’s restrictions. Our extensive simulations provide empirical evaluation of the FWER and model selection accuracy, demonstrating that our proposed three-stage approach outperforms existing alternatives. Furthermore, we provide detailed proofs and software implementation in R to support our theoretical contributions. Finally, we apply our method to real data from cancer genetic studies.

Purpose:Critically ill patients with sepsis account for significant disease morbidity and healthcare costs. Sarcopenia has been proposed as an independent risk factor for poor short-term outcomes, although its effect on long-term outcomes remains unclear.Methods:Retrospective cohort analysis of patients treated at a tertiary care medical center over 6 years (09/2014 - 12/2020). Critically ill patients meeting Sepsis-3 criteria were included, with sarcopenia defined by skeletal muscle index at the L3 lumbar area on abdominal Computed-Tomography scan. The prevalence of sarcopenia and its association with clinical outcomes was analyzed.Results:Sarcopenia was present in 34 (23%) of 150 patients, with median skeletal muscle indices of 28.1 cm 2 /m 2 and 37.3 cm 2 /m 2 in sarcopenic females and males, respectively. In-hospital mortality was not associated with sarcopenia when adjusted for age and illness severity. One year mortality was increased in sarcopenic patients, after adjustment for illness severity (HR 1.9, p = 0.02) and age (HR 2.4, p = 0.001). However, it was not associated with increased likelihood for discharge to long-term rehabilitation or hospice care in adjusted analyses.Conclusion:Sarcopenia independently predicts one year mortality but is not associated with unfavorable hospital discharge disposition in critically ill patients with sepsis.

PurposeLocal treatment of the primary tumor for patients with metastases is controversial, and prospective data across many disease sites have conflicting conclusions regarding benefits.Methods and MaterialsA comprehensive search was conducted in PubMed/MEDLINE including randomized controlled trials (RCTs) published in the past 50 years. Inclusion criteria were multi-institutional RCTs of patients with metastatic disease receiving systemic therapy randomized to addition of local treatment to the primary tumor. Two primary outcome measures, overall survival (OS) and progression-free survival (PFS), were quantitatively assessed using random effects, and meta-analyses were conducted using the inverse variance method for pooling. Secondary endpoints were qualitatively assessed and included toxicity and patient-reported quality of life. Exploratory analyses were performed by treatment type and volume of disease.ResultsEleven studies comprising 4952 patients were included (1558 patients received radiation therapy and 913 patients received surgery as primary tumor treatment). OS and PFS were not significantly improved from treatment of the primary (OS: hazard ratio [HR], 0.91; 95% confidence interval [CI], 0.80-1.05; PFS: HR, 0.88; 95% CI, 0.72-1.07). Assessment of primary local treatment modality demonstrated a significant difference in summary effect size on PFS between trials using surgery (HR, 1.15; 95% CI, 0.99-1.33) compared with radiation therapy (HR, 0.73; 95% CI, 0.56-0.96) as the local treatment modality (P = .005). In low metastatic burden patients, radiation therapy was associated with significantly improved OS (HR, 0.67; 95% CI, 0.52-0.85), but surgery was not associated with improved OS compared with no local treatment (HR, 1.12; 95% CI, 0.94-1.34).ConclusionsIn RCTs conducted to date enrolling a variety of cancer types with variable metastatic burden, there is no consistent improvement in PFS or OS from the addition of local therapy to the primary tumor in unselected patients with metastatic disease. Carefully selected patients may derive oncologic benefit and should be discussed in tumor boards. Future prospective studies should aim to further optimize patient selection and the optimal systemic and local therapy treatment types.

BACKGROUND AND PURPOSE:The Phoenix definition for biochemical failure (BCF) after radiotherapy uses nadir PSA (nPSA) + 2 ng/mL to classify a BCF and was derived from conventionally fractionated radiotherapy, which produces significantly higher nPSAs than stereotactic body radiotherapy (SBRT). We investigated whether an alternative nPSA-based threshold could be used to define post-SBRT BCFs.MATERIALS AND METHODS:PSA kinetics data on 2038 patients from 9 institutions were retrospectively analyzed for low- and intermediate-risk PCa patients treated with SBRT without ADT. We evaluated the performance of various nPSA-based definitions. We also investigated the relationship of relative PSA decline (rPSA, PSA18month/PSA6month) and timing of reaching nPSA + 2 with BCF.RESULTS:Median follow-up was 71.9 months. BCF occurred in 6.9% of patients. Median nPSA was 0.16 ng/mL. False positivity of nPSA + 2 was 30.2%, compared to 40.9%, 57.8%, and 71.0% for nPSA + 1.5, nPSA + 1.0, and nPSA + 0.5, respectively. Among patients with BCF, the median lead time gained from an earlier nPSA + threshold definition over the Phoenix definition was minimal. Patients with BCF had significantly lower rates of early PSA decline (mean rPSA 1.19 vs. 0.39, p < 0.0001) and were significantly more likely to reach nPSA + 2 ≥ 18 months (83.3% vs. 21.1%, p < 0.0001). The proposed criterion (rPSA ≥ 2.6 or nPSA + 2 ≥ 18 months) had a sensitivity and specificity of 92.4% and 81.5%, respectively, for predicting BCF in patients meeting the Phoenix definition and decreased its false positivity to 6.4%.CONCLUSION:The Phoenix definition remains an excellent definition for BCF post-SBRT. Its high false positivity can be mitigated by applying additional criteria (rPSA ≥ 2.6 or time to nPSA + 2 ≥ 18 months).