Power and sample size calculation for non-inferiority trials with treatment switching in intention-to-treat analysis comparing RMSTs.

Background: Difference in Restricted Mean Survival Time (DRMST) has attracted attention and is increasingly used in non-inferiority (NI) trials because of its superior power in detecting treatment effects compared to hazard ratio. However, when treatment switching (also known as crossover) occurs, the widely used intention-to-treat (ITT) analysis can underpower or overpower NI trials.

Methods: We propose a simulation-based approach, named , to calculate powers and determine the necessary sample size to achieve a desired power for non-inferiority trials that allow treatment switching, in ITT analysis using DRMST.

VICTOR: Validation and inspection of cell type annotation through optimal regression.

Single-cell RNA sequencing provides unprecedent opportunities to explore the heterogeneity and dynamics inherent in cellular biology. An essential step in the data analysis involves the automatic annotation of cells. Despite development of numerous tools for automated cell annotation, assessing the reliability of predicted annotations remains challenging, particularly for rare and unknown cell types.

A distribution-free and analytic method for power and sample size calculation in single-cell differential expression.

Motivation: Differential expression analysis in single-cell transcriptomics unveils cell type-specific responses to various treatments or biological conditions. To ensure the robustness and reliability of the analysis, it is essential to have a solid experimental design with ample statistical power and sample size. However, existing methods for power and sample size calculation often assume a specific distribution for single-cell transcriptomics data, potentially deviating from the true data distribution.

Liver histology is associated with long-term clinical outcomes in patients with metabolic dysfunction-associated steatohepatitis.

Background: Few studies have examined the risk of long-term clinical outcomes in patients with metabolic dysfunction-associated steatohepatitis in relation to liver histology. We aimed to study this using a real-world cohort.

Methods: Adults (N = 702) recorded on Vanderbilt University Medical Center's Synthetic Derivative database (1984-2021) with evidence of metabolic dysfunction-associated steatohepatitis on liver biopsy were followed from the first biopsy until the first clinical event or last database entry (median: 4.

A Phase 1/2 Study to Evaluate the Safety and Activity of Nivolumab in Combination With Vorolanib, a Vascular Endothelial Growth Factor Tyrosine Kinase Inhibitor, in Patients With Refractory Thoracic Tumors.

Introduction: Targeting the tumor microenvironment may enhance response to immunotherapy (immune checkpoint inhibitors) and improve outcomes for patients. This study tested the safety and efficacy of vorolanib, a novel tyrosine kinase inhibitor of vascular endothelial growth factor, platelet-derived growth factor, and c-KIT, in combination with programmed cell death protein 1 blockade using nivolumab for refractory thoracic malignancies.

Methods: This single-arm multicenter study enrolled patients with extensive-stage SCLC, thymic carcinoma, and NSCLC, either naive or had progressed on previous chemotherapy or immune checkpoint inhibitors (either primary or acquired resistance).

scKWARN: Kernel-weighted-average robust normalization for single-cell RNA-seq data.

Motivation: Single-cell RNA-seq normalization is an essential step to correct unwanted biases caused by sequencing depth, capture efficiency, dropout, and other technical factors. Existing normalization methods primarily reduce biases arising from sequencing depth by modeling count-depth relationship and/or assuming a specific distribution for read counts. However, these methods may lead to over or under-correction due to presence of technical biases beyond sequencing depth and the restrictive assumption on models and distributions.

NCI10066: a Phase 1/2 study of olaparib in combination with ramucirumab in previously treated metastatic gastric and gastroesophageal junction adenocarcinoma.

Background: Our preclinical work revealed tumour hypoxia induces homologous recombination deficiency (HRD), increasing sensitivity to Poly (ADP-ribose) polymerase inhibitors. We aimed to induce tumour hypoxia with ramucirumab thereby sensitising tumours to olaparib.

Patients And Methods: This multi-institution single-arm Phase 1/2 trial enrolled patients with metastatic gastroesophageal adenocarcinoma refractory to ≥1 systemic treatment.

Atezolizumab in Combination With Carboplatin and Survival Outcomes in Patients With Metastatic Triple-Negative Breast Cancer: The TBCRC 043 Phase 2 Randomized Clinical Trial.

Importance: Agents targeting programmed death ligand 1 (PD-L1) have demonstrated efficacy in triple-negative breast cancer (TNBC) when combined with chemotherapy and are now the standard of care in patients with PD-L1-positive metastatic disease. In contrast to microtubule-targeting agents, the effect of combining platinum compounds with programmed cell death 1 (PD-1)/PD-L1 immunotherapy has not been extensively determined.

Objective: To evaluate the efficacy of atezolizumab with carboplatin in patients with metastatic TNBC.

Disparities in outcomes between Black and White patients in North America with thoracic malignancies and COVID-19 infection (TERAVOLT).

Background: Patients with thoracic malignancies who develop COVID-19 infection have a higher hospitalization rate compared to the general population and to those with other cancer types, but how this outcome differs by race and ethnicity is relatively understudied.

Methods: The TERAVOLT database is an international, multi-center repository of cross-sectional and longitudinal data studying the impact of COVID-19 on individuals with thoracic malignancies. Patients from North America with thoracic malignancies and confirmed COVID-19 infection were included for this analysis of racial and ethnic disparities.

Longitudinal nucleocapsid antibody testing reveals undocumented SARS-CoV-2 infections in patients with lung cancer.

Patients diagnosed with lung cancer (LC) exhibit increased susceptibility to SARS-CoV-2 infection. Rodilla et al. monitor the levels of plasma anti-nucleocapsid antibodies within a cohort of fully vaccinated LC patients and reveal that the actual infection rate is nearly twice the documented rate, indicating a significant prevalence of unreported cases.

Systemic Anticancer Therapy and Thromboembolic Outcomes in Hospitalized Patients With Cancer and COVID-19.

Importance: Systematic data on the association between anticancer therapies and thromboembolic events (TEEs) in patients with COVID-19 are lacking.

Objective: To assess the association between anticancer therapy exposure within 3 months prior to COVID-19 and TEEs following COVID-19 diagnosis in patients with cancer.

Design, Setting, And Participants: This registry-based retrospective cohort study included patients who were hospitalized and had active cancer and laboratory-confirmed SARS-CoV-2 infection.

Power and sample sizes estimation in clinical trials with treatment switching in intention-to-treat analysis: a simulation study.

Background: Treatment switching, also called crossover, is common in clinical trials because of ethical concerns or other reasons. When it occurs and the primary objective is to identify treatment effects, the most widely used intention-to-treat analysis may lead to underpowered trials. Here, we presented an approach to preview power reductions and to estimate sample sizes required to achieve the desired power when treatment switching occurs in the intention-to-treat analysis.

Associations of influenza vaccination with severity of immune-related adverse events in patients with advanced thoracic cancers on immune checkpoint inhibitors.

Background: Whether influenza vaccination (FV) is associated with the severity of immune-related adverse events (IRAEs) in patients with advanced thoracic cancer on immune checkpoint inhibitors (ICIs) is not fully understood.

Methods: Patients enrolled in this retrospective cohort study were identified from the Vanderbilt BioVU database and their medical records were reviewed. Patients with advanced thoracic cancer who received FV within 3 months prior to or during their ICI treatment period were enrolled in the FV-positive cohort and those who did not were enrolled in the FV-negative cohort.

Scalable and model-free detection of spatial patterns and colocalization.

The expeditious growth in spatial omics technologies enables the profiling of genome-wide molecular events at molecular and single-cell resolution, highlighting a need for fast and reliable methods to characterize spatial patterns. We developed SpaGene, a model-free method to discover spatial patterns rapidly in large-scale spatial omics studies. Analyzing simulation and a variety of spatially resolved transcriptomics data showed that SpaGene is more powerful and scalable than existing methods.

Cox Proportional Hazard Ratios Overestimate Survival Benefit of Immune Checkpoint Inhibitors: Cox-TEL Adjustment and Meta-Analyses of Programmed Death-Ligand 1 Expression and Immune Checkpoint Inhibitor Survival Benefit.

Introduction: Survival benefit of immune checkpoint inhibitor (ICI) therapy in lung cancer is not fully understood.

Methods: PubMed-cataloged publications through February 14, 2022, were queried for randomized controlled trials of ICI in lung cancer, and identified publications were reviewed for inclusion. Reported Cox hazard ratios (HRs) for overall survival were transformed to Cox-TEL HR for ICI short-term survivors (ST-HR) and difference in proportions for patients with long-term survival (LT-DP).

Analysis of Cancer Survival Associated With Immune Checkpoint Inhibitors After Statistical Adjustment: A Systematic Review and Meta-analyses.

Importance: Appropriate clinical decision-making relies on accurate data interpretation, which in turn relies on the use of suitable statistical models. Long tails and early crossover-2 features commonly observed in immune checkpoint inhibitor (ICI) survival curves-raise questions as to the suitability of Cox proportional hazards regression for ICI survival analysis. Cox proportional hazards-Taylor expansion adjustment for long-term survival data (Cox-TEL) adjustment may provide possible solutions in this setting.

A case report of right cardiac ventricle perforation by uncontrolled embolization coil inserted for treating penile veno-occlusive dysfunction.

Coil embolization (CE) is believed effective-safe for treating penile veno-occlusive dysfunction (VOD). From 2012 to 2016, refractory impotence prompted four men to seek further treatment, although they underwent six CEs elsewhere. Uncontrolled coils scattered along penile drainage veins including the deep dorsal veins (n = 3), periprostatic plexus (n = 1), iliac vein (n = 1), right pulmonary artery (n = 2), left pulmonary artery (n = 1), and right ventricle (n = 1).

Dysregulated ligand-receptor interactions from single-cell transcriptomics.

Motivation: Intracellular communication is crucial to many biological processes, such as differentiation, development, homeostasis and inflammation. Single-cell transcriptomics provides an unprecedented opportunity for studying cell-cell communications mediated by ligand-receptor interactions. Although computational methods have been developed to infer cell type-specific ligand-receptor interactions from one single-cell transcriptomics profile, there is lack of approaches considering ligand and receptor simultaneously to identifying dysregulated interactions across conditions from multiple single-cell profiles.