Scaling and interpreting treatment effects in clinical trials using restricted mean survival time.

Background: Restricted mean survival time is the expected duration of survival up to a chosen time of restriction . For comparison studies, the difference in restricted mean survival times between two groups provides a summary measure of the treatment effect that is free of assumptions regarding the relative shape of the two survival curves, such as proportional hazards. However, it can be difficult to judge the magnitude of the effect from a comparison of restricted means due to the truncation of observation at time .

Refining Risk Stratification of High-risk and Locoregional Prostate Cancer: A Pooled Analysis of Randomized Trials.

Background And Objective: Radiotherapy (RT) and long-term androgen deprivation therapy (ltADT; 18-36 mo) is a standard of care in the treatment of high-risk localized/locoregional prostate cancer (HRLPC). We evaluated the outcomes in patients treated with RT + ltADT to identify which patients have poorer prognosis with standard therapy.

Methods: Individual patient data from patients with HRLPC (as defined by any of the following three risk factors [RFs] in the context of cN0 disease-Gleason score ≥8, cT3-4, and prostate-specific antigen [PSA] >20 ng/ml, or cN1 disease) treated with RT and ltADT in randomized controlled trials collated by the Intermediate Clinical Endpoints in Cancer of the Prostate group.

Long-Term Analysis of NRG Oncology RTOG 0415: A Randomized Phase III Noninferiority Study Comparing Two Fractionation Schedules in Patients With Low-Risk Prostate Cancer.

JCO NRG Oncology RTOG 0415 is a randomized phase III noninferiority (NI) clinical trial comparing conventional fractionation (73.8 Gy in 41 fractions) radiotherapy (C-RT) with hypofractionation (H-RT; 70 Gy in 28) in patients with low-risk prostate cancer. The study included 1,092 protocol-eligible patients initially reported in 2016 with a median follow-up of 5.

Cardiovascular Mortality and Duration of Androgen Deprivation in Locally Advanced Prostate Cancer: Long-term Update of NRG/RTOG 9202.

Background: Androgen deprivation therapy (ADT) has been associated with coronary heart disease and myocardial infarction (MI) in prostate cancer patients, but controversy persists regarding its effects on cardiovascular mortality (CVM).

Objective: We assessed the long-term relationship between ADT and CVM in a prostate cancer randomized trial (NRG Oncology/Radiation Therapy Oncology Group 9202).

Design, Setting, And Participants: From 1992 to 1995, 1554 men with locally advanced prostate cancer (T2c-T4, prostate-specific antigen <150 ng/ml) received radiotherapy with 4 mo (short-term [STADT]) versus 28 mo (longer-term [LTADT]) of ADT.

Risk Factors for Hospital Readmission in Patients With Interstitial Lung Disease.

Background: Little is known about the rates, causes, or risk factors for hospital readmission among patients with interstitial lung disease (ILD). We investigated the prevalence, features, and comorbidities of subjects hospitalized with ILD and their subsequent re-hospitalizations in this retrospective study.

Methods: A retrospective analysis of subjects enrolled in the University of Chicago ILD Natural History registry was conducted.

Predictors of Pneumonitis in Combined Thoracic Stereotactic Body Radiation Therapy and Immunotherapy.

Purpose: Thoracic stereotactic body radiation therapy (SBRT) is associated with high rates of local control but carries a risk of pneumonitis. Immunotherapy is a standard treatment for patients with metastatic disease but can also cause pneumonitis. To evaluate the feasibility and safety of thoracic SBRT with systemic immunotherapy, clinical outcomes of patients treated with immune checkpoint blockade (ICB) and SBRT on prospective trials were reviewed.

Hematuria following Post-Prostatectomy Radiotherapy: Incidence Increases with Long-Term Followup.

Purpose: Hematuria following post-prostatectomy radiotherapy (PPRT) is inadequately characterized. We performed a consecutive cohort study of patients treated with PPRT at our institution to characterize this complication including impact on patient-reported quality of life.

Materials And Methods: Patients with potential followup ≥4 years following PPRT were identified.

Statistical Considerations in the Evaluation of Continuous Biomarkers.

Discovery of biomarkers has been steadily increasing over the past decade. Although a plethora of biomarkers has been reported in the biomedical literature, few have been sufficiently validated for broader clinical applications. One particular challenge that may have hindered the adoption of biomarkers into practice is the lack of reproducible biomarker cut points.

Validation of a 22-Gene Genomic Classifier in Patients With Recurrent Prostate Cancer: An Ancillary Study of the NRG/RTOG 9601 Randomized Clinical Trial.

Importance: Decipher (Decipher Biosciences Inc) is a genomic classifier (GC) developed to estimate the risk of distant metastasis (DM) after radical prostatectomy (RP) in patients with prostate cancer.

Objective: To validate the GC in the context of a randomized phase 3 trial.

Design, Setting, And Participants: This ancillary study used RP specimens from the phase 3 placebo-controlled NRG/RTOG 9601 randomized clinical trial conducted from March 1998 to March 2003.

Biomarker-Driven Oncology Clinical Trials: Key Design Elements, Types, Features, and Practical Considerations.

In this precision oncology era, where molecular profiling at the individual patient level becomes increasingly accessible and affordable, more and more clinical trials are now driven by biomarkers, with an overarching objective to optimize and personalize disease management. As compared with the conventional clinical development paradigms, where the key is to evaluate treatment effects in histology-defined populations, the choices of biomarker-driven clinical trial designs and analysis plans require additional considerations that are heavily dependent on the nature of biomarkers (eg, prognostic or predictive, integral or integrated) and the credential of biomarkers' performance and clinical utility. Most recently, another major paradigm change in biomarker-driven trials is to conduct multi-agent and/or multihistology master protocols or platform trials.

Do reminder emails and past due notifications improve patient completion and institutional data submission for patient-reported outcome measures?

Purpose: NRG Oncology, part of the National Cancer Institute's National Clinical Trials Network, took efforts to increase patient-reported outcome measures (PROMs) completion and institutional data submission rates within clinical trials. Lack of completion diminishes power to draw conclusions and can be a waste of resources. It is hypothesized that trials with automatic email reminders and past due notifications will have PROM forms submitted more timely with higher patient completion.

Characteristics of Participation in Patient-Reported Outcomes and Electronic Data Capture Components of NRG Oncology Clinical Trials.

Purpose: To assess the reasons why patients do not consent to patient-reported outcome (PRO) and electronic PRO data capture components of clinical trials and potential selection bias by having a separate consent.

Methods And Materials: Selected NRG Oncology trials were included based on disease site and inclusion of PROs and electronic PRO data capture via VisionTree Optimal Care as separate consent questions. Reasons for not participating were assessed.

Event-Free Survival, a Prostate-Specific Antigen-Based Composite End Point, Is Not a Surrogate for Overall Survival in Men With Localized Prostate Cancer Treated With Radiation.

Purpose: Recently, we have shown that metastasis-free survival is a strong surrogate for overall survival (OS) in men with intermediate- and high-risk localized prostate cancer and can accelerate the evaluation of new (neo)adjuvant therapies. Event-free survival (EFS), an earlier prostate-specific antigen (PSA)-based composite end point, may further expedite trial completion.

Methods: EFS was defined as the time from random assignment to the date of first evidence of disease recurrence, including biochemical failure, local or regional recurrence, distant metastasis, or death from any cause, or was censored at the date of last PSA assessment.

Association of Presalvage Radiotherapy PSA Levels After Prostatectomy With Outcomes of Long-term Antiandrogen Therapy in Men With Prostate Cancer.

Importance: In men with recurrent prostate cancer, addition of long-term antiandrogen therapy to salvage radiotherapy (SRT) was associated with overall survival (OS) in the NRG/RTOG 9601 study. However, hormone therapy has associated morbidity, and there are no validated predictive biomarkers to identify which patients derive most benefit from treatment.

Objective: To examine the role of pre-SRT prostate-specific antigen (PSA) levels to personalize hormone therapy use with SRT.

A Systematic Review and Recommendation for Reporting of Surrogate Endpoint Evaluation Using Meta-analyses.

Background: Meta-analysis of randomized controlled trials (RCTs) has been widely conducted for the evaluation of surrogate endpoints in oncology, but little attention has been given to the adequacy of reporting and interpretation. This review evaluated the reporting quality of published meta-analyses on surrogacy evaluation and developed recommendations for future reporting.

Methods: We searched PubMed through August 2017 to identify studies that evaluated surrogate endpoints using the meta-analyses of RCTs in oncology.

Association of Black Race With Prostate Cancer-Specific and Other-Cause Mortality.

Importance: Black men are more likely to die of prostate cancer than white men. In men with similar stages of disease, the contribution of biological vs nonbiological differences to this observed disparity is unclear.

Objective: To quantify the association of black race with long-term survival outcomes after controlling for known prognostic variables and access to care among men with prostate cancer.

Quality of Life in Patients With Low-Risk Prostate Cancer Treated With Hypofractionated vs Conventional Radiotherapy: A Phase 3 Randomized Clinical Trial.

Importance: Hypofractionated radiotherapy (HRT) would be more convenient for men with low-risk prostate cancer and cost less than conventional radiotherapy (CRT) as long as HRT is noninferior to CRT in terms of survival and quality of life (QOL) is not found to be worse.

Objective: To assess differences in QOL between men with low-risk prostate cancer who are treated with HRT vs CRT.

Design, Setting, And Participants: In this phase 3 randomized clinical trial, men with low-risk prostate cancer were enrolled from sites within the National Cancer Institute's National Clinical Trials Network in the United States, Canada, and Switzerland.