Patient, Physician, and Assessor Blinding in Phase III Randomized Trials in Oncology: A Meta-Epidemiological Analysis.

Background: Blinding mitigates bias in randomized trials and may be especially crucial for surrogate endpoints, such as progression-free survival (PFS). Here, we characterize utilization of and factors associated with blinding in Phase III oncology trials with PFS primary endpoints.

Methods: Two-arm, superiority-design trials investigating systemic therapy were identified in May 2024 from ClinicalTrials.

Iterative intraoperative 3T MRI (iMRI)-guided brachytherapy: A prospective study on enhancing implantation precision and dosimetric gains in advanced gynecologic cancers.

Purpose: To report on primary outcomes and dosimetric results of a prospective clinical trial and protocol for use of iterative intraoperative magnetic resonance imaging (iMRI) in gynecologic brachytherapy.

Methods: Patients with locally advanced cervical or vaginal cancer (FIGO stages IB2 - IVA, and stage II-IVA, respectively) undergoing pulsed dose rate (PDR) brachytherapy were enrolled in a prospective clinical trial (NCT03634267) using iterative 3T iMRI during brachytherapy implant placement. Applicator and optional interstitial needles were placed under iMRI guidance in a 3T clinical MRI scanner.

Bayesian interim analysis and efficiency of phase III randomized trials.

Background: Improving efficiency of phase III trials is paramount for reducing costs, hastening approvals, and mitigating exposure to disadvantageous randomizations. Compared to standard frequentist interim analysis, Bayesian early stopping rules may improve efficiency by the flexibility of differential priors for efficacy and futility coupled with evaluation of clinically meaningful effect sizes.

Methods: Individual patient-level data from 184,752 participants across 230 randomized two-arm parallel oncology phase III trials were manually reconstructed from primary endpoint Kaplan-Meier curves.

The state of the art in artificial intelligence and digital pathology in prostate cancer.

Prostate cancer is among the most common cancers worldwide, with ~1.5 million new diagnoses globally every year. The sheer mass of data becoming available on prostate cancer, as well as other types of cancer, is increasing exponentially.

Survival-inferred fragility of statistical significance in phase III oncology trials.

In phase III oncology trials, superiority is defined by statistical significance using P thresholds. However, this approach has been criticized because P is continuous. Here, we reconstruct patient-level data for 230 phase III oncology trials to model the robustness of statistical significance by estimating the survival-inferred fragility index (SIFI), defined as the smallest number of patients changing arms that alters the statistical significance interpretation.

Reproducibility of statistically significant phase III oncology trials: An In Silico meta-epidemiological analysis.

Purpose: The conventional assumption that P values ≤ 0.05 imply reproducible effects has come under recent criticism. This concern is particularly relevant in oncology, as phase III oncology trials, which directly inform practice, are usually not repeated.

Debate 1: High-Risk Localized Prostate Cancer: Why Combination Hormone Therapy and Radiotherapy is the Optimal Treatment Strategy for Most Men.

Prostate cancer is the most commonly diagnosed malignancy among men in the United States, with high-risk localized disease accounting for approximately 15% of new cases. High-risk cancer portends increased risk of locoregional recurrence and distant metastases. Despite the longstanding use of radical prostatectomy (RP) and definitive radiotherapy (RT) with androgen deprivation therapy (ADT) as primary treatment options, there remains a lack of randomized data directly comparing these modalities.

Use of natural language processing to identify patients with inflammatory breast cancer across a health-care system.

Early identification and referral of inflammatory breast cancer remains challenging within large health-care systems, limiting access to specialized care. We developed and evaluated an artificial intelligence-driven platform integrating natural language processing (NLP) with electronic health records to systematically identify potential inflammatory breast cancer patients across 5 campuses. Our platform analyzed 8 623 494 clinical notes, implementing a sequential review process: NLP screening followed by human validation and multidisciplinary confirmation.

Overall Survival and Quality-of-Life Superiority in Modern Phase 3 Oncology Trials: A Meta-Epidemiological Analysis.

Importance: Alternative end points, such as progression-free survival, are increasingly used in phase 3 randomized clinical trials (RCTs). However, alternative end points are often not valid surrogates for overall survival and quality of life (QOL) and may be less relevant to patients.

Objective: To determine the proportion of phase 3 RCTs with overall survival or QOL superiority.

Salvage Radiotherapy Following Nonradiotherapy Ablative Techniques for Primary Prostate Cancer: A Systematic Review and Meta-analysis.

Background And Objective: The treatment landscape for localized prostate cancer has evolved with the increasing use of nonradiotherapy ablative interventions (NRAIs) such as high-intensity focused ultrasound (HIFU) and cryotherapy. These minimally invasive therapies promise fewer side effects and quicker recovery but come with a higher risk of recurrence, often necessitating salvage treatments. Salvage radiotherapy (SRT) is a potential option, but its efficacy and safety following NRAIs remain uncertain.

Effect size estimation in cooperative group- and industry-sponsored phase 3 oncology trials.

Overly optimistic estimations of effect sizes may lead to underpowered studies and risk of erroneously dismissing effective treatments. To understand the prevalence and factors contributing to estimation of effect sizes, we evaluated 385 superiority-design phase 3 oncology randomized controlled trials with prespecified and observed hazard ratios in published manuscripts. Of these, 88% were sponsored by industry and 22.

Treatment group-specific inferences in Phase III Randomized Oncology Trials.

Background: Estimation of comparative treatment effects between randomized groups is well-supported in randomized trials. By contrast, treatment group-specific inferences are challenging, as patients are selectively chosen for enrollment, and such inferences are formally discouraged by the CONSORT guidelines. The present study is the first-large scale assessment of the proportion of phase III oncology trials that present treatment group-specific inferences.

Safety and early outcomes of proton therapy and low-dose rate brachytherapy boost for patients with prostate cancer.

Purpose: Brachytherapy boost improves biochemical control for patients with prostate cancer. Here, we report the safety and early efficacy of proton therapy (PT) with a low-dose-rate (LDR) brachytherapy boost.

Methods: This retrospective study included patients with intermediate- or high-risk prostate cancer treated with PT followed by LDR boost, with or without androgen deprivation therapy (ADT), from 2010 through 2023.

Postprogression therapy and confounding for the estimated treatment effect on overall survival in phase III oncology trials.

Objective: Estimations of the treatment effect on overall survival (OS) may be influenced by post-progression therapies (PPTs). It is unclear how often OS analyses account for PPT effects. The purpose of this cross-sectional analysis was to determine the prevalence of OS analyses accounting for PPT effects in phase III oncology trials.

Survival-Inferred Fragility of Statistical Significance in Phase III Oncology Trials.

Background: Statistical significance currently defines superiority in phase III oncology trials. However, this practice is increasingly questioned. Here, we estimated the fragility of phase III oncology trials.

Incomplete Toxicity Reporting and Use of Toxicity-Minimizing Language in Phase III Oncology Trials.

Purpose: This study aimed to determine complete toxicity reporting (CTR), and the use of subjective toxicity-minimizing language (TML) among phase III oncology trials.

Methods: Two-arm superiority-design phase III oncology trials published from 2002 to 2020 were reviewed for toxicity data. CTR was defined as reporting total adverse events (TAEs), total serious adverse events (SAEs), total deaths, and study therapy discontinuations because of toxicity.

Justification, margin values, and analysis populations for oncologic noninferiority and equivalence trials: a meta-epidemiological study.

Background: Noninferiority and equivalence trials evaluate whether an experimental therapy's effect on the primary endpoint is contained within an acceptable margin compared with standard of care. The reliability and impact of this conclusion, however, is largely dependent on the justification for this design, the choice of margin, and the analysis population used.

Methods: A meta-epidemiological study was performed of phase 3 randomized noninferiority and equivalence oncologic trials registered at ClinicalTrials.

Validation of the prognostic index for spine metastasis (PRISM) for stratifying survival in patients treated with spinal stereotactic body radiation.

Purpose: The Prognostic Index for Spinal Metastasis (PRISM) is a scoring system derived from prospective data from a single institution that stratifies patients undergoing spine stereotactic radiosurgery (SSRS) for spinal metastases into subgroups by overall (OS). We sought to further demonstrate its generalizability by performing validation with a large dataset from a second high-volume institution, Mayo Clinic.

Methods And Materials: Eight hundred seventy-nine patients-424 from Mayo Clinic and 455 from MD Anderson Cancer Center (MDACC)-who received SSRS between 2007 and 2019 were identified.

Off-Protocol Radiation Therapy in Phase 3 Metastatic Solid Tumor Trials.

Purpose: Increasing data suggest that radiation therapy, particularly ablative radiation therapy, alters the natural history of metastatic disease. For patients with metastatic disease enrolled in prospective trials testing systemic therapy, the use of off-protocol radiation therapy to improve clinical symptoms or extend the duration of study systemic therapy may influence study endpoints. We sought to evaluate how often off-protocol radiation therapy was permitted among systemic therapy phase 3 trials, how often off-protocol radiation therapy is used, and whether off-protocol radiation therapy correlated with study outcomes.

Evidenced-Based Prior for Estimating the Treatment Effect of Phase III Randomized Trials in Oncology.

Purpose: The primary results of phase III oncology trials may be challenging to interpret, given that results are generally based on value thresholds. The probability of whether a treatment is beneficial, although more intuitive, is not usually provided. Here, we developed and released a user-friendly tool that calculates the probability of treatment benefit using trial summary statistics.

Increasing Power in Phase III Oncology Trials With Multivariable Regression: An Empirical Assessment of 535 Primary End Point Analyses.

Purpose: A previous study demonstrated that power against the (unobserved) true effect for the primary end point (PEP) of most phase III oncology trials is low, suggesting an increased risk of false-negative findings in the field of late-phase oncology. Fitting models with prognostic covariates is a potential solution to improve power; however, the extent to which trials leverage this approach, and its impact on trial interpretation at scale, is unknown. To that end, we hypothesized that phase III trials using multivariable PEP analyses are more likely to demonstrate superiority versus trials with univariable analyses.