Moving from the background towards the spotlight: A critical review of radiation therapy for locally advanced pancreas cancer.

Radiation therapy for locally advanced pancreatic cancer (LAPC) continues to be controversial. Advances in both systemic therapy and radiation therapy techniques have changed the landscape of LAPC management in recent years. Clinical outcomes of ablative radiation therapy have been encouraging and randomized clinical trials may clarify the role of radiation therapy for LAPC.

Emerging evidence-based role for external-beam radiation therapy in hepatocellular carcinoma.

The primary curative therapies for hepatocellular carcinoma are resection or liver transplantation. For patients requiring downstaging or who are unresectable at presentation, the landscape of local treatment options has vastly changed over the past decades. This change is partly due to the paucity of high-level evidence to guide the selection of liver-directed therapies, where physician preference and treatment patterns have historically resulted in relegating external-beam radiation therapy (EBRT) to a secondary option in the treatment of hepatocellular carcinoma in cases where arterially directed therapies or thermal ablations were not possible.

Defining the Role of Adjuvant Radiotherapy for Biliary Tract Cancers: A Site-Specific Propensity-Matched Analysis.

: Biliary tract cancers (BTCs) have distinct tumor biology but share a poor prognosis, with a 5-year-survival-rate of 5-19%. Surgical resection is the only potential cure, but recurrences are common. The role of adjuvant radiotherapy (XRT) remains unclear.

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.

Time dependency for human papillomavirus circulating tumor DNA detection after chemoradiation as a prognostic biomarker for localized anal cancer.

Background: While detection of circulating tumor DNA (ctDNA) weeks after surgery is linked to recurrence for other solid tumors, the optimal time point for ctDNA assessment as a prognostic biomarker following chemoradiation for anal cancer is undefined.

Methods: Patients with stages I-III anal cancer treated with chemoradiation between 12/2020-5/2024 were evaluated for HPV ctDNA status at baseline, at the end of chemoradiation, and during surveillance using a droplet digital HPV ctDNA PCR assay targeting HPV E6 and E7 oncogenes for 13 oncogenic HPV types. Median recurrence-free survival (RFS) according to HPV ctDNA status was estimated via Kaplan-Meier and compared using a log-rank test.

Evolving Paradigms in the Treatment of Oligometastatic Pancreatic Ductal Adenocarcinoma.

Multiple randomized trials have suggested that the addition of comprehensive metastasis-directed therapy to best systemic therapy improves disease control and survival among patients with oligometastatic disease, even for histologies with a high propensity for rapid spread. Here, we review the growing literature supporting the oligometastatic paradigm in pancreatic ductal adenocarcinoma. We summarize key details from nascent institutional series and reflect on the recently reported phase II randomized EXTEND trial.

Proton Beam Therapy for Pancreatic Tumors: A Consensus Statement from the Particle Therapy Cooperative Group Gastrointestinal Subcommittee.

Radiation therapy manages pancreatic cancer in various settings; however, the proximity of gastrointestinal (GI) luminal organs at risk (OARs) poses challenges to conventional radiation therapy. Proton beam therapy (PBT) may reduce toxicities compared to photon therapy. This consensus statement summarizes PBT's safe and optimal delivery for pancreatic tumors.

Characterization of LiF TLD-100 in carbon ion beams for remote audits.

Background: A passive dosimeter framework for the measurement of dose in carbon ion beams has yet to be characterized or implemented for regular use.

Purpose: This work determined the dose calculation correction factors for absorbed dose in thermoluminescent dosimeters (TLDs) in a therapeutic carbon ion beam. TLD could be a useful tool for remote audits, particularly in the context of clinical trials as new protocols are developed for carbon ion radiotherapy.

Stereotactic Body Radiotherapy vs Sorafenib Alone in Hepatocellular Carcinoma: The NRG Oncology/RTOG 1112 Phase 3 Randomized Clinical Trial.

Importance: Most patients with locally advanced hepatocellular carcinoma (HCC) recur within the liver following systemic therapy.

Objective: To determine whether stereotactic body radiation therapy (SBRT) improves outcomes in patients with locally advanced HCC compared with sorafenib alone.

Design, Setting, And Participants: This multicenter phase 3 randomized clinical trial randomized patients with HCC 1:1 to sorafenib or SBRT followed by sorafenib, stratified by performance status, liver function, degree of metastases, and macrovascular invasion.

Best Practices for Delivering Neoadjuvant Therapy in Pancreatic Ductal Adenocarcinoma.

Importance: Neoadjuvant therapy (NT) is an increasingly used treatment strategy for patients with localized pancreatic ductal adenocarcinoma (PDAC). Little research has been conducted on cancer care delivery during NT, and the standards for optimal delivery of NT have not been defined.

Objective: To develop consensus best practices for delivering NT to patients with localized PDAC.

Early detection of pancreatic cancer: Study design and analytical considerations in biomarker discovery and early phase validation studies.

Objectives: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease that is challenging to detect at an early stage. Biomarkers are needed that can detect PDAC early in the course of disease when interventions lead to the best outcomes. We highlight study design and statistical considerations that inform pancreatic cancer early detection biomarker evaluation.

The Association between Sampling and Survival in Patients with Pancreatic Ductal Adenocarcinoma Who Received Neoadjuvant Therapy and Pancreaticoduodenectomy.

Adequate sampling is essential to an accurate pathologic evaluation of pancreatectomy specimens resected for pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant therapy (NAT). However, limited data are available for the association between the sampling and survival in these patients. We examined the association of the entire submission of the tumor (ESOT) and the entire submission of the pancreas (ESOP) with disease-free survival (DFS) and overall survival (OS), as well as their correlations with clinicopathologic features, for 627 patients with PDAC who received NAT and pancreaticoduodenectomy.

Evaluating pre-consult patient education videos for patients with newly-diagnosed anal squamous cell carcinoma: Impact on patient comprehension, satisfaction and distress.

We hypothesized that pre-consult patient education videos can improve patient understanding about their diagnosis, lead to high satisfaction and low distress. In this pilot study, we developed a patient education video curriculum for patients with newly-diagnosed anal cancer. Comprehension of key content was evaluated by comparing pre- and post-test scores.

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.

Hybridizing mechanistic modeling and deep learning for personalized survival prediction after immune checkpoint inhibitor immunotherapy.

We present a study where predictive mechanistic modeling is combined with deep learning methods to predict individual patient survival probabilities under immune checkpoint inhibitor (ICI) immunotherapy. This hybrid approach enables prediction based on both measures that are calculable from mechanistic models of key mechanisms underlying ICI therapy that may not be directly measurable in the clinic and easily measurable quantities or patient characteristics that are not always readily incorporated into predictive mechanistic models. A deep learning time-to-event predictive model trained on a hybrid mechanistic + clinical data set from 93 patients achieved higher per-patient predictive accuracy based on event-time concordance, Brier score, and negative binomial log-likelihood-based criteria than when trained on only mechanistic model-derived values or only clinical data.

Improving the clinical meaning of surrogate endpoints: An empirical assessment of clinical progression in phase III oncology trials.

Disease progression in clinical trials is commonly defined by radiologic measures. However, clinical progression may be more meaningful to patients, may occur even when radiologic criteria for progression are not met, and often requires a change in therapy in clinical practice. The objective of this study was to determine the utilization of clinical progression criteria within progression-based trial endpoints among phase III trials testing systemic therapies for metastatic solid tumors.

Addition of Metastasis-Directed Therapy to Systemic Therapy for Oligometastatic Pancreatic Ductal Adenocarcinoma (EXTEND): A Multicenter, Randomized Phase II Trial.

Purpose: The EXTEND trial tested the hypothesis that adding comprehensive metastasis-directed therapy (MDT) to chemotherapy would improve progression-free survival (PFS) over chemotherapy alone among patients with oligometastatic pancreatic ductal adenocarcinoma (PDAC).

Methods: EXTEND (ClinicalTrials.gov identifier: NCT03599765) is a multicenter, phase II basket trial randomly assigning patients with ≤five metastases 1:1 to MDT plus systemic therapy versus systemic therapy.

Translational modeling-based evidence for enhanced efficacy of standard-of-care drugs in combination with anti-microRNA-155 in non-small-cell lung cancer.

Background: Elevated microRNA-155 (miR-155) expression in non-small-cell lung cancer (NSCLC) promotes cisplatin resistance and negatively impacts treatment outcomes. However, miR-155 can also boost anti-tumor immunity by suppressing PD-L1 expression. Therapeutic targeting of miR-155 through its antagonist, anti-miR-155, has proven challenging due to its dual molecular effects.