Detecting Extranodal Extension in HPV-Related Oropharyngeal Cancer via Machine Learning.

Objective: To assess the performance of machine learning (ML) models trained on large publicly available databases in predicting extranodal extension (ENE) within a smaller single-institution cohort.

Methods: Patient data were derived from two datasets. The first, the NCDB containing 5551 patients, was used to train and validate the ML algorithms.

Randomized Phase II Study of Concurrent Versus Sequential Pembrolizumab in Combination With Chemoradiation in Locally Advanced Head and Neck Cancer.

Purpose: The optimal timing of pembrolizumab with chemoradiation (CRT) in locally advanced (LA) head and neck squamous cell carcinoma (HNSCC) is unknown.

Patients And Methods: Our phase II trial randomly assigned patients 1:1 to concurrent pembrolizumab (200 mg once every 3 weeks × 8) starting 1 week before CRT (cisplatin 40 mg/m once weekly + radiation 70 Gy) versus sequential pembrolizumab starting 2 weeks after CRT. Human papillomavirus (HPV)+ (>10 pack-years or T4 or N3) and HPV(-) LA HNSCC were included, stratified by HPV and N stage.

Comparative in vivo toxicology of ATR inhibitors ceralasertib, elimusertib, and berzosertib alone and in combination with ionizing radiation.

Ionizing radiation (IR) induces damage in the form of DNA strand breaks. As an apical initiator of the DNA damage response, Ataxia telangiectasia and Rad3-related (ATR) mitigates DNA damage, limiting therapeutic efficacy. Small molecule ATR inhibitors (ATRi) restrict this effect and sensitize cancer cells to radiation-induced damage.

Non-linear IV pharmacokinetics of the ATR inhibitor berzosertib (M6620) in mice.

Background: The Ataxia Telangiectasia and Rad3-related (ATR) protein complex is an apical initiator of DNA damage response pathways. Several ATR inhibitors (ATRi) are in clinical development including berzosertib (formerly M6620, VX-970). Although clinical studies have examined plasma pharmacokinetics (PK) in humans, little is known regarding dose/exposure relationships and tissue distribution.