10 Must-Read Posts in GI Oncology This Week

10 Must-Read Posts in GI Oncology This Week

The first week of December brought several notable advances across gastrointestinal oncology, including developments in neoadjuvant strategies, immunotherapy for complex populations, precision biomarkers, surgical quality, and translational science. Key items include whole-genome ctDNA–guided total neoadjuvant therapy (TNT) for gastroesophageal junction (GEJ) cancer, a landmark trial for liver-transplanted patients with recurrent hepatocellular carcinoma (HCC), and preclinical data showing durable KRAS-pathway–targeted tumor regression in pancreatic ductal adenocarcinoma (PDAC) models.

Kohei Shitara, MD, Chief of Gastrointestinal Oncology at the National Cancer Center Hospital East, described an ongoing phase II TNT protocol for resectable GEJ adenocarcinoma combining FLOT, pembrolizumab, and short-course radiotherapy. The trial integrates whole-genome ctDNA to support clinical-complete-response–based organ-preservation strategies.

A collaborative team led by the CNIO reported in PNAS that coordinated inhibition of KRAS-high signaling using RAF1-targeted, EGFR-targeted (afatinib), and STAT3-directed PROTAC (SD36) agents produced complete and durable regression of PDAC in patient-derived organoids, patient-derived xenografts, and murine models, with no relapse beyond 200 days and no detectable toxicity. The study highlights the need for simultaneous targeting of upstream, downstream, and parallel survival pathways to overcome resistance.

The PHRC Phase II IMMUNO-TH trial opened its first investigational site to evaluate atezolizumab plus bevacizumab in liver-transplanted patients with recurrent advanced HCC. The multicenter study uses a standardized immunosuppressive protocol designed to limit graft rejection and addresses a significant unmet need in this population.

A meta-analysis of 18 randomized trials examined progression-free survival (PFS) as a surrogate for overall survival (OS) in first-line immunotherapy trials for gastroesophageal cancers. The analysis found a moderate-to-strong PFS–OS correlation in gastroesophageal adenocarcinoma, particularly among patients with high PD-L1 expression, while correlations were weaker in esophageal squamous cell carcinoma, underscoring continued reliance on OS in that setting.

A molecular study of microsatellite-stable colorectal cancer metastases found largely similar genomic profiles between liver and non-liver metastases, suggesting that the liver microenvironment rather than distinct tumor genomics may underlie therapy resistance. The study also reported differing prognostic impacts by site: BRAF V600E appeared predominantly prognostic for patients without liver metastasis, while KRAS effects varied by metastatic site.

An analysis using the TriNetX global real-world network compared 87 patients with fibrolamellar hepatocellular carcinoma (FLC) to over 211,000 conventional HCC cases. The study found no significant difference in overall survival after propensity matching, while confirming distinct clinical features for FLC, including younger age and differing biochemical patterns, offering one of the largest real-world datasets for this rare subtype.

A study evaluating adjuvant celecoxib suggested a predictive role for circulating tumor DNA (ctDNA). In the ctDNA-positive subgroup, adding celecoxib was associated with an approximate 40% relative risk reduction in both disease-free survival and overall survival, indicating potential utility of ctDNA to select patients for adjuvant therapy.

A national analysis of 652 patients treated for gastric cancer in Slovenia between 2016 and 2020 found better long-term survival at high-volume university medical centers. High-volume centers treated 76.4% of patients and reported median overall survival of 4.9 years versus 3.2 years at lower-volume hospitals, supporting further centralization of gastric cancer surgery.

A literature review and expert-panel consensus defined key surgical and perioperative interventions that most influence rectal cancer outcomes. The consensus aims to standardize practice, inform quality-improvement efforts, and guide training and decision-making in rectal cancer care.

A single-institution retrospective analysis of ultra- and moderately hypofractionated radiotherapy for inoperable cholangiocarcinoma examined recurrence patterns, survival, and biliary event-free survival (BEFS). The study reports a quantitative association between biliary events and overall survival, highlighting BEFS as a clinically relevant endpoint for this population.

A related roundup covering 10 must-read posts from the fourth week of November is available on OncoDaily.