The second week of January 2026 brought a series of translational and practice-shaping updates in gastrointestinal oncology, highlighting a shift toward context-driven decision-making that integrates tumor biology, biomarkers, multidisciplinary coordination and real-world constraints.
Nelson Dusetti and colleagues published a review on pancreatic ductal adenocarcinoma (PDAC) arguing that oncogenic KRAS alone is insufficient to initiate or sustain malignancy. The review synthesizes mechanistic, experimental and translational studies showing that cooperative alterations—loss of tumor suppressors, telomerase activity, MYC, and microenvironmental signals—are required to overcome senescence and enable KRAS-driven tumorigenesis, underscoring the need for context-aware therapeutic strategies.
Myriam Chalabi and the NICHE team reported neoadjuvant nivolumab plus ipilimumab activity in mismatch repair–proficient (pMMR) colon cancer, with a 26% response rate including deep pathologic responses. Responses occurred across clinical stages and correlated with ctDNA clearance. Genomic and transcriptomic analyses linked response to higher chromosomal instability, whole-genome duplications and TP53 mutations, while KRAS G12 mutations associated with non-response. Responders showed higher proliferation signatures and increased Ki67+ and CD103+ CD8 T-cell populations; immune activation was observed in both responders and non-responders.
A pooled real-world analysis presented at ASCO GI described liver transplantation (LTx) for unresectable colorectal liver metastases (uCLM) from Belgian centers (29 patients). Median duration of chemotherapy before LTx was 13 months and median follow-up 20.5 months. There were 11 recurrences—predominantly pulmonary—with median time to recurrence 6.3 months. Two-year overall survival was 90.1% (95% CI 74.4–100), two-year relapse-free survival 54.8% (95% CI 37.3–80.1), and median overall survival after recurrence 26.5 months. Two patients with pMMR, BRAF V600E–mutant disease remained recurrence-free beyond four years. Belgium has adopted a national LTx selection protocol for uCLM, including an independent validation committee, requirements of unresectable CLM without extrahepatic disease, at least six months of partial response or stable disease on the same treatment line, and an eight-week therapeutic pause with no progression beyond the liver. The protocol anticipates about 15 uCLM transplants per year, expedited listing with 28 MELD points and transplantation within one to two months for listed patients.
Omnia Korani highlighted ctDNA as a biomarker to guide adjuvant therapy, reporting that 18.4% of patients were ctDNA-positive and that ctDNA positivity strongly predicted worse outcomes (adjusted HR for disease-free survival 6.12, for overall survival 5.86). In the ctDNA-positive subgroup, celecoxib use was associated with improved survival (DFS aHR 0.61; OS aHR 0.62), whereas ctDNA-negative patients showed no significant benefit. These patterns persisted after stratification by microsatellite instability and PIK3CA status, suggesting ctDNA’s potential predictive utility.
Lucjan Wyrwicz discussed organ-sparing strategies for select gastric cancer subtypes, presenting a European perspective at ASCO GI and noting that such approaches are not yet standard of care in many centers.
Gabriele Capurso reported a prospective multicenter study on nutrition in advanced PDAC (140 patients). Malnutrition affected 33.6% of patients and correlated with decreased ability to deliver chemotherapy: higher Mini Nutritional Assessment and EORTC-PAN26 scores were associated with better relative dose intensity. A FAACT-A/CS score below 28 independently predicted shorter overall survival (HR 1.90). The study supports routine nutritional assessment and consideration of targeted nutritional interventions.
Anthony Turpin presented ALTOPANC, a real-world cohort of 155 patients with oligometastatic PDAC, suggesting metastasis-directed therapies—particularly radiofrequency ablation—may benefit selected patients. The group proposed an ALTOPANC score incorporating CA19-9, number of oligometastases and their sites to refine patient selection.
Gagan Brar discussed adjuvant anti–PD-1 plus capecitabine in resected intrahepatic cholangiocarcinoma, reporting median recurrence-free survival similar to historical capecitabine alone and not yet showing overall survival improvement, and raised the possibility that occult micrometastatic disease at diagnosis may limit benefit from adjuvant immune strategies and support exploration of neoadjuvant approaches.
Arndt Vogel summarized MORPHEUS-EC phase 1b/2 data on first-line tiragolumab plus atezolizumab and chemotherapy in unresectable or metastatic esophageal cancer, with median overall survival figures reported at 10.9, 11.4 and 8.7 months across arms, supporting further evaluation of tiragolumab in combination regimens.
Erman Akkus noted feasibility data from the NOBEL trial evaluating nivolumab with definitive chemoradiotherapy for esophageal squamous cell carcinoma, reflecting ongoing interest in integrating immunotherapy with definitive locoregional treatment.
Collectively, these reports emphasize that progress in GI oncology increasingly requires integrating biological context, biomarker-driven selection, multidisciplinary care and pragmatic real-world evidence to tailor treatments to the right patients at the right time.
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