Journal of Gastrointestinal Cancer最新文献

{"title":"BRAF V600E-Mutated Metastatic Colorectal Cancer: Practical Management in the Post-BREAKWATER Era.","authors":"Tamotsu Sagawa, Hiroyuki Nagashima, Koshi Fujikawa","doi":"10.1007/s12029-026-01581-0","DOIUrl":"10.1007/s12029-026-01581-0","url":null,"abstract":"<p><strong>Introduction: </strong>BRAF V600E-mutated metastatic colorectal cancer (mCRC) is a biologically distinct subtype characterized by right-sided predominance, frequent overlap with serrated-pathway biology, and historically poor outcomes with conventional chemotherapy. Therapeutic progress has been driven by the recognition that BRAF inhibition alone is inadequate in colorectal cancer because adaptive epidermal growth factor receptor (EGFR)-mediated feedback rapidly restores MAPK signaling.</p><p><strong>Methods: </strong>This narrative review evaluates the clinical development and practical integration of BRAF-targeted therapy in BRAF V600E-mutated mCRC, with particular emphasis on first-line treatment, MMR/MSI status, patient fitness, and treatment sequencing in the post-BREAKWATER era.</p><p><strong>Results: </strong>Combined BRAF and EGFR inhibition established encorafenib plus cetuximab as a standard option after prior therapy. The phase 3 BREAKWATER program has now moved BRAF-targeted treatment into first-line practice by demonstrating improved outcomes with encorafenib plus cetuximab combined with fluoropyrimidine-basedchemotherapy, including mFOLFOX6 and FOLFIRI backbones. These data define a chemo-targeted approach for fit patients with non-MSI-H/dMMR disease. For MSI-H/dMMR tumors, first-line immune checkpoint blockade should be prioritized irrespective of BRAF V600E status unless immunotherapy is absolutely contraindicated.</p><p><strong>Conclusion: </strong>Important uncertainties remain regarding whether BRAF/EGFR targeting should be added to immunotherapy in MSI-H/dMMR disease, as well as the management of frail or oxaliplatin-ineligible patients, maintenance therapy, local treatment integration, and sequencing after frontline encorafenib exposure. Treatment selection in the post- BREAKWATER era should therefore integrate molecular context, patient fitness, and remaining evidence gaps.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":"57 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148865399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinicopathologic Characteristics, Treatments, and Survival Outcomes of Early-onset Compared to Later-onset Colorectal Mucinous Adenocarcinomas: A Population-based SEER Analysis.","authors":"Sameh Hany Emile, Spencer Barnes, Zoe Garoufalia, Steven D Wexner","doi":"10.1007/s12029-026-01576-x","DOIUrl":"10.1007/s12029-026-01576-x","url":null,"abstract":"<p><strong>Background: </strong>Colorectal mucinous adenocarcinoma (CMA) is a unique subtype of adenocarcinoma. This study aimed to compare characteristics, treatments, and survival outcomes of early-onset and later-onset CMA.</p><p><strong>Methods: </strong>This investigation was a retrospective cohort study from the National Cancer Institute's SEER Research Data database from 2000 to 2022 on patients with CMA. Patients aged < 50 years (early-onset) and patients aged ≥ 50 years (later-onset) were compared regarding disease characteristics, treatments, and survival. The main outcome measures were 5-year overall survival (OS) and cancer-specific survival (CSS).</p><p><strong>Results: </strong>The study included 55,853 patients; 10.4% of them presented with early-onset disease. Early-onset CMA more often affected males, Blacks, and Hispanics, and was more advanced and more often associated with liver metastases. Early-onset CMA was associated with higher 5-year OS (57.7% vs. 47.5%, p < 0.001) and CSS (58.4% vs. 45.4%, p < 0.001). In multivariable Cox proportional hazard analysis excluding postdiagnosis treatment variables, later-onset CMA was associated with higher all-cause mortality (HR: 1.69, 95% CI 1.53-1.87, p < 0.001) and cancer-specific mortality (HR: 1.45, 95% CI 1.30-1.61, p < 0.001) compared to early-onset disease. In a sensitivity analysis adjusting for treatment variables, these associations persisted, although they were attenuated for both OS (HR: 1.56, 95% CI 1.41-1.72, p < 0.001) and CSS (HR: 1.34, 95% CI 1.20-1.49, p < 0.001).</p><p><strong>Conclusions: </strong>Early-onset CMA presented with different demographic and disease characteristics and treatment patterns than later-onset disease. Survival of early-onset CMA was higher than later-onset CMA.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":"57 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148850811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HER2-Targeted Therapy for Metastatic Colorectal Cancer: Current Evidence, Patient Selection, and Practical Treatment Sequencing.","authors":"Tamotsu Sagawa, Hiroyuki Nagashima, Koshi Fujikawa","doi":"10.1007/s12029-026-01564-1","DOIUrl":"10.1007/s12029-026-01564-1","url":null,"abstract":"<p><p>HER2 has emerged as an actionable molecular alteration in metastatic colorectal cancer (mCRC), particularly in patients with RAS wild-type disease and tumors with strong HER2 overexpression or ERBB2 amplification. Once recognized mainly as a mechanism of resistance to anti-EGFR therapy, HER2 now defines a therapeutically relevant subgroup. Dual HER2 blockade with trastuzumab-based combinations and antibody-drug conjugates, particularly trastuzumab deruxtecan, have demonstrated clinically meaningful activity in treatment-refractory disease. Emerging phase III data with trastuzumab rezetecan further support HER2-directed therapy, although peer-reviewed publication, regulatory status, and regional availability remain important considerations. This narrative review focuses on the practical integration of HER2 testing and HER2-directed treatment into mCRC care. We summarize colorectal cancer-specific diagnostic approaches, evidence for established and emerging regimens, and treatment-selection considerations according to RAS/BRAF status, HER2 expression level, prior anti-EGFR exposure, comorbidities, toxicity risk, and local access. We also discuss the complementary roles of tissue testing and circulating tumor DNA, including repeat molecular assessment at progression. Finally, we propose a clinician-oriented framework for early patient identification, treatment sequencing, and resistance assessment. Optimal sequencing between dual HER2 blockade and antibody-drug conjugates remains uncertain and requires prospective evaluation.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":"57 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148850844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine Learning Prediction of Local Failure in GI Brain Metastases on the Day of Gamma Knife Radiosurgery.","authors":"Jheremy S Reyes, Alexandros Bouras, Andrew H Zureick, L Dade Lunsford, Ajay Niranjan, Constantinos G Hadjipanayis","doi":"10.1007/s12029-026-01583-y","DOIUrl":"10.1007/s12029-026-01583-y","url":null,"abstract":"<p><strong>Background: </strong>Time to local failure after stereotactic radiosurgery (SRS), including Gamma Knife radiosurgery (GKRS), for gastrointestinal (GI) brain metastases is difficult to predict and may vary substantially across tumors and patients. We developed and internally evaluated a survival machine learning framework to estimate tumor-specific time to local failure using pre-SRS features.</p><p><strong>Methods: </strong>We performed a retrospective study of GI brain metastases treated with GKRS. Local failure was modeled as a time-to-event outcome under right censoring. A Random Survival Forest survival model was trained using treatment-time demographic, clinical, tumor, histologic, and radiosurgical variables restricted to information available before or at GKRS. To avoid within-patient leakage, validation was performed using patient-grouped cross-validation. Model performance was assessed using the concordance index (C-index) and IBS. Among tumors with observed local failure, temporal prediction accuracy was additionally evaluated using mean absolute error (MAE) and coefficient of determination (R²).</p><p><strong>Results: </strong>The cohort included 90 patients and 218 treated tumors from 2014 to 2024. Median age at treatment was 68.0 years, median pre-treatment Karnofsky Performance Status was 60, and 91.3% of tumors occurred in patients with multiple metastases. Fifty-seven tumors experienced local failure. The model achieved a mean grouped cross-validated C-index of 0.79 and a mean IBS of 0.0031 (95% CI, 0.0014-0.0042). Among tumors with local failure, conditional MAE was 1.11 months and R² was 0.26.</p><p><strong>Conclusions: </strong>Pre-SRS survival machine learning is feasible for predicting time to local failure in GI brain metastases treated with GKRS and supports further validation in larger multicenter cohorts.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":"57 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Personalizing Postoperative Surveillance: A Risk-Stratified Predictive Model for Recurrence of Gastrointestinal Neuroendocrine Neoplasms.","authors":"Zhangchao Yao, Yue Liu, Jie Fan, Feiran Zhou, Luohai Chen, Jie Chen, Huae Xu, Xiaolin Li","doi":"10.1007/s12029-026-01582-z","DOIUrl":"10.1007/s12029-026-01582-z","url":null,"abstract":"<p><strong>Background: </strong>Current Ki-67-based prognostic tools have limitations in stratifying recurrence risk for gastrointestinal neuroendocrine neoplasms (GI-NENs) after primary tumor resection (PTR), necessitating personalized predictive models to optimize surveillance.</p><p><strong>Methods: </strong>Data from 316 GI-NEN patients undergoing PTR were analyzed. Variables selected via LASSO regression were incorporated into Cox and Random Survival Forest (RSF) models. A nomogram was constructed based on superior model, and cut-off scores stratified patients into three recurrence risk groups.</p><p><strong>Results: </strong>The RSF model showed superior accuracy (C-index: 0.854) with good discrimination and calibration. A nomogram integrating eight key predictors stratified patients into low-risk (n = 241), intermediate-risk (n = 57), and high-risk (n = 18) groups. The Kaplan-Meier curves among them were significantly distinct. High-risk group had a median recurrence-free survival of 11.4 months, with nearly all experiencing recurrence or progression within 26 months. Compared with traditional NET grading, this model reclassified some G2 patients into intermediateand even high-risk groups and down-stratified G3 patients with favorable prognoses into the intermediate-risk group.</p><p><strong>Conclusions: </strong>This study developed and validated a risk-stratified model that effectively identifies postoperative recurrence risk in GI-NENs, enabling tailored surveillance. High-risk patients require intensive follow-up every 2-3 months and early adjuvant intervention. Low-risk patients can safely extend to annually. Most intermediate-risk patients may recieve follow-up every 6-12 months, though G3 patients near the high-risk threshold may still require surveillance every 3-6 months. This model facilitates personalized follow-up to improve long-term outcomes.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":"57 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Lymph Node Ratio as a Predictive Biomarker for Individualized Benefit from Adjuvant Chemotherapy in Gastric Cancer: A Retrospective Cohort and Causal Machine Learning Study.","authors":"Wen-Qi Hong, Ren-Hao Hu, Xiao-Hua Jiang, Shun Zhang","doi":"10.1007/s12029-026-01556-1","DOIUrl":"10.1007/s12029-026-01556-1","url":null,"abstract":"<p><strong>Background: </strong>Optimizing adjuvant chemotherapy (AC) for gastric cancer (GC) remains challenging due to patient heterogeneity. While the lymph node ratio (LNR) is a known prognostic factor, its role in predicting individualized AC benefit remains underexplored. This study aimed to leverage causal machine learning to explore LNR's role for personalized treatment.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study of 2,748 patients undergoing radical gastrectomy (2007-2017, re-staged by AJCC 8th edition). While the full cohort provided a demographic overview, analytic models focused on untreated Stage IB patients (n = 325) for prognostic factors, and Stage II-III patients (n = 825) for AC benefit estimation using a Causal Forest model with out-of-bag (OOB) predictions. Propensity score matching (PSM) was employed to mitigate treatment allocation bias.</p><p><strong>Results: </strong>AC benefit was highly heterogeneous. In Stage IB, lymphovascular invasion (LVI) and elderly age were independent prognostic factors. Strikingly, the Causal Forest model (Area Under the Uplift Curve = 31.08) identified LNR as the most dominant predictor of AC benefit. Subgroup Cox interaction analysis within the PSM cohort (n = 434) confirmed a highly significant threshold effect (P for interaction < 0.001): AC significantly reduced mortality in the High LNR (> 0.25) group (HR = 0.41, P = 0.016), while showing potential harm in the Low LNR (< 0.1) group (HR = 2.58, P = 0.015). The top 20% of predicted beneficiaries achieved an Absolute Risk Reduction (ARR) of 21.59%, corresponding to a Number Needed to Treat (NNT) of 4.63.</p><p><strong>Conclusions: </strong>LNR is identified as a robust predictive biomarker for AC benefit in GC. This exploratory causal inference framework can help personalize treatment decisions, representing a valuable approach to complement clinical guidelines. To facilitate clinical application, an exploratory web-based decision support tool was developed.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":"57 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148794127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on \"Oncological Outcomes after Elective and Emergency Resection of Small Intestinal Neuroendocrine Tumours\".","authors":"Devasilpa Raju, Antaryami Sahoo, Dinesh Mohan","doi":"10.1007/s12029-026-01484-0","DOIUrl":"10.1007/s12029-026-01484-0","url":null,"abstract":"","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":"57 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148794089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"KRAS G12C-mutated Metastatic Colorectal Cancer: Current Therapeutic Strategies and Future Directions.","authors":"Tamotsu Sagawa, Hiroyuki Nagashima, Koshi Fujikawa","doi":"10.1007/s12029-026-01547-2","DOIUrl":"10.1007/s12029-026-01547-2","url":null,"abstract":"<p><p>KRAS G12C mutations define a small but clinically important molecular subset of metastatic colorectal cancer (mCRC), accounting for approximately 3% to 4% of cases and remaining associated with substantial unmet need after standard chemotherapy. Although direct KRAS G12C inhibitors have transformed treatment in other tumor types, their activity as monotherapy in mCRC has been modest, largely because colorectal cancer retains strong upstream EGFR and receptor tyrosine kinase dependency with adaptive MAPK pathway reactivation. These observations provide the biologic rationale for combined KRAS G12C and EGFR inhibition. Clinical results are line- and regimen-dependent: sotorasib plus panitumumab improved progression-free survival compared with standard later-line therapy in the randomized phase 3 CodeBreaK 300 trial, whereas adagrasib plus cetuximab demonstrated clinically meaningful activity in KRYSTAL-1 but did not improve progression-free or overall survival versus chemotherapy in the second-line phase 3 KRYSTAL-10 trial despite a higher objective response rate. Available evidence should therefore be interpreted with appropriate caution. Moreover, acquired resistance remains common and frequently polyclonal, involving secondary KRAS alterations, receptor tyrosine kinase bypass, and downstream pathway reactivation. In this review, we summarize the biologic rationale, current clinical evidence, practical guideline-based positioning, toxicity management considerations, resistance mechanisms, and emerging therapeutic strategies for KRAS G12C-mutated mCRC.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":"57 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148794132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"State-Level Prevalence of Obesity/overweight and Pancreatic Cancer Incidence in the United States: An Ecological Analysis Using BRFSS, CDC WONDER and ACS for the Year 2021.","authors":"Sanchit Mehta, Sai Sushrutha Mudupula Vemula, Abdul Aleem, Maria Khakwani, Ahsan Wahab, Karine Tawagi","doi":"10.1007/s12029-026-01562-3","DOIUrl":"10.1007/s12029-026-01562-3","url":null,"abstract":"<p><strong>Purpose: </strong>While obesity is established as an individual-level risk factor for pancreatic cancer (PC), population-level associations remain unclear. This study examines whether state-level overweight/obesity (O/OV) prevalence corresponds with age-adjusted PC incidence across the United States.</p><p><strong>Methods: </strong>We conducted an ecological, cross-sectional analysis using 2021 data from the Behavioral Risk Factor Surveillance System (BRFSS) for state-level O/OV prevalence (BMI ≥ 25 kg/m²) and CDC WONDER for age-adjusted incidence rates (AAIR) of PC per 100,000 population. Demographic covariates such as percentage of non-Hispanic Black (NHB) population and population ≥ 65 years old were extracted from American Community Survey (ACS) data. Prevalence of current smokers and diabetes were also extracted from BRFSS. As a descriptive exploratory approach, incidence rate ratios (IRR) were calculated relative to West Virginia (WV) which had the highest O/OV prevalence, 73.6%. For inferential analysis, a univariable ordinary least square (OLS) linear regression was used to determine the association between O/OV prevalence and PC incidence. Multivariable linear regression model was fitted to adjust for prevalence of age ≥ 65, NHB race/ethnicity, current smokers and diabetes prevalence.</p><p><strong>Results: </strong>Across 50 US jurisdictions, including DC, the mean O/OV prevalence was 67.72%, ranging from 55.4% in DC to 73.6% in WV. Florida was excluded from the complete-case analysis and OLS due to missing BRFSS values for O/OV. Twenty-nine states with O/OV prevalence lower than WV also had lower PC incidence (concordance) whereas 20 states including DC exhibited lower O/OV prevalence yet higher PC incidence (discordance). Univariable OLS model showed no statistically significant association between O/OV and AAIR (slope: -0.035, p = 0.56; R²=0.007). Multivariable OLS well fitted model showed no significant association between O/OV and AAIR. Only Black population proportion was significantly associated with PC incidence across the states.</p><p><strong>Conclusions: </strong>In this study, state-level O/OV prevalence failed to demonstrate a statistically significant association with PC incidence. Proportion of Black population was significantly associated with increased PC incidence. These findings suggest that population-level PC risk is likely influenced by multiple interacting metabolic, behavioral, sociodemographic, environmental, and healthcare-related factors beyond obesity alone. Further longitudinal and multivariable studies are needed to better delineate the complex relationship between obesity and PC at the population level.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":"57 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148794070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FOLFOX in Esophageal Squamous Cell Carcinoma: Current Evidence and Future Role as a Cisplatin-Sparing Chemoimmunotherapy Backbone.","authors":"Tamotsu Sagawa, Hiroyuki Nagashima, Koshi Fujikawa","doi":"10.1007/s12029-026-01540-9","DOIUrl":"10.1007/s12029-026-01540-9","url":null,"abstract":"<p><p>Fluorouracil plus cisplatin has historically served as the dominant platinum-fluoropyrimidine backbone for esophageal squamous cell carcinoma (ESCC). In the immunotherapy era, the key practical question is not whether oxaliplatin can universally replace cisplatin, but whether FOLFOX can provide a rational, patient-centered cisplatin-sparing backbone for selected patients receiving first-line chemoimmunotherapy. CheckMate 648 established nivolumab plus chemotherapy using fluorouracil plus cisplatin, whereas RATIONALE-306 demonstrated that oxaliplatin-containing backbones can be incorporated into successful global phase III immunochemotherapy. Recent Japanese retrospective data in cisplatin-unfit patients showed clinically meaningful activity of nivolumab plus FOLFOX, with reduced renal and hydration burden, outpatient feasibility, and treatment continuity representing potential practical advantages. Oxaliplatin-induced immunogenic cell death provides an additional mechanistic rationale, although this remains predominantly preclinical. Prospective evaluation is underway in Japan through the FLONTALE and OXA-REPLACE phase II trials. This review summarizes the clinical and biological rationale, current evidence, limitations, and future positioning of nivolumab plus FOLFOX. At present, it should be regarded as an emerging selective strategy rather than an established alternative to cisplatin-based chemoimmunotherapy.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":"57 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148794107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}