Journal of Gastrointestinal Cancer最新文献

{"title":"Safety of Immune-Targeted Therapy in Patients with Hepatocellular Carcinoma in the Real-World.","authors":"Menghuan Song, Tianyue Feng, Ning Deng, Zhirong Yang, Yunfeng Lai, Carolina Oi Lam Ung, Hao Hu","doi":"10.1007/s12029-026-01534-7","DOIUrl":"10.1007/s12029-026-01534-7","url":null,"abstract":"<p><strong>Background: </strong>Combining immunotherapy with targeted therapy represents a promising trajectory for cancer treatment; however, safety profiles remain insufficient. This study aimed to characterize adverse events associated with immune-targeted regimens in hepatocellular carcinoma (HCC).</p><p><strong>Methods: </strong>This study used Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), and Bayesian Confidence Propagation Neural Network (BCPNN) to detect signals of adverse events based on data from FDA Adverse Event Reporting System.</p><p><strong>Results: </strong>Signals of fulminant type-1 diabetes mellitus (ROR = 13.3, PRR = 13.2, IC = 3.7), myositis (8.5, 8.3, 3.1), encephalitis (8.4, 8.3, 3.0), and myocarditis (7.3, 7.2, 2.8) were identified in atezolizumab+bevacizumab. Immune-mediated hepatitis (5.6, 5.1, 2.4), hepatic encephalopathy (3.3, 3.0, 1.6), and uppergastrointestinal haemorrhage (4.3, 4.2, 2.1) were associated with pembrolizumab+lenvatinib. Signals of gastrointestinal haemorrhage (5.1, 4.8, 2.3) and malignant neoplasm progression (2.9, 2.7, 1.4) were in patients using atezolizumab+cabozantinib.</p><p><strong>Conclusion: </strong>This study delineated distinct profiles of adverse events associated with immunotargeted therapies, which serves as a critical reference for risk assessment and therapeutic selection. Though atezolizumab plus bevacizumab is recommended as first-line treatment for advanced HCC, potential severe immune-mediated adverse events affecting multiple organs suggested the importance of clinical vigilance. Extrapolation of pembrolizumab+lenvatinib and atezolizumab+cabozantinib from other cancers to HCC warrants caution in consideration of the associated bleeding risks and hepatic complications.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":"57 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148470968","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":"Preoperative CT Assessment of Portal Vein Contact Length Predicts Poor Prognosis in Resectable Pancreatic Head Cancer.","authors":"Shingo Kozono, Takaaki Tatsuguchi, Atsushi Fujii, Hirotaka Kuga, Keisuke Hirahata, Yuzo Shimokawa, Masayuki Hijioka, Masato Sakamoto, Sadafumi Tamiya, Toru Nakano","doi":"10.1007/s12029-026-01527-6","DOIUrl":"10.1007/s12029-026-01527-6","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate whether preoperative computed tomography (CT)-based tumor-portal/superior mesenteric vein (PV/SMV) contact angle and contact length predict pathological venous invasion and refine prognostic stratification in anatomically resectable pancreatic ductal adenocarcinoma (R-PDAC).</p><p><strong>Methods: </strong>We retrospectively reviewed 108 patients who underwent upfront pancreaticoduodenectomy without neoadjuvant chemotherapy for pancreatic head PDAC, including 101 anatomically resectable cases and 7 borderline resectable cases with PV involvement (BR-PV). Tumor-PV/SMV contact angle and contact length were measured on multidetector CT. Their associations with pathological PV/SMV invasion, PV/SMV resection, and overall survival (OS) were analyzed.</p><p><strong>Results: </strong>Both contact angle and contact length predicted pathological venous invasion, with optimal cutoff values of 90° for angle (AUC = 0.86) and 15 mm for length (AUC = 0.84), and both were significantly associated with pathological venous invasion and PV/SMV resection (all p < 0.001). In the subgroup with R-PDAC, however, only contact length provided meaningful prognostic stratification. Patients with contact length ≥ 15 mm had significantly worse OS than those with contact length < 15 mm (p = 0.0032) or no contact (p < 0.001), and their survival was comparable to that of BR-PV patients (p = 0.8548). In multivariable analysis, contact length ≥ 15 mm remained an independent adverse prognostic factor (HR 2.79, 95% CI 1.64-4.73, p < 0.001).</p><p><strong>Conclusion: </strong>Preoperative CT-based assessment of tumor-PV/SMV contact length may serve as a practical marker for identifying a high-risk subgroup within R-PDAC and may help refine selection of patients for neoadjuvant treatment.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":"57 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148470995","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":"Access or Engagement: The Potential Role of Financial Incentives in Colorectal Cancer Screening.","authors":"Riccardo Vecchio, Anna Odone","doi":"10.1007/s12029-026-01533-8","DOIUrl":"10.1007/s12029-026-01533-8","url":null,"abstract":"","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":"57 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148447491","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":"Optimal First-Line Immunotherapy for MSI-H/dMMR Metastatic Colorectal Cancer: Evidence, Gaps, and Clinical Decision-Making.","authors":"Tamotsu Sagawa, Hiroyuki Nagashima, Koshi Fujikawa","doi":"10.1007/s12029-026-01526-7","DOIUrl":"10.1007/s12029-026-01526-7","url":null,"abstract":"<p><strong>Background and aim: </strong>Microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) metastatic colorectal cancer (mCRC) has emerged as a model for biomarker-driven immunotherapy. Yet the optimal positioning of pembrolizumab, nivolumab, and nivolumab plus ipilimumab in routine practice remains unsettled.</p><p><strong>Methods: </strong>This narrative review examines landmark and contemporary evidence from KEYNOTE-164, KEYNOTE-177, CheckMate 142, CheckMate 8HW, and the COMMIT trial, together with high-quality non-randomized cohort studies and ongoing trial data.</p><p><strong>Results: </strong>Pembrolizumab is the most mature first-line single-agent standard, with superior progression-free and overall survival versus chemotherapy and a well-characterized long-term safety profile. Nivolumab plus ipilimumab provides the strongest evidence for intensified dual checkpoint blockade and has demonstrated superiority over both chemotherapy and nivolumab monotherapy in randomized trials, but at the cost of substantially higher immune-related toxicity and treatment discontinuation rates. The COMMIT trial suggests a role for chemo-immunotherapy combinations, though sample size and early closure limit interpretation. Key factors influencing treatment selection include disease burden, metastatic pattern, performance status, biomarker confidence, and ability to manage immune-related adverse events.</p><p><strong>Conclusion: </strong>In the absence of a direct head-to-head comparison between pembrolizumab and nivolumab plus ipilimumab, treatment selection must integrate evidence strength, toxicity profile, patient fitness, and biologic context. Ongoing trials, including SEAMARK and the overall survival analysis of CheckMate 8HW, will further refine optimal first-line strategy.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":"57 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148412065","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":"Treatment Selection Beyond Second Line in Metastatic Colorectal Cancer: Practical Sequencing of Cytotoxic Salvage Therapy, Anti-angiogenic Agents, Rechallenge Strategies, and Biomarker-Guided Treatments.","authors":"Tamotsu Sagawa, Hiroyuki Nagashima, Koshi Fujikawa","doi":"10.1007/s12029-026-01524-9","DOIUrl":"10.1007/s12029-026-01524-9","url":null,"abstract":"<p><p>Treatment selection beyond second line in metastatic colorectal cancer (mCRC) has evolved from empirical salvage therapy to individualized sequencing. Regorafenib, trifluridine/tipiracil (FTD/TPI), FTD/TPI plus bevacizumab, and fruquintinib have established roles in refractory disease, but their optimal order remains patient-dependent. In parallel, biomarker-guided options for BRAF V600E, KRAS G12C, HER2-positive, MSI-H/dMMR, and rare fusion-positive tumors have expanded the treatment framework. After BREAKWATER, BRAF V600E-mutated mCRC should no longer be viewed only as a later-line subgroup, because eligible patients may already have received first-line encorafenib, cetuximab, and fluoropyrimidine-based chemotherapy. Anti-EGFR rechallenge, preferably guided by circulating tumor DNA, provides another biologically dynamic strategy for selected RAS/BRAF wild-type, left-sided tumors. In Japan, OncoGuide EpiLight has introduced clinically implementable DNA methylation testing, which may complement anti-EGFR sensitivity assessment but does not replace resistance-mutation testing. This review summarizes key evidence and proposes a practical scenario-based framework integrating molecular reassessment, comprehensive genomic profiling, residual toxicity, vascular risk, marrow reserve, frailty, patient preference, and trial access.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":"57 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148412119","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":"Inflammation and RNA-Related Polymorphisms in Resected Cholangiocarcinoma: Prognostic Associations in Intrahepatic and Perihilar Tumors.","authors":"Guanwu Wang, Dong Liu, Tarick M Al-Masri, Smiths S Lueong, Jens T Siveke, Tom Luedde, Florian W R Vondran, Georg Lurje, Ulf P Neumann, Lara R Heij, Jan Bednarsch","doi":"10.1007/s12029-026-01520-z","DOIUrl":"10.1007/s12029-026-01520-z","url":null,"abstract":"<p><strong>Background: </strong>Cholangiocarcinoma (CCA) is a heterogeneous and aggressive malignancy of the biliary tract, often classified into intrahepatic (iCCA) and perihilar (pCCA) subtypes. Inflammatory and RNA-regulatory pathways are implicated in CCA pathogenesis. However, the prognostic significance of related single nucleotide polymorphisms (SNPs) remains unclear.</p><p><strong>Method: </strong>We retrospectively analyzed nine candidate SNPs in inflammation- and RNA-related genes (IL4 rs2243250, IL17A rs4711998, TNIP1 rs7708392, CD274 rs822336, CDKN2B-AS1 rs10965215, NSRP1 rs6505162, MEG3 rs7158663, LOC105370003 rs7315438 and LncRNA PTCSC3 rs944289) in 229 patients with resected CCA (112 iCCA and 117 pCCA). Genotyping was performed using TaqMan assays. Associations between SNP genotypes and recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) were evaluated using Kaplan-Meier and Cox regression analyses stratified by anatomical subtype.</p><p><strong>Results: </strong>The study cohort comprised 229 patients undergoing curative-intent resection for CCA, including 112 iCCA and 117 pCCA cases. Median follow-up was 63 months for iCCA and 89 months for pCCA. Tumor recurrence occurred in 68.8% of iCCA and 54.7% of pCCA patients. No significant associations between SNP genotypes and clinical outcomes were identified in the pCCA cohort. In iCCA, isolated associations with overall survival were observed for TNIP1 rs7708392 and NSRP1 rs6505162, but these findings were not consistently supported across analyses and were limited by small subgroup sizes. No SNP demonstrated consistent associations with recurrence-free survival or cancer-specific survival.</p><p><strong>Conclusion: </strong>The investigated inflammation- and RNA-related SNPs showed no clinically relevant prognostic value in resected cholangiocarcinoma. Independent validation in larger multicenter cohorts remains warranted.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":"57 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13346121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148404939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Radiomics Models as Tools for Predicting Genetic Mutations in Colorectal Cancer: A Systematic Review and Meta-Analysis.","authors":"Yassin Rahnama, Amir Shahbazi, Anita Dadashi, Fatemeh Fathabadi, Faeze Salahshour, Sina Delazar, Mojtaba Sedaghat, Amir Keshvari, Alireza Kazemeini, Mohammad Reza Keramati, Mohammad Sadegh Fazeli, Behnam Behboudi, Seyed Mohsen Ahmadi-Tafti","doi":"10.1007/s12029-026-01522-x","DOIUrl":"10.1007/s12029-026-01522-x","url":null,"abstract":"<p><strong>Background: </strong>The evaluation of genetic mutations is crucial for personalized therapy in colorectal cancer (CRC), but the invasive tissue biopsy is subject to sampling bias and other complications. Radiomics has emerged as a non-invasive tool to predict these mutations from standard medical images. In this systematic review and meta-analysis, we aimed to evaluate the diagnostic accuracy and methodological quality of radiomics models for predicting key genetic mutations in CRC.</p><p><strong>Methods: </strong>A comprehensive search of PubMed, Scopus, Web of Science, and Embase was conducted in accordance with PRISMA guidelines. Studies evaluating radiomics models for predicting genetic mutations in CRC patients using pre-operative CT, MRI, or PET/CT were included. A meta-analysis of diagnostic accuracy was performed to calculate the pooled sensitivity, specificity. Methodological quality was assessed using the Radiomics Quality Score (RQS) and QUADAS-2 tools.</p><p><strong>Results: </strong>Sixteen studies were included in the quantitative analysis. The pooled sensitivity and specificity were 0.75 (95% CI, 0.67-0.81) and 0.78 (95% CI, 0.70-0.85), respectively, with an overall AUC of 0.79. Subgroup analyses revealed that radio-clinical models integrating both clinical and radiomics features achieved superior sensitivity compared to models with only radiological input. However, the overall methodological quality of the included studies was low, with a mean RQS of 45%.</p><p><strong>Conclusion: </strong>Conventional radiomics models demonstrate promising results for the non-invasive prediction of genetic mutations in CRC, with sensitivity enhanced by the integration of clinical data. Despite this potential, significant methodological shortcomings and heterogeneity across studies highlight the need for standardized protocols and large-scale, prospective validation before these models can be translated into routine clinical practice.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":"57 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148412063","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":"Tumour-Associated Neutrophils in Colorectal Cancer: a Systematic Review, Meta-analysis, and Comprehensive Literature Review.","authors":"Ana Beatriz Kinupe Abrahao, Tiago Cordeiro Felismino, David Kerr","doi":"10.1007/s12029-026-01517-8","DOIUrl":"10.1007/s12029-026-01517-8","url":null,"abstract":"<p><strong>Purpose: </strong>Neutrophils are at the forefront of innate immune response. The prognostic impact of tumour-associated neutrophils (TANs) remains unclear. This study aimed to evaluate the prognostic role of TANs in colorectal cancer (CRC).</p><p><strong>Methods: </strong>A systematic review and meta-analysis were conducted using PubMed, Embase, and Scopus to identify studies correlating TANs with time-to-event survival analysis in patients with stages I-IV CRC from the date of inception until April 2024. Articles were included if they involved the identification of TANs through hematoxylin-eosin (HE) or immunohistochemistry (IHC) and reported survival analysis. Data was collected from the tumour core (TC) and invasive margin (IM). The hazard ratios (HRs) were extracted from the study results. Heterogeneity was evaluated using Cochran's Q and I². Primary and secondary endpoints were overall survival (OS) and disease-free survival (DFS).</p><p><strong>Results: </strong>Of 4,292 citations found, 18 studies fulfilled eligibility criteria, encompassing 7,406 patients. IHC was used to identify TANs in 12 trials, while six performed HE. Five studies included patients with disease stages I-III, and 13 had stages I-IV. High TANs at the IM were associated with improved OS (HR = 0.64, 95% Confidence Interval [CI] 0.50-0.81, I² = 48%) and DFS (HR = 0.47, 95% CI 0.25-0.88, I² = 32%). At the TC, high TANs showed a trend towards better OS (HR = 0.82, 95% CI 0.61-1.10, I² = 83%) and DFS (HR = 0.48, 95% CI 0.21-1.07, I² = 93%), although not statistically significant and with high heterogeneity.</p><p><strong>Conclusion: </strong>In this systematic review and meta-analysis, high TANs at the invasive margin (IM), the tumour-host interface, was associated with improved prognosis in CRC. In contrast, no statistically significant association was observed for high TANs at the tumour core (TC).</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":"57 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13346145/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148404967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reverse-Bevel (ProCore) EUS-Guided Fine-Needle Biopsy for Solid Pancreatic Mass Lesions: a GRADE-Assessed Systematic Review and Meta-Analysis of Prospective Randomized Trials.","authors":"Wajahat Mirza, Maaz Bin Badshah, Interventional Gastroenterologist, Abdalla M Hadhoud, Muhammad Bilal Moeen-Ud-Din, Abdullah Imtiaz","doi":"10.1007/s12029-026-01518-7","DOIUrl":"10.1007/s12029-026-01518-7","url":null,"abstract":"<p><strong>Background and aims: </strong>Endoscopic ultrasound-guided tissue acquisition is used to diagnose pancreatic mass lesions, but optimal needle selection remains uncertain. Reverse bevel ProCore fine needle biopsy (FNB) needles aim to enhance histologic procurement and reduce sampling burden; randomized evidence versus standard fine needle aspiration (FNA) is limited. We synthesized randomized trials to compare diagnostic performance, efficiency, and safety.</p><p><strong>Methods: </strong>We searched MEDLINE (PubMed), Embase, Cochrane CENTRAL, Scopus, Web of Science, and ClinicalTrials.gov for randomized trials (parallel or crossover) comparing reverse bevel ProCore FNB with standard FNA in pancreatic masses. The primary outcome was diagnostic yield. Secondary outcomes included sensitivity, specificity, number of passes, sample adequacy, technical failure, and complications. Random effects meta-analysis pooled risk ratios and mean differences with 95% confidence intervals. Heterogeneity was assessed using I²; leave-one-out analyses explored high heterogeneity. Certainty of evidence was assessed with GRADE.</p><p><strong>Results: </strong>Five randomized trials (412 patients) were included. Diagnostic yield was equivalent (RR 0.99, 95% CI 0.94-1.05; I²=55%). Sensitivity (RR 1.03, 95% CI 0.96-1.11) and specificity (RR 1.05, 95% CI 0.87-1.27) were similar. ProCore required fewer passes (MD - 0.69, 95% CI - 1.11 to - 0.27; I²=79%). Sample adequacy was comparable (RR 1.02, 95% CI 0.90-1.16; I²=66%). Complications were uncommon (RR 1.93, 95% CI 0.57-6.58; I²=0%). Trial design did not modify diagnostic yield.</p><p><strong>Conclusions: </strong>Reverse bevel ProCore FNB provides diagnostic yield comparable to standard FNA while reducing needle passes. Low to very low certainty supports individualized needle choice based on resources and tissue requirements.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":"57 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148391174","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":"Outcomes of Epidermal Growth Factor Receptor Inhibitors in Locally Advanced and Metastatic Anal Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis.","authors":"Muhammad Shaheer Mannan, Adeena Musheer, Ahmad Basharat, Fatima Sial, Muhammad Waqas Khan, Anas Al-Sadi, Muhammad Kashif Amin, Moazzam Shahzad","doi":"10.1007/s12029-026-01521-y","DOIUrl":"10.1007/s12029-026-01521-y","url":null,"abstract":"<p><strong>Background: </strong>Anal squamous cell carcinoma (ASCC) is a rare malignancy with rising incidence and limited systemic options in recurrent or metastatic disease. Although epidermal growth factor receptor (EGFR) inhibitors show activity in other squamous cancers, their role in ASCC remains unclear due to fragmented evidence. This systematic review and meta-analysis evaluated the efficacy and safety of EGFR inhibitors in adults with locally advanced or metastatic ASCC.</p><p><strong>Methods: </strong>PubMed/MEDLINE, Cochrane CENTRAL, and ClinicalTrials.gov were searched from inception to December 2025 for studies of EGFR inhibitors in ASCC. Eligible designs included randomized trials, phase II studies, prospective or retrospective cohorts, and case series. Proportional meta-analyses were performed using fixed- or random-effects models according to heterogeneity.</p><p><strong>Results: </strong>Twelve studies including 404 patients were analyzed. Median age ranged from 47 to 65 years, and both locally advanced and metastatic settings were represented. The EGFR inhibitors cetuximab and panitumumab were administered with chemoradiotherapy in locally advanced disease or with systemic therapy in metastatic or refractory settings. The pooled objective response rate was 52% (95% CI: 36-68; I²=84.2%, τ²=0.0518, p < 0.0001), with a complete response rate of 37% (95% CI: 15-61; I²=94.0%, τ²=0.1287, p < 0.0001). Median overall survival was 11.9 months and progression-free survival 4.5 months. Grade ≥ 3 adverse events occurred in 56% of patients; treatment discontinuation was infrequent (8%), and no treatment-related deaths were reported.</p><p><strong>Conclusion: </strong>EGFR inhibitors show a reproducible signal of activity in locally advanced and metastatic ASCC with manageable toxicity, though evidence is limited by nonrandomized designs and heterogeneity; prospective, biomarker-driven studies are needed.</p>","PeriodicalId":15895,"journal":{"name":"Journal of Gastrointestinal Cancer","volume":"57 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148375302","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}