Pub Date : 2026-03-01Epub Date: 2026-02-17DOI: 10.1016/j.esmogo.2026.100307
H. Kodama , Y. Narita , K. Honda , T. Masuishi , H. Taniguchi , S. Kadowaki , M. Ando , M. Tajika , T. Yamaguchi , H. Nishikawa , K. Muro
Background
Nivolumab (NIVO), an immune checkpoint inhibitor (ICI) combined with chemotherapy, represents the standard of care for patients with human epidermal growth factor receptor 2-negative advanced gastric cancer (AGC). Although ICI readministration either as a rechallenge following disease progression or as a reintroduction after refractory has demonstrated clinical benefit and safety in patients with lung cancer or melanoma, evidence in AGC remains limited.
Patients and methods
This case series analyzed eight patients with AGC who received NIVO readministration monotherapy between September 2017 and December 2021.
Results
Six patients transitioned after disease progression, while two patients discontinued initial NIVO due to grade 2 pneumonitis. Among six patients with NIVO rechallenge, median progression-free survival (PFS) after rechallenge was 1.8 months [95% confidence interval (CI) 0.6-19.3 months], and median overall survival (OS) was 17.9 months (95% CI 1.8-42 months). Two patients achieved stable disease. Patients with ascites, Eastern Cooperative Oncology Group performance status of 1, or bulky liver/peritoneal metastasis tended toward shorter PFS and OS. Among two patients with NIVO reintroduction, one patient experienced a grade 2 rash; however, neither patient developed pneumonitis.
Conclusions
NIVO readministration may offer clinical benefit to selected patients with AGC, without inducing severe adverse events.
背景：Nivolumab （NIVO）是一种免疫检查点抑制剂（ICI）联合化疗，代表了人类表皮生长因子受体2阴性晚期胃癌（AGC）患者的标准护理。尽管在肺癌或黑色素瘤患者中，作为疾病进展后的再挑战或作为难治性复发后的再引入ICI已显示出临床益处和安全性，但在AGC中的证据仍然有限。患者和方法：本病例系列分析了2017年9月至2021年12月期间接受NIVO再给药单药治疗的8例AGC患者。结果：6例患者在疾病进展后过渡，2例患者因2级肺炎而停止初始NIVO。在6例NIVO再挑战患者中，再挑战后的中位无进展生存期（PFS）为1.8个月[95%置信区间（CI） 0.6-19.3个月]，中位总生存期（OS）为17.9个月（95% CI 1.8-42个月）。2例患者病情稳定。腹水、东部肿瘤合作组表现状态为1分或肝/腹膜转移较大的患者PFS和OS较短。在2例再次引入NIVO的患者中，1例患者出现2级皮疹；然而，两名患者均未发生肺炎。结论：NIVO再给药可为选定的AGC患者提供临床获益，且不会引起严重不良事件。
{"title":"Readministration of nivolumab for patients with advanced gastric cancer: a case series","authors":"H. Kodama , Y. Narita , K. Honda , T. Masuishi , H. Taniguchi , S. Kadowaki , M. Ando , M. Tajika , T. Yamaguchi , H. Nishikawa , K. Muro","doi":"10.1016/j.esmogo.2026.100307","DOIUrl":"10.1016/j.esmogo.2026.100307","url":null,"abstract":"<div><h3>Background</h3><div>Nivolumab (NIVO), an immune checkpoint inhibitor (ICI) combined with chemotherapy, represents the standard of care for patients with human epidermal growth factor receptor 2-negative advanced gastric cancer (AGC). Although ICI readministration either as a rechallenge following disease progression or as a reintroduction after refractory has demonstrated clinical benefit and safety in patients with lung cancer or melanoma, evidence in AGC remains limited.</div></div><div><h3>Patients and methods</h3><div>This case series analyzed eight patients with AGC who received NIVO readministration monotherapy between September 2017 and December 2021.</div></div><div><h3>Results</h3><div>Six patients transitioned after disease progression, while two patients discontinued initial NIVO due to grade 2 pneumonitis. Among six patients with NIVO rechallenge, median progression-free survival (PFS) after rechallenge was 1.8 months [95% confidence interval (CI) 0.6-19.3 months], and median overall survival (OS) was 17.9 months (95% CI 1.8-42 months). Two patients achieved stable disease. Patients with ascites, Eastern Cooperative Oncology Group performance status of 1, or bulky liver/peritoneal metastasis tended toward shorter PFS and OS. Among two patients with NIVO reintroduction, one patient experienced a grade 2 rash; however, neither patient developed pneumonitis.</div></div><div><h3>Conclusions</h3><div>NIVO readministration may offer clinical benefit to selected patients with AGC, without inducing severe adverse events.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"11 ","pages":"Article 100307"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147313943","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}
Pub Date : 2026-03-01Epub Date: 2026-02-10DOI: 10.1016/j.esmogo.2025.100299
T. Wakatsuki , T. Mashima , N. Miyazaki , H. Osumi , S. Fukuoka , A. Ooki , K. Shimozaki , M. Ogura , K. Yoshino , S. Udagawa , E. Shinozaki , K. Chin , N. Ishida , H. Seimiya , K. Yamaguchi
Background
Plasma vascular endothelial growth factor-A (VEGF-A) concentrations markedly increased immediately after ramucirumab administration, and the high VEGF-A concentrations were significantly associated with worse outcomes in advanced gastric cancer. In a preclinical study, combination therapy with anti-VEGF-A and anti-vascular endothelial growth factor receptor 2 (VEGFR2) antibodies showed superior tumor suppression compared with monotherapy, suggesting dual VEGF-A/VEGFR2 blockade may be a promising therapeutic strategy.
Design
The BevRam-GC01 trial is a phase I trial evaluating the tolerability and safety of bevacizumab biosimilar (5 or 10 mg/kg) plus ramucirumab (8 mg/kg) and paclitaxel (80 mg/m2) in patients with advanced gastric cancer refractory to first-line fluoropyrimidine–platinum chemotherapy. The study includes a safety part and an expansion part, in which, after confirming tolerability, patients will be randomized into three arms, including a control group, to obtain proof of concept and determine the optimal BEV-BS dose. Primary endpoints are dose-limiting toxicities in the safety part and adverse events in the expansion part. Key secondary endpoints include objective response rate and day 8 free VEGF-A suppression rate. Biomarker analysis will clarify the synergistic and complementary effects of anti-VEGFR2 and anti-VEGF-A antibodies on tumor biology, including angiogenesis, proliferation, and antitumor immunity, through multi-omics analysis and immune monitoring.
{"title":"BevRam-GC01 study protocol: a phase I trial of bevacizumab plus ramucirumab and paclitaxel in advanced gastric cancer","authors":"T. Wakatsuki , T. Mashima , N. Miyazaki , H. Osumi , S. Fukuoka , A. Ooki , K. Shimozaki , M. Ogura , K. Yoshino , S. Udagawa , E. Shinozaki , K. Chin , N. Ishida , H. Seimiya , K. Yamaguchi","doi":"10.1016/j.esmogo.2025.100299","DOIUrl":"10.1016/j.esmogo.2025.100299","url":null,"abstract":"<div><h3>Background</h3><div>Plasma vascular endothelial growth factor-A (VEGF-A) concentrations markedly increased immediately after ramucirumab administration, and the high VEGF-A concentrations were significantly associated with worse outcomes in advanced gastric cancer. In a preclinical study, combination therapy with anti-VEGF-A and anti-vascular endothelial growth factor receptor 2 (VEGFR2) antibodies showed superior tumor suppression compared with monotherapy, suggesting dual VEGF-A/VEGFR2 blockade may be a promising therapeutic strategy.</div></div><div><h3>Design</h3><div>The BevRam-GC01 trial is a phase I trial evaluating the tolerability and safety of bevacizumab biosimilar (5 or 10 mg/kg) plus ramucirumab (8 mg/kg) and paclitaxel (80 mg/m<sup>2</sup>) in patients with advanced gastric cancer refractory to first-line fluoropyrimidine–platinum chemotherapy. The study includes a safety part and an expansion part, in which, after confirming tolerability, patients will be randomized into three arms, including a control group, to obtain proof of concept and determine the optimal BEV-BS dose. Primary endpoints are dose-limiting toxicities in the safety part and adverse events in the expansion part. Key secondary endpoints include objective response rate and day 8 free VEGF-A suppression rate. Biomarker analysis will clarify the synergistic and complementary effects of anti-VEGFR2 and anti-VEGF-A antibodies on tumor biology, including angiogenesis, proliferation, and antitumor immunity, through multi-omics analysis and immune monitoring.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"11 ","pages":"Article 100299"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146188607","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}
Pub Date : 2026-03-01Epub Date: 2026-02-13DOI: 10.1016/j.esmogo.2025.100284
L.M. Stoffels , E.S. Espinoza Rodriguez , J. Theys , R. Shiri-Sverdlov
Hepatocellular carcinoma (HCC) ranks as the fourth leading cause of cancer-related mortality worldwide and poses a substantial challenge in the field of oncology. The majority of patients are diagnosed at advanced stages of the disease, where systemic therapies remain the primary treatment modality. These interventions, however, are frequently constrained by limited efficacy and considerable adverse effects, highlighting the pressing need for more precise and effective therapeutic strategies. Emerging evidence has identified cholesterol as a critical factor in HCC pathogenesis, influencing key processes such as tumor initiation, cellular proliferation, immune dysregulation, and metastatic progression. Moreover, disruptions in cholesterol metabolism have been increasingly implicated in resistance to systemic treatments. This review provides a concise overview of therapeutic approaches targeting cholesterol in HCC and examines the influence of cholesterol metabolism on the efficacy of systemic therapies, particularly those currently considered standard of care. Finally, we discuss existing challenges and propose future directions for integrating cholesterol-lowering strategies to enhance treatment outcomes in patients with HCC.
{"title":"Revisiting cholesterol metabolism in hepatocellular carcinoma: a hidden driver of systemic therapy response","authors":"L.M. Stoffels , E.S. Espinoza Rodriguez , J. Theys , R. Shiri-Sverdlov","doi":"10.1016/j.esmogo.2025.100284","DOIUrl":"10.1016/j.esmogo.2025.100284","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) ranks as the fourth leading cause of cancer-related mortality worldwide and poses a substantial challenge in the field of oncology. The majority of patients are diagnosed at advanced stages of the disease, where systemic therapies remain the primary treatment modality. These interventions, however, are frequently constrained by limited efficacy and considerable adverse effects, highlighting the pressing need for more precise and effective therapeutic strategies. Emerging evidence has identified cholesterol as a critical factor in HCC pathogenesis, influencing key processes such as tumor initiation, cellular proliferation, immune dysregulation, and metastatic progression. Moreover, disruptions in cholesterol metabolism have been increasingly implicated in resistance to systemic treatments. This review provides a concise overview of therapeutic approaches targeting cholesterol in HCC and examines the influence of cholesterol metabolism on the efficacy of systemic therapies, particularly those currently considered standard of care. Finally, we discuss existing challenges and propose future directions for integrating cholesterol-lowering strategies to enhance treatment outcomes in patients with HCC.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"11 ","pages":"Article 100284"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146188604","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}
Pub Date : 2026-03-01Epub Date: 2026-02-24DOI: 10.1016/j.esmogo.2026.100310
Y. Nagata , H. Arai , N. Izawa , C. Inagaki , A. Sugaya , K. Hirata , T. Tsushima , T. Moriwaki , T. Masuishi , Y. Nagatani , K. Harada , M. Taguri , Y. Sunakawa
Introduction
The addition of immune checkpoint inhibitors (ICIs) to chemotherapy has significantly improved the prognosis of patients with metastatic esophageal cancer. Although fluorouracil and cisplatin (FP) combined with an ICI is considered one of the most effective first-line treatments, patients with severe dysphagia have not been adequately evaluated. Radiotherapy (RT) and chemoradiotherapy (CRT), however, have been established as effective treatment options for dysphagia, based on the results of a phase III clinical trial conducted before the approval of ICIs for esophageal cancer. This study aims to evaluate the efficacy and safety of FP plus ICI and FP plus ICI following RT/CRT in patients with stage IVB esophageal cancer and severe dysphagia.
Methods
This is a randomized, non-comparative, pragmatic phase II trial enrolling untreated patients with metastatic esophageal or esophagogastric squamous cell carcinoma and severe dysphagia. Patients are randomized to receive either FP plus ICI (arm A) or FP plus ICI following RT/CRT (arm B) in accordance with clinical practice. The primary endpoint is dysphagia relief rate at 9 weeks from the initiation of treatment. This trial has been ongoing since December 2024.
{"title":"A pragmatic phase II trial evaluating treatment strategies using immune checkpoint inhibitors for metastatic esophageal cancer patients with severe dysphagia","authors":"Y. Nagata , H. Arai , N. Izawa , C. Inagaki , A. Sugaya , K. Hirata , T. Tsushima , T. Moriwaki , T. Masuishi , Y. Nagatani , K. Harada , M. Taguri , Y. Sunakawa","doi":"10.1016/j.esmogo.2026.100310","DOIUrl":"10.1016/j.esmogo.2026.100310","url":null,"abstract":"<div><h3>Introduction</h3><div>The addition of immune checkpoint inhibitors (ICIs) to chemotherapy has significantly improved the prognosis of patients with metastatic esophageal cancer. Although fluorouracil and cisplatin (FP) combined with an ICI is considered one of the most effective first-line treatments, patients with severe dysphagia have not been adequately evaluated. Radiotherapy (RT) and chemoradiotherapy (CRT), however, have been established as effective treatment options for dysphagia, based on the results of a phase III clinical trial conducted before the approval of ICIs for esophageal cancer. This study aims to evaluate the efficacy and safety of FP plus ICI and FP plus ICI following RT/CRT in patients with stage IVB esophageal cancer and severe dysphagia.</div></div><div><h3>Methods</h3><div>This is a randomized, non-comparative, pragmatic phase II trial enrolling untreated patients with metastatic esophageal or esophagogastric squamous cell carcinoma and severe dysphagia. Patients are randomized to receive either FP plus ICI (arm A) or FP plus ICI following RT/CRT (arm B) in accordance with clinical practice. The primary endpoint is dysphagia relief rate at 9 weeks from the initiation of treatment. This trial has been ongoing since December 2024.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"11 ","pages":"Article 100310"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147358358","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}
Pub Date : 2026-03-01Epub Date: 2026-01-06DOI: 10.1016/j.esmogo.2025.100280
Y. Sekiguchi , K. Shibuya , S. Tomogane , Y. Miyasaka , S. Kakizaki , M. Okamoto , K. Araki , K. Shirabe , T. Ohno
Background
Transarterial chemoembolization (TACE) or embolization (TAE) for hepatocellular carcinoma (HCC) is often followed by an incomplete response or local recurrence, necessitating effective salvage therapies. Carbon-ion radiotherapy (CIRT) offers potential radiobiological advantages for treating TACE-refractory tumors. This study aimed to evaluate the efficacy and safety of CIRT for residual or recurrent HCC after TACE/TAE.
Patients and methods
We retrospectively analyzed 99 patients (106 lesions) treated with CIRT between 2010 and 2021. Eligible patients had residual or recurrent HCC after 52.8-60.0 Gy [relative biological effectiveness (RBE)] in 4 fractions, or 60.0 Gy (RBE) in 12 fractions for tumors near critical structures. Efficacy endpoints were local control (LC), overall survival (OS), and progression-free survival (PFS). Toxicities were graded using the Common Terminology Criteria for Adverse Events version 4.0, and liver function was monitored using Child–Pugh and albumin–bilirubin (ALBI) scores.
Results
At a median follow-up of 38 months, the 3-year OS, PFS, and LC rates were 70.3%, 34.8%, and 90.7%, respectively. On multivariate analysis, larger tumor size (≥3.5 cm) and poorer baseline liver function (modified ALBI grade ≥2b) were significant predictors of worse OS. The treatment was well tolerated; severe (grade ≥3) late toxicities were rare, including two cases of encephalopathy. There was no statistically significant deterioration in Child–Pugh or ALBI scores following treatment.
Conclusions
CIRT is a safe and effective salvage therapy for TACE-refractory HCC, offering excellent LC, favorable survival outcomes, and preserved liver function.
{"title":"Clinical outcomes of carbon-ion radiotherapy for residual or recurrent hepatocellular carcinoma after transarterial chemoembolization","authors":"Y. Sekiguchi , K. Shibuya , S. Tomogane , Y. Miyasaka , S. Kakizaki , M. Okamoto , K. Araki , K. Shirabe , T. Ohno","doi":"10.1016/j.esmogo.2025.100280","DOIUrl":"10.1016/j.esmogo.2025.100280","url":null,"abstract":"<div><h3>Background</h3><div>Transarterial chemoembolization (TACE) or embolization (TAE) for hepatocellular carcinoma (HCC) is often followed by an incomplete response or local recurrence, necessitating effective salvage therapies. Carbon-ion radiotherapy (CIRT) offers potential radiobiological advantages for treating TACE-refractory tumors. This study aimed to evaluate the efficacy and safety of CIRT for residual or recurrent HCC after TACE/TAE.</div></div><div><h3>Patients and methods</h3><div>We retrospectively analyzed 99 patients (106 lesions) treated with CIRT between 2010 and 2021. Eligible patients had residual or recurrent HCC after 52.8-60.0 Gy [relative biological effectiveness (RBE)] in 4 fractions, or 60.0 Gy (RBE) in 12 fractions for tumors near critical structures. Efficacy endpoints were local control (LC), overall survival (OS), and progression-free survival (PFS). Toxicities were graded using the Common Terminology Criteria for Adverse Events version 4.0, and liver function was monitored using Child–Pugh and albumin–bilirubin (ALBI) scores.</div></div><div><h3>Results</h3><div>At a median follow-up of 38 months, the 3-year OS, PFS, and LC rates were 70.3%, 34.8%, and 90.7%, respectively. On multivariate analysis, larger tumor size (≥3.5 cm) and poorer baseline liver function (modified ALBI grade ≥2b) were significant predictors of worse OS. The treatment was well tolerated; severe (grade ≥3) late toxicities were rare, including two cases of encephalopathy. There was no statistically significant deterioration in Child–Pugh or ALBI scores following treatment.</div></div><div><h3>Conclusions</h3><div>CIRT is a safe and effective salvage therapy for TACE-refractory HCC, offering excellent LC, favorable survival outcomes, and preserved liver function.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"11 ","pages":"Article 100280"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145926804","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}
Pub Date : 2026-03-01Epub Date: 2026-01-08DOI: 10.1016/j.esmogo.2025.100282
M.P.G. Camandaroba, S. Aguiar Jr., V. Souza e Silva, R.P. Riechelmann
Background
Squamous-cell carcinoma of the anal canal (SCCA) is a rare gastrointestinal malignancy, and its incidence is increasing among the aging population. This study aims to examine treatment efficacy and toxicity in elderly patients and to compare treatment outcomes between elderly and non-elderly patients to inform optimal management strategies for SCCA in older adults.
Patients and methods
This retrospective study evaluates clinical outcomes in elderly (≥70 years) versus non-elderly (<70 years) patients with localized SCCA treated with definitive chemoradiotherapy or radiotherapy alone. The primary endpoints were overall survival (OS) and disease-free survival (DFS), whereas secondary endpoints were cancer-specific survival (CSS), complete response rates and grade 3 or 4 toxicity profiles. Statistical analyses were conducted using descriptive statistics, Kaplan–Meier methods, and Cox proportional hazards models.
Results
The study analyzed 269 patients. Elderly patients had a median age of 77.3 (range 70-83) years and presented with a higher burden of comorbidities and a lower prevalence of human immunodeficiency virus. No significant differences in treatment types or toxicity rates were observed between the groups. The median DFS for elderly patients was 103 months versus 128 months for non-elderly patients (P = 0.43). CSS rates were comparable, showing a rate of 83% at five years for the elderly compared with 85% for non-elderly patients (P = 0.74). Cox regression analyses revealed that cancer stage and treatment completion were significant predictors of DFS and OS.
Conclusion
This study highlights that while elderly patients with SCCA experience similar survival outcomes to their younger counterparts, age-related factors and comorbidities require careful management to optimize treatment efficacy while minimizing toxicity.
{"title":"The outcomes of elderly patients with localized squamous-cell carcinoma of the anal canal treated with chemoradiation","authors":"M.P.G. Camandaroba, S. Aguiar Jr., V. Souza e Silva, R.P. Riechelmann","doi":"10.1016/j.esmogo.2025.100282","DOIUrl":"10.1016/j.esmogo.2025.100282","url":null,"abstract":"<div><h3>Background</h3><div>Squamous-cell carcinoma of the anal canal (SCCA) is a rare gastrointestinal malignancy, and its incidence is increasing among the aging population. This study aims to examine treatment efficacy and toxicity in elderly patients and to compare treatment outcomes between elderly and non-elderly patients to inform optimal management strategies for SCCA in older adults.</div></div><div><h3>Patients and methods</h3><div>This retrospective study evaluates clinical outcomes in elderly (≥70 years) versus non-elderly (<70 years) patients with localized SCCA treated with definitive chemoradiotherapy or radiotherapy alone. The primary endpoints were overall survival (OS) and disease-free survival (DFS), whereas secondary endpoints were cancer-specific survival (CSS), complete response rates and grade 3 or 4 toxicity profiles. Statistical analyses were conducted using descriptive statistics, Kaplan–Meier methods, and Cox proportional hazards models.</div></div><div><h3>Results</h3><div>The study analyzed 269 patients. Elderly patients had a median age of 77.3 (range 70-83) years and presented with a higher burden of comorbidities and a lower prevalence of human immunodeficiency virus. No significant differences in treatment types or toxicity rates were observed between the groups. The median DFS for elderly patients was 103 months versus 128 months for non-elderly patients (<em>P</em> = 0.43). CSS rates were comparable, showing a rate of 83% at five years for the elderly compared with 85% for non-elderly patients (<em>P</em> = 0.74). Cox regression analyses revealed that cancer stage and treatment completion were significant predictors of DFS and OS.</div></div><div><h3>Conclusion</h3><div>This study highlights that while elderly patients with SCCA experience similar survival outcomes to their younger counterparts, age-related factors and comorbidities require careful management to optimize treatment efficacy while minimizing toxicity.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"11 ","pages":"Article 100282"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145926897","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}
Pub Date : 2026-03-01Epub Date: 2026-03-02DOI: 10.1016/j.esmogo.2026.100314
L.B. Callesen , K.-L.G. Spindler
Background
Circulating tumor DNA (ctDNA) kinetics have emerged as a promising biomarker for monitoring treatment response in metastatic colorectal cancer (mCRC). We carried out a systematic review and meta-analysis to comprehensively assess the prognostic value of ctDNA kinetics during palliative systemic therapy, aiming to consolidate the current evidence and clarify its potential role in clinical practice.
Materials and methods
PubMed, Embase, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials were searched (last search 12 September 2025). Eligible studies assessed the association between ctDNA kinetics and outcomes in patients with mCRC receiving systemic palliative treatment. Meta-analyses were carried out to evaluate associations with survival outcomes.
Results
A total of 64 studies, including data from >2760 patients with mCRC receiving palliative systemic therapy, met the eligibility criteria. Across studies, unfavorable ctDNA kinetics were consistently associated with poorer outcomes, including shorter overall survival (OS) [pooled hazard ratio (HR) 2.6, 95% confidence interval (CI) 2.2-3.2, n = 1086] and progression-free survival (PFS) (pooled HR 2.7, 95% CI 2.4-3.1, n = 1093).
Conclusion
ctDNA kinetics during palliative systemic therapy have strong prognostic value in mCRC. However, clinical implementation is hampered by methodological heterogeneity, particularly the use of study-specific ctDNA markers and non-validated cut-offs. Standardized and externally validated approaches are needed to support clinical implementation.
循环肿瘤DNA （ctDNA）动力学已成为监测转移性结直肠癌（mCRC）治疗反应的一种有前景的生物标志物。我们进行了一项系统回顾和荟萃分析，以全面评估姑息性全身治疗中ctDNA动力学的预后价值，旨在巩固现有证据并阐明其在临床实践中的潜在作用。检索spubmed、Embase、Cochrane系统评价数据库和Cochrane中央对照试验注册库（最后检索日期为2025年9月12日）。符合条件的研究评估了ctDNA动力学与接受全身姑息治疗的mCRC患者预后之间的关系。进行了荟萃分析来评估与生存结果的关系。结果共有64项研究（包括2760例接受姑息性全身治疗的mCRC患者）符合入选标准。在所有研究中，不利的ctDNA动力学始终与较差的结果相关，包括较短的总生存期（OS）[合并风险比（HR） 2.6, 95%置信区间（CI） 2.2-3.2, n = 1086]和无进展生存期（PFS）（合并风险比2.7,95% CI 2.4-3.1, n = 1093）。结论姑息性全身治疗期间dna动力学对mCRC患者的预后有较强的预测价值。然而，临床实施受到方法学异质性的阻碍，特别是使用研究特异性ctDNA标记和未经验证的切断。需要标准化和外部验证的方法来支持临床实施。
{"title":"Systematic review and meta-analysis of studies assessing circulating tumor DNA kinetics in metastatic colorectal cancer","authors":"L.B. Callesen , K.-L.G. Spindler","doi":"10.1016/j.esmogo.2026.100314","DOIUrl":"10.1016/j.esmogo.2026.100314","url":null,"abstract":"<div><h3>Background</h3><div>Circulating tumor DNA (ctDNA) kinetics have emerged as a promising biomarker for monitoring treatment response in metastatic colorectal cancer (mCRC). We carried out a systematic review and meta-analysis to comprehensively assess the prognostic value of ctDNA kinetics during palliative systemic therapy, aiming to consolidate the current evidence and clarify its potential role in clinical practice.</div></div><div><h3>Materials and methods</h3><div>PubMed, Embase, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials were searched (last search 12 September 2025). Eligible studies assessed the association between ctDNA kinetics and outcomes in patients with mCRC receiving systemic palliative treatment. Meta-analyses were carried out to evaluate associations with survival outcomes.</div></div><div><h3>Results</h3><div>A total of 64 studies, including data from >2760 patients with mCRC receiving palliative systemic therapy, met the eligibility criteria. Across studies, unfavorable ctDNA kinetics were consistently associated with poorer outcomes, including shorter overall survival (OS) [pooled hazard ratio (HR) 2.6, 95% confidence interval (CI) 2.2-3.2, <em>n</em> = 1086] and progression-free survival (PFS) (pooled HR 2.7, 95% CI 2.4-3.1, <em>n</em> = 1093).</div></div><div><h3>Conclusion</h3><div>ctDNA kinetics during palliative systemic therapy have strong prognostic value in mCRC. However, clinical implementation is hampered by methodological heterogeneity, particularly the use of study-specific ctDNA markers and non-validated cut-offs. Standardized and externally validated approaches are needed to support clinical implementation.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"11 ","pages":"Article 100314"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147421126","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}
Pub Date : 2026-03-01Epub Date: 2026-01-14DOI: 10.1016/j.esmogo.2025.100271
C. Smolenschi , M. Rémond , M. Valéry , M. Brugel , M. Ducreux , A. Turpin , A. Boilève
Biliary tract cancer and pancreatic cancer are aggressive malignancies, typically diagnosed in patients >50 years of age. Lately, <50 years of age has been rising, presenting unique challenges and clinical features that distinguish them from late-onset cases.
Here, we review the clinical, biological, and molecular characteristics of early-onset biliary tract cancer and pancreatic cancer and compare them with their late-onset counterparts. We also examine treatment patterns, efficacy, and the potential role of targeted therapies, as well as the potential psychological and social effects on younger patients, with particular emphasis on fertility. We therefore offer insights into the unique challenges and therapeutic strategies in managing early-onset disease.
{"title":"Clinical and molecular characteristics of early-onset pancreatic and biliary cancers","authors":"C. Smolenschi , M. Rémond , M. Valéry , M. Brugel , M. Ducreux , A. Turpin , A. Boilève","doi":"10.1016/j.esmogo.2025.100271","DOIUrl":"10.1016/j.esmogo.2025.100271","url":null,"abstract":"<div><div>Biliary tract cancer and pancreatic cancer are aggressive malignancies, typically diagnosed in patients >50 years of age. Lately, <50 years of age has been rising, presenting unique challenges and clinical features that distinguish them from late-onset cases.</div><div>Here, we review the clinical, biological, and molecular characteristics of early-onset biliary tract cancer and pancreatic cancer and compare them with their late-onset counterparts. We also examine treatment patterns, efficacy, and the potential role of targeted therapies, as well as the potential psychological and social effects on younger patients, with particular emphasis on fertility. We therefore offer insights into the unique challenges and therapeutic strategies in managing early-onset disease.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"11 ","pages":"Article 100271"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145978116","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}
Pub Date : 2026-03-01Epub Date: 2026-02-04DOI: 10.1016/j.esmogo.2025.100273
H.C. Wilbur , L.X. Zhao , M. Nakazawa , C. Kao , J.D. Gordan , T.P. Gade , L. Cope , L.T. Kagohara , D. Zabransky , W.J. Ho , M. Baretti , M. Yarchoan
Background
Immune checkpoint inhibitors (ICIs), or the combination of ICIs and vascular endothelial growth factor (VEGF) inhibitors, are the preferred treatments for advanced hepatocellular carcinoma (HCC). However, the immunomodulatory effects of anti-VEGF therapy in HCC remain poorly understood. Predictive biomarkers are needed to guide therapy selection.
Patients and methods
We prospectively analyzed circulating cytokines in patients with advanced HCC receiving ICIs with or without anti-VEGF inhibitor therapy as standard of care. Serum samples were collected at baseline and ∼2 months after treatment initiation. A 32-cytokine Luminex panel was used to assess systemic immune changes. We examined associations between treatment group, cytokine dynamics, and clinical outcomes.
Results
Among 56 enrolled patients, 35 patients were treated with ICIs only (ICI-only), and 21 patients were treated with ICIs plus the VEGF inhibitor bevacizumab (ICI + Bev). Demographic characteristics and treatment outcomes were generally balanced between the two groups. As compared with ICI-only, patients receiving ICI + Bev exhibited significantly reduced fold changes in multiple cytokines on treatment, including sCD40L, macrophage inflammatory protein-1β (MIP-1β), monokine induced by interferon-γ (MIG), and interleukin (IL)-1Ra, of which above-median circulating baseline levels of MIP-1β were associated with inferior clinical outcomes. In addition, patients with above-median circulating levels of IL-6 and IL-12p40 at baseline had longer progression-free survival with ICI + Bev versus ICI-only. Treatment-associated reductions in IL-1Ra, IL-8, IL-18, and VEGF-A were associated with favorable clinical outcomes.
Conclusions
In a highly exploratory analysis, myeloid-inflammatory signatures at baseline and treatment-associated reductions in key myeloid cytokines may identify patients most likely to benefit from adding Bev to ICI. Prospective validation of these markers in independent cohorts is warranted.
{"title":"Baseline and dynamic cytokines as biomarkers for immune checkpoint and anti-VEGF therapy in advanced hepatocellular carcinoma","authors":"H.C. Wilbur , L.X. Zhao , M. Nakazawa , C. Kao , J.D. Gordan , T.P. Gade , L. Cope , L.T. Kagohara , D. Zabransky , W.J. Ho , M. Baretti , M. Yarchoan","doi":"10.1016/j.esmogo.2025.100273","DOIUrl":"10.1016/j.esmogo.2025.100273","url":null,"abstract":"<div><h3>Background</h3><div>Immune checkpoint inhibitors (ICIs), or the combination of ICIs and vascular endothelial growth factor (VEGF) inhibitors, are the preferred treatments for advanced hepatocellular carcinoma (HCC). However, the immunomodulatory effects of anti-VEGF therapy in HCC remain poorly understood. Predictive biomarkers are needed to guide therapy selection.</div></div><div><h3>Patients and methods</h3><div>We prospectively analyzed circulating cytokines in patients with advanced HCC receiving ICIs with or without anti-VEGF inhibitor therapy as standard of care. Serum samples were collected at baseline and ∼2 months after treatment initiation. A 32-cytokine Luminex panel was used to assess systemic immune changes. We examined associations between treatment group, cytokine dynamics, and clinical outcomes.</div></div><div><h3>Results</h3><div>Among 56 enrolled patients, 35 patients were treated with ICIs only (ICI-only), and 21 patients were treated with ICIs plus the VEGF inhibitor bevacizumab (ICI + Bev). Demographic characteristics and treatment outcomes were generally balanced between the two groups. As compared with ICI-only, patients receiving ICI + Bev exhibited significantly reduced fold changes in multiple cytokines on treatment, including sCD40L, macrophage inflammatory protein-1β (MIP-1β), monokine induced by interferon-γ (MIG), and interleukin (IL)-1Ra, of which above-median circulating baseline levels of MIP-1β were associated with inferior clinical outcomes. In addition, patients with above-median circulating levels of IL-6 and IL-12p40 at baseline had longer progression-free survival with ICI + Bev versus ICI-only. Treatment-associated reductions in IL-1Ra, IL-8, IL-18, and VEGF-A were associated with favorable clinical outcomes.</div></div><div><h3>Conclusions</h3><div>In a highly exploratory analysis, myeloid-inflammatory signatures at baseline and treatment-associated reductions in key myeloid cytokines may identify patients most likely to benefit from adding Bev to ICI. Prospective validation of these markers in independent cohorts is warranted.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"11 ","pages":"Article 100273"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146188601","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}
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