ESMO Gastrointestinal Oncology最新文献

Treatment attrition between lines of therapy and its impact on outcomes for well-differentiated neuroendocrine tumors in British Columbia 不列颠哥伦比亚省分化良好的神经内分泌肿瘤治疗线之间的治疗损耗及其对预后的影响

ESMO Gastrointestinal Oncology

Pub Date : 2026-01-31 DOI: 10.1016/j.esmogo.2026.100305

R. Fedrigo , T. do Amaral Miranda , R. D’Alpino Peioxoto , S. Gill , F. Benard , D. Wilson , P. Martineau , I. Alberts , J.P. Solar Vasconcelos , J.M. Loree

Background

Neuroendocrine neoplasms are uncommon malignancies with variable prognosis. With a growing number of available therapies and recent data supporting earlier initiation of radioligand therapy, we aimed to characterize attrition between lines of therapy to inform treatment sequencing and establish baseline assumptions for future health technology assessments.

Patients and methods

In this retrospective chart review, patients with metastatic gastroenteropancreatic neuroendocrine tumors (NETs) who received one or more systemic therapies from January 2010 to December 2023 were reviewed. The primary endpoint was attrition between treatment lines. Logistic regression model was used to identify predictors of attrition.

Results

Among 234 patients, 65 (28%) had pancreatic NETs (pNETs) and 169 (72%) had extra-pancreatic gastrointestinal NETs (ep-GI-NETs); median age at diagnosis was 65 years. Maximum number of treatment lines was six for pNETs and four for ep-GI-NETs. First-to-second-line attrition rates were 22% [95% confidence interval (CI) 13% to 36%] and 34% (95% CI 25% to 44%) for pNETs and ep-GI-NETs, respectively. Somatostatin analogs were the preferred first line in 194 patients (83%). Peptide receptor radionuclide therapy was administered to 13 pNETs (20%) and 42 ep-GI-NETs (25%). Median first-line progression-free survival (PFS) was 8.8 months and 26.1 months for pNETs and ep-GI-NETs, respectively. Patients treated in the latter cohort (2021-2023) had a lower risk of attrition compared with those in the earlier cohort (2010-2020) (odds ratio 0.38, 95% CI 0.14-0.94, P = 0.046).

Conclusions

Despite longer first-line PFS, patients with ep-GI-NETs faced higher attrition rates. These findings emphasize the need to prioritize the most effective therapies early during treatment sequencing to ensure patients are exposed to the most active agents.

背景：神经内分泌肿瘤是一种少见的恶性肿瘤，预后不一。随着越来越多的可用治疗方法和最近的数据支持早期开始放射配体治疗，我们的目标是表征治疗线之间的损耗，为治疗排序提供信息，并为未来的卫生技术评估建立基线假设。患者和方法本研究回顾性分析了2010年1月至2023年12月期间接受一种或多种全身治疗的转移性胃肠胰神经内分泌肿瘤（NETs）患者。主要终点是治疗线之间的损耗。采用Logistic回归模型确定减员的预测因子。结果234例患者中，65例（28%）存在胰腺NETs (pNETs)， 169例（72%）存在胰腺外胃肠道NETs (ep-GI-NETs)；确诊时的中位年龄为65岁。pNETs最多处理6条，ep-GI-NETs最多处理4条。pNETs和ep-GI-NETs的一线至二线流失率分别为22%[95%置信区间（CI） 13%至36%]和34% （95% CI 25%至44%）。生长抑素类似物是194例（83%）患者首选的一线药物。对13例pNETs（20%）和42例ep-GI-NETs（25%）进行肽受体放射性核素治疗。pNETs和ep-GI-NETs的中位一线无进展生存期（PFS）分别为8.8个月和26.1个月。与早期队列（2010-2020）相比，后一队列（2021-2023）患者的磨耗风险较低（优势比0.38,95% CI 0.14-0.94, P = 0.046）。结论：尽管有较长的一线PFS， ep-GI-NETs患者面临较高的损耗率。这些发现强调需要在治疗排序的早期优先考虑最有效的治疗方法，以确保患者接触到最活跃的药物。

{"title":"Treatment attrition between lines of therapy and its impact on outcomes for well-differentiated neuroendocrine tumors in British Columbia","authors":"R. Fedrigo , T. do Amaral Miranda , R. D’Alpino Peioxoto , S. Gill , F. Benard , D. Wilson , P. Martineau , I. Alberts , J.P. Solar Vasconcelos , J.M. Loree","doi":"10.1016/j.esmogo.2026.100305","DOIUrl":"10.1016/j.esmogo.2026.100305","url":null,"abstract":"<div><h3>Background</h3><div>Neuroendocrine neoplasms are uncommon malignancies with variable prognosis. With a growing number of available therapies and recent data supporting earlier initiation of radioligand therapy, we aimed to characterize attrition between lines of therapy to inform treatment sequencing and establish baseline assumptions for future health technology assessments.</div></div><div><h3>Patients and methods</h3><div>In this retrospective chart review, patients with metastatic gastroenteropancreatic neuroendocrine tumors (NETs) who received one or more systemic therapies from January 2010 to December 2023 were reviewed. The primary endpoint was attrition between treatment lines. Logistic regression model was used to identify predictors of attrition.</div></div><div><h3>Results</h3><div>Among 234 patients, 65 (28%) had pancreatic NETs (pNETs) and 169 (72%) had extra-pancreatic gastrointestinal NETs (ep-GI-NETs); median age at diagnosis was 65 years. Maximum number of treatment lines was six for pNETs and four for ep-GI-NETs. First-to-second-line attrition rates were 22% [95% confidence interval (CI) 13% to 36%] and 34% (95% CI 25% to 44%) for pNETs and ep-GI-NETs, respectively. Somatostatin analogs were the preferred first line in 194 patients (83%). Peptide receptor radionuclide therapy was administered to 13 pNETs (20%) and 42 ep-GI-NETs (25%). Median first-line progression-free survival (PFS) was 8.8 months and 26.1 months for pNETs and ep-GI-NETs, respectively. Patients treated in the latter cohort (2021-2023) had a lower risk of attrition compared with those in the earlier cohort (2010-2020) (odds ratio 0.38, 95% CI 0.14-0.94, <em>P</em> = 0.046).</div></div><div><h3>Conclusions</h3><div>Despite longer first-line PFS, patients with ep-GI-NETs faced higher attrition rates. These findings emphasize the need to prioritize the most effective therapies early during treatment sequencing to ensure patients are exposed to the most active agents.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"11 ","pages":"Article 100305"},"PeriodicalIF":0.0,"publicationDate":"2026-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078106","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}

引用次数: 0

Impact of nutritional risk screening on outcomes of first-line treatment in metastatic esophagogastric adenocarcinoma: a secondary analysis of the AIO-MATEO trial 营养风险筛查对转移性食管胃腺癌一线治疗结果的影响：AIO-MATEO试验的二次分析

ESMO Gastrointestinal Oncology

Pub Date : 2026-01-27 DOI: 10.1016/j.esmogo.2025.100297

R. Stelmach , S. Lorenzen , T.J. Ettrich , F.R. Longo , B. Chibaudel , R. Greil , M. Perwög , J. Larcher-Steiner , D. Jäger , F. Lordick , G. Stocker , G.M. Haag

Background

Malnutrition is common in patients with metastatic esophagogastric adenocarcinoma (EGA). However, the prognostic impact of nutritional risk screening (NRS) in advanced EGA remains underexplored. This preplanned analysis of the phase II AIO-MATEO trial evaluated the impact of NRS on clinical outcomes for patients with advanced EGA.

Patients and methods

Patients enrolled in the MATEO trial (exploring S-1 maintenance therapy) with an available baseline NRS before induction chemotherapy were included. Patients were stratified by their baseline NRS score (<3 versus ≥3). Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan–Meier and Cox regression methods.

Results

Of the 136 patients, 86 had an NRS score <3 and 50 had an NRS score ≥3 at baseline. Baseline median European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ C30) global health score was lower for the NRS ≥3 group (37.5 versus 58.3). Nutritional interventions were more frequent in the NRS ≥3 group (45.8% versus 10.6%; P < 0.001). Patients with NRS ≥3 had inferior median PFS (4.9 months versus 6.9 months; P = 0.025) and OS (8.2 months versus 13.2 months; P = 0.003). Patients whose NRS score improved during induction chemotherapy showed superior median PFS (7.4 months versus 4.1 months; P = 0.085) and OS (20.1 months versus 8.0 months; P = 0.054) compared with those without improvement. No significant differences in overall toxicity were observed.

Conclusions

Baseline NRS is a significant predictor of outcome in patients with metastatic EGA. Our findings underscore the importance of routinely assessing the nutritional status of patients with metastatic EGA and intervening early.

背景：营养不良在转移性食管胃腺癌（EGA）患者中很常见。然而，营养风险筛查（NRS）对晚期EGA的预后影响仍未得到充分探讨。这项预先计划的II期AIO-MATEO试验分析了NRS对晚期EGA患者临床结果的影响。患者和方法纳入在诱导化疗前具有可用基线NRS的MATEO试验（探索S-1维持治疗）的患者。根据基线NRS评分（<；3和≥3）对患者进行分层。采用Kaplan-Meier和Cox回归分析无进展生存期（PFS）和总生存期（OS）。结果136例患者中，86例基线时NRS评分为<；3, 50例基线时NRS评分≥3。欧洲癌症研究和治疗组织生活质量问卷核心30 （EORTC QLQ C30）总体健康评分基线中位数在NRS≥3组较低（37.5比58.3）。营养干预在NRS≥3组更为频繁（45.8% vs 10.6%; P < 0.001）。NRS≥3的患者中位PFS（4.9个月对6.9个月，P = 0.025）和OS（8.2个月对13.2个月，P = 0.003）较差。诱导化疗期间NRS评分改善的患者的中位PFS（7.4个月对4.1个月，P = 0.085）和OS（20.1个月对8.0个月，P = 0.054）优于未改善的患者。总体毒性没有观察到显著差异。结论基线NRS是转移性EGA患者预后的重要预测指标。我们的研究结果强调了常规评估转移性EGA患者营养状况和早期干预的重要性。

{"title":"Impact of nutritional risk screening on outcomes of first-line treatment in metastatic esophagogastric adenocarcinoma: a secondary analysis of the AIO-MATEO trial","authors":"R. Stelmach , S. Lorenzen , T.J. Ettrich , F.R. Longo , B. Chibaudel , R. Greil , M. Perwög , J. Larcher-Steiner , D. Jäger , F. Lordick , G. Stocker , G.M. Haag","doi":"10.1016/j.esmogo.2025.100297","DOIUrl":"10.1016/j.esmogo.2025.100297","url":null,"abstract":"<div><h3>Background</h3><div>Malnutrition is common in patients with metastatic esophagogastric adenocarcinoma (EGA). However, the prognostic impact of nutritional risk screening (NRS) in advanced EGA remains underexplored. This preplanned analysis of the phase II AIO-MATEO trial evaluated the impact of NRS on clinical outcomes for patients with advanced EGA.</div></div><div><h3>Patients and methods</h3><div>Patients enrolled in the MATEO trial (exploring S-1 maintenance therapy) with an available baseline NRS before induction chemotherapy were included. Patients were stratified by their baseline NRS score (<3 versus ≥3). Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan–Meier and Cox regression methods.</div></div><div><h3>Results</h3><div>Of the 136 patients, 86 had an NRS score <3 and 50 had an NRS score ≥3 at baseline. Baseline median European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ C30) global health score was lower for the NRS ≥3 group (37.5 versus 58.3). Nutritional interventions were more frequent in the NRS ≥3 group (45.8% versus 10.6%; <em>P</em> < 0.001). Patients with NRS ≥3 had inferior median PFS (4.9 months versus 6.9 months; <em>P</em> = 0.025) and OS (8.2 months versus 13.2 months; <em>P</em> = 0.003). Patients whose NRS score improved during induction chemotherapy showed superior median PFS (7.4 months versus 4.1 months; <em>P</em> = 0.085) and OS (20.1 months versus 8.0 months; <em>P</em> = 0.054) compared with those without improvement. No significant differences in overall toxicity were observed.</div></div><div><h3>Conclusions</h3><div>Baseline NRS is a significant predictor of outcome in patients with metastatic EGA. Our findings underscore the importance of routinely assessing the nutritional status of patients with metastatic EGA and intervening early.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"11 ","pages":"Article 100297"},"PeriodicalIF":0.0,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078108","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}

引用次数: 0

Impact of claudin 18.2 expression on the efficacy of trastuzumab deruxtecan in patients with HER2-positive gastric or gastroesophageal junction cancer claudin 18.2表达对曲妥珠单抗德鲁西替康治疗her2阳性胃癌或胃食管结癌疗效的影响

ESMO Gastrointestinal Oncology

Pub Date : 2026-01-27 DOI: 10.1016/j.esmogo.2025.100300

D. Okemoto , I. Nakayama , A. Jubashi , N. Sakamoto , M. Okunaka , Y. Matsubara , Y. Miyashita , A. Kobayashi , U. Okazaki , K. Yamamoto , K. Seguchi , T. Hosokai , T. Ogura , S. Mishima , D. Kotani , A. Kawazoe , T. Hashimoto , Y. Kuboki , H. Bando , T. Kojima , K. Shitara

Background

Human epidermal growth factor receptor 2 (HER2) and claudin 18.2 (CLDN18.2) are key therapeutic targets in metastatic gastric and gastroesophageal junction cancer (mGC/GEJC). Trastuzumab deruxtecan (T-DXd) is standard care for previously treated HER2-positive mGC/GEJC, but the prognostic impact of CLDN18.2 remains unclear.

Patients and methods

We retrospectively reviewed patients with HER2-positive mGC/GEJC treated with T-DXd at National Cancer Center Hospital East until February 2025. T-DXd outcomes were compared between CLDN18.2-positive (≥2+ in ≥75% of tumor cells) and -negative patients in two cohorts: those with HER2 positivity before first-line therapy (overall cohort) and those maintaining HER2 positivity immediately before T-DXd (remaining HER2 cohort). CLDN18.2 expression was evaluated at any time before T-DXd administration.

Results

Eighty-seven patients were included in the overall cohort and 30 in the remaining HER2 cohort. In the overall cohort, progression-free survival (PFS) was shorter in CLDN18.2-positive patients [3.9 versus 5.3 months; hazard ratio (HR) 1.87, 95% confidence interval (CI) 1.04-3.34, P = 0.036], with an adjusted HR of 1.82 (95% CI 1.02-3.28, P = 0.047). Overall survival (OS) showed a shorter trend (8.6 versus 11.2 months, HR 1.36, 95% CI 0.76-2.45, P = 0.30). In the remaining HER2 cohort, CLDN18.2-positive patients had shorter PFS (3.2 versus 8.0 months, HR 3.40, 95% CI 1.38-8.40, P = 0.008) and OS (7.1 versus 12.9 months, HR 2.44, 95% CI 1.04-5.74, P = 0.041).

Conclusions

CLDN18.2 positivity may attenuate the efficacy of T-DXd in HER2-positive mGC/GEJC, supporting the rationale for dual blockade of CLDN18.2 and HER2.

人表皮生长因子受体2 （HER2）和claudin 18.2 （CLDN18.2）是转移性胃癌和胃食管结癌（mGC/GEJC）的关键治疗靶点。曲妥珠单抗德鲁西替康（T-DXd）是先前治疗过的her2阳性mGC/GEJC的标准治疗，但CLDN18.2的预后影响尚不清楚。患者和方法我们回顾性地回顾了到2025年2月在国立癌症中心东医院接受T-DXd治疗的her2阳性mGC/GEJC患者。比较cldn18.2阳性（≥75%的肿瘤细胞≥2+）和阴性患者的T-DXd结果，分为两个队列：一线治疗前HER2阳性患者（总队列）和T-DXd前立即保持HER2阳性的患者（剩余HER2队列）。在给药前的任何时间检测CLDN18.2的表达。结果87例患者被纳入总队列，30例患者被纳入剩余HER2队列。在整个队列中，cldn18.2阳性患者的无进展生存期（PFS）较短[3.9个月对5.3个月；风险比（HR） 1.87, 95%可信区间（CI） 1.04 ~ 3.34, P = 0.036]，调整后的风险比为1.82 （95% CI 1.02 ~ 3.28, P = 0.047）。总生存期（OS）呈短趋势（8.6个月vs 11.2个月，HR 1.36, 95% CI 0.76-2.45, P = 0.30）。在其余的HER2队列中，CLDN18.2阳性患者的PFS（3.2个月vs 8.0个月，HR 3.40, 95% CI 1.38-8.40, P = 0.008）和OS（7.1个月vs 12.9个月，HR 2.44, 95% CI 1.04-5.74, P = 0.041）较短。结论CLDN18.2阳性可能会减弱T-DXd在HER2阳性mGC/GEJC中的疗效，支持CLDN18.2和HER2双重阻断的理论基础。

{"title":"Impact of claudin 18.2 expression on the efficacy of trastuzumab deruxtecan in patients with HER2-positive gastric or gastroesophageal junction cancer","authors":"D. Okemoto , I. Nakayama , A. Jubashi , N. Sakamoto , M. Okunaka , Y. Matsubara , Y. Miyashita , A. Kobayashi , U. Okazaki , K. Yamamoto , K. Seguchi , T. Hosokai , T. Ogura , S. Mishima , D. Kotani , A. Kawazoe , T. Hashimoto , Y. Kuboki , H. Bando , T. Kojima , K. Shitara","doi":"10.1016/j.esmogo.2025.100300","DOIUrl":"10.1016/j.esmogo.2025.100300","url":null,"abstract":"<div><h3>Background</h3><div>Human epidermal growth factor receptor 2 (HER2) and claudin 18.2 (CLDN18.2) are key therapeutic targets in metastatic gastric and gastroesophageal junction cancer (mGC/GEJC). Trastuzumab deruxtecan (T-DXd) is standard care for previously treated HER2-positive mGC/GEJC, but the prognostic impact of CLDN18.2 remains unclear.</div></div><div><h3>Patients and methods</h3><div>We retrospectively reviewed patients with HER2-positive mGC/GEJC treated with T-DXd at National Cancer Center Hospital East until February 2025. T-DXd outcomes were compared between CLDN18.2-positive (≥2+ in ≥75% of tumor cells) and -negative patients in two cohorts: those with HER2 positivity before first-line therapy (overall cohort) and those maintaining HER2 positivity immediately before T-DXd (remaining HER2 cohort). CLDN18.2 expression was evaluated at any time before T-DXd administration.</div></div><div><h3>Results</h3><div>Eighty-seven patients were included in the overall cohort and 30 in the remaining HER2 cohort. In the overall cohort, progression-free survival (PFS) was shorter in CLDN18.2-positive patients [3.9 versus 5.3 months; hazard ratio (HR) 1.87, 95% confidence interval (CI) 1.04-3.34, <em>P</em> = 0.036], with an adjusted HR of 1.82 (95% CI 1.02-3.28, <em>P</em> = 0.047). Overall survival (OS) showed a shorter trend (8.6 versus 11.2 months, HR 1.36, 95% CI 0.76-2.45, <em>P</em> = 0.30). In the remaining HER2 cohort, CLDN18.2-positive patients had shorter PFS (3.2 versus 8.0 months, HR 3.40, 95% CI 1.38-8.40, <em>P</em> = 0.008) and OS (7.1 versus 12.9 months, HR 2.44, 95% CI 1.04-5.74, <em>P</em> = 0.041).</div></div><div><h3>Conclusions</h3><div>CLDN18.2 positivity may attenuate the efficacy of T-DXd in HER2-positive mGC/GEJC, supporting the rationale for dual blockade of CLDN18.2 and HER2.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"11 ","pages":"Article 100300"},"PeriodicalIF":0.0,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078107","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}

引用次数: 0

Real-world treatment outcomes for pancreatic neuroendocrine tumours: a single tertiary referral institute experience 胰腺神经内分泌肿瘤的真实世界治疗结果：单一三级转诊机构经验

ESMO Gastrointestinal Oncology

Pub Date : 2026-01-27 DOI: 10.1016/j.esmogo.2025.100293

L.L. Chan , A.C.Y. Lam , H.H.W. Leung , S.H. Chok , S.Y.W. Liu , J.W.C. Kung , R. Ozaki , A.P.S. Kong , R.C.W. Ma , S.L. Chan

Background

Pancreatic neuroendocrine tumours (PNETs) are rare neoplasms of the pancreas. Real-world treatment outcomes in Asia are seldom reported. The aim of this study was to provide the real-world treatment outcomes of PNETs at a single tertiary cancer centre in Hong Kong over an 18-year period.

Materials and methods

This was a retrospective cohort study that recruits patients with local or metastatic PNETs treated at Prince of Wales Hospital, Hong Kong between 2005 and 2023. Five-year overall survival (OS), progression-free survival (PFS), recurrence-free survival (RFS) of the surgical cohort, and survival outcomes in patients with metastatic disease were summarized.

Results

A total of 98 patients were recruited (median age: 59 years, 51% male). Among them, 18 patients (18.4%) had functioning tumours, of which majority were insulinoma (72.2%). Most tumours (64.8%) were classified as grade 1 disease. More than 80% of patients had early-stage disease on presentation, with only 14 patients presented with stage IV disease. Five-year OS for the entire cohort was 88.4% and the 5-year PFS was 73.7%. Older age [hazard ratio (HR) 1.06, 95% confidence interval (CI) 1.00-1.13, P = 0.04] and larger tumour size (HR 1.20, 95% CI 1.00-1.44, P = 0.05) were associated with worse OS, whereas patients with metastatic disease had a shorter PFS (HR 7.95, 95% CI 2.55-24.8, P < 0.001). In the cohort treated with curative surgery, metastatic disease (HR 7.49, 95% CI 1.40-40.0, P = 0.018) and tumour grade (HR 8.03, 95% CI 1.58-40.8, P = 0.012) were associated with worse RFS. Microscopic margin involvement did not influence RFS in patients treated with curative surgery. In the 20 patients who received systemic therapy, everolimus showed a trend towards improved PFS compared with chemotherapy (5-year PFS: 46.9% versus 16.7%).

Conclusion

Patients with PNETs in Hong Kong have early presentation and excellent prognosis with most patients being eligible for curative surgery reaching 90% of 5-year OS.

胰腺神经内分泌肿瘤（PNETs）是一种罕见的胰腺肿瘤。亚洲的实际治疗结果很少被报道。本研究的目的是提供PNETs在香港单一三级癌症中心18年期间的实际治疗结果。材料和方法本研究是一项回顾性队列研究，招募2005年至2023年间在香港威尔斯亲王医院接受治疗的局部或转移性PNETs患者。总结了手术队列的5年总生存期（OS）、无进展生存期（PFS）、无复发生存期（RFS）以及转移性疾病患者的生存结局。结果共纳入98例患者（中位年龄59岁，男性占51%）。其中功能性肿瘤18例（18.4%），以胰岛素瘤居多（72.2%）。大多数肿瘤（64.8%）被归类为1级疾病。超过80%的患者在就诊时为早期疾病，只有14例患者表现为IV期疾病。整个队列的5年OS为88.4%，5年PFS为73.7%。年龄较大[危险比（HR） 1.06, 95%可信区间（CI） 1.00-1.13, P = 0.04]和肿瘤大小较大（HR 1.20, 95% CI 1.00-1.44, P = 0.05）与较差的OS相关，而转移性疾病患者的PFS较短（HR 7.95, 95% CI 2.55-24.8, P < 0.001）。在接受根治性手术治疗的队列中，转移性疾病（HR 7.49, 95% CI 1.40-40.0, P = 0.018）和肿瘤分级（HR 8.03, 95% CI 1.58-40.8, P = 0.012）与较差的RFS相关。显微切缘受累不影响根治性手术患者的RFS。在接受全身治疗的20例患者中，与化疗相比，依维莫司显示出改善PFS的趋势（5年PFS: 46.9%对16.7%）。结论香港PNETs患者临床表现较早，预后较好，大多数患者的5年总生存率达到90%。

{"title":"Real-world treatment outcomes for pancreatic neuroendocrine tumours: a single tertiary referral institute experience","authors":"L.L. Chan , A.C.Y. Lam , H.H.W. Leung , S.H. Chok , S.Y.W. Liu , J.W.C. Kung , R. Ozaki , A.P.S. Kong , R.C.W. Ma , S.L. Chan","doi":"10.1016/j.esmogo.2025.100293","DOIUrl":"10.1016/j.esmogo.2025.100293","url":null,"abstract":"<div><h3>Background</h3><div>Pancreatic neuroendocrine tumours (PNETs) are rare neoplasms of the pancreas. Real-world treatment outcomes in Asia are seldom reported. The aim of this study was to provide the real-world treatment outcomes of PNETs at a single tertiary cancer centre in Hong Kong over an 18-year period.</div></div><div><h3>Materials and methods</h3><div>This was a retrospective cohort study that recruits patients with local or metastatic PNETs treated at Prince of Wales Hospital, Hong Kong between 2005 and 2023. Five-year overall survival (OS), progression-free survival (PFS), recurrence-free survival (RFS) of the surgical cohort, and survival outcomes in patients with metastatic disease were summarized.</div></div><div><h3>Results</h3><div>A total of 98 patients were recruited (median age: 59 years, 51% male). Among them, 18 patients (18.4%) had functioning tumours, of which majority were insulinoma (72.2%). Most tumours (64.8%) were classified as grade 1 disease. More than 80% of patients had early-stage disease on presentation, with only 14 patients presented with stage IV disease. Five-year OS for the entire cohort was 88.4% and the 5-year PFS was 73.7%. Older age [hazard ratio (HR) 1.06, 95% confidence interval (CI) 1.00-1.13, <em>P</em> = 0.04] and larger tumour size (HR 1.20, 95% CI 1.00-1.44, <em>P</em> = 0.05) were associated with worse OS, whereas patients with metastatic disease had a shorter PFS (HR 7.95, 95% CI 2.55-24.8, <em>P</em> < 0.001). In the cohort treated with curative surgery, metastatic disease (HR 7.49, 95% CI 1.40-40.0, <em>P</em> = 0.018) and tumour grade (HR 8.03, 95% CI 1.58-40.8, <em>P</em> = 0.012) were associated with worse RFS. Microscopic margin involvement did not influence RFS in patients treated with curative surgery. In the 20 patients who received systemic therapy, everolimus showed a trend towards improved PFS compared with chemotherapy (5-year PFS: 46.9% versus 16.7%).</div></div><div><h3>Conclusion</h3><div>Patients with PNETs in Hong Kong have early presentation and excellent prognosis with most patients being eligible for curative surgery reaching 90% of 5-year OS.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"11 ","pages":"Article 100293"},"PeriodicalIF":0.0,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078110","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}

引用次数: 0

The role of stereotactic body radiotherapy in the management of hepatocellular carcinoma with macroscopic vascular invasion: a narrative review 立体定向放疗在肝细胞癌伴宏观血管侵犯治疗中的作用：综述

ESMO Gastrointestinal Oncology

Pub Date : 2026-01-27 DOI: 10.1016/j.esmogo.2025.100298

I.J. Gerard , A.M. Glynn , M.D. Faye , M. Yan , A. Mesci , T.K. Kim , R. Vanner , L.A. Dawson

Hepatocellular carcinoma (HCC) is the most common primary liver cancer, with a rising global incidence. Prognosis in HCC remains poor, particularly in patients presenting with macrovascular invasion (MVI), which is associated with high rates of hepatic decompensation, diffuse disease progression, and a median survival of only 2-5 months without treatment. Management of HCC with MVI is complex, requiring multidisciplinary and multimodality approaches. While surgery and transplantation may be considered in select cases, systemic therapy with immunotherapy-based regimens currently represents standard of care. Limitations due to complications with MVI often makes optimal treatment challenging. Advances in modern radiotherapy, particularly stereotactic body radiotherapy (SBRT), have established it as a safe and effective local therapy capable of delivering ablative doses while sparing normal liver tissue. Retrospective series and prospective trials have demonstrated that SBRT provides high local control rates, objective response rates exceeding 50%, and survival benefits when combined with systemic or locoregional therapies alone. SBRT has also shown promise in improving liver function and palliating symptoms in patients with poor hepatic reserve. Emerging evidence suggests synergistic effects when combined with immunotherapy or transarterial therapies, with ongoing studies poised to clarify its role in modern treatment paradigms. Collectively, data support the use of SBRT as a crucial tool in the multidisciplinary management of HCC with MVI, offering durable local control, symptom relief, and the potential to enhance systemic therapy efficacy.

肝细胞癌（HCC）是最常见的原发性肝癌，全球发病率呈上升趋势。HCC的预后仍然很差，特别是出现大血管侵犯（MVI）的患者，这与肝功能失代偿率高、弥漫性疾病进展以及不治疗的中位生存期仅为2-5个月有关。肝细胞癌合并MVI的治疗是复杂的，需要多学科和多模式的方法。虽然在某些情况下可以考虑手术和移植，但目前以免疫治疗为基础的全身治疗是标准的治疗方案。由于MVI并发症的限制往往使最佳治疗具有挑战性。现代放射治疗的进展，特别是立体定向体放射治疗（SBRT），已使其成为一种安全有效的局部治疗，能够提供消融剂量，同时保留正常肝组织。回顾性系列和前瞻性试验表明，SBRT具有较高的局部控制率，客观缓解率超过50%，并且在与全身或局部治疗单独联合时具有生存益处。SBRT还显示出改善肝功能和缓解肝储备不良患者症状的希望。新出现的证据表明，与免疫治疗或经动脉治疗联合使用时具有协同作用，正在进行的研究准备阐明其在现代治疗范例中的作用。总的来说，数据支持将SBRT作为HCC合并MVI的多学科管理的关键工具，提供持久的局部控制，症状缓解，并有可能提高全身治疗的疗效。

{"title":"The role of stereotactic body radiotherapy in the management of hepatocellular carcinoma with macroscopic vascular invasion: a narrative review","authors":"I.J. Gerard , A.M. Glynn , M.D. Faye , M. Yan , A. Mesci , T.K. Kim , R. Vanner , L.A. Dawson","doi":"10.1016/j.esmogo.2025.100298","DOIUrl":"10.1016/j.esmogo.2025.100298","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) is the most common primary liver cancer, with a rising global incidence. Prognosis in HCC remains poor, particularly in patients presenting with macrovascular invasion (MVI), which is associated with high rates of hepatic decompensation, diffuse disease progression, and a median survival of only 2-5 months without treatment. Management of HCC with MVI is complex, requiring multidisciplinary and multimodality approaches. While surgery and transplantation may be considered in select cases, systemic therapy with immunotherapy-based regimens currently represents standard of care. Limitations due to complications with MVI often makes optimal treatment challenging. Advances in modern radiotherapy, particularly stereotactic body radiotherapy (SBRT), have established it as a safe and effective local therapy capable of delivering ablative doses while sparing normal liver tissue. Retrospective series and prospective trials have demonstrated that SBRT provides high local control rates, objective response rates exceeding 50%, and survival benefits when combined with systemic or locoregional therapies alone. SBRT has also shown promise in improving liver function and palliating symptoms in patients with poor hepatic reserve. Emerging evidence suggests synergistic effects when combined with immunotherapy or transarterial therapies, with ongoing studies poised to clarify its role in modern treatment paradigms. Collectively, data support the use of SBRT as a crucial tool in the multidisciplinary management of HCC with MVI, offering durable local control, symptom relief, and the potential to enhance systemic therapy efficacy.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"11 ","pages":"Article 100298"},"PeriodicalIF":0.0,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078105","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}

引用次数: 0

Semiquantitative CLDN18 expression and clinical outcomes in patients with CLDN18-positive gastric cancer treated with zolbetuximab plus chemotherapy zolbetuximab联合化疗CLDN18阳性胃癌患者的半定量CLDN18表达及临床结果

ESMO Gastrointestinal Oncology

Pub Date : 2026-01-27 DOI: 10.1016/j.esmogo.2026.100304

A. Ooki , K. Nakano , K. Shimozaki , M. Takamatsu , S. Fukuoka , S. Sakata , H. Osumi , K. Yoshikawa , E. Toyokawa , K. Yoshino , S. Udagawa , T. Wakatsuki , M. Ogura , E. Shinozaki , K. Chin , H. Kawachi , K. Yamaguchi

Background

Zolbetuximab plus chemotherapy improves survival in patients with human epidermal growth factor receptor 2 (HER2)-negative, claudin 18 (CLDN18)-positive advanced gastric cancer (AGC), which is defined as ≥75% of tumor cells with moderate-to-strong membranous staining. Whether semiquantitative expression within this range influences treatment outcomes is unknown.

Patients and methods

This single-center retrospective study evaluated patients with AGC treated with zolbetuximab plus chemotherapy between July 2024 and September 2025. Tumors were independently reviewed by three pathologists and categorized as having moderate (75%-94%) or high (95%-100%) CLDN18 expression. Survival, response, and safety were compared across expression levels.

Results

Fifty-one patients were included in the study. Baseline characteristics were similar across the groups. The median progression-free survival was 6.7 months in both expression groups, and the median overall survival was not reached. The objective response rates were 62.5% and 71.4%, and the disease control rates were 87.5% and 85.7% in the moderate and high expression groups, respectively. The depth of response (−33.6% versus −45.8%) and early tumor shrinkage (43.8% versus 71.4%) differed modestly. The profile of treatment-related adverse events was similar across the expression groups. Specimen type (biopsy or surgical resection) had no apparent impact on treatment outcomes.

Conclusions

Within the approved CLDN18-positive threshold, the semiquantitative staining proportion showed no detectable differences in the efficacy or safety of zolbetuximab plus chemotherapy.

zolbetuximab联合化疗可提高人表皮生长因子受体2 （HER2）阴性，CLDN18 （CLDN18）阳性的晚期胃癌（AGC）患者的生存率，AGC定义为≥75%的肿瘤细胞具有中至强膜性染色。该范围内的半定量表达是否影响治疗结果尚不清楚。患者和方法本单中心回顾性研究评估了2024年7月至2025年9月期间接受唑仑妥昔单抗联合化疗的AGC患者。肿瘤由三位病理学家独立审查，并将其分类为中度（75%-94%）或高（95%-100%）CLDN18表达。在不同的表达水平上比较生存、反应和安全性。结果共纳入51例患者。各组的基线特征相似。两组患者的中位无进展生存期均为6.7个月，中位总生存期均未达到。中、高表达组的客观有效率分别为62.5%和71.4%，疾病控制率分别为87.5%和85.7%。反应深度（- 33.6%对- 45.8%）和早期肿瘤缩小（43.8%对71.4%）略有差异。治疗相关不良事件的概况在表达组之间相似。标本类型（活检或手术切除）对治疗结果无明显影响。结论在批准的cldn18阳性阈值内，半定量染色比例显示唑苯妥昔单抗联合化疗的疗效和安全性无明显差异。

{"title":"Semiquantitative CLDN18 expression and clinical outcomes in patients with CLDN18-positive gastric cancer treated with zolbetuximab plus chemotherapy","authors":"A. Ooki , K. Nakano , K. Shimozaki , M. Takamatsu , S. Fukuoka , S. Sakata , H. Osumi , K. Yoshikawa , E. Toyokawa , K. Yoshino , S. Udagawa , T. Wakatsuki , M. Ogura , E. Shinozaki , K. Chin , H. Kawachi , K. Yamaguchi","doi":"10.1016/j.esmogo.2026.100304","DOIUrl":"10.1016/j.esmogo.2026.100304","url":null,"abstract":"<div><h3>Background</h3><div>Zolbetuximab plus chemotherapy improves survival in patients with human epidermal growth factor receptor 2 (HER2)-negative, claudin 18 (CLDN18)-positive advanced gastric cancer (AGC), which is defined as ≥75% of tumor cells with moderate-to-strong membranous staining. Whether semiquantitative expression within this range influences treatment outcomes is unknown.</div></div><div><h3>Patients and methods</h3><div>This single-center retrospective study evaluated patients with AGC treated with zolbetuximab plus chemotherapy between July 2024 and September 2025. Tumors were independently reviewed by three pathologists and categorized as having moderate (75%-94%) or high (95%-100%) CLDN18 expression. Survival, response, and safety were compared across expression levels.</div></div><div><h3>Results</h3><div>Fifty-one patients were included in the study. Baseline characteristics were similar across the groups. The median progression-free survival was 6.7 months in both expression groups, and the median overall survival was not reached. The objective response rates were 62.5% and 71.4%, and the disease control rates were 87.5% and 85.7% in the moderate and high expression groups, respectively. The depth of response (−33.6% versus −45.8%) and early tumor shrinkage (43.8% versus 71.4%) differed modestly. The profile of treatment-related adverse events was similar across the expression groups. Specimen type (biopsy or surgical resection) had no apparent impact on treatment outcomes.</div></div><div><h3>Conclusions</h3><div>Within the approved CLDN18-positive threshold, the semiquantitative staining proportion showed no detectable differences in the efficacy or safety of zolbetuximab plus chemotherapy.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"11 ","pages":"Article 100304"},"PeriodicalIF":0.0,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078109","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}

引用次数: 0

Regorafenib use in patients with unresectable hepatocellular carcinoma: analyses of subgroups of special interest in the observational REFINE study 瑞非尼在不可切除肝细胞癌患者中的应用：观察性REFINE研究中特别关注的亚组分析

ESMO Gastrointestinal Oncology

Pub Date : 2026-01-22 DOI: 10.1016/j.esmogo.2025.100292

Y.J. Kim , P. Merle , R.S. Finn , H.-J. Klümpen , H.Y. Lim , M. Ikeda , A. Granito , G. Masi , R. Gerolami , M. Pinter , S. Babajanyan , P. Twumasi-Ankrah , M. Ghadessi , K. Ozgurdal , S. Qin

Background

The findings of the prospective, real-world REFINE trial supported the safety and efficacy of regorafenib reported in the phase III RESORCE study, in a broader population of patients with unresectable hepatocellular carcinoma (HCC). This post hoc analysis evaluated patient subgroups based on liver function, liver cancer stage, and prior treatment.

Patients and methods

Patients were analyzed by subgroups based on liver function [Child–Pugh (CP)–B/B7], prior treatment [prior orthotopic liver transplant (pOLT), transarterial chemoembolization (TACE)/transarterial radioembolization (TARE)], and Barcelona Clinic Liver Cancer (BCLC) stage. The primary objective was to evaluate the safety of regorafenib. Secondary objectives included effectiveness endpoints of overall survival (OS) and duration of treatment. All analyses were descriptive with no adjustment for confounders.

Results

A total of 1005 patients were evaluable (overall population). In patients with CP–B (n = 123) compared with the overall population, the incidence of grade ≥3 (28% versus 27%) and serious drug-related treatment-emergent adverse events (TEAEs) was similar (11% versus 9%), whereas TEAEs leading to permanent discontinuation of regorafenib were more common (28% versus 16%). In patients with prior TACE (n = 584), the incidence of TEAEs was generally similar to patients without prior TACE (n = 421) and the overall population (92%, 91%, and 92%, respectively). Median OS was 12.3-19.3 months across all subgroups except CP–B/B7 (6.4/6.7 months).

Conclusions

This subgroup analysis of REFINE provides further evidence on the safety and effectiveness of regorafenib demonstrated in RESORCE, in underrepresented subgroups (CP–B, BCLC stage B/C, pOLT) and in those previously treated with TACE/TARE.

前瞻性、现实世界的REFINE试验结果支持reorafenib在更广泛的不可切除肝细胞癌（HCC）患者人群中的安全性和有效性。这项事后分析评估了基于肝功能、肝癌分期和既往治疗的患者亚组。患者和方法根据肝功能[Child-Pugh (CP) -B /B7]、既往治疗[既往原位肝移植（pOLT）、经动脉化疗栓塞(TACE)/经动脉放射栓塞（TARE）]和巴塞罗那临床肝癌（BCLC）分期进行亚组分析。主要目的是评估瑞非尼的安全性。次要目标包括总生存期（OS）和治疗时间的有效性终点。所有的分析都是描述性的，没有对混杂因素进行调整。结果1005例患者（总体）可评估。在CP-B患者（n = 123）中，与总体人群相比，≥3级（28%对27%）和严重药物相关治疗不良事件（teae）的发生率相似（11%对9%），而导致瑞非尼永久停药的teae更为常见（28%对16%）。在有TACE病史的患者（n = 584）中，teae的发生率与没有TACE病史的患者（n = 421）和总体人群（分别为92%、91%和92%）大致相似。除CP-B /B7（6.4/6.7个月）外，所有亚组的中位OS为12.3-19.3个月。REFINE的亚组分析进一步证明了reorafenib在resource、代表性不足的亚组（CP-B、BCLC B/C期、pOLT）和先前接受过TACE/TARE治疗的患者中的安全性和有效性。

{"title":"Regorafenib use in patients with unresectable hepatocellular carcinoma: analyses of subgroups of special interest in the observational REFINE study","authors":"Y.J. Kim , P. Merle , R.S. Finn , H.-J. Klümpen , H.Y. Lim , M. Ikeda , A. Granito , G. Masi , R. Gerolami , M. Pinter , S. Babajanyan , P. Twumasi-Ankrah , M. Ghadessi , K. Ozgurdal , S. Qin","doi":"10.1016/j.esmogo.2025.100292","DOIUrl":"10.1016/j.esmogo.2025.100292","url":null,"abstract":"<div><h3>Background</h3><div>The findings of the prospective, real-world REFINE trial supported the safety and efficacy of regorafenib reported in the phase III RESORCE study, in a broader population of patients with unresectable hepatocellular carcinoma (HCC). This <em>post hoc</em> analysis evaluated patient subgroups based on liver function, liver cancer stage, and prior treatment.</div></div><div><h3>Patients and methods</h3><div>Patients were analyzed by subgroups based on liver function [Child–Pugh (CP)–B/B7], prior treatment [prior orthotopic liver transplant (pOLT), transarterial chemoembolization (TACE)/transarterial radioembolization (TARE)], and Barcelona Clinic Liver Cancer (BCLC) stage. The primary objective was to evaluate the safety of regorafenib. Secondary objectives included effectiveness endpoints of overall survival (OS) and duration of treatment. All analyses were descriptive with no adjustment for confounders.</div></div><div><h3>Results</h3><div>A total of 1005 patients were evaluable (overall population). In patients with CP–B (<em>n</em> = 123) compared with the overall population, the incidence of grade ≥3 (28% versus 27%) and serious drug-related treatment-emergent adverse events (TEAEs) was similar (11% versus 9%), whereas TEAEs leading to permanent discontinuation of regorafenib were more common (28% versus 16%). In patients with prior TACE (<em>n</em> = 584), the incidence of TEAEs was generally similar to patients without prior TACE (<em>n</em> = 421) and the overall population (92%, 91%, and 92%, respectively). Median OS was 12.3-19.3 months across all subgroups except CP–B/B7 (6.4/6.7 months).</div></div><div><h3>Conclusions</h3><div>This subgroup analysis of REFINE provides further evidence on the safety and effectiveness of regorafenib demonstrated in RESORCE, in underrepresented subgroups (CP–B, BCLC stage B/C, pOLT) and in those previously treated with TACE/TARE.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"11 ","pages":"Article 100292"},"PeriodicalIF":0.0,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146038191","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}

引用次数: 0

Early- and advanced-stage MSI-H non-colorectal cancers: best management and challenges in 2025 早期和晚期MSI-H非结直肠癌：2025年的最佳管理和挑战

ESMO Gastrointestinal Oncology

Pub Date : 2026-01-22 DOI: 10.1016/j.esmogo.2025.100296

R. Fazio, M. Ambrosini, A. Raimondi, C.C. Pircher, C. Leli, C. Sciortino, S. Marchesi, C. Damonte, C. Villa, C. Silvestri, F. Manoni, G. Gronchi, F. Pietrantonio

Gastrointestinal malignancies account for the vast majority of tumours within the microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) phenotype. Over the past decade, evidence on the prognostic and predictive role of MSI-H/dMMR status has steadily accumulated, and immune checkpoint inhibitors (ICIs) are now considered the cornerstone of treatment for all patients with advanced MSI-H/dMMR cancers. However, in non-colorectal tumours the available evidence is less robust, raising important challenges, such as defining the optimal therapeutic regimen across different treatment lines and establishing the appropriate duration of therapy. More recently, the efficacy of ICIs has also been demonstrated in localized disease, prompting new questions regarding their integration into curative-intent strategies, such as the risk of overtreatment given the favourable prognosis of early-stage tumours, the role of nonoperative management, the optimal treatment regimen, and schedule. In this review, we summarize the available literature and the evidence supporting treatment strategies for patients with early- and advanced-stage MSI-H/dMMR non-colorectal cancers.

胃肠道恶性肿瘤占绝大多数微卫星不稳定性高(MSI-H)/错配修复缺陷（dMMR）表型的肿瘤。在过去的十年中，关于MSI-H/dMMR状态的预后和预测作用的证据不断积累，免疫检查点抑制剂（ICIs）现在被认为是所有晚期MSI-H/dMMR癌症患者治疗的基石。然而，在非结直肠肿瘤中，现有的证据不太有力，提出了重要的挑战，例如确定不同治疗线的最佳治疗方案和确定适当的治疗持续时间。最近，ICIs在局部疾病中的疗效也得到了证实，这引发了关于将其纳入治疗意图策略的新问题，例如，鉴于早期肿瘤预后良好，过度治疗的风险、非手术治疗的作用、最佳治疗方案和时间表。在这篇综述中，我们总结了支持早期和晚期MSI-H/dMMR非结直肠癌患者治疗策略的现有文献和证据。

{"title":"Early- and advanced-stage MSI-H non-colorectal cancers: best management and challenges in 2025","authors":"R. Fazio, M. Ambrosini, A. Raimondi, C.C. Pircher, C. Leli, C. Sciortino, S. Marchesi, C. Damonte, C. Villa, C. Silvestri, F. Manoni, G. Gronchi, F. Pietrantonio","doi":"10.1016/j.esmogo.2025.100296","DOIUrl":"10.1016/j.esmogo.2025.100296","url":null,"abstract":"<div><div>Gastrointestinal malignancies account for the vast majority of tumours within the microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) phenotype. Over the past decade, evidence on the prognostic and predictive role of MSI-H/dMMR status has steadily accumulated, and immune checkpoint inhibitors (ICIs) are now considered the cornerstone of treatment for all patients with advanced MSI-H/dMMR cancers. However, in non-colorectal tumours the available evidence is less robust, raising important challenges, such as defining the optimal therapeutic regimen across different treatment lines and establishing the appropriate duration of therapy. More recently, the efficacy of ICIs has also been demonstrated in localized disease, prompting new questions regarding their integration into curative-intent strategies, such as the risk of overtreatment given the favourable prognosis of early-stage tumours, the role of nonoperative management, the optimal treatment regimen, and schedule. In this review, we summarize the available literature and the evidence supporting treatment strategies for patients with early- and advanced-stage MSI-H/dMMR non-colorectal cancers.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"11 ","pages":"Article 100296"},"PeriodicalIF":0.0,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146038189","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}

引用次数: 0

Controversies in upper gastrointestinal cancers: adoptive cell therapies 上消化道肿瘤的争议：过继细胞治疗

ESMO Gastrointestinal Oncology

Pub Date : 2026-01-21 DOI: 10.1016/j.esmogo.2026.100306

M. Donia , W. Mansoor , S. Valpione

引用次数: 0

DESTINY-Gastric05 phase III trial of first-line trastuzumab deruxtecan, chemotherapy, and pembrolizumab in HER2-positive gastric or gastroesophageal junction cancer DESTINY-Gastric05 III期临床试验，一线曲妥珠单抗、德鲁德替康、化疗和派姆单抗治疗her2阳性胃癌或胃食管结癌

ESMO Gastrointestinal Oncology

Pub Date : 2026-01-20 DOI: 10.1016/j.esmogo.2025.100294

Y.Y. Janjigian , E. Smyth , L. Shen , J. Lee , P.M. Hoff , S. Lonardi , D. Barrios , K. Kobayashi , Y. Okuda , T. Kamio , K. Shitara

Background

Gastric or gastroesophageal junction (GEJ) cancers are usually diagnosed at advanced stages with poor prognoses and 5-year survival rates. Standard-of-care first-line treatment of human epidermal growth factor receptor 2 (HER2)-positive locally advanced or metastatic disease is chemotherapy and trastuzumab, plus pembrolizumab for programmed death-ligand 1 (PD-L1)-positive [combined positive score (CPS) ≥1] tumors. Trastuzumab deruxtecan (T-DXd) 6.4 mg/kg monotherapy is approved as second-line treatment for patients with HER2-positive gastric or GEJ cancer. DESTINY-Gastric03 (NCT04379596) showed that first-line T-DXd 5.4 mg/kg plus chemotherapy with or without pembrolizumab in the advanced setting had manageable safety and promising efficacy in HER2-positive gastric or GEJ cancer.

Aim

To investigate a first-line T-DXd plus platinum-free chemotherapy with pembrolizumab treatment approach for patients with HER2-positive gastric or GEJ cancer.

Trial design

DESTINY-Gastric05 (NCT06731478) is a global, multicenter, open-label, randomized, phase III trial to evaluate the efficacy and safety of first-line T-DXd 5.4 mg/kg plus 5-fluorouracil or capecitabine and pembrolizumab versus platinum-based chemotherapy with trastuzumab and pembrolizumab in patients with unresectable, locally advanced or metastatic, centrally confirmed HER2-positive (immunohistochemistry 3+ or immunohistochemistry 2+/in situ hybridization positive) gastric or GEJ cancer with a PD-L1 CPS ≥1. An exploratory cohort is to evaluate T-DXd plus 5-fluorouracil or capecitabine in patients with PD-L1 CPS <1.

背景：胃或胃食管交界处（GEJ）癌通常在晚期诊断，预后差，5年生存率低。人类表皮生长因子受体2 （HER2）阳性的局部晚期或转移性疾病的标准护理一线治疗是化疗和曲妥珠单抗加派姆单抗治疗程序性死亡配体1 （PD-L1）阳性[联合阳性评分(CPS)≥1]的肿瘤。Trastuzumab deruxtecan (T-DXd) 6.4 mg/kg单药疗法被批准作为her2阳性胃癌或GEJ癌患者的二线治疗。DESTINY-Gastric03 （NCT04379596）显示，在晚期治疗中，一线T-DXd 5.4 mg/kg加化疗加或不加派姆单抗治疗her2阳性胃癌或GEJ癌具有可控的安全性和良好的疗效。目的探讨一线T-DXd +无铂化疗联合派姆单抗治疗her2阳性胃癌或GEJ癌的方法。宿命- gastric05 （NCT06731478）是一项全球性、多中心、开放标签、随机III期试验，旨在评估一线T-DXd 5.4 mg/kg加5-氟尿嘧啶或卡培他滨和派姆单抗与曲妥珠单抗和派姆单抗联合铂基化疗在不可切除、局部晚期或转移性、中心证实her2阳性（免疫组织化学3+或免疫组织化学2+/原位杂交阳性）胃癌或胃癌，PD-L1 CPS≥1。一项探索性队列研究旨在评估T-DXd联合5-氟尿嘧啶或卡培他滨对PD-L1 CPS患者的治疗效果。

{"title":"DESTINY-Gastric05 phase III trial of first-line trastuzumab deruxtecan, chemotherapy, and pembrolizumab in HER2-positive gastric or gastroesophageal junction cancer","authors":"Y.Y. Janjigian , E. Smyth , L. Shen , J. Lee , P.M. Hoff , S. Lonardi , D. Barrios , K. Kobayashi , Y. Okuda , T. Kamio , K. Shitara","doi":"10.1016/j.esmogo.2025.100294","DOIUrl":"10.1016/j.esmogo.2025.100294","url":null,"abstract":"<div><h3>Background</h3><div>Gastric or gastroesophageal junction (GEJ) cancers are usually diagnosed at advanced stages with poor prognoses and 5-year survival rates. Standard-of-care first-line treatment of human epidermal growth factor receptor 2 (HER2)-positive locally advanced or metastatic disease is chemotherapy and trastuzumab, plus pembrolizumab for programmed death-ligand 1 (PD-L1)-positive [combined positive score (CPS) ≥1] tumors. Trastuzumab deruxtecan (T-DXd) 6.4 mg/kg monotherapy is approved as second-line treatment for patients with HER2-positive gastric or GEJ cancer. DESTINY-Gastric03 (NCT04379596) showed that first-line T-DXd 5.4 mg/kg plus chemotherapy with or without pembrolizumab in the advanced setting had manageable safety and promising efficacy in HER2-positive gastric or GEJ cancer.</div></div><div><h3>Aim</h3><div>To investigate a first-line T-DXd plus platinum-free chemotherapy with pembrolizumab treatment approach for patients with HER2-positive gastric or GEJ cancer.</div></div><div><h3>Trial design</h3><div>DESTINY-Gastric05 (NCT06731478) is a global, multicenter, open-label, randomized, phase III trial to evaluate the efficacy and safety of first-line T-DXd 5.4 mg/kg plus 5-fluorouracil or capecitabine and pembrolizumab versus platinum-based chemotherapy with trastuzumab and pembrolizumab in patients with unresectable, locally advanced or metastatic, centrally confirmed HER2-positive (immunohistochemistry 3+ or immunohistochemistry 2+/<em>in situ</em> hybridization positive) gastric or GEJ cancer with a PD-L1 CPS ≥1. An exploratory cohort is to evaluate T-DXd plus 5-fluorouracil or capecitabine in patients with PD-L1 CPS <1.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"11 ","pages":"Article 100294"},"PeriodicalIF":0.0,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146038192","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}

引用次数: 0