Pub Date : 2025-10-06DOI: 10.1016/j.esmogo.2025.100248
M. Ghidini , A. Parisi , I.V. Zurlo , M.M. Laterza , L. Gervaso , A.D. Ricci , A. Biasi , A. Nicastro , O. Garrone , G. Tomasello , A. Petrillo , F. Petrelli
Small bowel adenocarcinoma (SBA) is a rare and increasingly recognised malignancy, accounting for only 3.4% of all gastrointestinal cancers. It often presents with non-specific or late-stage symptoms, resulting in delayed diagnosis and poor prognosis. For advanced disease, treatment recommendations rely primarily on small phase II trials and retrospective series with no established standard therapy. Moreover, although SBA commonly harbours KRAS mutations (43%), CDKN2A (p16) loss, and HER2/ERBB2 mutations (12%), no targeted biological agents have demonstrated clinical efficacy against this disease. Our systematic review was conducted to comprehensively evaluate the available evidence on systemic therapies for patients with advanced or metastatic SBA, with particular focus on treatment efficacy, safety profiles, and the potential influence of molecular biomarkers.
{"title":"Treatment options for advanced small bowel adenocarcinoma: a systematic review","authors":"M. Ghidini , A. Parisi , I.V. Zurlo , M.M. Laterza , L. Gervaso , A.D. Ricci , A. Biasi , A. Nicastro , O. Garrone , G. Tomasello , A. Petrillo , F. Petrelli","doi":"10.1016/j.esmogo.2025.100248","DOIUrl":"10.1016/j.esmogo.2025.100248","url":null,"abstract":"<div><div>Small bowel adenocarcinoma (SBA) is a rare and increasingly recognised malignancy, accounting for only 3.4% of all gastrointestinal cancers. It often presents with non-specific or late-stage symptoms, resulting in delayed diagnosis and poor prognosis. For advanced disease, treatment recommendations rely primarily on small phase II trials and retrospective series with no established standard therapy. Moreover, although SBA commonly harbours <em>KRAS</em> mutations (43%), <em>CDKN2A</em> (p16) loss, and <em>HER2/ERBB2</em> mutations (12%), no targeted biological agents have demonstrated clinical efficacy against this disease. Our systematic review was conducted to comprehensively evaluate the available evidence on systemic therapies for patients with advanced or metastatic SBA, with particular focus on treatment efficacy, safety profiles, and the potential influence of molecular biomarkers.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"10 ","pages":"Article 100248"},"PeriodicalIF":0.0,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145268339","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 : 2025-09-30DOI: 10.1016/j.esmogo.2025.100242
N. Starling , L. Zhang , K. Dunton , A. Strübing , Y. Xiong , C. Livings , L. Brannman , M.Y. Beykloo , H. Mohamed , N. Trankov , P. Egger
Background
This study aimed to examine real-world treatment patterns and outcomes in patients with human epidermal growth factor receptor 2 (HER2)-positive gastric cancer (GC) or gastroesophageal junction (GEJ) adenocarcinoma receiving anticancer therapy in England.
Methods
Using the Cancer Analysis System English Cancer Outcomes Services Dataset, we retrospectively analyzed real-world (rw) treatment patterns, overall survival (rwOS), time to treatment discontinuation/death (rwTTD), and time to next treatment/death (rwTTNTD) in adults with inoperable, locally advanced or metastatic GC/GEJ adenocarcinoma on trastuzumab-based first line of treatment (1LoT) between January 2015 and December 2019.
Results
Among 948 patients included (median age 67.0 years), most were male (82.1%), with GEJ adenocarcinoma (57.4%) and de novo disease (81.8%); 33.3% patients received 2LoT and 6.6% received 3LoT. The most common regimen was capecitabine + cisplatin + trastuzumab in 1LoT (54.9%), paclitaxel in 2LoT (36.4%), and fluorouracil + irinotecan in 3LoT (19.1%). Median (Q1-Q3) rwOS and rwTTD for 1LoT were 11.8 months (6.2-21.5 months) and 6.3 months (3.0-10.6 months), respectively; these reduced to 6.1 months (3.4-11.2 months) and 2.8 months (1.7-4.6 months) for 2LoT, and 5.9 months (3.2-9.5 months) and 2.3 months (1.5-4.6 months) for 3LoT. Median rwTTNTD was 9.0 months (5.1-15.0 months), 5.5 months (3.0-8.5 months), and 5.7 months (3.0-9.2 months) for 1LoT, 2LoT, and 3LoT, respectively.
Conclusions
Poor outcomes persist for HER2-positive GC/GEJ adenocarcinoma progressing after 1LoT. More effective treatments, ideally ones targeting HER2, are needed.
本研究旨在研究在英国接受抗癌治疗的人表皮生长因子受体2 （HER2）阳性胃癌（GC）或胃食管交界处（GEJ）腺癌患者的现实世界治疗模式和结果。方法：使用Cancer Analysis System English Cancer Outcomes Services数据集，我们回顾性分析了2015年1月至2019年12月期间接受曲妥珠单抗一线治疗（1LoT）的不能手术、局部晚期或转移性GC/GEJ腺癌成人患者的现实世界（rw）治疗模式、总生存期（rwOS）、停药时间/死亡时间（rwTTD）和下一次治疗时间/死亡时间（rwTTNTD）。结果948例患者（中位年龄67.0岁）中，男性居多（82.1%），有GEJ腺癌（57.4%）和新发疾病（81.8%）；33.3%的患者接受2LoT， 6.6%的患者接受3LoT。最常见的方案是卡培他滨+顺铂+曲妥珠单抗1LoT(54.9%)，紫杉醇2LoT(36.4%)，氟尿嘧啶+伊立替康3LoT（19.1%）。1LoT的中位（Q1-Q3） rwOS和rwTTD分别为11.8个月（6.2-21.5个月）和6.3个月（3.0-10.6个月）；2个lot组减少到6.1个月（3.4-11.2个月）和2.8个月（1.7-4.6个月），3个lot组减少到5.9个月（3.2-9.5个月）和2.3个月（1.5-4.6个月）。1LoT、2LoT和3LoT的中位rwTTNTD分别为9.0个月（5.1-15.0个月）、5.5个月（3.0-8.5个月）和5.7个月（3.0-9.2个月）。结论her2阳性GC/GEJ腺癌在1LoT后进展的预后不稳定。需要更有效的治疗方法，理想的是针对HER2的治疗方法。
{"title":"Real-world treatment patterns and outcomes in advanced/metastatic gastric cancer or gastroesophageal junction adenocarcinoma treated with first-line anti-HER2 therapy in England","authors":"N. Starling , L. Zhang , K. Dunton , A. Strübing , Y. Xiong , C. Livings , L. Brannman , M.Y. Beykloo , H. Mohamed , N. Trankov , P. Egger","doi":"10.1016/j.esmogo.2025.100242","DOIUrl":"10.1016/j.esmogo.2025.100242","url":null,"abstract":"<div><h3>Background</h3><div>This study aimed to examine real-world treatment patterns and outcomes in patients with human epidermal growth factor receptor 2 (HER2)-positive gastric cancer (GC) or gastroesophageal junction (GEJ) adenocarcinoma receiving anticancer therapy in England.</div></div><div><h3>Methods</h3><div>Using the Cancer Analysis System English Cancer Outcomes Services Dataset, we retrospectively analyzed real-world (rw) treatment patterns, overall survival (rwOS), time to treatment discontinuation/death (rwTTD), and time to next treatment/death (rwTTNTD) in adults with inoperable, locally advanced or metastatic GC/GEJ adenocarcinoma on trastuzumab-based first line of treatment (1LoT) between January 2015 and December 2019.</div></div><div><h3>Results</h3><div>Among 948 patients included (median age 67.0 years), most were male (82.1%), with GEJ adenocarcinoma (57.4%) and <em>de novo</em> disease (81.8%); 33.3% patients received 2LoT and 6.6% received 3LoT. The most common regimen was capecitabine + cisplatin + trastuzumab in 1LoT (54.9%), paclitaxel in 2LoT (36.4%), and fluorouracil + irinotecan in 3LoT (19.1%). Median (Q1-Q3) rwOS and rwTTD for 1LoT were 11.8 months (6.2-21.5 months) and 6.3 months (3.0-10.6 months), respectively; these reduced to 6.1 months (3.4-11.2 months) and 2.8 months (1.7-4.6 months) for 2LoT, and 5.9 months (3.2-9.5 months) and 2.3 months (1.5-4.6 months) for 3LoT. Median rwTTNTD was 9.0 months (5.1-15.0 months), 5.5 months (3.0-8.5 months), and 5.7 months (3.0-9.2 months) for 1LoT, 2LoT, and 3LoT, respectively.</div></div><div><h3>Conclusions</h3><div>Poor outcomes persist for HER2-positive GC/GEJ adenocarcinoma progressing after 1LoT. More effective treatments, ideally ones targeting HER2, are needed.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"10 ","pages":"Article 100242"},"PeriodicalIF":0.0,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145220915","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 : 2025-09-29DOI: 10.1016/j.esmogo.2025.100243
W.Y. Chua , A. Yong , O. Lim , I. Seow-En , D. Chong , E. Wong , S. Han , S.-L. Koo , I. Tan , K.Y.Y. Ng
Introduction
Colorectal cancer (CRC) is the third most common malignancy and the third leading cause of cancer-related mortality worldwide. Patients are typically diagnosed at an early stage due to widespread use of colonoscopy screenings and stool testing. Despite the efficacy of early detection in CRC, there are concerns about the accessibility of these treatments for patients of lower socioeconomic status (SES), which may lead to poorer outcomes and exacerbate health inequity.
Patients and methods
We searched Medline and Embase from inception to 26 April 2024 to identify cohort studies comparing SES indicators and CRC outcomes. We computed hazard ratios (HRs) with accompanying 95% confidence intervals (CIs) for each study, and pooled the results using a random-effects meta-analysis. Quality assessment was carried out using Newcastle–Ottawa Quality Assessment Scale for cohort studies.
Results
In this meta-analysis of 37 studies involving 2 017 509 patients, we analysed the impact of SES on overall survival in patients with CRC. All but three studies were conducted in high-income countries. Our main findings demonstrated that lower income (HR 1.16, 95% CI 1.08-1.23, P < 0.0001), lower educational level (HR 1.24, 95% CI 1.17-1.31, P < 0.0001), lower neighbourhood SES (HR 1.22, 95% CI 1.19-1.25, P < 0.0001), and lower insurance coverage (HR 1.29, 95% CI 1.25-1.32, P < 0.0001) had a negative impact on overall survival in patients with CRC.
Conclusion
Lower income, educational level, insurance coverage, and neighbourhood SES had a negative impact on overall survival in patients with CRC. There is an urgent need to develop and implement interventions to reduce disparities in outcomes for patients with CRC who are of lower SES.
结直肠癌（CRC）是世界上第三大最常见的恶性肿瘤，也是导致癌症相关死亡的第三大原因。由于结肠镜检查和粪便检查的广泛使用，患者通常在早期被诊断出来。尽管早期发现结直肠癌有效，但人们担心这些治疗对社会经济地位较低的患者的可及性，这可能导致较差的结果并加剧健康不平等。患者和方法我们检索了Medline和Embase从成立到2024年4月26日，以确定比较SES指标和CRC结果的队列研究。我们计算了每项研究的风险比（hr）和随附的95%置信区间（ci），并使用随机效应荟萃分析汇总了结果。采用纽卡斯尔-渥太华质量评估量表对队列研究进行质量评估。在这项涉及2017509例患者的37项研究的荟萃分析中，我们分析了SES对结直肠癌患者总生存的影响。除了三项研究外，其他研究都是在高收入国家进行的。我们的主要研究结果表明，较低的收入（HR 1.16, 95% CI 1.08-1.23, P < 0.0001）、较低的教育水平（HR 1.24, 95% CI 1.17-1.31, P < 0.0001）、较低的社区经济地位（HR 1.22, 95% CI 1.19-1.25, P < 0.0001）和较低的保险覆盖率（HR 1.29, 95% CI 1.25-1.32, P < 0.0001）对结直肠癌患者的总体生存有负面影响。结论较低的收入、教育程度、保险覆盖率和社区社会经济地位对结直肠癌患者的总体生存有负面影响。迫切需要制定和实施干预措施，以减少社会经济地位较低的结直肠癌患者预后的差异。
{"title":"The impact of socioeconomic status on overall survival in patients with colorectal cancer: a systematic review and meta-analysis","authors":"W.Y. Chua , A. Yong , O. Lim , I. Seow-En , D. Chong , E. Wong , S. Han , S.-L. Koo , I. Tan , K.Y.Y. Ng","doi":"10.1016/j.esmogo.2025.100243","DOIUrl":"10.1016/j.esmogo.2025.100243","url":null,"abstract":"<div><h3>Introduction</h3><div>Colorectal cancer (CRC) is the third most common malignancy and the third leading cause of cancer-related mortality worldwide. Patients are typically diagnosed at an early stage due to widespread use of colonoscopy screenings and stool testing. Despite the efficacy of early detection in CRC, there are concerns about the accessibility of these treatments for patients of lower socioeconomic status (SES), which may lead to poorer outcomes and exacerbate health inequity.</div></div><div><h3>Patients and methods</h3><div>We searched Medline and Embase from inception to 26 April 2024 to identify cohort studies comparing SES indicators and CRC outcomes. We computed hazard ratios (HRs) with accompanying 95% confidence intervals (CIs) for each study, and pooled the results using a random-effects meta-analysis. Quality assessment was carried out using Newcastle–Ottawa Quality Assessment Scale for cohort studies.</div></div><div><h3>Results</h3><div>In this meta-analysis of 37 studies involving 2 017 509 patients, we analysed the impact of SES on overall survival in patients with CRC. All but three studies were conducted in high-income countries. Our main findings demonstrated that lower income (HR 1.16, 95% CI 1.08-1.23, <em>P</em> < 0.0001), lower educational level (HR 1.24, 95% CI 1.17-1.31, <em>P</em> < 0.0001), lower neighbourhood SES (HR 1.22, 95% CI 1.19-1.25, <em>P</em> < 0.0001), and lower insurance coverage (HR 1.29, 95% CI 1.25-1.32, <em>P</em> < 0.0001) had a negative impact on overall survival in patients with CRC.</div></div><div><h3>Conclusion</h3><div>Lower income, educational level, insurance coverage, and neighbourhood SES had a negative impact on overall survival in patients with CRC. There is an urgent need to develop and implement interventions to reduce disparities in outcomes for patients with CRC who are of lower SES.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"10 ","pages":"Article 100243"},"PeriodicalIF":0.0,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145220914","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 : 2025-09-25DOI: 10.1016/j.esmogo.2025.100240
A. Ooki , H. Osumi , K. Shimada , N. Machida , H. Hara , M. Takamatsu , N. Ishizuka , Y. Fukuda , W. Hashimoto , K. Yamaguchi
Background
Human epidermal growth factor receptor 2 (HER2) is overexpressed in ∼20% of advanced gastroesophageal adenocarcinomas (GEAs). Trastuzumab (T-mab) is the standard first-line treatment for HER2-positive GEA, and trastuzumab deruxtecan (T-DXd) has demonstrated clinical efficacy in later-line settings. However, the potential loss of HER2 expression following T-mab treatment raises concerns about the subsequent effectiveness of T-DXd. The temporal dynamics of HER2 expression across treatment lines are not well understood.
Design
We designed a prospective, single-arm, multicenter study to investigate the association between the efficacy of third-line T-DXd and changes in HER2 status in tumor tissue and blood after first-line T-mab treatment in patients with HER2-positive GEA. The aim is to inform the optimal clinical use of T-DXd. Serial tumor and/or blood re-biopsies will be carried out at each line of treatment following first-line therapy. The study consists of two parts. In part 1, we will evaluate biomarker dynamics—specifically HER2 status and circulating tumor DNA alterations—during second-line therapy. In part 2, we will assess the efficacy and safety of third-line T-DXd in relation to these biomarker changes. Approximately 120 patients will be enrolled in part 1 and 50 in part 2.
{"title":"Multicenter prospective EN-MARK study: efficacy of third-line trastuzumab deruxtecan and dynamic changes in biomarkers, including HER2 status","authors":"A. Ooki , H. Osumi , K. Shimada , N. Machida , H. Hara , M. Takamatsu , N. Ishizuka , Y. Fukuda , W. Hashimoto , K. Yamaguchi","doi":"10.1016/j.esmogo.2025.100240","DOIUrl":"10.1016/j.esmogo.2025.100240","url":null,"abstract":"<div><h3>Background</h3><div>Human epidermal growth factor receptor 2 (HER2) is overexpressed in ∼20% of advanced gastroesophageal adenocarcinomas (GEAs). Trastuzumab (T-mab) is the standard first-line treatment for HER2-positive GEA, and trastuzumab deruxtecan (T-DXd) has demonstrated clinical efficacy in later-line settings. However, the potential loss of HER2 expression following T-mab treatment raises concerns about the subsequent effectiveness of T-DXd. The temporal dynamics of HER2 expression across treatment lines are not well understood.</div></div><div><h3>Design</h3><div>We designed a prospective, single-arm, multicenter study to investigate the association between the efficacy of third-line T-DXd and changes in HER2 status in tumor tissue and blood after first-line T-mab treatment in patients with HER2-positive GEA. The aim is to inform the optimal clinical use of T-DXd. Serial tumor and/or blood re-biopsies will be carried out at each line of treatment following first-line therapy. The study consists of two parts. In part 1, we will evaluate biomarker dynamics—specifically HER2 status and circulating tumor DNA alterations—during second-line therapy. In part 2, we will assess the efficacy and safety of third-line T-DXd in relation to these biomarker changes. Approximately 120 patients will be enrolled in part 1 and 50 in part 2.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"10 ","pages":"Article 100240"},"PeriodicalIF":0.0,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145159274","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 : 2025-09-22DOI: 10.1016/j.esmogo.2025.100239
R.P. Riechelmann , T.C. Felismino , B. Müller , R. D’Alpino Peixoto , D.A. Goldstein
The cost of cancer care has significantly increased, with a major cause being the high cost of new drugs, limiting their access worldwide. Drug dose optimization (DDO) and substitutions may help improve treatment access for patients residing in financially resource-limited countries. We propose and discuss these strategies for patients with gastrointestinal (GI) cancers and neuroendocrine tumors (NET) who are treated in low- and middle-income countries, considering the available scientific evidence. Overall recommendations include dose-reductions of palliative chemotherapy, avoiding colony-stimulation growth factors when unnecessary, lower doses of immune checkpoint inhibitors and paclitaxel as a substitute for nab-paclitaxel. Specific proposals by tumor type are discussed and recommended according to resource availability.
{"title":"Drug dose optimization and substitutions to improve access for patients with gastrointestinal and neuroendocrine cancers","authors":"R.P. Riechelmann , T.C. Felismino , B. Müller , R. D’Alpino Peixoto , D.A. Goldstein","doi":"10.1016/j.esmogo.2025.100239","DOIUrl":"10.1016/j.esmogo.2025.100239","url":null,"abstract":"<div><div>The cost of cancer care has significantly increased, with a major cause being the high cost of new drugs, limiting their access worldwide. Drug dose optimization (DDO) and substitutions may help improve treatment access for patients residing in financially resource-limited countries. We propose and discuss these strategies for patients with gastrointestinal (GI) cancers and neuroendocrine tumors (NET) who are treated in low- and middle-income countries, considering the available scientific evidence. Overall recommendations include dose-reductions of palliative chemotherapy, avoiding colony-stimulation growth factors when unnecessary, lower doses of immune checkpoint inhibitors and paclitaxel as a substitute for nab-paclitaxel. Specific proposals by tumor type are discussed and recommended according to resource availability.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"10 ","pages":"Article 100239"},"PeriodicalIF":0.0,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109179","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 : 2025-09-22DOI: 10.1016/j.esmogo.2025.100235
I. Chau , J. Bridgewater , L. Wyrwicz , M. Greenwood , S.I. Blum , A. Moreno-Koehler , E. Martin , F. Taylor , C. Davis , P. Singh
Background
First-line nivolumab plus chemotherapy (NIVO + CHEMO) and nivolumab plus ipilimumab (NIVO + IPI) improves overall survival for patients with advanced esophageal squamous-cell carcinoma (ESCC). This analysis aimed to use quality-adjusted time without symptoms or toxicity (Q-TWiST) analyses to assess the overall risk–benefit profile of these treatments in the CheckMate 648 study.
Materials and methods
A post hoc analysis of CheckMate 648 assessed the association of quality-adjusted survival with treatment types (first-line NIVO + CHEMO, NIVO + IPI, or CHEMO alone) using the Q-TWiST methodology. The analysis included all randomized patients and those with tumor cell programmed death-ligand 1 (PD-L1) ≥1% at baseline, with a minimum follow-up of 45 months. Health-related quality of life was assessed using the EuroQoL 5-Dimension 3-Level (EQ-5D-3L) questionnaire. Differences in Q-TWiST exceeding 1.5 months were deemed clinically important.
Results
The analysis included 970 patients in the all-randomized population. Q-TWiST values were 12.8 and 12.9 months for NIVO + CHEMO and NIVO + IPI, respectively, compared with 10.8 months for CHEMO alone, showing gains of 2.0 and 2.1 months, respectively. In patients with tumor cell PD-L1 ≥1% (473 patients), Q-TWiST values were higher for NIVO + CHEMO (13.0 months) and NIVO + IPI (13.3 months) compared with CHEMO alone (9.1 months), with gains of 3.9 and 4.2 months, respectively. All gains surpassed the clinically important threshold.
Conclusion
These findings support NIVO + CHEMO and NIVO + IPI as first-line treatments for patients with advanced ESCC, particularly those with tumor cell PD-L1 ≥1%.
{"title":"A quality-adjusted time without symptoms and toxicity (Q-TWiST) analysis comparing nivolumab plus ipilimumab or nivolumab plus chemotherapy versus chemotherapy in patients with advanced esophageal squamous-cell carcinoma in CheckMate 648","authors":"I. Chau , J. Bridgewater , L. Wyrwicz , M. Greenwood , S.I. Blum , A. Moreno-Koehler , E. Martin , F. Taylor , C. Davis , P. Singh","doi":"10.1016/j.esmogo.2025.100235","DOIUrl":"10.1016/j.esmogo.2025.100235","url":null,"abstract":"<div><h3>Background</h3><div>First-line nivolumab plus chemotherapy (NIVO + CHEMO) and nivolumab plus ipilimumab (NIVO + IPI) improves overall survival for patients with advanced esophageal squamous-cell carcinoma (ESCC). This analysis aimed to use quality-adjusted time without symptoms or toxicity (Q-TWiST) analyses to assess the overall risk–benefit profile of these treatments in the CheckMate 648 study.</div></div><div><h3>Materials and methods</h3><div>A <em>post hoc</em> analysis of CheckMate 648 assessed the association of quality-adjusted survival with treatment types (first-line NIVO + CHEMO, NIVO + IPI, or CHEMO alone) using the Q-TWiST methodology. The analysis included all randomized patients and those with tumor cell programmed death-ligand 1 (PD-L1) ≥1% at baseline, with a minimum follow-up of 45 months. Health-related quality of life was assessed using the EuroQoL 5-Dimension 3-Level (EQ-5D-3L) questionnaire. Differences in Q-TWiST exceeding 1.5 months were deemed clinically important.</div></div><div><h3>Results</h3><div>The analysis included 970 patients in the all-randomized population. Q-TWiST values were 12.8 and 12.9 months for NIVO + CHEMO and NIVO + IPI, respectively, compared with 10.8 months for CHEMO alone, showing gains of 2.0 and 2.1 months, respectively. In patients with tumor cell PD-L1 ≥1% (473 patients), Q-TWiST values were higher for NIVO + CHEMO (13.0 months) and NIVO + IPI (13.3 months) compared with CHEMO alone (9.1 months), with gains of 3.9 and 4.2 months, respectively. All gains surpassed the clinically important threshold.</div></div><div><h3>Conclusion</h3><div>These findings support NIVO + CHEMO and NIVO + IPI as first-line treatments for patients with advanced ESCC, particularly those with tumor cell PD-L1 ≥1%.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"10 ","pages":"Article 100235"},"PeriodicalIF":0.0,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109178","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 : 2025-09-15DOI: 10.1016/j.esmogo.2025.100237
L.M. Veen , A.P. van der Zalm , D. Blangé , P. Manoukian , M. van Mourik , R.R. de Goeij-de Haas , S.R. Piersma , T.V. Pham , C.R. Jimenez , S.L. Meijer , H.W. van Laarhoven , M.F. Bijlsma
Background
Despite combination therapies, less than half of patients with resectable esophageal cancer (EC) survive beyond 5 years. Previous studies, primarily using transcriptomics, revealed high plasticity in these cancer cells. In other cancer contexts, such plasticity has been demonstrated to also result in aberrant tubulin expression and resistance to taxanes. Given that taxanes are a cornerstone in EC treatment, we established a multi-omics analysis of neoadjuvantly treated EC cells and tissues with a focus on tubulins.
Materials and methods
We applied transcriptomics and proteomics to pretreated EC resection samples and primary cell lines from various treatment settings. RNA-Sequencing and MS-based proteomics data were correlated with clinical outcomes to identify response-associated tubulin genes and proteins. In vitro experiments included lentiviral gene silencing of candidate resistance mediators and pharmacological interventions.
Results
In both the transcriptomics and proteomics datasets, tubulin isoforms that are not typically expressed in the esophagus were found to associate with survival outcome. Specifically, we found that beta-tubulin 3 (TUBB3) was associated with unfavorable outcomes. However, TUBB3 silencing in vitro did not render cells sensitive to taxanes, nor did it prevent transitions to resistant cell states. Pharmacological inhibition did not improve the efficacy of chemoradiation. Instead, we found that TUBB3 is highly correlated with mesenchymal cell states, and that its expression is a consequence of such transitions rather than a cause.
Conclusions
A neuronal tubulin isoform was found to increase in cells undergoing mesenchymal transition and acquiring resistance. These abundant proteins could serve as biomarkers for acquired therapy resistance in EC.
{"title":"Proteome and transcriptome analysis reveals tubulin isotype switching in paclitaxel-treated esophageal cancer","authors":"L.M. Veen , A.P. van der Zalm , D. Blangé , P. Manoukian , M. van Mourik , R.R. de Goeij-de Haas , S.R. Piersma , T.V. Pham , C.R. Jimenez , S.L. Meijer , H.W. van Laarhoven , M.F. Bijlsma","doi":"10.1016/j.esmogo.2025.100237","DOIUrl":"10.1016/j.esmogo.2025.100237","url":null,"abstract":"<div><h3>Background</h3><div>Despite combination therapies, less than half of patients with resectable esophageal cancer (EC) survive beyond 5 years. Previous studies, primarily using transcriptomics, revealed high plasticity in these cancer cells. In other cancer contexts, such plasticity has been demonstrated to also result in aberrant tubulin expression and resistance to taxanes. Given that taxanes are a cornerstone in EC treatment, we established a multi-omics analysis of neoadjuvantly treated EC cells and tissues with a focus on tubulins.</div></div><div><h3>Materials and methods</h3><div>We applied transcriptomics and proteomics to pretreated EC resection samples and primary cell lines from various treatment settings. RNA-Sequencing and MS-based proteomics data were correlated with clinical outcomes to identify response-associated tubulin genes and proteins. <em>In vitro</em> experiments included lentiviral gene silencing of candidate resistance mediators and pharmacological interventions.</div></div><div><h3>Results</h3><div>In both the transcriptomics and proteomics datasets, tubulin isoforms that are not typically expressed in the esophagus were found to associate with survival outcome. Specifically, we found that beta-tubulin 3 (TUBB3) was associated with unfavorable outcomes. However, TUBB3 silencing <em>in vitro</em> did not render cells sensitive to taxanes, nor did it prevent transitions to resistant cell states. Pharmacological inhibition did not improve the efficacy of chemoradiation. Instead, we found that TUBB3 is highly correlated with mesenchymal cell states, and that its expression is a consequence of such transitions rather than a cause.</div></div><div><h3>Conclusions</h3><div>A neuronal tubulin isoform was found to increase in cells undergoing mesenchymal transition and acquiring resistance. These abundant proteins could serve as biomarkers for acquired therapy resistance in EC.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"10 ","pages":"Article 100237"},"PeriodicalIF":0.0,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145061400","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 : 2025-09-12DOI: 10.1016/j.esmogo.2025.100238
I. Ben-Aharon , N. Fokter Dovnik , H.W.M. van Laarhoven , M.G. Guren , I. Baraibar , N. Gordon , T. Goshen-Lago , R. Verhoeven , T. Sokop , R. Obermannova , F. Lordick
Background
While the rising incidence of early-onset colorectal cancer has been documented worldwide, there is a paucity of data on the epidemiological changes in other gastrointestinal (GI) cancers in the young population in Europe. We sought to characterize incidence patterns of GI cancers in young patients in different European/Mediterranean countries.
Patients and methods
National cancer registries in several European countries were contacted to obtain the absolute number of GI cancer cases per age group (15-49 years) at 5-year intervals and the absolute population size for each of these age groups annually from 2008 to 2018. Data were analyzed to calculate year-to-year incidence rate change and average annual percentage change.
Results
Seven countries were included in the analysis: the Czech Republic, Germany, Israel, the Netherlands, Norway, Slovenia, and Spain. Different trends were observed for different GI cancers. For colorectal cancer, all countries except Germany showed increasing incidence rates in a similar pattern for males and females. An increasing trend in pancreatic cancer was documented in the Czech Republic, more in males, and in Slovenia and Israel significantly more in females. There was a slight increase in Spain and Germany, with no difference by sex. The incidence of early-onset gastric and esophageal cancer was very low and non-rising.
Conclusions
Early-onset cancers along the GI tract show different patterns in different European countries. For some types of GI tumors the incidence was fairly stable between 2008 and 2018 while some were increasing, in particular colorectal cancer in both sexes, and pancreatic cancer in females.
{"title":"Sex differences in the incidence trends of early-onset gastrointestinal cancer—the European/Mediterranean perspective","authors":"I. Ben-Aharon , N. Fokter Dovnik , H.W.M. van Laarhoven , M.G. Guren , I. Baraibar , N. Gordon , T. Goshen-Lago , R. Verhoeven , T. Sokop , R. Obermannova , F. Lordick","doi":"10.1016/j.esmogo.2025.100238","DOIUrl":"10.1016/j.esmogo.2025.100238","url":null,"abstract":"<div><h3>Background</h3><div>While the rising incidence of early-onset colorectal cancer has been documented worldwide, there is a paucity of data on the epidemiological changes in other gastrointestinal (GI) cancers in the young population in Europe. We sought to characterize incidence patterns of GI cancers in young patients in different European/Mediterranean countries.</div></div><div><h3>Patients and methods</h3><div>National cancer registries in several European countries were contacted to obtain the absolute number of GI cancer cases per age group (15-49 years) at 5-year intervals and the absolute population size for each of these age groups annually from 2008 to 2018. Data were analyzed to calculate year-to-year incidence rate change and average annual percentage change.</div></div><div><h3>Results</h3><div>Seven countries were included in the analysis: the Czech Republic, Germany, Israel, the Netherlands, Norway, Slovenia, and Spain. Different trends were observed for different GI cancers. For colorectal cancer, all countries except Germany showed increasing incidence rates in a similar pattern for males and females. An increasing trend in pancreatic cancer was documented in the Czech Republic, more in males, and in Slovenia and Israel significantly more in females. There was a slight increase in Spain and Germany, with no difference by sex. The incidence of early-onset gastric and esophageal cancer was very low and non-rising.</div></div><div><h3>Conclusions</h3><div>Early-onset cancers along the GI tract show different patterns in different European countries. For some types of GI tumors the incidence was fairly stable between 2008 and 2018 while some were increasing, in particular colorectal cancer in both sexes, and pancreatic cancer in females.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"10 ","pages":"Article 100238"},"PeriodicalIF":0.0,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145049850","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号