Pub Date : 2025-08-26DOI: 10.1016/j.esmogo.2025.100230
F. Salvà , G. Catani , N. Saoudi , I. Baraibar , J. Ros , M. Rodriguez , C. Salvà de Torres , A. Alcaraz , A. Garcia , R. Comas , F. Ruiz-Pace , A. Rezqallah , R. Dienstmann , J. Tabernero , E. Elez
Background
Oxaliplatin, a key agent used for managing metastatic colorectal cancer (mCRC), is often discontinued due to cumulative toxicity. Its reintroduction in later treatment lines remains a common clinical practice, despite the absence of robust prospective trials supporting this therapeutic strategy. This study aimed to evaluate the efficacy of oxaliplatin rechallenge in refractory mCRC and to identify patient characteristics predictive of improved outcomes with this approach.
Patients and methods
We retrospectively analyzed patients treated with oxaliplatin in the third- or fourth-line setting at Vall d’Hebron Hospital between 2015 and 2021. Outcomes included overall response rate (ORR), disease control rate (DCR), and median progression-free survival (PFS). Patients achieving median PFS >6 months were classified as best-responders. Factors affecting PFS were analyzed with a Cox regression model. Amplicon-seq analysis of 61 genes was carried out using Illumina technology.
Results
Of 735 patients receiving third- or fourth-line treatment, 102 (14%) received oxaliplatin retreatment (69% in third line; 31% in fourth line). Median PFS was 4.0 months (95% CI 3.29-5.03 months), with an ORR of 12% and DCR of 39%. Twenty-eight patients (27%) were best-responders. Predictors of efficacy included response to first-line oxaliplatin, planned oxaliplatin discontinuation, and an oxaliplatin-free interval of at least 22.0 months. No significant associations were identified between molecular alterations and prognostic subgroups.
Conclusions
Oxaliplatin-based reintroduction therapy is a viable strategy in mCRC, particularly for patients with a favorable prior response and prolonged oxaliplatin-free intervals. However, identifying more precise biomarkers is essential to improve patient selection and maximize treatment efficacy.
多沙利铂是治疗转移性结直肠癌（mCRC）的关键药物，由于累积毒性经常被停药。尽管缺乏强有力的前瞻性试验支持这种治疗策略，但在后期治疗中重新引入它仍然是一种常见的临床实践。本研究旨在评估奥沙利铂再挑战在难治性mCRC中的疗效，并确定预测该方法改善预后的患者特征。患者和方法：我们回顾性分析了2015年至2021年间在Vall d 'Hebron医院接受奥沙利铂治疗的三线或四线患者。结果包括总缓解率（ORR）、疾病控制率（DCR）和中位无进展生存期（PFS）。中位PFS达到6个月的患者被归类为最佳应答者。采用Cox回归模型分析影响PFS的因素。利用Illumina技术对61个基因进行扩增子序列分析。结果735例接受三线或四线治疗的患者中，102例（14%）接受奥沙利铂再治疗（三线69%，四线31%）。中位PFS为4.0个月（95% CI 3.29-5.03个月），ORR为12%，DCR为39%。28名患者（27%）是最佳应答者。疗效的预测指标包括对一线奥沙利铂的反应，计划停用奥沙利铂，以及至少22.0个月的无奥沙利铂间隔。未发现分子改变与预后亚组之间存在显著关联。结论以索沙利铂为基础的再引入治疗是治疗mCRC的一种可行策略，特别是对于既往疗效良好且无奥沙利铂治疗间隔延长的患者。然而，确定更精确的生物标志物对于改善患者选择和最大化治疗效果至关重要。
{"title":"Retreatment with oxaliplatin-based regimens in refractory metastatic colorectal cancer: characterization of high-response patients","authors":"F. Salvà , G. Catani , N. Saoudi , I. Baraibar , J. Ros , M. Rodriguez , C. Salvà de Torres , A. Alcaraz , A. Garcia , R. Comas , F. Ruiz-Pace , A. Rezqallah , R. Dienstmann , J. Tabernero , E. Elez","doi":"10.1016/j.esmogo.2025.100230","DOIUrl":"10.1016/j.esmogo.2025.100230","url":null,"abstract":"<div><h3>Background</h3><div>Oxaliplatin, a key agent used for managing metastatic colorectal cancer (mCRC), is often discontinued due to cumulative toxicity. Its reintroduction in later treatment lines remains a common clinical practice, despite the absence of robust prospective trials supporting this therapeutic strategy. This study aimed to evaluate the efficacy of oxaliplatin rechallenge in refractory mCRC and to identify patient characteristics predictive of improved outcomes with this approach.</div></div><div><h3>Patients and methods</h3><div>We retrospectively analyzed patients treated with oxaliplatin in the third- or fourth-line setting at Vall d’Hebron Hospital between 2015 and 2021. Outcomes included overall response rate (ORR), disease control rate (DCR), and median progression-free survival (PFS). Patients achieving median PFS >6 months were classified as best-responders. Factors affecting PFS were analyzed with a Cox regression model. Amplicon-seq analysis of 61 genes was carried out using Illumina technology.</div></div><div><h3>Results</h3><div>Of 735 patients receiving third- or fourth-line treatment, 102 (14%) received oxaliplatin retreatment (69% in third line; 31% in fourth line). Median PFS was 4.0 months (95% CI 3.29-5.03 months), with an ORR of 12% and DCR of 39%. Twenty-eight patients (27%) were best-responders. Predictors of efficacy included response to first-line oxaliplatin, planned oxaliplatin discontinuation, and an oxaliplatin-free interval of at least 22.0 months. No significant associations were identified between molecular alterations and prognostic subgroups.</div></div><div><h3>Conclusions</h3><div>Oxaliplatin-based reintroduction therapy is a viable strategy in mCRC, particularly for patients with a favorable prior response and prolonged oxaliplatin-free intervals. However, identifying more precise biomarkers is essential to improve patient selection and maximize treatment efficacy.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"9 ","pages":"Article 100230"},"PeriodicalIF":0.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144904584","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 : 2025-08-18DOI: 10.1016/j.esmogo.2025.100225
J. Ros , V. Navarro , G. Villacampa , I. Baraibar , F. Salvà , M. Rodriguez , C. Vaghi , A. Garcia , A. Alcaraz , J. Tabernero , E. Élez , R. Dienstmann
Background
The BRAF V600E mutation, found in up to 12% of patients with metastatic colorectal cancer, is associated with aggressive disease and poor response to standard chemotherapy. However, the advent of BRAF inhibitors has led to improved clinical outcomes and survival. While surrogate endpoints for predicting overall survival (OS) have been extensively studied in the overall colorectal cancer population treated with chemotherapy, their applicability in patients with BRAF V600E-mutant colorectal cancer receiving either BRAF inhibitor combinations or conventional chemotherapy remains unclear, and needs to be better elucidated. The aim of the study was to evaluate surrogate endpoints to predict OS in patients with BRAF V600E-mutant colorectal cancer treated with either BRAF inhibitor combinations or chemotherapy.
Materials and methods
A systematic review was carried out to identify clinical trials or real-world cohorts evaluating patients with BRAF-mutant colorectal cancer treated either with chemotherapy or BRAF inhibitor combinations. A control cohort of melanoma patients treated with BRAF inhibitors in a phase III randomized trial was included. Adjusted R2 (R2adj) values were calculated to quantify the association between surrogate endpoints and median OS.
Results
Overall, a total of 5227 patients included in 29 cohorts were analyzed. Among patients with colorectal cancer treated with chemotherapy, overall response rate (ORR) and disease control rate (DCR) showed a high correlation with OS (R2adj > 0.90). Among patients treated with targeted therapy, progression-free survival (PFS) showed the highest correlation with OS (R2adj = 0.90). In the melanoma cohort, PFS was strongly associated with OS (R2adj = 0.92).
Conclusions
In BRAF-mutant colorectal cancer, standard surrogate endpoints for chemotherapy-based treatments accurately predict OS; however, when patients are treated with targeted therapies, both ORR and PFS have proven to be reliable predictors of survival.
{"title":"Surrogate to predict overall survival in patients with BRAF V600E-mutant colorectal cancer treated with BRAF inhibitor combinations","authors":"J. Ros , V. Navarro , G. Villacampa , I. Baraibar , F. Salvà , M. Rodriguez , C. Vaghi , A. Garcia , A. Alcaraz , J. Tabernero , E. Élez , R. Dienstmann","doi":"10.1016/j.esmogo.2025.100225","DOIUrl":"10.1016/j.esmogo.2025.100225","url":null,"abstract":"<div><h3>Background</h3><div>The <em>BRAF</em> V600E mutation, found in up to 12% of patients with metastatic colorectal cancer, is associated with aggressive disease and poor response to standard chemotherapy. However, the advent of BRAF inhibitors has led to improved clinical outcomes and survival. While surrogate endpoints for predicting overall survival (OS) have been extensively studied in the overall colorectal cancer population treated with chemotherapy, their applicability in patients with <em>BRAF</em> V600E-mutant colorectal cancer receiving either BRAF inhibitor combinations or conventional chemotherapy remains unclear, and needs to be better elucidated. The aim of the study was to evaluate surrogate endpoints to predict OS in patients with <em>BRAF</em> V600E-mutant colorectal cancer treated with either BRAF inhibitor combinations or chemotherapy.</div></div><div><h3>Materials and methods</h3><div>A systematic review was carried out to identify clinical trials or real-world cohorts evaluating patients with <em>BRAF</em>-mutant colorectal cancer treated either with chemotherapy or BRAF inhibitor combinations. A control cohort of melanoma patients treated with BRAF inhibitors in a phase III randomized trial was included. Adjusted <em>R</em><sup>2</sup> (<em>R</em><sup>2</sup><sub>adj</sub>) values were calculated to quantify the association between surrogate endpoints and median OS.</div></div><div><h3>Results</h3><div>Overall, a total of 5227 patients included in 29 cohorts were analyzed. Among patients with colorectal cancer treated with chemotherapy, overall response rate (ORR) and disease control rate (DCR) showed a high correlation with OS (<em>R</em><sup>2</sup><sub>adj</sub> > 0.90). Among patients treated with targeted therapy, progression-free survival (PFS) showed the highest correlation with OS (<em>R</em><sup>2</sup><sub>adj</sub> = 0.90). In the melanoma cohort, PFS was strongly associated with OS (<em>R</em><sup>2</sup><sub>adj</sub> = 0.92).</div></div><div><h3>Conclusions</h3><div>In <em>BRAF</em>-mutant colorectal cancer, standard surrogate endpoints for chemotherapy-based treatments accurately predict OS; however, when patients are treated with targeted therapies, both ORR and PFS have proven to be reliable predictors of survival.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"9 ","pages":"Article 100225"},"PeriodicalIF":0.0,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144860474","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 : 2025-08-14DOI: 10.1016/j.esmogo.2025.100223
K. Sugiyama , S. Kumar , A. Chaudry , N. Patel , P. Patel , D. Cunningham , N. Starling , S. Rao , C. Fribbens , L. Eldridge , I. Chau
Background
Malnutrition, prevalent in locally advanced oesophagogastric adenocarcinoma (LA-OGA), has an undetermined impact on survival. This study aimed to elucidate the association between survival and nutritional status in patients with LA-OGA undergoing perioperative 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) treatment.
Materials and methods
We screened patients with LA-OGA (cT2-4 and/or N1-3) treated with FLOT from 423 patients who underwent radical resection at The Royal Marsden Hospital between 2017 and 2023. Nutritional status was assessed using body weight and prognostic nutritional index (PNI). The primary outcome was 3-year recurrence-free survival (RFS) rate. Survival time was estimated using Kaplan–Meier curves and restricted mean survival time at 36 months. Multivariate analyses were carried out. Pathological response was defined as a tumour regression grade of 1-2 using the Mandard criteria.
Results
A total of 210 patients met the inclusion criteria [median follow-up time, 26.5 months; 3-year RFS rate, 53% (95% confidence interval 45% to 60%)]. Weight loss and PNI at diagnosis and after neoadjuvant chemotherapy were not significant predictors of RFS. A decrease in PNI during neoadjuvant chemotherapy was associated with a significantly shorter 3-year RFS rate than a maintained or increased PNI (46% versus 69%, P < 0.01). The restricted mean survival time difference was 5.46 months (95% confidence interval 1.73-9.19 months, P < 0.001). A decreased PNI (P = 0.03) independently and negatively predicted RFS. The pathological response was not associated with PNI changes (28.2% versus 30.4%, P = 0.75).
Conclusions
Our findings suggest that changes in PNI during neoadjuvant therapy may be associated with survival outcomes.
{"title":"Impact of nutritional status on pathological response and recurrence-free survival in locally advanced oesophagogastric adenocarcinoma treated with perioperative FLOT therapy","authors":"K. Sugiyama , S. Kumar , A. Chaudry , N. Patel , P. Patel , D. Cunningham , N. Starling , S. Rao , C. Fribbens , L. Eldridge , I. Chau","doi":"10.1016/j.esmogo.2025.100223","DOIUrl":"10.1016/j.esmogo.2025.100223","url":null,"abstract":"<div><h3>Background</h3><div>Malnutrition, prevalent in locally advanced oesophagogastric adenocarcinoma (LA-OGA), has an undetermined impact on survival. This study aimed to elucidate the association between survival and nutritional status in patients with LA-OGA undergoing perioperative 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) treatment.</div></div><div><h3>Materials and methods</h3><div>We screened patients with LA-OGA (cT2-4 and/or N1-3) treated with FLOT from 423 patients who underwent radical resection at The Royal Marsden Hospital between 2017 and 2023. Nutritional status was assessed using body weight and prognostic nutritional index (PNI). The primary outcome was 3-year recurrence-free survival (RFS) rate. Survival time was estimated using Kaplan–Meier curves and restricted mean survival time at 36 months. Multivariate analyses were carried out. Pathological response was defined as a tumour regression grade of 1-2 using the Mandard criteria.</div></div><div><h3>Results</h3><div>A total of 210 patients met the inclusion criteria [median follow-up time, 26.5 months; 3-year RFS rate, 53% (95% confidence interval 45% to 60%)]. Weight loss and PNI at diagnosis and after neoadjuvant chemotherapy were not significant predictors of RFS. A decrease in PNI during neoadjuvant chemotherapy was associated with a significantly shorter 3-year RFS rate than a maintained or increased PNI (46% versus 69%, <em>P</em> < 0.01). The restricted mean survival time difference was 5.46 months (95% confidence interval 1.73-9.19 months, <em>P</em> < 0.001). A decreased PNI (<em>P</em> = 0.03) independently and negatively predicted RFS. The pathological response was not associated with PNI changes (28.2% versus 30.4%, <em>P</em> = 0.75).</div></div><div><h3>Conclusions</h3><div>Our findings suggest that changes in PNI during neoadjuvant therapy may be associated with survival outcomes.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"9 ","pages":"Article 100223"},"PeriodicalIF":0.0,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144829440","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 : 2025-08-13DOI: 10.1016/j.esmogo.2025.100217
S. Lonardi , K. Potthoff , L. Procaccio , C. Yoo , T. Macarulla , F. Hedouin-Biville , G.W. Prager
Pancreatic cancer (PAC) is an aggressive disease with poor clinical outcomes. Liposomal irinotecan in combination with 5-fluorouracil and leucovorin (nal-IRI+5-FU/LV) is the only approved therapy for metastatic PAC following gemcitabine-based therapy, based on the survival benefit demonstrated in the phase III NAPOLI-1 trial. Factors associated with long-term survival in this trial included age ≤65 years, Karnofsky performance status (KPS) ≥90, neutrophil-to-lymphocyte (N/L) ratio ≤5, carbohydrate antigen (CA) 19-9 <59-times the upper limit of normal (ULN), and no liver metastases. Using real-world data from studies conducted in Korea, Italy, and Germany, this review aims to assess the suitability of prognostic factors identified in the NAPOLI-1 trial nomogram. In these real-world studies, a high CA19-9 level and a low N/L ratio were associated with long-term survival in patients treated with nal-IRI+5-FU/LV. The impact of albumin levels, body mass index (BMI), liver metastasis, and KPS on survival identified from the NAPOLI-1 trial was confirmed in some real-world analyses but not consistently. Factors such as patient age and number of previous lines of treatment that were not identified in the NAPOLI-1 nomogram may be associated with long-term survival with nal-IRI+5-FU/LV in the real-world. In conclusion, this review has shown that while prognostic factors are useful for patient stratification, their predictive value on the efficacy of nal-IRI+5-FU/LV is low, thus this treatment may also result in long-term survival in patients with apparently unfavorable characteristics.
{"title":"Long-term survival in patients with pancreatic cancer treated with second-line liposomal irinotecan plus 5-fluorouracil/leucovorin: observations from Korea, Italy, and Germany","authors":"S. Lonardi , K. Potthoff , L. Procaccio , C. Yoo , T. Macarulla , F. Hedouin-Biville , G.W. Prager","doi":"10.1016/j.esmogo.2025.100217","DOIUrl":"10.1016/j.esmogo.2025.100217","url":null,"abstract":"<div><div>Pancreatic cancer (PAC) is an aggressive disease with poor clinical outcomes. Liposomal irinotecan in combination with 5-fluorouracil and leucovorin (nal-IRI+5-FU/LV) is the only approved therapy for metastatic PAC following gemcitabine-based therapy, based on the survival benefit demonstrated in the phase III NAPOLI-1 trial. Factors associated with long-term survival in this trial included age ≤65 years, Karnofsky performance status (KPS) ≥90, neutrophil-to-lymphocyte (N/L) ratio ≤5, carbohydrate antigen (CA) 19-9 <59-times the upper limit of normal (ULN), and no liver metastases. Using real-world data from studies conducted in Korea, Italy, and Germany, this review aims to assess the suitability of prognostic factors identified in the NAPOLI-1 trial nomogram. In these real-world studies, a high CA19-9 level and a low N/L ratio were associated with long-term survival in patients treated with nal-IRI+5-FU/LV. The impact of albumin levels, body mass index (BMI), liver metastasis, and KPS on survival identified from the NAPOLI-1 trial was confirmed in some real-world analyses but not consistently. Factors such as patient age and number of previous lines of treatment that were not identified in the NAPOLI-1 nomogram may be associated with long-term survival with nal-IRI+5-FU/LV in the real-world. In conclusion, this review has shown that while prognostic factors are useful for patient stratification, their predictive value on the efficacy of nal-IRI+5-FU/LV is low, thus this treatment may also result in long-term survival in patients with apparently unfavorable characteristics.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"9 ","pages":"Article 100217"},"PeriodicalIF":0.0,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144829441","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 : 2025-08-12DOI: 10.1016/j.esmogo.2025.100221
M. Sugimori , A. Hirotani , H. Yamazaki , M. Oshi , K. Kawashima , H. Tsuchiya , Y. Kanemaru , Y. Suzuki , S. Onodera , H. Miwa , A. Nozaki , K. Sugimori , C. Kunisaki , M. Kudo , M. Morimoto , S. Maeda
Background
Gemcitabine plus nab-paclitaxel (GnP) and FOLFIRINOX (FFX) therapies are widely used to treat advanced pancreatic ductal adenocarcinoma (PDAC). This study aimed to identify the prognostic factors associated with these regimens, focusing on key genomic alterations in the ‘Big Four’ genes (KRAS, TP53, CDKN2A, and SMAD4).
Materials and methods
This retrospective observational study analysed real-world data from 5205 PDAC patients registered in the national database, Center for Cancer Genomics and Advanced Therapeutics (C-CAT), who underwent comprehensive genomic profiling between June 2019 and December 2023 in Japan. Clinical characteristics and genomic alterations were analysed. Time to progression (TTP) was compared between patients treated with GnP or FFX as first-line therapy. Gene alterations were classified as truncating or missense mutations to assess prognostic relevance.
Results
GnP was more frequently selected than FFX as first-line treatment (2315 versus 1181). FFX was more commonly used in younger, male patients without prior adjuvant therapy. After matching for age, sex, and adjuvant history, GnP demonstrated superior TTP compared with FFX (median TTP: 6.0 versus 5.5 months, P = 0.019). In the GnP group, TP53 alterations were associated with significantly shorter TTP compared with wild-type TP53 (median TTP: 5.8 versus 7.0 months; P < 0.0001). Furthermore, truncating TP53 mutations were linked to shorter TTP than missense mutations (median TTP: 5.3 versus 5.9 months; P = 0.021).
Conclusions
In Japanese real-world data, GnP showed superior TTP compared with FFX for advanced PDAC. TP53 status may serve as a prognostic biomarker in patients receiving GnP therapy.
{"title":"Real-world evidence of chemotherapy effects in advanced pancreatic ductal adenocarcinoma: prognostic significance of TP53 status in gemcitabine plus nab-paclitaxel therapy","authors":"M. Sugimori , A. Hirotani , H. Yamazaki , M. Oshi , K. Kawashima , H. Tsuchiya , Y. Kanemaru , Y. Suzuki , S. Onodera , H. Miwa , A. Nozaki , K. Sugimori , C. Kunisaki , M. Kudo , M. Morimoto , S. Maeda","doi":"10.1016/j.esmogo.2025.100221","DOIUrl":"10.1016/j.esmogo.2025.100221","url":null,"abstract":"<div><h3>Background</h3><div>Gemcitabine plus nab-paclitaxel (GnP) and FOLFIRINOX (FFX) therapies are widely used to treat advanced pancreatic ductal adenocarcinoma (PDAC). This study aimed to identify the prognostic factors associated with these regimens, focusing on key genomic alterations in the ‘Big Four’ genes (<em>KRAS, TP53, CDKN2A,</em> and <em>SMAD4</em>).</div></div><div><h3>Materials and methods</h3><div>This retrospective observational study analysed real-world data from 5205 PDAC patients registered in the national database, Center for Cancer Genomics and Advanced Therapeutics (C-CAT), who underwent comprehensive genomic profiling between June 2019 and December 2023 in Japan. Clinical characteristics and genomic alterations were analysed. Time to progression (TTP) was compared between patients treated with GnP or FFX as first-line therapy. Gene alterations were classified as truncating or missense mutations to assess prognostic relevance.</div></div><div><h3>Results</h3><div>GnP was more frequently selected than FFX as first-line treatment (2315 versus 1181). FFX was more commonly used in younger, male patients without prior adjuvant therapy. After matching for age, sex, and adjuvant history, GnP demonstrated superior TTP compared with FFX (median TTP: 6.0 versus 5.5 months, <em>P</em> = 0.019). In the GnP group, <em>TP53</em> alterations were associated with significantly shorter TTP compared with wild-type <em>TP53</em> (median TTP: 5.8 versus 7.0 months; <em>P</em> < 0.0001). Furthermore, truncating <em>TP53</em> mutations were linked to shorter TTP than missense mutations (median TTP: 5.3 versus 5.9 months; <em>P</em> = 0.021).</div></div><div><h3>Conclusions</h3><div>In Japanese real-world data, GnP showed superior TTP compared with FFX for advanced PDAC. <em>TP53</em> status may serve as a prognostic biomarker in patients receiving GnP therapy.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"9 ","pages":"Article 100221"},"PeriodicalIF":0.0,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144813910","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 : 2025-08-12DOI: 10.1016/j.esmogo.2025.100228
A. Petrillo , G. Piessen , H.W.M. van Laarhoven
{"title":"Controversies in upper GI oncology: definition and management of oligometastatic gastroesophageal adenocarcinoma","authors":"A. Petrillo , G. Piessen , H.W.M. van Laarhoven","doi":"10.1016/j.esmogo.2025.100228","DOIUrl":"10.1016/j.esmogo.2025.100228","url":null,"abstract":"","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"9 ","pages":"Article 100228"},"PeriodicalIF":0.0,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144813911","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 : 2025-08-08eCollection Date: 2025-09-01DOI: 10.1016/j.esmogo.2025.100220
J Dekervel, F Castet, A Vogel
{"title":"ESMO Podcast on upper gastrointestinal cancers-highlights in biliary and pancreatic cancers from ASCO 2025.","authors":"J Dekervel, F Castet, A Vogel","doi":"10.1016/j.esmogo.2025.100220","DOIUrl":"https://doi.org/10.1016/j.esmogo.2025.100220","url":null,"abstract":"","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"9 ","pages":"100220"},"PeriodicalIF":0.0,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12836566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146128439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-08eCollection Date: 2025-09-01DOI: 10.1016/j.esmogo.2025.100218
D William, M Bermúdez, A Kübler, C Kahlert, M Distler, J Weitz, S Uhrig, M Fröhlich, B Hutter, D Aust, G Baretton, P Wimberger, K Kast, C Meisel, L Gieldon, J Porrmann, J Wagner, M Arlt, M Franke, J Fischer, K Hackmann, S Kreutzfeldt, A Mock, C E Heilig, D B Lipka, M-V Teleanu, R F Schlenk, B Brors, D Hübschmann, N Paramasivam, D Richter, K Beck, K Pfütze, I Buchhalter, W Weichert, T Herold, K Spiekermann, P J Jost, U Keilholz, F Klauschen, S Bauer, J T Siveke, T Kindler, M Boerries, A L Illert, M Bitzer, K Schulze-Osthoff, P Schirmacher, A Stenzinger, P Horak, C Heining, G Folprecht, S Fröhling, H Glimm, E Schröck, A Jahn
Background: Yields for (likely) pathogenic germline variants (PGVs) in cancer predisposition genes (CPGs) in pancreatic cancer (PCA) cases range from 5% to 10% in initial literature to 15% to 20% in recent literature. PGVs can impact therapy recommendations and cancer surveillance for individuals and families.
Patients and methods: We retrospectively evaluated prospective cancer predisposition testing in 125 patients with exocrine PCA from a single-center clinical genetics clinic (n = 41) and a multicenter precision oncology program (n = 84) within 64 genes, including 14 established PCA risk genes. Associations with clinical and somatic molecular parameters, as well as therapy recommendations, were assessed.
Results: PGVs were identified in 21.6% of patients (n = 27/125) across 14 CPGs. A genetic tumor syndrome was diagnosed in 17.6% of patients (n = 22/125). Existing inclusion criteria for germline testing [European Society for Medical Oncology (ESMO), American Society of Clinical Oncology (ASCO), National Comprehensive Cancer Network (NCCN)] would have missed up to 23.8% of PGV carriers (n = 5/21). Age of onset was not associated with PGV yield. A meta-analysis of 10 other PCA cohorts showed a median PGV yield of 14.1%.In a precision oncology program, 10.7% (n = 9/84) of PCA patients received treatment recommendations supported by PGVs. Genetic testing was carried out on relatives of 73.3% of PGV-positive patients (n = 11/15), with one family demonstrating PGV confirmation in 7 of 13 tested relatives.
Conclusions: These findings support ASCO and NCCN recommendations for germline testing in all PCA patients. We suggest offering large-panel genetic diagnostics early in clinical management, regardless of clinical parameters, with ongoing evaluation and adjustment of the gene panel.
{"title":"17.6% of patients in a German cohort with exocrine pancreatic cancer were diagnosed with a genetic tumor syndrome-a case for universal genetic testing?","authors":"D William, M Bermúdez, A Kübler, C Kahlert, M Distler, J Weitz, S Uhrig, M Fröhlich, B Hutter, D Aust, G Baretton, P Wimberger, K Kast, C Meisel, L Gieldon, J Porrmann, J Wagner, M Arlt, M Franke, J Fischer, K Hackmann, S Kreutzfeldt, A Mock, C E Heilig, D B Lipka, M-V Teleanu, R F Schlenk, B Brors, D Hübschmann, N Paramasivam, D Richter, K Beck, K Pfütze, I Buchhalter, W Weichert, T Herold, K Spiekermann, P J Jost, U Keilholz, F Klauschen, S Bauer, J T Siveke, T Kindler, M Boerries, A L Illert, M Bitzer, K Schulze-Osthoff, P Schirmacher, A Stenzinger, P Horak, C Heining, G Folprecht, S Fröhling, H Glimm, E Schröck, A Jahn","doi":"10.1016/j.esmogo.2025.100218","DOIUrl":"10.1016/j.esmogo.2025.100218","url":null,"abstract":"<p><strong>Background: </strong>Yields for (likely) pathogenic germline variants (PGVs) in cancer predisposition genes (CPGs) in pancreatic cancer (PCA) cases range from 5% to 10% in initial literature to 15% to 20% in recent literature. PGVs can impact therapy recommendations and cancer surveillance for individuals and families.</p><p><strong>Patients and methods: </strong>We retrospectively evaluated prospective cancer predisposition testing in 125 patients with exocrine PCA from a single-center clinical genetics clinic (<i>n</i> = 41) and a multicenter precision oncology program (<i>n</i> = 84) within 64 genes, including 14 established PCA risk genes. Associations with clinical and somatic molecular parameters, as well as therapy recommendations, were assessed.</p><p><strong>Results: </strong>PGVs were identified in 21.6% of patients (<i>n</i> = 27/125) across 14 CPGs. A genetic tumor syndrome was diagnosed in 17.6% of patients (<i>n</i> = 22/125). Existing inclusion criteria for germline testing [European Society for Medical Oncology (ESMO), American Society of Clinical Oncology (ASCO), National Comprehensive Cancer Network (NCCN)] would have missed up to 23.8% of PGV carriers (<i>n</i> = 5/21). Age of onset was not associated with PGV yield. A meta-analysis of 10 other PCA cohorts showed a median PGV yield of 14.1%.In a precision oncology program, 10.7% (<i>n</i> = 9/84) of PCA patients received treatment recommendations supported by PGVs. Genetic testing was carried out on relatives of 73.3% of PGV-positive patients (<i>n</i> = 11/15), with one family demonstrating PGV confirmation in 7 of 13 tested relatives.</p><p><strong>Conclusions: </strong>These findings support ASCO and NCCN recommendations for germline testing in all PCA patients. We suggest offering large-panel genetic diagnostics early in clinical management, regardless of clinical parameters, with ongoing evaluation and adjustment of the gene panel.</p>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"9 ","pages":"100218"},"PeriodicalIF":0.0,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12836536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146128462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-07eCollection Date: 2025-09-01DOI: 10.1016/j.esmogo.2025.100216
M Ishizaka, I Nakayama, K Shitara
{"title":"A case of gastritis developing in a patient receiving zolbetuximab-containing chemotherapy for CLDN18.2-positive advanced gastric cancer.","authors":"M Ishizaka, I Nakayama, K Shitara","doi":"10.1016/j.esmogo.2025.100216","DOIUrl":"10.1016/j.esmogo.2025.100216","url":null,"abstract":"","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"9 ","pages":"100216"},"PeriodicalIF":0.0,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12836721/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146128387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-07eCollection Date: 2025-09-01DOI: 10.1016/j.esmogo.2025.100215
H F Kennecke, J A Zell, H Pham, V V Simianu, K Herz, A Kelley, J C Carmichael, H Hochster, L A Kachnic
Background: Trifluridine/tipiracil (FTD/TPI) is approved for metastatic colorectal cancer as monotherapy or in combination with bevacizumab, though dosing in combination with oxaliplatin has not yet been established. The objective of the phase II SHORT trial (NCT04417699) was to determine the efficacy of short-course radiation (SC RT) followed by 3 months of FTD/TPI + oxaliplatin (TASOX) as a condensed total neoadjuvant therapy (TNT) regimen for intermediate-risk rectal cancer.
Methods: Eligible patients with clinical T3N0 or T1-3N1 nonlow rectal tumors and negative radial tumor margins (>1 mm) were enrolled. The primary endpoint was reduction in neoadjuvant response (NAR) score compared with historic controls. Patients received 25 Gy in five 5 Gy fractions of conformal pelvic radiation followed by six planned 14-day cycles of TASOX: FTD/TPI (35 mg/m2/dose) orally b.i.d. day 1-5, oxaliplatin 85 mg/m2 i.v. day 1. Surgery was recommended within 4 weeks after cycle 6 of TASOX.
Results: Between 2020 and 2023, 13 patients with stage II (n = 5) and III (n = 8) rectal adenocarcinoma were enrolled at three institutions. Dose delivered was 100% of planned radiation, 99% of planned FTD/TPI and 95% oxaliplatin. Diarrhea was documented with a frequency of 11%, and was grade 1 only. Only 9% (8/87) of adverse events were grade 3/4, predominantly related to neutropenia. Among 10 patients who proceeded to total mesorectal excision surgery, 2 experienced a pathological complete response and 2 had a complete clinical response, of which 1 had no evidence of regrowth on continued watch and wait.
Conclusions: SC RT and 3 months of TASOX can be safely delivered to patients with intermediate-risk rectal cancer, offering a convenient regimen that should be further explored for rectal cancer treatment. The TASOX regimen may be of particular relevance for patients with suspected dihydropyrimidine dehydrogenase deficiency who require oxaliplatin-based therapy.
{"title":"Results of a phase II trial of short-course radiation and TASOX [trifluridine/tipiracil (TAS-102) plus oxaliplatin] chemotherapy in operable rectal cancer.","authors":"H F Kennecke, J A Zell, H Pham, V V Simianu, K Herz, A Kelley, J C Carmichael, H Hochster, L A Kachnic","doi":"10.1016/j.esmogo.2025.100215","DOIUrl":"10.1016/j.esmogo.2025.100215","url":null,"abstract":"<p><strong>Background: </strong>Trifluridine/tipiracil (FTD/TPI) is approved for metastatic colorectal cancer as monotherapy or in combination with bevacizumab, though dosing in combination with oxaliplatin has not yet been established. The objective of the phase II SHORT trial (NCT04417699) was to determine the efficacy of short-course radiation (SC RT) followed by 3 months of FTD/TPI + oxaliplatin (TASOX) as a condensed total neoadjuvant therapy (TNT) regimen for intermediate-risk rectal cancer.</p><p><strong>Methods: </strong>Eligible patients with clinical T3N0 or T1-3N1 nonlow rectal tumors and negative radial tumor margins (>1 mm) were enrolled. The primary endpoint was reduction in neoadjuvant response (NAR) score compared with historic controls. Patients received 25 Gy in five 5 Gy fractions of conformal pelvic radiation followed by six planned 14-day cycles of TASOX: FTD/TPI (35 mg/m<sup>2</sup>/dose) orally b.i.d. day 1-5, oxaliplatin 85 mg/m<sup>2</sup> i.v. day 1. Surgery was recommended within 4 weeks after cycle 6 of TASOX.</p><p><strong>Results: </strong>Between 2020 and 2023, 13 patients with stage II (<i>n</i> = 5) and III (<i>n</i> = 8) rectal adenocarcinoma were enrolled at three institutions. Dose delivered was 100% of planned radiation, 99% of planned FTD/TPI and 95% oxaliplatin. Diarrhea was documented with a frequency of 11%, and was grade 1 only. Only 9% (8/87) of adverse events were grade 3/4, predominantly related to neutropenia. Among 10 patients who proceeded to total mesorectal excision surgery, 2 experienced a pathological complete response and 2 had a complete clinical response, of which 1 had no evidence of regrowth on continued watch and wait.</p><p><strong>Conclusions: </strong>SC RT and 3 months of TASOX can be safely delivered to patients with intermediate-risk rectal cancer, offering a convenient regimen that should be further explored for rectal cancer treatment. The TASOX regimen may be of particular relevance for patients with suspected dihydropyrimidine dehydrogenase deficiency who require oxaliplatin-based therapy.</p>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"9 ","pages":"100215"},"PeriodicalIF":0.0,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12836750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146128390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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