ESMO Gastrointestinal Oncology最新文献_第3页

What is the role of physical exercise after surgery for gastric cancer? A scoping review

ESMO Gastrointestinal Oncology

Pub Date : 2025-01-08 DOI: 10.1016/j.esmogo.2024.100117

M. Monticone , B. Rocca , A. Pretta , A. Scribante , M. Scartozzi , F. Del Farra

The overall role of physical exercise (PE) in addressing the disabling effects of gastric cancer (GC) after surgery remains uncertain. This scoping review (ScR) aims to systematically collect, map, and present the current evidence on studies reporting data on PE in individuals with GC. This ScR followed the 2020 recommendations of the Joanna Briggs Institute Methodological Guidance and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews. A comprehensive search was conducted in PubMed, Scopus, and the Cochrane Central Register of Controlled Trials (CENTRAL) up to January 2024. Original studies were identified, and findings were presented both numerically and thematically. Out of 1115 articles initially identified, 9 studies met the inclusion criteria. The number of publications on this topic has increased over time, with most studies conducted in Western countries. Of the included studies, 6 (66.7%) were primary research articles, while 3 (33.3%) were systematic reviews. The overall sample size comprised 226 individuals, with a mean age of 61 ± 5.3 years. The studies consistently reported a positive impact of PE in both inpatient and outpatient settings. However, significant heterogeneity was observed in the types and characteristics of PE, outcome measures, and reference populations. Physiotherapists were the primary healthcare professionals involved in delivering care. This review highlights the need for further high-quality studies dedicated to investigating the role of PE after surgery for GC. In addition, multidisciplinary rehabilitation is recommended to address the complex needs of this patient population.

{"title":"What is the role of physical exercise after surgery for gastric cancer? A scoping review","authors":"M. Monticone , B. Rocca , A. Pretta , A. Scribante , M. Scartozzi , F. Del Farra","doi":"10.1016/j.esmogo.2024.100117","DOIUrl":"10.1016/j.esmogo.2024.100117","url":null,"abstract":"<div><div>The overall role of physical exercise (PE) in addressing the disabling effects of gastric cancer (GC) after surgery remains uncertain. This scoping review (ScR) aims to systematically collect, map, and present the current evidence on studies reporting data on PE in individuals with GC. This ScR followed the 2020 recommendations of the <em>Joanna Briggs Institute Methodological Guidance</em> and adhered to the <em>Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews</em>. A comprehensive search was conducted in PubMed, Scopus, and the Cochrane Central Register of Controlled Trials (CENTRAL) up to January 2024. Original studies were identified, and findings were presented both numerically and thematically. Out of 1115 articles initially identified, 9 studies met the inclusion criteria. The number of publications on this topic has increased over time, with most studies conducted in Western countries. Of the included studies, 6 (66.7%) were primary research articles, while 3 (33.3%) were systematic reviews. The overall sample size comprised 226 individuals, with a mean age of 61 ± 5.3 years. The studies consistently reported a positive impact of PE in both inpatient and outpatient settings. However, significant heterogeneity was observed in the types and characteristics of PE, outcome measures, and reference populations. Physiotherapists were the primary healthcare professionals involved in delivering care. This review highlights the need for further high-quality studies dedicated to investigating the role of PE after surgery for GC. In addition, multidisciplinary rehabilitation is recommended to address the complex needs of this patient population.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"7 ","pages":"Article 100117"},"PeriodicalIF":0.0,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143159538","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}

引用次数: 0

Managing zolbetuximab-induced nausea and vomiting: a proposal for a pragmatic approach in clinical practice

ESMO Gastrointestinal Oncology

Pub Date : 2025-01-06 DOI: 10.1016/j.esmogo.2024.100128

K. Shimozaki , A. Ooki , Y. Yamahata , T. Aoyama , K. Yoshino , M. Tamba , S. Udagawa , S. Fukuoka , H. Osumi , T. Wakatsuki , E. Shinozaki , M. Ogura , K. Chin , K. Yamaguchi

Background

The global phase III SPOTLIGHT and GLOW trials confirmed the superiority of zolbetuximab plus chemotherapy over chemotherapy alone for claudin 18.2-positive advanced gastric cancer (AGC). However, severe nausea/vomiting during zolbetuximab infusion remains a significant safety concern. Our study aimed to evaluate the safety management strategy’s applicability in our institution.

Patients and methods

This registry-based observational study assessed the combination of fosnetupitant, dexamethasone, and 5-HT₃-receptor antagonist in patients receiving zolbetuximab plus chemotherapy. The initial zolbetuximab infusion rate was set at 75 ml/h for the first 60 min, and then 250 ml/h thereafter. The primary endpoint was the feasibility of our management and vomiting prevention during cycle 1.

Results

Among 21 patients (median age 61 years; male 48%; diffuse-type histology 81%; prior gastrectomy 38%; peritoneal metastases 57%), the incidence of nausea/vomiting during zolbetuximab initiation in cycle 1 was 62%/9.5%, with a 62% infusion interruption rate. The median time to first nausea was 93 min (range 77-127 min); median interruption time was 40 min (16-68 min); and median total infusion time of zolbetuximab was 257 min (154-343 min). All patients successfully completed zolbetuximab administration in cycle 1, with an 81% vomiting prevention rate. At cycle 2 day 1, 3 of 14 patients (21%) experienced nausea, with no vomiting.

Conclusion

First-line zolbetuximab plus chemotherapy was safely introduced to real-world patients with claudin 18.2-positive AGC, with effective management of nausea and vomiting, applicable in clinical practice.

{"title":"Managing zolbetuximab-induced nausea and vomiting: a proposal for a pragmatic approach in clinical practice","authors":"K. Shimozaki , A. Ooki , Y. Yamahata , T. Aoyama , K. Yoshino , M. Tamba , S. Udagawa , S. Fukuoka , H. Osumi , T. Wakatsuki , E. Shinozaki , M. Ogura , K. Chin , K. Yamaguchi","doi":"10.1016/j.esmogo.2024.100128","DOIUrl":"10.1016/j.esmogo.2024.100128","url":null,"abstract":"<div><h3>Background</h3><div>The global phase III SPOTLIGHT and GLOW trials confirmed the superiority of zolbetuximab plus chemotherapy over chemotherapy alone for claudin 18.2-positive advanced gastric cancer (AGC). However, severe nausea/vomiting during zolbetuximab infusion remains a significant safety concern. Our study aimed to evaluate the safety management strategy’s applicability in our institution.</div></div><div><h3>Patients and methods</h3><div>This registry-based observational study assessed the combination of fosnetupitant, dexamethasone, and 5-HT<sub>3</sub>-receptor antagonist in patients receiving zolbetuximab plus chemotherapy. The initial zolbetuximab infusion rate was set at 75 ml/h for the first 60 min, and then 250 ml/h thereafter. The primary endpoint was the feasibility of our management and vomiting prevention during cycle 1.</div></div><div><h3>Results</h3><div>Among 21 patients (median age 61 years; male 48%; diffuse-type histology 81%; prior gastrectomy 38%; peritoneal metastases 57%), the incidence of nausea/vomiting during zolbetuximab initiation in cycle 1 was 62%/9.5%, with a 62% infusion interruption rate. The median time to first nausea was 93 min (range 77-127 min); median interruption time was 40 min (16-68 min); and median total infusion time of zolbetuximab was 257 min (154-343 min). All patients successfully completed zolbetuximab administration in cycle 1, with an 81% vomiting prevention rate. At cycle 2 day 1, 3 of 14 patients (21%) experienced nausea, with no vomiting.</div></div><div><h3>Conclusion</h3><div>First-line zolbetuximab plus chemotherapy was safely introduced to real-world patients with claudin 18.2-positive AGC, with effective management of nausea and vomiting, applicable in clinical practice.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"7 ","pages":"Article 100128"},"PeriodicalIF":0.0,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143159959","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}

引用次数: 0

German guidelines for the diagnosis and treatment of squamous-cell carcinoma and adenocarcinoma of the esophagus—version 4.0

ESMO Gastrointestinal Oncology

Pub Date : 2025-01-06 DOI: 10.1016/j.esmogo.2024.100112

M.P. Ebert , W. Fischbach , S. Hollerbach , J. Höppner , D. Lorenz , M. Stahl , M. Stuschke , O. Pech , U. Vanhoefer , C. Bruns , C. Ell , M. Follmann , U. Goerling , L. Grenacher , J. Haardt , A.H. Hölscher , R. Hummel , W.T. Knoefel , J. Körber , R. Langer , R. Porschen

This guideline for the diagnosis and treatment of squamous-cell carcinoma and adenocarcinoma of the esophagus was developed and managed by the German Guideline Program in Oncology (GGPO) of the Association of the Scientific Medical Societies in Germany (AWMF), German Cancer Society (DKG), and German Cancer Aid (DKH). The guideline commission comprised multidisciplinary experts from various professional associations and organizations involved in the management of esophageal cancer, as well as a patient representative. Quality of the evidence is presented using Oxford evidence-based medicine system, and recommendations were graded in a formal consensus process using a recommendation grading scheme.

引用次数: 0

Eligibility and workload implications of adjuvant immunotherapy in patients with resected esophageal and gastroesophageal junction (ESO/GEJ) cancer

ESMO Gastrointestinal Oncology

Pub Date : 2025-01-04 DOI: 10.1016/j.esmogo.2024.100115

T.H. Lee , S. Gill

Background

The CheckMate (CM) 577 trial demonstrated the efficacy of 12 months of adjuvant nivolumab for esophageal (ESO)/gastroesophageal junction (GEJ) cancer patients with residual pathological disease after neoadjuvant chemoradiation. Nivolumab is now an approved and funded regimen in British Columbia (BC). This retrospective study examines its real-world eligibility and resource implications.

Materials and methods

We conducted an ethics board-approved chart review of patients who underwent CROSS chemoradiation at BC Cancer from January 2016 to December 2020. Patient eligibility was determined per CM577 and GIAJNIV criteria. We assessed the resource impact of nivolumab by projecting the number of MD and chemotherapy visits, and anticipated G3/4 toxicity events per the CM577 trial.

Results

We identified 677 patients (63% ESO and 37% GEJ; 74% adenocarcinomas and 25% squamous cell carcinomas). Among the 460 who had resection, 79% had residual pathological disease. 68% (n = 249) and 88% (n = 321) were eligible for adjuvant nivolumab per CM577 and GIAJNIV criteria, respectively. In BC, this equates to ∼60 patients/year, resulting in 768 additional chemotherapy and potentially an equal number of MD visits, totaling 256 MD workhours annually. With a 34% G3/4 toxicity rate, an estimated 20 patients/year may require medical intervention.

Conclusions

Adjuvant nivolumab is an important treatment option for resected ESO/GEJ cancer patients. Our findings suggest that a substantial portion (88%) of those with residual pathological disease would be eligible for 12 months of therapy. In addition to treatments costs, the implementation of new therapy indications should consider the additional workload impact on oncologists.

{"title":"Eligibility and workload implications of adjuvant immunotherapy in patients with resected esophageal and gastroesophageal junction (ESO/GEJ) cancer","authors":"T.H. Lee , S. Gill","doi":"10.1016/j.esmogo.2024.100115","DOIUrl":"10.1016/j.esmogo.2024.100115","url":null,"abstract":"<div><h3>Background</h3><div>The CheckMate (CM) 577 trial demonstrated the efficacy of 12 months of adjuvant nivolumab for esophageal (ESO)/gastroesophageal junction (GEJ) cancer patients with residual pathological disease after neoadjuvant chemoradiation. Nivolumab is now an approved and funded regimen in British Columbia (BC). This retrospective study examines its real-world eligibility and resource implications.</div></div><div><h3>Materials and methods</h3><div>We conducted an ethics board-approved chart review of patients who underwent <em>CROSS</em> chemoradiation at BC Cancer from January 2016 to December 2020. Patient eligibility was determined per CM577 and <em>GIAJNIV</em> criteria. We assessed the resource impact of nivolumab by projecting the number of MD and chemotherapy visits, and anticipated G3/4 toxicity events per the CM577 trial.</div></div><div><h3>Results</h3><div>We identified 677 patients (63% ESO and 37% GEJ; 74% adenocarcinomas and 25% squamous cell carcinomas). Among the 460 who had resection, 79% had residual pathological disease. 68% (<em>n</em> = 249) and 88% (<em>n</em> = 321) were eligible for adjuvant nivolumab per CM577 and <em>GIAJNIV</em> criteria, respectively. In BC, this equates to ∼60 patients/year, resulting in 768 additional chemotherapy and potentially an equal number of MD visits, totaling 256 MD workhours annually. With a 34% G3/4 toxicity rate, an estimated 20 patients/year may require medical intervention.</div></div><div><h3>Conclusions</h3><div>Adjuvant nivolumab is an important treatment option for resected ESO/GEJ cancer patients. Our findings suggest that a substantial portion (88%) of those with residual pathological disease would be eligible for 12 months of therapy. In addition to treatments costs, the implementation of new therapy indications should consider the additional workload impact on oncologists.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"7 ","pages":"Article 100115"},"PeriodicalIF":0.0,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143160897","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}

引用次数: 0

Maintenance chemotherapy in biliary tract tumours in the era of immuno-chemotherapy

ESMO Gastrointestinal Oncology

Pub Date : 2025-01-04 DOI: 10.1016/j.esmogo.2024.100116

A. Lamarca , J. Adeva , I. Ales Díaz , R. Alvarez Gallego , A.J. Muñoz Martín , T. Macarulla Mercade

Biliary tract tumours (BTCs) are malignancies with a poor prognosis. Regarding first-line therapy options, cisplatin and gemcitabine (CisGem) alone has been the standard therapy option for more than a decade. This has changed recently, due to the incorporation of immunotherapy into this combo, with latest studies showing how the addition of immunotherapy with either durvalumab or pembrolizumab can improve patients’ outcomes. However, the adequate duration of CisGem in advanced BTCs has remained an open debate. We provide a detailed summary and discussion on current evidence in terms of adequate duration of chemotherapy in the immuno-chemotherapy era, with the aim of informing best practice. Based on the data available and summarised here, the differences are small and individual decisions should be pursued for the sake of not compromising the bone marrow reserve for delivering second-line therapies. In the era of immuno-chemotherapy, maintenance chemotherapy seems to be of very limited benefit and maintenance with the checkpoint inhibitors being utilised seems sufficient. For patients being treated with chemotherapy alone, maintenance chemotherapy should also be carefully considered and decisions individualised.

{"title":"Maintenance chemotherapy in biliary tract tumours in the era of immuno-chemotherapy","authors":"A. Lamarca , J. Adeva , I. Ales Díaz , R. Alvarez Gallego , A.J. Muñoz Martín , T. Macarulla Mercade","doi":"10.1016/j.esmogo.2024.100116","DOIUrl":"10.1016/j.esmogo.2024.100116","url":null,"abstract":"<div><div>Biliary tract tumours (BTCs) are malignancies with a poor prognosis. Regarding first-line therapy options, cisplatin and gemcitabine (CisGem) alone has been the standard therapy option for more than a decade. This has changed recently, due to the incorporation of immunotherapy into this combo, with latest studies showing how the addition of immunotherapy with either durvalumab or pembrolizumab can improve patients’ outcomes. However, the adequate duration of CisGem in advanced BTCs has remained an open debate. We provide a detailed summary and discussion on current evidence in terms of adequate duration of chemotherapy in the immuno-chemotherapy era, with the aim of informing best practice. Based on the data available and summarised here, the differences are small and individual decisions should be pursued for the sake of not compromising the bone marrow reserve for delivering second-line therapies. In the era of immuno-chemotherapy, maintenance chemotherapy seems to be of very limited benefit and maintenance with the checkpoint inhibitors being utilised seems sufficient. For patients being treated with chemotherapy alone, maintenance chemotherapy should also be carefully considered and decisions individualised.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"7 ","pages":"Article 100116"},"PeriodicalIF":0.0,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143160880","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}

引用次数: 0

Concomitant proton pump inhibitors and capecitabine-based chemoradiotherapy in rectal cancer: an ancillary study from the PRODIGE 23 trial

ESMO Gastrointestinal Oncology

Pub Date : 2025-01-03 DOI: 10.1016/j.esmogo.2024.100119

M. Bridoux , E. Aymes , T. Conroy , S. Gourgou , A. Carnot , C. Borg , M.-C. Le Deley , A. Turpin

Background

Approximately one in five cancer patients use proton pump inhibitors (PPIs). In this work, we studied the effect of PPI co-medication during neoadjuvant chemoradiotherapy (NCRT) for locally advanced rectal cancer (LARC) based on the phase III PRODIGE 23 trial.

Materials and methods

We gathered data on PPI exposure for patients from the PRODIGE 23 trial. PPI exposure was defined as PPI use during capecitabine treatment, either during CRT or as adjuvant therapy. The oncological outcomes included recurrence-free survival (RFS), overall survival (OS), cumulative incidence of metastatic recurrence, and pathological response to preoperative treatment. The association of PPI use with RFS, metastatic recurrence, and histological complete response was evaluated using univariate and multivariate Cox models.

Results

We analyzed data from 332 patients [165 in the NAC group with mFOLFIRINOX, capecitabine-based (CAP50) CRT, and surgery, and 167 in the standard-of-care control arm with CAP50 CRT and surgery]. Thirty-eight patients were co-administered a PPI during capecitabine administration. After a median follow-up of 49.4 months, the 3-year RFS rates were 74.1% [95% confidence interval (CI) 68.6% to 78.8%] and 68.4% (95% CI 51.2% to 80.7%) in the non-PPI and PPI groups, respectively, with no significant differences (P = 0.16). The 3-year OS rates were 91.2% (95% CI 87.2% to 93.9%) and 83% (95% CI 65.7% to 92%) in the non-PPI group and PPI groups, respectively, with no significant differences (P = 0.38). We observed no difference in the pathological complete response rate between both groups.

Conclusions

We observed no significant association between PPI exposure and survival or pathological response of patients receiving capecitabine-based CRT for LARC, supporting earlier research findings.

{"title":"Concomitant proton pump inhibitors and capecitabine-based chemoradiotherapy in rectal cancer: an ancillary study from the PRODIGE 23 trial","authors":"M. Bridoux , E. Aymes , T. Conroy , S. Gourgou , A. Carnot , C. Borg , M.-C. Le Deley , A. Turpin","doi":"10.1016/j.esmogo.2024.100119","DOIUrl":"10.1016/j.esmogo.2024.100119","url":null,"abstract":"<div><h3>Background</h3><div>Approximately one in five cancer patients use proton pump inhibitors (PPIs). In this work, we studied the effect of PPI co-medication during neoadjuvant chemoradiotherapy (NCRT) for locally advanced rectal cancer (LARC) based on the phase III PRODIGE 23 trial.</div></div><div><h3>Materials and methods</h3><div>We gathered data on PPI exposure for patients from the PRODIGE 23 trial. PPI exposure was defined as PPI use during capecitabine treatment, either during CRT or as adjuvant therapy. The oncological outcomes included recurrence-free survival (RFS), overall survival (OS), cumulative incidence of metastatic recurrence, and pathological response to preoperative treatment. The association of PPI use with RFS, metastatic recurrence, and histological complete response was evaluated using univariate and multivariate Cox models.</div></div><div><h3>Results</h3><div>We analyzed data from 332 patients [165 in the NAC group with mFOLFIRINOX, capecitabine-based (CAP50) CRT, and surgery, and 167 in the standard-of-care control arm with CAP50 CRT and surgery]. Thirty-eight patients were co-administered a PPI during capecitabine administration. After a median follow-up of 49.4 months, the 3-year RFS rates were 74.1% [95% confidence interval (CI) 68.6% to 78.8%] and 68.4% (95% CI 51.2% to 80.7%) in the non-PPI and PPI groups, respectively, with no significant differences (<em>P</em> = 0.16). The 3-year OS rates were 91.2% (95% CI 87.2% to 93.9%) and 83% (95% CI 65.7% to 92%) in the non-PPI group and PPI groups, respectively, with no significant differences (<em>P</em> = 0.38). We observed no difference in the pathological complete response rate between both groups.</div></div><div><h3>Conclusions</h3><div>We observed no significant association between PPI exposure and survival or pathological response of patients receiving capecitabine-based CRT for LARC, supporting earlier research findings.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"7 ","pages":"Article 100119"},"PeriodicalIF":0.0,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143160881","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}

引用次数: 0

PD-L1 expression as a negative predictive biomarker in advanced esophageal squamous-cell cancer treated with chemotherapy alone

ESMO Gastrointestinal Oncology

Pub Date : 2024-12-18 DOI: 10.1016/j.esmogo.2024.100109

M. Sachdeva , J.J. Zhao , K.X. Zhu , D.T.W. Yap , N.Z.H. Wong , N.B. Kumarakulasinghe , J. Tey , R. Sundar

Background

Programmed death-ligand 1 (PD-L1) expression is a well-established positive predictive biomarker for response to immunotherapy in advanced esophageal squamous-cell carcinoma (aESCC). However, the association between PD-L1 and response to chemotherapy alone remains unclear. This study aims to determine the prognostic significance of PD-L1 expression in patients treated with first-line chemotherapy alone in aESCC.

Materials and methods

First-line phase III randomized trials that included PD-L1 expression as a biomarker in aESCC were extracted after a systematic search. A graphical reconstructive algorithm was used to estimate time-to-event outcomes from reported Kaplan–Meier (KM) plots and, where unavailable, KMSubtraction was utilized to derive KM plots of unreported PD-L1 subgroups. Thereafter, an individual patient data meta-analysis was conducted. Survival analyses for overall survival (OS) and progression-free survival (PFS) were conducted with Cox proportional hazards models with a shared-frailty term incorporated to account for interstudy differences.

Results

Chemotherapy arms from five randomized phase III trials—CheckMate-648, ESCORT-1st, KEYNOTE-590, RATIONALE-306 and ORIENT-15—comprising 1517 patients were included in the OS analysis. Compared with PD-L1-low-expressing tumors, patients with PD-L1-high-expressing tumors were at a significantly higher risk of mortality [hazard ratio (HR) 1.153, 95% confidence interval (CI) 1.018-1.305, P = 0.025]. Three trials—CheckMate-648, ESCORT-1st and ORIENT-15—comprising 949 patients treated with chemotherapy alone were included in the PFS analysis. Patients with PD-L1-high-expressing tumors had a non-significant increased risk of tumor progression (HR 1.076, 95% CI 0.923 –1.253, P = 0.349).

Conclusions

Our study found PD-L1 expression is a negative predictor of OS in aESCC treated with first-line chemotherapy.

{"title":"PD-L1 expression as a negative predictive biomarker in advanced esophageal squamous-cell cancer treated with chemotherapy alone","authors":"M. Sachdeva , J.J. Zhao , K.X. Zhu , D.T.W. Yap , N.Z.H. Wong , N.B. Kumarakulasinghe , J. Tey , R. Sundar","doi":"10.1016/j.esmogo.2024.100109","DOIUrl":"10.1016/j.esmogo.2024.100109","url":null,"abstract":"<div><h3>Background</h3><div>Programmed death-ligand 1 (PD-L1) expression is a well-established positive predictive biomarker for response to immunotherapy in advanced esophageal squamous-cell carcinoma (aESCC). However, the association between PD-L1 and response to chemotherapy alone remains unclear. This study aims to determine the prognostic significance of PD-L1 expression in patients treated with first-line chemotherapy alone in aESCC.</div></div><div><h3>Materials and methods</h3><div>First-line phase III randomized trials that included PD-L1 expression as a biomarker in aESCC were extracted after a systematic search. A graphical reconstructive algorithm was used to estimate time-to-event outcomes from reported Kaplan–Meier (KM) plots and, where unavailable, KMSubtraction was utilized to derive KM plots of unreported PD-L1 subgroups. Thereafter, an individual patient data meta-analysis was conducted. Survival analyses for overall survival (OS) and progression-free survival (PFS) were conducted with Cox proportional hazards models with a shared-frailty term incorporated to account for interstudy differences.</div></div><div><h3>Results</h3><div>Chemotherapy arms from five randomized phase III trials—CheckMate-648, ESCORT-1st, KEYNOTE-590, RATIONALE-306 and ORIENT-15—comprising 1517 patients were included in the OS analysis. Compared with PD-L1-low-expressing tumors, patients with PD-L1-high-expressing tumors were at a significantly higher risk of mortality [hazard ratio (HR) 1.153, 95% confidence interval (CI) 1.018-1.305, <em>P</em> = 0.025]. Three trials—CheckMate-648, ESCORT-1st and ORIENT-15—comprising 949 patients treated with chemotherapy alone were included in the PFS analysis. Patients with PD-L1-high-expressing tumors had a non-significant increased risk of tumor progression (HR 1.076, 95% CI 0.923 –1.253, <em>P</em> = 0.349).</div></div><div><h3>Conclusions</h3><div>Our study found PD-L1 expression is a negative predictor of OS in aESCC treated with first-line chemotherapy.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"7 ","pages":"Article 100109"},"PeriodicalIF":0.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143159539","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}

引用次数: 0

Single-cell RNA sequencing via endoscopic ultrasound-guided fine-needle biopsy for pancreatic tumors uncovered an aggressive subclone with a poor prognosis

ESMO Gastrointestinal Oncology

Pub Date : 2024-12-16 DOI: 10.1016/j.esmogo.2024.100113

Y.-Y. Su , M.-Y. Lin , S.M. Cheng , W.-L. Chang , C.-W. Hsu , C.-M. Yeh , C.-C. Yu , Y.-C. Hou , C.-J. Huang , Y.-S. Liu , Y.-J. Chao , D.-Y. Hwang , Y.S. Shan , L.-T. Chen

Background

Single-cell RNA sequencing (scRNA-seq) is a powerful tool which can unveil regulatory connections between genes and cells. However, due to the high demand for tissue quality, most scRNA-seq for pancreatic cancer is carried out by surgical specimen. This study (NCT05767697) aims to gain practical experience in carrying out scRNA-seq using endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB).

Materials and methods

With a within-subjects design, two punctures from the same lesion, with a negative pressure of 5 ml (suction group) and without applying suction (non-suction group), were evaluated. Each biopsy sample was separated into three parts: white tissue, red material, and buffer for living cell counting. scRNA-seq was carried out according to the manufacturer’s protocol. The pancreatic adenocarcinoma dataset in The Cancer Genome Atlas (TCGA) was used as external validation.

Results

A total of 20 patients with 40 specimens were enrolled. The suction group achieved a success rate of 80% (16/20), which was significantly higher than the 10% (2/20) success rate in the non-suction group (P < 0.001). scRNA-seq data were generated for four patients, including two early stage and two late stage. Overall, 15 major cell subtypes, including 4 cancer subclones, were identified across early and late stages. Analysis of differentially expressed genes identified an aggressive subclone highlighted by ubiquitin-conjugating enzyme E2 C (UBE2C) high expression, commonly in late stage. The TCGA dataset also demonstrated that UBE2C high-expression pancreatic cancer had a poor prognosis.

Conclusions

EUS-FNB with a negative pressure of 5 ml is feasible for scRNA-seq in clinical practice. A UBE2C high-expression subclone correlates with a poor prognosis, potentially becoming a new therapeutic target in future studies.

{"title":"Single-cell RNA sequencing via endoscopic ultrasound-guided fine-needle biopsy for pancreatic tumors uncovered an aggressive subclone with a poor prognosis","authors":"Y.-Y. Su , M.-Y. Lin , S.M. Cheng , W.-L. Chang , C.-W. Hsu , C.-M. Yeh , C.-C. Yu , Y.-C. Hou , C.-J. Huang , Y.-S. Liu , Y.-J. Chao , D.-Y. Hwang , Y.S. Shan , L.-T. Chen","doi":"10.1016/j.esmogo.2024.100113","DOIUrl":"10.1016/j.esmogo.2024.100113","url":null,"abstract":"<div><h3>Background</h3><div>Single-cell RNA sequencing (scRNA-seq) is a powerful tool which can unveil regulatory connections between genes and cells. However, due to the high demand for tissue quality, most scRNA-seq for pancreatic cancer is carried out by surgical specimen. This study (NCT05767697) aims to gain practical experience in carrying out scRNA-seq using endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB).</div></div><div><h3>Materials and methods</h3><div>With a within-subjects design, two punctures from the same lesion, with a negative pressure of 5 ml (suction group) and without applying suction (non-suction group), were evaluated. Each biopsy sample was separated into three parts: white tissue, red material, and buffer for living cell counting. scRNA-seq was carried out according to the manufacturer’s protocol. The pancreatic adenocarcinoma dataset in The Cancer Genome Atlas (TCGA) was used as external validation.</div></div><div><h3>Results</h3><div>A total of 20 patients with 40 specimens were enrolled. The suction group achieved a success rate of 80% (16/20), which was significantly higher than the 10% (2/20) success rate in the non-suction group (<em>P</em> < 0.001). scRNA-seq data were generated for four patients, including two early stage and two late stage. Overall, 15 major cell subtypes, including 4 cancer subclones, were identified across early and late stages. Analysis of differentially expressed genes identified an aggressive subclone highlighted by ubiquitin-conjugating enzyme E2 C (UBE2C) high expression, commonly in late stage. The TCGA dataset also demonstrated that UBE2C high-expression pancreatic cancer had a poor prognosis.</div></div><div><h3>Conclusions</h3><div>EUS-FNB with a negative pressure of 5 ml is feasible for scRNA-seq in clinical practice. A UBE2C high-expression subclone correlates with a poor prognosis, potentially becoming a new therapeutic target in future studies.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"7 ","pages":"Article 100113"},"PeriodicalIF":0.0,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143160896","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}

引用次数: 0

Evaluating trastuzumab deruxtecan in patients with gastrooesophageal adenocarcinoma who are ctDNA and HER2 positive: DECIPHER 评价曲妥珠单抗在ctDNA和HER2阳性的胃食管腺癌患者中的应用：DECIPHER

ESMO Gastrointestinal Oncology

Pub Date : 2024-12-01 DOI: 10.1016/j.esmogo.2024.100114

E. Smyth , D. Griffiths , K. Cozens , S. Ewings , R. Waugh , R.C. Turkington , K. Foley , R. Roy , S. Ngan , R. Owen , D. Chuter , C. Steele , G. Griffiths

Operable gastrooesophageal adenocarcinoma (GOA) is treated with multimodality therapy which is curative in <50% of patients. Patients in the UK with operable GOA are treated with chemotherapy before and following surgery. Patients who have circulating tumour DNA (ctDNA) present after surgery have worse survival than ctDNA-negative patients. Trastuzumab deruxtecan (T-DXd), a novel human epidermal growth factor receptor 2 (HER2)-targeting antibody–drug conjugate is an effective drug in multiple tumour types and has been licensed to treat advanced HER2-positive GOA that has progressed after chemotherapy and trastuzumab and is European Society for Medical Oncology (ESMO) Guideline recommended. Evaluation of T-DXd in operable but micrometastatic GOA is an attractive option. DECIPHER is a multicentre, phase II trial testing the efficacy of T-DXd in reducing micrometastatic disease burden in HER2-positive GOA patients who are ctDNA positive after neoadjuvant chemotherapy and surgery. Patients will have their resection specimen and plasma analysed to confirm HER2 and ctDNA status post-operatively. Twenty-five ctDNA- and HER2-positive patients will be treated with 6.4 mg/kg T-DXd intravenously every 21 days for a maximum of eight cycles. Study follow-up visits will take place for a maximum of 2 years after treatment, with survival follow-up until the end of the study.

可手术胃食管腺癌（GOA）的治疗采用多模式治疗，治愈率为50%。在英国，可手术的GOA患者在手术前和手术后接受化疗。术后存在循环肿瘤DNA （ctDNA）的患者比ctDNA阴性的患者生存率更差。曲妥珠单抗德鲁西替康（T-DXd）是一种新型的人表皮生长因子受体2 （HER2）靶向抗体-药物偶联物，是多种肿瘤类型的有效药物，已被许可用于治疗化疗和曲妥珠单抗后进展的晚期HER2阳性GOA，是欧洲医学肿瘤学会（ESMO）指南推荐的药物。在可手术但微转移的GOA中评估T-DXd是一个有吸引力的选择。DECIPHER是一项多中心II期试验，旨在测试T-DXd在新辅助化疗和手术后ctDNA阳性的her2阳性GOA患者中减轻微转移性疾病负担的疗效。患者将进行切除标本和血浆分析，以确认术后HER2和ctDNA状态。25例ctDNA和her2阳性患者将每21天静脉注射6.4 mg/kg T-DXd，最多8个周期。研究随访将在治疗后最多进行2年，并进行生存随访，直到研究结束。

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引用次数: 0

This is not Lynch syndrome: lessons from misattributed diagnoses in constitutional mismatch repair deficiency

ESMO Gastrointestinal Oncology

Pub Date : 2024-12-01 DOI: 10.1016/j.esmogo.2024.100111

A.H. Mohammad , E. Rohr , A. Moise , R.M. Abdulsalam , W. Davalan , A. Rizzolo , A.S. Liberman , C. Goudie , L. Palma , W.D. Foulkes

Background

Underdiagnosis of constitutional mismatch repair deficiency (CMMRD) syndrome leads to suboptimal cancer surveillance and management of CMMRD patients. Assessing pitfalls that led to the misdiagnosis of CMMRD is important to improve care trajectories, and to highlight the importance of accurate molecular and pathology-based assessment of patients presenting with CMMRD-associated features.

Materials and methods

A retrospective chart review of two patients with molecularly confirmed CMMRD ascertained through the Medical Genetics service of the McGill University Health Centre (MUHC) was conducted to study the pathway and pitfalls to diagnosis. Records were reviewed and summarized as timelines to depict important events relating to diagnosis and management of CMMRD patients.

Results

Unfamiliarity with CMMRD contributed to a diagnosis delay and initiation of CMMRD-specific surveillance. Pitfalls along the diagnostic pathway included inaccurate clinical information relayed to pathologists, unfamiliarity with CMMRD-defining features on immunohistochemistry (IHC) analyses, IHC variability and unreliability, and lack of awareness of the pivotal role for medical genetics in the diagnosis of CMMRD.

Conclusions

Improved awareness of CMMRD in patients presenting with CMMRD-associated features can help guide IHC analysis and expedite referral to medical genetics for accurate molecular diagnosis. Consequently, timely CMMRD diagnosis improves surveillance and patient management and allows for appropriate genetic counseling for family members.

{"title":"This is not Lynch syndrome: lessons from misattributed diagnoses in constitutional mismatch repair deficiency","authors":"A.H. Mohammad , E. Rohr , A. Moise , R.M. Abdulsalam , W. Davalan , A. Rizzolo , A.S. Liberman , C. Goudie , L. Palma , W.D. Foulkes","doi":"10.1016/j.esmogo.2024.100111","DOIUrl":"10.1016/j.esmogo.2024.100111","url":null,"abstract":"<div><h3>Background</h3><div>Underdiagnosis of constitutional mismatch repair deficiency (CMMRD) syndrome leads to suboptimal cancer surveillance and management of CMMRD patients. Assessing pitfalls that led to the misdiagnosis of CMMRD is important to improve care trajectories, and to highlight the importance of accurate molecular and pathology-based assessment of patients presenting with CMMRD-associated features.</div></div><div><h3>Materials and methods</h3><div>A retrospective chart review of two patients with molecularly confirmed CMMRD ascertained through the Medical Genetics service of the McGill University Health Centre (MUHC) was conducted to study the pathway and pitfalls to diagnosis. Records were reviewed and summarized as timelines to depict important events relating to diagnosis and management of CMMRD patients.</div></div><div><h3>Results</h3><div>Unfamiliarity with CMMRD contributed to a diagnosis delay and initiation of CMMRD-specific surveillance. Pitfalls along the diagnostic pathway included inaccurate clinical information relayed to pathologists, unfamiliarity with CMMRD-defining features on immunohistochemistry (IHC) analyses, IHC variability and unreliability, and lack of awareness of the pivotal role for medical genetics in the diagnosis of CMMRD.</div></div><div><h3>Conclusions</h3><div>Improved awareness of CMMRD in patients presenting with CMMRD-associated features can help guide IHC analysis and expedite referral to medical genetics for accurate molecular diagnosis. Consequently, timely CMMRD diagnosis improves surveillance and patient management and allows for appropriate genetic counseling for family members.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"6 ","pages":"Article 100111"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143147137","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}

引用次数: 0