ESMO Gastrointestinal Oncology最新文献

{"title":"Risk factor of severe diarrhea and enterocolitis induced by CAPOX: a retrospective multicenter study","authors":"A. Teixeira ,&nbsp;T. Felismino ,&nbsp;M.D. Donadio ,&nbsp;G. Catani ,&nbsp;A.L.M. da Silva ,&nbsp;R. Weschenfelder ,&nbsp;R.D. Peixoto ,&nbsp;J.M. O’Connor ,&nbsp;A.K. Coutinho ,&nbsp;R.P. Riechelmann","doi":"10.1016/j.esmogo.2024.100110","DOIUrl":"10.1016/j.esmogo.2024.100110","url":null,"abstract":"<div><h3>Background</h3><div>We have previously suggested that concurrent use of capecitabine plus oxaliplatin (CAPOX) and angiotensin receptor blockers (ARBs) significantly increased the risk of severe diarrhea and/or enterocolitis. We conducted a multicenter larger study to validate this finding, adjusting for other risk factors.</div></div><div><h3>Patients and methods</h3><div>This was a retrospective multicenter study of patients with colorectal cancer treated with at least one cycle of CAPOX. The primary endpoint was grade (G) ≥3 diarrhea and/or enterocolitis induced by CAPOX. Unadjusted and adjusted logistic regression models were used to evaluate risk factors for G ≥3 diarrhea and/or enterocolitis. <em>P</em> &lt; 0.05 was deemed significant.</div></div><div><h3>Results</h3><div>From April 2010 to December 2023, 362 patients were included. In univariate analyses, age ≥65 years, right-sided tumors, use of ARBs or angiotensin-converting enzyme inhibitors (ACEi), age-adjusted Charlson Comorbidity Index, and estimated glomerular filtration rate (eGFR) &lt;60 ml/min were associated with G ≥3 diarrhea and/or enterocolitis. In the multivariable analysis, age ≥65 years [odds ratio (OR) 2.71, 95% confidence interval (CI) 1.38-5.33, <em>P</em> = 0.004] and eGFR &lt;60 ml/min (OR 5.4, 95% CI 2.25-13.8, <em>P</em> &lt; 0.001), but not use of ARBs or ACEi, were significant.</div></div><div><h3>Conclusions</h3><div>Age ≥65 years and eGFR &lt;60 ml/min were independent risk factors for G ≥3 diarrhea/enterocolitis in patients treated with CAPOX. Concurrent use of ARBs or ACEi was not associated with G ≥3 diarrhea/enterocolitis.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"6 ","pages":"Article 100110"},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142704082","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}

{"title":"Genetic and transcriptomic analyses of early-onset colon cancer (EOCC): a post hoc analysis of 2973 patients from two adjuvant randomized trials","authors":"A. Gandini ,&nbsp;C. Gallois ,&nbsp;H. Blons ,&nbsp;C. Mulot ,&nbsp;N. Agueeff ,&nbsp;C. Lepage ,&nbsp;R. Guimbaud ,&nbsp;L. Mineur ,&nbsp;J. Desramé ,&nbsp;B. Chibaudel ,&nbsp;A. de Reyniès ,&nbsp;T. André ,&nbsp;P. Laurent-Puig ,&nbsp;J. Taieb","doi":"10.1016/j.esmogo.2024.100106","DOIUrl":"10.1016/j.esmogo.2024.100106","url":null,"abstract":"<div><h3>Background</h3><div>Despite decreasing colon cancer (CC) incidence worldwide, an inverse trend is being registered since the late 1990s in people &lt;50 years old, possibly due to an increasing exposure to lifestyle-related risk factors/exposome. Early-onset CC (EOCC) typically manifests in more advanced stages and may harbor a distinct genetic profile. However, its prognosis remains controversial, and disease stratification through gene expression-based subtyping could potentially provide insight.</div></div><div><h3>Materials and methods</h3><div>We collected data from stage III CC patients enrolled in PETACC-8 and IDEA-France and we analyzed them according to a cut-off of 50 years of age, defining EOCC and late-onset CC (LOCC). Molecular analyses were carried out to evaluate mismatch repair deficiency (dMMR) and extended genetic profile. RNA-sequencing analyses were carried out to determine consensus molecular subtypes (CMS).</div></div><div><h3>Results</h3><div>A total of 2607 LOCC and 366 EOCC were included. When compared to LOCC, EOCC were in better general conditions and presented more advanced-stage diseases. EOCC were more often dMMR, CMS1, <em>RAS</em> wild-type, and mutated for <em>PTEN, CTNNB1, ERBB2,</em> and <em>DDR2</em>. Relapse-free survival (RFS) was similar in the two age groups (3-year rate 74% versus 76%), but differences were observed according to CMS. In CMS1, a better RFS was observed in mismatch repair-proficient (pMMR) EOCC versus LOCC (3-year rate 82% versus 63%, <em>P</em> = 0.041), while this was not observed in dMMR CMS1.</div></div><div><h3>Conclusions</h3><div>In conclusion, EOCCs are diagnosed in more advanced stages, are more often dMMR, harbor a specific genetic profile, and have similar RFS when compared to LOCC, even if the age effect on RFS appeared to vary among CMS groups.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"7 ","pages":"Article 100106"},"PeriodicalIF":0.0,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143159961","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}

{"title":"Gastrin-releasing peptide receptor expression in gastrointestinal stromal tumours","authors":"M. Berndsen ,&nbsp;F. Puls ,&nbsp;A. Thornell ,&nbsp;Y. Arvidsson ,&nbsp;A. Muth ,&nbsp;S. Lindskog ,&nbsp;E. Elias","doi":"10.1016/j.esmogo.2024.100105","DOIUrl":"10.1016/j.esmogo.2024.100105","url":null,"abstract":"<div><h3>Background</h3><div>There are limited treatment options for patients with advanced or metastatic gastrointestinal stromal tumours (GISTs) that lack mutations targetable by tyrosine kinase inhibitors (TKIs) or that have developed resistance to TKIs. Gastrin-releasing peptide receptor (GRPR) theranostics may offer a viable option in GISTs. However, the expression of the GRPR in GIST has not been extensively studied.</div></div><div><h3>Materials and methods</h3><div>GRPR expression was evaluated using immunohistochemistry in two separate tissue microarrays from patients treated at Sahlgrenska University Hospital, one from the pre-TKI era (1983-2001) and the other from the post-TKI era (2014-2020). In total, 205 tumour samples were characterized as having low/none or moderate/high expression of the GRPR, and these were correlated with clinical characteristics and survival outcomes.</div></div><div><h3>Results</h3><div>In total, 80% of the tumour samples exhibited moderate or high expression of GRPR. GRPR expression was not associated with gender, age, tumour location, or risk group, as defined by the modified National Institutes of Health (NIH) consensus criteria. Neoadjuvant treatment with TKI was correlated with low/none GRPR expression (<em>P</em> = 0.04). In patients who underwent surgery with curative intent and did not receive neoadjuvant treatment, GRPR expression was not associated with survival outcomes.</div></div><div><h3>Conclusions</h3><div>This study is the first to investigate GRPR expression in a large cohort of GIST tumours. Our results demonstrate that most GIST tumours exhibit a moderate to high expression of the receptor, suggesting that GRPR theranostics could be a viable option for TKI-resistant GIST. Interestingly, tumours that were pretreated with TKI showed lower expression levels of GRPR, indicating a need for further studies to explore this finding.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"6 ","pages":"Article 100105"},"PeriodicalIF":0.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142578047","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}

{"title":"Single-cell RNA sequencing of appendiceal adenocarcinoma reveals a low proportion of epithelial cells and a fibroblast enriched tumor microenvironment","authors":"B.B. Gunes ,&nbsp;N.J. Hornstein ,&nbsp;M. Wang ,&nbsp;M. Yousef ,&nbsp;M.M. Fanaeian ,&nbsp;A. Yousef ,&nbsp;S. Chowdhury ,&nbsp;M.A. Zeineddine ,&nbsp;C. Haymaker ,&nbsp;B. Helmink ,&nbsp;K. Fournier ,&nbsp;J.P. Shen","doi":"10.1016/j.esmogo.2024.100094","DOIUrl":"10.1016/j.esmogo.2024.100094","url":null,"abstract":"<div><h3>Background</h3><div>Appendiceal adenocarcinoma (AA) is an understudied gastrointestinal malignancy. Treatment is guided by its proximal counterpart, colorectal cancer (CRC), despite recent studies demonstrating AA’s unique mutational landscape and poor response to CRC chemotherapy. In this study, we describe AA on a single-cell level and uncover features highlighting the contrast between AA and CRC; we believe these findings will support AA as a unique disease entity and encourage further disease-specific focus.</div></div><div><h3>Materials and methods</h3><div>Three patients with peritoneal metastases from AA and one from CRC profiled with 5′ single-cell RNA sequencing.</div></div><div><h3>Results</h3><div>Traditional k-means clustering analysis of &gt;30 000 cells revealed three canonical compartments and 11 major cell types. AA samples were mostly comprised of stromal cells (56%), while healthy appendix samples had significantly more immune and epithelial cells. Strikingly, fibroblasts were the most abundant cell type in AA with cancer-associated fibroblasts from the mucinous AA tumors showing a distinct profile from goblet cell AA or CRC. Pseudobulk analysis comparing tumor cells from AA with normal appendiceal epithelial cells demonstrated up-regulation of a diverse range of oncogenic pathways including inflammatory, epithelial–mesenchymal transition, and angiogenesis.</div></div><div><h3>Conclusions</h3><div>As the first application of single-cell technology to AA these data provide insight into the intratumor heterogeneity of AA and highlight the important contribution of the tumor microenvironment in this orphan disease. These results also reinforce multiple observations that AA is a unique disease entity from CRC and targeting the tumor microenvironment should be considered as a therapeutic strategy.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"6 ","pages":"Article 100094"},"PeriodicalIF":0.0,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142527264","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}

{"title":"DNA methylation markers for sensitive detection of circulating tumor DNA in patients with gastroesophageal cancers","authors":"N. Øgaard ,&nbsp;C.R. Iden ,&nbsp;S.Ø. Jensen ,&nbsp;S.M. Mustafa ,&nbsp;E. Aagaard ,&nbsp;J.B. Bramsen ,&nbsp;L.B. Ahlborn ,&nbsp;J.P. Hasselby ,&nbsp;K.S. Rohrberg ,&nbsp;M.P. Achiam ,&nbsp;C.L. Andersen ,&nbsp;M. Mau-Sørensen","doi":"10.1016/j.esmogo.2024.100104","DOIUrl":"10.1016/j.esmogo.2024.100104","url":null,"abstract":"<div><h3>Background</h3><div>Patients with gastric and gastroesophageal junction adenocarcinomas (G-GEJ ACs) face poor outcomes. Thus sensitive biomarkers for improved clinical management are highly warranted. Detection of circulating tumor DNA (ctDNA) using DNA methylation biomarkers is a highly sensitive approach for cancer detection and management. Here, we explored the potential of a tumor-agnostic test targeting DNA methylation to detect ctDNA in patients with resectable and advanced G-GEJ ACs.</div></div><div><h3>Material and methods</h3><div>A tumor-agnostic digital PCR test—TriMeth—targeting the gastrointestinal cancer-specific methylated genes <em>C9orf50</em>, <em>KCNQ5</em>, and <em>CLIP4</em> was carried out on a total of 131 study patients. DNA from surgical tumor specimens of 29 patients with G-GEJ ACs and plasma cell-free DNA from 52 patients with advanced and resectable G-GEJ ACs, and from 50 healthy controls, were analyzed.</div></div><div><h3>Results</h3><div>Methylated tumor DNA was detected by TriMeth in all of the surgical tumor specimens (29/29, 100%). Furthermore, TriMeth detected ctDNA in plasma from 31/52 (60%) patients with G-GEJ AC, including in 13/17 (76%) advanced cases, and 18/35 (51%) resectable cases. ctDNA was not detected in healthy controls (0/50, 0%).</div></div><div><h3>Conclusions</h3><div>This study demonstrates that TriMeth may hold potential as a biomarker for identifying ctDNA in patients with G-GEJ ACs. The study sets the scene for ongoing larger clinical studies investigating the performance of TriMeth in different clinical settings.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"6 ","pages":"Article 100104"},"PeriodicalIF":0.0,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142441720","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}

{"title":"Prognostic markers in oesophageal and gastric cancer review. Are they ready for clinical practice?","authors":"V. Kunene ,&nbsp;M. Ding ,&nbsp;M. Yap ,&nbsp;E.A. Griffiths ,&nbsp;P. Taniere ,&nbsp;D. Fackrell ,&nbsp;S. Butler ,&nbsp;G. Contino","doi":"10.1016/j.esmogo.2024.100091","DOIUrl":"10.1016/j.esmogo.2024.100091","url":null,"abstract":"<div><div>Oesophageal and gastric cancer outcomes remain poor despite the introduction of new treatments in the past decade. Most patients subjected to chemotherapy or surgery do not, in the long term, benefit from treatment but suffer side-effects. Although next-generation sequencing has accelerated the identification of various genomic aberrations, most have yet to be applied to routine clinical practice. Here, we review published data from systemic reviews and meta-analyses from the past 8 years reporting prognostic markers and why these have not gained traction in clinical practice and how we can improve on this.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"6 ","pages":"Article 100091"},"PeriodicalIF":0.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142419896","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}

{"title":"Health-related quality of life with bemarituzumab plus mFOLFOX6 in patients with FGFR2b-overexpressing, advanced gastric or gastroesophageal junction cancer","authors":"Z.A. Wainberg ,&nbsp;P.C. Enzinger ,&nbsp;S. Qin ,&nbsp;K. Yamaguchi ,&nbsp;J. Wang ,&nbsp;X. Zhou ,&nbsp;A. Gnanasakthy ,&nbsp;K. Taylor ,&nbsp;A. Yusuf ,&nbsp;I. Majer ,&nbsp;A. Jamotte ,&nbsp;Y.-K. Kang","doi":"10.1016/j.esmogo.2024.100095","DOIUrl":"10.1016/j.esmogo.2024.100095","url":null,"abstract":"<div><h3>Background</h3><div>In the phase II, randomized, double-blind FIGHT trial (NCT03694522), treatment with bemarituzumab plus mFOLFOX6 resulted in improvements in progression-free survival and overall survival relative to mFOLFOX6 alone in previously untreated locally advanced or metastatic gastric or gastroesophageal junction cancer with fibroblast growth factor receptor 2b overexpression. Using data from the final analysis, we analyzed patient-reported outcomes (PROs) to evaluate the impact of adding bemarituzumab to mFOLFOX6 on health-related quality of life (HRQoL).</div></div><div><h3>Materials and methods</h3><div>Patients were randomized 1 : 1 to bemarituzumab plus mFOLFOX6 (<em>n</em> = 77) or placebo plus mFOLFOX (<em>n</em> = 78). European Organisation for Research and Treatment of Cancer Core 30-item Quality of Life (EORTC QLQ-C30) and the EuroQol EQ-5D-5L questionnaires were administered at baseline, week 6, every 8 weeks thereafter, and at end-of-treatment visit. Least-squares mean changes from baseline in PRO scale scores were estimated using mixed models for repeated measures; time to deterioration and improvement were assessed using Cox proportional hazards models. Analyses were exploratory <em>post hoc</em>.</div></div><div><h3>Results</h3><div>PRO scale scores at baseline and compliance rates across PRO assessments over time were similar between the bemarituzumab and placebo arms. Least-squares mean changes from baseline on key EORTC QLQ-C30 scales (global health status/QoL, physical functioning, fatigue, nausea and vomiting, and appetite loss) and the EQ-5D-5L visual analog scale were similar over time between treatment arms. Analyses of time to deterioration, sustained deterioration, and improvement suggested similar HRQoL between treatment arms.</div></div><div><h3>Conclusions</h3><div>Treatment with bemarituzumab plus mFOLFOX6 was associated with sustained HRQoL relative to mFOLFOX6 alone.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"6 ","pages":"Article 100095"},"PeriodicalIF":0.0,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142419895","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}

{"title":"Gastric cancer hospital-based registry: real-world gastric cancer data from Latin America and Europe","authors":"B. Freile ,&nbsp;T.S. van Schooten ,&nbsp;S. Derks ,&nbsp;F. Carneiro ,&nbsp;C. Figueiredo ,&nbsp;R. Barros ,&nbsp;C. Gauna ,&nbsp;R. Pereira ,&nbsp;M. Romero ,&nbsp;A. Riquelme ,&nbsp;M. Garrido ,&nbsp;G. Owen ,&nbsp;E. Ruiz-García ,&nbsp;E.A. Fernández-Figueroa ,&nbsp;A. Hernández-Guerrero ,&nbsp;M. Alsina ,&nbsp;C. Viaplana ,&nbsp;M. Diez ,&nbsp;S. Romero-Alcaide ,&nbsp;E. Jiménez-Martí ,&nbsp;T. Fleitas Kanonnikoff","doi":"10.1016/j.esmogo.2024.100088","DOIUrl":"10.1016/j.esmogo.2024.100088","url":null,"abstract":"<div><h3>Background</h3><p>Gastric cancer has a high incidence and mortality rate worldwide. Epidemiological, clinical, and molecular features significantly impact patient outcomes. In regions lacking a national gastric cancer registry, hospital-based registries can provide crucial data that may aid in planning therapeutic strategies for the disease.</p></div><div><h3>Methods</h3><p>A retrospective observational cohort design was carried out in European Union (EU) and Latin American (LATAM) countries participating in the LEGACy project. Survival estimates were determined using actuarial Kaplan–Meier curves. Comparison was carried out with the log-rank test, and differences were considered statistically significant for <em>P</em> values ≤0.05.</p></div><div><h3>Results</h3><p>A total of 689 patients diagnosed with gastric cancer from November 2018 to November 2019 were included. Both cohorts had the body as the most common site reported (34.4% for EU and 51% for LATAM). The most used method for staging was computed tomography for both cohorts, although 6.9% of the LATAM population had positron emission tomography/computed tomography instead. Intestinal histological subtype was the most common (41.9% and 46.3% reported by EU and LATAM), while diffuse subtype was 44.9% for the LATAM and 21.3% for the EU population. Among patients tested for human epidermal growth factor receptor 2 (HER2), 12.5% were positive in the EU cohort and 13.8% in the LATAM cohort. For both cohorts, the most common site of human epidermal growth factor receptor 2 positivity was the gastroesophageal junction. Systemic treatment with curative intention was indicated in 50.7% in the EU cohort and 46.4% of the LATAM cohort. The most frequent scheme indicated for both the localized and the advanced setting was platinum-based (42.6% and 84.8% for EU and LATAM). Considering both cohorts, only 14.4% of the patients received second-line treatment, and 3% received a third-line treatment. After using Cox regression analysis, no difference in overall survival was reported, with a median of 10.9 months.</p></div><div><h3>Conclusions</h3><p>Despite the limitations of hospital-based registry analysis, our study has provided valuable insights into clinical characteristics and treatment approaches of EU and LATAM populations.</p></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"6 ","pages":"Article 100088"},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949819824000499/pdfft?md5=5402a74d1083f8a4a81cbaad9c35b6ba&pid=1-s2.0-S2949819824000499-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142242232","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}

{"title":"Geriatric Assessment-guided therapy modification and outcomes in patients with non-metastatic gastroesophageal cancer: a retrospective cohort study☆","authors":"V. Noronha ,&nbsp;M. Shah ,&nbsp;A. Pillai ,&nbsp;N. Menon ,&nbsp;A. Ramaswamy ,&nbsp;V. Ostwal ,&nbsp;A.R. Rao ,&nbsp;A. Kumar ,&nbsp;R. Dhekale ,&nbsp;A. Shetake ,&nbsp;S. Mahajan ,&nbsp;A. Daptardar ,&nbsp;L. Sonkusare ,&nbsp;M. Vagal ,&nbsp;P. Mahajan ,&nbsp;S. Timmanpyati ,&nbsp;V. Gota ,&nbsp;D. Niyogi ,&nbsp;R. Badwe ,&nbsp;K. Prabhash","doi":"10.1016/j.esmogo.2024.100093","DOIUrl":"10.1016/j.esmogo.2024.100093","url":null,"abstract":"<div><h3>Background</h3><p>Despite aggressive multimodal treatment for locally advanced esophagogastric cancer (LA-EGC), many patients experience early disease progression/death. We aimed to explore the role of Geriatric Assessment (GA) in optimizing patient care in older patients with LA-EGC.</p></div><div><h3>Materials and methods</h3><p>A retrospective cohort study was conducted in patients aged ≥60 years with LA-EGC referred to the geriatric oncology clinic at our institute between June 2018 and November 2022, who were planned for curative treatment. We explored the role of GA-guided therapy modifications on survival, identification of factors predicting potential ‘overtreatment’ (arbitrarily defined as patients in whom disease recurrence or death occurred within 6 months of treatment completion), and utility of the GA in identification of this patient subset.</p></div><div><h3>Results</h3><p>We enrolled 199 patients. The median age was 68 years (interquartile range 64-73 years). There were 131 (65.8%) males and 157 patients (78.9%) had a performance status of 0-1. Based on the GA, 110 (55.3%) patients were deemed fit (≤2 domains affected). Therapy modification (primarily de-intensification) occurred in 72 (36.2%) patients. At a median follow-up of 34.1 months [95% confidence interval (CI) 31.5-36.7 months], median event-free survival with de-intensified treatment was 12.2 months (95% CI 9.1-15.3 months) versus 18.8 months (95% CI 14.7-22.9 months) with standard treatment; <em>P</em> = 0.113. Median overall survival was 15.4 months (95% CI 9.3-21.5 months) with de-intensified treatment versus 21.1 months (95% CI 16.1-26.1 months) with standard treatment, <em>P</em> = 0.116. Six months following treatment completion, 79 (39.7%) patients were potentially overtreated. Initial GA failed to identify patients who were potentially overtreated (<em>P</em> = 0.923).</p></div><div><h3>Conclusion</h3><p>GA-tailored treatment de-escalation does not impair survival in older patients with LA-EGC but fails to identify the patient cohort at risk for overtreatment.</p></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"6 ","pages":"Article 100093"},"PeriodicalIF":0.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949819824000542/pdfft?md5=91ec064e979d0034844d3c1e7188b953&pid=1-s2.0-S2949819824000542-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142172971","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}

{"title":"PRABITAS study design: a pragmatic, randomized phase III trial of bi-weekly versus conventional trifluridine/tipiracil plus bevacizumab for metastatic colorectal cancer","authors":"T. Sakakida ,&nbsp;T. Masuishi ,&nbsp;M. Asayama ,&nbsp;S. Mitani ,&nbsp;A. Makiyama ,&nbsp;T. Shimura ,&nbsp;H. Takeda ,&nbsp;Y. Suwa ,&nbsp;Y. Takano ,&nbsp;K. Sawada ,&nbsp;T. Yomoda ,&nbsp;H. Mushiake ,&nbsp;Y. Okumura ,&nbsp;M. Yokota ,&nbsp;M. Yamamoto ,&nbsp;Y. Kito ,&nbsp;K. Ogawa ,&nbsp;H. Matsuoka ,&nbsp;M. Ando ,&nbsp;M. Tajika ,&nbsp;H. Taniguchi","doi":"10.1016/j.esmogo.2024.100090","DOIUrl":"10.1016/j.esmogo.2024.100090","url":null,"abstract":"<div><p>Trifluridine/tipiracil (FTD/TPI) plus bevacizumab (BEV) is the established therapy for refractory metastatic colorectal cancer, but there are concerns regarding the regimen’s complexity and hematotoxic effects, especially for patients with organ dysfunction, comorbidities, or a reduced performance status—groups often excluded from conventional clinical trials. Preliminary studies demonstrated that bi-weekly FTD/TPI + BEV may mitigate these hematotoxic effects compared with the conventional schedule without compromising efficacy. No clinical trials, however, have directly compared these two regimens. Therefore, we initiated the PRABITAS trial, a multicenter, randomized, phase III non-inferiority trial, to evaluate the efficacy and safety of bi-weekly FTD/TPI + BEV compared with conventional FTD/TPI + BEV. This was designed as a pragmatic trial, a novel approach in clinical trials aiming to aid decision-making in daily practice by mimicking real-world clinical settings. The PRABITAS trial incorporates minimal eligibility criteria to include a more representative patient population, allows flexibility in intervention adherence and assessment, and employs streamlined data collection to reduce the burden on both patients and healthcare providers. The primary endpoint is overall survival in the intention-to-treat population. Launched in December 2023, the trial aimed to enroll a total of 890 patients.</p></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"5 ","pages":"Article 100090"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949819824000517/pdfft?md5=c62af2a7047f63261d89de04561562d4&pid=1-s2.0-S2949819824000517-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142096601","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}