Pub Date : 2025-11-10DOI: 10.1016/j.esmogo.2025.100264
S.H.R. Kim, M.K. Harrison
Stereotactic ablative radiotherapy (SABR), which is already used as the standard-of-care treatment in other cancers such as lung, is being increasingly used in the treatment of liver metastases in the oligometastatic setting in unresectable, pre-treated patients. Various phase I/II trials and retrospective series have demonstrated its efficacy in terms of local control (LC), progression-free and overall survival. Tumour characteristics of <6 cm, <3 tumours and absence of extrahepatic disease, and favourable histologies including colorectal, breast and renal primaries have been associated with favourable outcomes. Radiation dose is also important, with a biological effective dose ≥120 Gy giving optimal LC. To be determined in SABR is the exact dose and fractionation employed, which is variable without evidence from randomised controlled trials to date. The aforementioned trials have established that SABR is well-tolerated. In the short-term, it can cause gastrointestinal disturbances, transaminitis and radiation-induced liver disease. In the longer-term, gastrointestinal bleeding and bone fractures have been rarely reported, though follow-up periods for studies were limited. Other treatments such as radiofrequency ablation (RFA) and surgery are also standard-of-care. There have been no prospective randomised trials to date comparing these treatments. Smaller trials demonstrated no survival differences between SABR and RFA, though these studies favour better LC in SABR for larger tumours (>3 cm). To summarise, SABR for liver metastases leads to good LC and survival and is well-tolerated, especially with favourable tumour characteristics. Prospective studies will need to help establish its exact role in comparison with other localised therapies.
{"title":"Stereotactic ablative radiotherapy (SABR) for liver metastases: where we currently stand","authors":"S.H.R. Kim, M.K. Harrison","doi":"10.1016/j.esmogo.2025.100264","DOIUrl":"10.1016/j.esmogo.2025.100264","url":null,"abstract":"<div><div>Stereotactic ablative radiotherapy (SABR), which is already used as the standard-of-care treatment in other cancers such as lung, is being increasingly used in the treatment of liver metastases in the oligometastatic setting in unresectable, pre-treated patients. Various phase I/II trials and retrospective series have demonstrated its efficacy in terms of local control (LC), progression-free and overall survival. Tumour characteristics of <6 cm, <3 tumours and absence of extrahepatic disease, and favourable histologies including colorectal, breast and renal primaries have been associated with favourable outcomes. Radiation dose is also important, with a biological effective dose ≥120 Gy giving optimal LC. To be determined in SABR is the exact dose and fractionation employed, which is variable without evidence from randomised controlled trials to date. The aforementioned trials have established that SABR is well-tolerated. In the short-term, it can cause gastrointestinal disturbances, transaminitis and radiation-induced liver disease. In the longer-term, gastrointestinal bleeding and bone fractures have been rarely reported, though follow-up periods for studies were limited. Other treatments such as radiofrequency ablation (RFA) and surgery are also standard-of-care. There have been no prospective randomised trials to date comparing these treatments. Smaller trials demonstrated no survival differences between SABR and RFA, though these studies favour better LC in SABR for larger tumours (>3 cm). To summarise, SABR for liver metastases leads to good LC and survival and is well-tolerated, especially with favourable tumour characteristics. Prospective studies will need to help establish its exact role in comparison with other localised therapies.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"10 ","pages":"Article 100264"},"PeriodicalIF":0.0,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145528859","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 : 2025-11-04DOI: 10.1016/j.esmogo.2025.100261
D.R. Castillo , M. Guo , P. Shah , M. Hazeltin , D. Tai , F. Al-Manaseer , S. Mlamba , D. Perez , S. Yeremian , S. Guzman , R. Mannan , C. Crook , C. Lau , N. Tawar , G. Brar , M. Raoof , Y. Woo , S.P. Wu , D. Li
Background
Claudin 18.2 (CLDN18.2)-targeted therapy and immune checkpoint blockade have transformed the frontline treatment landscape of gastric and gastroesophageal junction (GC/GEJ) cancers, marking a major advance in precision oncology. However, the optimal sequencing and integration of these biomarker-driven therapies remain undefined. A comprehensive evaluation of the relationship between CLDN18.2 and programmed death-ligand 1 (PD-L1) expression, along with co-occurring genomic alterations and metastatic patterns, is critical to refine patient selection and improve survival outcomes.
Materials and methods
We retrospectively analyzed 70 patients with microsatellite-stable, human epidermal growth factor receptor 2 (HER2)-negative metastatic GC/GEJ adenocarcinoma treated with first-line chemoimmunotherapy. CLDN18.2 positivity was defined as ≥75% of tumor cells with moderate to strong membranous staining, and PD-L1 positivity as a combined positive score (CPS) ≥1. Molecular profiling of pretreatment tumor biopsies was carried out using a hybrid DNA/RNA sequencing panel covering 720 cancer-related genes. The incidence of key genomic alterations (TP53, KRAS, CDH1, PIK3CA, RHOA, POLE, and CLDN18–ARHGAP6 fusion) was compared between CLDN18.2-positive and -negative tumors. Clinicopathological variables, including age, sex, race, Lauren classification, metastatic site, PD-L1 CPS, CLDN18.2 status, and receipt of hyperthermic intraperitoneal chemotherapy (HIPEC), were evaluated. Survival outcomes were estimated using the Kaplan–Meier method, and univariate and multivariate Cox regression analyses were carried out to identify prognostic factors.
Results
Thirty-eight tumors (54%) were CLDN18.2-positive. CLDN18.2-negative tumors were more likely to harbor KRAS mutations and higher PD-L1 CPS. No significant differences in overall survival (OS) or progression-free survival (PFS) were observed between CLDN18.2-positive and -negative groups. Among all covariates, metastatic burden (oligometastatic versus polymetastatic) and race were independently associated with OS. In contrast, age, sex, histology, PD-L1 CPS, and CLDN18.2 expression were not prognostic. HIPEC did not significantly improve PFS or OS compared with non-HIPEC treatment; however, a trend toward improved outcomes suggests potential benefit in selected patients, supporting further prospective evaluation.
Conclusions
CLDN18.2 and PD-L1 expression delineate distinct molecular and metastatic subgroups of GC/GEJ cancer. Personalized strategies integrating biomarker-driven systemic and regional therapies may enhance outcomes in this heterogeneous disease. Although HIPEC did not significantly improve survival, the observed trend warrants further validation in prospective studies.
{"title":"Distinct clinicopathological and survival profiles of CLDN18.2 and PD-L1 expression in advanced gastric cancer and gastroesophageal junction adenocarcinoma","authors":"D.R. Castillo , M. Guo , P. Shah , M. Hazeltin , D. Tai , F. Al-Manaseer , S. Mlamba , D. Perez , S. Yeremian , S. Guzman , R. Mannan , C. Crook , C. Lau , N. Tawar , G. Brar , M. Raoof , Y. Woo , S.P. Wu , D. Li","doi":"10.1016/j.esmogo.2025.100261","DOIUrl":"10.1016/j.esmogo.2025.100261","url":null,"abstract":"<div><h3>Background</h3><div>Claudin 18.2 (CLDN18.2)-targeted therapy and immune checkpoint blockade have transformed the frontline treatment landscape of gastric and gastroesophageal junction (GC/GEJ) cancers, marking a major advance in precision oncology. However, the optimal sequencing and integration of these biomarker-driven therapies remain undefined. A comprehensive evaluation of the relationship between CLDN18.2 and programmed death-ligand 1 (PD-L1) expression, along with co-occurring genomic alterations and metastatic patterns, is critical to refine patient selection and improve survival outcomes.</div></div><div><h3>Materials and methods</h3><div>We retrospectively analyzed 70 patients with microsatellite-stable, human epidermal growth factor receptor 2 (HER2)-negative metastatic GC/GEJ adenocarcinoma treated with first-line chemoimmunotherapy. CLDN18.2 positivity was defined as ≥75% of tumor cells with moderate to strong membranous staining, and PD-L1 positivity as a combined positive score (CPS) ≥1. Molecular profiling of pretreatment tumor biopsies was carried out using a hybrid DNA/RNA sequencing panel covering 720 cancer-related genes. The incidence of key genomic alterations (<em>TP53, KRAS, CDH1, PIK3CA, RHOA, POLE, and CLDN18–ARHGAP6</em> fusion) was compared between CLDN18.2-positive and -negative tumors. Clinicopathological variables, including age, sex, race, Lauren classification, metastatic site, PD-L1 CPS, CLDN18.2 status, and receipt of hyperthermic intraperitoneal chemotherapy (HIPEC), were evaluated. Survival outcomes were estimated using the Kaplan–Meier method, and univariate and multivariate Cox regression analyses were carried out to identify prognostic factors.</div></div><div><h3>Results</h3><div>Thirty-eight tumors (54%) were CLDN18.2-positive. CLDN18.2-negative tumors were more likely to harbor <em>KRAS</em> mutations and higher PD-L1 CPS. No significant differences in overall survival (OS) or progression-free survival (PFS) were observed between CLDN18.2-positive and -negative groups. Among all covariates, metastatic burden (oligometastatic versus polymetastatic) and race were independently associated with OS. In contrast, age, sex, histology, PD-L1 CPS, and CLDN18.2 expression were not prognostic. HIPEC did not significantly improve PFS or OS compared with non-HIPEC treatment; however, a trend toward improved outcomes suggests potential benefit in selected patients, supporting further prospective evaluation.</div></div><div><h3>Conclusions</h3><div>CLDN18.2 and PD-L1 expression delineate distinct molecular and metastatic subgroups of GC/GEJ cancer. Personalized strategies integrating biomarker-driven systemic and regional therapies may enhance outcomes in this heterogeneous disease. Although HIPEC did not significantly improve survival, the observed trend warrants further validation in prospective studies.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"10 ","pages":"Article 100261"},"PeriodicalIF":0.0,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145466171","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 : 2025-10-23DOI: 10.1016/j.esmogo.2025.100259
W.Y. Chua , O. Lim , D. Tai , S.Y. Lee , J.J.X. Lee , H.C. Toh , B.K.P. Goh , H.L. Tan , Y.X. Koh , J.P.E. Chang , K.Y.Y. Ng
Background
Hepatocellular carcinoma (HCC) is the sixth most common malignancy and the second leading cause of cancer-related mortality worldwide. Patients are typically diagnosed at an advanced stage, with a poor prognosis. Despite recent therapeutic advances in HCC, there are concerns about the accessibility of these treatments for patients of lower socioeconomic status (SES), which may lead to poorer outcomes and exacerbate health inequity.
Methods
We searched MEDLINE and Embase from inception to 26 April 2024 to identify cohort studies comparing SES indicators and HCC outcomes. We computed hazard ratios (HRs) with accompanying 95% confidence intervals (CIs) for each study and pooled the results using a random-effects meta-analysis. Quality assessment was carried out using the Newcastle–Ottawa Quality Assessment Scale.
Results
In this meta-analysis of 15 studies involving 199 404 patients, we analysed the impact of SES on overall survival in patients with HCC. Lower income (HR 1.10, 95% CI 1.02-1.18, P < 0.01) and lower insurance coverage (HR 1.22, 95% CI 1.12-1.32, P = 0.01) had a negative impact on overall survival from HCC, but we were unable to stratify by stage. Absent or reduced insurance status had a negative impact on overall survival from HCC, regardless of the stage of HCC (early-stage HR 1.18, 95% CI 1.03-1.36 versus all-stage HR 1.25, 95% CI 1.13-1.38).
Conclusion
Lower income and insurance coverage negatively impacted overall survival from HCC. Absent or reduced insurance status negatively impacted overall survival from HCC, regardless of the stage of HCC. Further studies from low- to middle-income and Asian countries are needed. There is an urgent need to develop policies to reduce the survival gap between patients with HCC of differing SES status.
背景：肝细胞癌（HCC）是全球第六大常见恶性肿瘤，也是导致癌症相关死亡的第二大原因。患者通常在晚期确诊，预后较差。尽管最近HCC的治疗取得了进展，但人们担心社会经济地位较低的患者能否获得这些治疗，这可能导致较差的结果并加剧健康不平等。方法：我们检索MEDLINE和Embase从成立到2024年4月26日，以确定比较SES指标和HCC结局的队列研究。我们计算了每项研究的风险比（hr）和随附的95%置信区间（ci），并使用随机效应荟萃分析汇总了结果。使用纽卡斯尔-渥太华质量评估量表进行质量评估。结果：在这项包含15项研究199404例患者的荟萃分析中，我们分析了SES对HCC患者总生存期的影响。较低的收入（HR 1.10, 95% CI 1.02-1.18, P < 0.01）和较低的保险覆盖率（HR 1.22, 95% CI 1.12-1.32, P = 0.01）对HCC的总生存率有负面影响，但我们无法按分期进行分层。无论HCC分期如何，缺乏或减少保险状况对HCC的总生存率有负面影响（早期HR为1.18,95% CI为1.03-1.36，而全期HR为1.25,95% CI为1.13-1.38）。结论：较低的收入和保险覆盖率对HCC患者的总生存率有负面影响。无论HCC的分期如何，缺乏或减少保险状况都会对HCC的总生存率产生负面影响。需要对中低收入国家和亚洲国家进行进一步研究。迫切需要制定政策来减少不同社会经济地位的HCC患者之间的生存差距。
{"title":"The impact of socioeconomic status with overall survival in hepatocellular carcinoma: a systematic review and meta-analysis","authors":"W.Y. Chua , O. Lim , D. Tai , S.Y. Lee , J.J.X. Lee , H.C. Toh , B.K.P. Goh , H.L. Tan , Y.X. Koh , J.P.E. Chang , K.Y.Y. Ng","doi":"10.1016/j.esmogo.2025.100259","DOIUrl":"10.1016/j.esmogo.2025.100259","url":null,"abstract":"<div><h3>Background</h3><div>Hepatocellular carcinoma (HCC) is the sixth most common malignancy and the second leading cause of cancer-related mortality worldwide. Patients are typically diagnosed at an advanced stage, with a poor prognosis. Despite recent therapeutic advances in HCC, there are concerns about the accessibility of these treatments for patients of lower socioeconomic status (SES), which may lead to poorer outcomes and exacerbate health inequity.</div></div><div><h3>Methods</h3><div>We searched MEDLINE and Embase from inception to 26 April 2024 to identify cohort studies comparing SES indicators and HCC outcomes. We computed hazard ratios (HRs) with accompanying 95% confidence intervals (CIs) for each study and pooled the results using a random-effects meta-analysis. Quality assessment was carried out using the Newcastle–Ottawa Quality Assessment Scale.</div></div><div><h3>Results</h3><div>In this meta-analysis of 15 studies involving 199 404 patients, we analysed the impact of SES on overall survival in patients with HCC. Lower income (HR 1.10, 95% CI 1.02-1.18, <em>P</em> < 0.01) and lower insurance coverage (HR 1.22, 95% CI 1.12-1.32, <em>P</em> = 0.01) had a negative impact on overall survival from HCC, but we were unable to stratify by stage. Absent or reduced insurance status had a negative impact on overall survival from HCC, regardless of the stage of HCC (early-stage HR 1.18, 95% CI 1.03-1.36 versus all-stage HR 1.25, 95% CI 1.13-1.38).</div></div><div><h3>Conclusion</h3><div>Lower income and insurance coverage negatively impacted overall survival from HCC. Absent or reduced insurance status negatively impacted overall survival from HCC, regardless of the stage of HCC. Further studies from low- to middle-income and Asian countries are needed. There is an urgent need to develop policies to reduce the survival gap between patients with HCC of differing SES status.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"10 ","pages":"Article 100259"},"PeriodicalIF":0.0,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145362425","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 : 2025-10-17DOI: 10.1016/j.esmogo.2025.100245
A. Fernandes , A. Lambert , A. Tarabay , A. Hollebecque , C. Smolenschi , M. Valéry , T. Pudlarz , A. Fuerea , G. Camilleri , M. Delaye , V. Boige , M. Ducreux , A. Boilève
Background
Pancreatic ductal adenocarcinoma (PDAC) is expected to become the second deadliest cancer in Europe by 2030. Given the underlying differences in embryogenesis, the objectives of this study were to describe the clinical and molecular features and outcomes of PDAC based on the primary tumor location [head (H) or body/tail (B/T)].
Patients and methods
A retrospective single-center study included patients with a histologically confirmed PDAC and known tumor location from 2012 to 2024. The molecular panels included in-house panel on tumor tissue, FoundationMedicine® (tumor tissue) or FoundationOne Liquid CDx® (liquid biopsy) panels. HR and P value were computed via Cox regression between H versus B/T tumors.
Results
A total of 1011 patients were included, among them 520 patients (51%) with H-tumor. Molecular alterations were available for 373 patients. Most common genes altered were KRAS (78%), TP53 (69%), CDKN2A (24%), and SMAD4 (12%), without significant differences between the two groups. Median overall survival (OS) from diagnosis was 20.6 months [95% confidence interval (CI) 19.2-22.6 months] in H tumors compared with 16.2 months in B/T tumors (95% CI 14.2-17.8 months, P = 0.00057). Median OS from metastatic diagnosis was 14.4 months in H tumors (95% CI 13.4-16.7 months) versus 12.9 months in B/T tumors (95% CI 11.0-14.9 months, P = 0.033). In multivariable analysis, operated patients [hazard ratio (HR) 0.36, P < 0.001], lung-only metastases (HR 0.55, P = 0.003) and low neutrophil/lymphocyte ratio (HR 0.56, P < 0.001) were associated with a longer OS while liver metastases (HR 1.25, P = 0.02) and B/T primary tumor site (HR 1.23, P = 0.03) worsened the prognosis.
Conclusions
In a large retrospective cohort, H-PDAC was found to have a longer median OS than B/T-PDAC from initial and metastatic diagnosis.
预计到2030年，胰腺导管腺癌（PDAC）将成为欧洲第二大致命癌症。鉴于胚胎发生的潜在差异，本研究的目的是描述基于原发肿瘤位置[头(H)或体/尾（B/T）]的PDAC的临床和分子特征和结局。患者和方法一项回顾性单中心研究纳入了2012年至2024年组织学证实的PDAC和已知肿瘤位置的患者。分子小组包括肿瘤组织内部小组、FoundationMedicine®（肿瘤组织）或FoundationOne Liquid CDx®（液体活检）小组。通过Cox回归计算H /T肿瘤与B/T肿瘤之间的HR和P值。结果共纳入1011例患者，其中h -肿瘤520例（51%）。373名患者进行了分子改变。最常见的基因改变是KRAS（78%）、TP53（69%）、CDKN2A（24%）和SMAD4(12%)，两组间无显著差异。诊断后H肿瘤的中位总生存期（OS）为20.6个月[95%可信区间（CI） 19.2-22.6个月]，B/T肿瘤为16.2个月（95% CI 14.2-17.8个月，P = 0.00057）。H肿瘤转移诊断的中位生存期为14.4个月（95% CI 13.4-16.7个月），B/T肿瘤为12.9个月（95% CI 11.0-14.9个月，P = 0.033）。在多变量分析中，手术患者[危险比（HR） 0.36, P <； 0.001]、仅肺转移（HR 0.55, P = 0.003）和低中性粒细胞/淋巴细胞比率（HR 0.56, P < 0.001）与较长的生存期相关，而肝转移（HR 1.25, P = 0.02）和B/T原发肿瘤部位（HR 1.23, P = 0.03）使预后恶化。结论在一项大型回顾性队列研究中，从初始诊断和转移诊断来看，H-PDAC的中位生存期比B/T-PDAC更长。
{"title":"Heads or tails? In-depth analysis of pancreatic cancer outcome according to tumor location","authors":"A. Fernandes , A. Lambert , A. Tarabay , A. Hollebecque , C. Smolenschi , M. Valéry , T. Pudlarz , A. Fuerea , G. Camilleri , M. Delaye , V. Boige , M. Ducreux , A. Boilève","doi":"10.1016/j.esmogo.2025.100245","DOIUrl":"10.1016/j.esmogo.2025.100245","url":null,"abstract":"<div><h3>Background</h3><div>Pancreatic ductal adenocarcinoma (PDAC) is expected to become the second deadliest cancer in Europe by 2030. Given the underlying differences in embryogenesis, the objectives of this study were to describe the clinical and molecular features and outcomes of PDAC based on the primary tumor location [head (H) or body/tail (B/T)].</div></div><div><h3>Patients and methods</h3><div>A retrospective single-center study included patients with a histologically confirmed PDAC and known tumor location from 2012 to 2024. The molecular panels included in-house panel on tumor tissue, FoundationMedicine® (tumor tissue) or FoundationOne Liquid CDx® (liquid biopsy) panels. HR and <em>P</em> value were computed via Cox regression between H versus B/T tumors.</div></div><div><h3>Results</h3><div>A total of 1011 patients were included, among them 520 patients (51%) with H-tumor. Molecular alterations were available for 373 patients. Most common genes altered were <em>KRAS</em> (78%), <em>TP53</em> (69%), <em>CDKN2A</em> (24%), and <em>SMAD4</em> (12%), without significant differences between the two groups. Median overall survival (OS) from diagnosis was 20.6 months [95% confidence interval (CI) 19.2-22.6 months] in H tumors compared with 16.2 months in B/T tumors (95% CI 14.2-17.8 months, <em>P</em> = 0.00057). Median OS from metastatic diagnosis was 14.4 months in H tumors (95% CI 13.4-16.7 months) versus 12.9 months in B/T tumors (95% CI 11.0-14.9 months, <em>P</em> = 0.033). In multivariable analysis, operated patients [hazard ratio (HR) 0.36, <em>P</em> < 0.001], lung-only metastases (HR 0.55, <em>P</em> = 0.003) and low neutrophil/lymphocyte ratio (HR 0.56, <em>P</em> < 0.001) were associated with a longer OS while liver metastases (HR 1.25, <em>P</em> = 0.02) and B/T primary tumor site (HR 1.23, <em>P</em> = 0.03) worsened the prognosis.</div></div><div><h3>Conclusions</h3><div>In a large retrospective cohort, H-PDAC was found to have a longer median OS than B/T-PDAC from initial and metastatic diagnosis.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"10 ","pages":"Article 100245"},"PeriodicalIF":0.0,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145324496","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 : 2025-10-14DOI: 10.1016/j.esmogo.2025.100257
K. Shimozaki , A. Ooki , S. Fukuoka , T. Hirasawa , M. Takamatsu , H. Kawachi , T. Wakatsuki , K. Yoshikawa , K. Yoshino , S. Udagawa , H. Osumi , M. Ogura , E. Shinozaki , K. Chin , K. Yamaguchi
Background
Despite several studies highlighting the importance of zolbetuximab-induced gastrointestinal toxicity, the incidence of and risk factors for severe hypoalbuminemia during zolbetuximab plus chemotherapy for the treatment of claudin 18.2-positive advanced gastric cancer have not been fully elucidated.
Materials and methods
We retrospectively evaluated 29 patients (median age, 62 years; men, 45%; diffuse-type histology, 76%; prior total gastrectomy, 24%). Severe hypoalbuminemia was defined as a serum albumin level ≤2.5 g/dl during or a maximum decrease of ≥1.0 g/dl from baseline during cycle 1 day 1 and cycle 3 day 1 in this cohort.
Results
Median serum albumin levels at baseline, cycle 2, and cycle 3 day 1 were 4.0, 3.1, and 3.4 g/dl, respectively. The median maximum change in serum albumin from baseline was –1.0 (range –1.6 to 0.3) g/dl. Grade 3 hypoalbuminemia was observed in two patients (6.9%). The absence of a history of total gastrectomy before systemic treatment, the use of oxaliplatin and capecitabine, body mass index ≥19.8, and nausea/vomiting during zolbetuximab infusion at cycle 1 were identified as predictive biomarkers for developing severe hypoalbuminemia.
Conclusion
This study highlights the clinical significance of developing severe hypoalbuminemia during treatment with zolbetuximab plus chemotherapy and identifies possible risk factors.
{"title":"Hypoalbuminemia during zolbetuximab plus chemotherapy for claudin 18.2-positive advanced gastric cancer: a need for caution?","authors":"K. Shimozaki , A. Ooki , S. Fukuoka , T. Hirasawa , M. Takamatsu , H. Kawachi , T. Wakatsuki , K. Yoshikawa , K. Yoshino , S. Udagawa , H. Osumi , M. Ogura , E. Shinozaki , K. Chin , K. Yamaguchi","doi":"10.1016/j.esmogo.2025.100257","DOIUrl":"10.1016/j.esmogo.2025.100257","url":null,"abstract":"<div><h3>Background</h3><div>Despite several studies highlighting the importance of zolbetuximab-induced gastrointestinal toxicity, the incidence of and risk factors for severe hypoalbuminemia during zolbetuximab plus chemotherapy for the treatment of claudin 18.2-positive advanced gastric cancer have not been fully elucidated.</div></div><div><h3>Materials and methods</h3><div>We retrospectively evaluated 29 patients (median age, 62 years; men, 45%; diffuse-type histology, 76%; prior total gastrectomy, 24%). Severe hypoalbuminemia was defined as a serum albumin level ≤2.5 g/dl during or a maximum decrease of ≥1.0 g/dl from baseline during cycle 1 day 1 and cycle 3 day 1 in this cohort.</div></div><div><h3>Results</h3><div>Median serum albumin levels at baseline, cycle 2, and cycle 3 day 1 were 4.0, 3.1, and 3.4 g/dl, respectively. The median maximum change in serum albumin from baseline was –1.0 (range –1.6 to 0.3) g/dl. Grade 3 hypoalbuminemia was observed in two patients (6.9%). The absence of a history of total gastrectomy before systemic treatment, the use of oxaliplatin and capecitabine, body mass index ≥19.8, and nausea/vomiting during zolbetuximab infusion at cycle 1 were identified as predictive biomarkers for developing severe hypoalbuminemia.</div></div><div><h3>Conclusion</h3><div>This study highlights the clinical significance of developing severe hypoalbuminemia during treatment with zolbetuximab plus chemotherapy and identifies possible risk factors.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"10 ","pages":"Article 100257"},"PeriodicalIF":0.0,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145324497","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 : 2025-10-14DOI: 10.1016/j.esmogo.2025.100241
K.-N. Kwok , K.-M. Chueng , S.J.-L. Lam , M. Seo , C.Y. Lau , P.Y.-M. Woo , H.-S. Lam , S.-M. Yip , S. Lam , O.-P. Chiu , W.W.Y. Sung , H.H.-W. Liu , K.K.-H. Bao , J.C.-H. Chow , S.K.-K. Ng , H.H.-Y. Yiu , D.C.C. Lam
Background
Current guidelines for hepatocellular carcinoma (HCC) screening in patients with chronic liver disease (CLD) recommend ultrasound and/or α-fetoprotein (AFP) testing every 6 months. However, both methods exhibit low sensitivity for early-stage HCC. Building on our previous study that identified a novel blood test signature for HCC, this study aims to develop a routine blood-based artificial intelligence (AI) model for HCC detection.
Patients and methods
Records from 2000 to 2018 were retrieved from Hospital Authority Data Collaboration Laboratory, a territory-wide database. CLD (hepatitis/cirrhosis) patients with and without HCC were identified with International Classification of Diseases codes, anti-viral drug history, virology test, and radiology reports. Decompensated cases were excluded. Blood records within 1 month before the diagnosis of HCC and CLD patients were retrieved. Data from 2000 to 2015 were split into training and testing cohorts in an 80 : 20 ratio, while data from 2016 to 2018 were used as the validation set. Machine learning models were applied and their performances were compared with AFP.
Results
The cohort yielded >75 000 patients including 19 670 patients with HCC. Results from the test set demonstrated promising capabilities in excluding CLD patients, achieving a sensitivity of 80% and a specificity of 81% (area under the receiver operating characteristic curve = 0.894) at a cut-off value of 0.43. The AI model outperformed AFP in early-stage detection, maintaining higher sensitivity across all Barcelona Clinic Liver Cancer stages.
Conclusions
This novel AI model, which uses only standard blood test results, shows strong potential for improving the detection of HCC, significantly outperforming the traditional alpha-fetoprotein (AFP) test. Its straightforward design offers a practical and widely accessible screening option that could be integrated into existing healthcare pathways to aid earlier diagnosis.
{"title":"Development of a novel routine blood-based AI model for HCC screening—a territory-wide study","authors":"K.-N. Kwok , K.-M. Chueng , S.J.-L. Lam , M. Seo , C.Y. Lau , P.Y.-M. Woo , H.-S. Lam , S.-M. Yip , S. Lam , O.-P. Chiu , W.W.Y. Sung , H.H.-W. Liu , K.K.-H. Bao , J.C.-H. Chow , S.K.-K. Ng , H.H.-Y. Yiu , D.C.C. Lam","doi":"10.1016/j.esmogo.2025.100241","DOIUrl":"10.1016/j.esmogo.2025.100241","url":null,"abstract":"<div><h3>Background</h3><div>Current guidelines for hepatocellular carcinoma (HCC) screening in patients with chronic liver disease (CLD) recommend ultrasound and/or α-fetoprotein (AFP) testing every 6 months. However, both methods exhibit low sensitivity for early-stage HCC. Building on our previous study that identified a novel blood test signature for HCC, this study aims to develop a routine blood-based artificial intelligence (AI) model for HCC detection.</div></div><div><h3>Patients and methods</h3><div>Records from 2000 to 2018 were retrieved from Hospital Authority Data Collaboration Laboratory, a territory-wide database. CLD (hepatitis/cirrhosis) patients with and without HCC were identified with International Classification of Diseases codes, anti-viral drug history, virology test, and radiology reports. Decompensated cases were excluded. Blood records within 1 month before the diagnosis of HCC and CLD patients were retrieved. Data from 2000 to 2015 were split into training and testing cohorts in an 80 : 20 ratio, while data from 2016 to 2018 were used as the validation set. Machine learning models were applied and their performances were compared with AFP.</div></div><div><h3>Results</h3><div>The cohort yielded >75 000 patients including 19 670 patients with HCC. Results from the test set demonstrated promising capabilities in excluding CLD patients, achieving a sensitivity of 80% and a specificity of 81% (area under the receiver operating characteristic curve = 0.894) at a cut-off value of 0.43. The AI model outperformed AFP in early-stage detection, maintaining higher sensitivity across all Barcelona Clinic Liver Cancer stages.</div></div><div><h3>Conclusions</h3><div>This novel AI model, which uses only standard blood test results, shows strong potential for improving the detection of HCC, significantly outperforming the traditional alpha-fetoprotein (AFP) test. Its straightforward design offers a practical and widely accessible screening option that could be integrated into existing healthcare pathways to aid earlier diagnosis.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"10 ","pages":"Article 100241"},"PeriodicalIF":0.0,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145324498","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 : 2025-10-09DOI: 10.1016/j.esmogo.2025.100244
R.K. Yang , A. Rashid , S. Roy-Chowdhuri , D.S. Hong , J. Bryan
Background
KRAS-activating mutations characterize ∼40% of colorectal carcinomas (CRCs) and predict resistance to anti-epidermal growth factor receptor therapy. Because the location of KRAS mutations conveys distinct biophysical consequences, we investigated whether CRCs’ clinicopathological features varied by KRAS mutation codon.
Patients and methods
CRC patients from 2018 to 2022 were identified from the United States National Cancer Database, which reports KRAS as wild-type versus codon 12/13/61-mutant versus codon 146-mutant. KRAS codon mutations were compared using multivariable logistic regression for clinicopathological features and multivariable Cox regression for overall survival (OS). Notable limitations include a lack of granular codon characterization and detailed treatment data.
Results
Nationally, n = 76 581 CRC patients were identified, 43.3% of whom were KRAS mutated (including n = 16 366 at codon 12/13/61 and n = 784 at codon 146). Among tumor characteristics, codon 146-mutated CRCs were less likely poorly differentiated (12.1%) and more likely moderately differentiated (80.7%) than codon 12/13/61-mutated CRCs (15.9% and 76.0%, respectively; P = 0.003). Additionally, codon 146-mutated CRCs less likely involved the sigmoid colon (14.4% versus 18.1% of codon 12/13/61-mutated CRCs; P = 0.004). KRAS codon 146-mutated CRCs were enriched with microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) (10.1% versus 5.9% of codon 12/13/61-mutated; P < 0.001) and were less likely concurrently NRAS mutant (1.5% versus 8.0% of codon 12/13/61-mutated; chi-square P < 0.001). Adjusting for patient characteristics and treatments, no OS difference was observed between KRAS codon 146-mutated and 12/13/61-mutated stage IV CRCs (hazard ratio 0.97, 95% confidence interval 0.84-1.12, P = 0.69).
Conclusion
Nationally, CRCs with KRAS mutations at codon 146 exhibited select pathological and MSI/MMR differences—illustrating that KRAS mutations have codon-specific manifestations that warrant further investigation, particularly as the armamentarium of alteration-specific KRAS inhibitors grows.
kras激活突变表征约40%的结直肠癌（crc），并预测抗表皮生长因子受体治疗的耐药性。由于KRAS突变的位置传达了不同的生物物理后果，我们研究了CRCs的临床病理特征是否因KRAS突变密码子而变化。患者和方法从美国国家癌症数据库中确定2018年至2022年的scrc患者，该数据库报告KRAS为野生型，密码子12/13/61突变型和密码子146突变型。采用临床病理特征的多变量logistic回归和总生存期（OS）的多变量Cox回归对KRAS密码子突变进行比较。值得注意的局限性包括缺乏颗粒密码子特征和详细的治疗数据。结果全国共检出76 581例结直肠癌患者，其中KRAS突变占43.3%（其中密码子12/13/61处n = 16 366，密码子146处n = 784）。在肿瘤特征中，密码子146突变的crc与密码子12/13/61突变的crc相比，低分化的可能性较小（12.1%），中分化的可能性较大（80.7%）（分别为15.9%和76.0%,P = 0.003）。此外，密码子146突变的crc不太可能涉及乙状结肠（密码子12/13/61突变的crc 14.4% vs 18.1%, P = 0.004）。KRAS密码子146突变的crc富含微卫星不稳定性高(MSI-H)/错配修复缺陷（dMMR）（10.1%比5.9%的密码子12/13/61突变；P < 0.001），同时NRAS突变的可能性较小（1.5%比8.0%的密码子12/13/61突变；χ 2 P < 0.001）。调整患者特征和治疗后，KRAS密码子146突变和12/13/61突变的IV期crc无OS差异（风险比0.97,95%可信区间0.84-1.12,P = 0.69）。在全国范围内，KRAS密码子146突变的crc表现出选择性病理和MSI/MMR差异，这表明KRAS突变具有密码子特异性表现，值得进一步研究，特别是随着改变特异性KRAS抑制剂的增加。
{"title":"Clinicopathological features and outcomes for colorectal carcinomas with KRAS codon 146 mutations","authors":"R.K. Yang , A. Rashid , S. Roy-Chowdhuri , D.S. Hong , J. Bryan","doi":"10.1016/j.esmogo.2025.100244","DOIUrl":"10.1016/j.esmogo.2025.100244","url":null,"abstract":"<div><h3>Background</h3><div><em>KRAS</em>-activating mutations characterize ∼40% of colorectal carcinomas (CRCs) and predict resistance to anti-epidermal growth factor receptor therapy. Because the location of <em>KRAS</em> mutations conveys distinct biophysical consequences, we investigated whether CRCs’ clinicopathological features varied by <em>KRAS</em> mutation codon.</div></div><div><h3>Patients and methods</h3><div>CRC patients from 2018 to 2022 were identified from the United States National Cancer Database, which reports <em>KRAS</em> as wild-type versus codon 12/13/61-mutant versus codon 146-mutant. <em>KRAS</em> codon mutations were compared using multivariable logistic regression for clinicopathological features and multivariable Cox regression for overall survival (OS). Notable limitations include a lack of granular codon characterization and detailed treatment data.</div></div><div><h3>Results</h3><div>Nationally, <em>n</em> = 76 581 CRC patients were identified, 43.3% of whom were <em>KRAS</em> mutated (including <em>n</em> = 16 366 at codon 12/13/61 and <em>n</em> = 784 at codon 146). Among tumor characteristics, codon 146-mutated CRCs were less likely poorly differentiated (12.1%) and more likely moderately differentiated (80.7%) than codon 12/13/61-mutated CRCs (15.9% and 76.0%, respectively; <em>P</em> = 0.003). Additionally, codon 146-mutated CRCs less likely involved the sigmoid colon (14.4% versus 18.1% of codon 12/13/61-mutated CRCs; <em>P</em> = 0.004). <em>KRAS</em> codon 146-mutated CRCs were enriched with microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) (10.1% versus 5.9% of codon 12/13/61-mutated; <em>P</em> < 0.001) and were less likely concurrently <em>NRAS</em> mutant (1.5% versus 8.0% of codon 12/13/61-mutated; chi-square <em>P</em> < 0.001). Adjusting for patient characteristics and treatments, no OS difference was observed between <em>KRAS</em> codon 146-mutated and 12/13/61-mutated stage IV CRCs (hazard ratio 0.97, 95% confidence interval 0.84-1.12, <em>P</em> = 0.69).</div></div><div><h3>Conclusion</h3><div>Nationally, CRCs with <em>KRAS</em> mutations at codon 146 exhibited select pathological and MSI/MMR differences—illustrating that <em>KRAS</em> mutations have codon-specific manifestations that warrant further investigation, particularly as the armamentarium of alteration-specific KRAS inhibitors grows.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"10 ","pages":"Article 100244"},"PeriodicalIF":0.0,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145268338","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 : 2025-10-06DOI: 10.1016/j.esmogo.2025.100248
M. Ghidini , A. Parisi , I.V. Zurlo , M.M. Laterza , L. Gervaso , A.D. Ricci , A. Biasi , A. Nicastro , O. Garrone , G. Tomasello , A. Petrillo , F. Petrelli
Small bowel adenocarcinoma (SBA) is a rare and increasingly recognised malignancy, accounting for only 3.4% of all gastrointestinal cancers. It often presents with non-specific or late-stage symptoms, resulting in delayed diagnosis and poor prognosis. For advanced disease, treatment recommendations rely primarily on small phase II trials and retrospective series with no established standard therapy. Moreover, although SBA commonly harbours KRAS mutations (43%), CDKN2A (p16) loss, and HER2/ERBB2 mutations (12%), no targeted biological agents have demonstrated clinical efficacy against this disease. Our systematic review was conducted to comprehensively evaluate the available evidence on systemic therapies for patients with advanced or metastatic SBA, with particular focus on treatment efficacy, safety profiles, and the potential influence of molecular biomarkers.
{"title":"Treatment options for advanced small bowel adenocarcinoma: a systematic review","authors":"M. Ghidini , A. Parisi , I.V. Zurlo , M.M. Laterza , L. Gervaso , A.D. Ricci , A. Biasi , A. Nicastro , O. Garrone , G. Tomasello , A. Petrillo , F. Petrelli","doi":"10.1016/j.esmogo.2025.100248","DOIUrl":"10.1016/j.esmogo.2025.100248","url":null,"abstract":"<div><div>Small bowel adenocarcinoma (SBA) is a rare and increasingly recognised malignancy, accounting for only 3.4% of all gastrointestinal cancers. It often presents with non-specific or late-stage symptoms, resulting in delayed diagnosis and poor prognosis. For advanced disease, treatment recommendations rely primarily on small phase II trials and retrospective series with no established standard therapy. Moreover, although SBA commonly harbours <em>KRAS</em> mutations (43%), <em>CDKN2A</em> (p16) loss, and <em>HER2/ERBB2</em> mutations (12%), no targeted biological agents have demonstrated clinical efficacy against this disease. Our systematic review was conducted to comprehensively evaluate the available evidence on systemic therapies for patients with advanced or metastatic SBA, with particular focus on treatment efficacy, safety profiles, and the potential influence of molecular biomarkers.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"10 ","pages":"Article 100248"},"PeriodicalIF":0.0,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145268339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-30DOI: 10.1016/j.esmogo.2025.100242
N. Starling , L. Zhang , K. Dunton , A. Strübing , Y. Xiong , C. Livings , L. Brannman , M.Y. Beykloo , H. Mohamed , N. Trankov , P. Egger
Background
This study aimed to examine real-world treatment patterns and outcomes in patients with human epidermal growth factor receptor 2 (HER2)-positive gastric cancer (GC) or gastroesophageal junction (GEJ) adenocarcinoma receiving anticancer therapy in England.
Methods
Using the Cancer Analysis System English Cancer Outcomes Services Dataset, we retrospectively analyzed real-world (rw) treatment patterns, overall survival (rwOS), time to treatment discontinuation/death (rwTTD), and time to next treatment/death (rwTTNTD) in adults with inoperable, locally advanced or metastatic GC/GEJ adenocarcinoma on trastuzumab-based first line of treatment (1LoT) between January 2015 and December 2019.
Results
Among 948 patients included (median age 67.0 years), most were male (82.1%), with GEJ adenocarcinoma (57.4%) and de novo disease (81.8%); 33.3% patients received 2LoT and 6.6% received 3LoT. The most common regimen was capecitabine + cisplatin + trastuzumab in 1LoT (54.9%), paclitaxel in 2LoT (36.4%), and fluorouracil + irinotecan in 3LoT (19.1%). Median (Q1-Q3) rwOS and rwTTD for 1LoT were 11.8 months (6.2-21.5 months) and 6.3 months (3.0-10.6 months), respectively; these reduced to 6.1 months (3.4-11.2 months) and 2.8 months (1.7-4.6 months) for 2LoT, and 5.9 months (3.2-9.5 months) and 2.3 months (1.5-4.6 months) for 3LoT. Median rwTTNTD was 9.0 months (5.1-15.0 months), 5.5 months (3.0-8.5 months), and 5.7 months (3.0-9.2 months) for 1LoT, 2LoT, and 3LoT, respectively.
Conclusions
Poor outcomes persist for HER2-positive GC/GEJ adenocarcinoma progressing after 1LoT. More effective treatments, ideally ones targeting HER2, are needed.
本研究旨在研究在英国接受抗癌治疗的人表皮生长因子受体2 （HER2）阳性胃癌（GC）或胃食管交界处（GEJ）腺癌患者的现实世界治疗模式和结果。方法：使用Cancer Analysis System English Cancer Outcomes Services数据集，我们回顾性分析了2015年1月至2019年12月期间接受曲妥珠单抗一线治疗（1LoT）的不能手术、局部晚期或转移性GC/GEJ腺癌成人患者的现实世界（rw）治疗模式、总生存期（rwOS）、停药时间/死亡时间（rwTTD）和下一次治疗时间/死亡时间（rwTTNTD）。结果948例患者（中位年龄67.0岁）中，男性居多（82.1%），有GEJ腺癌（57.4%）和新发疾病（81.8%）；33.3%的患者接受2LoT， 6.6%的患者接受3LoT。最常见的方案是卡培他滨+顺铂+曲妥珠单抗1LoT(54.9%)，紫杉醇2LoT(36.4%)，氟尿嘧啶+伊立替康3LoT（19.1%）。1LoT的中位（Q1-Q3） rwOS和rwTTD分别为11.8个月（6.2-21.5个月）和6.3个月（3.0-10.6个月）；2个lot组减少到6.1个月（3.4-11.2个月）和2.8个月（1.7-4.6个月），3个lot组减少到5.9个月（3.2-9.5个月）和2.3个月（1.5-4.6个月）。1LoT、2LoT和3LoT的中位rwTTNTD分别为9.0个月（5.1-15.0个月）、5.5个月（3.0-8.5个月）和5.7个月（3.0-9.2个月）。结论her2阳性GC/GEJ腺癌在1LoT后进展的预后不稳定。需要更有效的治疗方法，理想的是针对HER2的治疗方法。
{"title":"Real-world treatment patterns and outcomes in advanced/metastatic gastric cancer or gastroesophageal junction adenocarcinoma treated with first-line anti-HER2 therapy in England","authors":"N. Starling , L. Zhang , K. Dunton , A. Strübing , Y. Xiong , C. Livings , L. Brannman , M.Y. Beykloo , H. Mohamed , N. Trankov , P. Egger","doi":"10.1016/j.esmogo.2025.100242","DOIUrl":"10.1016/j.esmogo.2025.100242","url":null,"abstract":"<div><h3>Background</h3><div>This study aimed to examine real-world treatment patterns and outcomes in patients with human epidermal growth factor receptor 2 (HER2)-positive gastric cancer (GC) or gastroesophageal junction (GEJ) adenocarcinoma receiving anticancer therapy in England.</div></div><div><h3>Methods</h3><div>Using the Cancer Analysis System English Cancer Outcomes Services Dataset, we retrospectively analyzed real-world (rw) treatment patterns, overall survival (rwOS), time to treatment discontinuation/death (rwTTD), and time to next treatment/death (rwTTNTD) in adults with inoperable, locally advanced or metastatic GC/GEJ adenocarcinoma on trastuzumab-based first line of treatment (1LoT) between January 2015 and December 2019.</div></div><div><h3>Results</h3><div>Among 948 patients included (median age 67.0 years), most were male (82.1%), with GEJ adenocarcinoma (57.4%) and <em>de novo</em> disease (81.8%); 33.3% patients received 2LoT and 6.6% received 3LoT. The most common regimen was capecitabine + cisplatin + trastuzumab in 1LoT (54.9%), paclitaxel in 2LoT (36.4%), and fluorouracil + irinotecan in 3LoT (19.1%). Median (Q1-Q3) rwOS and rwTTD for 1LoT were 11.8 months (6.2-21.5 months) and 6.3 months (3.0-10.6 months), respectively; these reduced to 6.1 months (3.4-11.2 months) and 2.8 months (1.7-4.6 months) for 2LoT, and 5.9 months (3.2-9.5 months) and 2.3 months (1.5-4.6 months) for 3LoT. Median rwTTNTD was 9.0 months (5.1-15.0 months), 5.5 months (3.0-8.5 months), and 5.7 months (3.0-9.2 months) for 1LoT, 2LoT, and 3LoT, respectively.</div></div><div><h3>Conclusions</h3><div>Poor outcomes persist for HER2-positive GC/GEJ adenocarcinoma progressing after 1LoT. More effective treatments, ideally ones targeting HER2, are needed.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"10 ","pages":"Article 100242"},"PeriodicalIF":0.0,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145220915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-29DOI: 10.1016/j.esmogo.2025.100243
W.Y. Chua , A. Yong , O. Lim , I. Seow-En , D. Chong , E. Wong , S. Han , S.-L. Koo , I. Tan , K.Y.Y. Ng
Introduction
Colorectal cancer (CRC) is the third most common malignancy and the third leading cause of cancer-related mortality worldwide. Patients are typically diagnosed at an early stage due to widespread use of colonoscopy screenings and stool testing. Despite the efficacy of early detection in CRC, there are concerns about the accessibility of these treatments for patients of lower socioeconomic status (SES), which may lead to poorer outcomes and exacerbate health inequity.
Patients and methods
We searched Medline and Embase from inception to 26 April 2024 to identify cohort studies comparing SES indicators and CRC outcomes. We computed hazard ratios (HRs) with accompanying 95% confidence intervals (CIs) for each study, and pooled the results using a random-effects meta-analysis. Quality assessment was carried out using Newcastle–Ottawa Quality Assessment Scale for cohort studies.
Results
In this meta-analysis of 37 studies involving 2 017 509 patients, we analysed the impact of SES on overall survival in patients with CRC. All but three studies were conducted in high-income countries. Our main findings demonstrated that lower income (HR 1.16, 95% CI 1.08-1.23, P < 0.0001), lower educational level (HR 1.24, 95% CI 1.17-1.31, P < 0.0001), lower neighbourhood SES (HR 1.22, 95% CI 1.19-1.25, P < 0.0001), and lower insurance coverage (HR 1.29, 95% CI 1.25-1.32, P < 0.0001) had a negative impact on overall survival in patients with CRC.
Conclusion
Lower income, educational level, insurance coverage, and neighbourhood SES had a negative impact on overall survival in patients with CRC. There is an urgent need to develop and implement interventions to reduce disparities in outcomes for patients with CRC who are of lower SES.
结直肠癌（CRC）是世界上第三大最常见的恶性肿瘤，也是导致癌症相关死亡的第三大原因。由于结肠镜检查和粪便检查的广泛使用，患者通常在早期被诊断出来。尽管早期发现结直肠癌有效，但人们担心这些治疗对社会经济地位较低的患者的可及性，这可能导致较差的结果并加剧健康不平等。患者和方法我们检索了Medline和Embase从成立到2024年4月26日，以确定比较SES指标和CRC结果的队列研究。我们计算了每项研究的风险比（hr）和随附的95%置信区间（ci），并使用随机效应荟萃分析汇总了结果。采用纽卡斯尔-渥太华质量评估量表对队列研究进行质量评估。在这项涉及2017509例患者的37项研究的荟萃分析中，我们分析了SES对结直肠癌患者总生存的影响。除了三项研究外，其他研究都是在高收入国家进行的。我们的主要研究结果表明，较低的收入（HR 1.16, 95% CI 1.08-1.23, P < 0.0001）、较低的教育水平（HR 1.24, 95% CI 1.17-1.31, P < 0.0001）、较低的社区经济地位（HR 1.22, 95% CI 1.19-1.25, P < 0.0001）和较低的保险覆盖率（HR 1.29, 95% CI 1.25-1.32, P < 0.0001）对结直肠癌患者的总体生存有负面影响。结论较低的收入、教育程度、保险覆盖率和社区社会经济地位对结直肠癌患者的总体生存有负面影响。迫切需要制定和实施干预措施，以减少社会经济地位较低的结直肠癌患者预后的差异。
{"title":"The impact of socioeconomic status on overall survival in patients with colorectal cancer: a systematic review and meta-analysis","authors":"W.Y. Chua , A. Yong , O. Lim , I. Seow-En , D. Chong , E. Wong , S. Han , S.-L. Koo , I. Tan , K.Y.Y. Ng","doi":"10.1016/j.esmogo.2025.100243","DOIUrl":"10.1016/j.esmogo.2025.100243","url":null,"abstract":"<div><h3>Introduction</h3><div>Colorectal cancer (CRC) is the third most common malignancy and the third leading cause of cancer-related mortality worldwide. Patients are typically diagnosed at an early stage due to widespread use of colonoscopy screenings and stool testing. Despite the efficacy of early detection in CRC, there are concerns about the accessibility of these treatments for patients of lower socioeconomic status (SES), which may lead to poorer outcomes and exacerbate health inequity.</div></div><div><h3>Patients and methods</h3><div>We searched Medline and Embase from inception to 26 April 2024 to identify cohort studies comparing SES indicators and CRC outcomes. We computed hazard ratios (HRs) with accompanying 95% confidence intervals (CIs) for each study, and pooled the results using a random-effects meta-analysis. Quality assessment was carried out using Newcastle–Ottawa Quality Assessment Scale for cohort studies.</div></div><div><h3>Results</h3><div>In this meta-analysis of 37 studies involving 2 017 509 patients, we analysed the impact of SES on overall survival in patients with CRC. All but three studies were conducted in high-income countries. Our main findings demonstrated that lower income (HR 1.16, 95% CI 1.08-1.23, <em>P</em> < 0.0001), lower educational level (HR 1.24, 95% CI 1.17-1.31, <em>P</em> < 0.0001), lower neighbourhood SES (HR 1.22, 95% CI 1.19-1.25, <em>P</em> < 0.0001), and lower insurance coverage (HR 1.29, 95% CI 1.25-1.32, <em>P</em> < 0.0001) had a negative impact on overall survival in patients with CRC.</div></div><div><h3>Conclusion</h3><div>Lower income, educational level, insurance coverage, and neighbourhood SES had a negative impact on overall survival in patients with CRC. There is an urgent need to develop and implement interventions to reduce disparities in outcomes for patients with CRC who are of lower SES.</div></div>","PeriodicalId":100490,"journal":{"name":"ESMO Gastrointestinal Oncology","volume":"10 ","pages":"Article 100243"},"PeriodicalIF":0.0,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145220914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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