Clinical and Genomic Characterization of ERBB2-Altered Gallbladder Cancer: Exploring Differences Between an American and a Chilean Cohort.

IF 3.2 Q2 ONCOLOGY JCO Global Oncology Pub Date : 2024-10-01 Epub Date: 2024-10-10 DOI:10.1200/GO.24.00090
Sebastián Mondaca, Henry Walch, Santiago Sepúlveda, Nikolaus Schultz, Gonzalo Muñoz, Amin Yaqubie, Patricia Macanas, Claudia Pareja, Patricia Garcia, Walid Chatila, Bruno Nervi, Bob Li, James J Harding, Paola Viviani, Juan Carlos Roa, Ghassan K Abou-Alfa
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Abstract

Purpose: Gallbladder cancer (GBC) is a biliary tract malignancy characterized by its high lethality. Although the incidence of GBC is low in most countries, specific areas such as Chile display a high incidence. Our collaborative study sought to compare clinical and molecular features of GBC cohorts from Chile and the United States with a focus on ERBB2 alterations.

Methods: Patients were accrued at Memorial Sloan Kettering Cancer Center (MSK) or the Pontificia Universidad Católica de Chile (PUC). Clinical information was retrieved from medical records. Genomic analysis was performed by the next-generation sequencing platform MSK-Integrated Mutation Profiling of Actionable Cancer Targets.

Results: A total of 260 patients with GBC were included, 237 from MSK and 23 from PUC. There were no significant differences in the clinical characteristics between the patients identified at MSK and at PUC except in terms of lithiasis prevalence which was significantly higher in the PUC cohort (85% v 44%; P = .0003). The prevalence of ERBB2 alterations was comparable between the two cohorts (15% v 9%; P = .42). Overall, ERBB2 alterations were present in 14% of patients (8% with ERBB2 amplification, 4% ERBB2 mutation, 1.5% concurrent amplification and mutation, and 0.4% ERBB2 fusion). Notably, patients with GBC that harbored ERBB2 alterations had better overall survival (OS) versus their ERBB2-wild type counterparts (22.3 months v 11.8 months; P = .024).

Conclusion: The prevalence of lithiasis seems to be higher in Chilean versus US patients with GBC. A similar prevalence of ERBB2 alterations of overall 14% and better OS suggests that a proportion of them could benefit from human epidermal growth factor receptor type 2-targeted therapies. The smaller cohort of Chile, where the disease prevalence is higher, is a reminder and invitation for the need of more robust next-generation sequencing analyses globally.

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ERBB2改变的胆囊癌的临床和基因组特征:探索美国和智利队列之间的差异
目的:胆囊癌(GBC)是一种胆道恶性肿瘤,其特点是致死率高。虽然大多数国家的 GBC 发病率较低,但智利等特定地区的发病率却很高。我们的合作研究旨在比较智利和美国 GBC 群体的临床和分子特征,重点关注 ERBB2 的改变:患者均来自纪念斯隆-凯特琳癌症中心(MSK)或智利天主教大学(PUC)。临床信息取自医疗记录。基因组分析由新一代测序平台 MSK-Integrated Mutation Profiling of Actionable Cancer Targets 完成:结果:共纳入 260 名 GBC 患者,其中 237 名来自 MSK,23 名来自 PUC。在MSK和PUC发现的患者在临床特征上没有明显差异,但在结石患病率方面,PUC队列中的结石患病率明显更高(85%对44%;P = .0003)。两个队列的ERBB2改变发生率相当(15% v 9%; P = .42)。总体而言,14%的患者存在ERBB2改变(8%的患者存在ERBB2扩增,4%的患者存在ERBB2突变,1.5%的患者同时存在扩增和突变,0.4%的患者存在ERBB2融合)。值得注意的是,与ERBB2野生型患者相比,携带ERBB2改变的GBC患者总生存期(OS)更长(22.3个月对11.8个月;P = .024):结论:在智利和美国的GBC患者中,碎石症的发病率似乎更高。总的ERBB2改变发生率为14%,但OS较好,这表明其中一部分患者可从人类表皮生长因子受体2型靶向疗法中获益。智利的队列规模较小,但疾病的发病率较高,这提醒我们需要在全球范围内进行更强大的新一代测序分析。
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来源期刊
JCO Global Oncology
JCO Global Oncology Medicine-Oncology
CiteScore
6.70
自引率
6.70%
发文量
310
审稿时长
7 weeks
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