Landscape of homologous recombination deficiency in gastric cancer and clinical implications for first-line chemotherapy.

IF 6 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Gastric Cancer Pub Date : 2024-11-01 Epub Date: 2024-08-07 DOI:10.1007/s10120-024-01542-1
Hiroshi Ichikawa, Masaki Aizawa, Yosuke Kano, Takaaki Hanyu, Yusuke Muneoka, Sou Hiroi, Hiroto Ueki, Kazuki Moro, Yuki Hirose, Kohei Miura, Yoshifumi Shimada, Jun Sakata, Hiroshi Yabusaki, Satoru Nakagawa, Takashi Kawasaki, Shujiro Okuda, Toshifumi Wakai
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Abstract

Background: Homologous recombination deficiency (HRD) is one of the crucial hallmarks of cancer. It is associated with a favorable response to platinum-based chemotherapy. We explored the distinctive clinicopathological features of gastric cancer (GC) with HRD and the clinical significance of HRD in platinum-based first-line chemotherapy for unresectable metastatic GC.

Methods: We enrolled 160 patients with GC in this study. Their tumor samples were subjected to genomic profiling utilizing targeted tumor sequencing. HRD was defined as the presence of alterations in any of 16 HR genes (BARD1, BLM, BRCA1, BRCA2, BRIP1, MRE11A, NBN, PALB2, PARP1, POLD1, RAD50, RAD51, RAD51C, RAD51D, WRN, and XRCC2). The clinicopathological features and treatment outcomes of first-line chemotherapy for unresectable metastatic GC were compared between HRD and non-HRD groups.

Results: Forty-seven patients (29.4%) were classified into the HRD group. This group had a significantly lower proportion of macroscopic type 3 or 4 tumors and higher TMB than the non-HRD group. Among patients who underwent platinum-based first-line chemotherapy, the HRD group had a greater response rate and longer progression-free survival after treatment (median 8.0 months vs. 3.0 months, P = 0.010), with an adjusted hazard ratio of 0.337 (95% confidence interval 0.151-0.753). HRD status was not associated with treatment outcomes in patients who did not undergo platinum-based chemotherapy.

Conclusions: Low proportion of macroscopic type 3 or 4 tumors and a high TMB are distinctive features of GC with HRD. HRD status is a potential predictive marker in platinum-based first-line chemotherapy for unresectable metastatic GC.

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胃癌中同源重组缺陷的分布及对一线化疗的临床影响
背景:同源重组缺陷(HRD)是癌症的重要特征之一。它与铂类化疗的良好反应相关。我们探讨了伴有 HRD 的胃癌(GC)的独特临床病理特征,以及 HRD 在以铂类为基础的一线化疗治疗不可切除的转移性胃癌中的临床意义:本研究共纳入 160 例胃癌患者。他们的肿瘤样本通过肿瘤靶向测序进行了基因组学分析。HRD的定义是16个HR基因(BARD1、BLM、BRCA1、BRCA2、BRIP1、MRE11A、NBN、PALB2、PARP1、POLD1、RAD50、RAD51、RAD51C、RAD51D、WRN和XRCC2)中任何一个基因发生改变。比较了HRD组和非HRD组不可切除转移性GC的临床病理特征和一线化疗的疗效:结果:47 例患者(29.4%)被归入 HRD 组。与非HRD组相比,该组患者中3型或4型大肿瘤的比例明显较低,TMB也较高。在接受铂类一线化疗的患者中,HRD 组的反应率更高,治疗后无进展生存期更长(中位 8.0 个月对 3.0 个月,P = 0.010),调整后危险比为 0.337(95% 置信区间为 0.151-0.753)。HRD状态与未接受铂类化疗患者的治疗结果无关:结论:3型或4型大肿瘤比例低和TMB高是伴有HRD的GC的显著特征。HRD状态是不可切除转移性GC铂类一线化疗的潜在预测指标。
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来源期刊
Gastric Cancer
Gastric Cancer 医学-胃肠肝病学
CiteScore
14.70
自引率
2.70%
发文量
80
审稿时长
6-12 weeks
期刊介绍: Gastric Cancer is an esteemed global forum that focuses on various aspects of gastric cancer research, treatment, and biology worldwide. The journal promotes a diverse range of content, including original articles, case reports, short communications, and technical notes. It also welcomes Letters to the Editor discussing published articles or sharing viewpoints on gastric cancer topics. Review articles are predominantly sought after by the Editor, ensuring comprehensive coverage of the field. With a dedicated and knowledgeable editorial team, the journal is committed to providing exceptional support and ensuring high levels of author satisfaction. In fact, over 90% of published authors have expressed their intent to publish again in our esteemed journal.
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