同源重组缺陷（HRD）是癌症的重要标志之一。它与对铂类化疗的良好反应有关。我们探讨了伴有 HRD 的胃癌 (GC) 独特的临床病理特征以及 HRD 在不可切除的转移性 GC 铂类一线化疗中的临床意义。 本研究纳入了 160 名 GC 患者。利用靶向肿瘤测序对他们的肿瘤样本进行基因组分析。 HRD 被定义为 16 个 HR 基因（BARD1、BLM、BRCA1、BRCA2、BRIP1、MRE11A、NBN、PALB2、PARP1、POLD1、RAD50、RAD51、RAD51C、RAD51D、WRN 和 XRCC2）中任何一个存在改变。比较HRD组和非HRD组不可切除的转移性GC的临床病理特征和一线化疗的治疗结果。47例患者（29.4%）被分为HRD组。与非 HRD 组相比，该组肉眼可见的 3 型或 4 型肿瘤比例显着较低，TMB 较高。在接受铂类一线化疗的患者中，HRD 组的缓解率更高，治疗后无进展生存期更长（中位 8.0 个月 vs. 3.0 个月，P = 0.010），调整后的风险比为 0.337（ 95% 置信区间 0.151-0.753）。 HRD 状态与未接受铂类化疗的患者的治疗结果无关。肉眼可见的 3 型或 4 型肿瘤比例低以及 TMB 高是伴有 HRD 的 GC 的显着特征。 HRD 状态是不可切除的转移性 GC 铂类一线化疗的潜在预测标志物。© 2024。作者获得国际胃癌协会和日本胃癌协会的独家许可。

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.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.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.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.© 2024. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.