Purpose: Neuroendocrine carcinomas (NECs) are aggressive tumors treated with cisplatin-based chemotherapy, though responses vary. As DNA damage response (DDR) pathways influence cisplatin sensitivity, this single-center retrospective study evaluates the efficacy of first-line cisplatin in recurrent or metastatic NEC based on DDR mutation status. Materials and Methods: This study analyzed patients with grade 3 recurrent or metastatic NEC treated with first-line etoposide plus cisplatin at Samsung Medical Center between January 2019 and September 2023. All patients underwent next-generation sequencing to determine DDR mutation status, defined by pathogenic alterations in major DNA repair pathways. Clinical outcomes were assessed per RECIST v1.1. Survival analyses were conducted using Kaplan–Meier methods and Cox regression models, with significance set atp≤ 0.05. Results: A total of 40 patients with NEC were included in this study. There were 16 patients with DDR wild-type (WT) and 24 patients with DDR mutant type (MT). The most common primary tumor sites were the pancreas (25.0%), stomach (20.0%), and gallbladder/duct (12.5%). Among 40 patients, those with DDR mutations (n= 24) showed significantly higher objective response (58.3% vs. 12.5%) and disease control rates (91.7% vs. 50.0%) compared to patients with DDR WT (n= 16). The median progression-free survival (PFS) showed the favorable trend in the DDR mutant group (8.0 vs. 4.3 months;p= 0.15), with similar trends observed across homologous recombination repair (HRR), Fanconi anemia (FA), and mismatch repair (MMR) subgroups. Conclusions: This study revealed that patients with DDR mutations had significantly higher response to first-line etoposide–cisplatin, suggesting DDR mutation status as a potential predictive marker to guide treatment and improve outcomes in recurrent or metastatic NEC.
目的：神经内分泌癌（NEC）是一种侵袭性肿瘤，通常采用以顺铂为基础的化疗方案治疗，但患者反应存在差异。鉴于DNA损伤反应（DDR）通路影响顺铂敏感性，本项单中心回顾性研究旨在基于DDR突变状态，评估一线顺铂方案在复发或转移性NEC中的疗效。 材料与方法：本研究分析了2019年1月至2023年9月期间在三星医疗中心接受一线依托泊苷联合顺铂治疗的3级复发或转移性NEC患者。所有患者均接受了二代测序以确定DDR突变状态，其定义为主要DNA修复通路中存在致病性改变。临床疗效依据RECIST v1.1标准进行评估。采用Kaplan-Meier法和Cox回归模型进行生存分析，显著性水平设定为p≤0.05。 结果：本研究共纳入40例NEC患者。其中16例为DDR野生型（WT），24例为DDR突变型（MT）。最常见的原发肿瘤部位为胰腺（25.0%）、胃（20.0%）和胆囊/胆管（12.5%）。在40例患者中，与DDR WT患者（n=16）相比，携带DDR突变的患者（n=24）显示出显著更高的客观缓解率（58.3% vs. 12.5%）和疾病控制率（91.7% vs. 50.0%）。DDR突变组的中位无进展生存期（PFS）呈现更优趋势（8.0个月 vs. 4.3个月；p=0.15），在同源重组修复（HRR）、范可尼贫血（FA）和错配修复（MMR）亚组中也观察到相似趋势。 结论：本研究表明，携带DDR突变的患者对一线依托泊苷-顺铂方案的反应率显著更高，提示DDR突变状态可能作为潜在的预测性标志物，用于指导复发或转移性NEC的治疗并改善患者预后。
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