Department of Gastroenterology and Hepatology, Okayama University Hospital.
Acta Med Okayama. 2023 Oct;77(5):517-525. doi: 10.18926/AMO/65974.
We investigated the effect of modified FOLFIRINOX (mFFX) in unresectable pancreatic cancer by retrospectively analyzing the cases of 43 patients who underwent BRCA testing (germline, n=11; somatic, n=26; both germline and somatic, n=6). The association between BRCA mutations and therapeutic effect was clarified. Six patients tested positive for germline pathogenic variants. Familial pancreatic cancer (33% vs. 3%, p=0.006) and peritoneal disseminated lesions (66% vs. 8%, p<0.001) were significantly more common in patients with germline pathogenic variants. The partial response (PR) rate was 100% in the germline BRCA-positive patients, and 27% in the germline BRCA-negative patients (p<0.001). The median progression-free survival (PFS) was not reached for any germline BRCA-positive patients but was 9.0 months for the germline BRCA-negative patients (p=0.042). Patients with stage IV BRCA-associated pancreatic cancer had better overall survival than those with non-BRCA-associated pancreatic cancer, although the difference was nonsignificant (not reached vs. 655 days, p=0.061). Our results demonstrate that a PR and prolonged PFS can be expected in germline BRCA-positive patients after treatment with mFFX. Our findings also suggest that germline BRCA pathogenic variants may be useful as biomarkers for the therapeutic effect of mFFX in patients with pancreatic cancer.
我们通过回顾性分析 43 例接受 BRCA 检测（胚系，n=11；体细胞，n=26；胚系和体细胞均，n=6）的患者病例，研究了改良 FOLFIRINOX（mFFX）在不可切除胰腺癌中的作用。阐明了 BRCA 突变与治疗效果之间的关联。6 例患者检测出胚系致病性变异。胚系致病性变异患者中家族性胰腺癌（33%比 3%，p=0.006）和腹膜播散性病变（66%比 8%，p<0.001）更为常见。胚系 BRCA 阳性患者的部分缓解（PR）率为 100%，而胚系 BRCA 阴性患者为 27%（p<0.001）。任何胚系 BRCA 阳性患者的中位无进展生存期（PFS）均未达到，但胚系 BRCA 阴性患者为 9.0 个月（p=0.042）。BRCA 相关胰腺癌患者的总生存期优于非 BRCA 相关胰腺癌患者，但差异无统计学意义（未达到 vs. 655 天，p=0.061）。我们的研究结果表明，mFFX 治疗后，胚系 BRCA 阳性患者可获得 PR 和延长的 PFS。我们的研究结果还表明，胚系 BRCA 致病性变异可能可作为胰腺癌患者 mFFX 治疗效果的生物标志物。
