Kim Min Kyu, Cho In Rae, Kim Yooeun, Choi Jin Ho, Jung Kwangrok, Kim Jaihwan, Kim Sheehyun, Yun Hongseok, Yoon Jeesun, Oh Do-Youn, Kim Kwangsoo, Lee Sang Hyub
Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
Ther Adv Med Oncol. 2024 Oct 23;16:17588359241290482. doi: 10.1177/17588359241290482. eCollection 2024.
, , , and have been the main driver mutations in pancreatic ductal adenocarcinoma (PDAC). Studies on the clinical significance and treatment response to 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) regimen in terms of the presence of these mutations remain inconclusive.
This study aimed to compare the survival outcome and response to FOLFIRINOX chemotherapy based on the presence of four driver mutation genes.
A multi-center retrospective study conducted at two tertiary medical centers.
This study analyzed PDAC patients who were treated with FOLFIRINOX chemotherapy as the initial treatment. Tumor specimens were analyzed by a targeted next-generation sequencing platform at two tertiary referral hospitals from January 2016 to March 2022. Patients' demographics, survival outcomes, and chemotherapeutic response were investigated and compared according to the presence of driver mutations.
The analysis included 100 patients. mutation was identified in 92 (92.0%) patients, followed by , , and in 63 (63.0%), 18 (18.0%), and 17 (17.0%) patients, respectively. The wild-type group demonstrated longer overall survival (OS) than the mutated group (median OS: 29 vs 19 months, = 0.03), and served as a prognostic factor for survival (hazard ratio = 1.74, 95% confidence interval: 1.00-3.00, = 0.048). The difference in OS according to mutation was intensified in localized pancreatic adenocarcinoma (37 vs 19 months, = 0.01). The wild-type group demonstrated a higher objective response rate to FOLFIRINOX chemotherapy than the mutation group in localized pancreatic adenocarcinoma (50.0% vs 17.6%, = 0.024).
PDAC patients with wild-type demonstrated longer OS than those with mutation, and this trend was intensified in patients with localized disease. This result may be due to an impaired response to FOLFIRINOX chemotherapy in patients with mutation.
KRAS、NRAS、BRAF和PIK3CA一直是胰腺导管腺癌（PDAC）的主要驱动基因突变。关于这些基因突变状态下5-氟尿嘧啶、亚叶酸钙、伊立替康和奥沙利铂（FOLFIRINOX）方案的临床意义和治疗反应的研究尚无定论。
本研究旨在比较基于四种驱动基因突变状态的生存结局及对FOLFIRINOX化疗的反应。
在两家三级医疗中心进行的多中心回顾性研究。
本研究分析了以FOLFIRINOX化疗作为初始治疗的PDAC患者。2016年1月至2022年3月期间，在两家三级转诊医院通过靶向二代测序平台对肿瘤标本进行分析。根据驱动基因突变状态调查并比较患者的人口统计学特征、生存结局和化疗反应。
分析纳入100例患者。92例（92.0%）患者检测到KRAS基因突变，其次分别有63例（63.0%）、18例（18.0%）和17例（17.0%）患者检测到NRAS、BRAF和PIK3CA基因突变。KRAS野生型组的总生存期（OS）长于KRAS突变组（中位OS：29个月 vs 19个月，P = 0.03），KRAS可作为生存的预后因素（风险比 = 1.74，95%置信区间：1.00 - 3.00，P = 0.048）。在局限性胰腺腺癌中，KRAS基因突变状态导致的OS差异更为明显（37个月 vs 19个月，P = 0.01）。在局限性胰腺腺癌中，KRAS野生型组对FOLFIRINOX化疗的客观缓解率高于KRAS突变组（50.0% vs 17.6%，P = 0.024）。
KRAS野生型的PDAC患者的OS长于KRAS突变患者，且在局限性疾病患者中这种趋势更为明显。这一结果可能是由于KRAS突变患者对FOLFIRINOX化疗反应受损所致。
