ナカイ　ヨウスケ   NAKAI Yousuke   中井　陽介    所属   医学部 医学科（東京女子医科大学病院）    職種   教授・基幹分野長
論文種別	原著
言語種別	英語
査読の有無	査読なし
表題	Association between homologous recombination deficiency and time to treatment failure to platinum-based chemotherapy for pancreatic cancer by using the C-CAT database
掲載誌名	正式名：Journal of gastroenterology 略　 称：J Gastroenterol ISSNコード：14355922/09441174
掲載区分	国内
巻・号・頁	60(2),pp.247-256
著者・共著者	ISHIGAKI Kazunaga, TOKITO Yurie, TAKAHARA Naminatsu, NISHIO Hiroto, ENDO Go, FUKUDA Koshiro, ISHIDA Kota, FUKADA Rintaro, TAKAOKA Shinya, OYAMA Hiroki, NOGUCHI Kensaku, SUZUKI Tatsunori, SATO Tatsuya, SAITO Tomotaka, HAMADA Tsuyoshi, MIYABAYASHI Koji, SATO Yasuyoshi, NAKAI Yosuke, KAGE Hidenori, ODA Katsutoshi, FUJISHIRO Mitsuhiro
発行年月	2025/02
概要	BACKGROUND:Since homologous recombination deficiency (HRD) is relatively uncommon in pancreatic cancer (PC), its impact on time-to-treatment failure (TTF) among patients undergoing systemic chemotherapy for unresectable and recurrent PC remains uncertain.METHODS:Among patients with unresectable and recurrent PC enrolled in the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database by July 2023, a total of 1394 patients who underwent first-line chemotherapy with either gemcitabine plus nab-paclitaxel (GnP) or FOLFIRINOX (FFX) and received tissue-based CGP tests after disease progression were included in this study. HRD was defined as the presence of germline or somatic genetic mutations in homologous recombination repair (HRR)-related genes such as ATM, BARD1, BRIP1, BRCA1/2, CHEK2, CDK12, PALB, and RAD51C/D. We investigated the correlation between HRD and TTF among patients treated with GnP and FFX.RESULTS:First-line chemotherapy consisted of GnP in 69% of the cases and FFX in 31%. The CGP tests used were NCC OncoPanel and FoundationOne CDx in 26% and 74%, respectively. HRR-related genetic abnormalities were identified in 107 patients (7.6%): BRCA2 (n = 51), ATM (n = 34), BRCA1 (n = 9), PALB2 (n = 9), among others. In the GnP cohort, the median TTF was comparable between the HRD and non-HRD groups (5.3 vs 4.6 months, P = 0.44). Conversely, in the FFX cohort, it was significantly longer in the HRD group compared to the non-HRD group (7.3 vs. 4.7 months, p < 0.01).CONCLUSIONS:Our findings suggest that HRR-related genetic abnormalities might be predictive of TTF in platinum-based chemotherapy for PC.
DOI	10.1007/s00535-024-02173-0
PMID	39570378