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Background: In Japan, which has a universal health insurance system, cancer genomic profiling (CGP) testing was approved by the authority in June 2019. 99.7% of CGP data under insurance coverage have been registered with a nationwide database; C-CAT (Center for Cancer Genomics and Advanced Therapeutics). This study aims to clarify the real-world data of CGP for pancreatic ductal adenocarcinoma (PDAC) in Japan with particular attention to KRAS mutation and homologous recombination deficiency (HRD) status. Method: 2568 PDAC patients enrolled in C-CAT from June 2019 to January 2022 were analyzed retrospectively. The clinical background, treatment outcomes and the detection rate of gene alterations such as Big4 genes (KRAS, TP53, SMAD4, CDKN2A) or other druggable genes, especially HRD genes, were evaluated. We defined it significant when genetic alterations are described as oncogenic/pathogenic in C-CAT report. Results: 85.7% and 14.3% of patients underwent tissue DNA sequence (FoundationOne (F1) CDx 62.9%, NCC OncoPanel 22.8%) and ctDNA assays (F1 Liquid), respectively. 70.3% of the analyzed tissue were obtained from the primary pancreatic lesions. Big4 genes mutations were most frequently prevalent such as KRAS (85.1%), TP53 (69.1%) and CDKN2A (35.4%). Big4 genes mutations were detected significantly more frequently in the tissue samples than in the liquid: KRAS (92.2% vs 42.1%) and TP53 (73.0% vs 45.6%). 16.1% of enrolled patients carried pathogenic variants related to HRD, such as ARID1A, BRCA2, ATM, PALB2 and BRCA1. Therapeutic agents were proposed in 27.6% of cases, the proportion of successfully treated patients eligible for targeted therapy was 2.6%. The median OS of KRAS-wild patients was prolonged than KRAS-mutated patients (65.4 vs 27.1 months, p Conclusion: Detection rates of gene alteration vary widely between tissue and liquid samples. KRAS mutation is confirmed as a poor prognostic factor for PDAC and patients with BRCA1/2 mutation are sensitive to FOLFIRINOX. Further accumulation of cases will help us to elucidate the more details of the relationship between gene alteration and therapeutic efficacy. Citation Format: Toshifumi Doi, Takeshi Ishikawa, Tomoki Sakakida, Ryuichi Morita, Daiki Sone, Junichiro Itani, Seita Kataoka, Hayato Miyake, Masahiro Iwasaku, Yoshio Sogame, Hideyuki Konishi, Koichi Takayama, Yoshito Itoh. The real-world data of the cancer genome profiling testing for pancreatic ductal adenocarcinoma from a nationwide database in Japan [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 935. |
