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- Title
Genomic profile and clinical features of MSI-H and TMB-high pancreatic cancers: real-world data from C-CAT database.
- Authors
Sakakida, Tomoki; Ishikawa, Takeshi; Doi, Toshifumi; Morita, Ryuichi; Kataoka, Seita; Miyake, Hayato; Yamaguchi, Kanji; Moriguchi, Michihisa; Sogame, Yoshio; Yasuda, Hiroaki; Iwasaku, Masahiro; Konishi, Hideyuki; Takayama, Koichi; Itoh, Yoshito
- Abstract
Background: Microsatellite instability high (MSI-H) and tumor mutational burden high (TMB-high) pancreatic cancer are rare, and information is lacking. Based on the C-CAT database, we analyzed the clinical and genomic characteristics of patients with these subtypes. Methods: We retrospectively reviewed data on 2206 patients with unresectable pancreatic adenocarcinoma enrolled in C-CAT between July 2019 and January 2022. The clinical features, proportion of genomic variants classified as oncogenic/pathogenic in C-CAT, overall response rate (ORR), disease control rate (DCR), and time to treatment failure (TTF) of chemotherapy as first-line treatment were evaluated. Results: Numbers of patients with MSI-H and TMB-high were 7 (0.3%) and 39 (1.8%), respectively. All MSI-H patients were TMB-high. MSI-H and TMB-high patients harbored more mismatch repair genes, such as MSH2, homologous recombination-related genes, such as ATR and BRCA2, and other genes including BRAF, KMT2D, and SMARCA4. None of the 6 MSI-H patients who received chemotherapy achieved a clinical response, including 4 patients treated with gemcitabine plus nab-paclitaxel (GnP) therapy, whose DCR was significantly lower than that of microsatellite stable (MSS) patients (0 vs. 67.0%, respectively, p = 0.01). Among the TMB-high and TMB-low groups, no significant differences were shown in ORR, DCR (17.1 vs. 23.1% and 57.1 vs. 63.1%, respectively), or median TTF (25.9 vs. 28.0 weeks, respectively) of overall first-line chemotherapy. Conclusions: MSI-H and TMB-high pancreatic cancers showed some distinct genomic and clinical features from our real-world data. These results suggest the importance of adapting optimal treatment strategies according to the genomic alterations.
- Subjects
PANCREATIC cancer; DATABASES; PANCREATIC tumors; HEREDITARY nonpolyposis colorectal cancer; TREATMENT failure; MICROSATELLITE repeats; BRCA genes
- Publication
Journal of Gastroenterology, 2024, Vol 59, Issue 2, p145
- ISSN
0944-1174
- Publication type
Article
- DOI
10.1007/s00535-023-02058-8