DNA damage repair mutations in pancreatic cancer- prognostic or predictive?

Ya-Fei Hu; Hai-Jie Hu; Heng-Chung Kung; Tian-Run Lv; Jun Yu; Fu-Yu Li

doi:10.3389/fonc.2023.1267577

DNA damage repair mutations in pancreatic cancer- prognostic or predictive?

Front Oncol. 2023 Oct 25:13:1267577. doi: 10.3389/fonc.2023.1267577. eCollection 2023.

Authors

Ya-Fei Hu¹, Hai-Jie Hu¹, Heng-Chung Kung², Tian-Run Lv¹, Jun Yu^{3

4}, Fu-Yu Li¹

Affiliations

¹ Department of Biliary Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
² Krieger School of Arts and Sciences, Johns Hopkins University, Baltimore, MD, United States.
³ Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
⁴ Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, United States.

Abstract

Objective: The efficacy of platinum-based chemotherapy (PtCh) for pancreatic cancer (PC) patients with DNA damage repair gene mutations (DDRm) compared to those without DDRm remains uncertain.

Methods: After a thorough database searching in PubMed, Embase, and Web of Science, a total of 19 studies that met all the inclusion criteria were identified. The primary outcomes were overall survival (OS) and progression-free survival (PFS) for PC patients with DDRm versus those without DDRm after PtCh.

Results: Patients with advanced-stage PC who have DDRm tend to have longer OS compared to patients without DDRm, regardless of their exposure to PtCh (HR=0.63; I² = 66%). Further analyses indicated that the effectiveness of PtCh for OS was modified by DDRm (HR=0.48; I² = 59%). After the first- line PtCh (1L-PtCh), the PFS of advanced-stage PC with DDRm was also significantly improved (HR=0.41; I² = 0%). For patients with resected PC, regardless of their exposure to PtCh, the OS for patients with DDRm was comparable to those without DDRm (HR=0.82; I² = 71%). Specifically, for patients with resected PC harboring DDRm who received PtCh (HR=0.85; I² = 65%) and for those after non-PtCh (HR=0.87; I² = 0%), the presence of DDRm did not show a significant association with longer OS.

Conclusion: 1L-PtCh treatment is correlated with favorable survival for advanced-stage PC patients with DDRm. For resected-stage PC harboring DDRm, adjuvant PtCh had limited effectiveness. The prognostic value of DDRm needs to be further verified by prospective randomized controlled trials.

Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022302275.

Keywords: DNA damage repair gene; overall survival; pancreatic cancer; platinum-based chemotherapy; progression-free survival.

Publication types

Systematic Review

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. Supported by 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University (ZYJC21046); 1.3.5 project for disciplines of excellence Clinical Research Incubation Project, West China Hospital, Sichuan University (2021HXFH001); Natural Science Foundation of Sichuan Province (2022NSFSC0806); National Natural Science Foundation of China for Young Scientists Fund (82203650, 82203782), Sichuan Science and Technology Program (2021YJ0132, 2021YFS0100); The fellowship of China Postdoctoral Science Foundation (2021M692277); Sichuan University-Zigong School-local Cooperation project (2021CDZG-23); Sichuan University-Sui Lin School-local Cooperation project (2022CDSN-18); Science and Technology project of the Health planning committee of Sichuan (21PJ046); Post-Doctor Research Project, West China Hospital, Sichuan University (2020HXBH127).