Prognostic utility of preoperative and postoperative KRAS-mutated circulating tumor DNA (ctDNA) in resected pancreatic ductal adenocarcinoma: A systematic review and meta-analysis

Ali Alqahtani; Abdurahman Alloghbi; Philip Coffin; Chao Yin; Reetu Mukherji; Benjamin A Weinberg

doi:10.1016/j.suronc.2023.102007

Prognostic utility of preoperative and postoperative KRAS-mutated circulating tumor DNA (ctDNA) in resected pancreatic ductal adenocarcinoma: A systematic review and meta-analysis

Surg Oncol. 2023 Dec:51:102007. doi: 10.1016/j.suronc.2023.102007. Epub 2023 Oct 10.

Authors

Ali Alqahtani¹, Abdurahman Alloghbi², Philip Coffin³, Chao Yin⁴, Reetu Mukherji⁴, Benjamin A Weinberg⁵

Affiliations

¹ The Ruesch Center for the Cure of Gastrointestinal Cancers, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, 20057, USA; Medical Oncology Department, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
² Cancer Research Unit and Department of Oncology, King Khalid University, Abha, Saudi Arabia.
³ Department of Internal Medicine, Georgetown University Medical Center, Washington, DC, 20057, USA.
⁴ The Ruesch Center for the Cure of Gastrointestinal Cancers, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, 20057, USA.
⁵ The Ruesch Center for the Cure of Gastrointestinal Cancers, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, 20057, USA. Electronic address: benjamin.a.weinberg@gunet.georgetown.edu.

PMID: 37852124
DOI: 10.1016/j.suronc.2023.102007

Abstract

Background: Pancreatic ductal adenocarcinoma (PDAC) is a challenging disease, with surgery being the only possible cure. However, despite surgery, the majority of patients experience recurrence. Recent evidence suggests that perioperative KRAS-mutated circulating tumor DNA (ctDNA) may have prognostic value. Therefore, we conducted a systematic review and meta-analysis to explore the prognostic significance of preoperative and postoperative KRAS-mutated ctDNA testing in resected PDAC.

Methods: We searched PubMed/MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases for studies that reported the effect of preoperative and postoperative KRAS-mutated ctDNA on overall survival (OS) and/or relapse-free survival (RFS) in resected PDAC. We used a random-effects model to determine the pooled OS and RFS hazard ratios (HR) and their corresponding 95 % confidence intervals (CI).

Results: We identified 15 studies (868 patients) eligible for analysis. In the preoperative setting, positive ctDNA correlated with worse RFS in 8 studies (HR, 2.067; 95 % CI, 1.346-3.174, P < 0.001) and worse OS in 10 studies (HR, 2.170; 95 % CI, 1.451-3.245, P < 0.001) compared to negative ctDNA. In the postoperative setting, positive ctDNA correlated with worse RFS across 9 studies (HR, 3.32; 95 % CI, 2.19-5.03, P < 0.001) and worse OS in 6 studies (HR, 6.62; 95 % CI, 2.18-20.16, P < 0.001) compared to negative ctDNA.

Conclusion: Our meta-analysis supports the utility of preoperative and postoperative KRAS-mutated ctDNA testing as a prognostic marker for resected PDAC. Further controlled studies are warranted to confirm these results and to investigate the potential therapeutic implications of positive KRAS-mutated ctDNA.

Keywords: Biomarkers; Circulating tumor DNA; Liquid biopsy; Minimal residual disease; Pancreatic adenocarcinoma.

Publication types

Meta-Analysis
Systematic Review
Review

MeSH terms

Biomarkers, Tumor / genetics
Carcinoma, Pancreatic Ductal* / genetics
Carcinoma, Pancreatic Ductal* / surgery
Circulating Tumor DNA* / genetics
Circulating Tumor DNA* / therapeutic use
Humans
Mutation
Pancreatic Neoplasms* / genetics
Pancreatic Neoplasms* / pathology
Pancreatic Neoplasms* / surgery
Prognosis
Proto-Oncogene Proteins p21(ras) / genetics

Substances

Circulating Tumor DNA
Proto-Oncogene Proteins p21(ras)
Biomarkers, Tumor
KRAS protein, human