Exploring predictive factors for detecting KRAS mutations in pancreatic cancer using liquid biopsy.

Abstract

782 Background: Liquid biopsy offers an alternative to tissue specimens for comprehensive genetic profiling. However, circulating tumor DNA is sometimes insufficient to detect genomic alterations in pancreatic cancer (PC). The detection rate of KRAS mutations was reportedly increased in PC with liver metastasis. In contrast, the predictive value of CA19-9 levels, the timing of liquid biopsy, or the type of liquid biopsy for detecting KRAS mutations remains unclear. We investigated whether these factors could be predictive of detecting KRAS mutations in PC. Methods: From September 2021 to August 2024, we retrospectively reviewed patients with PC who underwent liquid biopsy. Results: A total of 106 patients were enrolled (median age: 64 years, male: 66). Patient characteristics were as follows: tumor status: locally advanced: 10, metastatic: 90, recurrence: 6; metastatic site: liver: 51, lung: 26, lymph nodes: 20, peritoneum: 38, others: 7; number of metastatic sites: 1: 63, 2: 25, ≥3: 8; treatment line at liquid biopsy: 1: 21, 2: 77, 3:8; median CA19-9 level: 1053.4 U/mL; type of liquid biopsy: FoundationOne Liquid CDx (FL): 75 or Guardant360 (G): 31. The overall rate of KRAS mutations was 47%, with a median variant allele frequency of 0.83 [range:0.1-71.0]. The patterns of KRAS mutations were as follows: G12D: 23, G12V: 18, G12R: 4, and others: 14. The detection rate of KRAS mutations varied by the follows factors: metastatic site: liver: 65%, other organs: 44%; number of metastatic sites: ≥2: 47%, <2: 48%; CA19-9 level: ≥2,000 U/mL: 68%, <2,000: 38%; timing of liquid biopsy: 1st line: 42%, ≥2nd line: 67%; types of liquid biopsy: FL: 49%, G: 42%. In multivariate analysis, liver metastasis and CA19-9 level ≥2,000 U/mL were identified as independent factors associated with improved detection of KRAS mutations. In PC with these two factors, the detection rate of KRAS mutation increased to 76%. Conclusions: Our findings indicate that liver metastasis and CA19-9 levels above 2,000 U/mL are predictive factors for detecting KRAS mutations in PC through liquid biopsy.