Circulating cell-free tumor DNA (ctDNA) is an emerging tool under investigation in pancreatic cancer (PC). This study aimed to evaluate the prognostic value of ctDNA variant allele frequency (VAF) in advanced PC collected at diagnosis.
Patients with advanced pancreatic cancer and ctDNA collected at time of initial diagnosis were retrospectively evaluated. For analysis we considered the detected gene with highest VAF as the dominant clone allele frequency (DCAF). The DCAF was evaluated in relation to patients’ demographics, systemic treatment response, progression-free survival (PFS) and overall survival (OS).
A total of 104 patients were included in the analysis. The median age was 70 years (range 43-91), 50% were male, 38.5% with locally advanced disease and 61.5% with metastatic disease. Somatic alterations were detected in 84.6 % of the patients and were more pronounced in metastatic PC, 91% of metastatic PC patients had at least one genetic alteration detected compared to 74% of patients with locally advanced disease (p=0.03). 66 patients underwent chemotherapy with gemcitabine and paclitaxel (64%) and 29 patients with FOLFIRINOX (28%). The most detected genes were KRAS, TP53, CDKN2A and SMAD4. The median DCAF was 0.45% (0-55%). DCAF >0.45% was associated with worse median PFS (median PFS: 6 vs. 14 months, p=0.00013) and median OS (median OS: 10 vs. 24 months, p=0.00027).
Patients with advanced PC with DCAF > 0.45% at diagnosis have worse PFS and OS compared to patients with low ctDNA.
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All authors have declared no conflicts of interest.