Using circulating tumor DNA (ctDNA) to predict surgical outcome after neoadjuvant chemoradiation for locally advanced pancreatic cancer (LAPC).

Abstract

272 Background: Curative resection is possible following neoadjuvant treatment for LAPC, yet there is no method to identify patients beforehand who will have a favorable surgical outcome. This study was designed to assess the ability of ctDNA measured during neoadjuvant chemoradiation (CRT) to predict surgical outcome for LAPC. Methods: 38 LAPC pts were enrolled at our institution between 10/2015 - 5/2017. Pts received neoadjuvant FOLFIRINOX followed by CRT: either short-course ( n = 9, 25 Gy/5 fractions), or long-course ( n = 29, 50.4 Gy/28 fractions). Serum ctDNA was measured at baseline, weekly during CRT, and preoperatively. After extracting DNA from plasma, a tumor mutation specific droplet digital PCR assay was used to detect the fraction of ctDNA molecules. The following clinical and pathologic outcomes were noted: CA19-9, CEA, RECIST score, tumor grade, T stage, tumor regression grade (TRG), R-resection status, pathologically involved lymph nodes, LVI, and PNI. Results: The median age of the cohort was 67 years (range 42-85 years). Following CRT, 32 (84%) were operable. The overall R0-node negative (R0-NN) resection rate was 66% for the entire cohort. The rate of R0-NN resection was significantly higher among patients with an undetectable preoperative ctDNA ( n= 16) compared to those with a detectable ( n= 22) preoperative ctDNA (88% R0-NN vs 50% R0-NN, respectively, Fisher’s exact p = 0.036). On univariate logistic regression, only ctDNA status was significantly associated with R0-NN resection (p = 0.025), whereas preoperative RECIST score, CA19-9, and CEA were not associated. On multivariable logistic regression, ctDNA remained a borderline significant predictor for R0-NN resection when controlling for CA19-9 ( p = 0.058). For patients who received surgery, the ctDNA allele fraction was significantly correlated with TRG ( Pearson R = 0.399, p = 0.024). Conclusions: Undetectable preoperative ctDNA is associated with R0-NN surgical outcome in a cohort of patients treated with neoadjuvant CRT for LAPC. This approach is worthy of further study to establish guidelines for incorporating ctDNA into clinic with the goal of improving patient selection for surgery.