Circulating tumor DNA (ctDNA) as a predictor of treatment for locally advanced pancreatic cancer

Abstract

Introduction: By today R0 - curative resection is possible following neoadjuvant treatment for LAPC, however still there is no method to determine patients beforehand who will have a favorable surgical outcome. The aim of this study was to evaluate the prediction possibilities of ctDNA during chemo-radiotherapy after surgical treatment of locally advanced pancreatic cancer. Methods: 42 patients were enrolled in this study who were treated in National Cancer Research Centre. Pts received neoadjuvant FOLFIRINOX followed by CRT: either short-course (n=12, 25 Gy/5 fractions), or longcourse (n=30, 50.4 Gy/28 fractions). Serum ctDNA was measured at baseline, every week 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. Outcomes of treatment were based on: 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 patients was 64 years (range 39-82 years). Following CRT, 33 (78,5%) were operable. The overall R0-node negative (R0-NN) resection rate was 59% for the entire cohort. The rate of R0-NN resection higher among patients with an undetectable preoperative ctDNA (n=16) compared to those with a detectable (n=26) preoperative ctDNA (88% R0-NN vs 50% R0-NN, respectively). Only ctDNA status was significantly associated with R0-NN resection (p=0.025), whereas preoperative RECIST score, CA19-9, and CEA were not associated. For patients who received surgery, the ctDNA was significantly correlated with TRG (Pearson R=0.399, p=0.024). Conclusion: Detection of ctDNA is associated with poorer surgical outcome in patients treated with neoadjuvant CRT for locally advance pancreatic cancer. At the same time absence of ctDNA in blood serum leads to a better surgical outcomes, this fact is one more evidence for implementing this technique into a daily routine for more appropriate selection of patients who will benefit from surgical treatment.