Abstract 88P
Background
Circulating tumor DNA (ctDNA) has emerged as a promising biomarker displaying systemic tumor burden in presumed localized pancreatic cancer (lPC). However, clinical applicability for neoadjuvant chemotherapy (NACT) guidance was flawed by low preoperative detection rates (10.2%) without NGS until now. Recently, CA 19-9 >500 U/ml has been implemented into the Austrian guidelines for administration of NACT.
Methods
Liquid Biopsy samples of n=147 patients with lPC were collected 1 day before, 1 day after and 10 days after curative intended surgery and have been analyzed by ddPCR for KRAS G12/13 and, if negative, KRAS Q61. Results have been correlated with tumor volume and outcome.
Results
Detection rates have improved by x3.6 to 36.8% (preop.), 19.7% (1d postop.) and 13.3% (10d postop.). ctDNA showed no correlation with primary tumor volume (p=0.605), but with nodal positivity (p=0.029). Pretherapeutic ctDNA detectability was associated with worse OS (10. (95%CI 4-16.2) vs. 36 (95%CI 22.1-49.9) months, p<0.001) and DFS (6 (95%CI 2.6-9.4) vs. 23.5 (95%CI 17.9-29.1) months, p<0.001), whereas CA 19-9 >500 U/ml was not (p=0.285, p=0.162). Also, postoperative ctDNA detectability showed correlation to DFS (12.9 vs. 29.1 months, p=0.027) and OS (HR 3.120).
Conclusions
This study represents the currently largest prospective cohort on this topic (formerly n=113 by Guo et al., China, 2020). ctDNA allows detection of actual systemic tumor burden and offers a cost effective and clinical applicable method to eventually guide NACT vs. upfront surgery as precision medicine approach in the future adding a biological criteria for high risk of relapse to the up to now radiological resectability.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Krebshilfe Oberösterreich, Vinzenzgruppe.
Disclosure
All authors have declared no conflicts of interest.