Abstract 89P
Background
ctDNA has emerged as a promising biomarker in gastrointestinal cancer. However, definitions for detectability and cut-offs are reported very heterogeneously. We evaluated for the first time in humans responses to treatment at an unifiable cut-off for dynamic changes during chemotherapy in 3 different major GI-cancer types (n=924 samples).
Methods
Liquid biopsy samples for n=185 stage IV patients with gastroesophageal (GEC, n=37), pancreatic (PC, n=70) and colorectal cancer (CRC, n=78) have been prospectively acquired pre-therapeutically and every 2 weeks during chemotherapy until restaging, analyzed using ddPCR and correlated with response to treatment and outcome.
Results
Detection rates were 88.5% (CRC), 77.8% (GEC) and 64.3% (PC). ROC analysis (AUC > 0.9) revealed a decline of under 58% of the pre-therapeutic MAF to predict response to treatment already after 2 weeks (CRC spec. 97.8%, sens. 92.3%, GEC spec. 100%, sens. 66.7%, PC spec. 100%, sens. 91.7%). This was accompanied with a significant impact on OS and PFS for all tumor entities: GEC: 3.2 (95%CI 1.9-4.5) vs. 9.5 (95%CI 5.5-13.5) months, p= 0.001 PC: 2.5 (95%CI 2.2-2.9) vs. 7.7 (95%CI 4.0-11.3) months, p < 0.001 CRC: 2 (95%CI 1.3-2.7) vs. 11 (95%CI 9.0-13.0) months, p <0.001.
Conclusions
ctDNA represents an already clinical applicable biomarker with remarkable sensitivity and specificity in displaying actual tumor burden, prediction of prognosis and response to treatment. This biomarker is superior to current gold standard markers CEA, CA19-9 and CA72-4 and predicts response to systemic treatment after 2 weeks (>80% faster than computed tomography).
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Oberösterreichische Krebshilfe, Vinzenzgruppe OÖ.
Disclosure
All authors have declared no conflicts of interest.