O-026 - Total circulating cell-free DNA (cfDNA) as a prognostic biomarker in metastatic colorectal cancer prior to first-line oxaliplatin-based chemotherapy

Abstract

Introduction: Small fragments of circulating cell-free DNA (cfDNA) can be detected in blood from cancer patients. Previous studies have shown a prognostic value mainly prior to second and subsequent lines of metastatic colorectal cancer (mCRC). We aimed to analyze the prognostic value of total plasma cfDNA in a patient population prior to first-line oxaliplatin-based chemotherapy for non-resectable mCRC in the NORDIC-VII study. Methods: A total of 547 patients had blood samples available for pre-treatment quantification of total cfDNA. Plasma samples were used for DNA purification and quantification of total cfDNA by droplet digital polymerase chain reaction (measuring beta-2-microglobulin DNA concentration) with controls for contamination from normal lymphocytes. Clinical endpoint was overall survival (OS). Results: Total cfDNA levels were successfully quantified in plasma from 499 patients, 48 samples were excluded mainly due to lymphocyte contamination. The median level was 7,833 alleles per mL plasma (range 1,050 – 1,645,000). High total cfDNA levels were associated with poor performance status, intact primary tumor and presence of liver metastases. There was no significant difference in cfDNA levels according to treatment arms. When dividing patients into groups of cfDNA quartiles, worse survival was seen with increasing pre-treatment levels of total cfDNA ( p < 0.001). Patients with total cfDNA above median levels (n = 250) had an OS of 16.1 months (95% CI 14.4 – 17.8) compared to patients with below median levels (n = 249) with an OS of 25.1 months (95% CI 22.4 –27.8, p < 0.001). In a Cox regression multivariate analysis (n = 496), total cfDNA level remained an independent prognostic marker ( p = 0.001) after adjusting for performance status, carcinoembryonic antigen (CEA) and alkaline phosphatase (ALP) levels. Conclusion: The level of total cfDNA in plasma has prognostic value in patients with mCRC prior to first-line oxaliplatin-based chemotherapy.