Plasma total cell-free DNA is a prognostic biomarker of overall survival in metastatic solid tumour patients

• Published in: British journal of cancer Vol. 121; no. 2; pp. 125 - 130
• Main Authors: Viller Tuxen, Ida, Barlebo Ahlborn, Lise, Mau-Soerensen, Morten, Staal Rohrberg, Kristoffer, Cilius Nielsen, Finn, Oestrup, Olga, Westmose Yde, Christina, Richter Vogelius, Ivan, Lassen, Ulrik
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 16.07.2019; Nature Publishing Group
• Subjects: 631/337; 631/67/69; Adult; Aged; Aged, 80 and over; Biomarkers; Biomarkers, Tumor - blood; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cell survival; Cell-Free Nucleic Acids - blood; Clinical trials; Deoxyribonucleic acid; DNA; Drug Resistance; Epidemiology; Female; Humans; Male; Medical prognosis; Metastases; Middle Aged; Molecular Medicine; Neoplasms - blood; Neoplasms - mortality; Oncology; Patients; Prognosis; Solid tumors; Statistical models; Survival
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/s41416-019-0491-9

Background Selecting patients for early clinical trials is a challenging process and clinicians lack sufficient tools to predict overall survival (OS). Circulating cell-free DNA (cfDNA) has recently been shown to be a promising prognostic biomarker. The aim of this study was to investigate whether baseline cfDNA measurement could improve the prognostic information of the Royal Marsden Hospital (RMH) score. Methods Solid tumour patients referred for phase I trials were included in the Copenhagen Personalized Oncology (CoPPO) programme. Baseline characteristics were collected prospectively, including the RMH prognostic score, Eastern Cooperative Oncology Group (ECOG) performance status and concentration of cfDNA per millilitre plasma. Cox proportional hazards model was used to assess the prognostic value of baseline variables. Results Plasma cfDNA concentration was quantifiable in 302 patients out of a total of 419 included in the study period of 2 years and 5 months. The RMH score was confirmed to be associated with OS. Cell-free DNA was shown to be an independent prognostic marker of OS and improved the risk model, including RMH, performance status and age. Furthermore, both plasma cfDNA concentration and RMH score were associated with treatment allocation ( p  < 0.00001). Conclusion Our model based on RMH score, age, ECOG performance status and cfDNA improved prediction of OS and constitutes a clinically valuable tool when selecting patients for early clinical trials. An interactive version of the prognostic model is published on http://bit.ly/phase1survival .