TY - JOUR

T1 - Plasma total cell-free DNA is a prognostic biomarker of overall survival in metastatic solid tumour patients

AU - Viller Tuxen, Ida

AU - Barlebo Ahlborn, Lise

AU - Mau-Soerensen, Morten

AU - Staal Rohrberg, Kristoffer

AU - Cilius Nielsen, Finn

AU - Oestrup, Olga

AU - Westmose Yde, Christina

AU - Richter Vogelius, Ivan

AU - Lassen, Ulrik

PY - 2019

Y1 - 2019

N2 - 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 https://bit.ly/phase1survival.

AB - 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 https://bit.ly/phase1survival.

U2 - 10.1038/s41416-019-0491-9

DO - 10.1038/s41416-019-0491-9

M3 - Journal article

C2 - 31186525

AN - SCOPUS:85067287153

VL - 121

SP - 125

EP - 130

JO - The British journal of cancer. Supplement

JF - The British journal of cancer. Supplement

SN - 0007-0920

IS - 2

ER -