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

Ida Viller Tuxen,Olga Oestrup,Morten Mau-Soerensen,Kristoffer Staal Rohrberg,Finn Cilius Nielsen,Ivan Richter Vogelius,Lise Barlebo Ahlborn,Ulrik Lassen,Christina Westmose Yde

doi:10.1038/s41416-019-0491-9

Ida Viller Tuxen, Olga Oestrup + Show 7 more

Open Access

https://doi.org/10.1038/s41416-019-0491-9

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Abstract

BackgroundSelecting 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.MethodsSolid 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.ResultsPlasma 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).ConclusionOur 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.

Highlights

Selecting patients for early clinical trials is a challenging process and clinicians lack sufficient tools to predict overall survival (OS)
Measurable plasma cell-free DNA (cfDNA) concentration at inclusion was obtained from 302 patients and 169 patients were allocated to treatment and 133 received no further treatment (Fig. 1)
Both Royal Marsden Hospital (RMH) score and cfDNA quartile was highly associated with the probability of not being offered treatment (Fig. 3, P < 0.00001 for both RMH score and cfDNA)

Summary

Introduction

Selecting patients for early clinical trials is a challenging process and clinicians lack sufficient tools to predict overall survival (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 Both plasma cfDNA concentration and RMH score were associated with treatment allocation (p < 0.00001). Different prognostic scores have been introduced in order to select patients for phase 1 trials.[6,7] The Royal Marsden Hospital (RMH) score has been validated in various phase 1 cohorts[8,9,10,11] and consist of three variables: Elevated lactate dehydrogenase (LDH) (> upper limit), low serum-albumin (< 35 g/L) and more than two metastatic sites These prognostic scores have been validated, the clinical use is limited

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