Fluorometric Quantification of Total Cell-Free DNA as a Prognostic Biomarker in Non-Small-Cell Lung Cancer Patients Treated with Immune Checkpoint Blockade

Author:

Oliver Javier1ORCID,Onieva Juan Luis12ORCID,Garrido-Barros María12,Cobo-Dols Manuel1ORCID,Martínez-Gálvez Beatriz1,García-Pelícano Ana Isabel1,Dubbelman Jaime1,Benítez José Carlos1ORCID,Martín Juan Zafra123ORCID,Cantero Alejandra1,Pérez-Ruiz Elisabeth1ORCID,Rueda-Domínguez Antonio1ORCID,Barragán Isabel14ORCID

Affiliation:

1. Medical Oncology Service (Group of Translational Research in Cancer Immunotherapy), Regional and Virgen de la Victoria University Hospitals, Institute of Biomedical Research in Malaga and BIONAND Nanomedicine Platform (IBIMA BIONAND Platform), C/Marqués de Beccaría n°3, 29010 Málaga, Spain

2. Faculty of Medicine, Campus de Teatinos s/n, Universidad de Málaga, 29071 Málaga, Spain

3. Department of Radiation Oncology, Virgen de la Victoria University Hospital, 29010 Málaga, Spain

4. Group of Pharmacoepigenetics, Department of Physiology and Pharmacology, Karolinska Institutet, 171 77 Stockholm, Sweden

Abstract

The present study aimed to investigate the potential of basal cell-free fluorometric DNA (cfDNA) quantification as a prognostic biomarker in advanced non-small cell lung cancer (NSCLC) patients treated with an Immune Checkpoint Blockade (ICB). A discovery and validation cohort of 61 and 31 advanced lung cancer patients treated with ICB were included in this study. Quantification of cfDNA concentration was performed before the start of the treatment and patients were followed up for a median of 34 (30–40) months. The prognostic predicted value of cfDNA was evaluated based on ROC, and Cox regression was conducted via univariate and multivariate analyses to estimate the hazard ratio. We observed that a cfDNA cut-off of 0.55 ng/µL before the ICB determines the overall survival of patients with a log rank p-value of 3.3 × 10−4. That represents median survivals of 3.8 vs. 17.5 months. Similar results were obtained in the validation cohort being the log rank p-value 3.8 × 10−2 with median survivals of 5.9 vs. 24.3. The univariate and multivariate analysis revealed that the cut-off of 0.55 ng/µL before ICB treatment was an independent predictive factor and was significantly associated with a better survival outcome. High cfDNA concentrations identify patients with advanced NSCLC who do not benefit from the ICB. The determination of cfDNA is a simple test that could select a group of patients in whom new therapeutic strategies are needed.

Funder

Instituto de Salud Carlos III

Sociedad Española de Oncología Médica

Sistema Andaluz de Salud

Nicolás Monardes

Consejería de Transformación económica, Industria, Conocimiento y Universidades

Spanish Group of Melanoma

Fundación Bancaria Unicaja

Asociación Española Contra el Cáncer

Andalusia-Roche Network Mixed Alliance in Precision Medical Oncology

Publisher

MDPI AG

Subject

Cancer Research,Oncology

Reference38 articles.

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