Monitoring of Circulating Tumor DNA Predicts Response to Treatment and Early Progression in Follicular Lymphoma: Results of a Prospective Pilot Study.

Autor: Fernández-Miranda I; Department of Medical Oncology, Lymphoma Research Group, Hospital Universitario Puerta de Hierro-Majadahonda, IDIPHISA, Madrid, Spain.; PhD Program in Molecular Biosciences, Doctoral School, Universidad Autónoma de Madrid, Madrid, Spain., Pedrosa L; Department of Medical Oncology, Lymphoma Research Group, Hospital Universitario Puerta de Hierro-Majadahonda, IDIPHISA, Madrid, Spain.; PhD Program in Molecular Biosciences, Doctoral School, Universidad Autónoma de Madrid, Madrid, Spain., Llanos M; Department of Medical Oncology, Hospital Universitario de Canarias, Tenerife, Spain.; Grupo Oncológico para el Tratamiento y Estudio de los Linfomas (GOTEL), Madrid, Spain., Franco FF; Department of Medical Oncology, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain., Gómez S; Department of Medical Oncology, Lymphoma Research Group, Hospital Universitario Puerta de Hierro-Majadahonda, IDIPHISA, Madrid, Spain., Martín-Acosta P; Department of Pathology, Cancer Molecular Pathology Group, Hospital Universitario Puerta de Hierro-Majadahonda, IDIPHISA, CIBERONC, Madrid, Spain., García-Arroyo FR; Grupo Oncológico para el Tratamiento y Estudio de los Linfomas (GOTEL), Madrid, Spain.; Department of Medical Oncology, Complejo Hospitalario de Pontevedra, Spain., Gumá J; Grupo Oncológico para el Tratamiento y Estudio de los Linfomas (GOTEL), Madrid, Spain.; Department of Medical Oncology, IISPV-URV, Hospital Universitari Sant Joan de Reus, Reus, Spain., Horcajo B; Department of Medical Oncology, Lymphoma Research Group, Hospital Universitario Puerta de Hierro-Majadahonda, IDIPHISA, Madrid, Spain., Ballesteros AK; Department of Medical Oncology, Lymphoma Research Group, Hospital Universitario Puerta de Hierro-Majadahonda, IDIPHISA, Madrid, Spain., Gálvez L; Grupo Oncológico para el Tratamiento y Estudio de los Linfomas (GOTEL), Madrid, Spain.; Department of Medical Oncology, Hospitales Universitarios Regional y Virgen de la Victoria de Málaga, Spain., Martínez N; Grupo Oncológico para el Tratamiento y Estudio de los Linfomas (GOTEL), Madrid, Spain.; Department of Medical Oncology, Dr. Balmis General University Hospital, Alicante Institute for Health and Biomedical Research (ISABIAL), Alicante, Spain., Marín M; Grupo Oncológico para el Tratamiento y Estudio de los Linfomas (GOTEL), Madrid, Spain.; Department of Medical Oncology, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain., Sequero S; Grupo Oncológico para el Tratamiento y Estudio de los Linfomas (GOTEL), Madrid, Spain.; Department of Medical Oncology, Hospital Universitario San Cecilio, Granada, Spain., Navarro M; Department of Medical Oncology, Lymphoma Research Group, Hospital Universitario Puerta de Hierro-Majadahonda, IDIPHISA, Madrid, Spain., Yanguas-Casás N; Department of Medical Oncology, Lymphoma Research Group, Hospital Universitario Puerta de Hierro-Majadahonda, IDIPHISA, Madrid, Spain.; Centro de Investigación Biomédica en Red Fragilidad y Envejecimiento Saludable (CIBERFES), Madrid, Spain., Calvo V; Grupo Oncológico para el Tratamiento y Estudio de los Linfomas (GOTEL), Madrid, Spain.; Department of Medical Oncology, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain., Rueda-Domínguez A; Grupo Oncológico para el Tratamiento y Estudio de los Linfomas (GOTEL), Madrid, Spain.; Department of Medical Oncology, Hospitales Universitarios Regional y Virgen de la Victoria de Málaga, Spain., Provencio M; Grupo Oncológico para el Tratamiento y Estudio de los Linfomas (GOTEL), Madrid, Spain.; Department of Medical Oncology, Hospital Universitario Puerta de Hierro-Majadahonda, Facultad de Medicina, Universidad Autónoma de Madrid, IDIPHISA, Madrid, Spain., Sánchez-Beato M; Department of Medical Oncology, Lymphoma Research Group, Hospital Universitario Puerta de Hierro-Majadahonda, IDIPHISA, Madrid, Spain.; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.
Jazyk: angličtina
Zdroj: Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2023 Jan 04; Vol. 29 (1), pp. 209-220.
DOI: 10.1158/1078-0432.CCR-22-1654
Abstrakt: Purpose: Follicular lymphoma (FL) is the most frequent indolent non-Hodgkin lymphoma. Around 20% of patients suffer early disease progression within 24 months (POD24) of diagnosis. This study examined the significance of circulating tumor DNA (ctDNA) in predicting response to therapy and POD24 in patients with FL.
Experimental Design: We collected 100 plasma samples, before and during the treatment, from 36 patients with FL prospectively enrolled in 8 Spanish hospitals. They were treated with a chemotherapy-rituximab regimen and followed up for a median of 3.43 years. We performed targeted deep sequencing in cell-free DNA (cfDNA) and tumor genomic DNA from 31 diagnostic biopsy samples.
Results: Of the alterations detected in the diagnostic tissue samples, 73% (300/411) were also identified in basal cfDNA. The mean numbers of alterations per basal cfDNA sample in patients who suffered progression of disease within 24 months (POD24-pos) or did not achieve complete response (non-CR) were significantly higher than in POD24-neg or CR patients (unpaired samples t test, P = 0.0001 and 0.001, respectively). Pretreatment ctDNA levels, as haploid genome equivalents per milliliter of plasma, were higher in patients without CR (P = 0.02) and in POD24-pos patients compared with POD24-neg patients (P < 0.001). Dynamic analysis showed that ctDNA levels decreased dramatically after treatment, although the reduction was more significant in patients with CR and POD24-neg patients.
Conclusions: Basal ctDNA levels are associated with the risk of early progression and response to treatment in FL. cfDNA monitoring and genotyping during treatment and follow-up predict response to treatment and early progression.
(©2022 The Authors; Published by the American Association for Cancer Research.)
Databáze: MEDLINE