title: Circulating tumor DNA as a non-invasive substitute to metastasis biopsy for tumor genotyping and personalized medicine in a prospective trial across all tumor types.
abstract: Cell-free tumor DNA (ctDNA) has the potential to enable non-invasive diagnostic tests for personalized medicine in providing similar molecular information as that derived from invasive tumor biopsies. The histology-independent phase II SHIVA trial matches patients with targeted therapeutics based on previous screening of multiple somatic mutations using metastatic biopsies. To evaluate the utility of ctDNA in this trial, as an ancillary study we performed de novo detection of somatic mutations using plasma DNA compared to metastasis biopsies in 34 patients covering 18 different tumor types, scanning 46 genes and more than 6800 COSMIC mutations with a multiplexed next-generation sequencing panel. In 27 patients, 28 of 29 mutations identified in metastasis biopsies (97%) were detected in matched ctDNA. Among these 27 patients, one additional mutation was found in ctDNA only. In the seven other patients, mutation detection from metastasis biopsy failed due to inadequate biopsy material, but was successful in all plasma DNA samples providing three more potential actionable mutations. These results suggest that ctDNA analysis is a potential alternative and/or replacement to analyses using costly, harmful and lengthy tissue biopsies of metastasis, irrespective of cancer type and metastatic site, for multiplexed mutation detection in selecting personalized therapies based on the patient's tumor genetic content.
authors.affiliation: Circulating Cancer Biomarkers Lab, SiRIC, Translational Research Department, Institut Curie, Paris, France.
authors.forename: Ronald
authors.initials: R
authors.lastname: Lebofsky
authors.affiliation: Circulating Cancer Biomarkers Lab, SiRIC, Translational Research Department, Institut Curie, Paris, France; CNRS UMR144, Institut Curie, Paris, France.
authors.forename: Charles
authors.initials: C
authors.lastname: Decraene
authors.affiliation: ICGex NGS Platform, Institut Curie, Paris, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Bernard
authors.affiliation: Department of Medical Oncology, Institut Curie, Paris and Saint-Cloud, France.
authors.forename: Maud
authors.initials: M
authors.lastname: Kamal
authors.affiliation: ICGex NGS Platform, Institut Curie, Paris, France.
authors.forename: Anthony
authors.initials: A
authors.lastname: Blin
authors.affiliation: ICGex NGS Platform, Institut Curie, Paris, France.
authors.forename: Quentin
authors.initials: Q
authors.lastname: Leroy
authors.affiliation: ICGex NGS Platform, Institut Curie, Paris, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Rio Frio
authors.affiliation: Oncogenetic Laboratory, Institut Curie, Paris, France.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Pierron
authors.affiliation: Oncogenetic Laboratory, Institut Curie, Paris, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Callens
authors.affiliation: Oncogenetic Laboratory, Institut Curie, Paris, France.
authors.forename: Ivan
authors.initials: I
authors.lastname: Bieche
authors.affiliation: Circulating Cancer Biomarkers Lab, SiRIC, Translational Research Department, Institut Curie, Paris, France.
authors.forename: Adrien
authors.initials: A
authors.lastname: Saliou
authors.affiliation: Circulating Cancer Biomarkers Lab, SiRIC, Translational Research Department, Institut Curie, Paris, France.
authors.forename: Jordan
authors.initials: J
authors.lastname: Madic
authors.affiliation: Oncogenetic Laboratory, Institut Curie, Paris, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Rouleau
authors.affiliation: Circulating Cancer Biomarkers Lab, SiRIC, Translational Research Department, Institut Curie, Paris, France; Department of Medical Oncology, Institut Curie, Paris and Saint-Cloud, France.
authors.forename: François-Clément
authors.initials: FC
authors.lastname: Bidard
authors.affiliation: INSERM U932, Institut Curie, Paris, France; CIC-BT-507, Institut Curie, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Lantz
authors.affiliation: INSERM U830, Institut Curie, Paris, France.
authors.forename: Marc-Henri
authors.initials: MH
authors.lastname: Stern
authors.affiliation: Department of Medical Oncology, Institut Curie, Paris and Saint-Cloud, France; INSERM U900, Institut Curie, Paris, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Le Tourneau
authors.affiliation: Circulating Cancer Biomarkers Lab, SiRIC, Translational Research Department, Institut Curie, Paris, France; Department of Medical Oncology, Institut Curie, Paris and Saint-Cloud, France; University Paris Descartes, Paris, France. Electronic address: jean-yves.pierga@curie.fr.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Pierga
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D004273:DNA, Neoplasm / Q000097:blood* / Q000378:metabolism; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D060005:Genotyping Techniques; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D009360:Neoplastic Cells, Circulating / Q000378:metabolism* / Q000473:pathology; D057285:Precision Medicine
chemical_list: D004273:DNA, Neoplasm
keywords: Circulating tumor DNA; Liquid biopsy; Multiple tumor types; Next-generation sequencing; SHIVA trial