Dynamic changes in circulating tumor assessed by shallow whole-genome sequencing associate with clinical efficacy of checkpoint inhibitors in
Carbonell, Caterina (Vall d'Hebron Institut d'Oncologia)
Frigola Rissech, Joan (Vall d'Hebron Institut d'Oncologia)
Pardo Aranda, Nuria (Vall d'Hebron Institut d'Oncologia)
Callejo, Ana (Vall d'Hebron Institut d'Oncologia)
Iranzo, Patricia (Vall d'Hebron Institut d'Oncologia)
Valdivia, Augusto (Vall d'Hebron Institut d'Oncologia)
Priano, Ilaria (Vall d'Hebron Institut d'Oncologia)
Cedrés, Susana (Vall d'Hebron Institut d'Oncologia)
Martinez-Marti, Alex (Vall d'Hebron Institut d'Oncologia)
Navarro, Alejandro (Vall d'Hebron Institut d'Oncologia)
Lenza, Laura (Vall d'Hebron Institut d'Oncologia)
Soleda, Mireia (Vall d'Hebron Institut d'Oncologia)
Gonzalo-Ruiz, Javier (Vall d'Hebron Institut d'Oncologia)
Vivancos, Ana (Vall d'Hebron Institut d'Oncologia)
Sansó, Miriam (Institut d'Investigació Sanitària Illes Balears)
Carcereny, Enric (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Morán, Teresa (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Amat, Ramon (Vall d'Hebron Institut d'Oncologia)
Felip, Enriqueta (Hospital Universitari Vall d'Hebron)
Universitat Autònoma de Barcelona

Date:	2023
Abstract:	Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis are the main therapeutic option for patients with advanced non-small cell lung cancer (NSCLC) without a druggable oncogenic alteration. Nevertheless, only a portion of patients benefit from this type of treatment. Here, we assessed the value of shallow whole-genome sequencing (sWGS) on plasma samples to monitor ICI benefit. We applied sWGS on cell-free DNA (cfDNA) extracted from plasma samples of 45 patients with metastatic NSCLC treated with ICIs. Over 150 samples were obtained before ICI treatment initiation and at several time points throughout treatment. From sWGS data, we computed the tumor fraction (TFx) and somatic copy number alteration (SCNA) burden and associated them with ICI benefit and clinical features. TFx at baseline correlated with metastatic lesions at the bone and the liver, and high TFx (≥ 10%) associated with ICI benefit. Moreover, its assessment in on-treatment samples was able to better predict clinical efficacy, regardless of the TFx levels at baseline. Finally, for a subset of patients for whom SCNA burden could be computed, increased burden correlated with diminished benefit following ICI treatment. Thus, our data indicate that the analysis of cfDNA by sWGS enables the monitoring of two potential biomarkers-TFx and SCNA burden-of ICI benefit in a cost-effective manner, facilitating multiple serial-sample analyses. Larger cohorts will be needed to establish its clinical potential. The authors applied shallow whole-genome sequencing on cfDNA to study the association between tumor fraction (TFx) or somatic copy number alteration (SCNA) burden and immune checkpoint inhibitors (ICIs) efficacy in patients with metastatic NSCLC. Samples were sequenced before and during treatment: although high baseline TFx is associated with higher ICIs efficacy, its assessment in on-treatment samples was able to better predict clinical efficacy, regardless of the TFx levels at baseline.
Grants:	Instituto de Salud Carlos III PI22/01585 Instituto de Salud Carlos III PI20/00987
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Aneuploidy ; Cfdna ; Immune checkpoint inhibitors ; Liquid biopsy ; NSCLC ; Shallow whole-genome sequencing
Published in:	Molecular Oncology, Vol. 17 (march 2023) , p. 779-791, ISSN 1878-0261

DOI: 10.1002/1878-0261.13409
PMID: 36852704

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
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