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dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorFrigola Rissech, Joan
dc.contributor.authorCarbonell, Caterina
dc.contributor.authorIranzo Gómez, Patricia
dc.contributor.authorPardo Aranda, Nuria
dc.contributor.authorCallejo Perez, Ana
dc.contributor.authorCedres Perez, Susana
dc.contributor.authorMartínez Marti, Alexandre
dc.contributor.authorNavarro Mendivil, Alejandro
dc.contributor.authorSoleda, Mireia
dc.contributor.authorJiménez Flores, José Antonio
dc.contributor.authorHernandez Losa, Javier
dc.contributor.authorVivancos Prellezo, Ana
dc.contributor.authorFelip Font, Enriqueta
dc.contributor.authorAmat, Ramon
dc.date.accessioned2022-09-06T08:56:57Z
dc.date.available2022-09-06T08:56:57Z
dc.date.issued2022-04
dc.identifier.citationFrigola J, Carbonell C, Irazno P, Pardo N, Callejo A, Cedres S, et al. High levels of chromosomal aberrations negatively associate with benefit to checkpoint inhibition in NSCLC. J Immunother Cancer. 2022 Apr;10(4):e004197.
dc.identifier.issn2051-1426
dc.identifier.urihttp://hdl.handle.net/11351/8030
dc.descriptionImmunotherapy; Lung neoplasms; Tumor biomarkers
dc.description.abstractBackground Immune checkpoint inhibitors (ICIs) targeting the programmed cell death 1/programmed death-ligand 1 axis have transformed the management of advanced non-small cell lung cancer (NSCLC). However, many patients do not benefit from this type of treatment, and thus several molecular biomarkers of benefit have been explored. The value of somatic copy number alterations (SCNAs) burden remains elusive. Patients and methods We assembled a cohort of 109 patients with NSCLC treated with ICIs and available tumor samples. We performed shallow whole-genome sequencing on 89 patients to determine genome-wide SCNAs and targeted gene expression analysis on 63 patients to study immune infiltration. We analyzed SCNAs burden in different ways (ie, the fraction of the genome altered or number of events) and studied their association with ICIs benefit based on survival analysis. We correlated SCNAs burden and immune infiltration on 35 patients of our cohort and on patients with lung adenocarcinoma from The Cancer Genome Atlas (TCGA). Results High SCNAs burden, computed in diverse ways, is negatively associated with ICIs progression-free survival (PFS), with the fraction of the genome altered (FGA) by arm and chromosome events showing the strongest association with PFS (p=0.002) (n=77). Nevertheless, we found differences in SCNAs across some clinicopathological features (sample site origin). A multivariate analysis adjusted for relevant characteristics showed that the FGA of arm and chromosome alterations was strongly associated with PFS (HR=2.21, p=3.3 x 10−5). Finally, we confirmed that SCNAs burden negatively correlates with tumor immune infiltration (n=35), although this correlation was not found for the males studied. Similar results were observed in the TCGA cohort. Conclusions SCNAs burden is a potential biomarker of benefit to ICIs in patients with NSCLC, although there appear to be some nuances worth consideration. Further studies will be needed to establish its role as a biomarker of benefit to ICIs.
dc.language.isoeng
dc.publisherBMJ
dc.relation.ispartofseriesJournal for ImmunoTherapy of Cancer;10(4)
dc.rightsAttribution-NonCommercial 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/
dc.sourceScientia
dc.subjectAnomalies cromosòmiques
dc.subjectPulmons - Càncer - Tractament
dc.subject.meshCarcinoma, Non-Small-Cell Lung
dc.subject.mesh/drug therapy
dc.subject.meshChromosome Aberrations
dc.titleHigh levels of chromosomal aberrations negatively associate with benefit to checkpoint inhibition in NSCLC
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.1136/jitc-2021-004197
dc.subject.decscarcinoma de pulmón de células no pequeñas
dc.subject.decs/farmacoterapia
dc.subject.decsaberraciones cromosómicas
dc.relation.publishversionhttp://dx.doi.org/10.1136/jitc-2021-004197
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.organismesInstitut Català de la Salut
dc.contributor.authoraffiliation[Frigola J, Carbonell C, Soleda M, Amat R] Thoracic Cancers Translational Genomics Unit, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. Clinical Research Department, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Irazno P, Pardo N, Callejo A, Cedres S, Martinez-Marti A, Navarro A] Clinical Research Department, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. Servei d’Oncologia Mèdica, Vall d'Hebron Hospital Universitari, Barcelona, Spain. [Jimenez J] Molecular Oncology Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Hernandez-Losa J] Servei de Patologia, Vall d'Hebron Hospital Universitari, Barcelona, Spain. [Vivancos A] Cancer Genomics Laboratory, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Felip E] Thoracic Cancers Translational Genomics Unit, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. Clinical Research Department, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. Servei d’Oncologia Mèdica, Vall d'Hebron Hospital Universitari, Barcelona, Spain
dc.identifier.pmid35477861
dc.identifier.wos000788620500001
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


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