Sistema de Salut de Catalunya
Institut Català de la Salut
[Lazar V, Raynaud J] Worldwide Innovative Network—WIN Consortium, Villejuif, France. [Girard N] Institut Curie, Paris, France. Institut du Thorax Curie—Institut Montsouris, Paris, France. [Raymond E] Groupe Hospitalier Saint-Joseph, Paris, France. [Martini JF] Pfizer Inc, San Diego, CA. [Galbraith S] AstraZeneca Plc, Cambridge, United Kingdom. [Felip E, Tabernero J] Vall d'Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. UVic-UCC, Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
2022-10-26T10:16:26Z
2022-10-26T10:16:26Z
2022-09-15
Terapias adyuvantes; Cáncer de pulmón; Pronóstico
Teràpies adjuvants; Càncer de pulmó; Pronòstic
Adjuvant therapies; Lung cancer; Prognosis
PURPOSE The prognosis of patients with non–small-cell lung cancer (NSCLC), traditionally determined by anatomic histology and TNM staging, neglects the biological features of the tumor that may be important in determining patient outcome and guiding therapeutic interventions. Identifying patients with NSCLC at increased risk of recurrence after curative-intent surgery remains an important unmet need so that known effective adjuvant treatments can be offered to those at highest risk of recurrence. METHODS Relative gene expression level in the primary tumor and normal bronchial tissues was used to retrospectively assess their association with disease-free survival (DFS) in a cohort of 120 patients with NSCLC who underwent curative-intent surgery. RESULTS Low versus high Digital Display Precision Predictor (DDPP) score (a measure of relative gene expression) was significantly associated with shorter DFS (highest recurrence risk; P = .006) in all patients and in patients with TNM stages 1-2 (P = .00051; n = 83). For patients with stages 1-2 and low DDPP score (n = 29), adjuvant chemotherapy was associated with improved DFS (P = .0041). High co-overexpression of CTLA-4, PD-L1, and ICOS in normal lung (28 of 120 patients) was also significantly associated with decreased DFS (P = .0013), suggesting an immune tolerance to tumor neoantigens in some patients. Patients with DDPP low and immunotolerant normal tissue had the shortest DFS (P = 2.12E–11). CONCLUSION TNM stage, DDPP score, and immune competence status of normal lung are independent prognostic factors in multivariate analysis. Our findings open new avenues for prospective prognostic assessment and treatment assignment on the basis of transcriptomic profiling of tumor and normal lung tissue in patients with NSCLC.
Article
Published version
English
Pulmons - Càncer - Tractament; Transcriptomes; Pulmons - Càncer - Recaiguda; DISEASES::Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms::Bronchial Neoplasms::Carcinoma, Bronchogenic::Carcinoma, Non-Small-Cell Lung; PHENOMENA AND PROCESSES::Genetic Phenomena::Gene Expression::Transcription, Genetic::Genetic Phenomena::Transcriptome; DISEASES::Neoplasms::Neoplastic Processes::Neoplasm Recurrence, Local; ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias torácicas::neoplasias del tracto respiratorio::neoplasias pulmonares::neoplasias de los bronquios::carcinoma broncogénico::carcinoma de pulmón de células no pequeñas; FENÓMENOS Y PROCESOS::fenómenos genéticos::expresión génica::transcripción genética::fenómenos genéticos::transcriptoma; ENFERMEDADES::neoplasias::procesos neoplásicos::recurrencia neoplásica local
American Society of Clinical Oncology
JCO Precision Oncology;6
https://doi.org/10.1200/PO.22.00072
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
Articles científics - HVH [3440]
