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Prognostic value of tumor mutations in radically treated locally advanced non-small cell lung cancer patients

2017; Impact Journals LLC; Volume: 8; Issue: 15 Linguagem: Inglês

10.18632/oncotarget.15966

1949-2553

A. Boros, Ludovic Lacroix, Benjamin Lacas, Julien Adam, Jean‐Pierre Pignon, Caroline Caramella, David Planchard, Vincent de Montpréville, Éric Deutsch, Antonin Lévy, Benjamin Besse, C. Le Péchoux,

Lung Cancer Research Studies

// Angela Boros 1 , Ludovic Lacroix 2 , Benjamin Lacas 3, 8, 10 , Julien Adam 2 , Jean-Pierre Pignon 3, 8, 10 , Caroline Caramella 4 , David Planchard 5 , Vincent de Montpreville 6 , Eric Deutsch 1, 7, 9 , Antonin Levy 1 , Benjamin Besse 5, 7 , Cécile Le Pechoux 1 1 Radiation Oncology Department, Gustave Roussy, Villejuif, France 2 Biopathology Department, Gustave Roussy, Villejuif, France 3 Biostatistics and Epidemiolgy Unit, Villejuif, France 4 Imaging Department, Gustave Roussy, Villejuif, France 5 Medical Oncology Department, Gustave Roussy, Villejuif, France 6 Pathology Department, Marie Lannelongue, Le Plessis Robinson, France 7 Paris-Sud University, DHU TORINO, Paris, France 8 Paris-Saclay University, Paris, France 9 INSERM U1030, Villejuif, France 10 INSERM U1018, Villejuif, France Correspondence to: Benjamin Besse, email: Benjamin.BESSE@gustaveroussy.fr Keywords: locally advanced, non-small cell lung cancer, mutation, prognostic, chemotherapy Received: July 04, 2016 Accepted: February 15, 2017 Published: March 07, 2017 ABSTRACT Introduction: Chemo-radiation is standard treatment in locally advanced non-small cell lung cancers (NSCLC). The prognostic value of mutations has been poorly explored in this population. Results: Clinical data were collected from 190 patients and mutational profiles were obtained in 78 of them; 58 (74%) were males, 31 (40%) current smokers, 47/31 stage IIIA/IIIB and 40 (51%) adenocarcinoma. The following mutations were identified: EGFR 12% (9/78), KRAS 15% (12/78), BRAF 5% (3/65), PI3KCA 2% (1/57), NRAS 3% (1/32), and ALK+ (FISH) 4% (2/51). HER2 was not detected. Median follow-up was 3.1 years. Overall survival was evaluated by group; no significant differences were identified in median overall survival ( p = 0.21), with 29.4 months for the EGFR/ALK group ( n = 11), 12.8 months for other mutations ( n = 17), and 23.4 months for wild-type ( n = 50). The EGFR/ALK and other mutations groups had poorer median progression-free survival (9.6 and 6.0 months) compared to the wild-type group (12.0 months; multivariate hazard ratio 2.0 [95% CI, 0.9–4.2] and 2.8 [95% CI, 1.5–5.2] respectively, p = 0.003). Materials and Methods: We retrospectively reviewed all patients receiving radical treatment for locally advanced NSCLC in a single institution between January 2002 and June 2013. Next generation sequencing was performed on DNA from paraffin-embedded tissue. ALK rearrangements were detected by immunohistochemistry and/or FISH. Mutational prognostic value for Kaplan-Meier survival parameters was determined by log-rank tests and Cox proportional hazards models. Conclusions: Selected gene alterations may be associated with poorer progression-free survival in locally advanced radically treated NSCLC and their prognostic and/or predictive value merits further evaluation in a larger population.