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

被引:11
作者
Boros, Angela [1 ]
Lacroix, Ludovic [2 ]
Lacas, Benjamin [3 ,8 ,10 ]
Adam, Julien [2 ]
Pignon, Jean-Pierre [3 ,8 ,10 ]
Caramella, Caroline [4 ]
Planchard, David [5 ]
de Montpreville, Vincent [6 ]
Deutsch, Eric [1 ,7 ,9 ]
Levy, Antonin [1 ]
Besse, Benjamin [5 ,7 ]
Le Pechoux, Cecile [1 ]
机构
[1] Gustave Roussy, Radiat Oncol Dept, Villejuif, France
[2] Gustave Roussy, Biopathol Dept, Villejuif, France
[3] Biostat & Epidemiolgy Unit, Villejuif, France
[4] Gustave Roussy, Imaging Dept, Villejuif, France
[5] Gustave Roussy, Med Oncol Dept, Villejuif, France
[6] Marie Lannelongue, Pathol Dept, Le Plessis Robinson, France
[7] Paris Sud Univ, DHU TORINO, Paris, France
[8] Paris Saclay Univ, Paris, France
[9] INSERM, U1030, Villejuif, France
[10] INSERM, U1018, Villejuif, France
关键词
locally advanced; non-small cell lung cancer; mutation; prognostic; chemotherapy; GROWTH-FACTOR RECEPTOR; RADIATION-THERAPY; EGFR MUTATIONS; PHASE-III; THORACIC ONCOLOGY; PROGRESSION-FREE; POOLED ANALYSIS; FREE SURVIVAL; FOLLOW-UP; CHEMOTHERAPY;
D O I
10.18632/oncotarget.15966
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:25189 / 25199
页数:11
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