Oncotarget

Research Papers:

Overall survival in patients with lung adenocarcinoma harboring “niche” mutations: an observational study

Beatrice Aramini _, Federico Banchelli, Stefania Bettelli, Samantha Manfredini, Roberto D’Amico, Valentina Masciale, Massimo Pinelli, Margherita Moretti, Alessandro Stefani, Federica Bertolini, Massimo Dominici, Uliano Morandi and Antonino Maiorana

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Abstract

Beatrice Aramini1, Federico Banchelli3, Stefania Bettelli4, Samantha Manfredini4, Roberto D’Amico3, Valentina Masciale1, Massimo Pinelli5, Margherita Moretti1, Alessandro Stefani1, Federica Bertolini2, Massimo Dominici2, Uliano Morandi1 and Antonino Maiorana4

1 Division of Thoracic Surgery, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy

2 Division of Oncology, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy

3 Center of Statistics, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy

4 Institute of Pathology, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy

5 Division of Plastic Surgery, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy

Correspondence to:

Beatrice Aramini,email: beatrice.aramini@unimore.it

Keywords: somatic mutations; non-small cell lung cancer (NSCLC); lung cancer treatment; overall survival; target therapy

Received: November 14, 2019     Accepted: January 21, 2020     Published: February 04, 2020

ABSTRACT

Objective: In addition to the most common somatic lung cancer mutations (i. e., KRAS and EGFR mutations), other genes may harbor mutations that could be relevant for lung cancer. We defined BRAF, c-MET, DDR2, HER2, MAP2K1, NRAS, PIK3CA, and RET mutations as “niche” mutations and analyzed. The aim of this retrospective cohort study was to assess the differences in the overall survival (OS) of patients with lung adenocarcinoma harboring niche somatic mutations.

Results: Data were gathered for 252 patients. Mutations were observed in all genes studied, except c-MET, DDR2, MAP2K1, and RET. The multivariable analysis showed that 1) niche mutations had a higher mortality than EGFR mutations (HR = 2.3; 95% CI = 1.2–4.4; p = 0.009); 2) KRAS mutations had a higher mortality than EGFR mutations (HR = 2.5; 95% CI = 1.4–4.5; p = 0.003); 3) niche mutations presented a similar mortality to KRAS mutations (HR = 0.9; 95% CI = 0.6–1.5; p = 0.797).

Methods: Three cohorts of mutations were selected from patients with lung adenocarcinoma and their OS was compared. Mutations that were searched for, were 1) BRAF, c-MET, DDR2, HER2, MAP2K1, NRAS, PIK3CA, and RET; 2) K-RAS; and 3) EGFR. Differences in OS between these three cohorts were assessed by means of a multivariable Cox model that adjusted for age, sex, smoking habits, clinical stages, and treatments.

Conclusions: Niche mutations exhibited an increased risk of death when compared with EGFR mutations and a similar risk of death when compared with KRAS mutations.


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