Hyo Jae Kang1, Hyo-Jeong Lim2, Jong Sun Park2, Young-Jae Cho2, Ho-Il Yoon2, Jin-Haeng Chung3, Jae Ho Lee2, Choon-Taek Lee4. 1. Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam 463-707, South Korea. 2. Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam 463-707, South Korea; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea. 3. Department of Pathology, Seoul National University Bundang Hospital, Seongnam 463-707, South Korea. 4. Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam 463-707, South Korea; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea. Electronic address: ctlee@snu.ac.kr.
Abstract
BACKGROUND: The discovery of the chromosomal fusion product of anaplastic lymphoma kinase (ALK) with echinoderm microtubule-associated protein-like 4 (EML4) (EML4-ALK) has changed the treatment paradigm of lung cancer. In this study, we analysed the clinical characteristics, including bronchoscopic findings, of patients with EML4-ALK-positive adenocarcinoma and compared them with those of EGFR mutation-positive patients. MATERIALS AND METHODS: In this retrospective cohort study, the clinical characteristics and bronchoscopic findings of patients with ALK fusion-positive lung cancers were compared to patients with EGFR-mutant lung cancers. RESULTS: Among the 440 patients with adenocarcinoma of lung screened for this study, 46 (10.4%) harboured the EML4-ALK fusion, 90 (20.4%) harboured an activating EGFR mutation, and all had adenocarcinoma. In univariate analysis, ALK-positive patients were significantly younger than EGFR-positive patients (p = 0.004) and were more commonly male (p = 0.021). An initial status of stage IV metastatic cancer was more frequently noted in EML4-ALK-positive patients (p = 0.012), with initial brain metastasis frequently observed (p = 0.007). Compared with EGFR-positive patients, EML4-ALK-positive patients were significantly more likely to have positive bronchoscopic findings, which suggested a more centralized origin (p = 0.001). EML4-ALK patients also had significantly more positive bronchoscopic findings and were more commonly male in multivariate analysis. CONCLUSIONS: The EML4-ALK fusion defines a new molecular subset of NSCLC that has distinct clinical and bronchoscopic findings suggesting more proximal origin when compared to tumours harbouring EGFR mutations.
BACKGROUND: The discovery of the chromosomal fusion product of anaplastic lymphoma kinase (ALK) with echinoderm microtubule-associated protein-like 4 (EML4) (EML4-ALK) has changed the treatment paradigm of lung cancer. In this study, we analysed the clinical characteristics, including bronchoscopic findings, of patients with EML4-ALK-positive adenocarcinoma and compared them with those of EGFR mutation-positive patients. MATERIALS AND METHODS: In this retrospective cohort study, the clinical characteristics and bronchoscopic findings of patients with ALK fusion-positive lung cancers were compared to patients with EGFR-mutant lung cancers. RESULTS: Among the 440 patients with adenocarcinoma of lung screened for this study, 46 (10.4%) harboured the EML4-ALK fusion, 90 (20.4%) harboured an activating EGFR mutation, and all had adenocarcinoma. In univariate analysis, ALK-positive patients were significantly younger than EGFR-positive patients (p = 0.004) and were more commonly male (p = 0.021). An initial status of stage IV metastatic cancer was more frequently noted in EML4-ALK-positive patients (p = 0.012), with initial brain metastasis frequently observed (p = 0.007). Compared with EGFR-positive patients, EML4-ALK-positive patients were significantly more likely to have positive bronchoscopic findings, which suggested a more centralized origin (p = 0.001). EML4-ALKpatients also had significantly more positive bronchoscopic findings and were more commonly male in multivariate analysis. CONCLUSIONS: The EML4-ALK fusion defines a new molecular subset of NSCLC that has distinct clinical and bronchoscopic findings suggesting more proximal origin when compared to tumours harbouring EGFR mutations.
Authors: Elsa Davidsson; Nicola Murgia; Cristian Ortiz-Villalón; Emil Wiklundh; Magnus Sköld; Karl Gustav Kölbeck; Giovanni Ferrara Journal: Multidiscip Respir Med Date: 2017-05-29