Min Hwan Kim1, Hyo Sup Shim2, Dae Ryong Kang3, Ji Ye Jung4, Chang Young Lee5, Dae Joon Kim5, Jin Gu Lee5, Mi Kyung Bae5, Hye Ryun Kim1, Sun Min Lim1, Eun Young Kim4, Ji Soo Park1, Kyung Young Chung5, Hyun-Jung Kim6, Joo Hang Kim1, Byoung Chul Cho7. 1. Yonsei Cancer Center, Division of Medical Oncology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea. 2. Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea. 3. Biostatistics Collaboration Unit, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea. 4. Division of Pulmonology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea. 5. Department of Thoracic and Cardiovascular Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea. 6. JEUK Institute for Cancer Research, JEUK Co., Ltd., Gumi-City, Kyungbuk, Republic of Korea. 7. Yonsei Cancer Center, Division of Medical Oncology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: cbc1971@yuhs.ac.
Abstract
OBJECTIVES: The aim of this study is to evaluate the prevalence and prognostic significance of anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) rearrangement in never-smokers with surgically resected lung adenocarcinoma. METHODS: We retrospectively analyzed 162 consecutive never-smokers who underwent curative resection for stage IB to IIIA lung adenocarcinoma at a single institution. We concurrently analyzed mutations in the epidermal growth factor receptor (EGFR) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) genes, and investigated ALK rearrangements by fluorescence in situ hybridization assay. ROS1 rearrangement was also determined in all triple (EGFR/KRAS/ALK)-negative tumors. RESULTS: Of 162 never smokers with lung adenocarcinoma, 14 (8.6%) and 5 (3.1%) had ALK and ROS1 rearrangements, respectively. Nineteen of the 74 (25.7%) EGFR and KRAS mutation-negative patients were fusion-positive (ALK or ROS1 fusion). Fusion-positive patients tended to have shorter median disease-free survival (DFS) than fusion-negative patients (28.0 vs. 33.9 months; p=0.128). In multivariate analysis, fusion-positive patients had significantly poorer DFS than fusion-negative patients after adjustment for age, sex, T stage, N stage, and adjuvant chemotherapy use (p=0.022; hazard ratio, 2.11; 95% confidence interval, 1.19-4.30). The first recurrence sites were not significantly different between fusion-positive and fusion-negative patients in this study. CONCLUSION: This study shows significantly poorer DFS of ALK or ROS1 fusion-positive lung adenocarcinoma in never-smokers after curative surgery.
OBJECTIVES: The aim of this study is to evaluate the prevalence and prognostic significance of anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) rearrangement in never-smokers with surgically resected lung adenocarcinoma. METHODS: We retrospectively analyzed 162 consecutive never-smokers who underwent curative resection for stage IB to IIIA lung adenocarcinoma at a single institution. We concurrently analyzed mutations in the epidermal growth factor receptor (EGFR) and v-Ki-ras2 Kirsten ratsarcoma viral oncogene homolog (KRAS) genes, and investigated ALK rearrangements by fluorescence in situ hybridization assay. ROS1 rearrangement was also determined in all triple (EGFR/KRAS/ALK)-negative tumors. RESULTS: Of 162 never smokers with lung adenocarcinoma, 14 (8.6%) and 5 (3.1%) had ALK and ROS1 rearrangements, respectively. Nineteen of the 74 (25.7%) EGFR and KRAS mutation-negative patients were fusion-positive (ALK or ROS1 fusion). Fusion-positive patients tended to have shorter median disease-free survival (DFS) than fusion-negative patients (28.0 vs. 33.9 months; p=0.128). In multivariate analysis, fusion-positive patients had significantly poorer DFS than fusion-negative patients after adjustment for age, sex, T stage, N stage, and adjuvant chemotherapy use (p=0.022; hazard ratio, 2.11; 95% confidence interval, 1.19-4.30). The first recurrence sites were not significantly different between fusion-positive and fusion-negative patients in this study. CONCLUSION: This study shows significantly poorer DFS of ALK or ROS1 fusion-positive lung adenocarcinoma in never-smokers after curative surgery.
Authors: Francesco Facchinetti; Marcello Tiseo; Massimo Di Maio; Paolo Graziano; Emilio Bria; Giulio Rossi; Silvia Novello Journal: Transl Lung Cancer Res Date: 2016-06
Authors: Jamie E Chaft; Ibiayi Dagogo-Jack; Fernando C Santini; Juliana Eng; Beow Y Yeap; Benjamin Izar; Emily Chin; David R Jones; Mark G Kris; Alice T Shaw; Justin F Gainor Journal: Lung Cancer Date: 2018-05-22 Impact factor: 5.705