Clinical and prognostic implications of ALK and ROS1 rearrangements in never-smokers with surgically resected lung adenocarcinoma

Min Hwan Kim, Hyo Sup Shim, Dae Ryong Kang, Ji Ye Jung, Chang Young Lee, Dae Joon Kim, Jin Gu Lee, Mi Kyung Bae, Hye Ryun Kim, Sun Min Lim, Eun Young Kim, Ji Soo Park, Kyung Young Chung, Hyun Jung Kim, Joo Hang Kim, ByoungChul Cho

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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.

Original languageEnglish
Pages (from-to)389-395
Number of pages7
JournalLung Cancer
Volume83
Issue number3
DOIs
Publication statusPublished - 2014 Mar 1

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Oncogenes
Oncogene Fusion
Epidermal Growth Factor Receptor
Disease-Free Survival
Mutation
Adjuvant Chemotherapy
Fluorescence In Situ Hybridization
Sarcoma
anaplastic lymphoma kinase
Adenocarcinoma of lung
Multivariate Analysis
Confidence Intervals
Recurrence
Genes
Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

Cite this

Kim, Min Hwan ; Shim, Hyo Sup ; Kang, Dae Ryong ; Jung, Ji Ye ; Lee, Chang Young ; Kim, Dae Joon ; Lee, Jin Gu ; Bae, Mi Kyung ; Kim, Hye Ryun ; Lim, Sun Min ; Kim, Eun Young ; Park, Ji Soo ; Chung, Kyung Young ; Kim, Hyun Jung ; Kim, Joo Hang ; Cho, ByoungChul. / Clinical and prognostic implications of ALK and ROS1 rearrangements in never-smokers with surgically resected lung adenocarcinoma. In: Lung Cancer. 2014 ; Vol. 83, No. 3. pp. 389-395.
@article{d474608ffa274fd8a597929d5a3f2882,
title = "Clinical and prognostic implications of ALK and ROS1 rearrangements in never-smokers with surgically resected lung adenocarcinoma",
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.",
author = "Kim, {Min Hwan} and Shim, {Hyo Sup} and Kang, {Dae Ryong} and Jung, {Ji Ye} and Lee, {Chang Young} and Kim, {Dae Joon} and Lee, {Jin Gu} and Bae, {Mi Kyung} and Kim, {Hye Ryun} and Lim, {Sun Min} and Kim, {Eun Young} and Park, {Ji Soo} and Chung, {Kyung Young} and Kim, {Hyun Jung} and Kim, {Joo Hang} and ByoungChul Cho",
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Kim, MH, Shim, HS, Kang, DR, Jung, JY, Lee, CY, Kim, DJ, Lee, JG, Bae, MK, Kim, HR, Lim, SM, Kim, EY, Park, JS, Chung, KY, Kim, HJ, Kim, JH & Cho, B 2014, 'Clinical and prognostic implications of ALK and ROS1 rearrangements in never-smokers with surgically resected lung adenocarcinoma', Lung Cancer, vol. 83, no. 3, pp. 389-395. https://doi.org/10.1016/j.lungcan.2014.01.003

Clinical and prognostic implications of ALK and ROS1 rearrangements in never-smokers with surgically resected lung adenocarcinoma. / Kim, Min Hwan; Shim, Hyo Sup; Kang, Dae Ryong; Jung, Ji Ye; Lee, Chang Young; Kim, Dae Joon; Lee, Jin Gu; Bae, Mi Kyung; Kim, Hye Ryun; Lim, Sun Min; Kim, Eun Young; Park, Ji Soo; Chung, Kyung Young; Kim, Hyun Jung; Kim, Joo Hang; Cho, ByoungChul.

In: Lung Cancer, Vol. 83, No. 3, 01.03.2014, p. 389-395.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Clinical and prognostic implications of ALK and ROS1 rearrangements in never-smokers with surgically resected lung adenocarcinoma

AU - Kim, Min Hwan

AU - Shim, Hyo Sup

AU - Kang, Dae Ryong

AU - Jung, Ji Ye

AU - Lee, Chang Young

AU - Kim, Dae Joon

AU - Lee, Jin Gu

AU - Bae, Mi Kyung

AU - Kim, Hye Ryun

AU - Lim, Sun Min

AU - Kim, Eun Young

AU - Park, Ji Soo

AU - Chung, Kyung Young

AU - Kim, Hyun Jung

AU - Kim, Joo Hang

AU - Cho, ByoungChul

PY - 2014/3/1

Y1 - 2014/3/1

N2 - 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.

AB - 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.

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U2 - 10.1016/j.lungcan.2014.01.003

DO - 10.1016/j.lungcan.2014.01.003

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VL - 83

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EP - 395

JO - Lung Cancer

JF - Lung Cancer

SN - 0169-5002

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