TY - JOUR
T1 - Impact of somatic mutations on prognosis in resected non-small-cell lung cancer
T2 - The Japan Molecular Epidemiology for lung cancer study
AU - Tamiya, Akihiro
AU - Koh, Yasuhiro
AU - Isa, Shun ichi
AU - Kubo, Akihito
AU - Ando, Masahiko
AU - Saka, Hideo
AU - Yoshimoto, Naoki
AU - Takeo, Sadanori
AU - Adachi, Hirofumi
AU - Tagawa, Tsutomu
AU - Kawashima, Osamu
AU - Yamashita, Motohiro
AU - Kataoka, Kazuhiko
AU - Takenoyama, Mitsuhiro
AU - Takeuchi, Yukiyasu
AU - Watanabe, Katsuya
AU - Matsumura, Akihide
AU - Kawaguchi, Tomoya
N1 - Publisher Copyright:
© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
PY - 2020/4/1
Y1 - 2020/4/1
N2 - Background: To report the follow up data and clinical outcomes of the JME study (UMIN 000008177), a prospective, multicenter, molecular epidemiology examination of 876 surgically resected non-small-cell lung cancer (NSCLC) cases, and the impact of somatic mutations (72 cancer-associated genes) on recurrence-free survival (RFS) and overall survival (OS). Methods: Patients were enrolled between July 2012 and December 2013, with follow up to 30th November 2017. A Cox proportional hazards model was used to assess the impact of gene mutations on RFS and OS, considering sex, smoking history, age, stage, histology, EGFR, KRAS, TP53, and number of coexisting mutations. Results: Of 876 patients, 172 had ≥2 somatic mutations. Median follow-up was 48.4 months. On multivariate analysis, number of coexisting mutations (≥2 vs 0 or 1, HR = 2.012, 95% CI: 1.488-2.695), age (≥70 vs <70 years, HR = 1.583, 95% CI: 1.229-2.049), gender (male vs female, HR = 1.503, 95% CI: 1.045-2.170) and pathological stage (II vs I, HR = 3.386, 95% CI: 2.447-4.646; ≥III vs I, HR = 6.307, 95% CI: 4.680-8.476) were significantly associated with RFS, while EGFR mutation (yes vs no, HR = 0.482, 95% CI: 0.309-0.736), number of coexisting mutations (≥2 vs 0 or 1, HR = 1.695, 95% CI: 1.143-2.467), age (≥70 vs <70 years, HR = 1.932, 95% CI: 1.385-2.726), and pathological stage (II vs I, HR = 2.209, 95% CI: 1.431-3.347; ≥III vs I, HR = 5.286, 95% CI: 3.682-7.566) were also significant for OS. Conclusion: A smaller number of coexisting mutations, earlier stage, and younger age were associated with longer RFS and OS, while EGFR mutations were significantly associated with improved OS.
AB - Background: To report the follow up data and clinical outcomes of the JME study (UMIN 000008177), a prospective, multicenter, molecular epidemiology examination of 876 surgically resected non-small-cell lung cancer (NSCLC) cases, and the impact of somatic mutations (72 cancer-associated genes) on recurrence-free survival (RFS) and overall survival (OS). Methods: Patients were enrolled between July 2012 and December 2013, with follow up to 30th November 2017. A Cox proportional hazards model was used to assess the impact of gene mutations on RFS and OS, considering sex, smoking history, age, stage, histology, EGFR, KRAS, TP53, and number of coexisting mutations. Results: Of 876 patients, 172 had ≥2 somatic mutations. Median follow-up was 48.4 months. On multivariate analysis, number of coexisting mutations (≥2 vs 0 or 1, HR = 2.012, 95% CI: 1.488-2.695), age (≥70 vs <70 years, HR = 1.583, 95% CI: 1.229-2.049), gender (male vs female, HR = 1.503, 95% CI: 1.045-2.170) and pathological stage (II vs I, HR = 3.386, 95% CI: 2.447-4.646; ≥III vs I, HR = 6.307, 95% CI: 4.680-8.476) were significantly associated with RFS, while EGFR mutation (yes vs no, HR = 0.482, 95% CI: 0.309-0.736), number of coexisting mutations (≥2 vs 0 or 1, HR = 1.695, 95% CI: 1.143-2.467), age (≥70 vs <70 years, HR = 1.932, 95% CI: 1.385-2.726), and pathological stage (II vs I, HR = 2.209, 95% CI: 1.431-3.347; ≥III vs I, HR = 5.286, 95% CI: 3.682-7.566) were also significant for OS. Conclusion: A smaller number of coexisting mutations, earlier stage, and younger age were associated with longer RFS and OS, while EGFR mutations were significantly associated with improved OS.
KW - next-generation sequencing
KW - non-small cell lung cancer
KW - overall survival
KW - recurrence free survival
KW - somatic mutation
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U2 - 10.1002/cam4.2897
DO - 10.1002/cam4.2897
M3 - Article
C2 - 32022477
AN - SCOPUS:85079055806
SN - 2045-7634
VL - 9
SP - 2343
EP - 2351
JO - Cancer Medicine
JF - Cancer Medicine
IS - 7
ER -