New insights into the impact of primary lung adenocarcinoma location on metastatic sites and sequence: A multicenter cohort study

Thomas Klikovits, Zoltán Lohinai, Katalin Fábián, Márton Gyulai, Mária Szilasi, Judit Varga, Erika Baranya, Orsolya Pipek, I. Csabai, Zoltán Szállási, J. Tímár, Mir Alireza Hoda, Viktoria Laszlo, Balázs Hegedűs, Ferenc Renyi-Vamos, Walter Klepetko, G. Ostoros, B. Döme, Judit Moldvay

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2 Citations (Scopus)


Introduction: The presence of organ metastases is a major factor for unfavorable prognosis in lung adenocarcinoma (LADC). However, the influence of primary tumor location on metastatic sites and sequence has not been extensively analyzed. Methods: We performed a multicenter cohort study, evaluating clinicopathological data of 1126 Caucasian LADC patients, focusing on the distinct location of primary tumors and metastatic sites during disease progression. Results: Metastases to the lung (p < 0.001), pleura (p < 0.001) and adrenal glands (p < 0.001) occurred earlier during disease progression and central primary tumors were associated with early metastases (OR 1.43, p = 0.02). In secondary exploratory analysis we found that bone metastases were more frequent in patients with central tumors (OR 1.86, p = 0.017), whereas lung metastases in those with peripheral tumors (OR 1.35, p = 0.015). Central primary LADCs were associated with decreased median overall survival (vs. peripheral tumors, 10.2 vs. 22 months) both in univariate (HR 2.075, p = 0.001) and in multivariate (HR 1.558, p < 0.001) analyses and independent from stage and T factor. By subsequent analysis, we found that bone metastases tend to appear together with adrenal and liver metastases, and adrenal with skin, and pleural with pericardial metastases more frequently than expected if metastatic events occurred independently. Conclusion: This comprehensive large cohort analysis demonstrates metastatic site- and sequence-specific variations in patients with LADC. Central LADC is associated with early metastatic disease, bone involvement and, consequently, decreased survival.

Original languageEnglish
Pages (from-to)139-148
Number of pages10
JournalLung Cancer
Publication statusPublished - Dec 1 2018



  • Lung adenocarcinoma
  • Metastases
  • Metastatic pattern
  • Metastatic sites
  • Primary tumor location
  • Survival

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

Cite this

Klikovits, T., Lohinai, Z., Fábián, K., Gyulai, M., Szilasi, M., Varga, J., Baranya, E., Pipek, O., Csabai, I., Szállási, Z., Tímár, J., Hoda, M. A., Laszlo, V., Hegedűs, B., Renyi-Vamos, F., Klepetko, W., Ostoros, G., Döme, B., & Moldvay, J. (2018). New insights into the impact of primary lung adenocarcinoma location on metastatic sites and sequence: A multicenter cohort study. Lung Cancer, 126, 139-148.