Thomas Klikovits1, Zoltán Lohinai2, Katalin Fábián3, Márton Gyulai4, Mária Szilasi5, Judit Varga6, Erika Baranya7, Orsolya Pipek8, István Csabai9, Zoltán Szállási10, József Tímár11, Mir Alireza Hoda12, Viktoria Laszlo13, Balázs Hegedűs14, Ferenc Renyi-Vamos15, Walter Klepetko16, Gyula Ostoros17, Balázs Döme18, Judit Moldvay19. 1. Division of Thoracic Surgery, Medical University of Vienna, Austria. Electronic address: thomas.klikovits@meduniwien.ac.at. 2. National Korányi Institute of Pulmonology, Budapest, Hungary. Electronic address: lohinaiz@gmail.com. 3. Department of Pulmonology, Semmelweis University, Budapest, Hungary. Electronic address: drfabian.katalin@gmail.com. 4. County Hospital of Pulmonology, Törökbálint, Hungary. Electronic address: marton.gyulai@gmail.com. 5. Department of Pulmonology, University of Debrecen Clinical Centre, Debrecen, Hungary. Electronic address: mszilasi@dote.hu. 6. Department of Pulmonology and Thoracic Oncology, Szent György Hospital, Székesfehérvár, Hungary. Electronic address: vjudit@yahoo.com. 7. National Korányi Institute of Pulmonology, Budapest, Hungary. Electronic address: bgoldaera@gmail.com. 8. Department of Physics of Complex Systems, Eötvös Loránd University, Budapest, Hungary. Electronic address: porsika@gmail.com. 9. Department of Physics of Complex Systems, Eötvös Loránd University, Budapest, Hungary. Electronic address: csabai@complex.elte.hu. 10. Children's Hospital Informatics Program at the Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Harvard Medical School, US; Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Denmark; MTA-SE NAP, Brain Metastasis Research Group, Hungarian Academy of Sciences, 2nd Department of Pathology, Semmelweis University, Budapest, Hungary. Electronic address: zoltan.szallasi@childrens.harvard.edu. 11. MTA-SE NAP, Brain Metastasis Research Group, Hungarian Academy of Sciences, 2nd Department of Pathology, Semmelweis University, Budapest, Hungary. Electronic address: jtimar@gmail.com. 12. Division of Thoracic Surgery, Medical University of Vienna, Austria. Electronic address: mir.hoda@meduniwien.ac.at. 13. Division of Thoracic Surgery, Medical University of Vienna, Austria; Department of Biomedical Imaging and Image-guided Therapy, Division of Molecular and Gender Imaging, Medical University of Vienna, Austria. Electronic address: viktoria.laszlo@meduniwien.ac.at. 14. Department of Thoracic Surgery, Ruhrlandklinik, University Hospital Essen, Germany. Electronic address: balazs.hegedues@rlk.uk-essen.de. 15. Department of Thoracic Surgery, National Institute of Oncology-Semmelweis University, Budapest, Hungary. Electronic address: ferenc.renyi-vamos@meduniwien.ac.at. 16. Division of Thoracic Surgery, Medical University of Vienna, Austria. Electronic address: walter.klepetko@meduniwien.ac.at. 17. National Korányi Institute of Pulmonology, Budapest, Hungary. Electronic address: drostorosgyula@gmail.com. 18. Division of Thoracic Surgery, Medical University of Vienna, Austria; National Korányi Institute of Pulmonology, Budapest, Hungary; Department of Thoracic Surgery, National Institute of Oncology-Semmelweis University, Budapest, Hungary. Electronic address: balazs.dome@meduniwien.ac.at. 19. National Korányi Institute of Pulmonology, Budapest, Hungary. Electronic address: drmoldvay@hotmail.com.
Abstract
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.
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.