Clinicopathologic and genomic features associated with brain metastasis after resection of lung adenocarcinomaCentral MessagePerspective
Elizabeth G. Dunne, MD,
Cameron N. Fick, MD,
Brooke Mastrogiacomo, MS,
Kay See Tan, PhD,
Nicolas Toumbacaris, MSPH,
Stijn Vanstraelen, MD,
Gaetano Rocco, MD,
Jaime E. Chaft, MD,
Puneeth Iyengar, MD,
Daniel Gomez, MD,
Prasad S. Adusumilli, MD,
Bernard J. Park, MD,
James M. Isbell, MD,
Matthew J. Bott, MD,
Smita Sihag, MD,
Daniela Molena, MD,
James Huang, MD,
David R. Jones, MD
Affiliations
Elizabeth G. Dunne, MD
Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
Cameron N. Fick, MD
Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
Brooke Mastrogiacomo, MS
Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY; Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY
Kay See Tan, PhD
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY
Nicolas Toumbacaris, MSPH
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY
Stijn Vanstraelen, MD
Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
Gaetano Rocco, MD
Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY; Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY
Jaime E. Chaft, MD
Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
Puneeth Iyengar, MD
Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY
Daniel Gomez, MD
Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY
Prasad S. Adusumilli, MD
Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY; Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY
Bernard J. Park, MD
Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY; Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY
James M. Isbell, MD
Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY; Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY
Matthew J. Bott, MD
Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY; Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY
Smita Sihag, MD
Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY; Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY
Daniela Molena, MD
Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY; Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY
James Huang, MD
Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY; Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY
David R. Jones, MD
Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY; Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY; Address for reprints: David R. Jones, MD, Thoracic Surgery Service, Druckenmiller Chair of Lung Cancer Research, Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Ave, Box 7, New York, NY 10065.
Objective: To identify clinicopathologic and genomic features associated with brain metastasis after resection of lung adenocarcinoma (LUAD) and to evaluate survival after brain metastasis. Methods: Patients who underwent complete resection of stage I-IIIA LUAD between 2011 and 2020 were included. A subset of patients had broad-based panel next-generation sequencing performed on their tumors. Fine-Gray models for the development of brain metastasis were constructed, with death without brain metastasis as a competing risk. Results: A total of 2660 patients were included. The median duration of follow-up was 71 months (95% confidence interval [CI], 69-73 months). The cumulative incidence of brain metastasis at 10 years was 9.8%. Among patients who developed a brain metastasis, the median time from surgery to brain metastasis was 21 months (interquartile range, 10-42 months). Higher maximum standardized uptake value of the primary tumor, neoadjuvant therapy, lymphovascular invasion, and stage III disease were associated with the development of brain metastasis. Among patients who underwent next-generation sequencing, a multivariable analysis identified neoadjuvant therapy, pathologic stage, and TP53 mutations as associated with development of brain metastasis. The median survival after brain metastasis was 18 months (95% CI, 13-24 months). Better performance status, lack of extracranial metastasis, stereotactic radiosurgery, and targeted therapy were associated with better survival after brain metastasis. Conclusions: Brain metastasis is common after complete resection of LUAD and often occurs within 2 years. Markers of aggressive tumor biology, including higher maximum standardized uptake value, lymphovascular invasion, and TP53 mutations, and neoadjuvant therapy are associated with brain metastasis.