Vasileios K Kavouridis1,2, Maya Harary3,4, Alexander F C Hulsbergen3,4, Yu T Lo3,4, David A Reardon4,5, Ayal A Aizer4,6, J Bryan Iorgulescu3,4,5,6,7, Timothy R Smith3,4. 1. Department of Neurosurgery, Computational Neuroscience Outcomes Center, Brigham and Women's Hospital, 60 Fenwood Rd., 4th Floor, Boston, MA, 02115, USA. vkavouridis@bwh.harvard.edu. 2. Harvard Medical School, Boston, MA, USA. vkavouridis@bwh.harvard.edu. 3. Department of Neurosurgery, Computational Neuroscience Outcomes Center, Brigham and Women's Hospital, 60 Fenwood Rd., 4th Floor, Boston, MA, 02115, USA. 4. Harvard Medical School, Boston, MA, USA. 5. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. 6. Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Boston, MA, USA. 7. Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
Abstract
PURPOSE: While surgery and radiation remain the mainstays of therapy for all patients with brain metastases (BM), the management is moving to a more individualized approach based on the underlying tumor. We sought to identify prognostic factors of both intracranial progression (IC-PFS) and overall survival (OS) in a surgical cohort. METHODS: We retrospectively reviewed the records of 1015 patients treated surgically for BM at Brigham and Women's Hospital (2007-2017). Kaplan-Meier curves were used for OS and IC-PFS and Cox proportional hazards models were built to assess for predictive factors. RESULTS: Common origins were lung (43.9%), breast (14.4%), and melanoma (13.8%). Median OS for the cohort was 15.4 months (95% confidence interval [95%CI] 14.1-17.1). Breast cancer (22.1 months, 95%CI 17.8-30.3) and colorectal cancer (10.6 months, 95%CI 7.2-15.4) had the longest and shortest OS, respectively. On multivariable Cox regression, significant prognostic factors of shorter OS were age (HR 1.01, 95%CI 1.01-1.02), number of lesions (HR 1.56, 95%CI 1.28-1.89), extracranial spread at BM diagnosis (HR 1.26, 95%CI 1.05-1.52), and KPS (HR 0.98, 95%CI 0.98-0.99). Regarding molecular factors, all driver mutations in lung adenocarcinoma had a favorable effect (EGFR, HR 0.53, 95%CI 0.31-0.89; ALK, HR 0.28, 95%CI 0.12-0.66; KRAS, HR 0.65, 95%CI 0.47-0.92), triple negative status predicted poor prognosis in breast adenocarcinoma (HR 2.04, 95%CI 1.13-3.69), while no effect of BRAF/NRAS mutations was demonstrated in melanoma BMs. CONCLUSIONS: Our results corroborate the role of tumor origin and systemic as well as intracranial spread in OS. Heterogeneity within histologies was further explained by molecular alterations.
PURPOSE: While surgery and radiation remain the mainstays of therapy for all patients with brain metastases (BM), the management is moving to a more individualized approach based on the underlying tumor. We sought to identify prognostic factors of both intracranial progression (IC-PFS) and overall survival (OS) in a surgical cohort. METHODS: We retrospectively reviewed the records of 1015 patients treated surgically for BM at Brigham and Women's Hospital (2007-2017). Kaplan-Meier curves were used for OS and IC-PFS and Cox proportional hazards models were built to assess for predictive factors. RESULTS: Common origins were lung (43.9%), breast (14.4%), and melanoma (13.8%). Median OS for the cohort was 15.4 months (95% confidence interval [95%CI] 14.1-17.1). Breast cancer (22.1 months, 95%CI 17.8-30.3) and colorectal cancer (10.6 months, 95%CI 7.2-15.4) had the longest and shortest OS, respectively. On multivariable Cox regression, significant prognostic factors of shorter OS were age (HR 1.01, 95%CI 1.01-1.02), number of lesions (HR 1.56, 95%CI 1.28-1.89), extracranial spread at BM diagnosis (HR 1.26, 95%CI 1.05-1.52), and KPS (HR 0.98, 95%CI 0.98-0.99). Regarding molecular factors, all driver mutations in lung adenocarcinoma had a favorable effect (EGFR, HR 0.53, 95%CI 0.31-0.89; ALK, HR 0.28, 95%CI 0.12-0.66; KRAS, HR 0.65, 95%CI 0.47-0.92), triple negative status predicted poor prognosis in breast adenocarcinoma (HR 2.04, 95%CI 1.13-3.69), while no effect of BRAF/NRAS mutations was demonstrated in melanoma BMs. CONCLUSIONS: Our results corroborate the role of tumor origin and systemic as well as intracranial spread in OS. Heterogeneity within histologies was further explained by molecular alterations.
Authors: Nayan Lamba; Rachel Brigell Kearney; Paul J Catalano; Michael J Hassett; Patrick Y Wen; Daphne A Haas-Kogan; Ayal A Aizer Journal: Neuro Oncol Date: 2021-04-12 Impact factor: 12.300
Authors: Matan Ben-Zion Berliner; Rinat Yerushalmi; Inbar Lavie; Alexandra Benouaich-Amiel; Daliah Tsoref; Daniel Hendler; Hadar Goldvaser; Michal Sarfaty; Ofer Rotem; Olga Ulitsky; Tali Siegal; Victoria Neiman; Shlomit Yust-Katz Journal: Breast Cancer Res Treat Date: 2020-10-10 Impact factor: 4.872
Authors: Johannes Kerschbaumer; Aleksandrs Krigers; Matthias Demetz; Daniel Pinggera; Julia Klingenschmid; Nadine Pichler; Claudius Thomé; Christian F Freyschlag Journal: J Neurooncol Date: 2022-04-13 Impact factor: 4.506
Authors: Martin Proescholdt; Stephanie T Jünger; Petra Schödel; Karl-Michael Schebesch; Christian Doenitz; Tobias Pukrop; Julius Höhne; Nils-Ole Schmidt; Martin Kocher; Holger Schulz; Maximilian Ruge; Kevin König; Roland Goldbrunner; Stefan Grau Journal: Brain Sci Date: 2021-01-18
Authors: Muriel Heimann; Niklas Schäfer; Christian Bode; Valeri Borger; Lars Eichhorn; Frank A Giordano; Erdem Güresir; Andreas H Jacobs; Yon-Dschun Ko; Jennifer Landsberg; Felix Lehmann; Alexander Radbruch; Christina Schaub; Katjana S Schwab; Johannes Weller; Ulrich Herrlinger; Hartmut Vatter; Patrick Schuss; Matthias Schneider Journal: Front Oncol Date: 2021-07-26 Impact factor: 6.244
Authors: Erica Shen; Amanda E D Van Swearingen; Meghan J Price; Ketan Bulsara; Roeland G W Verhaak; César Baëta; Brice D Painter; Zachary J Reitman; April K S Salama; Jeffrey M Clarke; Carey K Anders; Peter E Fecci; C Rory Goodwin; Kyle M Walsh Journal: Front Oncol Date: 2022-01-25 Impact factor: 6.244
Authors: Alexander F C Hulsbergen; Abdullah M Abunimer; Fidelia Ida; Vasileios K Kavouridis; Logan D Cho; Ishaan A Tewarie; Rania A Mekary; Philippe Schucht; John G Phillips; Joost J C Verhoeff; Marike L D Broekman; Timothy R Smith Journal: Neuro Oncol Date: 2021-12-01 Impact factor: 13.029