title: Survival but not brain metastasis response relates to lung cancer mutation status after radiosurgery.
abstract: We prospectively addressed whether EGFR and KRAS mutations, EML4-ALK, ROS1 and RET rearrangements, or wild-type (WT), affects radiosurgery outcomes and overall survival (OS) in non-small cell lung cancer (NSCLC) patients with brain metastases (BM). Of 326 patients with BM treated in 2012-2014 with Gamma Knife radiosurgery (GKRS), 112 NSCLC patients received GKRS as their initial intracranial treatment. OS, intracranial progression-free survival, and time to intracranial failure were determined. Univariate and multivariate analysis were performed to determine factors affecting OS. Toxicity of treatment was evaluated. Median follow-up was 9 months. Patients with EGFR mutant BM had improved survival compared to WT. Median time to development of BM was higher in EGFR mutant patients, but this difference was not significant (2.2 vs 0.9 months; p = 0.2). Median time to distant brain failure was independent of EGFR mutation status. Karnofsky performance status (KPS), non-squamous histopathology, targeted therapy, systemic disease control, EGFR mutation, and low tumor volume were predictive of increased OS on univariate analysis. KPS (p = 0.001) and non-squamous histopathology (p = 0.03) continued to be significant on multivariate analysis. Patients with EGFR mutant BM underwent salvage treatment more often than those without (p = 0.04). Treatment-related toxicity was no different in patients treated with GKRS combined with targeted therapies versus GKRS alone (5 vs 7%, p = 0.7). Patients with EGFR mutant BM had improved survival compared to a WT cohort. Intracranial disease control following radiosurgery was similar for all tumor subtypes. Radiosurgery is effective for BM and concurrent treatment with targeted therapy appears to be safe.
authors.affiliation: Department of Radiation Oncology, Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY, USA.
authors.forename: Samuel M
authors.initials: SM
authors.lastname: Shin
authors.affiliation: Department of Radiation Oncology, Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY, USA.
authors.forename: Benjamin T
authors.initials: BT
authors.lastname: Cooper
authors.affiliation: Division of Medical Oncology, Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY, USA.
authors.forename: Abraham
authors.initials: A
authors.lastname: Chachoua
authors.affiliation: Department of Radiation Oncology, Maimonides Cancer Center, Brooklyn, NY, USA.
authors.forename: James
authors.initials: J
authors.lastname: Butler
authors.affiliation: Department of Radiation Oncology, Maimonides Cancer Center, Brooklyn, NY, USA.
authors.forename: Bernadine
authors.initials: B
authors.lastname: Donahue
authors.affiliation: Department of Radiation Oncology, Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY, USA.
authors.forename: Joshua S
authors.initials: JS
authors.lastname: Silverman
authors.affiliation: Department of Neurosurgery, New York University Langone Medical Center, Suite 8R, 530 First Avenue, New York, NY, 10016, USA. douglas.kondziolka@nyumc.org.
authors.forename: Douglas
authors.initials: D
authors.lastname: Kondziolka
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality / Q000556:secondary / Q000601:surgery; D018278:Carcinoma, Neuroendocrine / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D016634:Radiosurgery / Q000401:mortality*; D015996:Survival Rate
chemical_list: C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Brain metastases; EGFR; Non-small cell lung cancer; Prospective registry; Radiosurgery