title: Significance of targeted therapy and genetic alterations in EGFR, ALK, or KRAS on survival in patients with non-small cell lung cancer treated with radiotherapy for brain metastases.
abstract: BACKGROUND
  We determined the impact of genetic alterations in EGFR, ALK, or KRAS on survival after radiotherapy for brain metastases in non-small cell lung cancer (NSCLC).
  
  
  METHODS
  Of 172 genotyped NSCLC patients treated with radiotherapy for brain metastases in 2005-2012, 54 had cancers with EGFR mutations, 12 had ALK rearrangements, 38 had KRAS mutations, and 68 were wild-type (WT). Overall survival (OS) was determined.
  
  
  RESULTS
  Median follow-up was 8.6 months. Median OS was 13.6 months for patients with EGFR mutations and 26.3 months for patients with ALK rearrangements, in contrast to 5.7 months for KRAS-mutant patients and 5.5 months for WT patients (P = .001). On multivariate analysis, adjusting for receipt of targeted therapy after cranial radiotherapy, ALK rearrangements were associated with improved OS (HR, 0.31; 95% CI, 0.13-0.74; P = .008). EGFR mutations were not significantly associated with improved OS on multivariate analysis (HR, 0.71; 95% CI, 0.37-1.38; P = .3). KRAS mutations were also not associated with improved OS (HR, 0.93; 95% CI, 0.59-1.47; P = .8). Receipt of targeted therapy after cranial radiotherapy was independently associated with improved OS (HR, 0.30; 95% CI, 0.17-0.54; P < .001). Receipt of chemotherapy after cranial radiotherapy, number of brain metastases, extracranial metastases, age, and performance status were also associated with OS.
  
  
  CONCLUSIONS
  NSCLC patients with genetic alterations in ALK have improved survival outcomes after radiotherapy for brain metastases compared with EGFR, KRAS, or WT. Subsequent receipt of targeted therapy was associated with additional improvement in OS.
authors: Harvard Radiation Oncology Program, Massachusetts General Hospital, Boston, Massachusetts (K.S.M.); Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts (J.F.G.); Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (A.N., K.S.O., H.W., N.C.C., J.S.L., H.A.S.); Massachusetts General Hospital Cancer Center, Boston, Massachusetts (L.V.S., A.T.S.).
authors: Kimberley S
authors: KS
authors: Mak
authors: Harvard Radiation Oncology Program, Massachusetts General Hospital, Boston, Massachusetts (K.S.M.); Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts (J.F.G.); Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (A.N., K.S.O., H.W., N.C.C., J.S.L., H.A.S.); Massachusetts General Hospital Cancer Center, Boston, Massachusetts (L.V.S., A.T.S.).
authors: Justin F
authors: JF
authors: Gainor
authors: Harvard Radiation Oncology Program, Massachusetts General Hospital, Boston, Massachusetts (K.S.M.); Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts (J.F.G.); Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (A.N., K.S.O., H.W., N.C.C., J.S.L., H.A.S.); Massachusetts General Hospital Cancer Center, Boston, Massachusetts (L.V.S., A.T.S.).
authors: Andrzej
authors: A
authors: Niemierko
authors: Harvard Radiation Oncology Program, Massachusetts General Hospital, Boston, Massachusetts (K.S.M.); Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts (J.F.G.); Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (A.N., K.S.O., H.W., N.C.C., J.S.L., H.A.S.); Massachusetts General Hospital Cancer Center, Boston, Massachusetts (L.V.S., A.T.S.).
authors: Kevin S
authors: KS
authors: Oh
authors: Harvard Radiation Oncology Program, Massachusetts General Hospital, Boston, Massachusetts (K.S.M.); Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts (J.F.G.); Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (A.N., K.S.O., H.W., N.C.C., J.S.L., H.A.S.); Massachusetts General Hospital Cancer Center, Boston, Massachusetts (L.V.S., A.T.S.).
authors: Henning
authors: H
authors: Willers
authors: Harvard Radiation Oncology Program, Massachusetts General Hospital, Boston, Massachusetts (K.S.M.); Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts (J.F.G.); Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (A.N., K.S.O., H.W., N.C.C., J.S.L., H.A.S.); Massachusetts General Hospital Cancer Center, Boston, Massachusetts (L.V.S., A.T.S.).
authors: Noah C
authors: NC
authors: Choi
authors: Harvard Radiation Oncology Program, Massachusetts General Hospital, Boston, Massachusetts (K.S.M.); Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts (J.F.G.); Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (A.N., K.S.O., H.W., N.C.C., J.S.L., H.A.S.); Massachusetts General Hospital Cancer Center, Boston, Massachusetts (L.V.S., A.T.S.).
authors: Jay S
authors: JS
authors: Loeffler
authors: Harvard Radiation Oncology Program, Massachusetts General Hospital, Boston, Massachusetts (K.S.M.); Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts (J.F.G.); Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (A.N., K.S.O., H.W., N.C.C., J.S.L., H.A.S.); Massachusetts General Hospital Cancer Center, Boston, Massachusetts (L.V.S., A.T.S.).
authors: Lecia V
authors: LV
authors: Sequist
authors: Harvard Radiation Oncology Program, Massachusetts General Hospital, Boston, Massachusetts (K.S.M.); Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts (J.F.G.); Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (A.N., K.S.O., H.W., N.C.C., J.S.L., H.A.S.); Massachusetts General Hospital Cancer Center, Boston, Massachusetts (L.V.S., A.T.S.).
authors: Alice T
authors: AT
authors: Shaw
authors: Harvard Radiation Oncology Program, Massachusetts General Hospital, Boston, Massachusetts (K.S.M.); Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts (J.F.G.); Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (A.N., K.S.O., H.W., N.C.C., J.S.L., H.A.S.); Massachusetts General Hospital Cancer Center, Boston, Massachusetts (L.V.S., A.T.S.).
authors: Helen A
authors: HA
authors: Shih
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality / Q000532:radiotherapy* / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult; D018631:ras Proteins / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
keywords: ALK; EGFR; brain metastases; non–small cell lung cancer; radiotherapy