title: Aggressive therapy for patients with non-small cell lung carcinoma and synchronous brain-only oligometastatic disease is associated with long-term survival.
abstract: OBJECTIVE
  Optimal therapy for patients with non-small cell lung carcinoma (NSCLC) presenting with synchronous brain-only oligometastases (SBO) is not well defined. We sought to analyze the effect of differing therapeutic paradigms in this subpopulation.
  
  
  METHODS
  We retrospectively analyzed NSCLC patients with 1-4 SBO diagnosed between 1/2000 and 1/2011 at our institution. Patients with T0 tumors or documented Karnofsky Performance Status <70 were excluded. Aggressive thoracic therapy (ATT) was defined as resection of the primary disease or chemoradiotherapy whose total radiation dose exceeded 45 Gy. Cox proportional hazards and competing risks models were used to analyze factors affecting survival and first recurrence in the brain.
  
  
  RESULTS
  Sixty-six patients were included. Median follow-up was 31.9 months. Intrathoracic disease extent included 9 stage I, 10 stage II and 47 stage III patients. Thirty-eight patients received ATT, 28 did not. Patients receiving ATT were younger (median age 55 vs. 60.5 years, p=0.027) but were otherwise similar to those who did not. Receipt of ATT was associated with prolonged median overall survival (OS) (26.4 vs. 10.5 months; p<0.001) with actuarial 2-year rates of 54% vs. 26%. ATT remained associated with OS after controlling for age, thoracic stage, performance status and initial brain therapy (HR 0.40, p=0.009). On multivariate analysis, the risk of first failure in the brain was associated with receipt of ATT (HR 3.62, p=0.032) and initial combined modality brain therapy (HR 0.34, p=0.046).
  
  
  CONCLUSIONS
  Aggressive management of thoracic disease in NSCLC patients with SBO is associated with improved survival. Careful management of brain disease remains important, especially for those treated aggressively.
authors: Harvard Radiation Oncology Program, Boston, USA.
authors: Phillip J
authors: PJ
authors: Gray
authors: Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, USA.
authors: Raymond H
authors: RH
authors: Mak
authors: Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, USA.
authors: Beow Y
authors: BY
authors: Yeap
authors: Department of Medicine, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, USA.
authors: Sarah K
authors: SK
authors: Cryer
authors: Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, USA.
authors: Nancy E
authors: NE
authors: Pinnell
authors: Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, USA.
authors: Laura W
authors: LW
authors: Christianson
authors: Department of Radiation Oncology, Rush University Medical Center, Chicago, USA.
authors: David J
authors: DJ
authors: Sher
authors: Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, USA.
authors: Nils D
authors: ND
authors: Arvold
authors: Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, USA.
authors: Elizabeth H
authors: EH
authors: Baldini
authors: Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, USA.
authors: Aileen B
authors: AB
authors: Chen
authors: Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, USA.
authors: David E
authors: DE
authors: Kozono
authors: Division of Thoracic Surgery, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, MA, USA.
authors: Scott J
authors: SJ
authors: Swanson
authors: Department of Medicine, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, USA.
authors: David M
authors: DM
authors: Jackman
authors: Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, USA. Electronic address: bmalexander@partners.org.
authors: Brian M
authors: BM
authors: Alexander
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000401:mortality / Q000473:pathology / Q000556:secondary* / Q000628:therapy*; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012189:Retrospective Studies; D012307:Risk Factors; D017211:Treatment Failure; D016896:Treatment Outcome; D047368:Tumor Burden
keywords: Aggressive therapy; Brain metastases; Non-small cell lung cancer; Oligometastases; Radiation therapy; Stereotactic radiosurgery; Whole brain radiotherapy