title: Comparative effectiveness of aggressive thoracic radiation therapy and concurrent chemoradiation therapy in metastatic lung cancer.
abstract: OBJECTIVE
  We aimed to determine the comparative effectiveness of radiation dose escalation and concurrent chemoradiation therapy (CCRT) in a population-based cohort of patients with stage IV non-small cell lung cancer who underwent palliative thoracic radiation therapy (RT).
  
  
  METHODS
  The cohort consisted of 27,063 patients in the National Cancer Database with stage IV non-small cell lung cancer treated with thoracic RT between 20 and 55 Gy in 2004 to 2011. High- versus intermediate- vs low-dose (HD vs ID vs LD, respectively) RT was defined as biologically effective dose above 50 Gy, between 35 and 50 Gy, and below 35 Gy, respectively. Among patients who received any chemotherapy, separate analyses were performed to examine the impact of CCRT on overall survival (OS).
  
  
  RESULTS
  The median follow-up was 3.9 months for the entire cohort and 18 months for surviving patients. The 5 most common treatment schemes were 30/10 (Gy/fraction, 23% of entire cohort), 35/14 (8%), 37.5/15 (7%), 40/20 (3%), and 50/20 (3%). On multivariable analysis, the survival hazard ratios (HRs) for HD and ID compared with LD RT were 0.37 and 0.51, respectively (P < .0001). Propensity score matching found a superior survival benefit for ID and HD (HR, 0.41 and 0.57 for HD and ID RT, respectively, vs LD, P < .0001). Among those who received any chemotherapy (59% of total), the median OS for patients treated with CCRT (19% of total) was 5.3 versus 5.6 months (P = .667). On multivariable analysis, the HR for CCRT was 1.01 (P = .46).
  
  
  CONCLUSIONS
  The delivery of higher-dose RT but not concurrent chemotherapy was associated with a significant improvement of OS. This population-based study supports higher-dose palliative regimens and motivates prospective study of escalation beyond a biologically effective dose of 35 Gy.
authors.affiliation: Department of Radiation Oncology, University of Illinois at Chicago, Chicago, Illinois; Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, Illinois. Electronic address: mkoshy@radonc.uchicago.edu.
authors.forename: Matthew
authors.initials: M
authors.lastname: Koshy
authors.affiliation: Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, Illinois.
authors.forename: Renuka
authors.initials: R
authors.lastname: Malik
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Usama
authors.initials: U
authors.lastname: Mahmood
authors.affiliation: Department of Radiation Oncology, University of Colorado, Aurora, Colorado.
authors.forename: Chad G
authors.initials: CG
authors.lastname: Rusthoven
authors.affiliation: Department of Radiation Oncology, UT Southwestern Medical Center, Dallas, Texas.
authors.forename: David J
authors.initials: DJ
authors.lastname: Sher
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000532:radiotherapy / Q000556:secondary / Q000628:therapy*; D002294:Carcinoma, Squamous Cell / Q000532:radiotherapy / Q000556:secondary / Q000628:therapy*; D059248:Chemoradiotherapy; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D058958:Organs at Risk; D011379:Prognosis; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods; D050397:Radiotherapy, Intensity-Modulated; D015996:Survival Rate; D013899:Thoracic Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D047368:Tumor Burden; D055815:Young Adult