title: Improved survival with dose-escalated radiotherapy in stage III non-small-cell lung cancer: analysis of the National Cancer Database.
abstract: Concurrent chemoradiation is the standard of care in non-operable stage III non-small-cell lung cancer (NSCLC). Data have suggested a benefit of dose escalation; however, results from the randomized dose-escalation trial RTOG 0617 revealed a lower survival rate with high-dose radiation. To evaluate the impact of dose escalation on overall survival (OS) in stage III NSCLC treated with chemoradiotherapy outside the controlled setting of a randomized trial, we carried out an observational, population-based investigation of the National Cancer Database (NCDB).
  
  
  
  A total of 33 566 patients with stage III NSCLC treated with chemoradiation from 2004 to 2012 and radiation doses between 59.4 and 85 Gy were included. The primary end point was OS, with median survival calculated via Kaplan-Meier. Univariate, multivariable and propensity-score matching analyses were carried out.
  
  
  
  Patients were stratified by dose with median OS of: 18.8, 19.8 and 21.6 months for cohorts receiving 59.4-60, 61-69 and ≥70 Gy, respectively (P < 0.001). Granular dose analyses were carried out demonstrating increased OS with increasing radiation dose: median survival of 18.8, 21.1, 22.0 and 21.0 months for 59.4-60, 66, 70 and ≥71 Gy, respectively. While 66, 70 and ≥71 Gy resulted in increased OS in comparison with 59.4-60 Gy, no significant difference in OS was observed when comparing 66 with ≥71 Gy (P = 0.38).
  
  
  
  Dose escalation above 60 Gy was associated with improved OS in this cohort of stage III NSCLC patients treated with chemoradiotherapy. A plateau of benefit was observed, with no additional improvement in OS with increased dose (≥71 Gy) compared with 66-70 Gy. With evidence suggesting worse OS and quality of life with increased dose, these data support investigation of the role of intermediate-dose radiation, and in the absence of randomized evidence, may be leveraged to justify utilization of intermediate-dose radiation.
authors: Department of Human Oncology, University of Wisconsin Hospital and Clinics, Madison.
authors: J V
authors: JV
authors: Brower
authors: Department of Radiation Oncology, University of Colorado, Anschutz Medical Campus, Aurora.
authors: A
authors: A
authors: Amini
authors: Department of Biostatistics and Medical Informatics, University of Wisconsin, Madison, USA.
authors: S
authors: S
authors: Chen
authors: Department of Human Oncology, University of Wisconsin Hospital and Clinics, Madison.
authors: C R
authors: CR
authors: Hullett
authors: Department of Human Oncology, University of Wisconsin Hospital and Clinics, Madison.
authors: R J
authors: RJ
authors: Kimple
authors: Department of Human Oncology, University of Wisconsin Hospital and Clinics, Madison.
authors: A P
authors: AP
authors: Wojcieszynski
authors: Department of Human Oncology, University of Wisconsin Hospital and Clinics, Madison.
authors: M
authors: M
authors: Bassetti
authors: Department of Human Oncology, University of Wisconsin Hospital and Clinics, Madison.
authors: M E
authors: ME
authors: Witek
authors: Department of Biostatistics and Medical Informatics, University of Wisconsin, Madison, USA.
authors: M
authors: M
authors: Yu
authors: Department of Human Oncology, University of Wisconsin Hospital and Clinics, Madison.
authors: P M
authors: PM
authors: Harari
authors: Department of Human Oncology, University of Wisconsin Hospital and Clinics, Madison baschnagel@humonc.wisc.edu.
authors: A M
authors: AM
authors: Baschnagel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology / Q000532:radiotherapy*; D059248:Chemoradiotherapy; D002986:Clinical Trials as Topic; D016208:Databases, Factual; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011788:Quality of Life; D011879:Radiotherapy Dosage
keywords: NSCLC; dose escalation; improved survival; lung cancer; radiation therapy