title: Increased Biological Effective Dose of Radiation Correlates with Prolonged Survival of Patients with Limited-Stage Small Cell Lung Cancer: A Systematic Review.
abstract: OBJECTIVE
  Thoracic radiotherapy (TRT) is a critical component of the treatment of limited-stage small cell lung cancer (LS-SCLC). However, the optimal radiation dose/fractionation remains elusive. This study reviewed current evidence and explored the dose-response relationship in patients with LS-SCLC who were treated with radiochemotherapy.
  
  
  METHODS
  A quantitative analysis was performed through a systematic search of PubMed, Web of Science, and the Cochrane Library. The correlations between the biological effective dose (BED) and median overall survival (mOS), median progression-free survival (mPFS), 1-, 3-, and 5-year overall survival (OS) as well as local relapse (LR) were evaluated.
  
  
  RESULTS
  In all, 2389 patients in 19 trials were included in this study. Among these 19 trials, seven were conducted in Europe, eight were conducted in Asia and four were conducted in the United States. The 19 trials that were included consisted of 29 arms with 24 concurrent and 5 sequential TRT arms. For all included studies, the results showed that a higher BED prolonged the mOS (R2 = 0.198, p<0.001) and the mPFS (R2 = 0.045, p<0.001). The results also showed that increased BED improved the 1-, 3-, and 5-year OS. A 10-Gy increment added a 6.3%, a 5.1% and a 3.7% benefit for the 1-, 3-, and 5-year OS, respectively. Additionally, BED was negatively correlated with LR (R2 = 0.09, p<0.001). A subgroup analysis of concurrent TRT showed that a high BED prolonged the mOS (p<0.001) and the mPFS (p<0.001), improved the 1-, 3-, and 5-year OS (p<0.001) and decreased the rate of LR (p<0.001).
  
  
  CONCLUSIONS
  This study showed that an increased BED was associated with improved OS, PFS and decreased LR in patients with LS-SCLC who were treated with combined chemoradiotherapy, which indicates that the strategy of radiation dose escalation over a limited time frame is worth exploring in a prospective clinical trial.
authors.affiliation: Affiliated Hangzhou Hospital of Nanjing Medical University, Hangzhou 310006, PR China.|Hangzhou First People's Hospital, Hangzhou 310006, PR China.
authors.forename: Lucheng
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Affiliated Hangzhou Hospital of Nanjing Medical University, Hangzhou 310006, PR China.|Hangzhou First People's Hospital, Hangzhou 310006, PR China.
authors.forename: Shirong
authors.initials: S
authors.lastname: Zhang
authors.affiliation: HangZhou Cancer Hospital, Hangzhou 310006, PR China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Xu
authors.affiliation: HangZhou Cancer Hospital, Hangzhou 310006, PR China.
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.affiliation: HangZhou Cancer Hospital, Hangzhou 310006, PR China.
authors.forename: Kan
authors.initials: K
authors.lastname: Wu
authors.affiliation: HangZhou Cancer Hospital, Hangzhou 310006, PR China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Deng
authors.affiliation: Affiliated Hangzhou Hospital of Nanjing Medical University, Hangzhou 310006, PR China.|Hangzhou First People's Hospital, Hangzhou 310006, PR China.
authors.forename: Bing
authors.initials: B
authors.lastname: Xia
authors.affiliation: Affiliated Hangzhou Hospital of Nanjing Medical University, Hangzhou 310006, PR China.|Hangzhou First People's Hospital, Hangzhou 310006, PR China.
authors.forename: Shenglin
authors.initials: S
authors.lastname: Ma
mesh_terms: D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality* / Q000532:radiotherapy*; D008297:Male; D011879:Radiotherapy Dosage; D055752:Small Cell Lung Carcinoma / Q000401:mortality* / Q000532:radiotherapy*; D015996:Survival Rate