title: Hypo- or conventionally fractionated radiotherapy combined with chemotherapy in patients with limited stage small cell lung cancer.
abstract: BACKGROUND
  Previous data from our institution showed that hypofractionated thoracic radiotherapy (HypoTRT) with concurrent etoposide/platinum chemotherapy yielded favorable survival in patients with limited-stage small cell lung cancer (LS-SCLC). The present study retrospectively compared the survival outcomes, failure patterns and toxicities between groups of LS-SCLC patients treated with conventionally fractionated thoracic radiotherapy (ConvTRT) or HypoTRT combined with chemotherapy.
  
  
  METHODS
  Medical records of LS-SCLC patients between January 2010 and December 2013 at Fudan University Shanghai Cancer Center were retrospectively reviewed. All patients treated with chemotherapy and ConvTRT (2 Gy per fraction daily, DT ≥ 56 Gy) or HypoTRT (2.5 Gy per fraction daily, DT = 55 Gy) were eligible for analysis. Progression-free survival (PFS) and overall survival (OS) were generated for different populations using the Kaplan-Meier method and compared using the log-rank test. Comparisons of failure patterns and toxicity were analyzed using the χ2test.
  
  
  RESULTS
  A total of 170 patients treated with HypoTRT (n = 69) or ConvTRT (n = 101) were eligible for analysis. The median PFS and OS were 13.7 and 25.3 months, respectively, in the ConvTRT cohort, which was similar to the HypoTRT cohort (PFS 18.2 months, p = 0.991, and OS 27.2 months, p = 0.698), with a median follow-up of 30 months. Multivariate analysis revealed that PCI and TNM stage were prognostic factors for PFS and that PCI was prognostic for OS. The patterns of failure (stratified by local-regional recurrence, distant metastasis or both as first relapse) were similar between the dose cohorts (p = 0.693, p = 0.330, p = 0.572). Distant metastasis remained the main failure pattern. The brain was the most frequent remote failure site, followed by bone, liver and adrenal gland. PCI improved the 2-year survival rate from 46.1% to 70.0% and the 2-year PFS rate from 20.9% to 45.3%, respectively (p < 0.001). Grade ≥3 esophagitis and pneumonitis occurred in 9.9% and 11.9%, respectively, of the patients in the ConvTRT cohort and in 11.6% and 10.0%, respectively, of those in the HypoTRT cohort (p = 0.815).
  
  
  CONCLUSIONS
  This retrospective analysis demonstrated that HypoTRT or ConvTRT combined with etoposide/platinum chemotherapy yielded statistically similar survival, treatment failure outcomes, and toxicity profiles. PCI correlated with improved PFS and OS.
authors.affiliation: Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dong an Road, Shanghai, 200032, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dong an Road, Shanghai, 200032, China. fanmin_zlyy@sina.com.
authors.forename: Min
authors.initials: M
authors.lastname: Fan
authors.affiliation: Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dong an Road, Shanghai, 200032, China.
authors.forename: Di
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dong an Road, Shanghai, 200032, China.
authors.forename: Kuai-Le
authors.initials: KL
authors.lastname: Zhao
authors.affiliation: Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dong an Road, Shanghai, 200032, China.
authors.forename: Kai-Liang
authors.initials: KL
authors.lastname: Wu
authors.affiliation: Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dong an Road, Shanghai, 200032, China.
authors.forename: Wei-Xin
authors.initials: WX
authors.lastname: Zhao
authors.affiliation: Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dong an Road, Shanghai, 200032, China.
authors.forename: Zheng-Fei
authors.initials: ZF
authors.lastname: Zhu
authors.affiliation: Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dong an Road, Shanghai, 200032, China.
authors.forename: Xiao-Long
authors.initials: XL
authors.lastname: Fu
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D059248:Chemoradiotherapy / Q000009:adverse effects / Q000379:methods*; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D055752:Small Cell Lung Carcinoma / Q000401:mortality / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D005047:Etoposide; D002945:Cisplatin
keywords: Conventionally fractionated radiotherapy; Failure patterns; Hypofractionated radiotherapy; Limited-stage small cell lung cancer; Survival; Toxicity