title: Evaluation of factors associated with loco-regional failure and survival in limited disease small cell lung cancer patients treated with chemoradiotherapy.
abstract: BACKGROUND
  Loco-regional failure (LRF) remains a significant problem in limited disease small cell lung cancer (LD-SCLC) patients treated with definitive chemoradiotherapy. Dose-escalation may be a way forward to reduce the failure rate. However, the risk of toxicity rises with increasing doses. Knowledge on factors associated with LRF could aid the selection of patients for more aggressive treatment. Therefore, the aim of this study is to evaluate factors correlated with LRF in a cohort of LD-SCLC patients treated with definitive chemoradiotherapy. Moreover, factors associated with improved survival were investigated.
  
  
  METHODS
  We included 147 consecutive LD-SCLC patients treated from 2007 to 2013. Radiotherapy was delivered as either 45 Gy in 1.5-Gy fractions twice daily or 46-50 Gy in 2-Gy fractions once daily. Chemotherapy was etoposide combined with either carboplatin or cisplatin given mainly concomitantly with radiotherapy. Pattern of first failure and survival were evaluated retrospectively. Cumulative LRF (CLRF) and overall survival (OS) were calculated by the Kaplan-Meier method. The impact of covariates on LRF and OS was evaluated by using Cox proportional hazards model.
  
  
  RESULTS
  With a median follow-up time of 42.2 months, 37 patients experienced LRF as first failure. Isolated LRF was seen in 16 patients, but no isolated regional failure was seen. The CLRF rate was 22% at 1-year and 43% at 3-years. N3-stage was an independent prognostic factor correlated with LRF development (p = 0.043). Median OS was 24.1 months (95% CI 19-29 months) and a three-year survival of 34%. Prognostic factors associated with improved OS were staging including a positron emission tomography (PET) scan (p = 0.004) and receiving prophylactic cranial irradiation (PCI) (p = 0.006).
  
  
  CONCLUSIONS
  N3-stage was an independent prognostic factor for LRF. Receiving a pretreatment PET scan and receiving PCI were prognostic factors for improved OS. Reduction in LRF may be achieved with dose-escalation in patients with N3-stage. This can be evaluated in prospective dose-escalation trials.
authors.affiliation: a Department of Oncology , Aarhus University Hospital , Aarhus , Denmark.
authors.forename: Anne
authors.initials: A
authors.lastname: Winther-Larsen
authors.affiliation: b Department of Medical Physics , Aarhus University Hospital , Aarhus , Denmark.
authors.forename: Lone
authors.initials: L
authors.lastname: Hoffmann
authors.affiliation: b Department of Medical Physics , Aarhus University Hospital , Aarhus , Denmark.
authors.forename: Ditte S
authors.initials: DS
authors.lastname: Moeller
authors.affiliation: a Department of Oncology , Aarhus University Hospital , Aarhus , Denmark.
authors.forename: Azza A
authors.initials: AA
authors.lastname: Khalil
authors.affiliation: a Department of Oncology , Aarhus University Hospital , Aarhus , Denmark.
authors.forename: Marianne M
authors.initials: MM
authors.lastname: Knap
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000517:prevention & control / Q000556:secondary; D016190:Carboplatin / Q000008:administration & dosage; D059248:Chemoradiotherapy; D002945:Cisplatin / Q000008:administration & dosage; D019583:Dose Fractionation, Radiation; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology*; D009367:Neoplasm Staging; D049268:Positron-Emission Tomography; D012189:Retrospective Studies; D055752:Small Cell Lung Carcinoma / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D015996:Survival Rate
chemical_list: D005047:Etoposide; D016190:Carboplatin; D002945:Cisplatin