title: Mature results of a phase II trial on individualised accelerated radiotherapy based on normal tissue constraints in concurrent chemo-radiation for stage III non-small cell lung cancer.
abstract: BACKGROUND
  Sequential chemotherapy and individualised accelerated radiotherapy (INDAR) has been shown to be effective in non-small cell lung cancer (NSCLC), allowing delivering of high biological doses. We therefore performed a phase II trial (clinicaltrials.gov; NCT00572325) investigating the same strategy in concurrent chemo-radiation in stage III NSCLC.
  
  
  METHODS
  137 stage III patients fit for concurrent chemo-radiation (PS 0-2; FEV(1) and DLCO ≥ 30%) were included from April 2006 till December 2009. An individualised prescribed dose based on normal tissue dose constraints was applied: mean lung dose (MLD) 19 Gy, spinal cord 54 Gy, brachial plexus 66 Gy, central structures 74 Gy. A total dose between 51 and 69 Gy was delivered in 1.5 Gy BID up to 45 Gy, followed by 2 Gy QD. Radiotherapy was started at the 2nd or 3rd course of chemotherapy. Primary end-point was overall survival (OS) and secondary end-point toxicity common terminology criteria for adverse events v3.0 (CTCAEv3.0).
  
  
  RESULTS
  The median tumour volume was 76.4 ± 94.1 cc; 49.6% of patients had N2 and 32.1% N3 disease. The median dose was 65.0 ± 6.0 Gy delivered in 35 ± 5.7 days. Six patients (4.4%) did not complete radiotherapy. With a median follow-up of 30.9 months, the median OS was 25.0 months (2-year OS 52.4%). Severe acute toxicity (≥ G3, 35.8%) consisted mainly of G3 dysphagia during radiotherapy (25.5%). Severe late toxicity (≥ G3) was observed in 10 patients (7.3%).
  
  
  CONCLUSIONS
  INDAR in concurrent chemo-radiation based on normal tissue constraints is feasible, even in patients with large tumour volumes and multi-level N2-3 disease, with acceptable severe late toxicity and promising 2-year survival.
authors.affiliation: Department of Radiation Oncology (MAASTRO Clinic), GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands. angela.vanbaardwijk@maastro.nl
authors.forename: Angela
authors.initials: A
authors.lastname: van Baardwijk
authors.forename: Bart
authors.initials: B
authors.lastname: Reymen
authors.forename: Stofferinus
authors.initials: S
authors.lastname: Wanders
authors.forename: Jacques
authors.initials: J
authors.lastname: Borger
authors.forename: Michel
authors.initials: M
authors.lastname: Ollers
authors.forename: Anne-Marie C
authors.initials: AM
authors.lastname: Dingemans
authors.forename: Gerben
authors.initials: G
authors.lastname: Bootsma
authors.forename: Wiel
authors.initials: W
authors.lastname: Geraedts
authors.forename: Cordula
authors.initials: C
authors.lastname: Pitz
authors.forename: Ragnar
authors.initials: R
authors.lastname: Lunde
authors.forename: Frank
authors.initials: F
authors.lastname: Peters
authors.forename: Philippe
authors.initials: P
authors.lastname: Lambin
authors.forename: Dirk
authors.initials: D
authors.lastname: De Ruysscher
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D059248:Chemoradiotherapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016019:Survival Analysis