title: Tolerability of accelerated chest irradiation and impact on survival of prophylactic cranial irradiation in patients with limited-stage small cell lung cancer: review of a single institution's experience.
abstract: BACKGROUND
  Evidence that has been published in the last decade indicates that in patients with limited-stage small-cell lung cancer (SCLC), hyperfractionated accelerated thoracic radiotherapy (RT) given twice daily and prophylactic cranial irradiation (PCI) have each separately improved survival. Concerns about the toxicities associated with these treatments and uncertainty about their impact on survival outside the trial setting may have restricted the extent to which they have been incorporated into standard treatment protocols. We have reviewed the experience at Peter MacCallum Cancer Centre to determine the tolerability of these treatments in routine practice and to determine their effects on survival.
  
  
  METHODS
  A retrospective review of patients with limited-stage SCLC receiving a radical course of thoracic RT between June 1998 and May 2002, including either conventional fractionation at 50 Gy for 5 weeks, or hyperfractionated accelerated RT at 45 Gy for 3 weeks. Patients achieving a complete response were offered PCI at 36 Gy in 18 fractions. The main outcomes recorded were RT toxicity (graded using CTCAE v. 3.0 and RTOG/EORTC late scoring criteria), response, relapse-free survival, and overall survival.
  
  
  RESULTS
  Ninety patients were identified as having undergone radical-intent thoracic RT, with a median potential follow-up of 4.2 years. Fifty-seven patients (63%) were treated with hyperfractionated accelerated RT, and 33 (37%) were treated with conventional fractionation. Forty-six patients (51%) received PCI. Patients receiving hyperfractionated accelerated RT compared with conventional fractionation had higher rates of grade 3 and 4 esophagitis (14% versus 6%; p = 0.312), a higher rate of treatment interruptions (12% versus 3%; p = 0.250), and a higher hospital admission rate (39% versus 15%; p = 0.031). The majority of patients were able to complete the planned treatment, and there were no treatment-related deaths. Median survival for all patients from commencement of RT was 14.2 months (95% confidence interval [CI]: 11.9-18.1 months), and survival at 2 years was 24.8% (95% CI: 16.9-35.0%). On multifactor analysis, the only factor associated with longer survival was PCI (hazard ratio = 0.40; p < 0.001).
  
  
  CONCLUSIONS
  Hyperfractionated accelerated RT was more toxic than conventional fractionation, but it was possible to deliver treatment as planned in the majority of patients. PCI was associated with improved survival. Both treatments can be incorporated into routine practice.
authors.affiliation: Department of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Ng
authors.forename: Jennifer
authors.initials: J
authors.lastname: Chong
authors.forename: Alvin
authors.initials: A
authors.lastname: Milner
authors.forename: Michael
authors.initials: M
authors.lastname: MacManus
authors.forename: Greg
authors.initials: G
authors.lastname: Wheeler
authors.forename: Andrew
authors.initials: A
authors.lastname: Wirth
authors.forename: Michael
authors.initials: M
authors.lastname: Michael
authors.forename: Vinod
authors.initials: V
authors.lastname: Ganju
authors.forename: Joe
authors.initials: J
authors.lastname: McKendrick
authors.forename: David
authors.initials: D
authors.lastname: Ball
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018288:Carcinoma, Small Cell / Q000473:pathology / Q000532:radiotherapy*; D016371:Cranial Irradiation; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011882:Radiotherapy, High-Energy; D012189:Retrospective Studies; D015996:Survival Rate; D035441:Thoracic Wall / Q000528:radiation effects*; D016896:Treatment Outcome