title: A modelled comparison of prostate cancer control rates after high-dose-rate brachytherapy (3145 multicentre patients) combined with, or in contrast to, external-beam radiotherapy.
abstract: OBJECTIVE
  To analyse biochemical relapse-free-survival results for prostate cancer patients receiving combined external beam and high-dose-rate brachytherapy, in comparison with expected results using projections based on dose/fractionation/response parameter values deduced from a previous external-beam-alone 5969-patient multicentre dataset.
  
  
  METHODS
  Results on a total of 3145 prostate cancer patients receiving brachytherapy (BT) as part or all of their treatment were collected from 10 institutions, and subjected to linear-quadratic (LQ) modelling of dose response and fractionation parameters.
  
  
  RESULTS
  Treatments with BT components of less than 25Gy, 3-4 BT fractions, doses per BT fraction up to 6Gy, and treatment times of 3-7weeks, all gave outcomes expected from LQ projections of the external-beam-alone data (α/β=1.42Gy). However, BT doses higher than 30Gy, 1-2 fractions, 9 fractions (BT alone), doses per fraction of 9-15Gy, and treatment in only 1week (one example), gave local control levels lower than the expected levels by up to ∼35%.
  
  
  CONCLUSIONS
  There are various potential causes of the lower-than-projected control levels for some schedules of brachytherapy: it seems plausible that cold spots in the brachytherapy dose distribution may be contributory, and the applicability of the LQ model at high doses per fraction remains somewhat uncertain. The results of further trials may help elucidate the true benefit of hypofractionated high-dose-rate brachytherapy.
authors.affiliation: Centre for Biostatistics, Institute of Population Health, Manchester Academic Health Sciences Centre, University of Manchester, United Kingdom. Electronic address: steve.roberts@manchester.ac.uk.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Roberts
authors.affiliation: University Hospital, Geneva, Switzerland; Institut Oncològic Teknon, Barcelona, Spain.
authors.forename: Raymond
authors.initials: R
authors.lastname: Miralbell
authors.affiliation: International Atomic Energy Agency, Vienna, Austria.
authors.forename: Eduardo H
authors.initials: EH
authors.lastname: Zubizarreta
authors.affiliation: 150 Lambeth Road, London SE1 7DF, United Kingdom.
authors.forename: Jack F
authors.initials: JF
authors.lastname: Fowler
authors.affiliation: Christie Medical Physics and Engineering, The Christie NHS Foundation Trust, Manchester, United Kingdom.
authors.forename: Jolyon H
authors.initials: JH
authors.lastname: Hendry
mesh_terms: D001918:Brachytherapy / Q000379:methods*; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D016014:Linear Models; D008297:Male; D015233:Models, Statistical; D011471:Prostatic Neoplasms / Q000532:radiotherapy*
keywords: Biochemical relapse free survival; High dose-rate brachytherapy; Prostate cancer; Radiotherapy