title: Methodology for biologically-based treatment planning for combined low-dose-rate (permanent implant) and high-dose-rate (fractionated) treatment of prostate cancer.
abstract: OBJECTIVE
  The combination of permanent low-dose-rate interstitial implantation (LDR-BRT) and external beam radiotherapy (EBRT) has been used in the treatment of clinically localized prostate cancer. While a high radiation dose is delivered to the prostate in this setting, the actual biologic dose equivalence compared to monotherapy is not commonly invoked. We describe methodology for obtaining the fused dosimetry of this combined treatment and assigning a dose equivalence which in turn can be used to develop desired normal tissue and target constraints for biologic-based treatment planning.
  
  
  METHODS
  Patients treated with this regimen initially receive an I-125 implant prescribed to 110 Gy followed, 2 months later, by 50.4 Gy in 28 fractions using intensity-modulated external beam radiotherapy. Ab initio methodology is described, using clinically derived biologic parameters (alpha, beta, potential doubling time for prostate cancer cells [T(pot)], cell loss factor), for calculating tumor control probability isoeffective doses for the combined LDR and conventional fraction EBRT treatment regimen. As no such formalism exists for assessing rectal or urethral toxicity, we make use of semi-empirical expressions proposed for describing urethral and rectal complication probabilities for specific treatment situations (LDR and fractionation, respectively) and utilize the notion of isoeffective dose to extend these results to combined LDR-EBRT regimens.
  
  
  RESULTS
  The application to treatment planning of the methodology described in this study is illustrated with real-patient data. We evaluate the effect of changing LDR and EBRT prescription doses (in a manner that remains isoeffective with 81 Gy EBRT alone or with 144 Gy LDR monotherapy) on rectal and urethral complication probabilities, and suggest that it should be possible to improve the therapeutic ratio by exploiting joint LDR-EBRT planning.
  
  
  CONCLUSIONS
  We describe new methodology for biologically based treatment planning for patients who receive combined low-dose-rate brachytherapy and external beam radiotherapy for prostate cancer. Using relevant mathematical tools, we demonstrate the feasibility of fusing dose distributions from each treatment for this combined regimen, which can then be expressed as isoeffective dose distributions. Based on this information, dose constraints for the rectum and urethra are described which could be used for planning such combination regimens.
authors.affiliation: Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. zaiderm@mskcc.org
authors.forename: Marco
authors.initials: M
authors.lastname: Zaider
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Zelefsky
authors.forename: Gilad N
authors.initials: GN
authors.lastname: Cohen
authors.forename: Chen-Shou
authors.initials: CS
authors.lastname: Chui
authors.forename: Ellen D
authors.initials: ED
authors.lastname: Yorke
authors.forename: Leah
authors.initials: L
authors.lastname: Ben-Porat
authors.forename: Laura
authors.initials: L
authors.lastname: Happersett
mesh_terms: D000465:Algorithms; D001918:Brachytherapy / Q000379:methods*; D019583:Dose Fractionation, Radiation; D005240:Feasibility Studies; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D008297:Male; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D011836:Radiation Tolerance; D020266:Radiotherapy, Conformal / Q000379:methods*
chemical_list: D007457:Iodine Radioisotopes