title: Normal tissue complication probability estimation by the Lyman-Kutcher-Burman method does not accurately predict spinal cord tolerance to stereotactic radiosurgery.
abstract: OBJECTIVE
  To determine whether normal tissue complication probability (NTCP) analyses of the human spinal cord by use of the Lyman-Kutcher-Burman (LKB) model, supplemented by linear-quadratic modeling to account for the effect of fractionation, predict the risk of myelopathy from stereotactic radiosurgery (SRS).
  
  
  METHODS
  From November 2001 to July 2008, 24 spinal hemangioblastomas in 17 patients were treated with SRS. Of the tumors, 17 received 1 fraction with a median dose of 20 Gy (range, 18-30 Gy) and 7 received 20 to 25 Gy in 2 or 3 sessions, with cord maximum doses of 22.7 Gy (range, 17.8-30.9 Gy) and 22.0 Gy (range, 20.2-26.6 Gy), respectively. By use of conventional values for α/β, volume parameter n, 50% complication probability dose TD(50), and inverse slope parameter m, a computationally simplified implementation of the LKB model was used to calculate the biologically equivalent uniform dose and NTCP for each treatment. Exploratory calculations were performed with alternate values of α/β and n.
  
  
  RESULTS
  In this study 1 case (4%) of myelopathy occurred. The LKB model using radiobiological parameters from Emami and the logistic model with parameters from Schultheiss overestimated complication rates, predicting 13 complications (54%) and 18 complications (75%), respectively. An increase in the volume parameter (n), to assume greater parallel organization, improved the predictive value of the models. Maximum-likelihood LKB fitting of α/β and n yielded better predictions (0.7 complications), with n = 0.023 and α/β = 17.8 Gy.
  
  
  CONCLUSIONS
  The spinal cord tolerance to the dosimetry of SRS is higher than predicted by the LKB model using any set of accepted parameters. Only a high α/β value in the LKB model and only a large volume effect in the logistic model with Schultheiss data could explain the low number of complications observed. This finding emphasizes that radiobiological models traditionally used to estimate spinal cord NTCP may not apply to the dosimetry of SRS. Further research with additional NTCP models is needed.
authors.affiliation: Department of Radiation Oncology, Stanford University, Stanford, CA, USA.
authors.forename: Megan E
authors.initials: ME
authors.lastname: Daly
authors.forename: Gary
authors.initials: G
authors.lastname: Luxton
authors.forename: Clara Y H
authors.initials: CY
authors.lastname: Choi
authors.forename: Iris C
authors.initials: IC
authors.lastname: Gibbs
authors.forename: Steven D
authors.initials: SD
authors.lastname: Chang
authors.forename: John R
authors.initials: JR
authors.lastname: Adler
authors.forename: Scott G
authors.initials: SG
authors.lastname: Soltys
mesh_terms: D000328:Adult; D005260:Female; D018325:Hemangioblastoma / Q000601:surgery*; D006801:Humans; D016013:Likelihood Functions; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D058958:Organs at Risk / Q000528:radiation effects; D011336:Probability; D011832:Radiation Injuries / Q000150:complications*; D011836:Radiation Tolerance; D016634:Radiosurgery / Q000009:adverse effects*; D011879:Radiotherapy Dosage; D013116:Spinal Cord / Q000528:radiation effects*; D013125:Spinal Neoplasms / Q000601:surgery*; D055815:Young Adult