title: A brain tumor dose escalation protocol based on effective dose equivalence to prior experience.
abstract: OBJECTIVE
  The current study describes the design of a dose escalation protocol for conformal irradiation of primary brain tumors that preserves the safe experience of a previous, sequential dose escalation scheme while enabling the delivery of substantially higher effective doses to a central target volume.
  
  
  METHODS
  Normalized isoeffective composite dose distributions were formed for 20 patients treated on the original protocol (which specified three progressively smaller planning target volumes [PTVs]) using the linear quadratic model (here corrected to equivalent 2 Gy fractions using alpha/beta=10 Gy). These distributions were investigated and a new protocol was designed to preserve a similar level of efficacy and lack of toxicity for the outer volumes, but allowing a higher dose to the inner PTV. Treatment plans were then investigated to determine if the objectives of the new protocol were achievable. In particular, plans that simultaneously achieved all biological treatment planning objectives (all fields treated each day) were investigated. Finally, the success of the protocol design was demonstrated by analysis of the effective dose distributions of 10 patients treated using the new protocol.
  
  
  RESULTS
  The composite normalized isoeffective minimum doses to the outer PTVs (PTV3 and PTV2) in the original protocol were close to 60 Gy and 75 Gy, respectively, and these values are specified as the minimum doses to those volumes for the new protocol. Homogeneity requirements to maintain equivalence for the outer target volume domains are: not more than 25% of [PTV3 exclusive of PTV2] >75 Gy; and not more than 50% of [PTV2 exclusive of PTV1] >85 Gy. Treatment plans using multiple noncoplanar arrangements of beams and static intensity modulation treat all volumes at each session. DVHs of the normalized isoeffective dose distributions reveal the equivalence of the new protocol plans to the sequential plans in the previous protocol as well as the ability to achieve a higher dose of 90 Gy to the isocenter of PTV1 (+/-5% homogeneity required).
  
  
  CONCLUSIONS
  The ability to incorporate past experience through use of the linear quadratic model in the design of a new dose escalation protocol is demonstrated.
authors.affiliation: Department of Radiation Oncology, The University of Michigan, Ann Arbor 48109-0010, USA.
authors.forename: R K
authors.initials: RK
authors.lastname: Ten Haken
authors.forename: B A
authors.initials: BA
authors.lastname: Fraass
authors.forename: A S
authors.initials: AS
authors.lastname: Lichter
authors.forename: L H
authors.initials: LH
authors.lastname: Marsh
authors.forename: E H
authors.initials: EH
authors.lastname: Radany
authors.forename: H M
authors.initials: HM
authors.lastname: Sandler
mesh_terms: D001932:Brain Neoplasms / Q000532:radiotherapy*; D019583:Dose Fractionation, Radiation; D006801:Humans; D016014:Linear Models; D008954:Models, Biological; D011880:Radiotherapy Planning, Computer-Assisted; D011881:Radiotherapy, Computer-Assisted / Q000379:methods*