title: Dose fractionation in stereotactic radiotherapy for parasellar meningiomas: radiobiological considerations of efficacy and optic nerve tolerance.
abstract: OBJECTIVE
  Benign meningiomas have been shown to be equally well controlled with single-dose radiosurgery (15 Gy) and fractionated doses of 54 Gy in 30 fractions after adequate follow up. For a subset of patients with meningioma, the optic apparatus is dose limiting when considering single-dose stereotactic radiosurgery, with tolerance estimated to be 8 to 10 Gy. Recently, hypofractionated regimens have been used to treat benign meningiomas with a small number of fractions. An analysis of the expected efficacy of hypofractionation compared with the estimated optic tolerance to fractionated radiotherapy was undertaken.
  
  
  METHODS
  Using the assumption that 15 Gy in one fraction and 54 Gy in 30 fractions are isoeffective for control of benign meningioma, an alpha/beta for meningioma is calculated to be 3.28 Gy. Invoking a 10% error for these doses (15 Gy+/-10% is equivalent to 54 Gy+/-10%) results in upper and lower limits of the estimate for alpha/beta of 3.85 Gy and 2.7 Gy. Using these estimates, isoeffect curves for control of meningioma were constructed for fraction numbers of one to 45. Best estimates of optic nerve/chiasm tolerance to single doses of radiation are 8 to 10 Gy, with the reported incidence of optic neuropathy increasing significantly at higher doses. This is consistent with the optic ret model, which also predicts for optic tolerance following fractionated radiotherapy. Comparison of optic tolerance and estimates of efficacious doses at fraction numbers between one and 30 were made. Statistical estimates of patient numbers and duration of follow up required to rule out optic neuropathy following radiotherapy were made. Single doses of radiation required to treat benign meningioma optimally (13.5-16.5 Gy) clearly exceed the estimated and reported clinical tolerance of the optic nerves and chiasm. The application of equivalent biological doses in a small number of fractions continues to exceed optic tolerance until at least 25 fractions are applied.
  
  
  CONCLUSIONS
  The use of small numbers of fractions to treat patients with meningioma when portions of optic nerve or chiasm receive full dose may result in undertreatment of the tumor and/or exceeding optic nerve tolerance. In such cases standard fractionation is recommended. Ruling out a low, yet unacceptable, risk of optic neuropathy may require the close study of many patients with long-term follow-up evaluation.
authors.affiliation: Department of Radiation Oncology, The Huntsman Cancer Institute, University of Utah Health Sciences Center, Salt Lake City, Utah 84132, USA. dennis.shrieve@hsc.utah.edu
authors.forename: Dennis C
authors.initials: DC
authors.lastname: Shrieve
authors.forename: Lisa
authors.initials: L
authors.lastname: Hazard
authors.forename: Kenneth
authors.initials: K
authors.lastname: Boucher
authors.forename: Randy L
authors.initials: RL
authors.lastname: Jensen
mesh_terms: D019583:Dose Fractionation, Radiation; D006801:Humans; D008577:Meningeal Neoplasms / Q000601:surgery*; D008579:Meningioma / Q000601:surgery*; D009900:Optic Nerve / Q000528:radiation effects*; D009901:Optic Nerve Diseases / Q000209:etiology; D016634:Radiosurgery / Q000009:adverse effects / Q000379:methods*; D011879:Radiotherapy Dosage; D016896:Treatment Outcome