Assessment Of The Alpha/Beta Ratios Of Pituitary Adenomas And Craniopharyngiomas For The Quantification Of Single Fraction Equivalent Dose Benefits From Hypofractionated Radiosurgery

Abstract

Hypofractionated radiosurgery (HFSRS) has been recently considered as an alternative to stereotactic radiosurgery (SRS) of lesions close to the anterior visual pathway (AVP). To estimate and quantify a possible benefit from HFSRS versus SRS, the value of the alpha/beta ratio has to be known, for both lesions and organs at risk, primarily the AVP. Recently the α/β ratio for the AVP has been found to be relatively small (1.03 Gy) and published by our group. While a/b ratios for Meningiomas and Chordomas have been investigated and mentioned in the literature, α/β ratios for Pituitary Adenomas (PA) or Craniopharyngiomas (CFG) have never been published to the best of our knowledge. The α/β ratios of PA and CFG were estimated from meta-analyses of studies on treatments performed including stereotactic radiosurgery, hypofractionated radiosurgery, and conventional radiotherapy, using the Fraction Equivalent (FE) plot method. Following inclusion criteria were applied: studies published between 2000 and 2018, follow up period of at least 18 months, overall tumor growth control of at least 90% for PA and at least 70% for CFG. 31 studies with fraction numbers 1 – 30 were included to assess the α/β ratio of PA, while 35 studies with fraction numbers 1 – 31 were included to assess the α/β ratio of CFG. Clinical data provided from our center were added, including HFSRS treatments for 41 PA and 10 CFG, and SRS treatments for 84 PA and 8 CFG, with a mean follow up period of 23 months (HFSRS) and 27 months (SRS). The FE plot method revealed an α/β ratio for non-functional PA of 5.81 Gy, confidence interval [5.31-6.27 Gy]. No meaningful α/β value could be determined for functional PA. Functional PA require relatively high single fraction doses (generally 25-30 Gy to the tumor margin) to achieve local control, doses that fall far away from the commonly accepted range of the validity of the Linear Quadratic (LQ) model, which is the basic model for the FE plot method. For CFG we found an α/β ratio of 2.42 Gy, confidence interval [1.88-2.91 Gy]. As expected, both α/β ratios for non-functional PA and for CFG are much larger compared to the α/β ratio of the optic pathway. A significant benefit from HFSRS relative to SRS can be expected and calculated for non-functional PA and, to a lesser extent, for HFSRS of CFG when located close to the optic system. No meaningful α/β value could be determined for functional PA. An increased Single Fraction Equivalent Dose (SFED) of up to 17% for non-functional PA and of more than 5% for CFG can be achieved with optimized HFSRS schedules.