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Is Biological Effective Dose (BED) Predictive of Outcomes After Radiosurgery for Cerebral Arteriovenous Malformations?

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Reports have shown that radiation dose directly correlates with the chance of nidus obliteration after stereotactic radiosurgery (SRS) for arteriovenous malformations (AVMs). However, recent studies have shown that the rate… Click to show full abstract

Reports have shown that radiation dose directly correlates with the chance of nidus obliteration after stereotactic radiosurgery (SRS) for arteriovenous malformations (AVMs). However, recent studies have shown that the rate of obliteration was greater in patients having SRS before 2000. As the effect of radiation on cell viability is both dose- and time-dependent, one explanation may be that contemporary SRS, which utilizes more isocenters of radiation to improve dose conformality, takes longer to deliver the same radiation dose, thereby reducing its effectiveness. Biological effective dose (BED) is a metric that incorporates both dose and treatment time and has been shown to correlate with enhanced cell kill in Vitro, as well as normal tissue toxicity in animal models. A retrospective study of patients having single-session AVM SRS between 1990 and 2009 with a minimum of 2 yr follow-up. Excluded were patients having prior radiation or embolization, as well as patients having volume-staged SRS. BED was calculated using the mono-exponential model described by Jones and Hopewell. The primary outcomes of the study were time to obliteration and chance of excellent outcome (nidus obliteration with no new deficits). Three hundred twenty-one patients (328 AVMs) met inclusion criteria (median follow-up, 6.7 yr). BED was associated with both decreased time to obliteration and excellent outcome in univariate Cox regression analyses, both when treated as a dichotomous (P = .002, HR = 1.51 for obliteration; P = .001, HR = 1.61 for outcome) or continuous variable (P = .049, HR = 1.002 for obliteration; P = .01, HR = 1.00 for outcome). In multivariable analyses including dichotomized BED and modified Radiosurgery-Based Arteriovenous Malformation Score as covariates, BED remained significantly associated with both time to obliteration (P = .01, HR = 1.46) and excellent outcome (P = .04, HR = 1.40). BED was predictive of outcomes after AVM SRS. Further study is warranted to determine whether BED optimization should be considered as well as a prescribed treatment dose for SRS treatment planning.

Keywords: time; dose; outcome; arteriovenous malformations; biological effective; obliteration

Journal Title: Neurosurgery
Year Published: 2019

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