Radiation dose-volume effects in the brain

Abstract

We have reviewed the published data regarding radiotherapy (RT)-induced brain injury. Radiation necrosis appears a median of 1-2 years after RT; however, cognitive decline develops over many years. The incidence and severity is dose and volume dependent and can also be increased by chemotherapy, age, diabetes, and spatial factors. For fractionated RT with a fraction size of <2.5 Gy, an incidence of radiation necrosis of 5% and 10% is predicted to occur at a biologically effective dose of 120 Gy (range, 100-140) and 150 Gy (range, 140-170), respectively. For twice-daily fractionation, a steep increase in toxicity appears to occur when the biologically effective dose is >80 Gy. For large fraction sizes (>or=2.5 Gy), the incidence and severity of toxicity is unpredictable. For single fraction radiosurgery, a clear correlation has been demonstrated between the target size and the risk of adverse events. Substantial variation among different centers' reported outcomes have prevented us from making toxicity-risk predictions. Cognitive dysfunction in children is largely seen for whole brain doses of >or=18 Gy. No substantial evidence has shown that RT induces irreversible cognitive decline in adults within 4 years of RT.

Fig. 1

Relationship between volume receiving high-dose irradiation and incidence of radiation necrosis in single-fraction stereotactic radiosurgery. Studies differed in their completeness of follow-up, definition of volume, and definition of radiation necrosis. Graph based on data presented in Table 1. Volume plotted as a point, representing mid-point of volume range. V₁₀ = volume receiving 10 Gy; V₁₂ = volume receiving 12 Gy; RxV = treatment volume. Flickinger data is shown for patients with either radiologic or symptomatic evidence of necrosis (marked as “All”), or only those with symptomatic necrosis (Symp). The other authors’ data refers to symptomatic necrosis.

Fig. 2

Relationship between biologically effective dose (BED) and radiation necrosis after fractionated radiotherapy. Fit was done using nonlinear least-squares algorithm using Matlab software (The MathWorks, Natick, MA). Nonlinear function chosen was probit model (similar functional form to Lyman model). Dotted lines represent 95% confidence levels; each dot represents data from specific study (Table 2), n = patient numbers as shown. (a) Fraction size <2.5 Gy; (b) fraction size ≥2.5 Gy (data too scattered to allow plotting of “best-fit” line); and (c) twice-daily radiotherapy.