BRAIN-STEM TOLERANCE TO CONFORMAL RADIOTHERAPY OF SKULL BASE TUMORS

Purpose: The aim of this study was to analyze the long-term incidence of brainstem toxicity in patients treated for skull base tumors with h igh dose conformal radiotherapy. Methods and Materials: Between 1974 a nd 1995, 367 patients with chordomas (n = 195) and chondrosarcomas (II = 172) of the base of skull have been treated with combined megavolta ge photon and 160 MeV proton radiotherapy. Following 3D treatment plan ning with delineation of target volumes and critical nontarget structu res dose distributions and dose-volume histograms were calculated. Rad iotherapy was given an 1.8 Gy or CGE (=Cobalt Gray Equivalent) dose pe r fraction, with prescribed target doses ranging from 63 CGE to 79.2 C GE (mean = 67.8 CGE). Doses to the brainstem surface were limited to l ess than or equal to 64 CGE and to the brainstem center to less than o r equal to 53 CGE. Results: Follow-up time ranged from 6 months to 21. 4 Sears (mean = 42.5 months). Brainstem toxicity was observed in 17 of 367 patients attributable to treatment, resulting in death of three p atients. Actuarial rates of 5 and 10-year high-grade toxicity-free sur vival were 94 and 88%, respectively. Increased risk of brainstem toxic ity was significantly associated with maximum dose to brainstem, volum e of brainstem receiving greater than or equal to 50 CGE, greater than or equal to 55 CGE, and greater than or equal to 60 CGE, number of su rgical procedures, and prevalence of diabetes or high blood pressure. Multivariate analysis identified three independent factors as importan t prognosticators: number of surgical procedures (p < 0.001), volume o f the brainstem receiving 60 CGE (p < 0.001), and prevalence of diabet es (p < 0.01). Conclusions: Tolerance of brainstem to fractionated rad iotherapy appears to be a steep function of tissue volume included in high dose regions rather than the maximum dose of brainstem alone. In addition, presence of predisposing factors as well as extent of surgic al manipulation can significantly lower brainstem tolerance in the ind ividual patient. (C) 1997 Elsevier Science Inc.