TEMPORAL-LOBE (TL) DAMAGE FOLLOWING SURGERY AND HIGH-DOSE PHOTON AND PROTON IRRADIATION IN 96 PATIENTS AFFECTED BY CHORDOMAS AND CHONDROSARCOMAS OF THE BASE OF THE SKULL

Purpose: To determine the temporal lobe (TL) damage rate in 96 patient s treated with high-dose proton and photon irradiation for chordomas a nd chondrosarcomas of the base of the skull. Methods and Materials: Th e records of 96 consecutive patients treated at Massachusetts General Hospital (MGH) and Harvard Cyclotron Laboratory (HCL) between June 198 4 and 1993, for chordomas and chondrosarcomas of the base of the skull were reviewed. All the patients had undergone some degree of resectio n of the tumor prior to radiation therapy. Seventy-five patients were classified as ''primary tumors'' and 21 as recurrent or regrowing tumo rs after one or more surgical procedures. All the patients were random ized to receive 66.6 or 72 cobalt Gray equivalent (CGE) on a prospecti ve dose-searching study by proton and photon irradiation (Radiation Th erapy Oncology Group #85-26) with conventional fractionation (1.8 CGE/ day, 5 fractions/week). All treatments were planned using the three-di mensional (3D) planning system developed at the Massachusetts General Hospital, and the dose was delivered using opposed lateral fields for the photon component and a noncoplanar isocentric technique for the pr oton component. Clinical symptoms of TL damage were classified into 4 grades. Computerized tomography (CT) and magnetic resonance imaging (M RI) scans were evaluated for white matter changes. Abnormalities assoc iated with persistent or recurrent tumor were distinguished from radia tion-induced changes. TLs were delineated on the original scans of the 10 patients with damage and those of a group of 33 patients with no c linical or MRI evidence of injury. Dose distributions were calculated and dose-volume histograms were obtained for these patients. Results: Of the patients, 10 developed TL damage, with bilateral injury in 2 an d unilateral injury in 8. The cumulative TL damage incidence at 2 and 5 years was 7.6 and 13.2%, respectively. The MRI areas suggestive of T L damage were always separated from the tumor bed. Symptoms were sever e to moderate in 8 patients. Several baseline factors, tumor- or host- related, were analyzed to evaluate their predictivity for TL damage: a ge, gender, tumor site, histology, type of presentation, type and numb er of surgical procedures, primary tumor volume, prescribed dose, norm al tissue involvement, and volume of TL receiving doses ranging betwee n 10 and 50 CGE or more. Only gender, in a univariate analysis (log ra nk) was a significant predictor of damage (0.0155), with male patients being at significantly higher risk of TL injury. In a stepwise Cox re gression that included gender as a variable, no other baseline variabl e improved the prediction of damage. Conclusions: The 2- and 5-year cu mulative TL damage rates were 7.6 and 13.2%, respectively. Despite the different TL damage rates related to age, tumor volume, number of sur gical procedures prior to radiation therapy, and prescribed doses to t he tumor, only gender was a significant predictor of damage (p = 0.015 5) using a univariate (log rank) test. Chordomas and chondrosarcomas o f the base of the skull may represent an interesting model to evaluate the TL damage rates because of their extradural origin, displacing th e white matter instead of infiltrating it as gliomas do, because of th eir longer local recurrence-free survival other than gliomas and other brain tumors and because of the high doses of irradiation delivered t o the target volume to obtain local control. (C) 1998 Elsevier Science Inc.