Radiosurgery and fractionated radiation therapy: comparison of different techniques in an in vivo rat glioma model.

To identify histological changes and effects on survival in rats harboring C6 gliomas, the authors compared radiosurgery to different fractionated radiation therapy regimens including doses of calculated biological equivalence. Rats were randomized to control (54 animals) or treatment groups after implantation of C6 glioma cells into the right frontal brain region. At 14 days, treated rats underwent stereotactic radiosurgery (35 Gy to tumor margin; 22 animals), whole-brain radiation therapy (WBRT) (20 Gy in five fractions; 18 animals), radiosurgery plus WBRT (13 animals), hemibrain radiation therapy (85 Gy in 10 fractions; 16 animals) or single-fraction hemibrain irradiation (35 Gy; 10 animals). When compared to the control group (median survival 22 days), prolonged survival was identified after radiosurgery (p < 0.0001), radiosurgery plus WBRT (p < 0.0001), WBRT alone (p = 0.0002), hemibrain radiation therapy to 85 Gy (p < 0.0001), and 35-Gy hemibrain single-fraction irradiation (p = 0.004). Compared to the control group (mean tumor diameter, 6.8 mm), the tumor size was reduced in all treatment groups except WBRT alone. Reduced tumor cell density was exhibited in rats that underwent radiosurgery (p = 0.006) and radiosurgery plus WBRT (p = 0.009) when compared with rats in the control group, a finding not observed after any fractionated regimen. Increased intratumoral edema was identified after radiosurgery (p = 0.03) and combined treatment (p = 0.05), but not after fractionated radiation therapy or 35-Gy single-fraction hemibrain irradiation. In this animal model, the addition of radiosurgery significantly increased tumor cytotoxicity, potentially at the expense of radiation effects to regional brain. We found no difference in survival benefit or tumor diameter in animals that underwent radiosurgery compared to the calculated biologically equivalent regimen of 10-fraction radiation therapy to 85 Gy. The histological responses after radiosurgery were generally greater than those achieved with biologically equivalent doses of fractionated radiation therapy.