D. Kondziolka et al., RADIOSURGERY AND FRACTIONATED RADIATION-THERAPY - COMPARISON OF DIFFERENT TECHNIQUES IN AN IN-VIVO RAT GLIOMA MODEL, Journal of neurosurgery, 84(6), 1996, pp. 1033-1038
To identify histological changes and effects on survival in rats harbo
ring C6 gliomas, the authors compared radiosurgery to different fracti
onated radiation therapy regimens including doses of calculated biolog
ical equivalence. Rats were randomized to control (54 animals) or trea
tment groups after implantation of C6 glioma cells into the right fron
tal brain region. At 14 days, treated rats underwent stereotactic radi
osurgery (35 Gy to tumor margin; 22 animals), whole-brain radiation th
erapy (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 anima
ls). When compared to the control group (median survival 22 days), pro
longed survival was identified after radiosurgery (p < 0.0001), radios
urgery plus WBRT (p < 0.0001), WBRT alone (p = 0.0002), hemibrain radi
ation therapy to 85 Gy (p < 0.0001), and 35-Gy hemibrain single-fracti
on 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 t
hat underwent radiosurgery (p = 0.006) and radiosurgery plus WBRT (p =
0.009) when compared with rats in the control group, a finding not ob
served after any fractionated regimen. Increased intratumoral edema wa
s identified after radiosurgery (p = 0.03) and combined treatment (p =
0.05), but not after fractionated radiation therapy or 35-Gy single-f
raction hemibrain irradiation. In this animal model, the addition of r
adiosurgery significantly increased tumor cytotoxicity, potentially at
the expense of radiation effects to regional brain. We found no diffe
rence in survival benefit or tumor diameter in animals that underwent
radiosurgery compared to the calculated biologically equivalent regime
n of 10-fraction radiation therapy to 85 Gy. The histological response
s after radiosurgery were generally greater than those achieved with b
iologically equivalent doses of fractionated radiation therapy.