Fraction size dependent sparing effects of clinically relevant fractionated radiotherapy protocols on human glioma multicellular spheroids

Clinically relevant X‐ray irradiation protocols were chosen to evaluate the radiation response of human glioma cell lines, A1207 and U‐373 MG, grown as multicellular spheroids. The protocols included single‐dose fraction (SF), conventional fractionation (CF; 2 Gy per fraction, 24 hr interval), hyperfractionation (HF; 1.0 Gy per fraction, 12 hr interval), and accelerated hyperfractionation (AHF; 1.5 Gy per fraction, 6 hr interval). Spheroids from both cell lines are clearly more refractory to the cytotoxic effects of multifractionated irradiation than the single‐dose irradiation. Dose‐sparing effects of CF or HF were comparable in the two cell ilnes. More detailed studies of A1207 spheroids showing sparing effects are fraction size dependent. The smaller the dose size per fraction, the larger the sparing effect. In order to achieve the same biological effect using multifractionated irradiation, compared to single dose, a higher dose is needed to compensate for sublethal damage repair which occurred in the fraction intervals. The relative doses required for achieving isoeffect as SF were 145%, 160%, and 169% for CF, AHF, and HF, respectively, when a total dose of 10 Gy was administered. The isoeffective doses for AHF and HF compared to CF were 113% and 126%, respectively. There was also an increase in sparing effect with increasing total dose administered as multifraction. Our results suggest that in the design of multifractionated radiotherapy regimens, fraction size dependent sparing effects related to dose per fraction and total dose on human gliomas should be taken into consideration to optimize therapeutic outcome. © 1994 Wiley‐Liss, Inc.