The response of two human tumor xenografts to fractionated irradiation. The derivation of alpha/beta ratios from growth delay, tumor control, and in vitro cell survival assays.

A series of growth delay experiments was performed to derive alpha/beta ratios for two human neoplasms growing as xenografts in the hind limbs of NCr/Sed nude mice. The tumors were irradiated at 6 mm mean diameter under clamp-hypoxic conditions in one, two, four, or eight fractions, 2 fractions per day with a minimum intertreatment interval of 4 hr and a maximum overall treatment time of 3 days. The alpha/beta ratios derived for the high grade glioma U87 and the pharyngeal squamous carcinoma FaDu were 38 and 20 Gy, respectively. Comparably high values were derived from the same two tumors in a reanalysis of fractionated TCD50 data. The alpha/beta ratios were similarly high whether the TCD50 data were analyzed using the Full Effect plot or the Direct Method. For comparison, cell survival assays were performed on U87 and FaDu irradiated in vitro under plateau-phase, aerobic conditions. The alpha/beta ratios obtained were 9.2 and 15.0 Gy, respectively. Such high alpha/beta values suggest a therapeutic gain could result from the use of small doses per fraction.