[Biological equivalency of high single doses used in intraoperative irradiation]

Intra-operative radiotherapy is being used more and more frequently; this raises the problem of the equivalence of these large doses delivered in a single fraction, especially when a second line, complementary external irradiation is planned afterwards. The linear quadratic (LQ) model is probably the most convenient way to compare 2 irradiation schedules delivered with different doses per fraction. However, in the case of intra-operative radiotherapy, one should question the use of the LQ equation; this model actually predicts a continuous bending of the survival curve, while most experimental curves show a trend towards exponential at high dose levels. As a result, with the very large doses (20-30 Gy) given here, the LQ model would lead to overestimate the efficacy--and the toxicity--of intra-operative irradiation. We thus propose to calculate the equivalent fractionated doses by combining 2 models; the LQ model, considered to be reliable up to 7 Gy, and the 2 components' target model, which tends towards an exponential at high dose level. Moreover, we must take into account the hypoxic component of the tumour, since the single fraction, intra-operative technique cannot benefit from the reoxygenation occurring during conventional fractionated irradiations. Calculations indicate that for a partially hypoxic tumour, the effect of a large dose (20-30 Gy) is very similar to the one which would be achieved by the same dose given in a conventionally fractionated way, increased by the dose necessary to compensate for the proliferation occurring during treatment. For healthy tissues, assuming that all cells are well oxygenated, the equivalent fractionated dose is, in particular, much higher for late responding tissues.

1) there is little hope for sterilizing any carcinoma with only one fraction of 20-30 Gy; 2) however, intra-operative irradiation, focussing on a small volume, could contribute to the tumour eradication; 3) the intra-operative irradiation technique should, as much as possible, spare the neighbouring normal tissues, regarding the risks of long term complications.