Dose-effect relation of interstitial low-dose-rate radiation (Ir 192) in an animal tumor model

Abstract

One way to deliver high doses of radiation to deep seated tumors without damaging the surrounding tissue is by interstitial techniques. This is commonly applied clinically; however, biological data of tumor response to interstitial low-dose-rate gamma irradiation are scarce. Therefore, we have studied the response of rhabdomyosarcoma R1 tumors implanted in the flanks of female Wag/Rij rats using an interstitial Ir 192 afterloading system. A template was developed by which four catheters can be implanted in a square geometry with a fixed spacing. Subsequently four Ir 192 wires of 2 cm length each are inserted. For dose prescription the highest isodose enveloping the tumor volume was chosen. Interstitial irradiation was performed using tumor volumes of 1500–2000 mm 3. A range of minimum tumor doses of 20 up to 115 Gy were given at a mean dose-rate of 48 cGy/hr. Dose-effect relations were obtained from tumor growth curves and tumor cure data, and compared to data from external irradiation. The dose required for 50% cures with interstitial irradiation (TCD50) appears to be 95 ± 9 Gy. The TCD50 for low-dose-rate interstitial gamma irradiation is 1.5 times the TCD50 for single dose external X ray irradiation at high dose rates, but is comparable to the TCD50 found after fractionated X ray irradiation at high dose rate. Sham treatment of the tumors had no effect on the time needed to reach twice the treatment volume. The growth rate of tumors regrowing after interstitial radiotherapy is not markedly different from the growth rate of untreated (control) tumors (volume doubting time 5.6 ± 1 day), in contrast to the decreased growth rate after external X ray irradiation. It is argued that the absence of a clear tumor bed effect may be explained by some sparing of the stroma by the low-dose-rate of the interstitial irradiation per se as well as by the physical dose distribution of the interstitial Ir 192 sources, giving a relative low dose of radiation to the surrounding normal tissues.