Tumor hypoxia-a confounding or exploitable factor in interstitial brachytherapy? Effects of tissue trauma in an experimental rat tumor model

Purpose: To evaluate the potential effects of tumor hypoxia induced by afterloading catheter implantation on the effectiveness of brachytherapy in a rat tumor model.Methods and Materials: Afterloading catheters (4) were implanted in subcutaneously growing R1M rhabdomyosarcoma in female Wag/Rij rats. A MicroSelectron (Nucletron) was used for interstitial high-dose-rate irradiation (192Ir). Tumor oxygenation, perfusion, and cell survival were assessed by pO2 histography (Eppendorf), Tc-99m injection, and excision assay, respectively.Results: Tumor perfusion was markedly reduced at 1 h after catheter implantation (33.9 ± 6.0% (SEM, n = 9) of control) and partly recovered after 5 h (61.5 ± 12.2%). At 24 h, the perfusion level reached control values (100.6 ± 25.7%), but was highly variable with some of the tumors showing hardly any recovery at all. Tumor oxygenation showed a similar pattern, but with less recovery. Median pO2 readings were 13.5, 1.2, and 5.3 mm Hg before and at 1 and 24 h after implantation, respectively (7 tumors). The percentages of pO2 readings ≤ 2.5 mm Hg were 18.9%, 55.6%, and 41.3% at these time points. The difference in cell survival after irradiation (10 Gy) at 1 or 24 h after implantation was compatible with a radiobiological oxygen effect.Conclusion: Implantation of brachytherapy afterloading catheters induces an increased level of hypoxia for several hours by disrupting tumor perfusion, causing both a modest degree of direct cell kill and a significant reduction of the radiation effect. This transient hypoxia might be exploited by combining irradiation with properly timed treatments targeting hypoxic cells. Copyright (C) 2000 Elsevier Science Inc.