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

Abstract

To evaluate the potential effects of tumor hypoxia induced by afterloading catheter implantation on the effectiveness of brachytherapy in a rat tumor model. 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 ((192)Ir). Tumor oxygenation, perfusion, and cell survival were assessed by pO(2) histography (Eppendorf), Tc-99m injection, and excision assay, respectively. 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 pO(2) 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 pO(2) 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. 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.