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 afte rloading catheter implantation on the effectiveness of brachytherapy in a r at tumor model. Methods and Materials: Afterloading catheters (4) Here implanted in subcuta neously growing R1M rhabdomyosarcoma in female Wag/Rij rats. A MicroSelectr on (Nucletron) was used for interstitial high-dose-rate irradiation (Ir-192 ). Tumor oxygenation, perfusion, anti cell survival were assessed by pO(2) histography (Eppendorf), Tc-99m injection, and excision assay, respectively . Results: Tumor perfusion was markedly reduced at 1 h after catheter implant ation (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 (10 0.6 +/- 25.7%), but was highly variable with some elf the tumors showing ha rdly any recovery at all. Tumor oxygenation showed a similar pattern, but w ith less recovery. Median pO(2) readings were 13.5, 1.2, and 5.3 mm Hg befo re and at 1 and 24 h after implantation, respectively (7 tumors). The perce ntages of pO(2) readings less than or equal to 2.5 mm Hg were 18.9%, 55.6%, and 41.3% at these time points. The difference in cell survival after irra diation (10 Gy) at 1 or 24 h after implantation was compatible with a radio biological 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 reduct ion of the radiation effect. This transient hypoxia might be exploited by c ombining irradiation with properly timed treatments targeting hypoxic cells . (C) 2000 Elsevier Science Inc.