Changes in tumor oxygenation during a combined treatment with fractionated irradiation and hyperthermia: An experimental study

Purpose: To determine the influence of adjuvant hyperthermia on the oxygenation status of fractionated irradiated tumors. Methods and Materials: Oxygen partial pressure (pO₂) in rat rhabdomyosarcomas (R1H) was measured sequentially at weekly intervals during a fractionated irradiation with ⁶⁰Co-γ-rays (60 Gy/20f/4 weeks) in combination with local hyperthermia (8 f(HT) at 43°C, 1 h/4 weeks). Tumors were heated twice weekly with a 2450 MHz microwave device at 43°C, 1 h starting 10 min after irradiation. The pO₂ measurements (pO₂-histograph, Eppendorf, Germany) were performed in anesthetized animals during mechanical ventilation and in hemodynamic steady state. All tumor pO₂ measurements were correlated to measurements of the arterial oxygen partial pressure (paO₂) determined by a blood gas analyzer. Results: The oxygenation status of R1H tumors decreased continuously from the start of the combined treatment, with increasing radiation dose and number of heat fractions. In untreated controls a median tumor pO₂ of 23 ± 2 mmHg (mean ± SEM) was measured. Tumor pO₂ decreased to 11 ± 2 mmHg after 30 Gy + 4 HT (2 weeks), and to 6 ± 2 mmHg after 60 Gy + 8HT (4 weeks). The increase in the frequency of pO₂-values below 5 mmHg and the decrease in the range of the pO₂ histograms [Δp(10/90)] further indicated that tumor hypoxia increased relatively rapidly from the start of combined treatment. After 60 Gy + 8HT 48 ± 5% (mean ± SEM) of the pO₂-values recorded were below 5 mmHg. Conclusions: These findings suggest that adjuvant hyperthermia to radiotherapy induces greater changes in tumor oxygenation than radiation alone [cf. (39)]. This might be of importance for the temporary application of hyperthermia in the course of a conventional radiation treatment.