Preclinical study of reirradiation with hyperthermia in recurrent murine tumors and normal mouse skin.

Background: Re-irradiation is an essential treatment option for recurrent tumours but is limited by normal tissue tolerance. Hyperthermia can enhance radiation efficacy by impairing DNA repair and improving tumor oxygenation; however, limited preclinical data are evaluating its combination with re-irradiation in recurrent tumor settings and normal skin.

Objective: The study aims to determine optimal priming doses for skin and tumor response and evaluate the radiosensitising effect of hyperthermia when combined with re-irradiation in preclinical models.

Methods: The right rear foot of non-tumor-bearing CDF1 mice or a C3H mammary carcinoma implanted in the foot were treated with a single radiation dose or reirradiation + hyperthermia (42.5°C, 1-h). Initial experiments identified a priming dose of 30 Gy that induced moderate but reversible acute skin toxicity and a tumor dose of 40 Gy that resulted in full regression with regrowth in 30-35 days from treatment. Reirradiation dose-response studies were conducted to determine the MDD₅₀ (skin) and TCD₅₀ (tumor) with and without hyperthermia. Thermal Enhancement Ratios (TER) and Therapeutic Gain Factor (TGF) were calculated.

Results: The MDD₅₀ for reirradiation-induced skin damage was 25 Gy, reduced to 18 Gy with hyperthermia (TER = 1.4). In tumours, the TCD₅₀ decreased from 49 Gy (reirradiation alone) to 29 Gy with hyperthermia (TER = 1.7). A TGF of 1.2 was observed, indicating selective enhancement of tumor response relative to skin toxicity.

Conclusion: Hyperthermia enhances the therapeutic effect of reirradiation by improving tumor control at lower doses, supporting its potential in recurrent cancer treatment strategies.