Preclinical study of reirradiation with hyperthermia in recurrent murine tumors and normal mouse skin
DOI:
https://doi.org/10.2340/1651-226X.2025.43995Keywords:
Re-irradiation, Hyperthermia, Recurrent tumor, Tumor Control, Acute toxicityAbstract
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.
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Copyright (c) 2025 Charlemagne A Folefac, Priyanshu M. Sinha, Niels Bassler, Brita S. Sørensen, Michael R. Horsman
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