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-i...
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Medical Journals Sweden
2025-07-01
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| Series: | Acta Oncologica |
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| Online Access: | https://medicaljournalssweden.se/actaoncologica/article/view/43995 |
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| author | Charlemagne A Folefac Priyanshu M. Sinha Niels Bassler Brita S. Sørensen Michael R. Horsman |
| author_facet | Charlemagne A Folefac Priyanshu M. Sinha Niels Bassler Brita S. Sørensen Michael R. Horsman |
| author_sort | Charlemagne A Folefac |
| collection | DOAJ |
| description | 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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| format | Article |
| id | doaj-art-dc5e9fca334945d2a3eae95976b5fbc6 |
| institution | DOAJ |
| issn | 1651-226X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Medical Journals Sweden |
| record_format | Article |
| series | Acta Oncologica |
| spelling | doaj-art-dc5e9fca334945d2a3eae95976b5fbc62025-08-20T03:08:55ZengMedical Journals SwedenActa Oncologica1651-226X2025-07-016410.2340/1651-226X.2025.43995Preclinical study of reirradiation with hyperthermia in recurrent murine tumors and normal mouse skinCharlemagne A Folefac0https://orcid.org/0009-0002-4001-7547Priyanshu M. Sinha1https://orcid.org/0000-0001-6115-1556Niels Bassler2https://orcid.org/0000-0002-4160-1078Brita S. Sørensen3https://orcid.org/0000-0002-3955-4735Michael R. Horsman4https://orcid.org/0000-0003-1578-5691Experimental Clinical Oncology-Department of Oncology, Aarhus, DenmarkExperimental Clinical Oncology-Department of Oncology, Aarhus, DenmarkDanish Center for Particle Therapy, Aarhus University Hospital, Aarhus, DenmarkExperimental Clinical Oncology-Department of Oncology, Aarhus, Denmark; Danish Center for Particle Therapy, Aarhus University Hospital, Aarhus, DenmarkExperimental Clinical Oncology-Department of Oncology, Aarhus, DenmarkBackground: 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. https://medicaljournalssweden.se/actaoncologica/article/view/43995Re-irradiationHyperthermiaRecurrent tumorTumor ControlAcute toxicity |
| spellingShingle | Charlemagne A Folefac Priyanshu M. Sinha Niels Bassler Brita S. Sørensen Michael R. Horsman Preclinical study of reirradiation with hyperthermia in recurrent murine tumors and normal mouse skin Acta Oncologica Re-irradiation Hyperthermia Recurrent tumor Tumor Control Acute toxicity |
| title | Preclinical study of reirradiation with hyperthermia in recurrent murine tumors and normal mouse skin |
| title_full | Preclinical study of reirradiation with hyperthermia in recurrent murine tumors and normal mouse skin |
| title_fullStr | Preclinical study of reirradiation with hyperthermia in recurrent murine tumors and normal mouse skin |
| title_full_unstemmed | Preclinical study of reirradiation with hyperthermia in recurrent murine tumors and normal mouse skin |
| title_short | Preclinical study of reirradiation with hyperthermia in recurrent murine tumors and normal mouse skin |
| title_sort | preclinical study of reirradiation with hyperthermia in recurrent murine tumors and normal mouse skin |
| topic | Re-irradiation Hyperthermia Recurrent tumor Tumor Control Acute toxicity |
| url | https://medicaljournalssweden.se/actaoncologica/article/view/43995 |
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