Keywords
Radiotherapy
Superficial tumors
Complete response
Breast cancer
Local recurrence
Head and neck cancer
Submitted : 2025-12-09
Accepted : 2025-12-24
Published : 2026-01-08
Abstract
Objective: Aim to evaluate the efficacy of hyperthermoradiotherapy (HTRT) VS radiation therapy (RT) alone in patients with superficial tumors, mainly including breast cancer, head and neck cancer, and melanoma. The study undertook a systematic review and meta-analysis, and a preset subgroup analysis. Methods: A systematic literature search was conducted of the PubMed database and the bibliographies of related studies. Results: A total of 15 articles (n = 1368) met our eligibility criteria. The meta-analysis of all patients in 19 groups from 15 articles showed HTRT with significant improvement in complete response (CR) versus the RT group (OR = 2.393, 95% CI 1.749–3.274, p = 0.000) with high heterogeneity (χ2 = 33.67, p = 0.014, I2 = 46.5%). Conclusion: HTRT have significant improvement in CR versus RT alone in superficial tumors. A well-researched but maybe underutilized method, HT can have a major clinical impact by improving local tumor management.
References
Folefac C, Sinha P, Bassler N, et al., 2025, Pre-Clinical Studies Investigating the Combination of Hypofractionated Radiation with Hyperthermia in a Murine Tumor and Normal Skin. International Journal of Hyperthermia, 42(1): 2545400.
Datta N, Bodis S, 2019, Hyperthermia with Radiotherapy Reduces Tumour Alpha/Beta: Insights from Trials of Thermoradiotherapy vs Radiotherapy Alone. Radiotherapy and Oncology, 138: 1–8.
Thomsen A, Saalmann M, Nicolay N, et al., 2022, Improved Oxygenation of Human Skin, Subcutis and Superficial Cancers Upon Mild Hyperthermia Delivered by WIRA-Irradiation. Advances in Experimental Medicine and Biology, 1395: 255–261.
Kok H, Cressman E, Ceelen W, et al., 2020, Heating Technology for Malignant Tumors: A Review. International Journal of Hyperthermia, 37(1): 711–741.
Ademaj A, Puric E, Timm O, et al., 2023, Real World Analysis of Quality of Life and Toxicity in Cancer Patients Treated with Hyperthermia Combined with Radio(chemo)therapy. Cancers, 15(4): 1241.
Knoblauch M, Werdel C, Arlt Y, et al., 2025, Surgery for Retroperitoneal Soft Tissue Sarcoma Is Safe Following Multimodal Treatment with Regional Hyperthermia. Annals of Surgical Oncology, 32(12): 9116–9126.
Roohani S, Ehret F, Beck M, et al., 2024, Regional Hyperthermia for Soft Tissue Sarcoma – A Survey on Current Practice, Controversies and Consensus among 12 European Centers. International Journal of Hyperthermia, 41(1): 2342348.
Piazena H, Vaupel P, 2025, Hyperhydration of Breast and Skin Cancers: Effects on Thermophysical Tissue Properties in Clinical Hyperthermia with Water-Filtered Infrared-A Radiation (wIRA) – An Updated Review. International Journal of Hyperthermia, 42(1): 2519352.
Crezee J, van Leeuwen C, Oei A, et al., 2016, Biological Modelling of the Radiation Dose Escalation Effect of Regional Hyperthermia in Cervical Cancer. Radiation Oncology, 11: 14.
Kok H, van der Zee J, Guirado F, et al., 2021, Treatment Planning Facilitates Clinical Decision Making for Hyperthermia Treatments. International Journal of Hyperthermia, 38(1): 532–551.
Chi M, Yang K, Chang Y, et al., 2018, Comparing the Effectiveness of Combined External Beam Radiation and Hyperthermia Versus External Beam Radiation Alone in Treating Patients With Painful Bony Metastases: A Phase 3 Prospective, Randomized, Controlled Trial. International Journal of Radiation Oncology Biology Physics, 100: 78–87.
Harima Y, Ohguri T, Imada H, et al., 2016, A Multicentre Randomised Clinical Trial of Chemoradiotherapy Plus Hyperthermia Versus Chemoradiotherapy Alone in Patients with Locally Advanced Cervical Cancer. International Journal of Hyperthermia, 32(7): 801–808.
Jones E, Oleson J, Prosnitz L, et al., 2005, Randomized Trial of Hyperthermia and Radiation for Superficial Tumors. Journal of Clinical Oncology, 23: 3079–3085.
Scott R, Johnson R, Story K, et al., 1984, Local Hyperthermia in Combination with Definitive Radiotherapy: Increased Tumor Clearance, Reduced Recurrence Rate in Extended Follow-Up. International Journal of Radiation Oncology Biology Physics, 10: 2119–2123.
Dunlop P, Hand J, Dickinson R, et al., 1986, An Assessment of Local Hyperthermia in Clinical Practice. International Journal of Hyperthermia, 2: 39–50.
Perez C, Kuske R, Emami B, et al., 1986, Irradiation Alone or Combined with Hyperthermia in the Treatment of Recurrent Carcinoma of the Breast in the Chest Wall: A Nonrandomized Comparison. International Journal of Hyperthermia, 2: 179–187.
Howard G, Sathiaseelan V, Freedman L, et al., 1987, Hyperthermia and Radiation in the Treatment of Superficial Malignancy: An Analysis of Treatment Parameters, Response and Toxicity. International Journal of Hyperthermia, 3: 1–8.
Lindholm C, Kjellén E, Nilsson P, et al., 1987, Microwave-Induced Hyperthermia and Radiotherapy in Human Superficial Tumours: Clinical Results with a Comparative Study of Combined Treatment Versus Radiotherapy Alone. International Journal of Hyperthermia, 3: 393–411.
Arcangeli G, Benassi M, Cividalli A, et al., 1987, Radiotherapy and Hyperthermia: Analysis of Clinical Results and Identification of Prognostic Variables. Cancer, 60: 950–956.
Egawa S, Tsukiyama I, Watanabe S, et al., 1989, A Randomized Clinical Trial of Hyperthermia and Radiation Versus Radiation Alone for Superficially Located Cancers. Japanese Journal of Therapeutic Radiology and Oncology, 1: 135–140.
Li R, Lin S, Zhang T, 1990, Assessment of Combined Thermoradiotherapy in Recurrent or Advanced Carcinoma of the Breast. Advances in Experimental Medicine and Biology, 267: 521–523.
Datta N, Bose A, Kapoor H, et al., 1990, Head and Neck Cancers: Results of Thermoradio Therapy Versus Radiotherapy. International Journal of Hyperthermia, 6: 479–486.
Perez C, Pajak T, Emami B, et al., 1991, Randomized Phase III Study Comparing Irradiation and Hyperthermia with Irradiation Alone in Superficial Measurable Tumors: Final Report by the Radiation Therapy Oncology Group. American Journal of Clinical Oncology, 14: 133–141.
Valdagni R, Amichetti M, 1994, Report of Long-Term Follow-Up in a Randomized Trial Comparing Radiation Therapy and Radiation Therapy Plus Hyperthermia to Metastatic Lymph Nodes in Stage IV Head and Neck Patients. International Journal of Radiation Oncology Biology Physics, 28: 163–169.
Vernon C, Hand J, Field S, et al., 1996, Radiotherapy with or without Hyperthermia in the Treatment of Superficial Localized Breast Cancer: Results from Five Randomized Controlled Trials—International Collaborative Hyperthermia Group. International Journal of Radiation Oncology Biology Physics, 35: 731–744.
Wahl A, Rademaker A, Kiel K, et al., 2008, Multi-Institutional Review of Repeat Irradiation of Chest Wall and Breast for Recurrent Breast Cancer. International Journal of Radiation Oncology Biology Physics, 70: 477–484.
Huilgol N, Gupta S, Sridhar C, 2010, Hyperthermia with Radiation in the Treatment of Locally Advanced Head and Neck Cancer: A Report of Randomized Trial. Journal of Cancer Research and Therapeutics, 6: 492–496.
Notter M, Stutz E, Thomsen A, 2021, Radiation-Associated Angiosarcoma of the Breast and Chest Wall Treated with Thermography-Controlled, Contactless wIRA-Hyperthermia and Hypofractionated Re-Irradiation. Cancers, 13(15): 3911.
De-Colle C, Beller A, Gani C, et al., 2022, Radiotherapy and Hyperthermia for Breast Cancer Patients at High Risk of Recurrence. International Journal of Hyperthermia, 39(1): 1010–1016.
Veltsista P, Oberacker E, Ademaj A, et al., 2023, Hyperthermia in the Treatment of High-Risk Soft Tissue Sarcomas: A Systematic Review. International Journal of Hyperthermia, 40(1): 2236337.
Ott O, Gaipl U, Lamrani A, et al., 2023, The Emerging Evidence Supporting Integration of Deep Regional Hyperthermia with Chemoradiation in Bladder Cancer. Seminars in Radiation Oncology, 33(1): 82–90.