Combined Hyperthermia and Re-Irradiation in Non-Breast Cancer Patients: A Systematic Review

SIMPLE SUMMARY: Hyperthermia in the range of 39–43 °C is associated with potent radiosensitization. The clinical benefit of combined radiotherapy and hyperthermia has been shown for a variety of indications. Regarding re-irradiation, added hyperthermia can be considered for locoregional breast cancer recurrence with isolated unresectable disease or as an adjuvant therapy after resection. For other cancer entities, the clinical evidence is scarce. This review aims to systematically summarize the currently available literature. The final search was performed on 29 August 2022. ABSTRACT: Purpose: This systematic literature review summarizes clinical studies and trials involving combined non-ablative hyperthermia and re-irradiation in locoregionally recurrent cancer except breast cancer. Methods: One database and one registry, MEDLINE and clinicaltrials.gov, respectively, were searched for studies on combined non-ablative hyperthermia and re-irradiation in non-breast cancer patients. Extracted study characteristics included treatment modalities and re-irradiation dose concepts. Outcomes of interest were tumor response, survival measures, toxicity data and palliation. Within-study bias assessment included the identification of conflict of interest (COI). The final search was performed on 29 August 2022. Results: Twenty-three articles were included in the final analysis, reporting on 603 patients with eight major tumor types. Twelve articles (52%) were retrospective studies. Only one randomized trial was identified. No COI statement was declared in 11 studies. Four of the remaining twelve studies exhibited significant COI. Low study and patient numbers, high heterogeneity in treatment modalities and endpoints, as well as significant within- and across-study bias impeded the synthesis of results. Conclusion: Outside of locoregionally recurrent breast cancer, the role of combined moderate hyperthermia and re-irradiation can so far not be established. This review underscores the necessity for more clinical trials to generate higher levels of clinical evidence for combined re-irradiation and hyperthermia.