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OBJECTIVE: Modulated electro-hyperthermia (mEHT) is a capacitive coupled hyperthermia technique which transmits amplitude modulated 13.56MHz radiofrequency waves between two electrodes. mEHT is being investigated as an adjunct to chemoradiotherapy (CRT) in a Phase III Randomised Controlled Trial  for locally advanced cervical cancer patients in South Africa. We reported previously on the improved local disease control with the addition of mEHT (45.5% versus 24.1%; p=0.003), without any significant effect on early toxicity, and a potential abscopal response in participants in whom extra-pelvic nodal disease was visualized on the pre-treatment ¹⁸F-FDG PET/CT studies. In this report we present updated data on three year survival.

MATERIALS AND METHODS: Inclusion criteria: FIGO stages IIB to IIIB carcinoma of the cervix, eligible for CRT with radical intent. HIV-positive participants were included provided they had a CD4 count >200cells/µL or had been treated with antiretroviral therapy for >6 months. All participants were required to sign an informed consent. 210 Participants were randomized into a control group and an intervention (mEHT) group (stratum: HIV status, accounting for age and stage). Both groups received CRT: 50Gy/25fractions external beam radiation (EBRT); three fractions of 8Gy HDR Brachytherapy; and two doses of cisplatin (80mg/m2). The mEHT group received two mEHT treatments per week (55 minutes at 130W), immediately before EBRT. Disease response was assessed at six months post treatment. Approval was obtained from the local ethics committee (M190295) and the trial was registered on the National Clinical Trials Register (ID:3012) prior to the enrolment of participants, (ClincialTrials.gov ID: NCT03332069).

98 out of 106[93%] and 99 out of 104[95%] participants in the mEHT and control groups respectively, were evaluated at three years. Participants in the mEHT group were significantly more likely to achieve three year all mortality survival (n=48[49%]) than those in the control group (n=38[38%]) (HR: 1.45; 95%CI: 1.0-2.1; p=0.044). Disease free survival at three years was significantly more likely in the mEHT group (n=33[34%]) than in the control group (n=14[14%]; p=0.001), (OR:2.4; 95%CI: 1.3-4.4; p=0.003). In the subset of participants in which a potential abscopal response was observed, 10 of the 13 participants in the mEHT group, and 2 of the 3 in the control group, are alive and disease free at three. There were no significant differences in late toxicities between the groups.

CONCLUSION: mEHT improves local disease control as well as three year survival and disease free survival at three years. These results provide strong motivation for the incorporation of mEHT into clinical practices as a radiosensitiser for locally advanced cervical cancer, especially in resource constrained settings.