A phase III randomised trial investigating the benefits of the addition of oncothermia to chemo-radiation for cervical cancer in HIV-positive and -negative women in South Africa

Abstract

Introduction: Outcomes for locally advanced cervical cancer (LACC) patients in low-tomiddle-income countries (LMICs), where HIV infection is prevalent and resources are limited, are poor. Hyperthermia is an effective radiosensitiser, but cost and complexity have prevented its use in LMICs. Modulated electro-hyperthermia (mEHT) challenges the dosing concepts of hyperthermia and is potentially an affordable alternative to conventional hyperthermia.

Methodology: In this Phase III controlled trial, participants with FIGO stages IIB to IIIB LACC were randomised (stratum: HIV status, accounting for age and disease stage) to receive chemoradiotherapy with/without mEHT (twice a week, 55 minutes, 130W). HIVpositive participants with a CD4 count >200cells/µL / on antiretroviral therapy for >6 months were included. Pre- and six months post-treatment 18F-FDG PET/CT scans were administered. Local disease control (LDC), six month local disease-free survival (LDFS) and disease pattern were assessed. Early toxicity was analysed (CTCAE V4.0 criteria) and quality of life questionnaires were administered. All participants signed an informed consent. The trial was approved by the Human Research Ethics Committee (M120477/M190295) and registered on ClincialTrials.gov (ID: NCT03332069).

Results: During the recruitment period (January 2014 to November 2017), 271 women were screened and 210 were randomised for trial. On pre-treatment 18F-FDG PET/CT studies, no significant difference in nodal presentation between HIV-positive and – negative participants was noted and 54 participants in each treatment group presented with extra-pelvic nodal disease. There was no significant difference in treatment toxicity, regardless of HIV status, between groups. In the participants eligible for analysis at six months (mEHT: n=101; Control: n=101), six month LDFS was significantly higher in the mEHT Group (n=39[38.6%] versus n=20[19.8%]; p=0.003), as was LDC (n=40[45.5%] versus n=20[24.1%]; p=0.003). In participants with extra-pelvic disease, complete metabolic resolution of all disease was seen in 13[24.1%] mEHT and 3[5.6%] Control Group participants (Chi2, Fisher’s exact: p=0.013) with no difference seen based on HIV status.

Conclusion: mEHT is a safe, effective and affordable adjunct to chemoradiotherapy for HIV-positive and –negative LACC patients in resource-constrained settings, resulting in improved local control rates and a possible potentiation of the abscopal effect. Long term follow-up is planned to determine the effect on survival rates.