The effect of modulated electro-hyperthermia on local disease control in HIV-positive and -negative cervical cancer women in South Africa: Early results from a phase III randomised controlled trial

Carrie Anne Minnaar, Jeffrey Allan Kotzen, Olusegun Akinwale Ayeni, Thanushree Naidoo, Mariza Tunmer, Vinay Sharma, Mboyo-Di-Tamba Vangu, Ans Baeyens, Carrie Anne Minnaar, Jeffrey Allan Kotzen, Olusegun Akinwale Ayeni, Thanushree Naidoo, Mariza Tunmer, Vinay Sharma, Mboyo-Di-Tamba Vangu, Ans Baeyens

Abstract

Background: The global burden of cervical cancer remains high with the highest morbidity and mortality rates reported in developing countries. Hyperthermia as a chemo- and radiosensitiser has shown to improve treatment outcomes. This is an analysis of the local control results at six months post-treatment of patients enrolled in an ongoing study investigating the effects of the addition of modulated electro-hyperthermia (mEHT) to chemoradiotherapy for the treatment of HIV-positive and -negative cervical cancer patients in a low-resource setting.

Methods: This ongoing Phase III randomised controlled trial, conducted at a state hospital in Johannesburg, South Africa, was registered with the appropriate ethics committee. After signing an informed consent, participants with FIGO stages IIB to IIIB squamous cell carcinoma of the cervix were randomised to receive chemoradiotherapy with/without mEHT using a secure online random-sampling tool (stratum: HIV status) accounting for age and stage. Reporting physicians were blind to treatment allocation. HIV-positive participants on antiretroviral treatment, or with a CD4 count >200cell/μL were included. mEHT was administered 2/weekly immediately before external beam radiation. The primary end point is local disease control (LDC) and secondary endpoints are toxicity; quality of life analysis; and two year survival. We report on six month LDC, including nodes visualised in the radiation field on 18F-FDG PET/CT (censored for six month survival), and six month local disease free survival (LDFS) (based on intention to treat). Trial status: Recruitment closed (ClinicalTrials.gov: NCT03332069).

Results: 271 participants were recruited between January 2014 and November 2017, of which 210 were randomised for trial and 202 were available for analysis at six months post-treatment (mEHT: n = 101; Control: n = 101). Six month LDFS was higher in the mEHT Group (n = 39[38.6%]), than in the Control Group (n = 20[19.8%]); p = 0.003). LDC was also higher in the mEHT Group (n = 40[45.5%]) than the Control Group (n = 20[24.1%]); (p = 0.003).

Conclusion: Our results show that mEHT is effective as a chemo-radiosensitiser for cervical cancer, even in high risk a patients and resource-constrained settings.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. Trial profile: Consort flow diagram.
Fig 1. Trial profile: Consort flow diagram.
Abbreviations: mEHT: Modulated Electro-Hyperthermia; LDFS: Local Disease Free Survival.
Fig 2. Tumour Response as Seen on…
Fig 2. Tumour Response as Seen on 18F-FDG PET/CT (PERCIST 1.0) by Treatment Group.
mEHT: Fischer’s exact table of association between all four metabolic responses and mEHT: p = 0.005*. Abbreviations: mEHT: Modulated electro-hyperthermia; CMR: Complete Metabolic Response; PMR: Partial Metabolic Response; SMD: Stable Metabolic Disease; PMD: Progressed Metabolic Disease.
Fig 3. Tumour Response on 18 F-FDG…
Fig 3. Tumour Response on 18F-FDG PET/CT (PERCIST 1.0) by Treatment Group and HIV Status.
Total participants in each subgroup: HIV-Positive mEHT: n = 40; HIV-Positive Control: n = 35; HIV-Negative mEHT: n = 45; HIV-Negative Control: n = 38. Abbreviations: mEHT: Modulated electro-hyperthermia.

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