Abstract
Introduction HIV infection is associated with increased treatment-related toxicity and worse outcomes in locally advanced cervical cancer patients (LACC), especially in resource-constrained settings. Local control (LC) in a phase III randomized, controlled trial investigating modulated electro-hyperthermia (mEHT) on LACC patients in South Africa (ethics registration: M120477/M190295), was significantly higher in participants randomized to receive chemoradiotherapy (CRT) with mEHT compared to CRT alone (stratum: HIV status, accounting for age and stage). This analysis investigates whether mEHT adds to the toxicity profile of CRT in HIV-positive LACC participants. Methods Inclusion criteria: signed informed consent; International Federation of Gynecology and Obstetrics stages IIB to IIIB squamous cell carcinoma of the cervix; HIV-positive patients: CD4 count >200 cell/µL/on antiretroviral treatment for >6 months; eligible for CRT with radical intent. Recruitment: January 2014 to November 2017 (ClinicalTrials.gov: NCT03332069). Acute toxicity (evaluated using CTCAE v4 criteria) and quality of life (according to EORTC forms) in 206 participants randomized for treatment were evaluated alongside the LC results to determine safety and efficacy in HIV-positive participants. Results Compliance to mEHT treatment was high (97% completed ≥8 treatments) with no significant differences in CRT-related toxicity between treatment groups or between HIV-positive and -negative participants. Adverse events attributed to mEHT were minor, even in obese patients, and did not affect CRT compliance. Participants treated with mEHT reported improved fatigue, pain, emotional and cognitive functioning. Conclusion mEHT did not cause unexpected CRT-related toxicities and is a safe treatment modality for HIV-positive patients, with minor limitations regarding body weight, even in a low-resource setting.
Highlights
HIV infection is associated with increased treatment-related toxicity and worse outcomes in locally advanced cervical cancer patients (LACC), especially in resource-constrained settings
The incidence of locally advanced cervical cancer (LACC) in developed countries has decreased since the introduction of screening and Human Papilloma Virus (HPV) vaccination programs [1,2], yet morbidity and mortality rates remain high in low-resource settings [3]
Radiotherapy (RT) with weekly concurrent cisplatin is the standard of care for LACC [4], in patients who are unable to receive cisplatin, hyperthermia (HT) delivered at 40–43 C for 60–90 min has shown to be as effective as a radiosensitizer [5]
Summary
The incidence of locally advanced cervical cancer (LACC) in developed countries has decreased since the introduction of screening and Human Papilloma Virus (HPV) vaccination programs [1,2], yet morbidity and mortality rates remain high in low-resource settings [3]. Studies have shown that HT plus RT improves local disease control (LDC) and survival in LACC patients, compared to RT alone, without significant effects on RT-related toxicity [6,7,8,9,10]. MEHT is being investigated in a phase III randomized controlled trial as a radiosensitizer (whole pelvic radiation), combined with cisplatin, for the treatment of LACC in a lowresource setting and in HIV-positive and -negative patients. The outcomes are the local disease control at six months post-treatment (reported by Minnaar et al [35]) and 2-year survival. The 2- and 5-year follow-up period is ongoing and is expected to be completed in 2023 This analysis includes the 206 participants who arrived for treatment after randomization (mEHT Group: n 1⁄4 105; Control Group: n 1⁄4 101). Eligibility for the trial, as well as randomization and masking, are described previously [35]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
