ESTRO 2024 - Abstract Book

S1088

Clinical - Gynaecology

ESTRO 2024

Despite significant advances in the prevention and treatment of locally advanced cervical cancer (LACC), the disease is still endemic in low-to-middle-income-countries (LMICs), with high morbidity and mortality rates. Modulated electro-hyperthermia (mEHT) has been investigated as an affordable adjunct to chemoradiotherapy (CRT) for the management of LACC in a phase III randomised controlled trial in Johannesburg, South Africa (2014 2023). In this report we summarise the previously published data on the trial and present results from the final 5yr follow-up.

Material/Methods:

Trial protocols were submitted prior to enrolment of the first participant an approval was obtained from the local ethics body (Human Research Ethics Committee approval: M1704133; ClincialTrials.gov ID: NCT03332069). Participants were randomized to receive chemoradiotherapy with/without mEHT and were followed-up for 5yrs post-treatment. 50Gy external beam radiation and 3x8Gy doses of HDR brachytherapy were prescribed, along with 80mg/m2 of cisplatin, administered 21 days apart. The mEHT group received two mEHT treatments/week immediately before radiation, for 55 minutes, at a planned power output of 130W. HIV-positive participants were included provided their CD4 count was >200cells/mm3 / they had been on ART for>6m at enrolment. Local disease control was evaluated by PET/CT studies pre-treatment and at 6m post-treatment. The last known disease status was used for participants who were lost to follow up. Kaplan-Meier charts were used to plot the survival probability of each group and Log rank tests were used to compare whether the survival curves of each group overlapped. Local disease control (LDC) at 6 months post-treatment was 24.1% in the control group (CG); and 45.5% in the mEHT group (chi2: p=0.003 )[1], and 3yr DFS was 13.7% in the CG and 35.4% in the mEHT group (OR: 3.4, 95%CI:1.71– 6.91, p=0.001 ).[2] There were no significant differences in CRT-related early or late toxicity between the groups at three years post-treatment [2] and the mEHT treatments were tolerated well, with 97% of participants able to receive ≥8 of 10 prescribed treatments.[3] A CEA at 3y post-treatment showed that the addition of mEHT dominated the Markov model, with an increased efficacy and potential for lowered costs.[2] 24% of the 54 participants with extra-pelvic nodal disease treated with mEHT showed complete metabolic resolution of all disease, compared to 5.4% of the 54 participants with extra-pelvic nodal disease in the CG. This systemic response was not associated with the number of cisplatin doses or the HIV-status of the participants and suggests a potentiation of the abscopal effect by mEHT.[4] 5y OS was achieved by 33%[33/99] of participants in the mEHT group and 26%[25/98] of participants in the CG (HR:0.74; 95%CI:0.53-1.03; p=0.083). When analysed according to stage of disease, 5y OS was increased by 35% with the addition of mEHT (HR:0.65; 95%CI:0.43-0.99; p=0.046 ) in participants with stage III disease. The odds of achieving 5y DF status was significantly higher in the mEHT group (OR:3.00; 95%CI:1.49-6.07; p=0.002 ; HR:0.73; 95%CI:0.53-1.00; p=0.049 ) with 32%[32/99] of mEHT participants and only 14%[14/102] of CG participants achieving 5y DFS (Chi2: p=0.002 ). There were no significant differences in late toxicity between the groups. Participants who had extra-pelvic nodal disease and achieved complete metabolic response at 6m post-treatment remained DF at 5 years, with the exception of 2 participants who died of unrelated causes. Results:

Conclusion:

The addition of mEHT to CRT for LACC significantly increases 5y DFS rates, has the potential to lower treatment costs, and can potentially promote a sustained long-term, immune-mediated, abscopal response to the disease. These results strongly motivate the inclusion of mEHT in standard protocols for LACC, especially in LMICs.