Objective: To evaluate the efficacy and acute toxicity of hybrid brachytherapy using Venezia applicators in patients with locally advanced squamous cell carcinoma of the cervix.

Methods: This prospective study involved 41 patients treated with external beam radiotherapy (EBRT) followed by brachytherapy. Patients received EBRT doses of 45–50.4 Gy with or without simultaneous integrated boost and concurrent chemotherapy. Brachytherapy was administered using Venezia applicators, delivering high-risk clinical target volume (HRCTV) doses of 80–90 Gy or >90 Gy. Treatment responses and toxicities were assessed using Response Evaluation Criteria in Solid Tumours Criteria 1.1, Common Terminology Criteria for Adverse Events Version 5.0, respectively.

Results: After five visits, 65.9% of patients achieved complete response, 29.3% partial response and 4.9% stable disease. Acute toxicities were primarily Grade 0–1, with no Grade III or IV toxicities observed. Complete responders exhibited higher rates of Grade 0 toxicities across various parameters, including urination frequency and abdominal pain. Middle-class patients showed higher response rates, although this was not statistically significant. 46.3% Human Papillomavirus positive patients converted to negative status after treatment. There was no significant correlation of response rate with disease stage, EBRT dosage or duration of treatment.

Discussion: Hybrid brachytherapy using Venezia applicators allowed for high-dose delivery to HRCTV without exceeding organ tolerance limits, resulting in effective local control (LC) and minimal acute toxicities. The study underscores the potential of hybrid brachytherapy in improving outcomes for cervical cancer patients, particularly in low-middle-income countries. Challenges included small sample size and patient follow-up limitations.

Conclusion: Hybrid brachytherapy with Venezia applicators is effective and safe for locally advanced cervical cancer, providing high LC with minimal acute toxicity.