Reirradiation and Total Ablative Strategies for Recurrent Gynecologic Cancer

Overview

REGYNERA(dia)TION is an international, multicenter, ambispective observational patient registry of adults with recurrent gynecologic malignancies after prior radiotherapy who are treated or planned for reirradiation and/or total ablative strategies as part of routine clinical care. The registry does not assign treatment. Radiotherapy technique, dose, systemic therapy, surgery, metastasis-directed therapy, imaging, and follow-up are selected by the treating multidisciplinary team according to local standards and patient-specific factors. The registry will collect harmonized retrospective and prospective data on disease characteristics, prior radiotherapy, recurrence pattern, reirradiation or ablative treatment exposure, response, progression, survival, severe treatment-related morbidity, fistula events, and patient-reported outcomes where available.

This study is a non-interventional patient registry designed to describe real-world outcomes after reirradiation and total ablative strategies in recurrent gynecologic malignancies. Eligible participants are adults with histologically confirmed uterine, cervical, vaginal, vulvar, ovarian, fallopian tube, primary peritoneal, or other rare gynecologic malignancy; documented prior radiotherapy; and recurrent or progressive disease for which reirradiation and/or a local ablative treatment strategy has been delivered, is ongoing, or is planned according to local multidisciplinary decision-making. The registry has an ambispective cohort structure. Historical retrospective participants are entered from medical records and treatment-planning data after local approval. Ambispective follow-up participants were treated before registry activation but remain under follow-up, allowing subsequent outcomes and adverse events to be captured prospectively where permitted. Prospective registry participants are enrolled before or at the time of reirradiation or total ablative strategy decision-making. Participation does not mandate, delay, prohibit, or modify any clinically indicated treatment, imaging, or follow-up. The registry will capture a common core dataset across participating centers, including demographics, performance status, primary tumor site and histology, primary treatment, prior radiotherapy details, recurrence anatomy, disease extent, number and site of active foci, treatment modality, dose and fractionation, equivalent dose metrics, systemic therapy timing, surgery or other metastasis-directed therapy, response at approximately 3 and 6 months, progression pattern, survival status, acute and late adverse events, severe morbidity, fistula events, and patient-reported outcomes where implemented. Recommended extended data domains include cumulative dose assessment, organ-at-risk metrics, imaging response method, molecular markers, systemic therapy sequencing, dosimetric data, and quality-of-life or symptom questionnaires. The primary registry endpoint is radiographic progression-free survival after reirradiation/total ablative strategy. Key safety analyses will describe grade 3 or higher treatment-related genitourinary, gastrointestinal, vaginal, soft-tissue, neurologic, vascular, or bone adverse events and fistula events within 24 months and during longer follow-up. Secondary analyses will describe complete response, overall survival, local, regional, and distant progression, freedom from oligometastatic or polymetastatic progression, and disease-site-specific outcomes when adequate sample size and event numbers are reached.