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.

Inclusion Criteria:

• - Age 18 years or older at the time of reirradiation or prospective enrollment.
• Histologically confirmed gynecologic malignancy, including uterine, cervical, vaginal, vulvar, ovarian, fallopian tube, primary peritoneal, or rare gynecologic primary.
• Documented prior radiotherapy delivered as part of previous treatment.
• Recurrent or progressive disease for which reirradiation and/or total ablative strategy has been delivered, is ongoing, or is planned according to local multidisciplinary decision-making.
• Recurrence or progression documented by imaging, clinical examination, pathology, and/or multidisciplinary tumor board assessment according to institutional practice.
• Availability of minimum essential data, including prior radiotherapy information, date of reirradiation or planned reirradiation, disease extent at reirradiation, and at least one follow-up, outcome, or survival-status record for retrospective patients.
• For prospective patients, written informed consent where required by local regulations and ethics approval.

Exclusion Criteria:

• No evidence of prior radiotherapy.
• No reirradiation or clinically meaningful local ablative radiotherapy component delivered or planned.
• Insufficient minimum data preventing assignment of reirradiation date, disease extent, or survival/follow-up status.
• Exclusively polymetastatic disease with more than 5 active non-regional lesions treated without a meaningful local reirradiation or total ablative component, unless included in an exploratory non-core substudy approved by the steering committee.
• Prospective refusal of consent when consent is required by local law or ethics approval.

Adult patients with histologically confirmed recurrent gynecologic malignancy after prior radiotherapy, treated with, planned for, or undergoing reirradiation and/or total ablative strategy according to local multidisciplinary decision-making.

Individual participant-level data will not be made publicly available because the registry includes rare gynecologic malignancy cohorts, retrospective and prospective international data, treatment-planning and imaging-derived variables, and potentially re-identifiable clinical details. Data will be pseudonymized or deidentified before central transfer and handled according to local ethics approvals, data-use agreements, GDPR, and applicable institutional data-protection requirements. Aggregate results and summary analyses are planned for dissemination through scientific publications and conference presentations.