Reirradiation and Total Ablative Strategies for Recurrent Gynecologic Cancer

Official title

REGYNERA(Dia)TION: An Ambispective International Multicenter Patient Registry of Reirradiation and Total Ablative Strategies for Recurrent Gynecologic Malignancies

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.

Detailed description

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.

Interventions

• Radiation Reirradiation
  Observed standard-of-care radiotherapy delivered in a previously irradiated patient or to a target region overlapping with or clinically affected by prior radiotherapy. Modalities may include brachytherapy, external-beam radiotherapy, stereotactic body radiotherapy, proton therapy, intraoperative radiotherapy, or combinations. Dose and fractionation are selected by the treating team.
• Other Total Ablative Strategy
  Observed standard-of-care curative-intent or ablative-intent treatment strategy directed at all visible active disease sites when technically feasible and clinically appropriate. This may include radiotherapy, surgery, ablation, metastasis-directed therapy, systemic therapy, or combinations, as selected by the treating multidisciplinary team.

Primary outcome measures

• Radiographic Progression-Free Survival [Time frame: From treatment start to progression or death, up to 5 years]

Secondary outcome measures (10)

• Severe Treatment-Related Adverse Events [Time frame: From treatment start through 24 months and longer follow-up, up to 5 years]
• Overall Survival [Time frame: From treatment start to death or last follow-up, up to 5 years]
• Fistula Events [Time frame: From treatment start through 24 months and long-term follow-up, up to 5 years]
• Complete Response [Time frame: From treatment completion through 5 years, with response assessed at approximately 3 and 6 months after treatment completion and during scheduled follow-up.]
• Local Recurrence-Free Survival [Time frame: From treatment completion to local progression or death, up to 5 years]
• From treatment completion to local progression or death, up to 5 years [Time frame: From treatment completion to regional progression or death, up to 5 years]
• Distant Metastasis-Free Survival [Time frame: From treatment completion to event or last follow-up, up to 5 years]
• Freedom From Oligometastatic Reccurence/Progression [Time frame: From treatment completion to event or last follow-up, up to 5 years]
• Freedom From Polymetastatic Recurrence/Progression [Time frame: From treatment completion to polymetastatic progression, up to 5 years]
• Pattern of First Failure [Time frame: From treatment completion to first progression, up to 5 years]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Poland · 1 center

• Affidea NU-MED Center of Oncological Diagnostics and Therapy — Zamość

Publications

• Mulani J, Jain J, Gupta A, Swamidas J, Paul S, Mittal P, Gurram L, Chopra S. Dose Accumulation for Multicourse Gynecological Reirradiation: A Methodological Narrative and Clinical Examples. Int J Radiat Oncol Biol Phys. 2022 Aug 1;113(5):1085-1090. doi: 10.1016/j.ijrobp.2022.04.046. Epub 2022 May 7. PMID 35537576
• Ling DC, Vargo JA, Burton SA, Heron DE, Beriwal S. Salvage Curative-Intent Reirradiation Stereotactic Body Radiation Therapy for Isolated Pelvic and/or Paraortic Recurrences of Gynecologic Malignancies. Pract Radiat Oncol. 2019 Nov;9(6):418-425. doi: 10.1016/j.prro.2019.05.012. Epub 2019 May 28. PMID 31150869
• Ling DC, Vargo JA, Glaser SM, Kim H, Beriwal S. Outcomes after definitive re-irradiation with 3D brachytherapy with or without external beam radiation therapy for vaginal recurrence of endometrial cancer. Gynecol Oncol. 2019 Mar;152(3):581-586. doi: 10.1016/j.ygyno.2018.12.022. Epub 2018 Dec 29. PMID 30600093
• Lee LJ, Alban GM, Cheng T, Buzurovic I, Pretz J, Singer L, King MT. Clinical outcomes and dosimetric predictors of toxicity for re-irradiation of vaginal recurrence of endometrial cancer. Brachytherapy. 2022 May-Jun;21(3):263-272. doi: 10.1016/j.brachy.2021.12.010. Epub 2022 Jan 22. PMID 35078717
• Bockel S, Espenel S, Sun R, Dumas I, Gouy S, Morice P, Chargari C. Image-Guided Brachytherapy for Salvage Reirradiation: A Systematic Review. Cancers (Basel). 2021 Mar 11;13(6):1226. doi: 10.3390/cancers13061226. PMID 33799617
• Critelli P, Pezzulla D, Lillo S, Arpa D, Scricciolo M, Di Carlo C, Argenone A, Borzillo V, Marsella AR, Tamburo M, Di Franco R, Di Marzo A, Settineri N, Mondello S, Macchia G, Belgioia L, Cerrotta A, Pontoriero A. Outcomes and toxicity in re-irradiation of gynecologic cancer: Systematic review of the Italian association of radiation and clinical oncology (AIRO). Gynecol Oncol. 2023 Dec;179:33-41. PMID 37913639
• Andratschke N, Willmann J, Appelt AL, Alyamani N, Balermpas P, Baumert BG, Hurkmans C, Hoyer M, Langendijk JA, Kaidar-Person O, van der Linden Y, Meattini I, Niyazi M, Reynaert N, De Ruysscher D, Tanadini-Lang S, Hoskin P, Poortmans P, Nieder C. European Society for Radiotherapy and Oncology and European Organisation for Research and Treatment of Cancer consensus on re-irradiation: definition, rep PMID 36174633

Identifiers

NCT: NCT07667192 · REGYNE(RA)DIATION

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗