Preoperative Partial Breast Reirradiation and Repeat Breast-conserving Surgery in Patients With Recurrent Breast Cancer: the REPEAT Trial

Официальное название

Preoperative Partial Breast Reirradiation and Repeat Breast-conserving Surgery in Patients With Recurrent Breast Cancer: the REPEAT Trial - a Study Protocol

Обзор

Over the past decades, interest in second breast-conserving therapy (BCT) has increased due to, among others, advancements in radiotherapy techniques. Preoperative partial breast irradiation (PBI) is an experimental treatment for patients with low-risk primary breast cancer. This approach can downstage the tumor, and may possibly reduce toxicity and improve cosmetic outcomes compared to postoperative radiotherapy. This study aims to evaluate the feasibility of single-dose preoperative PBI and second breast-conserving surgery (BCS) for patients with an ipsilateral recurrent breast event (IRBE) after previous BCT. The REPEAT trial is a multicenter, prospective, single-arm trial investigating ablative single-dose preoperative PBI in patients with an IRBE. Eligible patients are ≥ 50 years, have a unifocal non-lobular invasive breast cancer ≤ 2 cm, Bloom-Richardson grade 1 or 2, estrogen receptor-positive, HER2-negative and clinically negative axillary lymph nodes. The study plans to enroll 25 patients. Radiotherapy planning will involve the use of CT and MRI in the treatment position. Single-dose PBI of 20 Gy to the tumor and 15 Gy to the surrounding 2 cm of breast tissue will be delivered using a conventional or MR-guided linear accelerator. Tumor response will be monitored preoperatively using MRI and liquid biopsies to identify biomarkers for evaluating radiosensitivity. BCS will be performed 3 weeks post-PBI. The primary endpoint is the incidence of grade 2 or higher treatment-associated acute toxicity within 90 days. Secondary endpoints include the evaluation of acute (grade 1) and late toxicity, radiologic and pathologic response, mastectomy rate, patient-reported outcomes, cosmetic outcome, local, regional and distant recurrence rates, survival outcome, and biomarkers in liquid biopsies and tumor tissue. Patients will be followed up to 5 years after PBI. This trial will evaluate the feasibility of single-dose preoperative PBI and BCS for patients with IRBE. This treatment approach is expected to minimize the irradiated volume, reduce toxicity, and improve cosmetic outcomes compared to postoperative PBI after second BCS. Identifying biomarkers for radiosensitivity will help in selection patients and tailoring treatment.

Вмешательства

• Лучевая терапия ablative single-dose PBI
  ablative single-dose PBI followed by BCS after three weeks At baseline (prior to RT) and prior to BCS, toxicity, PROMS and cosmetic outcome will be assessed. Additionally, a preoperative MRI will be performed three weeks following RT to evaluate the acute tumor response.

Первичные конечные точки

• Acute toxicity [Срок оценки: 90 days]

Вторичные конечные точки (7)

• Toxicity [Срок оценки: 3,6,12 weeks and 1,2,3,4,5 years]
• response [Срок оценки: 3,6,12 weeks and 1,2,3,4,5 years]
• PROMS [Срок оценки: 3,6,12 weeks and 1,2,3,4,5 years]
• cosmetic results [Срок оценки: 3,6,12 weeks and 1,2,3,4,5 years]
• oncological outcomes [Срок оценки: 1,2,3,4,5 years]
• immune response [Срок оценки: 3,6,12 weeks and 1,2,3,4,5 years]
• patient comfort during RT treatment delivery [Срок оценки: during RT treatment]

Критерии участия

Критерии включения

• WHO performance scale ≤ 2
• Females at least 50 years of age with an ipsilateral invasive breast cancer event or DCIS (i.e. recurrence, second primary) after previous breast conserving surgery and radiotherapy (for invasive breast cancer/carcinoma in situ)
• Tumor characteristics: - - Tumor size ≤ 2 cm, unifocal on MRI

On tumor biopsy:

• Bloom-Richardson grade 1 or 2,
• non-lobular invasive histological type carcinoma,
• accompanying (non-extensive) DCIS is accepted within the tumor size of 2 cm on mammography and/or tumor biopsy, including no non-mass enhancement on MRI,
• ER-positive and HER2-negative tumor,
• No lymphovascular invasion.

• Clinical node negative on PET-CT, ultrasound and MRI
• No distant metastases
• Repeat breast-conserving surgery is feasible, if no or mild late toxicity (no grade 2 or higher) from previous breast-conserving therapy
• Adequate communication and understanding skills of the Dutch language
• Written informed consent

Критерии исключения

• Ipsilateral invasive breast cancer recurrence less than 2 years after first breast conserving therapy for breast cancer or ductal carcinoma in situ
• Legal incapacity
• Known breast cancer mutation gene carrier
• Previous ipsilateral mastectomy
• Collagen synthesis disease (e.g. Osteogeneis imperfecta, Ehlers-Danlos syndrome, systemic lupus erythematosus)
• Invasive lobular carcinoma
• MRI absolute contraindications as defined by the Department of Radiology
• Indication for treatment with neoadjuvant chemotherapy
• Non-feasible dosimetric RT plan
• Breast implants

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Нидерланды · 1 центр

• Amsterdam UMC / VU Medical Centre — Amsterdam

Публикации

• Civil Y, Wurfbain L, Jonker L, van der Sangen M, Oei A, Duvivier K, Bijker N, Meijnen P, van Kesteren Z, Palacios M, Barbe E, Menke-van der Houven van Oordt W, Diepenhorst G, Thijssen V, Slotman B, Verhoeff J, Schipper RJ, van den Bongard D. Preoperative partial breast reirradiation and repeat breast-conserving surgery in patients with recurrent breast cancer: the prospective single-arm REPEAT tri PMID 40681188

Идентификаторы

NCT: NCT06640881 · NL85983.018.24

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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