Single-dose Preoperative Partial Breast Irradiation in Low-risk Breast Cancer Patients

Overview

In this ABLATIVE-2 trial, low-risk breast cancer patients will be treated with MRI-guided single dose preoperative partial breast radiotherapy to assess the rate of pathologic complete response after an interval of six to twelve months between radiotherapy and surgery. Response monitoring will be assessed using MRI and markers in blood and tumor tissue to enable prediction of pathologic response.

Detailed description

Patients will receive single-dose preoperative radiotherapy followed by breast conserving surgery (BCS) at 12 months after radiotherapy, as long as follow-up MRI scans show a complete radiologic response. In case of incomplete radiologic response, BCS will be performed at 6 months after radiotherapy. BCS is performed earlier when progressive disease is found on MRI. In the follow-up period between radiotherapy and surgery, tumor response will be monitored using MRI every 3 months. After surgery, patients will be followed up until 10 years after radiotherapy treatment to assess oncological outcomes, toxicity, cosmetic outcome and quality of life.

Interventions

• Radiation Single dose ablative radiotherapy
  Patients will receive a single dose of 20Gy/15Gy on the gross tumor volume and clinical tumor volume respectively, in the context of pre-operative partial breast irradiation

Primary outcome measures

• Pathologic complete response [Time frame: 12 months after radiotherapy]

Secondary outcome measures (12)

• Radiologic complete response [Time frame: at baseline, 2 weeks, 3, 6, 9, and 12 months after radiotherapy]
• Treatment-related adverse events [Time frame: at baseline, 2 weeks, 3, 6, 9, 12 months, 2, 3, 4, 5, 6, 8 and 10 years after radiotherapy]
• Patient quality of life [Time frame: at baseline, 2 weeks, 3, 6, 9, 12 months, 2, 3, 4, 5, 6, 8 and 10 years after radiotherapy]
• Breast cancer specific quality of life [Time frame: at baseline, 2 weeks, 3, 6, 9, 12 months, 2, 3, 4, 5, 6, 8 and 10 years after radiotherapy]
• Patient distress [Time frame: at baseline, 2 weeks, 3, 6, 9, 12 months, 2, 3, 4, 5, 6, 8 and 10 years after radiotherapy]
• Physician reported cosmetic outcome [Time frame: at baseline, 2 weeks, 3, 6, 9, 12 months, 2, 3, 4, 5, 6, 8 and 10 years after radiotherapy]
• Patient reported cosmetic outcome [Time frame: at baseline, 2 weeks, 3, 6, 9, 12 months, 2, 3, 4, 5, 6, 8 and 10 years after radiotherapy]
• Objective cosmetic outcome [Time frame: at baseline, 2 weeks, 3, 6, 9, 12 months, 2, 3, 4, 5, 6, 8 and 10 years after radiotherapy]
• Local, regional and distant relapse rates [Time frame: Day of radiotherapy till end of follow-up of 10 years]
• Overall survival [Time frame: Day of radiotherapy till end of follow-up of 10 years]
• Radiotherapy-associated immune response markers [Time frame: 12 months after radiotherapy]
• Radiotherapy-associated biomarkers [Time frame: at baseline, 2 weeks, 3, 6, 9, and 12 months after radiotherapy]

Eligibility criteria

Inclusion criteria

• WHO performance scale ≤2.
• Females at least 50 years of age with unifocal cT1N0 breast cancer on mammography, ultrasound and MRI.

• Patients with an indication for chemotherapy or HER2-targeted therapy according to Dutch National Oncoline Guidelines or own hospital protocols are not eligible. Patients with an indication for endocrine therapy are eligible.
• Tumor size as assessed on MRI.
• On tumor biopsy:

• Bloom-Richardson grade 1 or 2.
• Non-lobular invasive histological type carcinoma.
• LCIS or (non-extensive) DCIS is accepted.
• ER positive tumor receptor.
• HER2 negative tumor.
• Tumor-negative sentinel node (excluding isolated tumor cells).
• Adequate communication and understanding skills of the Dutch language.

Exclusion criteria

• Legal incapacity.
• BRCA1, BRCA2 or CHEK2 gene mutation.
• Distant metastasis.
• Previous history of breast cancer or DCIS.
• Other type of malignancy within 5 years before breast cancer diagnosis. Patients with adequately treated malignancy longer than 5 years before breast cancer diagnosis are eligible for inclusion.
• For adequately treated carcinoma in situ of the cervix or basal cell carcinoma of the skin no specific time span to breast cancer diagnosis is required for inclusion.
• Collagen synthesis disease.
• Signs of extensive DCIS component on histological biopsy or on imaging (e.g. no extensive calcifications on mammography).
• Invasive lobular carcinoma.
• MRI absolute contraindications as defined by the Department of Radiology.
• Nodal involvement with cytological or histological confirmation.
• Indication for treatment with (neo-)adjuvant chemotherapy.
• Non-feasible dosimetric RT plan.

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

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Netherlands · 6 centers

• Flevoziekenhuis — Almere Stad
• Ziekenhuis Amstelland — Amstelveen
• Amsterdam UMC — Amsterdam
• Canisius Wilhelmina Ziekenhuis — Nijmegen
• Radboud UMC — Nijmegen
• Zaans Medisch Centrum — Zaandam

Australia · 1 center

• GenesisCare — Sydney

Publications

• Civil YA, Oei AL, Duvivier KM, Bijker N, Meijnen P, Donkers L, Verheijen S, van Kesteren Z, Palacios MA, Schijf LJ, Barbe E, Konings IRHM, -van der Houven van Oordt CWM, Westhoff PG, Meijer HJM, Diepenhorst GMP, Thijssen V, Mouliere F, Slotman BJ, van der Velde S, van den Bongard HJGD. Prediction of pathologic complete response after single-dose MR-guided partial breast irradiation in low-risk bre PMID 37161377

Identifiers

NCT: NCT05350722 · NL77000.029.21

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗