Prediction of pathologic complete response after single-dose MR-guided partial breast irradiation in low-risk breast cancer patients: the ABLATIVE-2 trial - a study protocol

Abstract

BACKGROUND: Partial breast irradiation (PBI) is standard of care in low-risk breast cancer patients after breast-conserving surgery (BCS). Pre-operative PBI can result in tumor downstaging and more precise target definition possibly resulting in less treatment-related toxicity. This study aims to assess the pathologic complete response (pCR) rate one year after MR-guided single-dose pre-operative PBI in low-risk breast cancer patients. METHODS: The ABLATIVE-2 trial is a multicenter prospective single-arm trial using single-dose ablative PBI in low-risk breast cancer patients. Patients ≥ 50 years with non-lobular invasive breast cancer ≤ 2 cm, grade 1 or 2, estrogen receptor-positive, HER2-negative, and tumor-negative sentinel node procedure are eligible. A total of 100 patients will be enrolled. PBI treatment planning will be performed using a radiotherapy planning CT and -MRI in treatment position. The treatment delivery will take place on a conventional or MR-guided linear accelerator. The prescribed radiotherapy dose is a single dose of 20 Gy to the tumor, and 15 Gy to the 2 cm of breast tissue surrounding the tumor. Follow-up MRIs, scheduled at baseline, 2 weeks, 3, 6, 9, and 12 months after PBI, are combined with liquid biopsies to identify biomarkers for pCR prediction. BCS will be performed 12 months after radiotherapy or after 6 months, if MRI does not show a radiologic complete response. The primary endpoint is the pCR rate after PBI. Secondary endpoints are radiologic response, toxicity, quality of life, cosmetic outcome, patient distress, oncological outcomes, and the evaluation of biomarkers in liquid biopsies and tumor tissue. Patients will be followed up to 10 years after radiation therapy. DISCUSSION: This trial will investigate the pathological tumor response after pre-operative single-dose PBI after 12 months in patients with low-risk breast cancer. In comparison with previous trial outcomes, a longer interval between PBI and BCS of 12 months is expected to increase the pCR rate of 42% after 6-8 months. In addition, response monitoring using MRI and biomarkers will help to predict pCR. Accurate pCR prediction will allow omission of surgery in future patients. TRIAL REGISTRATION: The trial was registered prospectively on April 28th 2022 at clinicaltrials.gov (NCT05350722).

Magnetic Resonance Imaging-Guided Single-Fraction Preoperative Radiotherapy for Early Stage Breast Cancer (The RICE Trial): Feasibility Study

“…Given the exploratory nature of this study, our decision to use this dose was based on prior studies [5,28,29,30] that have demonstrated its effectiveness without signi cant radiotherapy related side effects and improved overall quality of life. Given the variability among studies investigating singlefraction accelerated partial breast irradiation [4,5,6,28,29,30], particularly in terms of the time intervals and techniques used, it is anticipated that a portion of patients will demonstrate a response to treatment. Nevertheless, since no study to date has explored the response to treatment 6 weeks after single-fraction preoperative radiation therapy using the MR linac, these outcomes remain largely unexplored.…”

“…This trend is expected to continue, driven by the increasing prevalence of risk factors, population growth, and aging [1,2]. Despite this, mortality from early-stage breast cancer has signi cantly decreased, with the global 5-year net survival rate estimated to increase from 67.9-78.2% [3,4]. Simultaneously, there is a shift towards personalized and less invasive therapies, aimed at deescalating therapy, improving cosmetic outcomes, and reducing radiation therapy-related toxicity, all while ensuring the safety and e cacy of oncological care [4,5,6,7,8].…”

“…One promising alternative is pre-operative magnetic resonance-guided radiation therapy (MRgRT). With the exceptional soft tissue contrast provided by MRI, delivering preoperative accelerated partial breast irradiation using a magnetic resonance-integrated linear accelerator (MR linac) allows for greater distinction between the tumor and surrounding healthy tissue, as the tumor remains in its original location [4,6,28,31]. This approach leads to reduced inter-observer variability in contouring the tumor and thus enhanced de nition of the tumor volume [4,6,28].…”

“…With the exceptional soft tissue contrast provided by MRI, delivering preoperative accelerated partial breast irradiation using a magnetic resonance-integrated linear accelerator (MR linac) allows for greater distinction between the tumor and surrounding healthy tissue, as the tumor remains in its original location [4,6,28,31]. This approach leads to reduced inter-observer variability in contouring the tumor and thus enhanced de nition of the tumor volume [4,6,28]. Furthermore, since a smaller volume of tissue is treated, pre-operative accelerated partial breast irradiation enables the delivery of a higher dose per fraction.…”

“…Furthermore, since a smaller volume of tissue is treated, pre-operative accelerated partial breast irradiation enables the delivery of a higher dose per fraction. This facilitates the possibility of single-dose radiotherapy treatment, further reducing the treatment burden and radiotherapy-induced toxicity to the patient, thereby signi cantly improving the patient's quality of life [4,5,6,7,8].…”