Abstract P3-10-22: Preoperative radiotherapy versus postoperative radiotherapy after neoadjuvant chemotherapy in high-risk breast cancer: a prospective, randomized, international multicentre Phase III trial—NeoRad

Abstract Background: Preoperative radiotherapy is a well-established treatment for various tumor types (rectal cancer, sarcoma, bronchial carcinoma). Promising studies on preoperative radiotherapy also exist for breast cancer, but most of them were not randomized or very old. Recent studies suggest that preoperative radiotherapy followed by immediate reconstruction or flap reconstruction is a low-complication method. There is evidence that the immunogenic effects of radiotherapy may lead to improved immune recognition of tumor cells. These potential immunogenic effects make preoperative radiotherapy a promising modality in interdisciplinary cancer therapy. In addition, preoperative radiotherapy may obviate the need to irradiate implants, expanders, or autologous transplants. NeoRad (NCT04261244, GBG116) is a multicenter, prospective, international randomized Phase III trial. It aims to investigate whether pre- versus postoperative radiotherapy after neoadjuvant chemotherapy (NACT) improves disease-free survival in patients with high-risk breast cancer and show superiority of preoperative radiotherapy (PRT) of the experimental treatment schedule in terms of disease-free survival (DFS). In addition, several secondary endpoints (cosmetic outcomes, quality of life, overall survival, etc.) will be assessed to better understand the benefits and risks of preoperative radiotherapy compared to the current standard of care. Study Design: Only patients with high-risk breast cancer who are eligible for NACT will be enrolled and randomly assigned in a 1:1 ratio to two study arms. In the standard arm, patients will undergo surgery, sentinel lymph node biopsy, possibly axillary dissection or targeted axillary dissection according to current S3/AGO guidelines. After surgery, patients will receive adjuvant radiotherapy +/- lymphatic pathways and, if indicated, systemic treatment according to S3/AGO guidelines. In the experimental arm, patients will receive whole-breast irradiation (WBRT) +/- lymphatic pathway irradiation after NACT. Approximately 3-6 weeks after radiotherapy, patients will undergo surgery including sentinel lymph node biopsy or axillary dissection, followed, if indicated, by post-neoadjuvant systemic therapy according to S3/AGO guidelines. Enrolment in post-neoadjuvant studies is allowed. To assess the response to NACT before radiotherapy, a biopsy of the primary tumor and suspicious lymph nodes is recommended in the experimental arm. An interim analysis on wound healing will be conducted after 100 patients have received breast-conserving surgery or autologous flap reconstruction (in both arms combined) and after 40 and 100 patients have been reconstructed with an implant (also combined from both arms). The recruitment period will be four years. The total study duration, including follow-ups, is ten years. Recruitment: The first patients were enrolled in 02/24 at the University Hospital of Düsseldorf. A total of 1826 patients will be recruited across 40 centers within 4 years. Funding: This study was supported by a grant from Deutsche Krebshilfe. Citation Format: Christiane Matuschek, Tanja Fehm, Maria Hufnagel, Vesna Bjelic-Radisic, Michael Untch, Michael Golatta, Danny Jazmati, Thorsten Kühn, David Krug, Jens Blohmer, Carsten Denkert, Beyhan Ataseven, Carolin Nestle-Krämling, Stefanie Corradini, Jens Huober, Jens Huober, Eugen Ruckhaeberle, Andreas Hartkopf, Theresa Link, Kerstin Rhiem, Elmar Stickeler, Claus Hanusch, Jörg Heil, Christine Solbach, Mattea Reinisch, Inga Bekes, Johannes Holtschmidt, Valentina Nekljudova, Sibylle Loibl, Wilfried Budach. Preoperative radiotherapy versus postoperative radiotherapy after neoadjuvant chemotherapy in high-risk breast cancer: a prospective, randomized, international multicentre Phase III trial—NeoRad [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P3-10-22.