ESTRO 2025 - Abstract Book

S74

Invited Speaker

ESTRO 2025

to increased genomic instability and a heightened risk of second primary malignancies. While breast-conserving therapy (BCT) followed by radiation therapy (RT) remains the standard approach for early-stage breast cancer, concerns have been raised regarding the long-term efficacy and safety of RT in BRCA mutation carriers. The choice between breast-conserving therapy followed by RT and mastectomy remains a key consideration in BRCA-mutated breast cancer. BCT combined with RT has been shown to provide excellent local control and overall survival rates comparable to mastectomy. However, concerns exist regarding the risk of ipsilateral breast tumor recurrence (IBTR) and the development of second primary breast cancers, particularly in BRCA1 carriers who often present with triple-negative tumors. Retrospective studies suggest that BRCA1/2 carriers undergoing BCT with RT do not have significantly worse outcomes compared to those who undergo mastectomy, provided that appropriate systemic therapy is administered. Local recurrence rates following BCT with RT in BRCA1 carriers are slightly higher than in non-carriers, but this difference diminishes with adequate systemic therapy, including chemotherapy and endocrine therapy where applicable. The long-term outcomes of BCT in BRCA1/2 carriers are further influenced by age at diagnosis, tumor biology, and adjuvant therapy received. Mastectomy is often considered in BRCA mutation carriers due to their increased lifetime risk of contralateral breast cancer. Bilateral mastectomy is frequently recommended as a risk-reducing strategy, particularly in younger patients. However, for those opting for unilateral mastectomy, the role of post-mastectomy radiation therapy (PMRT) depends on tumor characteristics. High-risk features such as node-positive disease, large tumor size, and lymphovascular invasion warrant the use of PMRT to improve locoregional control and overall survival. Despite these advantages, PMRT does not eliminate the risk of a second primary cancer in the contralateral breast, which remains a significant concern in BRCA carriers. In summary, the decision between BCT with RT and mastectomy should be individualized, taking into account patient preferences, tumor characteristics, and long-term risks. BCT with RT offers a breast-preserving option with excellent oncologic outcomes, while mastectomy remains an effective approach, particularly for those seeking risk reduction. Further research is needed to refine RT protocols in BRCA carriers, ensuring optimal treatment strategies that balance efficacy with long-term safety.

4766

Speaker Abstracts Synthetic CT: The MESCAL project Davide Cusumano Medical Physics, Mater Olbia Hospital, Olbia, Italy

Abstract: The MESCAL project (Multicentric Evaluation of Synthetic CT Algorithms) is a research initiative designed to develop clear guidelines for implementing MRI-only workflows in radiation therapy. Born from the ESTRO Physics 2022 working group on “Next-generation MR-guided radiotherapy and AI applications for planning and image guidance”, the project seeks to assist new users in transitioning to MRI-only methods by thoroughly investigating the variability and accuracy of various commercially available synthetic CT (sCT) solutions. Its primary aim is to define acceptable ranges for sCT generation, thereby establishing a robust foundation for the clinical adoption of new imaging algorithms. The project is structured around two main clinical tracks: one that utilizes MRI simulation in conjunction with conventional linear accelerators (Track 1) and another that employs integrated MRI-Linac systems (Track 2). Each of these tracks is further subdivided by treatment site, such as brain, head and neck, thorax, abdomen, and pelvis.