S340
Clinical - Breast
ESTRO 2026
were requested for all patients during the follow-up. Results: The mean liver volume was 1422,58 cm3 [+-294,53]. Median Dmean, Dmax and Dmin were respectively of 2,63 Gy [0,29 - 9,57] ; 41,47 Gy [9,63 - 52,05] and 0,016 Gy [0,00 - 0,15].The mean V13, V22 et V31 were respectively of 5,15% [0,00 - 22,66] ; 3,68% [0,00 - 29,10] and 2,69 % [0 - 17,87].In more than 75% of cases Dmean, Dmax and Dmin were £ 4,88 Gy ; £ 43,19 Gy and £ 0,046 Gy respectively. For V13, V22 and V31 more than 75% of cases were £ 11,48% ; £9,14% and £7,15% respectively.Dosimetric data for the liver are summarized in the table below : After a median follow-up of 38 months [±4,5], clinico- biological data during post-treatment monitoring revealed no abnormalities in liver function tests among patients treated with this protocol. Conclusion: Radiation-induced liver toxicities are among the most underestimated complications in the HFRT of breast cancer. In the absence of established prevention guidelines, we propose the systematic delineation of the entire liver during RSBC to minimize the doses received. The results of this study suggest that the following constraints could be reasonably respected during treatment planning optimization: Dmean ≤ 5 Gy, V13 ≤ 12%, V22 ≤ 9% and V31 ≤ 7%. Keywords: hypofractionated radiotherapy, liver, toxicity biomarkers after pre-operative radiosurgery in early-stage breast cancer: The CRYSTAL study Marco Lucarelli 1 , Federica Conversano 2 , Chiara Frascarelli 2 , Simona Pessina 2 , Chiara Zanetti 2 , Elisa De Camilli 2 , Giuseppe Renne 2 , Maria Alessia Zerella 1 , Samantha Dicuonzo 1 , Damaris Patricia Rojas 1 , Anna Morra 1 , Marianna Alessandra Gerardi 1 , Cristiana Fodor 1 , Silvia Penco 3 , Manuela Sargenti 4 , Paola Baratella 4 , Elisa Vicini 4 , Consuelo Morigi 4 , Sabrina Kahler-Ribeiro-Fontana 4 , Viviana Enrica Galimberti 4 , Sara Gandini 5 , Paolo Veronesi 4,6 , Barbara Alicja Jereczek-Fossa 1,6 , Maria Cristina Leonardi 1 , Elena Guerini Rocco 2,6 1 Department of Radiation Oncology, European Institute of Oncology IRCCS, Milan, Italy. 2 Division of Pathology, European Institute of Oncology IRCCS, Milan, Italy. 3 Division of Breast Radiology, European Institute of Oncology IRCCS, Milan, Italy. 4 Division of Mini-Oral 4880 Pathological downstaging and molecular
Breast Surgery, European Institute of Oncology IRCCS, Milan, Italy. 5 Department of Experimental Oncology, European Institute of Oncology IRCCS, Milan, Italy. 6 Department of Oncology and Hemato-oncology, University of Milan, Milan, Italy Purpose/Objective: Preoperative stereotactic radiotherapy (SBRT) in breast cancer allows for a direct evaluation of tumor response and its biological effects. The CRYSTAL trial (NCT04679454), a phase I/II study, investigates single- fraction ablative radiosurgery in early-stage breast cancer. We aimed to identify molecular features associated with SBRT response, focusing on DNA damage response (DDR) markers and transcriptomic profiles. Material/Methods: Thirteen patients with early-stage breast cancer enrolled in the CRYSTAL trial received a single ablative dose (18–24 Gy) via CyberKnife at least four weeks before surgery. Response was defined by downstaging between the pre and the post-SBRT MRI. Post SBRT, formalin-fixed paraffin-embedded (FFPE) surgical resection specimens were analyzed. Assessment of DNA double-strand break (DSB) repair markers was performed using immunofluorescence for ỿ H2A.X, 53BP1, and RAD51 proteins. RNA extracted from FFPE samples was subjected to RNA-sequencing of 395 immune-related genes. Differentially expressed genes (DEGs) were analyzed with DESeq2 (p<0.05), and correlated with clinical outcome. Results: Of the 13 patients, 10 (76.9%) achieved downstaging (Responders), while 3 (23.1%) did not (Non- responders). Analysis of DSB markers in the non- responder cohort revealed heterogeneous profiles (Table I). Preliminary gene expression analysis identified 15 DEG between responder and non- responder tumor tissues. This included the significant downregulation in non-responders of genes critical for the immune response (e.g. CXCL9, HLA-B, IFIT1, TLR3, KLRD1, NCR1) (Figure 1). Furthermore, the DNA repair gene BRCA2 was also significantly downregulated in the non-responder group.
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