ESTRO 2020 Abstract book

S269 ESTRO 2020

Innsbruck- Tyrolean Cancer Research Institute, EXTRO- Lab- Dept. of Therapeutic Radiology and Oncology, Innsbruck, Austria Purpose or Objective Nowadays radiation therapy (RT) plays an important role in the management of early and advanced breast cancer. Although administration of postoperative RT markedly improves disease-free and overall survival in breast cancer patients, the problem of distant recurrence development is still not solved. It is possible to assume that breast carcinoma cells with increased metastatic abilities can possess any specific molecular properties protecting them from ionizing radiation. The main aim of this study was to determine whether breast carcinoma cells with increased invasive capacities are radiation resistant, and which molecular phenotypes can predict a diminished radiation response of invasive breast carcinoma cells. Material and Methods Parental breast carcinoma cells and their invasive counterparts (INV cells) (MDA-MB-231, basal type; T47D, luminal A type; Au565, Her2/ neu -positive cells) were used in the study. INV cells were obtained from parental breast carcinoma cells after repetitive cell migration through the 8µm-pore membrane in the Boyden chamber toward the medium containing an attractant. Cell morphology (3D tomographic microscopy); cell invasion/migration; cell viability and proliferation; expression and activities of CD24; CD44; ALDH1; proteomic assay were performed to better understand the molecular profiling of parental and INV breast carcinoma cells; radiation responses of parental and INV breast carcinoma cells were studied using cell viability and clonogenic survival assays. Tumorigenic abilities of the investigated cells were evaluated using athymic Nude-Foxn1 NU female mice. Results Although all INV breast carcinoma cells demonstrated similar morphological changes toward the formation of spindle-shaped cells, and upregulation of CD44+/CD24- /ALDH1+, they differed in their radiation responses and molecular profilings. Thus, MDA-MB-231-INV did not markedly change their radiation sensitivity, whereas T47D- INV cells demonstrated an increased radiation resistance, and Au565-INV became more sensitive to ionizing radiation compared to their parental counterparts. Detailed analysis of molecular patterns of parental and INV breast carcinoma cells allowed to detect the putative key regulators of radiation response. It is necessary to note that expression of cancer stem cells markers also did not correlate with tumorigenic capacities of the investigated cells. Increased metastatic properties of the INV cells were confirmed in the in vivo experiments. Conclusion Cancer stem cell markers CD44+/CD24-/ALDH1+ cannot predict radiation response in breast carcinoma cells with enhanced invasive and metastatic abilities. Additional profound evaluation of molecular properties of metastatically active breast carcinoma cells can help to elucidate the molecular mechanisms underlying the radiation responses of metastatic lesions in breast cancer patients.

Proffered Papers: Proffered papers 23 : Palliation

OC-0452 Mature results of a phase I dose-escalation trial of SBRT for bone and lymph node oligometastases C. Mercier 1 , M. Claessens 1 , G. De Kerf 1 , S. Gryshkevych 2 , C. Billiet 1 , I. Joye 1 , A. Buys 3 , S. Van Laere 3 , P. Vermeulen 3 , P. Meijnders 1 , F. Löfman 2 , L. Dirix 4 , D. Verellen 1 , P. Dirix 1 1 Iridium Kankernetwerk, Radiation Oncology, Antwerp, Belgium ; 2 RaySearch Laboratories, Machine Learning, Stockholm, Sweden ; 3 University of Antwerp, Translational Cancer Research Unit TCRU- Centre for Oncological Research CORE, Antwerp, Belgium ; 4 GZA Sint-Augustinus, Medical Oncology, Antwerp, Belgium Purpose or Objective To compare toxicity and efficacy of the three most commonly used SBRT (i.e. 5, 3 or single fraction) schedules for bone and lymph node oligometastases. Material and Methods Patients with ≤ 3 bone and/or lymph node metastases were included in this prospective trial. In the first, second and third cohort of each 30 patients, all metastases were treated to 5 x 7 Gy, 3 x 10 Gy and 1 x 20 Gy, respectively. SBRT could be combined with standard of care (SOC) systemic treatment. Dose constraints for OAR were prioritized over PTV coverage in accordance with the recommendations from the report of the American Association of Physicists in Medicine (AAPM) task group 101. Dose-limiting toxicity, defined as any ≥ grade 3 up to 6 months after SBRT, was the primary endpoint. Secondary endpoints were acute and late toxicity, local response (LR) at 6 months after SBRT, local failure (LF), and progression- free survival (PFS). Toxicity was graded using CTCAE version 4.03. LR was evaluated by RECIST version 1.1 or on functional imaging (PSMA or FDG PET/CT) if available. LF was scored as an event if an irradiated lesion showed an increase in size of ≥ 20% according to RECIST v1.1. Dosimetric evaluation was performed with RayAnalytics. Results From July 2017 until December 2018, 90 patients received SBRT to a total of 101 metastases. Seven patients were non-evaluable 6 months after SBRT and left out of the toxicity and LR analysis. Treatment groups were well balanced for patient and tumor characteristics (Table 1). Functional imaging was available in 78% of the lesions. Median follow-up was 15.0 months (range 6.3- 25.6). No dose-limiting toxicity was observed. No ≥ grade 3 acute or late toxicity occurred. Acute toxicity consisted of 3% grade 2 GI toxicity and 3% grade 2 pain flare. Late grade 2 toxicity was seen in 2 patients (1 patient with GI toxicity received 3 x 10 Gy, 1 rib fracture was seen after 1 x 20 Gy). Toxicity was not different between the different fractionation schemes. There was no difference in LR at 6 months between the treatment schedules. LF was seen in 4 patients, with a median time to local failure of 8.5 months (range 6.6-12). Median PFS was 14.8 months (95% CI 10.8-NA), Figure 1. Dosimetric analysis showed a difference in PTV coverage with the prescribed dose between the 3 schedules, with the lowest median coverage being reported for 5 x 7 Gy (p=0.03); however, GTV coverage was sufficient for all treatments. Flow cytometry of peripheral immune cells is being evaluated for the 3 vs 1 fraction groups.