S742
Clinical – Lower GI
ESTRO 2026
Digital Poster 4677
Local Response after SBRT for Colorectal Liver Metastases: Influence of Systemic Therapy and RAS Mutational Status Nikolay Tolev 1 , Manuela Vartanyan 2 , Georgi Ganev 1 , Magdalena Kisimova 1 , Dimo Dimov 1 , Veselina Yanakieva 1 , Yavor Yurukov-Tozzini 1 , Stanislav Koychev 1 , Rositsa Krasteva 3 , Zahari Zahariev 1 1 Radiation Oncology, Uni Hospital, Panagyurishte, Bulgaria. 2 Radiation Oncology, “Dr. Marko A. Markov” Oncology Hospital, Varna, Bulgaria. 3 Medical Oncology, Uni Hospital, Panagyurishte, Bulgaria Purpose/Objective: This single-institution retrospective study conducted at Uni Hospital, Bulgaria aimed to evaluate local tumor response and identify clinical, therapeutic and molecular factors influencing the efficacy of stereotactic body radiotherapy (SBRT) for liver metastases from colorectal cancer in patients receiving systemic therapy. Particular attention was given to the interaction between SBRT timing, systemic treatment line, targeted therapy type, chemotherapy backbone and RAS mutational status. Material/Methods: A total of 104 patients (54 males and 50 females ; median age 66 [range 35–88]) with histologically confirmed adenocarcinoma (n = 103) and neuroendocrine tumor (n = 1) were treated with SBRT. The median ECOG PS was 0. SBRT was delivered in 5 fractions of 7–10 Gy or in 3 fractions of 12.5 –20 Gy for a total dose of 35–60 Gy. Patients were categorized by the line of systemic therapy ongoing at the time of SBRT (first-line vs. later), targeted agent (EGFR vs. VEGFR inhibitor at first line), chemotherapy regimen (FOLFOX vs. FOLFIRI), molecular profile (RAS mutant vs. wild type) and timing of SBRT (at treatment initiation vs. after ≥ three months of systemic therapy). Local response was assessed radiologically as complete (CR), partial (PR), stable disease (SD) or progressive disease (PD). Statistical analyses used chi- square and Fisher’s exact tests, with Monte Carlo correction when appropriate. Results: Local response was significantly associated with systemic therapy line as patients irradiated during first-line therapy achieved higher CR and lower PD rates (Fisher’s exact p = 0.017). EGFR-based regimens showed superior efficacy to VEGFR-based regimens (CR 81% vs. 59.3%, p = 0.035). Among first-line patients, RAS wild-type tumors achieved higher CR (81.6% vs. 58.3%) and better local control than RAS- mutant tumors (p = 0.046), a finding confirmed in the expanded cohort (p = 0.019). A borderline trend suggested improved response when SBRT was performed after ≥ three months of systemic therapy (p
The ketogenic intervention significantly increased ketone levels (p < 0.001) and decreased glucose (p < 0.01), body weight, and BMI without loss of muscle mass or total body water. CD8 ⁺ T-cell counts increased (p < 0.0001) while Tregs decreased (p < 0.01) (figure 1). PD-1, PDL-1, and CTLA-4 expression was significantly downregulated (p = 0.01–0.0001) (figure 2). Cholesterol and CRP decreased only in the intervention group, whereas bilirubin increased in controls, suggesting relative hepatic protection. MRI-based TRG indicated better tumor regression in the intervention group, although the difference was not statistically significant (p = 0.297). No laboratory or clinical adverse effects or changes in quality of life were observed, except mild gastrointestinal symptoms in the intervention group, which did not require treatment interruption. Conclusion: A mild ketogenic diet combined with daily meta- Capridin during NCRT is safe, feasible, and promotes favorable immunometabolic remodeling in LARC. This intervention enhanced CD8 ⁺ T-cell activity, reduced Tregs, and induced metabolic stress on tumor cells without muscle loss or major toxicity. These findings support further trials investigating ketogenic strategies alongside standard oncologic therapy. References: 1. Pavlova, N. N., & Thompson, C. B. (2016). The emerging hallmarks of cancer metabolism. Cell Metabolism, 23(1), 27–47. https://doi.org/10.1016/j.cmet.2015.12.0062. Plitas, G., & Rudensky, A. Y. (2016). Regulatory T cells: Differentiation and function. Cancer Immunology Research, 4(9), 721–725. https://doi.org/10.1158/2326- 6066.CIR-16-01933. Klement, R. J., & Champ, C. E. (2014). Calories, carbohydrates, and cancer therapy with radiation: Exploiting the five R's through dietary manipulation. Cancer and Metastasis Reviews, 33(1), 217–229. https://doi.org/10.1007/s10555-014-9495-3 Keywords: Rectal cancer, ketogenic diet, Immunometabolism
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