S741
Clinical – Lower GI
ESTRO 2026
Purpose/Objective: Tumor cells rely heavily on glycolysis for energy (the Warburg effect), making them vulnerable to metabolic interventions1. Rectal cancer progression is also driven by tumor heterogeneity and an immune- suppressive microenvironment, where regulatory T cells (Tregs) suppress cytotoxic CD8 ⁺ T-cell activity2. A mild ketogenic diet combined with supplementation may enhance antitumor immunity while creating metabolic stress on tumor cells by limiting glucose availability.3 This study evaluated the safety, feasibility, and immunometabolic effects of ketogenic intervention during neoadjuvant chemoradiotherapy (NCRT) in locally advanced rectal cancer (LARC). Material/Methods: This prospective interventional study at the Iran Cancer Institute, Tehran, Iran, enrolled 18 patients with LARC, assigned to either the ketogenic intervention group (n = 9) or standard NCRT (n = 9). The intervention group received a mild ketogenic diet and daily medium-chain triglyceride supplementation (meta-Capridin) three hours before radiotherapy. Capillary ketone levels were measured daily to confirm the ketogenic state.Adverse events were monitored prospectively. Immune cells (Tregs, CD4 ⁺ , CD8 ⁺ T cells) were quantified by flow cytometry, and immune- checkpoint gene expression (PD-1, PDL-1, CTLA-4) was assessed by real-time PCR. Biochemical and metabolic parameters (glucose, ketone bodies, cholesterol, CRP, bilirubin) and body composition (skeletal muscle, fat mass, total body water) were measured. Clinical response was assessed by MRI-based tumor regression grade (TRG) 6–8 weeks after CRT, and patient-reported quality of life was evaluated. Results:
Conclusion: This analysis demonstrates the good tolerability of a short-course adaptive radiotherapy regimen given with concurrent chemotherapy in locally advanced rectal cancer. A substantial proportion of patients achieved complete or partial response. The treatment was associated with manageable acute toxicity, though a minority progressed during therapy. The findings suggest potential benefits of short-course adaptive radiotherapy with CTV-PTV margin of 3 mm. Regarding chronic toxicity, longer patient follow-up comparisons to standard is needed. References: 1. de Jong R, Crama KF, Visser J, van Wieringen N, Wiersma J, Geijsen ED, Bel A. Online adaptive radiotherapy compared to plan selection for rectal cancer: quantifying the benefit. Radiat Oncol. 2020 Jul 8;15(1):162. doi: 10.1186/s13014-020-01597-1. PMID: 32641080; PMCID: PMC7371470.2. Sauer R, Fietkau R, Wittekind C, Rödel C, Martus P, Hohenberger W, Tschmelitsch J, Sabitzer H, Karstens JH, Becker H, Hess C, Raab R; German Rectal Cancer Group. Adjuvant vs. neoadjuvant radiochemotherapy for locally advanced rectal cancer: the German trial CAO/ARO/AIO-94. Colorectal Dis. 2003 Sep;5(5):406-15. doi: 10.1046/j.1463-1318.2003.00509.x. PMID: 129250713. Protocolo Asistencial Cáncer de Recto Hospital Universitario de Navarra Keywords: rectum , adaptive radiotherapy, short- course Digital Poster Highlight 4572 Safety and efficacy of ketogenic diet and supplementation during chemoradiotherapy in rectal cancer:A prospective clinical trial(IRCT20170211032494N4) Nima Mousavi Darzikolaee 1 , Saeed Karima 2 , Maryam Abedini 1 , Nastaran Hamed 2 , Reyhaneh Bayani 1 1 Radiation oncology, Tehran University of Medical Sciences, Tehran, Iran, Islamic Republic of. 2 Clinical biochemistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran, Islamic Republic of
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