S2572
Radiobiology – Normal tissue radiobiology
ESTRO 2026
References: 1.Elad S, Yarom N, Zadik Y, et al. The broadening scope of oral mucositis and oral ulcerative mucosal toxicities of anticancer therapies. CA Cancer J Clin. 2022;72(1):57-77.2.Song B, Yang P, Zhang S. Cell fate regulation governed by p53: Friends or reversible foes in cancer therapy. Cancer Commun (Lond). 2024; 44(3):297-360.3.Herro R, Grimes HL. The diverse roles of neutrophils from protection to pathogenesis. Nat Immunol. 2024; 25(12):2209-2219. Keywords: RIOM, p53, transcriptomic Digital Poster Highlight 2404 Curcumin Mitigates Radiation Necrosis Induced by Concurrent Trastuzumab Emtansine and Radiotherapy via Aquaporin-4 Modulation Ezgi Gurlek Tumer 1 , Volkan Tumer 2 , Berrin Babaoglu 3 , Alper Bektas Iskit 2 , Huseyin Kıvanc 1 , Selcuk Surucu 4 , Sercan Aksoy 5 , Gozde Yazıcı 1 , Ferah Yıldız 1 , Melis Gultekin 1 1 Radiation Oncology, Hacettepe University, Ankara, Turkey. 2 Pharmacology, Hacettepe University, Ankara, Turkey. 3 Pathology, Hacettepe University, Ankara, Turkey. 4 Anatomy, Koc University, Istanbul, Turkey. 5 Medical Oncology, Hacettepe University, Ankara, Turkey
1 β expression levels were analyzed immunohistochemically, and oxidative stress index measurements were performed. Ultrastructural alterations were examined by transmission electron microscopy and scored quantitatively. In the chronic phase, histopathological assessments were conducted using light microscopy. Results: Curcumin significantly attenuated RT and T- DM1 induced increases in IL-1 β and AQP-4 expression during the acute phase (Image 1). RT alone elevated oxidative stress, further amplified by T-DM1; this effect was reduced by curcumin. Electron microscopy revealed that curcumin reduced axonal myelin injury, axonal and intracytoplasmic edema, nuclear damage and vascular endothelial swelling caused by RT + T- DM1 (Image 2). In the chronic phase, RT led to pronounced calcification and necrosis, which were aggravated by T-DM1 but significantly mitigated by curcumin treatment.
Purpose/Objective: Concurrent or sequential administration of
trastuzumab emtansine (T-DM1) with radiotherapy (RT) has been associated with an increased incidence of radiation necrosis. Vascular injury, inflammation, and cerebral edema play central roles in its pathophysiology1. T-DM1 upregulates aquaporin-4 (AQP-4) channels in astrocytic end-feet, thereby exacerbating brain edema and necrosis2. Curcumin, known for its anti-inflammatory and antioxidant effects, may modulate AQP-4 expression through interleukin-1 β (IL-1 β ) regulation3. This study aimed to investigate the potential neuroprotective effect of curcumin on radiation necrosis induced by concurrent RT and T-DM1 treatment. Material/Methods: Eighty male Wistar rats were randomly assigned to four groups: control, RT, RT + T-DM1, and RT + T-DM1 + curcumin. Half of the animals were sacrificed on day 2 (acute phase), and the remaining at week 10 (chronic phase). RT was delivered in a single 100 Gy fraction to the cerebral hemispheres along the bilateral lateral ventricles. Curcumin (200 mg/kg) was administered orally via gavage starting one week before RT and continued until sacrifice in the acute groups, and for two weeks in the chronic groups. T-DM1 (20 mg/kg) was administered intravenously through the tail vein at a dose of 1 mL/kg. In the acute phase, AQP-4 and IL-
Image 1:Immunohistochemical analysis of AQP-4 and IL-1 β expression in the acute groups (n = 5– 7/group;*p < 0.05, **p < 0.005).
Image 2: A) RT+T-DM1 acute phase. Normal capillary endothelial (E) cell is surrounded by edematous astrocytic processes (O). Axonal myelin layers (*) are separated showing ischemia. B) RT+T-DM1+curcumin acute phase. Intact capillary endothelial cell next to an erythrocyte is observed. There is no edema in the neuropile and most of the axons are intact. Conclusion: Curcumin may serve as a potential therapeutic agent for preventing radiation necrosis secondary to concurrent RT and T-DM1 administration. References: 1. Salvestrini V, Kim K, Caini S, et al. Safety profile of trastuzumab-emtansine (T-DM1) with concurrent radiation therapy: A systematic review and meta-
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