S2623
Radiobiology - Translational radiobiology
ESTRO 2026
The results may inform optimized treatment approaches and guide future radioimmunotherapy trial designs for HNSCC. Keywords: Head and Neck, Node Irradiation, Biodosimetry Digital Poster Highlight 3850 Development of AuX2R: a chemokine-directed gold nanoparticle for precision radiotherapy enhancement in prostate cancer Niall M Byrne 1 , Sarah EJ Chambers 1 , Jie Feng 1 , Lydia McQuoid 1 , Natalie J Owen 1 , Tongchuan Wang 1 , Wendy B Hyland 2 , Conor McGarry 3,4 , Suneil Jain 3,5 , Jonathan A Coulter 1 1 School of Pharmacy, Queen's University Belfast, Belfast, United Kingdom. 2 North West Cancer Centre, Altnagelvin Hospital, Londonderry, United Kingdom. 3 Johnston Cancer Research Centre, Queen's University Belfast, Belfast, United Kingdom. 4 Northern Ireland Cancer Centre, Belfast Health & Social Care Trust, Belfast, United Kingdom. 5 Clinical Oncology, Northern Ireland Cancer Centre, Belfast, United Kingdom Purpose/Objective: Hypofractionation regimens have transformed prostate cancer (PCa) radiotherapy (RT). However, 20– 30% of patients with high-risk localised PCa experience disease recurrence1. Furthermore, emerging clinical data has reported an elevated risk of genitourinary toxicity, negatively impacting patient quality-of-life2. High-Z nanoparticles, including those comprising gold, can act as effective radiosensitisers3. This study presents a novel, dual-functional gold nanoparticle termed AuX2R, designed to exploit the known physical radioenhancing properties of gold, whilst simultaneously antagonising pro-inflammatory interleukin-8 (IL-8) chemokine signalling. Material/Methods: In-housesynthesised AuX2R was characterised using analytic techniques including dynamic light scattering and UV-vis. AuX2R internalisation was evaluated in PCa cell models (VCaP, LNCaP, DU145, PC3) using hyperspectral microscopy and quantified using inductively coupled plasma atomic absorption spectroscopy (ICP-AAS). In vitro radiosensitisation was assessed by clonogenic assay, with DNA double strand break (DSB) damage quantified using 53BP1. In vivo, serum biochemistry and immune-profiling (flow cytometry) assessed biocompatibility following intravenous and intra-tumour (IT) administration of AuX2R in syngeneic DVL3 murine models. Tumour (PC3) retention and biodistribution of AuX2R were assessed using ICP-MS. The impact of IT AuX2R to enhance RT (2 x 2.5 Gy) and SBRT (3 x 7.25 Gy), delivered using a small animal radiation research
associated with poorer outcomes and reduced response to immune-checkpoint inhibitors, particularly after elective nodal irradiation (ENI). This study examined whether initial ENI omission in a delayed ENI concept reduces blood radiation exposure by analyzing biodosimetric DNA damage markers in peripheral blood lymphocytes (PBLs). Material/Methods: Twenty-one patients with laryngeal, hypopharyngeal, p16-negative oropharyngeal, or oral cavity carcinoma receiving definitive or adjuvant platinum-based chemoradiotherapy (CRT) were randomized to: (i) standard RT with ENI from the start (n=10) or (ii) an upfront boost to gross tumor volume and involved nodes without ENI, followed by delayed ENI after 2 (adjuvant) or 5 (definitive) early boost fractions (n=11). Venous blood was collected pre-RT (t1), 15 min (t2), and 24 h (t3) after the first fraction, and before the sixth fraction (t4, definitive only). DNA damage was quantified in PBLs via γ H2AX/53BP1 DNA double- strand break (DSB) foci (n=21, t1-4), dicentric chromosomes (n=8-10, t1,3,4), and cytokinesis-block micronucleus assay (n=9, t1,4). Baseline DNA damage and ex vivo radiosensitivity were assessed pre-RT (t1). Results: All patients exhibited comparable baseline DNA damage and similar ex vivo DSB-foci induction, confirming that post-RT differences stemmed from the treatment strategy. Following RT, ENI sparing consistently reduced RT-induced DNA damage biomarker frequencies in PBLs versus standard RT with ENI, with significant reductions only for RT- induced DSB foci after the first fraction (t2,3). RT- induced DSB foci frequencies correlated strongly with planning target volume (t2,3: R ≥ 0.57, p<0.05) and whole-body dose (t2,3: R ≥ 0.55, p<0.05), highlighting a dose–volume dependence of systemic genotoxic stress. Compared to standard RT with ENI, ENI sparing resulted in a 4.4-fold (t2, p<0.0001) and 2.3-fold (t3, p<0.05) reduction in RT-induced DSB foci per PBL, and a 13% decrease in PBLs harboring RT-induced DSB foci (t2, p<0.01). While ENI sparing tended to lower RT- induced chromosome aberrations and micronuclei, these showed high inter-patient variability and no significant correlation with planning target volume or whole-body dose. Conclusion: Overall, ENI sparing in HNSCC CRT yielded a strong blood-sparing effect, evidenced by reduced RT- induced DNA damage in PBLs. Its primary measurable benefit was an early, pronounced reduction of DSB foci in PBLs, constituting a sensitive biomarker of RT- induced blood damage. These findings suggest that omitting elective nodal fields can substantially decrease acute systemic DNA damage, potentially mitigating RT-related hematotoxicity and immunosuppression, thereby improving outcomes.
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