Kyveli Zourari

Background/Objectives: Cervical cancer treatment relies heavily on high-dose-rate (HDR) ¹⁹²Ir brachytherapy; however, therapeutic efficacy remains limited by tumor radioresistance and the inability to escalate dose without increasing toxicity to surrounding healthy tissues. The present study investigates the potential of gold nanoparticles (AuNPs) to enhance radiosensitivity under clinically relevant ¹⁹²Ir brachytherapy conditions through the combined action of physical dose amplification and radiobiological modulation. Particular emphasis is placed on the unique radiophysical interactions generated by the mixed gamma and secondary beta emissions of ¹⁹²Ir, which, in the presence of high atomic number nanoparticles, promote localized photoelectric absorption and the emission of low-range secondary electrons, including Auger electrons. The study further aims to determine how AuNPs size and post-irradiation temporal evolution influence radiation-induced cytotoxicity and apoptosis in cervical cancer cell lines, thereby providing a biologically representative model of nanoparticle-assisted brachytherapy. Methods: Clonogenic survival, dose enhancement factor (DEF), and apoptosis were evaluated following irradiation in the presence of 10 nm and 50 nm AuNPs in two independent biological experiments (n = 2). Results: A clear dose-dependent reduction in survival fraction and increase in apoptosis were observed in nanoparticle-treated groups compared with irradiation alone. Radiosensitization demonstrated strong size dependence, with 50 nm AuNPs producing the greatest enhancement, a finding that may reflect size-dependent differences in cellular internalization, intracellular distribution, and nanoscale energy deposition previously established in AuNP studies. Importantly, biological effects intensified at later post-irradiation intervals, demonstrating a sustained temporal evolution of the radiobiological response beyond the initial irradiation event, potentially involving oxidative and other delayed cellular stress mechanisms described in AuNP radiosensitization. Conclusions: These findings demonstrate the capacity of AuNPs to enhance the radiobiological response of cervical cancer cells to ¹⁹²Ir brachytherapy and identify nanoparticle size and post-irradiation time as important determinants of this effect. They therefore support AuNP-assisted brachytherapy as a promising strategy for further development toward biologically optimized radiotherapy capable of improving tumor response without escalation of the prescribed radiation dose.

Purpose:: To compare TG43‐based and Acuros deterministic radiation transport‐based calculations of the BrachyVision treatment planning system (TPS) with corresponding Monte Carlo (MC) simulation results in heterogeneous patient geometries, in order to validate Acuros and quantify the accuracy improvement it marks relative to TG43.Methods:: Dosimetric comparisons in the form of isodose lines, percentage dose difference maps, and dose volume histogram results were performed for two voxelized mathematical models resembling an esophageal and a breast brachytherapy patient, as well as an actual breast brachytherapy patient model. The mathematical models were converted to digital imaging and communications in medicine (DICOM) image series for input to the TPS. The MCNP5 v.1.40 general‐purpose simulation code input files for each model were prepared using information derived from the corresponding DICOM RT exports from the TPS.Results:: Comparisons of MC and TG43 results in all models showed significant differences, as reported previously in the literature and expected from the inability of the TG43 based algorithm to account for heterogeneities and model specific scatter conditions. A close agreement was observed between MC and Acuros results in all models except for a limited number of points that lay in the penumbra of perfectly shaped structures in the esophageal model, or at distances very close to the catheters in all models.Conclusions:: Acuros marks a significant dosimetry improvement relative to TG43. The assessment of the clinical significance of this accuracy improvement requires further work. Mathematical patient equivalent models and models prepared from actual patient CT series are useful complementary tools in the methodology outlined in this series of works for the benchmarking of any advanced dose calculation algorithm beyond TG43.