The Impact of Nanomedicine on Soft Tissue Sarcoma Treated by Radiotherapy and/or Hyperthermia: A Review.

This article presents a comprehensive review of nanoparticle-assisted treatment approaches for soft tissue sarcoma (STS). STS, a heterogeneous group of mesenchymal-origin tumors with aggressive behavior and low overall survival rates, necessitates the exploration of innovative therapeutic interventions. In contrast to conventional treatments like surgery, radiotherapy (RT), hyperthermia (HT), and chemotherapy, nanomedicine offers promising advancements in STS management. This review focuses on recent research in nanoparticle applications, including their role in enhancing RT and HT efficacy through improved drug delivery systems, novel radiosensitizers, and imaging agents. Reviewing the current state of nanoparticle-assisted therapies, this paper sheds light on their potential to revolutionize soft tissue sarcoma treatment and improve patient therapy outcomes.

Shedding Light on Colorectal Cancer: An In Vivo Raman Spectroscopy Approach Combined with Deep Learning Analysis.

Raman spectroscopy has emerged as a powerful tool in medical, biochemical, and biological research with high specificity, sensitivity, and spatial and temporal resolution. Recent advanced Raman systems, such as portable Raman systems and fiber-optic probes, provide the potential for accurate in vivo discrimination between healthy and cancerous tissues. In our study, a portable Raman probe spectrometer was tested in immunosuppressed mice for the in vivo localization of colorectal cancer malignancies from normal tissue margins. The acquired Raman spectra were preprocessed, and principal component analysis (PCA) was performed to facilitate discrimination between malignant and normal tissues and to highlight their biochemical differences using loading plots. A transfer learning model based on a one-dimensional convolutional neural network (1D-CNN) was employed for the Raman spectra data to assess the classification accuracy of Raman spectra in live animals. The 1D-CNN model yielded an 89.9% accuracy and 91.4% precision in tissue classification. Our results contribute to the field of Raman spectroscopy in cancer diagnosis, highlighting its promising role within clinical applications.

Nanoparticle-Mediated Radiotherapy: Unraveling Dose Enhancement and Apoptotic Responses in Cancer and Normal Cell Lines.

Cervical cancer remains a pressing global health concern, necessitating advanced therapeutic strategies. Radiotherapy, a fundamental treatment modality, has faced challenges such as targeted dose deposition and radiation exposure to healthy tissues, limiting optimal outcomes. To address these hurdles, nanomaterials, specifically gold nanoparticles (AuNPs), have emerged as a promising avenue. This study delves into the realm of cervical cancer radiotherapy through the meticulous exploration of AuNPs' impact. Utilizing ex vivo experiments involving cell lines, this research dissected intricate radiobiological interactions. Detailed scrutiny of cell survival curves, dose enhancement factors (DEFs), and apoptosis in both cancer and normal cervical cells revealed profound insights. The outcomes showcased the substantial enhancement of radiation responses in cancer cells following AuNP treatment, resulting in heightened cell death and apoptotic levels. Significantly, the most pronounced effects were observed 24 h post-irradiation, emphasizing the pivotal role of timing in AuNPs' efficacy. Importantly, AuNPs exhibited targeted precision, selectively impacting cancer cells while preserving normal cells. This study illuminates the potential of AuNPs as potent radiosensitizers in cervical cancer therapy, offering a tailored and efficient approach. Through meticulous ex vivo experimentation, this research expands our comprehension of the complex dynamics between AuNPs and cells, laying the foundation for their optimized clinical utilization.

Extended Analysis of Raman Spectra Using Artificial Intelligence Techniques for Colorectal Abnormality Classification.

Raman spectroscopy (RS) techniques are attracting attention in the medical field as a promising tool for real-time biochemical analyses. The integration of artificial intelligence (AI) algorithms with RS has greatly enhanced its ability to accurately classify spectral data in vivo. This combination has opened up new possibilities for precise and efficient analysis in medical applications. In this study, healthy and cancerous specimens from 22 patients who underwent open colorectal surgery were collected. By using these spectral data, we investigate an optimal preprocessing pipeline for statistical analysis using AI techniques. This exploration entails proposing preprocessing methods and algorithms to enhance classification outcomes. The research encompasses a thorough ablation study comparing machine learning and deep learning algorithms toward the advancement of the clinical applicability of RS. The results indicate substantial accuracy improvements using techniques like baseline correction, L2 normalization, filtering, and PCA, yielding an overall accuracy enhancement of 15.8%. In comparing various algorithms, machine learning models, such as XGBoost and Random Forest, demonstrate effectiveness in classifying both normal and abnormal tissues. Similarly, deep learning models, such as 1D-Resnet and particularly the 1D-CNN model, exhibit superior performance in classifying abnormal cases. This research contributes valuable insights into the integration of AI in medical diagnostics and expands the potential of RS methods for achieving accurate malignancy classification.

Patient Dose Estimation in Computed Tomography-Guided Biopsy Procedures.

This study establishes typical Diagnostic Reference Levels (DRL) values and assesses patient doses in computed tomography (CT)-guided biopsy procedures. The Effective Dose (ED), Entrance Skin Dose (ESD), and Size-Specific Dose Estimate (SSDE) were calculated using the relevant literature-derived conversion factors. A retrospective analysis of 226 CT-guided biopsies across five categories (Iliac bone, liver, lung, mediastinum, and para-aortic lymph nodes) was conducted. Typical DRL values were computed as median distributions, following guidelines from the International Commission on Radiological Protection (ICRP) Publication 135. DRLs for helical mode CT acquisitions were set at 9.7 mGy for Iliac bone, 8.9 mGy for liver, 8.8 mGy for lung, 7.9 mGy for mediastinal mass, and 9 mGy for para-aortic lymph nodes biopsies. In contrast, DRLs for biopsy acquisitions were 7.3 mGy, 7.7 mGy, 5.6 mGy, 5.6 mGy, and 7.4 mGy, respectively. Median SSDE values varied from 7.6 mGy to 10 mGy for biopsy acquisitions and from 11.3 mGy to 12.6 mGy for helical scans. Median ED values ranged from 1.6 mSv to 5.7 mSv for biopsy scans and from 3.9 mSv to 9.3 mSv for helical scans. The study highlights the significance of using DRLs for optimizing CT-guided biopsy procedures, revealing notable variations in radiation exposure between helical scans covering entire anatomical regions and localized biopsy acquisitions.

Isodose surface differences: A novel tool for the comparison of dose distributions.

BACKGROUND: Comparing dose distributions is a routine task in radiotherapy, mainly in patient-specific quality assurance (PSQA). Currently, the evaluation of the dose distributions is being performed mainly with statistical methods, which could underestimate the clinical importance of the spotted differences, as per the literature. PURPOSE: This paper aims to provide proof-of-concept for a novel dose distribution comparison method based on the difference of the isodose surfaces. The new method connects acceptance tolerance to QA limitations (equipment capabilities) and integrates a clinical approach into the analysis procedure. METHODS: The distance of dose points from the isocenter can be used as a function to define the shape of an isodose surface expressed as a histogram. Isodose surface differences (ISD) are defined as the normalized differences of reference and evaluated surface histograms plotted against their corresponding isodose. Acceptance tolerances originate from actual QA tolerances and are presented clinically intuitively. The ISD method was compared to the gamma index using intentionally erroneous VMAT and IMRT plans. RESULTS: Results revealed that the ISD method is sensitive to all errors induced in the plans. Discrepancies are presented per isodose, enabling the evaluation of the plan in two regions representing PTV and Normal Tissue. ISD manages to flag errors that would remain undetected under the gamma analysis. CONCLUSION: The ISD method is a meaningful, QA-related, registration-free, and clinically oriented technique of dose distribution evaluation. This method can be used either as a standalone or an auxiliary tool to the well-established evaluation procedures, overcoming significant limitations reported in the literature.

Clustered DNA Damage Patterns after Proton Therapy Beam Irradiation Using Plasmid DNA.

Modeling ionizing radiation interaction with biological matter is a major scientific challenge, especially for protons that are nowadays widely used in cancer treatment. That presupposes a sound understanding of the mechanisms that take place from the early events of the induction of DNA damage. Herein, we present results of irradiation-induced complex DNA damage measurements using plasmid pBR322 along a typical Proton Treatment Plan at the MedAustron proton and carbon beam therapy facility (energy 137-198 MeV and Linear Energy Transfer (LET) range 1-9 keV/µm), by means of Agarose Gel Electrophoresis and DNA fragmentation using Atomic Force Microscopy (AFM). The induction rate Mbp-1 Gy-1 for each type of damage, single strand breaks (SSBs), double-strand breaks (DSBs), base lesions and non-DSB clusters was measured after irradiations in solutions with varying scavenging capacity containing 2-amino-2-(hydroxymethyl)propane-1,3-diol (Tris) and coumarin-3-carboxylic acid (C3CA) as scavengers. Our combined results reveal the determining role of LET and Reactive Oxygen Species (ROS) in DNA fragmentation. Furthermore, AFM used to measure apparent DNA lengths provided us with insights into the role of increasing LET in the induction of highly complex DNA damage.

FDXR Gene Expression after in Vivo Radiation Exposure of Pediatric Patients Undergoing Interventional Cardiology Procedures.

BACKGROUND: Ferredoxin reductase (FDXR) has already been reported as a promising biomarker for estimating radiation doses in radiotherapy. This study aimed to investigate the responsiveness of FDXR on pediatric population exposed to ionizing radiation (X-rays) during pediatric interventional cardiology (IC) procedures. PATIENTS AND METHODS: Peripheral blood was collected by venipuncture from 24 pediatric donors before and 24 hours after the IC procedure. To estimate the effective dose, demographic data and Air Kerma-Area Product (PKA) were recorded for each patient. The relative quantification (RQ) of the FDXR gene in irradiated patient blood samples compared to the non-irradiated blood samples was determined using qPCR analysis. The relative values of FDXR were log- transformed. RESULTS: The effective dose ranged from 0.002 mSv to 8.004 mSv. Over this radiation exposure range, the FDXR gene expression varied randomly with the effective dose. Up-regulation in FDXR expression was observed in 17 patients and down-regulation in 7 patients. CONCLUSIONS: Further studies in a larger cohort of pediatric patients along with the record of clinical data are needed to determine whether FDXR gene expression is an effective biomarker for radiation exposure estimation in pediatric imaging.

Nanomedicine approaches for treatment of hematologic and oncologic malignancies.

Cancer is a leading cause of death worldwide. Nowadays, the therapies are inadequate and spur demand for improved technologies. Rapid growth in nanotechnology and novel nanomedicine products represents an opportunity to achieve sophisticated targeting strategies and multi-functionality. Nanomedicine is increasingly used to develop new cancer diagnosis and treatment methods since this technology can modulate the biodistribution and the target site accumulation of chemotherapeutic drugs, thereby reducing their toxicity. Cancer nanotechnology and cancer immunotherapy are two parallel themes that have emerged over the last few decades while searching for a cure for cancer. Immunotherapy is revolutionizing cancer treatment, as it can achieve unprecedented responses in advanced-stage patients, including complete cures and long-term survival. A deeper understanding of the human immune system allows the establishment of combination regimens in which immunotherapy is combined with other treatment modalities (as in the case of the nanodrug Ferumoxytol). Furthermore, the combination of gene therapy approaches with nanotechnology that aims to silence or express cancer-relevant genes via one-time treatment is gradually progressing from bench to bedside. The most common example includes lipid-based nanoparticles that target VEGF-Α and KRAS pathways. This review focuses on nanoparticle-based platforms utilized in recent advances aiming to increase the efficacy of currently available cancer therapies. The insights provided and the evidence obtained in this paper indicate a bright future ahead for immuno-oncology applications of engineering nanomedicines.

Implementation of TG-218 for patient-specific quality assurance tolerance and action limits determination: Gamma passing rate evaluation using 3DVH software.

PURPOSE: To determine the tolerance limit (TL) and action limit (AL) of gamma passing rates (%GP) for volumetric-modulated arc therapy (VMAT) patient-specific quality assurance (PSQA) according to the American Association of Physicists in Medicine (AAPM) Task Group (TG)-218 recommendations, and to comparatively evaluate the clinical relevance of 2D %GP and 3D %GP. METHODS: PSQA was performed for 100 head and neck (H&N) and 73 prostate cancer VMAT treatment plans. Measurements were acquired using a cylindrical water equivalent phantom, hollow in the center, allowing measurements with homogeneous or heterogeneous inserts. The LINAC-delivered dose distributions were compared to those calculated from the treatment planning system through the gamma index. TL and AL were determined through the computation of two-dimensional (2D) %GP using the recommended acceptance criteria. Dose-volume histograms were reconstructed from the measurements using a commercially available software to detect the dosimetric errors (%DE) between the compared dose distributions. Utilizing the estimated dose on the patient anatomy, structure-specific %GP (3D %GP) were calculated. The 3D %GP were compared to the 2D %GP ones based on their correlation with the %DE. Each metric's sensitivity was determined through receiver operator characteristic analysis. RESULTS: TL and AL were in concordance with the universal ones, regarding the prostate cancer cases, but were lower for the H&N cases. Evaluation of %DE did not deem the plans unacceptable. The 2D %GP and the 3D %GP did not differ significantly regarding their correlation with %DE. For prostate plans, %GP sensitivity was higher than for H&N cases. CONCLUSIONS: Determination of institutional-specific TL and AL allows the monitoring of the PSQA procedure, yet for plans close to the limits, clinically relevant metrics should be used before they are deemed unacceptable for the process to be of higher sensitivity and efficiency.

Quantification of Nanoscale Dose Enhancement in Gold Nanoparticle-Aided External Photon Beam Radiotherapy.

The recent progress in Nanotechnology has introduced Gold Nanoparticles (AuNPs) as promising radiosensitizing agents in radiation oncology. This work aims to estimate dose enhancement due to the presence of AuNPs inside an irradiated water region through Monte Carlo calculations. The GATE platform was used to simulate 6 MV photon histories generated from a TrueBeam® linear accelerator with and without a Flattening Filter (FF) and model AuNPs clusters. The AuNPs size, concentration and distribution pattern were examined. To investigate different clinical irradiation conditions, the effect of field size, presence of FF and placement of AuNPs in water were evaluated. The range of Dose Enhancement Factors (DEF = DoseAu/DoseWater) calculated in this study is 0.99 ± 0.01-1.26 ± 0.02 depending on photon beam quality, distance from AuNPs surface, AuNPs size and concentration and pattern of distribution. The highest DEF is reported for irradiation using un-flattened photon beams and at close distances from AuNPs. The obtained findings suggest that dose deposition could be increased in regions that represent whole cells or subcellular targets (mitochondria, cell nucleus, etc.). Nevertheless, further and consistent research is needed in order to make a step toward AuNP-aided radiotherapy in clinical practice.

Raman Spectroscopy: A Personalized Decision-Making Tool on Clinicians' Hands for In Situ Cancer Diagnosis and Surgery Guidance.

Accurate in situ diagnosis and optimal surgical removal of a malignancy constitute key elements in reducing cancer-related morbidity and mortality. In surgical oncology, the accurate discrimination between healthy and cancerous tissues is critical for the postoperative care of the patient. Conventional imaging techniques have attempted to serve as adjuvant tools for in situ biopsy and surgery guidance. However, no single imaging modality has been proven sufficient in terms of specificity, sensitivity, multiplexing capacity, spatial and temporal resolution. Moreover, most techniques are unable to provide information regarding the molecular tissue composition. In this review, we highlight the potential of Raman spectroscopy as a spectroscopic technique with high detection sensitivity and spatial resolution for distinguishing healthy from malignant margins in microscopic scale and in real time. A Raman spectrum constitutes an intrinsic "molecular finger-print" of the tissue and any biochemical alteration related to inflammatory or cancerous tissue state is reflected on its Raman spectral fingerprint. Nowadays, advanced Raman systems coupled with modern instrumentation devices and machine learning methods are entering the clinical arena as adjunct tools towards personalized and optimized efficacy in surgical oncology.

Ag/Au Bimetallic Nanoparticles Trigger Different Cell Death Pathways and Affect Damage Associated Molecular Pattern Release in Human Cell Lines.

Apoptosis induction is a common therapeutic approach. However, many cancer cells are resistant to apoptotic death and alternative cell death pathways including pyroptosis and necroptosis need to be triggered. At the same time, danger signals that include HMGB1 and HSP70 can be secreted/released by damaged cancer cells that boost antitumor immunity. We studied the cytotoxic effects of AgAu NPs, Ag NPs and Au NPs with regard to the programmed cell death (apoptosis, necroptosis, pyroptosis) and the secretion/release of HSP70 and HMGB1. Cancer cell lines were incubated with 30, 40 and 50 µg/mL of AgAu NPs, Ag NPs and Au NPs. Cytotoxicity was estimated using the MTS assay, and mRNA fold change of CASP1, CASP3, BCL-2, ZPB1, HMGB1, HSP70, CXCL8, CSF1, CCL20, NLRP3, IL-1ß and IL-18 was used to investigate the associated programmed cell death. Extracellular levels of HMGB1 and IL-1ß were investigated using the ELISA technique. The nanoparticles showed a dose dependent toxicity. Pyroptosis was triggered for LNCaP and MDA-MB-231 cells, and necroptosis for MDA-MB-231 cells. HCT116 cells experience apoptotic death and show increased levels of extracellular HMGB1. Our results suggest that in a manner dependent of the cellular microenvironment, AgAu NPs trigger mixed programmed cell death in P53 deficient MDA-MB-231 cells, while they also trigger IL-1ß release in MDA-MB-231 and LNCaP cells and release of HMGB1 in HCT116 cells.

SGLT-2 Inhibitors in NAFLD: Expanding Their Role beyond Diabetes and Cardioprotection.

Non-alcoholic fatty liver disease (NAFLD) is an 'umbrella' term, comprising a spectrum ranging from benign, liver steatosis to non-alcoholic steatohepatitis, liver fibrosis and eventually cirrhosis and hepatocellular carcinoma. NAFLD has evolved as a major health problem in recent years. Discovering ways to prevent or delay the progression of NAFLD has become a global focus. Lifestyle modifications remain the cornerstone of NAFLD treatment, even though various pharmaceutical interventions are currently under clinical trial. Among them, sodium-glucose co-transporter type-2 inhibitors (SGLT-2i) are emerging as promising agents. Processes regulated by SGLT-2i, such as endoplasmic reticulum (ER) and oxidative stress, low-grade inflammation, autophagy and apoptosis are all implicated in NAFLD pathogenesis. In this review, we summarize the current understanding of the NAFLD pathophysiology, and specifically focus on the potential impact of SGLT-2i in NAFLD development and progression, providing current evidence from in vitro, animal and human studies. Given this evidence, further mechanistic studies would advance our understanding of the exact mechanisms underlying the pathogenesis of NAFLD and the potential beneficial actions of SGLT-2i in the context of NAFLD treatment.

The Role of Ionizing Radiation for Diagnosis and Treatment against COVID-19: Evidence and Considerations.

The Coronavirus disease 2019 (COVID-19) pandemic continues to spread worldwide with over 260 million people infected and more than 5 million deaths, numbers that are escalating on a daily basis. Frontline health workers and scientists diligently fight to alleviate life-threatening symptoms and control the spread of the disease. There is an urgent need for better triage of patients, especially in third world countries, in order to decrease the pressure induced on healthcare facilities. In the struggle to treat life-threatening COVID-19 pneumonia, scientists have debated the clinical use of ionizing radiation (IR). The historical literature dating back to the 1940s contains many reports of successful treatment of pneumonia with IR. In this work, we critically review the literature for the use of IR for both diagnostic and treatment purposes. We identify details including the computed tomography (CT) scanning considerations, the radiobiological basis of IR anti-inflammatory effects, the supportive evidence for low dose radiation therapy (LDRT), and the risks of radiation-induced cancer and cardiac disease associated with LDRT. In this paper, we address concerns regarding the effective management of COVID-19 patients and potential avenues that could provide empirical evidence for the fight against the disease.

Requirements for Designing an Effective Metallic Nanoparticle (NP)-Boosted Radiation Therapy (RT).

Many different tumor-targeted strategies are under development worldwide to limit the side effects and improve the effectiveness of cancer therapies. One promising method is to enhance the radiosensitization of the cancer cells while reducing or maintaining the normal tissue complication probability during radiation therapy using metallic nanoparticles (NPs). Radiotherapy with MV photons is more commonly available and applied in cancer clinics than high LET particle radiotherapy, so the addition of high-Z NPs has the potential to further increase the efficacy of photon radiotherapy in terms of NP radiosensitization. Generally, when using X-rays, mainly the inner electron shells are ionized, which creates cascades of both low and high energy Auger electrons. When using high LET particles, mainly the outer shells are ionized, which give electrons with lower energies than when using X-rays. The amount of the produced low energy electrons is higher when exposing NPs to heavy charged particles than when exposing them to X-rays. Since ions traverse the material along tracks, and therefore give rise to a much more inhomogeneous dose distributions than X-rays, there might be a need to introduce a higher number of NPs when using ions compared to when using X-rays to create enough primary and secondary electrons to get the desired dose escalations. This raises the questions of toxicity. This paper provides a review of the fundamental processes controlling the outcome of metallic NP-boosted photon beam and ion beam radiation therapy and presents some experimental procedures to study the biological effects of NPs' radiosensitization. The overview shows the need for more systematic studies of the behavior of NPs when exposed to different kinds of ionizing radiation before applying metallic-based NPs in clinical practice to improve the effect of IR therapy.

The Importance of Radiation Protection Education and Training for Medical Professionals of All Specialties.

The article is part of the series of articles on radiation protection. You can find further articles in the special section of the CVIR issue. Lately, more advanced techniques have been introduced in medical imaging expanding the diagnostic and therapeutic applications of ionizing radiation. Among the various strategies that have been proposed for the management of radiation exposure, education and training seem to have a strong impact on radiation protection and dose reduction. However, according to several studies, medical professionals appear to lack knowledge on basic radiation protection aspects. Therefore, the establishment of an accreditation and certification system in radiation protection for all medical professionals employing ionizing radiation is considered as high priority. The purpose of this review article is to highlight the importance of education and training in radiation protection, provide recommendations for an effective educational program and propose an educational program structure for the different medical specialties.

Radiation Exposure in Pediatric Interventional Procedures.

The article is part of the series of articles on radiation protection. You can find further articles in the special section of the CVIR issue. The expanding applications of interventional procedures coupled with the potential harmful effects of ionizing radiation highlight the need to assess the delivered radiation dose and establish an effective radiation protection program, particularly in the radiosensitive pediatric population. Given the complexity and heterogeneity of interventional procedures as well as the unique characteristics of children, the management of radiation dose is proving to be quite challenging. The aim of the current article is to provide an overview of the radiation exposure in pediatric patients during interventional procedures focusing on the importance of radiation protection in the pediatric population, the reported radiation doses and the techniques of minimizing radiation dose.

Chemotherapy-Induced Brain Effects in Small-Cell Lung Cancer Patients: A Multimodal MRI Study.

The golden standard of treating Small Cell Lung Cancer (SCLC) entails application of platinum-based chemotherapy, is often accompanied by Prophylactic Cranial Irradiation (PCI), which have been linked to neurotoxic side-effects in cognitive functions. The related existing neuroimaging research mainly focuses on the effect of PCI treatment in life quality and expectancy, while little is known regarding the distinct adverse effects of chemotherapy. In this context, a multimodal MRI analysis based on structural and functional brain data is proposed in order to evaluate chemotherapy-specific effects on SCLC patients. Data from 20 patients (after chemotherapy and before PCI) and 14 healthy controls who underwent structural MRI, DTI and resting state fMRI were selected in this study. From a structural aspect, the proposed analysis included volumetry and thickness measurements on structural MRI data for assessing gray matter dissimilarities, as well as deterministic tractography and Tract-Based Spatial Statistics (TBSS) on DTI data, aiming to investigate potential white matter abnormalities. Functional data were also processed on the basis of connectivity analysis, evaluating brain network parameters to identify potential manifestation of functional inconsistencies. By comparing patients to healthy controls, the obtained results revealed statistically significant differences, with the patients' brains presenting reduced volumetry/thickness and fractional anisotropy values, accompanied by prominent differences in functional connectivity measurements. All above mentioned findings were observed in patients that underwent chemotherapy.

Monte Carlo studies in Gold Nanoparticles enhanced radiotherapy: The impact of modelled parameters in dose enhancement.

PURPOSE: Over the last decades, Gold Nanoparticles (AuNPs) have been presented as an innovative approach in radiotherapy (RT) enhancement. Several studies have proven that the irradiation of tumors containing AuNPs could lead to more effective tumor control than irradiation alone. Studies with low kV photons and AuNPs conclude in encouraging results regarding the level of radioenhancement. However, experimental and theoretical studies with MV photons report controversial findings concerning the correlation between dose enhancement effect and tumor cell killing. The great variation in the experimental protocols and simulations complicates the comparison of their outcomes and depicts the need for limiting the variety of investigated parameters. Our purpose is to point out a possible direction for building realistic Monte Carlo (MC) models that could end up with promising results in MV photons RT enhancement. METHODS: We explored published in silico studies concerning AuNPs enhanced RT from 2010 to 2019. In this review, we discuss the different AuNPs and MV photon beams characteristics that have been reported and their effect in dose enhancement. RESULTS: AuNPs size, concentration, type of distribution along with photon beams energy and the presence of flattening filter in linear accelerators seem to be the major parameters that determine AuNPs radioenhancement in silico. CONCLUSIONS: Prior to AuNPs clinical translation in photon radiotherapy, in silico studies should emphasize on nanodosimetry and track structure codes than condensed history ones. Toxicity estimation and biological aspects should be implemented in MC simulations so as to achieve accurate and realistic modelling of AuNPs driven RT.