Toward a multi-layer micro-structured detector for high-energy electron radiotherapy.

BACKGROUND: The use of electron beams has been rekindled by the advent of ultra-high-dose rate radiotherapy (FLASH) and very high energy electrons (VHEE). The need for development of novel technology for beam monitoring and dosimetry of such beams is of paramount importance prior to their clinical translation. PURPOSE: In this work we explore the potential of a multi-layer nanoporous aerogel High-Energy-Current (HEC) detector as a dosimeter for electron beam. The detector does not suffer from radiation damage or signal saturation, making it suitable for very-high-dose-rate applications. Standard dose rates and energies are used to establish reference for FLASH and VHEE. We explore detector response to electron energy and residual range both experimentally and computationally. METHODS: Multilayer HEC detectors were constructed using 1×-10× basic modules of Aluminum(Al)_aerogel(A)_Tantalum(Ta) with 10-70 µm layer thicknesses. Signals are collected from all electrodes (3-21, depending on module multiplicity) with zero external voltage bias. Measurements are acquired as a function of depth(z) in water equivalent plastic using Varian TrueBeam for energies E = 6,9,12,15 MeV (SAD = 105 cm, 6 × 6 cone, 1000 MU/min). Computational simulations of identical detector geometries are performed using the 1D deterministic code CEPXS/ONEDANT. Additionally, percent-depth-doses PDD(z), measured with diode in water, are used to explore the response of HEC for various energies and residual ranges. RESULTS: The current measured from Ta electrodes resembles the shape of deposited charges in water and it is proportional to the derivative of the clinical PDD corrected for contribution from photon contamination. The signal is positive on the surface, and it decreases with depth reaching a negative local minimum at z = R50, before increasing again, reaching zero at about the practical range z = Rp. In contrast, the signal from Al electrodes is shaped like the electron PDD(z) shape but with lower signal at the surface and higher bremsstrahlung tail. By subtracting the signal from Ta and Al electrodes we obtained a curve resembling PDD(z,E) after Bremsstrahlung contamination correction. CONCLUSIONS: Multi-layer HEC sensors exhibit characteristic responses to electron beams that are unlike responses of ion chambers or diodes. Since the sensor structures are sensitive to electronic disequilibrium, high-Z electrodes give a signal proportional to the charge deposition pattern and can be modeled using the derivative of PDD(z).

Investigating the Use of a Liquid Immunogenic Fiducial Eluter Biomaterial in Cervical Cancer Treatment.

Globally, cervical cancer is the fourth leading cancer among women and is dominant in resource-poor settings in its occurrence and mortality. This study focuses on developing liquid immunogenic fiducial eluter (LIFE) Biomaterial with components that include biodegradable polymers, nanoparticles, and an immunoadjuvant. LIFE Biomaterial is designed to provide image guidance during radiotherapy similar to clinically used liquid fiducials while enhancing therapeutic efficacy for advanced cervical cancer. C57BL6 mice were used to grow subcutaneous tumors on bilateral flanks. The tumor on one flank was then treated using LIFE Biomaterial prepared with the immunoadjuvant anti-CD40, with/without radiotherapy at 6 Gy. Computed tomography (CT) and magnetic resonance (MR) imaging visibility were also evaluated in human cadavers. A pharmacodynamics study was also conducted to assess the safety of LIFE Biomaterial in healthy C57BL6 female mice. Results showed that LIFE Biomaterial could provide both CT and MR imaging contrast over time. Inhibition in tumor growth and prolonged significant survival (* p < 0.05) were consistently observed for groups treated with the combination of radiotherapy and LIFE Biomaterial, highlighting the potential for this strategy. Minimal toxicity was observed for healthy mice treated with LIFE Biomaterial with/without anti-CD40 in comparison to non-treated cohorts. The results demonstrate promise for the further development and clinical translation of this approach to enhance the survival and quality of life of patients with advanced cervical cancer.

A 3D In Vitro Cortical Tissue Model Based on Dense Collagen to Study the Effects of Gamma Radiation on Neuronal Function.

Studies on gamma radiation-induced injury have long been focused on hematopoietic, gastrointestinal, and cardiovascular systems, yet little is known about the effects of gamma radiation on the function of human cortical tissue. The challenge in studying radiation-induced cortical injury is, in part, due to a lack of human tissue models and physiologically relevant readouts. Here, a physiologically relevant 3D collagen-based cortical tissue model (CTM) is developed for studying the functional response of human iPSC-derived neurons and astrocytes to a sub-lethal radiation exposure (5 Gy). Cytotoxicity, DNA damage, morphology, and extracellular electrophysiology are quantified. It is reported that 5 Gy exposure significantly increases cytotoxicity, DNA damage, and astrocyte reactivity while significantly decreasing neurite length and neuronal network activity. Additionally, it is found that clinically deployed radioprotectant amifostine ameliorates the DNA damage, cytotoxicity, and astrocyte reactivity. The CTM provides a critical experimental platform to understand cell-level mechanisms by which gamma radiation (GR) affects human cortical tissue and to screen prospective radioprotectant compounds.

Pre-Clinical Investigations of the Pharmacodynamics of Immunogenic Smart Radiotherapy Biomaterials (iSRB).

The use of an immunogenic smart radiotherapy biomaterial (iSRB) for the delivery of anti-CD40 is effective in treating different cancers in animal models. This study further characterizes the use of iSRBs to evaluate any associated toxicity in healthy C57BL6 mice. iSRBs were fabricated using a poly-lactic-co-glycolic-acid (PLGA) polymer mixed with titanium dioxide (TiO2) nanoparticles incorporated into its matrix. Animal studies included investigations of freely injected anti-CD40, anti-CD40-loaded iSRBs, unloaded iSRBs and control (healthy) animal cohorts. Mice were euthanized at pre-determined time points post-treatment to evaluate the serum chemistry pertaining to kidney and liver toxicity and cell blood count parameters, as well as pathology reports on organs of interest. Results showed comparable liver and kidney function in all cohorts. The results indicate that using iSRBs with or without anti-CD40 does not result in any significant toxicity compared to healthy untreated animals. The findings provide a useful reference for further studies aimed at optimizing the therapeutic efficacy and safety of iSRBs and further clinical translation work.

Smart Radiotherapy Biomaterials for Image-Guided In Situ Cancer Vaccination.

Recent studies have highlighted the potential of smart radiotherapy biomaterials (SRBs) for combining radiotherapy and immunotherapy. These SRBs include smart fiducial markers and smart nanoparticles made with high atomic number materials that can provide requisite image contrast during radiotherapy, increase tumor immunogenicity, and provide sustained local delivery of immunotherapy. Here, we review the state-of-the-art in this area of research, the challenges and opportunities, with a focus on in situ vaccination to expand the role of radiotherapy in the treatment of both local and metastatic disease. A roadmap for clinical translation is outlined with a focus on specific cancers where such an approach is readily translatable or will have the highest impact. The potential of FLASH radiotherapy to synergize with SRBs is discussed including prospects for using SRBs in place of currently used inert radiotherapy biomaterials such as fiducial markers, or spacers. While the bulk of this review focuses on the last decade, in some cases, relevant foundational work extends as far back as the last two and half decades.

Clinical application of a template-guided automated planning routine.

PURPOSE: Determine the dosimetric quality and the planning time reduction when utilizing a template-based automated planning application. METHODS: A software application integrated through the treatment planning system application programing interface, QuickPlan, was developed to facilitate automated planning using configurable templates for contouring, knowledge-based planning structure matching, field design, and algorithm settings. Validations are performed at various levels of the planning procedure and assist in the evaluation of readiness of the CT image, structure set, and plan layout for automated planning. QuickPlan is evaluated dosimetrically against 22 hippocampal-avoidance whole brain radiotherapy patients. The required times to treatment plan generation are compared for the validations set as well as 10 prospective patients whose plans have been automated by QuickPlan. RESULTS: The generations of 22 automated treatment plans are compared against a manual replanning using an identical process, resulting in dosimetric differences of minor clinical significance. The target dose to 2% volume and homogeneity index result in significantly decreased values for automated plans, whereas other dose metric evaluations are nonsignificant. The time to generate the treatment plans is reduced for all automated plans with a median difference of 9' 50″ ± 4' 33″. CONCLUSIONS: Template-based automated planning allows for reduced treatment planning time with consistent optimization structure creation, treatment field creation, plan optimization, and dose calculation with similar dosimetric quality. This process has potential expansion to numerous disease sites.

MRI of radiation chemistry: First images and investigation of potential mechanisms.

BACKGROUND: Paramagnetic species such as O2 and free radicals can enhance T1 and T2 relaxation times. If the change in relaxation time is sufficiently large, the contrast will be generated in magnetic resonance images. Since radiation is known to be capable of altering the concentration of O2 and free radicals during water radiolysis, it may be possible for radiation to induce MR signal change. PURPOSE: We present the first reported instance of x-ray-induced MR signal changes in water phantoms and investigate potential paramagnetic relaxation enhancement mechanisms associated with radiation chemistry changes in oxygen and free radical concentrations. METHODS: Images of water and 10 mM coumarin phantoms were acquired on a 0.35 T MR-linac before, during, and after a dose delivery of 80 Gy using an inversion-recovery dual-echo sequence with water nullified. Radiation chemistry simulations of these conditions were performed to calculate changes in oxygen and free radical concentrations. Published relaxivity values were then applied to calculate the resulting T1 change, and analytical MR signal equations were used to calculate the associated signal change. RESULTS: Compared to pre-irradiation reference images, water phantom images taken during and after irradiation showed little to no change, while coumarin phantom images showed a small signal loss in the irradiated region with a contrast-to-noise ratio (CNR) of 1.0-2.5. Radiation chemistry simulations found oxygen depletion of -11 µM in water and -31 µM in coumarin, resulting in a T1 lengthening of 24 ms and 68 ms respectively, and a simulated CNR of 1.0 and 2.8 respectively. This change was consistent with observations in both direction and magnitude. Steady-state superoxide, hydroxyl, hydroperoxyl, and hydrogen radical concentrations were found to contribute less than 1 ms of T1 change. CONCLUSION: Observed radiation-induced MR signal changes were dominated by an oxygen depletion mechanism. Free radicals were concluded to play a minor secondary role under steady-state conditions. Future applications may include in vivo FLASH treatment verification but would require an MR sequence with a better signal-to-noise ratio and higher temporal resolution than the one used in this study.

Resistive electrode array (REA) for radiotherapy beam monitoring and quality assurance.

We have developed a new type of detector array for monitoring of radiation beams in radiotherapy. The detector has parallel-plane architecture with multiple large-area uniform thin-film electrodes. At least one of the electrodes is resistive and has multiple signal readouts spread out along its perimeter. The integral dose deposited in the detector gives rise to multiple signals that depend on the distribution of radiation with respect to resistive electrode array (REA) geometry. The purpose of the present study was to experimentally determine basic detector response to MLC collimated x-ray fields. Two detector arrays have been characterized: circular and rectangular. The current and electrostatic potential distribution within the resistive electrode are governed by the Laplace and continuity equations with boundary conditions at the border with the readouts. Measurements for pencil beams showed that signal strength depends primarily on the distances between the location of the pencil beam and the readouts. Measurements for larger irregular MLC showed that signals as a function of time are quasi-linear with respect to MLC position and are proportional to the MLC area. Derivation of clinically relevant radiation beam parameters from REA signals, such as MLC position, MLC gap size and monitor unit per MLC segment relies on the detector response model with empirical model parameters. An approximate analytical detector response model was proposed and used to fit experiment data.

Technical Report: Development and Implementation of an Open Source Template Interpretation Class Library for Automated Treatment Planning.

PURPOSE: Widespread implementation of automated treatment planning in radiation therapy remains elusive owing to variability in clinic and physician preferences, making it difficult to ensure consistent plan parameters. We have developed an open-source class library with the aim to improve efficiency and consistency for automated treatment planning in radiation therapy. METHODS AND MATERIALS: An open-source class library has been developed that interprets clinical templates within a commercial treatment planning system into a treatment plan for automated planning. This code was leveraged for the automated planning of 39 patients and retrospectively compared with the 78 clinically approved manual plans. RESULTS: From the initial 39 patients, 74 of 78 plans were successfully generated without manual intervention. The target dose was more homogeneous for automated plans, with an average homogeneity index of 3.30 for manual plans versus 3.11 for automated plans (P = .107). The generalized equivalent uniform dose (gEUD) was decreased in the femurs and rectum for automated plans, with a mean gEUD of 3746 cGy versus 3338 cGy (P ≤ 0.001) and 5761 cGy versus 5634 cGy (P ≤ 0.001) for the femurs and rectum, respectively. Dose metrics for the bladder and rectum (V6500 cGy and V4000 cGy) showed recognizable but insignificant improvements. All automated plans delivered for quality assurance passed a gamma analysis (>95%), with an average composite pass rate of 99.3% for pelvis plans and 98.8% for prostate plans. Deliverability parameters such as total monitor units and aperture complexity indicated deliverable plans. CONCLUSIONS: Prostate cancer and pelvic node radiation therapy can be automated using volumetric modulated arc therapy planning and clinical templates based on a standardized clinical workflow. The class library developed in this study conveniently interfaced between the plan template and the treatment planning system to automatically generate high-quality plans on customizable templates.

Practical Guidelines on Implementing Hypofractionated Radiotherapy for Prostate Cancer in Africa.

Among a growing body of literature in global oncology, several articles project increased cost savings and radiotherapy access by adopting hypofractionated radiotherapy (HFRT) in low- and middle-income countries (LMICs) like those in Africa. Clinical trials in Europe and the USA have demonstrated HFRT to be non-inferior to conventional radiotherapy for eligible patients with several cancers, including prostate cancer. This could be a highly recommended option to battle a severely large and growing cancer burden in resource-limited regions. However, a level of implementation research may be needed in limited resource-settings like in Africa. In this article, we present a list of evidence-based recommendations to practice HFRT on eligible prostate cancer patients. As literature on HFRT is still developing, these guidelines were compiled from review of several clinical trials and professionally accredited material with minimal resource requirements in mind. HFRT guidelines presented here include patient eligibility, prescription dose schedules, treatment planning and delivery techniques, and quality assurance procedures. The article provides recommendations for both moderately hypofractionated (2.4-3.4Gy per fraction) and ultrahypofractionated (5Gy or more per fraction) radiation therapy when administered by 3D-Conformal Radiotherapy, Intensity Modulated Radiation Therapy, or Image-Guided Radiotherapy. In each case radiation oncology health professionals must make the ultimate judgment to ensure safety as more LMIC centers adopt HFRT to combat the growing scourge of cancer.

Application programming interface guided QA plan generation and analysis automation.

PURPOSE: Linear accelerator quality assurance (QA) in radiation therapy is a time consuming but fundamental part of ensuring the performance characteristics of radiation delivering machines. The goal of this work is to develop an automated and standardized QA plan generation and analysis system in the Oncology Information System (OIS) to streamline the QA process. METHODS: Automating the QA process includes two software components: the AutoQA Builder to generate daily, monthly, quarterly, and miscellaneous periodic linear accelerator QA plans within the Treatment Planning System (TPS) and the AutoQA Analysis to analyze images collected on the Electronic Portal Imaging Device (EPID) allowing for a rapid analysis of the acquired QA images. To verify the results of the automated QA analysis, results were compared to the current standard for QA assessment for the jaw junction, light-radiation coincidence, picket fence, and volumetric modulated arc therapy (VMAT) QA plans across three linacs and over a 6-month period. RESULTS: The AutoQA Builder application has been utilized clinically 322 times to create QA patients, construct phantom images, and deploy common periodic QA tests across multiple institutions, linear accelerators, and physicists. Comparing the AutoQA Analysis results with our current institutional QA standard the mean difference of the ratio of intensity values within the field-matched junction and ball-bearing position detection was 0.012 ± 0.053 (P = 0.159) and is 0.011 ± 0.224 mm (P = 0.355), respectively. Analysis of VMAT QA plans resulted in a maximum percentage difference of 0.3%. CONCLUSION: The automated creation and analysis of quality assurance plans using multiple APIs can be of immediate benefit to linear accelerator quality assurance efficiency and standardization. QA plan creation can be done without following tedious procedures through API assistance, and analysis can be performed inside of the clinical OIS in an automated fashion.

Self-powered multilayer radioisotope identification device.

PURPOSE: This is a computational study to develop a rugged self-powered Radioisotope Identification Device (RIID). The principle of operation relies on the High Energy Current (HEC) concept (Zygmanski and Sajo, Med Phys. 43 4-15, 2016) with measurement of fast electron currents between low-Z and high-Z thin-film electrodes separated by nanoporous aerogel films in a multilayer detector structure whose prototypes were previously investigated (Brivio, Albert, Freund, Gagne, Sajo and Zygmanski, Med Phys, 46 4233-4240, 2019), (Brivio, Albert, Gagne, Freund, Sajo and Zygmanski, J Phys D Appl Phys, 53 265303, 2020). Here, we present an optimal detector design that accounts for a wide energy range (keV-MeV) of x-ray-emitting radioisotopes that are of interest to national security and radiation therapy. MATERIALS: We studied numerous multilayer detector geometries with N = 1..24 basic detector elements composed of 3 electrodes: N x (Al-aerogel-Ta-aerogel-Al). The thicknesses of electrodes and their total number were varied depending on the incident x-ray spectra and its ability to penetrate and interact with the different layers, producing fast electrons. We used radiation transport simulations to find a balanced geometry that accounts for all energies from 10 keV to 6 MeV in a single design with relatively few detector elements (N = 24). In the balanced design, the electrodes have increasing thickness as a function of depth in the detector, ranging from 0.5 µm-Ta and 10 µm-Al at the entrance to 10 mm-Ta and 2.5 mm-Al at the exit. Aerogel thickness was fixed at 50 µm. Electron currents forming RIID signals were acquired from all Ta electrodes. A model function M(x, Ei ) representing the detector yield as a function of the cumulative Ta thickness (x) for 70 monoenergetic incident beams (E) was derived. We also investigated the detector response to selected radioactive isotopes (Pd-103, I-125, Pu-239, U-235, Ir-192, Cs-137, Co-60). Additional studies were performed with Bremsstrahlung spectra produced by electron beams in kVp tubes and in MV Linacs used in radiology and radiation therapy departments. We investigated different algorithms for radioisotope identification that would work for unknown unshielded as well as shielded sources. RESULTS: Characteristic features of response functions for monoenergetic beams and radioisotopes were determined and used to develop two inverse algorithms of radioisotope identification. Using these algorithms, we were able to identify the unshielded and shielded sources, quantify the minimum, mean and maximum effective energies of the shielded spectra, and estimate the amount of Compton background in the spectrum. CONCLUSIONS: A multilayer sensor based on fast electron current was optimized and studied in its abilities as RIID. A balanced design permits the identification of radioisotopes with of a wide range of keV-MeV energies. The device is low cost, rugged, self-powered and can withstand very high dose rates, allowing deployment in difficult conditions, including radiation incidents. The algorithm we developed for radioisotope identification and spectral unfolding is robust and it is an important component in practical applications.

Automated and robust beam data validation of a preconfigured ring gantry linear accelerator using a 1D tank with synchronized beam delivery and couch motions.

PURPOSE: To develop an efficient and automated methodology for beam data validation for a preconfigured ring gantry linear accelerator using scripting and a one-dimensional (1D) tank with automated couch motions. MATERIALS AND METHODS: Using an application programming interface, a program was developed to allow the user to choose a set of beam data to validate with measurement. Once selected the program generates a set of instructions for radiation delivery with synchronized couch motions for the linear accelerator in the form of an extensible markup language (XML) file to be delivered on the ring gantry linear accelerator. The user then delivers these beams while measuring with the 1D tank and data logging electrometer. The program also automatically calculates this set of beams on the measurement geometry within the treatment planning system (TPS) and extracts the corresponding calculated dosimetric data for comparison to measurement. Once completed the program then returns a comparison of the measurement to the predicted result from the TPS to the user and prints a report. In this work lateral, longitudinal, and diagonal profiles were taken for fields sizes of 6 × 6, 8 × 8, 10 × 10, 20 × 20, and 28 × 28 cm2 at depths of 1.3, 5, 10, 20, and 30 cm. Depth dose profiles were taken for all field sizes. RESULTS: Using this methodology, the TPS was validated to agree with measurement. All compared points yielded a gamma value less than 1 for a 1.5%/1.5 mm criteria (100% passing rate). Off axis profiles had >98.5% of data points producing a gamma value <1 with a 1%/1 mm criteria. All depth profiles produced 100% of data points with a gamma value <1 with a 1%/1 mm criteria. All data points measured were within 1.5% or 2 mm distance to agreement. CONCLUSIONS: This methodology allows for an increase in automation in the beam data validation process. Leveraging the application program interface allows the user to use a single system to create the measurement files, predict the result, and then compare to actual measurement increasing efficiency and reducing the chance for user input errors.

Hypofractionated Radiotherapy in African Cancer Centers.

In the advent of the coronavirus disease (COVID-19) pandemic, professional societies including the American Society for Radiation Oncology and the National Comprehensive Cancer Network recommended adopting evidence-based hypofractionated radiotherapy (HFRT). HFRT benefits include reduction in the number of clinical visits for each patient, minimizing potential exposure, and reducing stress on the limited workforce, especially in resource-limited settings as in Low-and-Middle-Income Countries (LMICs). Recent studies for LMICs in Africa have also shown that adopting HFRT can lead to significant cost reductions and increased access to radiotherapy. We assessed the readiness of 18 clinics in African LMICs to adopting HFRT. An IRB-approved survey was conducted at 18 RT clinics across 8 African countries. The survey requested information regarding the clinic's existing equipment and human infrastructure and current practices. Amongst the surveyed clinics, all reported to already practicing HFRT, but only 44% of participating clinics reported adopting HFRT as a common practice. Additionally, most participating clinical staff reported to have received formal training appropriate for their role. However, the survey data on treatment planning and other experience with contouring highlighted need for additional training for radiation oncologists. Although the surveyed clinics in African LMICs are familiar with HFRT, there is need for additional investment in infrastructure and training as well as better education of oncology leaders on the benefits of increased adoption of evidence-based HFRT during and beyond the COVID-19 era.

3D printing for rapid prototyping of low-Z/density ionization chamber arrays.

PURPOSE: To explore 3D printing for rapid development of prototype thin slab low-Z/density ionization chamber arrays viable for custom needs in radiotherapy dosimetry and quality assurance (QA). MATERIALS AND METHODS: We designed and fabricated parallel plate ionization chambers and ionization chamber arrays using an off-the-shelf 3D printing equipment. Conductive components of the detectors were made of conductive polylactic acid (cPLA) and insulating components were made of acrylonitrile butadiene styrene (ABS). We characterized the detector responses using a Varian TrueBeam linac at 95 cm SSD in slab solid water phantom at 5 cm depth. We measured the current-voltage (IV) curves, the response to different energy beam lines (2.5 MV, 6 MV, 6 MV FFF) for various dose rates and compared them to responses of a commercial Exradin A12 ionization chamber. We measured off-axis ratio (OAR) for several small field static multi-leaf collimators field sizes (0.5-3 cm) and compared them to OAR data obtained for commissioning of stereotactic radiotherapy. RESULTS: We identified the printing capability and the limitations of a low-cost off-the-shelf 3D printer for rapid prototyping of detector arrays. The design of the array with sub-millimeter size features conformed to the 3D printing capabilities. IV-curve for the array showed a strong polarity effect (8%) due to the design. Results for the parallel plate and the array compared well with A12 chamber: monitor unit (MU) dependence for the array was within a few % and the response to different energy beam lines was within 1%. Off-axis dose profiles measured with the array were comparable to dose profiles obtained in water tank and stereotactic diode after accounting for the size of the chambers. Dose error was within 2% at the center of the profile and slightly larger at the penumbra. CONCLUSIONS: Rapid prototyping of ion chambers by means of low-cost 3D printing is feasible with certain limitations in the design and spatial accuracy of the printed details.

Self-powered nano-porous aerogel x-ray sensor employing fast electron current.

PURPOSE: We developed a new class of aerogel-based thin-film self-powered radiation sensors employing high-energy electron current (HEC) in periodic multilayer (high-Z | polyimide aerogel (PA) | low-Z) electrode microstructures. MATERIALS: Low-Z (Al) and high-Z (Ta) electrodes were deposited on 50 µm-thick PA films to obtain sensors with Al-PA-Ta-PA-Al structures. Sensors were tested with x rays in the 40-120 kVp range and with 2.5 MV, 6 MV, and 6 MV-FFF linac beams (TrueBeam, Varian). Performance of PA-HEC sensors was compared to commercial A12 Farmer ionization chamber as well as to radiation transport simulations using CEPXS/ONEDANT with nanometer-to-micrometer spatial resolution. The computations included periodic and single-element structures N x (Al-PA-Ta-PA-Al) with variable layer thicknesses. RESULTS: Signal from PA-HEC sensors was proportional to the simulated net leakage electron current (averaged over the PA thickness). Experimental response was linear with dose and independent of dose rate. Detector responses to different x-ray sources show higher signals for kVp photon energies, as expected, though a strong signal was obtained for MV energies as well. The signal scaled with total effective area inside the multielemental structures; for example, the yield of a multielement sensor made with 20 Ta layers compared to a single-element structure with 1 Ta layer of the same total thickness of Ta was 10 times greater for 6 MV beam and 23 times greater for 120 kVp. Beam attenuation per element in the detector was 0.5%, 1%, 3%, and 46%, respectively for 6 MV, 6 MV FFF, 2.5 MV, and 120 kVp. CONCLUSION: We demonstrated the feasibility of aerogel-based multilayer HEC radiation detector and its application for flux/dose monitoring of kVp and radiotherapy MV beams with small beam attenuation.

Minimizing the potential of cancer recurrence and metastasis by the use of graphene oxide nano-flakes released from smart fiducials during image-guided radiation therapy.

An increasing number of studies show that cancer stem cells become more invasive and may escape into blood stream and lymph nodes before they have received a lethal dose during radiation therapy. Recently, it has been found that graphene oxide (GO) can selectively inhibit the proliferative expansion of cancer stem cells across multiple tumor types. In this study, we investigate the feasibility of using GO during radiotherapy to synergistically inhibit cancer stem cells, and lower the risk of cancer metastasis and recurrence. We hypothesize that graphene oxide nano-flakes (GONFs) released from newly-designed radiotherapy biomaterials (fiducial) can reach targeted tumor cells within 14-21 days. These are the typical time periods between the implantation of the fiducial and the start of image-guided radiation therapy. To test this hypothesis, the spatial-temporal diffusion of GONFs in soft tissue is investigated as a function of different particle sizes. Toxicity of GONFs to normal (HUVEC) and cancer (A549) cells has been assessed using the MTT assay. In addition, the survival fraction of A549 cells treated with GONFs is determined via clonogenic assay during radiotherapy. The diffusion study shows that only GONFs sizes of 50 and 200 nm could achieve the desired concentration of 50 µg/mL for 2 cm diameter tumor after 14 and 21 days respectively. The clonogenic and the MTT assay confirm the additional benefit of GONFs in killing lung cancer cells during radiotherapy. This work avails ongoing in vivo studies that use GONFs to enhance the treatment outcome for cancer patients during radiation therapy.

Equivalency of beam scan data collection using a 1D tank and automated couch movements to traditional 3D tank measurements.

This work shows the feasibility of collecting linear accelerator beam data using just a 1-D water tank and automated couch movements with the goal to maximize the cost effectiveness in resource-limited clinical settings. Two commissioning datasets were acquired: (a) using a standard of practice 3D water tank scanning system (3DS) and (b) using a novel technique to translate a commercial TG-51 complaint 1D water tank via automated couch movements (1DS). The Extensible Markup Language (XML) was used to dynamically move the linear accelerator couch position (and thus the 1D tank) during radiation delivery for the acquisition of inline, crossline, and diagonal profiles. Both the 1DS and 3DS datasets were used to generate beam models (BM1 DS and BM3 DS ) in a commercial treatment planning system (TPS). 98.7% of 1DS measured points had a gamma value (2%/2 mm) < 1 when compared with the 3DS. Static jaw defined field and dynamic MLC field dose distribution comparisons for the TPS beam models BM1 DS and BM3 DS had 3D gamma values (2%/2 mm) < 1 for all 24,900,000 data points tested and >99.5% pass rate with gamma value (1%/1 mm) < 1. In conclusion, automated couch motions and a 1D scanning tank were used to collect commissioning beam data with accuracy comparable to traditionally acquired data using a 3D scanning system. TPS beam models generated directly from 1DS measured data were clinically equivalent to a model derived from 3DS data.

The dichotomous nature of dose enhancement by gold nanoparticle aggregates in radiotherapy.

AIM: In nanoparticle-aided radiotherapy, the computational paradigm has been that inside the cell, nanoparticles are distributed sparsely and solitarily. However, experiments reveal significant cluster formation, which affects radiosensitization and must be considered in clinical treatment planning. We characterize the impact of gold nanoparticle agglomeration on the predicted radiation dose enhancement as function of size, geometry, morphology and incident beam energy. MATERIALS & METHODS: Next-generation coupled electron-photon deterministic computations were performed using subnanometric unstructured spatial mesh. RESULTS: Unlike single nanoparticles, agglomerates develop two types of dose enhancement, smooth peripheral distributions and isolated hotspots, which depend on the cluster size and geometry in opposite ways. CONCLUSION: The peripheral dose enhancement may have less importance than the hotspots, which can have greater contribution to cell kill via radical creation. Hence, aggregate formation may be beneficial in nanoparticle-aided radiotherapy.