Clonogenic assay and computational modeling using real cell images to study physical enhancement and cellular sensitization induced by metal nanoparticles under MV and kV X-ray irradiation.

This study was initiated due to the physically unexplainable tumor controls resulting from metal nanoparticle (MNP) experiments even under MV X-ray irradiation. A more accurate explanation of the mechanism of radiosensitization induced by MNP is warranted, considering both its physical dose enhancement and biological sensitization, as related research is lacking. Thus, we aimed to examine the intricate dynamics involved in MNP-induced radiosensitization. We conducted specifically designed clonogenic assays for the A549 lung cancer cell line with MNP irradiated by 6 MV and 300 kVp X-rays. Two types of MNP were employed: one based on iron oxide, promoting ferroptosis, and the other on gold nanoparticles known for inducing a significant dose enhancement, particularly at low-energy X-rays. We introduced the lethality enhancement factor (LEF) as the fraction in the cell killing attributed to biological sensitization. Subsequently, Monte Carlo simulations were conducted to evaluate the radial dose profiles for each MNP, corresponding to the physical enhancement. Finally, the local effect model was applied to the clonogenic assay results on real cell images. The LEF and the dose enhancement in the cytoplasm were incorporated to increase the accuracy in the average lethal events and, consequently, in the survival fraction. The results reveal an increased cell killing for both of the MNP under MV and kV X-ray irradiation. In both types of MNP, the LEF reveals a biological sensitization evident. The sensitizer enhancement ratio, derived from the calculations, exhibited only 3% and 1% relative differences compared to the conventional linear-quadratic model for gold and ferroptosis inducer nanoparticles, respectively. These findings indicate that MNPs sensitize cells via radiation through mechanisms akin to ferroptosis inducers, not exclusively relying on a physical dose enhancement. Their own contributions to survival fractions were successfully integrated into computational modeling.

Synergistic Effect of Ferroptosis-Inducing Nanoparticles and X-Ray Irradiation Combination Therapy.

Ferroptosis, characterized by the induction of cell death via lipid peroxidation, has been actively studied over the last few years and has shown the potential to improve the efficacy of cancer nanomedicine in an iron-dependent manner. Radiation therapy, a common treatment method, has limitations as a stand-alone treatment due to radiation resistance and safety as it affects even normal tissues. Although ferroptosis-inducing drugs help alleviate radiation resistance, there are no safe ferroptosis-inducing drugs that can be considered for clinical application and are still in the research stage. Here, the effectiveness of combined treatment with radiotherapy with Fe and hyaluronic acid-based nanoparticles (FHA-NPs) to directly induce ferroptosis, considering the clinical applications is reported. Through the induction of ferroptosis by FHA-NPs and apoptosis by X-ray irradiation, the therapeutic efficiency of cancer is greatly improved both in vitro and in vivo. In addition, Monte Carlo simulations are performed to assess the physical interactions of the X-rays with the iron-oxide nanoparticle. The study provides a deeper understanding of the synergistic effect of ferroptosis and X-ray irradiation combination therapy. Furthermore, the study can serve as a valuable reference for elucidating the role and mechanisms of ferroptosis in radiation therapy.

Enhancing Precision in L-band Electron Paramagnetic Resonance Tooth Dosimetry: Incorporating Digital Image Processing and Radiation Therapy Plans for Geometric Correction.

ABSTRACT: Following unforeseen exposure to radiation, quick dose determination is essential to prioritize potential patients that require immediate medical care. L-band electron paramagnetic resonance tooth dosimetry can be efficiently used for rapid triage as this poses no harm to the human incisor, although geometric variations among human teeth may hinder accurate dose estimation. Consequently, we propose a practical geometric correction method using a mobile phone camera. Donated human incisors were irradiated with calibrated 6-MV photon beam irradiation, and dose-response curves were developed by irradiation with a predetermined dose using custom-made poly(methyl methacrylate) slab phantoms. Three radiation treatment plans for incisors were selected and altered to suit the head phantom. The mean doses on tooth structures were calculated using a commercial treatment planning system, and the electron paramagnetic resonance signals of the incisors were measured. The enamel area was computed from camera-acquired tooth images. The relative standard uncertainty was rigorously estimated both with and without geometric correction. The effects on the electron paramagnetic resonance signal caused by axial and rotational movements of tooth samples were evaluated through finite element analysis. The mean absolute deviations of mean doses both with and without geometric correction showed marginal improvement. The average relative differences without and with geometric correction significantly decreased from 21.0% to 16.8% (p = 0.01). The geometric correction method shows potential in improving dose precision measurement with minimal delay. Furthermore, our findings demonstrated the viability of using treatment planning system doses in dose estimation for L-band electron paramagnetic resonance tooth dosimetry.

Enhanced Dosimetric Accuracy Using Quality Factor Compensation Method for In Vivo Electron Paramagnetic Resonance Tooth Dosimetry.

ABSTRACT: We aim to develop a dose assessment method compensating for quality factors (Q factor) observed during in vivo EPR tooth dosimetry. A pseudo-in-vivo phantom made of tissue-equivalent material was equipped with one each of four extracted human central incisors. A range of Q factors was measured at tooth-depths of -2, 0, and 2 mm in the pseudo-in-vivo phantom. In addition, in vivo Q factors were measured from nine human volunteers. For the dose-response data, the above four sample teeth were irradiated at 0, 1, 2, 5, and 10 Gy, and the radiation-induced signals were measured at the same tooth-depths using an in vivo EPR tooth dosimetry system. To validate the method, the signals of two post-radiotherapy patients and three unirradiated volunteers were measured using the same system. The interquartile range of the Q factors measured in the pseudo-in-vivo phantom covered that observed from the human volunteers, which implied that the phantom represented the Q factor distribution of in vivo conditions. The dosimetric sensitivities and background signals were decreased as increasing the tooth-depth in the phantom due to the decrease in Q factors. By compensating for Q factors, the diverged dose-response data due to various Q factors were converged to improve the dosimetric accuracy in terms of the standard error of inverse prediction (SEIP). The Q factors of patient 1 and patient 2 were 98 and 64, respectively, while the three volunteers were 100, 92, and 99. The assessed doses of patient 1 and patient 2 were 2.73 and 12.53 Gy, respectively, while expecting 4.43 and 13.29 Gy, respectively. The assessed doses of the unirradiated volunteers were 0.53, 0.50, and - 0.22 Gy. We demonstrated that the suggested Q factor compensation could mitigate the uncertainty induced by the variation of Q factors.

Dual imaging modality of fluorescence and transmission X-rays for gold nanoparticle-injected living mice.

BACKGROUND: X-ray fluorescence (XRF) imaging for metal nanoparticles (MNPs) is a promising molecular imaging modality that can determine dynamic biodistributions of MNPs. However, it has the limitation that it only provides functional information. PURPOSE: In this study, we aim to show the feasibility of acquiring functional and anatomic information on the same platform by demonstrating a dual imaging modality of pinhole XRF and computed tomography (CT) for gold nanoparticle (GNP)-injected living mice. METHODS: By installing a transmission CT detector in an existing pinhole XRF imaging system using a two-dimensional (2D) cadmium zinc telluride (CZT) gamma camera, XRF and CT images were acquired on the same platform. Due to the optimal X-ray spectra for XRF and CT image acquisition being different, XRF and CT imaging were performed by 140 and 50 kV X-rays, respectively. An amount of 40 mg GNPs (1.9 nm in diameter) suspended in 0.20 ml of phosphate-buffered saline were injected into the three BALB/c mice via a tail vein. Then, the kidney and tumor slices of mice were scanned at specific time points within 60 min to acquire time-lapse in vivo biodistributions of GNPs. XRF images were directly acquired without image reconstruction using a pinhole collimator and a 2D CZT gamma camera. Subsequently, CT images were acquired by performing CT scans. In order to confirm the validity of the functional information provided by the XRF image, the CT image was fused with the XRF image. After the XRF and CT scan, the mice were euthanized, and major organs (kidneys, tumor, liver, and spleen) were extracted. The ex vivo GNP concentrations of the extracted organs were measured by inductively coupled plasma mass spectrometry (ICP-MS) and L-shell XRF detection system using a silicon drift detector, then compared with the in vivo GNP concentrations measured by the pinhole XRF imaging system. RESULTS: Time-lapse XRF images were directly acquired without rotation and translation of imaging objects within an acquisition time of 2 min per slice. Due to the short image acquisition time, the time-lapse in vivo biodistribution of GNPs was acquired in the organs of the mice. CT images were fused with the XRF images and successfully confirmed the validity of the XRF images. The difference in ex vivo GNP concentrations measured by the L-shell XRF detection system and ICP-MS was 0.0005-0.02% by the weight of gold (wt%). Notably, the in vivo and ex vivo GNP concentrations in the kidneys of three mice were comparable with a difference of 0.01-0.08 wt%. CONCLUSIONS: A dual imaging modality of pinhole XRF and CT imaging system and L-shell XRF detection system were successfully developed. The developed systems are a promising modality for in vivo imaging and ex vivo quantification for preclinical studies using MNPs. In addition, we discussed further improvements for the routine preclinical applications of the systems.

Microdosimetric-Kinetic Model for Radio-enhancement of Gold Nanoparticles: Comparison with LEM.

Numerous studies have strongly supported the application of gold nanoparticles (GNPs) as radio-enhanced agents. In our previous study, the local effect model (LEM I) was adopted to predict the cell survival for MDA-MB-231 cells exposed to 150 kVp X rays after 500 µg/ml GNPs treatment. However, microdosimetric quantities could not be obtained, which were correlated with biological effects on cells. Thus, we developed microdosimetric kinetic model (MKM) for GNP radio-enhancement (GNP-MKM), which uses the microdosimetric quantities such as dose-mean lineal energy with subcellular domain size. Using the Monte Carlo simulation tool Geant4, we estimated the dose-mean lineal energy with secondary radiations from GNPs and absorbed dose in the nucleus. The variations in MKM parameters for different domain sizes, and GNP concentrations, were calculated to compare the survival fractions predicted by both models. With a domain radius of 500 nm and a threshold dose of 20 Gy, the sensitizer enhancement ratio predicted by GNP-MKM and GNP-LEM was 1.41 and 1.29, respectively. The GNP-MKM predictions were much more strongly dependent on the domain size than were the GNP-LEM on the threshold dose. These findings provide another method to predict survival fraction for the GNP radio-enhancement.

Dependence of Radiation-induced Signals on Geometry of Tooth Enamel Using a 1.15 GHz Electron Paramagnetic Resonance Spectrometer: Improvement of Dosimetric Accuracy.

ABSTRACT: We aim to improve the accuracy of electron paramagnetic resonance (EPR)-based in vivo tooth dosimetry using the relationship between tooth geometry and radiation-induced signals (RIS). A homebuilt EPR spectrometer at L-band frequency of 1.15 GHz originally designed for non-invasive and in vivo measurements of intact teeth was used to measure the RIS of extracted human teeth. Twenty human central incisors were scanned by microCT and irradiated by 220 kVp x-rays. The RISs of the samples were measured by the EPR spectrometer as well as simulated by using the finite element analysis of the electromagnetic field. A linear relationship between simulated RISs and tooth geometric dimensions, such as enamel area, enamel volume, and labial enamel volume, was confirmed. The dose sensitivity was quantified as a slope of the calibration curve (i.e., RIS vs. dose) for each tooth sample. The linear regression of these dose sensitivities was established for each of three tooth geometric dimensions. Based on these findings, a method for the geometry correction was developed by use of expected dose sensitivity of a certain tooth for one of the tooth geometric dimensions. Using upper incisors, the mean absolute deviation (MAD) without correction was 1.48 Gy from an estimated dose of 10 Gy; however, the MAD corrected by enamel area, volume, and labial volume was reduced to 1.04 Gy, 0.77 Gy, and 0.83 Gy, respectively. In general, the method corrected by enamel volume showed the best accuracy in this study. This homebuilt EPR spectrometer for the purpose of non-invasive and in vivo tooth dosimetry was successfully tested for achieving measurements in situ. We demonstrated that the developed correction method could reduce dosimetric uncertainties resulting from the variations in tooth geometric dimensions.

Europium-Diethylenetriaminepentaacetic Acid Loaded Radioluminescence Liposome Nanoplatform for Effective Radioisotope-Mediated Photodynamic Therapy.

Photodynamic therapy (PDT) is an effective anticancer strategy with a higher selectivity and fewer adverse effects than conventional therapies; however, shallow tissue penetration depth of light has hampered the clinical utility of PDT. Recently, reports have indicated that Cerenkov luminescence-induced PDT may overcome the tissue penetration limitation of conventional PDT. However, the effectiveness of this method is controversial because of its low luminescence intensity. Herein, we developed a radiolabeled diethylenetriaminepentaacetic acid chelated Eu3+ (Eu-DTPA)/photosensitizer (PS) loaded liposome (Eu/PS-lipo) that utilizes ionizing radiation from radioisotopes for effective in vivo imaging and radioluminescence-induced PDT. We utilized Victoria blue-BO (VBBO) as a PS and observed an efficient luminescence resonance energy transfer between Eu-DTPA and VBBO. Furthermore, 64Cu-labeled Eu lipo demonstrated a strong radioluminescence with a 2-fold higher intensity than Cerenkov luminescence from free 64Cu. In our radioluminescence liposome, radioluminescence energy transfer showed a 6-fold higher energy transfer efficiency to VBBO than Cerenkov luminescence energy transfer (CLET). 64Cu-labeled Eu/VBBO lipo (64Cu-Eu/VBBO lipo) showed a substantial tumor uptake of up to 19.3%ID/g by enhanced permeability and retention effects, as revealed by in vivo positron emission tomography. Finally, the PDT using 64Cu-Eu/VBBO lipo demonstrated significantly higher in vitro and in vivo therapeutic effects than Cerenkov luminescence-induced PDT using 64Cu-VBBO lipo. This study envisions a great opportunity for clinical PDT application by establishing the radioluminescence liposome which has high tumor targeting and efficient energy transfer capability from radioisotopes.

Artifact-free CT images for electron beam therapy using a patient-specific non metallic shield.

Patient's CT images taken with metallic shields for radiotherapy suffer from artifacts. Furthermore, the treatment planning system (TPS) has a limitation on accurate dose calculations for high density materials. In this study, a Monte Carlo (MC)-based method was developed to accurately evaluate the dosimetric effect of the metallic shield. Two patients with a commercial tungsten shield of lens and two patients with a custom-made lead shield of lip were chosen to produce their non-metallic dummy shields using 3D scanner and printer. With these dummy shields, we generated artifact-free CT images. The maximum CT number allowed in TPS was assigned to metallic shields. MC simulations with real material information were carried out. In addition, clinically relevant dose-volumetric parameters were calculated for the comparison between MC and TPS. Relative dosimetry was performed using radiochromic films. The dose reductions below metallic structures were shown on MC dose distributions, but not evident on TPS dose distributions. The differences in dose-volumetric parameters of PTV between TPS and MC for eye shield cases were not clearly shown. However, the mean dose of lens from TPS and MC was different. The MC results were in superior agreement with measured data in relative dosimetry. The lens dose could be overestimated by TPS. The differences in dose-volumetric parameters of PTV between TPS and MC were generally larger in lip cases than in eye cases. The developed method is useful in predicting the realistic dose distributions around the organs blocked by the metallic shields.

Reduced-dose whole-brain radiotherapy with tumor bed boost after upfront high-dose methotrexate for primary central nervous system lymphoma.

PURPOSE: This retrospective study compares higher-dose whole-brain radiotherapy (hdWBRT) with reduced-dose WBRT (rdWBRT) in terms of clinical efficacy and toxicity profile in patients treated for primary central nervous system lymphoma (PCNSL). MATERIALS AND METHODS: Radiotherapy followed by high-dose methotrexate (HD-MTX)-based chemotherapy was administered to immunocompetent patients with histologically confirmed PCNSL between 2000 and 2016. Response to chemotherapy was taken into account when prescribing the radiation dose to the whole brain and primary tumor bed. The whole brain dose was ≤23.4 Gy for rdWBRT (n = 20) and >23.4 Gy for hdWBRT (n = 68). Patients manifesting cognitive disturbance, memory impairment and dysarthria were considered to have neurotoxicity. A median follow-up was 3.62 years. RESULTS: The 3-year overall survival (OS) and progression-free survival (PFS) were 70.0% and 48.9% with rdWBRT, and 63.2% and 43.2% with hdWBRT. The 3-year OS and PFS among patients with partial response (n = 45) after chemotherapy were 77.8% and 53.3% with rdWBRT, and 58.3% and 45.8% with hdWBRT (p > 0.05). Among patients with complete response achieved during follow-up, the 3-year freedom from neurotoxicity (FFNT) rate was 94.1% with rdWBRT and 62.4% with hdWBRT. Among patients aged ≥60 years, the 3-year FFNT rate was 87.5% with rdWBRT and 39.1% with hdWBRT (p = 0.49). Neurotoxicity was not observed after rdWBRT in patients aged below 60 years. CONCLUSION: rdWBRT with tumor bed boost combined with upfront HD-MTX is less neurotoxic and results in effective survival as higher-dose radiotherapy even in partial response after chemotherapy.

Dose perturbation and inhomogeneity of multi-arrays of 125I seed-loaded stent for treatment of portal vein tumor thrombosis.

PURPOSE: To investigate the dosimetry of 125I seed-loaded stent system currently used for an adjuvant treatment of portal vein tumor thrombosis (PVTT). METHODS: The stent system consisted of an inner metallic stent and outer seed-loaded capsules. Four arrays of 125I seeds were attached longitudinally to the outer surface of the stent at 90° separation. 145 Gy was prescribed at 5 mm from the axes of seed-arrays. For the geometries of the 4-array, and potential 6- and 8-array configurations, treatment planning system (TPS) and Monte Carlo (MC) calculations were performed to evaluate 3D dose distributions and dosimetric impact of the metallic stent. RESULTS: The MC simulations indicated the metallic stent reduced a dose to the prescription points by over 10%, compared to the water-based TPS results. The total activity calculated by the water-based TPS to deliver the prescription dose should compensate for this amount of reduction. The MC- and TPS-calculated doses normalized to the prescription points for the current configuration were in agreements within 4.3% on a cylindrical surface along 5 mm from the axes of seed-arrays. The longitudinal underdosage worsened as approaching the edge of arrays, and ranged from 2.8% to 25.5%. The angular underdosage between neighboring arrays was 2.1%-8.9%. CONCLUSIONS: With this compensation and a special care of near-edge underdosage, the current 4-array system can provide adequate dose coverage for treatment of PVTT. Further dosimetric homogeneity can be achieved using 6-or 8-array configurations.

Characterization of radiochromic films as a micrometer-resolution dosimeter by confocal Raman spectroscopy.

PURPOSE: Micrometer spatial resolution dosimetry has become inevitable for advanced radiotherapy techniques. A new approach using radiochromic films was developed to measure a radiation dose at a micrometer spatial resolution by confocal Raman spectroscopy. METHODS: The commercial radiochromic films (RCF), EBT3 and EBT-XD, were irradiated with known doses using 50, 100, 200, and 300 kVp, and 6-MV x rays. The dose levels ranged from 0.3 to 50 Gy. The Raman mapping technique developed in our early study was used to readout an area of 100 × 100 µm2 on RCF with improved lateral and depth resolutions with confocal Raman spectrometry. The variation in Raman spectra of C-C-C deformation and C≡C stretching modes of diacetylene polymers around 676 and 2060 cm-1 , respectively, as a function of therapeutic x-ray doses, was measured. The single peak (SP) of C≡C and the peak ratio (PR) of C≡C band height to C-C-C band height with a spatial resolution of 10 µm on both types of RCF were evaluated, averaged, and plotted as a function of dose. An achievable spatial resolution, clinically useful dose range, dosimetric sensitivity, dose uniformity, and postirradiation stability as well as the orientation, energy, and dose rate dependence, of both types of RCFs, were characterized by the technique developed in this study. RESULTS: A spatial resolution on RCF achieved by SP and PR methods was ~4.5 and ~2.9 µm, respectively. Raman spectroscopy data showed dose nonuniformity of ~11% in SP method and <3% in PR method. The SP method provided dose ranges of up to ~10 and ~20 Gy for EBT3 and EBT-XD films, respectively while the PR method up to ~30 and ~50 Gy. The PR method diminished the orientation effect. The percent difference between landscape and portrait orientations for the EBT3 and the EBT-XD films at 4 Gy had an acceptable level of 1.2% and 2.4%, respectively. With both SP and PR methods, the EBT3 and the EBT-XD films showed weak energy (within ~10% and ~3% for SP and PR methods, respectively) and dose rate dependence (within ~5% and ~3% for SP and PR methods, respectively) and had a stable response after 24-h postirradiation. CONCLUSIONS: A technique for micrometer-resolution dosimetry was successfully developed by detecting radiation-induced Raman shift on EBT3 and EBT-XD. Both types of RCFs were suitable for micrometer-resolution dosimetry using CRS. With CRS both lateral and depth resolutions on RCF were improved. The PR method provided superior characteristics in dose uniformity, dose ranges, orientation dependence, and laser effect for both types of RCFs. The overall dosimetric characteristics of the RCFs determined by this technique were similar to those known by optical density scanning. The CRS with the PR method is advantageous over other the traditional scanning systems as a spatial resolution of <10 µm on RCF can be achieved with less deviations.

Characterization of a new tissue equivalent proportional counter for dosimetry of neutron and photon fields: comparison of measurements and Monte Carlo simulations.

The tissue equivalent proportional counter (TEPC) is widely recognized as an important dosimetric technique particularly for complex radiation fields. The Korea Astronomy and Space Science Institute (KASI) has recently developed a new spherical TEPC to monitor the space radiation environment in the low earth orbit. The purpose of this study is to examine the performance of the TEPC against standard photon (137Cs) and neutron (252Cf) sources through ground-based measurements and Monte Carlo simulations prior to its actual implementation. Lineal energy distributions, microdosimetric spectra and dosimetric quantities for a 2 µm simulated site in pure propane gas were determined for both sources. Both the measured and calculated 137Cs spectra were shown to occur below 11 keV µm-1 that is the typical range covered by photon sources. Complete coincidence of their electron edge regions was also observed. Meanwhile, the proton edge from the measured 252Cf spectra was found to be in good agreement with those from the simulated ones and the literature. The gamma, recoil proton and heavy ions peaks expected for neutron sources were well defined, albeit deviations in the gamma region. The absorbed dose and dose equivalent for both irradiation conditions were also successfully obtained. The dose equivalent for 252Cf was found to be ten times the absorbed dose whereas it remained the same for 137Cs. The discrepancies observed in the low lineal energy region for both irradiation conditions were caused by intrinsic limitations on the experimental set-up and simulation configurations. This mainly contributed to a difference in the measured and calculated dose mean lineal energies of about 4.1% and 8.7% for the photon and neutron cases, respectively. Nevertheless, fair consistency with published data suggested that our TEPC could adequately reproduce the expected microdosimetric distributions for complex radiation fields.

Remote afterloading patient-specific brachytherapy with liquid radioisotope for irradiation of extensive scalp lesions: A Monte Carlo study.

PURPOSE: The aim of this study is to propose a remote afterloading patient-specific brachytherapy technique for total scalp irradiation by utilizing liquid radioisotope as well as a three-dimensional (3D) printer and to find an optimal radioisotope for the suggested technique. METHODS: We designed a brachytherapy device composed of liquid radioisotope tank, tube, patient-specific applicator, and a thin flexible pouch. The liquid radioisotope tank, tube, and the flexible pouch are interconnected one another to constitute a closed loop system. The pouch is located inside the solid patient-specific applicator; therefore, when the liquid radioisotope is injected into the pouch, the pouch is inflated and fills the space inside the applicator. The 3D-printed patient-specific applicator keeps the uniform thickness of the liquid radioisotope conforming patient's contour. To investigate an optimum condition for the suggested system, we performed Monte Carlo simulation with the GEANT4 simulation toolkit. To find the optimal radioisotope, percent depth doses (PDDs) of P-32, Sr-89, Y-90, and I-125 solutions were acquired in a rectangular parallelepiped phantom. For the selected radiation source, PDDs as well as dose rates in spherical phantoms with radii of 7.7 cm (infant head size) and 9.1 cm (adult head size) were acquired. RESULTS: To deliver prescription doses at 4-mm depth regions (scalp region), 1-mm-thick Y-90 and 5-mm-thick I-125 in liquid form were found to be feasible for the suggested technique. For both spherical phantoms with radii of 7.7 and 9.1 cm, when delivering 2 Gy at the 4-mm depth region with the 1-mm-thick Y-90 and 5-mm-thick I-125 sources, 53.3 and 3.8 Gy were delivered at the surface regions, respectively (delivery time = 111.1 and 3.5 min with 1 GBq/ml solutions). The PDDs of Y-90 and I-125 became less than 1% at depths greater than 8 and 50 mm, respectively. CONCLUSIONS: The remote afterloading patient-patient specific brachytherapy with I-125 or Y-90 in liquid form seems feasible for total scalp irradiation.

A patient-specific three-dimensional couplant pad for ultrasound image-guided radiation therapy: a feasibility study.

BACKGROUND: A wide application of ultrasound for radiation therapy has been hindered by a few issues such as skin and target deformations due to probe pressure, optical tracking disabilities caused by irregular surfaces and inter-user variations. The purpose of this study was to overcome these barriers by using a patient-specific three-dimensional (3D) couplant pad (CP). METHODS: A patient skin mold was designed using a skin contour of simulation CT images and fabricated by a 3D printer. A CP was then casted by pouring gelatin solution into a container accommodating the mold. To validate the use of the CP in positioning accuracy and imaging quality, phantom tests were carried out in our ultrasound-based localization system and then daily ultrasound images of four patients were acquired with and without the CP before treatment. RESULTS: In the phantom study, the use of CP increased a contrast-to-noise ratio from 2.4 to 4.0. The positioning accuracies in the US scans with and without the CP were less than 1 mm in all directions. In the patient study, the use of CP decreased the centroid offset of the target volume after target position alignment from 4.4 mm to 2.9 mm. One patient with a small volume of target showed a substantial increase in the inter-fractional target contour agreement (from 0.07 (poor agreement) to 0.31 (fair agreement) in Kappa values) by using the CP. CONCLUSIONS: Our patient-specific 3D CP based on a 3D mold printing technique not only maintained the tracking accuracy but also reduced the inter-user variation, as well as that could potentially improve detectability of optical markers and target visibility for ultrasound image-guided radiotherapy.

Computational Modeling and Clonogenic Assay for Radioenhancement of Gold Nanoparticles Using 3D Live Cell Images.

Radioenhancement of gold nanoparticles (GNPs) has shown great potential for increasing the therapeutic efficiency of radiotherapy. Here we report on a computational model of radiation response, which was developed to predict the survival curves of breast cancer cells incubated with GNPs. The amount of GNP uptake was estimated using inductively coupled plasma-mass spectroscopy, and the three-dimensional (3D) intracellular distribution of GNPs was obtained using optical diffraction tomography. The developed computational model utilized the 3D live cell imaging and recent Monte Carlo techniques to calculate microscopic dose distributions within the cell. Clonogenic assays with and without GNPs were performed to estimate the radioenhancement for 150 kVp X rays in terms of cell survival fractions. Measured cell survival fractions were comparable with the computational model.

Clinical outcomes and prognostic factors in patients with mycosis fungoides who underwent radiation therapy in a single institution.

PURPOSE: We aimed to evaluate clinical outcomes including progression-free survival (PFS), overall survival (OS), partial response, and complete response in patients who underwent radiation therapy (RT) for mycosis fungoides (MF). Also, we sought to find prognostic factors for clinical outcomes. Materials and. METHODS: Total 19 patients confirmed with MF between 1999-2015 were retrospectively reviewed. Clinical and treatment characteristics, clinical outcomes, and and toxicities were analyzed. RESULTS: Eleven patients were treated with total skin electron beam radiotherapy (TSEBT) and 8 patients with involved field radiation therapy (IFRT) with median dose of 30 Gy, respectively. The median time interval from diagnosis to RT was 2.6 months (range, 0.4 to 87.3 months). The overall response rate was 100%; 11 patients (57.9%) had a complete response and 8 patients (42.1%) a partial response. The presence of positive lymph node at the time of consultation of RT was associated with lower OS (p = 0.043). In multivariate analysis, PFS was significantly lower for patients with increased previous therapies experienced following RT (p = 0.019) and for patients showing PR during RT (p = 0.044). There were no reported grade 3 or more skin toxicities related with RT. CONCLUSION: Both IFRT and TSEBT are effective treatment for MF patients. Patients with short disease course before RT or complete response during RT are expected to have longer PFS. Positive lymph node status at the initiation of RT was associated woth poor OS, suggesting other treatment modalities such as low-dose RT for patients with low life-expectancy.

Abstract ID: 13 Monte Carlo simulations for the beam quality factors of a parallel-plate ion-chamber in the presence of magnetic field.

Magnetic resonance imaging-guided radiotherapy provides real-time imaging with a superior soft-tissue contrast without radiation exposure. Recently, several groups have been developing such a new technology. Strong magnetic fields can influence trajectories of the secondary electrons by the Lorentz force. The reference dosimetry using an ion-chamber in magnetic fields needs additional correction factors [1]. In this study, we calculated magnetic field correction factors by the Monte Carlo method for the reference dosimetry using a parallel-plate ion-chamber. The EGSnrc user code, egs_chamber was used to simulate an ion-chamber. The full head and spectral source models of Varian therapeutic linear accelerator of 6 MV, 10 MV, and 15 MV photon beam have been simulated by BEAMnrc and beamdp. A parallel-plate ion-chamber (NACP-02 model) was positioned in the water phantom (30 × 30 × 30 cm3) at a depth of 10 cm (5 cm for Co-60 beam). The beam quality factors (KQ) and magnetic field correction factors (KQ,B) were calculated. The absorbed dose of a parallel-plate ion-chamber was scored with and without a 1.5 T of magnetic field. The KQ of 6 MV, 10 MV, and 15 MV were 0.994, 0.980, and 0.976, respectively. These values were compatible to the previous published data (<0.3%) [2]. In a 1.5 T of magnetic field, the KQ,B of 6, 10, and 15 MV were 0.935, 0.985, and 0.994, respectively, compared to 0.975, 0.983, and 0.983 in a 0.35 T of magnetic field. All of simulation uncertainties were within 0.2%. When photon energy increases, KQ,B is also increased, but KQ,B in high strength of a magnetic field are not always smaller than those in low strength of a magnetic field. The magnetic field correction factors of a parallel-plate ion-chamber were successfully calculated by the Monte Carlo method. The parallel-plate ion-chambers need several percent of correction factors when measuring doses in the presence of a magnetic field.

Monte Carlo simulation for scanning technique with scattering foil free electron beam: A proof of concept study.

This study investigated the potential of a newly proposed scattering foil free (SFF) electron beam scanning technique for the treatment of skin cancer on the irregular patient surfaces using Monte Carlo (MC) simulation. After benchmarking of the MC simulations, we removed the scattering foil to generate SFF electron beams. Cylindrical and spherical phantoms with 1 cm boluses were generated and the target volume was defined from the surface to 5 mm depth. The SFF scanning technique with 6 MeV electrons was simulated using those phantoms. For comparison, volumetric modulated arc therapy (VMAT) plans were also generated with two full arcs and 6 MV photon beams. When the scanning resolution resulted in a larger separation between beams than the field size, the plan qualities were worsened. In the cylindrical phantom with a radius of 10 cm, the conformity indices, homogeneity indices and body mean doses of the SFF plans (scanning resolution = 1°) vs. VMAT plans were 1.04 vs. 1.54, 1.10 vs. 1.12 and 5 Gy vs. 14 Gy, respectively. Those of the spherical phantom were 1.04 vs. 1.83, 1.08 vs. 1.09 and 7 Gy vs. 26 Gy, respectively. The proposed SFF plans showed superior dose distributions compared to the VMAT plans.

Dependence of gold nanoparticle radiosensitization on cell geometry.

The radiosensitization effect of gold nanoparticles (GNPs) has been demonstrated both in vitro and in vivo in radiation therapy. The purpose of this study was to systematically assess the biological effectiveness of GNPs distributed in the extracellular media for realistic cell geometries. TOPAS-nBio simulations were used to determine the nanometre-scale radial dose distributions around the GNPs, which were subsequently used to predict the radiation dose response of cells surrounded by GNPs. MDA-MB-231 human breast cancer cells and F-98 rat glioma cells were used as models to assess different cell geometries by changing (1) the cell shape, (2) the nucleus location within the cell, (3) the size of GNPs, and (4) the photon energy. The results show that the sensitivity enhancement ratio (SER) was increased up to a factor of 1.2 when the location of the nucleus is close to the cell membrane for elliptical-shaped cells. Heat-maps of damage-likelihoods show that most of the lethal events occur in the regions of the nuclei closest to the membrane, potentially causing highly clustered damage patterns. The effect of the GNP size on radiosensitization was limited when the GNPs were located outside the cell. The improved modelling of the cell geometry was shown to be crucial because the dose enhancement caused by GNPs falls off rapidly with distance from the GNPs. We conclude that radiosensitization can be achieved for kV photons even without cellular uptake of GNPs when the nucleus is shifted towards the cell membrane. Furthermore, damage was found to concentrate in a small region of the nucleus in close proximity to the extracellular, GNP-laden region.