Dose-response dependencies of OSL dosimeters in conventional linacs and 1.5T MR-linacs: an experimental and Monte Carlo study.

Objective. This work focuses on the optically stimulated luminescence dosimetry (OSLD) dose-response characterization, with emphasis on 1.5T MR-Linacs.Approach. Throughout this study, the nanoDots OSLDs (Landauer, USA) were considered. In groups of three, the mean OSLD response was measured in a conventional linac and an MR-Linac under various irradiation conditions to investigate (i) dose-response linearity with and without the 1.5T magnetic field, (ii) signal fading rate and its dependencies, (iii) beam quality, detector orientation and dose rate dependencies in a conventional linac, (iii) potential MR imaging related effects on OSLD response and (iv) detector orientation dependence in an MR-Linac. Monte Carlo calculations were performed to further quantify angular dependence after rotating the detector around its central axis parallel to the magnetic field, and determine the magnetic field correction factors,kB,Q,for all cardinal detector orientations.Main results. OSLD dose-response supralinearity in an MR-Linac setting was found to agree within uncertainties with the corresponding one in a conventional linac, for the axial detector orientation investigated. Signal fading rate does not depend on irradiation conditions for the range of 3-30 d considered. OSLD angular (orientation) dependence is more pronounced under the presence of a magnetic field. OSLDs irradiated with and without real-time T2w MR imaging enabled during irradiation yielded the same response within uncertainties.kB,Qvalues were determined for all three cardinal orientations. Corrections needed reached up to 6.4%. However, if OSLDs are calibrated in the axial orientation and then irradiated in an MR-Linac placed again in the axial orientation (perpendicular to the magnetic field), then simulations suggest thatkB,Qcan be considered unity within uncertainties, irrespective of the incident beam angle.Significance. This work contributes towards OSLD dose-response characterization and relevant correction factors availability. OSLDs are suitable for QA checks in MR-based beam gating applications andin vivodosimetry in MR-Linacs.

Scattered Radiation Distribution Utilizing Three Different Cone-Beam Computed Tomography Devices for Maxillofacial Diagnostics: A Research Study.

This study aimed to estimate scattered radiation and its spatial distribution around three cone-beam computed tomography (CBCT) devices, in order to determine potential positions for an operator to stand if they needed to be inside the CBCT room. The following devices were tested: Morita Accuitomo (CBCT1), Newtom Giano HR (CBCT2), Newtom VGi (CBCT3). Scattered radiation measurements were performed using different kVp, mA, and Field of View (FOV) options. An anthropomorphic phantom (NATHANIA) was placed inside the X-ray gantry to simulate clinical conditions. Scattered measurements were taken with the Inovision model 451P Victoreen ionization chamber once placed at fixed distances from each irradiation isocenter, away from the primary beam. A statistically significant (p < 0.001) difference was found in the mean value of the scattered radiation estimations between the CBCT devices. Scattered radiation was reduced with a different rate for each CBCT device as distance was increased. For CBCT1 the reduction was 0.047 µGy, for CBCT2 it was 0.036 µGy, and for CBCT3 it was 0.079 µGy, for every one meter from the X-ray gantry. Therefore, at certain distances from the central X-ray, the scattered radiation was below the critical level of 1 mGy, which is defined by the radiation protection guidelines as the exposure radiation limit of the general population. Consequently, an operator could stay inside the room accompanying the patient being scanned, if necessary.

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.

Dosimetric accuracy of the Convolution algorithm for Leksell Gamma Plan radiosurgery treatment planning: Evaluation in the presence of clinically relevant inhomogeneities.

PURPOSE: The Leksell Gamma Plan Convolution algorithm (LGP-Convolution) has not been widely adopted. This mainly stems from the higher calculated beam-on times relative to the standard ray tracing-based LGP-TMR10 dose calculation algorithm. This study aims to evaluate the accuracy of the LGP-Convolution in scenarios where the treated lesions are in the vicinity of or encompassed by bone and/or air inhomogeneities. METHODS: The solid water dosimetry phantom provided by the vendor was modified to include bone and air inhomogeneities. Two treatment planning scenarios were investigated involving a single shot and multiple shots, respectively. Treatment planning and dose prescription were performed using the LGP-Convolution algorithm. Triple channel film dosimetry was performed using GafChromic EBT3 films calibrated in terms of absorbed dose to water in a 60 Co beam. Monte Carlo (MC) simulation dosimetry was also performed in the inhomogeneous experimental geometry using the EGSnrc MC platform and a previously validated sector-based phase-space source model. MC simulations were also employed to determine correction factors required for converting EBT3 measurements at points within the bone and air inhomogeneities from dose-to-water values to the corresponding dose to medium values. RESULTS AND CONCLUSIONS: EBT3 dose to medium correction factors ranged with field size (4, 8, or 16 mm) within 0.941-0.946 for bone and 0.745-0.749 for air inhomogeneities. An excellent agreement was found between the LGP-Convolution calculations with corresponding EBT3 and MC dose to medium results at all measurement points, except those located inside the air inhomogeneity. The latter is of no clinical importance and excluding them yielded gamma index passing rates of nearly 100% for 3% local dose difference and 1 mm distance-to-agreement criteria. The excellent agreement observed between LGP-Convolution calculations and film as well as MC results of dose to medium indicates that the latter is the quantity reported by the LGP-Convolution.

Dosimetry in 1.5 T MR-Linacs: Monte Carlo determination of magnetic field correction factors and investigation of the air gap effect.

BACKGROUND: In Magnetic Resonance-Linac (MR-Linac) dosimetry formalisms, a new correction factor, kB,Q , has been introduced to account for corresponding changes to detector readings under the beam quality, Q, and the presence of magnetic field, B. PURPOSE: This study aims to develop and implement a Monte Carlo (MC)-based framework for the determination of kB,Q correction factors for a series of ionization chambers utilized for dosimetry protocols and dosimetric quality assurance checks in clinical 1.5 T MR-Linacs. Their dependencies on irradiation setup conditions are also investigated. Moreover, to evaluate the suitability of solid phantoms for dosimetry checks and end-to-end tests, changes to the detector readings due to the presence of small asymmetrical air gaps around the detector's tip are quantified. METHODS: Phase space files for three irradiation fields of the ELEKTA Unity 1.5 T/7 MV flattening-filter-free MR-Linac were provided by the manufacturer and used as source models throughout this study. Twelve ionization chambers (three farmer-type and nine small-cavity detectors, from three manufacturers) were modeled (including their dead volume) using the EGSnrc MC code package. kB,Q values were calculated for the 10 × 10 cm2 irradiation field and for four cardinal orientations of the detectors' axes with respect to the 1.5 T magnetic field. Potential dependencies of kB,Q values with respect to field size, depth, and phantom material were investigated by performing additional simulations. Changes to the detectors' readings due to the presence of small asymmetrical air gaps (0.1 up to 1 mm) around the chambers' sensitive volume in an RW3 solid phantom were quantified for three small-cavity chambers and two orientations. RESULTS: For both parallel (to the magnetic field) orientations, kB,Q values were found close to unity. The maximum correction needed was 1.1%. For each detector studied, the kB,Q values calculated for the two parallel orientations agreed within uncertainties. Larger corrections (up to 5%) were calculated when the detectors were oriented perpendicularly to the magnetic field. Results were compared with corresponding ones found in the literature, wherever available. No considerable dependence of kB,Q with respect to field size (down to 3 × 3 cm2 ), depth, or phantom material was noticed, for the detectors investigated. As compared to the perpendicular one, in the parallel to the magnetic field orientation, the air gap effect is minimized but is still considerable even for the smallest air gap considered (0.1 mm). CONCLUSION: For the 10 × 10 cm2 field, magnetic field correction factors for 12 ionization chambers and four orientations were determined. For each detector, the kB,Q value may be also applied for dosimetry procedures under different irradiation parameters provided that the orientation is taken into account. Moreover, if solid phantoms are used, even the smallest asymmetrical air gap may still bias small-cavity chamber response. This work substantially expands the availability and applicability of kB,Q correction factors that are detector- and orientation-specific, enabling more options in MR-Linac dosimetry checks, end-to-end tests, and quality assurance protocols.

Surgical Gesture Recognition in Laparoscopic Tasks Based on the Transformer Network and Self-Supervised Learning.

In this study, we propose a deep learning framework and a self-supervision scheme for video-based surgical gesture recognition. The proposed framework is modular. First, a 3D convolutional network extracts feature vectors from video clips for encoding spatial and short-term temporal features. Second, the feature vectors are fed into a transformer network for capturing long-term temporal dependencies. Two main models are proposed, based on the backbone framework: C3DTrans (supervised) and SSC3DTrans (self-supervised). The dataset consisted of 80 videos from two basic laparoscopic tasks: peg transfer (PT) and knot tying (KT). To examine the potential of self-supervision, the models were trained on 60% and 100% of the annotated dataset. In addition, the best-performing model was evaluated on the JIGSAWS robotic surgery dataset. The best model (C3DTrans) achieves an accuracy of 88.0%, a 95.2% clip level, and 97.5% and 97.9% (gesture level), for PT and KT, respectively. The SSC3DTrans performed similar to C3DTrans when training on 60% of the annotated dataset (about 84% and 93% clip-level accuracies for PT and KT, respectively). The performance of C3DTrans on JIGSAWS was close to 76% accuracy, which was similar to or higher than prior techniques based on a single video stream, no additional video training, and online processing.

Assessment of Radiation-Induced Bladder and Bowel Cancer Risks after Conventionally and Hypo-Fractionated Radiotherapy for the Preoperative Management of Rectal Carcinoma.

Preoperative management of rectal carcinoma can be performed by employing either conventionally or hypo-fractionated Radiotherapy (CFRT or HFRT, respectively), delivered by Intensity Modulated Radiotherapy (IMRT) or Volumetric Modulated Arc Therapy (VMAT) plans, employing 6 MV or 10 MV photon beams. This study aims to dosimetrically and radiobiologically compare all available approaches, with emphasis on the risk of radiation-induced second cancer to the bladder and bowel. Computed Tomography (CT) scans and relevant radiotherapy contours from 16 patients were anonymized and analyzed retrospectively. For each case, CFRT of 25 × 2 Gy and HFRT of 5 × 5 Gy were both considered. IMRT and VMAT plans using 6 MV and 10 MV photons were prepared. Plan optimization was performed, considering all clinically used plan quality indices and dose-volume constraints for the critical organs. Resulting dose distributions were analyzed and compared. Moreover, the Lifetime Attributable Risk (LAR) for developing radiation-induced bladder and bowel malignancies were assessed using a non-linear mechanistic model, assuming patient ages at treatment of 45, 50, 55 and 60 years. All 128 plans created were clinically acceptable. Risk of second bladder cancer reached 0.26% for HFRT (5 × 5 Gy) and 0.19% for CFRT (25 × 2 Gy) at the age of 45. Systematically higher risks were calculated for HFRT (5 × 5 Gy) as compared to CFRT (25 × 2 Gy), with 6 MV photons resulting in slightly increased LAR, as well. Similar or equal bowel cancer risks were calculated for all techniques and patient ages investigated (range 0.05-0.14%). This work contributes towards radiotherapy treatment protocol selection criteria for the preoperative irradiation of rectal carcinoma. However, more studies are needed to establish the associated radiation-induced risk of each RT protocol.

Early Prediction of Planning Adaptation Requirement Indication Due to Volumetric Alterations in Head and Neck Cancer Radiotherapy: A Machine Learning Approach.

BACKGROUND: During RT cycles, the tumor response pattern could affect tumor coverage and may lead to organs at risk of overdose. As such, early prediction of significant volumetric changes could therefore reduce potential radiation-related adverse effects. Nevertheless, effective machine learning approaches based on the radiomic features of the clinically used CBCT images to determine the tumor volume variations due to RT not having been implemented so far. METHODS: CBCT images from 40 HN cancer patients were collected weekly during RT treatment. From the obtained images, the Clinical Target Volume (CTV) and Parotid Glands (PG) regions of interest were utilized to calculate 104 delta-radiomics features. These features were fed on a feature selection and classification procedure for the early prediction of significant volumetric alterations. RESULTS: The proposed framework was able to achieve 0.90 classification performance accuracy while detecting a small subset of discriminative characteristics from the 1st week of RT. The selected features were further analyzed regarding their effects on temporal changes in anatomy and tumor response modeling. CONCLUSION: The use of machine learning algorithms offers promising perspectives for fast and reliable early prediction of large volumetric deviations as a result of RT treatment, exploiting hidden patterns in the overall anatomical characteristics.

Impact of systematic MLC positional uncertainties on the quality of single-isocenter multi-target VMAT-SRS treatment plans.

PURPOSE: To study the impact of systematic MLC leaf positional uncertainties (stemming from mechanical inaccuracies or sub-optimal MLC modeling) on the quality of intracranial single-isocenter multi-target VMAT-SRS treatment plans. An estimation of appropriate tolerance levels is attempted. METHODS: Five patients, with three to four metastases and at least one target lying in close proximity to organs-at-risk (OARs) were included in this study. A single-isocenter multi-arc VMAT plan per patient was prepared, which served as the reference for dosimetric impact evaluation. A range of leaf offsets was introduced (±0.03 mm up to ±0.30 mm defined at the MLC plane) to both leaf banks, by varying the leaf offset MLC modeling parameter in Monaco for all the prepared plans, in order to simulate projected leaf offsets of ±0.09 mm up to ±0.94 mm at the isocenter plane, respectively. For all offsets simulated and cases studied, dose distributions were re-calculated and compared with the corresponding reference ones. An experimental dosimetric procedure using the SRS mapCHECK diode array was also performed to support the simulation study results and investigate its suitability to detect small systematic leaf positional errors. RESULTS: Projected leaf offsets of ±0.09 mm were well-tolerated with respect to both target dosimetry and OAR-sparing. A linear relationship was found between D95% percentage change and projected leaf offset (slope: 12%/mm). Impact of projected offset on target dosimetry was strongly associated with target volume. In two cases, plans that could be considered potentially clinically unacceptable (i.e., clinical dose constraint violation) were obtained even for projected offsets as small as 0.19 mm. The performed experimental dosimetry check can detect potential small systematic leaf errors. CONCLUSIONS: Plan quality indices and dose-volume metrics are very sensitive to systematic sub-millimeter leaf positional inaccuracies, projected at the isocenter plane. Acceptable and tolerance levels in systematic MLC uncertainties need to be tailored to VMAT-SRS spatial and dosimetric accuracy requirements.

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.

Geometric distortion assessment in 3T MR images used for treatment planning in cranial Stereotactic Radiosurgery and Radiotherapy.

Magnetic Resonance images (MRIs) are employed in brain Stereotactic Radiosurgery and Radiotherapy (SRS/SRT) for target and/or critical organ localization and delineation. However, MRIs are inherently distorted, which also impacts the accuracy of the Magnetic Resonance Imaging/Computed Tomography (MRI/CT) co-registration process. In this phantom-based study, geometric distortion is assessed in 3T T2-weighted images (T2WIs), while the efficacy of an MRI distortion correction technique is also evaluated. A homogeneous polymer gel-filled phantom was CT-imaged before being irradiated with 26 4-mm Gamma Knife shots at predefined locations (reference control points). The irradiated phantom was MRI-scanned at 3T, implementing a T2-weighted protocol suitable for SRS/SRT treatment planning. The centers of mass of all shots were identified in the 3D image space by implementing an iterative localization algorithm and served as the evaluated control points for MRI distortion detection. MRIs and CT images were spatially co-registered using a mutual information algorithm. The inverse transformation matrix was applied to the reference control points and compared with the corresponding MRI-identified ones to evaluate the overall spatial accuracy of the MRI/CT dataset. The mean image distortion correction technique was implemented, and resulting MRI-corrected control points were compared against the corresponding reference ones. For the scanning parameters used, increased MRI distortion (>1mm) was detected at areas distant from the MRI isocenter (>5cm), while median radial distortion was 0.76mm. Detected offsets were slightly higher for the MRI/CT dataset (0.92mm median distortion). The mean image distortion correction improves geometric accuracy, but residual distortion cannot be considered negligible (0.51mm median distortion). For all three datasets studied, a statistically significant positive correlation between detected spatial offsets and their distance from the MRI isocenter was revealed. This work contributes towards the wider adoption of 3T imaging in SRS/SRT treatment planning. The presented methodology can be employed in commissioning and quality assurance programmes of corresponding treatment workflows.

Target localization accuracy in frame-based stereotactic radiosurgery: Comparison between MR-only and MR/CT co-registration approaches.

PURPOSE: In frame-based Gamma Knife (GK) stereotactic radiosurgery two treatment planning workflows are commonly employed; one based solely on magnetic resonance (MR) images and the other based on magnetic resonance/computed tomography (MR/CT) co-registered images. In both workflows, target localization accuracy (TLA) can be deteriorated due to MR-related geometric distortions and/or MR/CT co-registration uncertainties. In this study, the overall TLA following both clinical workflows is evaluated for cases of multiple brain metastases. METHODS: A polymer gel-filled head phantom, having the Leksell stereotactic headframe attached, was CT-imaged and irradiated by a GK Perfexion unit. A total of 26 4-mm shots were delivered at 26 locations directly defined in the Leksell stereotactic space (LSS), inducing adequate contrast in corresponding T2-weighted (T2w) MR images. Prescribed shot coordinates served as reference locations. An additional MR scan was acquired to implement the "mean image" distortion correction technique. The TLA for each workflow was assessed by comparing the radiation-induced target locations, identified in MR images, with corresponding reference locations. Using T1w MR and CT images of 15 patients (totaling 81 lesions), TLA in clinical cases was similarly assessed, considering MR-corrected data as reference. For the MR/CT workflow, both global and region of interest (ROI)-based MR/CT registration approaches were studied. RESULTS: In phantom measurements, the MR-corrected workflow demonstrated unsurpassed TLA (median offset of 0.2 mm) which deteriorated for MR-only and MR/CT workflows (median offsets of 0.8 and 0.6 mm, respectively). In real-patient cases, the MR-only workflow resulted in offsets that exhibit a significant positive correlation with the distance from the MR isocenter, reaching 1.1 mm (median 0.6 mm). Comparable results were obtained for the MR/CT-global workflow, although a maximum offset of 1.4 mm was detected. TLA was improved with the MR/CT-ROI workflow resulting in median/maximum offsets of 0.4 mm/1.1 mm. CONCLUSIONS: Subpixel TLA is achievable in all workflows. For the MR/CT workflow, a ROI-based MR/CT co-registration approach could considerably increase TLA and should be preferred instead of a global registration.

On the potential of 2D ion chamber arrays for high-dose rate remote afterloading brachytherapy quality assurance.

Objective. To investigate the potential of 2D ion chamber arrays to serve as a standalone tool for the verification of source strength, positioning and dwell time, within the framework of192Ir high-dose rate brachytherapy device quality assurance (QA).Approach.A commercially available ion chamber array was used. Fitting of a 2D Lorentzian peak function to experimental data from a multiple source dwell position irradiation on a frame-by-frame basis, facilitated tracking of the source center orthogonal projection on the array plane. For source air kerma strength verification, Monte Carlo simulation was employed to obtain a chamber array- and source-specific correction factor of calibration with a 6 MV photon beam. This factor converted the signal measured by each ion chamber element to air kerma in free space. A source positioning correction was also applied to lift potential geometry mismatch between experiment and Monte Carlo simulation.Main results.Spatial and temporal accuracy of source movement was verified within 0.5 mm and 0.02 s, respectively, in compliance with the test endpoints recommended by international professional societies. The source air kerma strength was verified experimentally within method uncertainties estimated as 1.44% (k = 1). The source positioning correction method employed did not introduce bias to experimental results of irradiations where source positioning was accurate. Development of a custom jig attachable to the chamber array for accurate and reproducible experimental set up would improve testing accuracy and obviate the need for source positioning correction in air kerma strength verification.Significance.Delivery of a single irradiation plan, optimized based on results of this work, to a 2D ion chamber array can be used for concurrent testing of source position, dwell time and air kerma strength, and the procedure can be expedited through automation. Chamber arrays merit further study in treatment planning QA and real time,in vivodose verification.

Monte Carlo-Based Radiobiological Investigation of the Most Optimal Ion Beam Forming SOBP for Particle Therapy.

Proton (p) and carbon (C) ion beams are in clinical use for cancer treatment, although other particles such as He, Be, and B ions have more recently gained attention. Identification of the most optimal ion beam for radiotherapy is a challenging task involving, among others, radiobiological characterization of a beam, which is depth-, energy-, and cell type- dependent. This study uses the FLUKA and MCDS Monte Carlo codes in order to estimate the relative biological effectiveness (RBE) for several ions of potential clinical interest such as p, 4He, 7Li, 10Be, 10B, and 12C forming a spread-out Bragg peak (SOBP). More specifically, an energy spectrum of the projectiles corresponding to a 5-cm SOBP at a depth of 8 cm was used. All secondary particles produced by the projectiles were considered and RBE was determined based on radiation-induced Double Strand Breaks (DSBs), as calculated by MCDS. In an attempt to identify the most optimal ion beam, using the latter data, biological optimization was performed and the obtained depth-dose distributions were inter-compared. The results showed that 12C ions are more effective inside the SOBP region, which comes at the expense of higher dose values at the tail (i.e., after the SOBP). In contrast, p beams exhibit a higher DSOPB/DEntrance ratio, if physical doses are considered. By performing a biological optimization in order to obtain a homogeneous biological dose (i.e., dose × RBE) in the SOBP, the corresponding advantages of p and 12C ions are moderated. 7Li ions conveniently combine a considerably lower dose tail and a DSOPB/DEntrance ratio similar to 12C. This work contributes towards identification of the most optimal ion beam for cancer therapy. The overall results of this work suggest that 7Li ions are of potential interest, although more studies are needed to demonstrate the relevant advantages. Future work will focus on studying more complex beam configurations.

The Use of Genotoxicity Endpoints as Biomarkers of Low Dose Radiation Exposure in Interventional Cardiology.

The effect of the reportedly low ionizing radiation doses, such as those very often delivered to patients in interventional cardiology, remains ambiguous. As interventional cardiac procedures may have a significant impact on total collective effective dose, there are radiation protection concerns for patients and physicians regarding potential late health effects. Given that very low doses (<100 mSv) are expected to be delivered during these procedures, the purpose of this study was to assess the potency and suitability of current genotoxicity biomarkers to detect and quantitate biological effects essential for risk estimation in interventional cardiology. Specifically, the biomarkers γ-H2AX foci, dicentric chromosomes, and micronuclei, which underpin radiation-induced DNA damage, were studied in blood lymphocytes of 25 adult patients before and after interventional cardiac procedures. Even though the mean values of all patients as a group for all three endpoints tested show increased yields relative to baseline following medical exposure, our results demonstrate that only the γ-H2AX biomarker enables detection of statistically significant differences at the individual level (p < 0.001) for almost all patients (91%). Furthermore, 24 h after exposure, residual γ-H2AX foci were still detectable in irradiated lymphocytes. Their decline was found to vary significantly among the individuals and the repair kinetics of γ-H2AX foci was found to range from 25 to 95.6% of their maximum values obtained.

Deformable image registration to assist clinical decision for radiotherapy treatment adaptation for head and neck cancer patients.

Head and neck (H&N) cancer patients often present anatomical and geometrical changes in tumors and organs at risk (OARs) during radiotherapy treatment. These changes may result in the need to adapt the existing treatment planning, using an expert's subjective opinion, for offline adaptive radiotherapy and a new treatment planning before each treatment, for online adaptive radiotherapy. In the present study, a fast methodology is proposed to assist in planning adaptation clinical decision using tumor and parotid glands percentage volume changes during treatment. The proposed approach was applied to 40 Η&Ν cases, with one planning Computed Tomography (pCT) image and CBCT scans for 6 weeks of treatment per case. Deformable registration was used for each patient's pCT image alignment to its weekly CBCT. The calculated transformations were used to align each patient's anatomical structures to the weekly anatomy. Clinical target volume (CTV) and parotid gland volume percentage changes were calculated in each case. The accuracy of the achieved image alignment was validated qualitatively and quantitatively. Furthermore, statistical analysis was performed to test if there is a statistically significant correlation between CTV and parotid glands volume percentage changes. Average MDA for CTV and parotid glands between corresponding structures defined by an expert in CBCTs and automatically calculated through registration was 1.4 ± 0.1 mm and 1.5 ± 0.1 mm, respectively. The mean registration time of the first CBCT image registration for 40 cases was lower than 3.4 min. Five patients show more than 20% tumor volume change. Six patients show more than 30% parotid glands volume change. Ten out of 40 patients proposed for planning adaptation. All the statistical tests performed showed no correlation between CTV/parotid glands percentage volume changes. The aim to assist in clinical decision making on a fast and automatic way was achieved using the proposed methodology, thereby reducing workload in clinical practice.

G2/M Checkpoint Abrogation With Selective Inhibitors Results in Increased Chromatid Breaks and Radiosensitization of 82-6 hTERT and RPE Human Cells.

While technological advances in radiation oncology have led to a more precise delivery of radiation dose and a decreased risk of side effects, there is still a need to better understand the mechanisms underlying DNA damage response (DDR) at the DNA and cytogenetic levels, and to overcome tumor resistance. To maintain genomic stability, cells have developed sophisticated signaling pathways enabling cell cycle arrest to facilitate DNA repair via the DDR-related kinases and their downstream targets, so that DNA damage or DNA replication stress induced by genotoxic therapies can be resolved. ATM, ATR, and Chk1 kinases are key mediators in DDR activation and crucial factors in treatment resistance. It is of importance, therefore, as an alternative to the conventional clonogenic assay, to establish a cytogenetic assay enabling reliable and time-efficient results in evaluating the potency of DDR inhibitors for radiosensitization. Toward this goal, the present study aims at the development and optimization of a chromosomal radiosensitivity assay using the DDR and G2-checkpoint inhibitors as a novel modification compared to the classical G2-assay. Also, it aims at investigating the strengths of this assay for rapid radiosensitivity assessments in cultured cells, and potentially, in tumor cells obtained from biopsies. Specifically, exponentially growing RPE and 82-6 hTERT human cells are irradiated during the G2/M-phase transition in the presence or absence of Caffeine, VE-821, and UCN-1 inhibitors of ATM/ATR, ATR, and Chk1, respectively, and the induced chromatid breaks are used to evaluate cell radiosensitivity and their potency for radiosensitization. The increased yield of chromatid breaks in the presence of DDR inhibitors, which underpins radiosensitization, is similar to that observed in cells from highly radiosensitive AT-patients, and is considered here as 100% radiosensitive internal control. The results highlight the potential of our modified G2-assay using VE-821 to evaluate cell radiosensitivity, the efficacy of DDR inhibitors in radiosensitization, and reinforce the concept that ATM, ATR, and Chk1 represent attractive anticancer drug targets in radiation oncology.

Lung cancer histology classification from CT images based on radiomics and deep learning models.

Adenocarcinoma (AC) and squamous cell carcinoma (SCC) are frequent reported cases of non-small cell lung cancer (NSCLC), responsible for a large fraction of cancer deaths worldwide. In this study, we aim to investigate the potential of NSCLC histology classification into AC and SCC by applying different feature extraction and classification techniques on pre-treatment CT images. The employed image dataset (102 patients) was taken from the publicly available cancer imaging archive collection (TCIA). We investigated four different families of techniques: (a) radiomics with two classifiers (kNN and SVM), (b) four state-of-the-art convolutional neural networks (CNNs) with transfer learning and fine tuning (Alexnet, ResNet101, Inceptionv3 and InceptionResnetv2), (c) a CNN combined with a long short-term memory (LSTM) network to fuse information about the spatial coherency of tumor's CT slices, and (d) combinatorial models (LSTM + CNN + radiomics). In addition, the CT images were independently evaluated by two expert radiologists. Our results showed that the best CNN was Inception (accuracy = 0.67, auc = 0.74). LSTM + Inception yielded superior performance than all other methods (accuracy = 0.74, auc = 0.78). Moreover, LSTM + Inception outperformed experts by 7-25% (p < 0.05). The proposed methodology does not require detailed segmentation of the tumor region and it may be used in conjunction with radiological findings to improve clinical decision-making. Lung cancer histology classification from CT images based on CNN + LSTM.

Comparison and Evaluation of Different Radiotherapy Techniques Using Biodosimetry Based on Cytogenetics.

While rapid technological advances in radiotherapy techniques have led to a more precise delivery of radiation dose and to a decreased risk of side effects, there is still a need to evaluate the efficacy of the new techniques estimating the biological dose and to investigate the radiobiological impact of the protracted radiotherapy treatment duration. The aim of this study is to compare, at a cytogenetic level, advanced radiotherapy techniques VMAT and IMRT with the conventional 3D-CRT, using biological dosimetry. A dicentric biodosimetry assay based on the frequency of dicentrics chromosomes scored in peripheral blood lymphocytes from prostate cancer patients and PC3 human prostate cancer cell line was used. For each patient blood sample and each subpopulation of the cultured cell line, three different irradiations were performed using the 3D-CRT, IMRT, and VMAT technique. The absorbed dose was estimated with the biodosimetry method based on the induced dicentric chromosomes. The results showed a statistically significant underestimation of the biological absorbed dose of ~6% for the IMRT and VMAT compared to 3D-CRT irradiations for peripheral blood lymphocytes, whereas IMRT and VMAT results were comparable without a statistically significant difference, although slightly lower values were observed for VMAT compared to IMRT irradiation. Similar results were obtained using the PC3 cell line. The observed biological dose underestimation could be associated with the relative decreased dose rate and increase irradiation time met in modulated techniques compared to the conventional 3D-CRT irradiations.

Evaluation of patient-specific MR distortion correction schemes for improved target localization accuracy in SRS.

PURPOSE: This work aims at promoting target localization accuracy in cranial stereotactic radiosurgery (SRS) applications by focusing on the correction of sequence-dependent (also patient induced) magnetic resonance (MR) distortions at the lesion locations. A phantom-based quality assurance (QA) methodology was developed and implemented for the evaluation of three distortion correction techniques. The same approach was also adapted to cranial MR images used for SRS treatment planning purposes in single or multiple brain metastases cases. METHODS: A three-dimensional (3D)-printed head phantom was filled with a 3D polymer gel dosimeter. Following treatment planning and dose delivery, volumes of radiation-induced polymerization served as hypothetical lesions, offering adequate MR contrast with respect to the surrounding unirradiated areas. T1-weighted (T1w) MR imaging was performed at 1.5 T using the clinical scanning protocol for SRS. Additional images were acquired to implement three distortion correction methods; the field mapping (FM), mean image (MI) and signal integration (SI) techniques. Reference lesion locations were calculated as the averaged centroid positions of each target identified in the forward and reverse read gradient polarity MRI scans. The same techniques and workflows were implemented for the correction of contrast-enhanced T1w MR images of 10 patients with a total of 27 brain metastases. RESULTS: All methods employed in the phantom study diminished spatial distortion. Median and maximum distortion magnitude decreased from 0.7 mm (2.10 ppm) and 0.8 mm (2.36 ppm), respectively, to <0.2 mm (0.61 ppm) at all target locations, using any of the three techniques. Image quality of the corrected images was acceptable, while contrast-to-noise ratio slightly increased. Results of the patient study were in accordance with the findings of the phantom study. Residual distortion in corrected patient images was found to be <0.3 mm in the vast majority of targets. Overall, the MI approach appears to be the most efficient correction method from the three investigated. CONCLUSIONS: In cranial SRS applications, patient-specific distortion correction at the target location(s) is feasible and effective, despite the expense of longer imaging time since additional MRI scan(s) need to be performed. A phantom-based QA methodology was developed and presented to reassure efficient implementation of correction techniques for sequence-dependent spatial distortion.