Voxel-Level Dosimetry for Combined Iodine 131 Radiopharmaceutical Therapy and External Beam Radiation Therapy Treatment Paradigms for Head and Neck Cancer.

PURPOSE: Targeted radiopharmaceutical therapy (RPT) in combination with external beam radiation therapy (EBRT) shows promise as a method to increase tumor control and mitigate potential high-grade toxicities associated with re-treatment for patients with recurrent head and neck cancer. This work establishes a patient-specific dosimetry framework that combines Monte Carlo-based dosimetry from the 2 radiation modalities at the voxel level using deformable image registration (DIR) and radiobiological constructs for patients enrolled in a phase 1 clinical trial combining EBRT and RPT. METHODS AND MATERIALS: Serial single-photon emission computed tomography (SPECT)/computed tomography (CT) patient scans were performed at approximately 24, 48, 72, and 168 hours postinjection of 577.2 MBq/m2 (15.6 mCi/m2) CLR 131, an iodine 131-containing RPT agent. Using RayStation, clinical EBRT treatment plans were created with a treatment planning CT (TPCT). SPECT/CT images were deformably registered to the TPCT using the Elastix DIR module in 3D Slicer software and assessed by measuring mean activity concentrations and absorbed doses. Monte Carlo EBRT dosimetry was computed using EGSnrc. RPT dosimetry was conducted using RAPID, a GEANT4-based RPT dosimetry platform. Radiobiological metrics (biologically effective dose and equivalent dose in 2-Gy fractions) were used to combine the 2 radiation modalities. RESULTS: The DIR method provided good agreement for the activity concentrations and calculated absorbed dose in the tumor volumes for the SPECT/CT and TPCT images, with a maximum mean absorbed dose difference of -11.2%. Based on the RPT absorbed dose calculations, 2 to 4 EBRT fractions were removed from patient EBRT treatments. For the combined treatment, the absorbed dose to target volumes ranged from 57.14 to 75.02 Gy. When partial volume corrections were included, the mean equivalent dose in 2-Gy fractions to the planning target volume from EBRT + RPT differed -3.11% to 1.40% compared with EBRT alone. CONCLUSIONS: This work demonstrates the clinical feasibility of performing combined EBRT + RPT dosimetry on TPCT scans. Dosimetry guides treatment decisions for EBRT, and this work provides a bridge for the same paradigm to be implemented within the rapidly emerging clinical RPT space.

Validation of Monte Carlo 131 I radiopharmaceutical dosimetry workflow using a 3D-printed anthropomorphic head and neck phantom.

PURPOSE: Approximately 50% of head and neck cancer (HNC) patients will experience loco-regional disease recurrence following initial courses of therapy. Retreatment with external beam radiotherapy (EBRT) is technically challenging and may be associated with a significant risk of irreversible damage to normal tissues. Radiopharmaceutical therapy (RPT) is a potential method to treat recurrent HNC in conjunction with EBRT. Phantoms are used to calibrate and add quantification to nuclear medicine images, and anthropomorphic phantoms can account for both the geometrical and material composition of the head and neck. In this study, we present the creation of an anthropomorphic, head and neck, nuclear medicine phantom, and its characterization for the validation of a Monte Carlo, SPECT image-based, 131 I RPT dosimetry workflow. METHODS: 3D-printing techniques were used to create the anthropomorphic phantom from a patient CT dataset. Three 131 I SPECT/CT imaging studies were performed using a homogeneous, Jaszczak, and an anthropomorphic phantom to quantify the SPECT images using a GE Optima NM/CT 640 with a high energy general purpose collimator. The impact of collimator detector response (CDR) modeling and volume-based partial volume corrections (PVCs) upon the absorbed dose was calculated using an image-based, Geant4 Monte Carlo RPT dosimetry workflow and compared against a ground truth scenario. Finally, uncertainties were quantified in accordance with recent EANM guidelines. RESULTS: The 3D-printed anthropomorphic phantom was an accurate re-creation of patient anatomy including bone. The extrapolated Jaszczak recovery coefficients were greater than that of the 3D-printed insert (∼22.8 ml) for both the CDR and non-CDR cases (with CDR: 0.536 vs. 0.493, non-CDR: 0.445 vs. 0.426, respectively). Utilizing Jaszczak phantom PVCs, the absorbed dose was underpredicted by 0.7% and 4.9% without and with CDR, respectively. Utilizing anthropomorphic phantom recovery coefficient overpredicted the absorbed dose by 3% both with and without CDR. All dosimetry scenarios that incorporated PVC were within the calculated uncertainty of the activity. The uncertainties in the cumulative activity ranged from 23.6% to 106.4% for Jaszczak spheres ranging in volume from 0.5 to 16 ml. CONCLUSION: The accuracy of Monte Carlo-based dosimetry for 131 I RPT in HNC was validated with an anthropomorphic phantom. In this study, it was found that Jaszczak-based PVCs were sufficient. Future applications of the phantom could involve 3D printing and characterizing patient-specific volumes for more personalized RPT dosimetry estimates.

Violence risk and personality assessment in adolescents by Structured Assessment of Violence Risk in Youth (SAVRY) and high school personality questionnaire (HSPQ): Focus on protective factors strengthening.

Background: Adolescents are most at risk of engaging in violent interaction. Targeting violence risk and protective factors is essential for correctly understanding and assessing their role in potential violence. We aimed to use the Structured Assessment of Violence Risk in Youth (SAVRY) tool within the sample of adolescents to capture violence risk and protective factors and personality variables related to risk and protective factors. We further aimed to identify which violence risk and protective factors were positively or negatively related to violence within personal history and if any personality traits are typical for violent and non-violent adolescents. Identifying broader or underlying constructs within the SAVRY tool factor analysis can enable appropriate therapeutic targeting. Methods: We used the Czech standardized version of the SAVRY tool. The study sample comprised 175 men and 226 women aged 12-18 years divided into two categories according to the presence or absence of violence in their personal history. Mann-Whitney U test was used to compare numerical variables between the two groups. SAVRY factor analysis with varimax rotation was used to determine the item factors. We administered the High School Personality Questionnaire (HSPQ) to capture adolescents' personality characteristics. Results: In our sample, there were 151 participants with violence in their personal histories and 250 non-violent participants. Non-violent adolescents had higher values for all six SAVRY protective factors. The strongest protective factor was P3, Strong attachment and bonds across gender or a history of violence. Using factor analysis, we identified three SAVRY internal factors: social conduct, assimilation, and maladaptation. The SAVRY protective factors were significantly positively related to several factors in the HSPQ questionnaire. Conclusion: The results highlight the significance of protective factors and their relationship with violence prevalence. HSPQ diagnostics could be helpful in clinically targeting personality-based violence risks and protective factors. The therapeutic focus should be on tension, peer rejection, and anxiety. It is also essential to foster positive attitudes toward authority, prosocial behavior, and attitudes toward school. These strategies can help strengthen protective factors of the SAVRY.

Facing the "new normal": How adjusting to the easing of COVID-19 lockdown restrictions exposes mental health inequalities.

BACKGROUND: Re-establishing societal norms in the wake of the COVID-19 pandemic will be important for restoring public mental health and psychosocial wellbeing as well as economic recovery. We investigated the impact on post-pandemic adjustment of a history of mental disorder, with particular reference to obsessive-compulsive (OC) symptoms or traits. METHODS: The study was pre-registered (Open Science Framework; https://osf.io/gs8j2/). Adult members of the public (n = 514) were surveyed between July and November 2020, to identify the extent to which they reported difficulties re-adjusting as lockdown conditions eased. All were assessed using validated scales to determine which demographic and mental health-related factors impacted adjustment. An exploratory analysis of a subgroup on an objective online test of cognitive inflexibility was also performed. RESULTS: Adjustment was related to a history of mental disorder and the presence of OC symptoms and traits, all acting indirectly and statistically-mediated via depression, anxiety and stress; and in the case of OC symptoms, also via COVID-related anxiety (all p < 0.001). One hundred and twenty-eight (25%) participants reported significant adjustment difficulties and were compared with those self-identifying as "good adjusters" (n = 231). This comparison revealed over-representation of those with a history or family history of mental disorder in the poor adjustment category (all p < 0.05). 'Poor-adjusters' additionally reported higher COVID-related anxiety, depression, anxiety and stress and OC symptoms and traits (all p < 0.05). Furthermore, history of mental disorder directly statistically mediated adjustment status (p < 0.01), whereas OC symptoms (not OC traits) acted indirectly via COVID-related anxiety (p < 0.001). Poor-adjusters also showed evidence of greater cognitive inflexibility on the intra-extra-dimensional set-shift task. CONCLUSION: Individuals with a history of mental disorder, OC symptoms and OC traits experienced greater difficulties adjusting after lockdown-release, largely statistically mediated by increased depression, anxiety, including COVID-related anxiety, and stress. The implications for clinical and public health policies and interventions are discussed.

New capabilities of the Monte Carlo dose engine ARCHER-RT: Clinical validation of the Varian TrueBeam machine for VMAT external beam radiotherapy.

PURPOSE: The Monte Carlo radiation transport method is considered the most accurate approach for absorbed dose calculations in external beam radiation therapy. In this study, an efficient and accurate source model of the Varian TrueBeam 6X STx Linac is developed and integrated with a fast Monte Carlo photon-electron transport absorbed dose engine, ARCHER-RT, which is capable of being executed on CPUs, NVIDIA GPUs, and AMD GPUs. This capability of fast yet accurate radiation dose calculation is essential for clinical utility of this new technology. This paper describes the software and algorithmic developments made to the ARCHER-RT absorbed dose engine. METHODS: AMD's Heterogeneous-Compute Interface for Portability (HIP) was implemented in ARCHER-RT to allow for device independent execution on NVIDIA and AMD GPUs. Architecture-specific atomic-add algorithms have been identified and both more accurate single-precision and double-precision computational absorbed dose calculation methods have been added to ARCHER-RT and validated through a test case to evaluate the accuracy and performance of the algorithms. The validity of the source model and the radiation transport physics were benchmarked against Monte Carlo simulations performed with EGSnrc. Secondary dose-check physics plans, and a clinical prostate treatment plan were calculated to demonstrate the applicability of the platform for clinical use. Absorbed dose difference maps and gamma analyses were conducted to establish the accuracy and consistency between the two Monte Carlo models. Timing studies were conducted on a CPU, an NVIDIA GPU, and an AMD GPU to evaluate the computational speed of ARCHER-RT. RESULTS: Percent depth doses were computed for different field sizes ranging from 1.5 cm2  × 1.5 cm2 to 22 cm2  × 40cm2 and the two codes agreed for all points outside high gradient regions within 3%. Axial profiles computed for a 10 cm2  × 10 cm2 field for multiple depths agreed for all points outside high gradient regions within 2%. The test case investigating the impact of native single-precision compared to double-precision showed differences in voxels as large as 71.47% and the implementation of KAS single-precision reduced the difference to less than 0.01%. The 3%/3mm gamma pass rates for an MPPG5a multileaf collimator (MLC) test case and a clinical VMAT prostate plan were 94.2% and 98.4% respectively. Timing studies demonstrated the calculation of a VMAT plan was completed in 50.3, 187.9, and 216.8 s on an NVIDIA GPU, AMD GPU, and Intel CPU, respectively. CONCLUSION: ARCHER-RT is capable of patient-specific VMAT external beam photon absorbed dose calculations and its potential has been demonstrated by benchmarking against a well validated EGSnrc model of a Varian TrueBeam. Additionally, the implementation of AMD's HIP has shown the flexibility of the ARCHER-RT platform for device independent calculations. This work demonstrates the significant addition of functionality added to ARCHER-RT framework which has marked utility for both research and clinical applications and demonstrates further that Monte Carlo-based absorbed dose engines like ARCHER-RT have the potential for widespread clinical implementation.