Patient vulnerability in stereotactic arrhythmia radioablation (STAR): a preliminary ethical appraisal from the STOPSTORM.eu consortium.

This preliminary ethical appraisal from the STOPSTORM.eu consortium is meant to raise critical points that clinicians administering stereotactic arrhythmia radioablation should consider to meet the highest standards in medical ethics and thus promote quality of life of patients recruited for radiotherapy treatments at a stage in which they experience a significant degree of vulnerability.

CCL18, CHI3L1, ANG2, IL-6 systemic levels are associated with the extent of lung damage and radiomic features in SARS-CoV-2 infection.

OBJECTIVE AND DESIGN: We aimed to identify cytokines whose concentrations are related to lung damage, radiomic features, and clinical outcomes in COVID-19 patients. MATERIAL OR SUBJECTS: Two hundred twenty-six patients with SARS-CoV-2 infection and chest computed tomography (CT) images were enrolled. METHODS: CCL18, CHI3L1/YKL-40, GAL3, ANG2, IP-10, IL-10, TNFα, IL-6, soluble gp130, soluble IL-6R were quantified in plasma samples using Luminex assays. The Mann-Whitney U test, the Kruskal-Wallis test, correlation and regression analyses were performed. Mediation analyses were used to investigate the possible causal relationships between cytokines, lung damage, and outcomes. AVIEW lung cancer screening software, pyradiomics, and XGBoost classifier were used for radiomic feature analyses. RESULTS: CCL18, CHI3L1, and ANG2 systemic levels mainly reflected the extent of lung injury. Increased levels of every cytokine, but particularly of IL-6, were associated with the three outcomes: hospitalization, mechanical ventilation, and death. Soluble IL-6R showed a slight protective effect on death. The effect of age on COVID-19 outcomes was partially mediated by cytokine levels, while CT scores considerably mediated the effect of cytokine levels on outcomes. Radiomic-feature-based models confirmed the association between lung imaging characteristics and CCL18 and CHI3L1. CONCLUSION: Data suggest a causal link between cytokines (risk factor), lung damage (mediator), and COVID-19 outcomes.

Incidence, mortality, and survival of hematological malignancies in Northern Italian patients: an update to 2020.

Background: Hematological malignancies (HMs) represent a heterogeneous group of diseases with diverse etiology, pathogenesis, and prognosis. HMs' accurate registration by Cancer Registries (CRs) is hampered by the progressive de-hospitalization of patients and the transition to molecular rather than microscopic diagnosis. Material and methods: A dedicated software capable of automatically identifying suspected HMs cases by combining several databases was adopted by Reggio Emilia Province CR (RE-CR). Besides pathological reports, hospital discharge archives, and mortality records, RE-CR retrieved information from general and biomolecular laboratories. Incidence, mortality, and 5-year relative survival (RS) reported according to age, sex, and 4 HMs' main categories, were noted. Results: Overall, 7,578 HM cases were diagnosed from 1996 to 2020 by RE-CR. HMs were more common in males and older patients, except for Hodgkin Lymphoma and Follicular Lymphoma (FL). Incidence showed a significant increase for FL (annual percent change (APC)=3.0), Myeloproliferative Neoplasms (MPN) in the first period (APC=6.0) followed by a significant decrease (APC=-7.4), and Myelodysplastic Syndromes (APC=16.4) only in the first period. Over the years, a significant increase was observed in 5-year RS for Hodgkin -, Marginal Zone -, Follicular - and Diffuse Large B-cell-Lymphomas, MPN, and Acute Myeloid Leukemia. The availability of dedicated software made it possible to recover 80% of cases automatically: the remaining 20% required direct consultation of medical records. Conclusions: The study emphasizes that HM registration needs to collect information from multiple sources. The digitalization of CRs is necessary to increase their efficiency.

Artificial Intelligence-Assisted Processing of Anterior Segment OCT Images in the Diagnosis of Vitreoretinal Lymphoma.

Anterior segment optical coherence tomography (AS-OCT) allows the explore not only the anterior chamber but also the front part of the vitreous cavity. Our cross-sectional single-centre study investigated whether AS-OCT can distinguish between vitreous involvement due to vitreoretinal lymphoma (VRL) and vitritis in uveitis. We studied AS-OCT images from 28 patients (11 with biopsy-proven VRL and 17 with differential diagnosis uveitis) using publicly available radiomics software written in MATLAB. Patients were divided into two balanced groups: training and testing. Overall, 3260/3705 (88%) AS-OCT images met our defined quality criteria, making them eligible for analysis. We studied five different sets of grey-level samplings (16, 32, 64, 128, and 256 levels), finding that 128 grey levels performed the best. We selected the five most effective radiomic features ranked by the ability to predict the class (VRL or uveitis). We built a classification model using the xgboost python function; through our model, 87% of eyes were correctly diagnosed as VRL or uveitis, regardless of exam technique or lens status. Areas under the receiver operating characteristic curves (AUC) in the 128 grey-level model were 0.95 [CI 0.94, 0.96] and 0.84 for training and testing datasets, respectively. This preliminary retrospective study highlights how AS-OCT can support ophthalmologists when there is clinical suspicion of VRL.

Reduction of EpCAM-Positive Cells from a Cell Salvage Product Is Achieved by Leucocyte Depletion Filters Alone.

Intraoperative cell salvage reduces the need for allogeneic blood transfusion in complex cancer surgery, but concerns about the possibility of it re-infusing cancer cells have hindered its application in oncology. We monitored the presence of cancer cells on patient-salvaged blood by means of flow cytometry; next, we simulated cell salvage, followed by leucodepletion and irradiation on blood contaminated with a known amount of EpCAM-expressing cancer cells, assessing also residual cancer cell proliferation as well as the quality of salvaged red blood cell concentrates (RBCs). We observed a significant reduction of EpCAM-positive cells in both cancer patients and contaminated blood, which was comparable to the negative control after leucodepletion. The washing, leucodepletion and leucodepletion plus irradiation steps of cell salvage were shown to preserve the quality of RBCs in terms of haemolysis, membrane integrity and osmotic resistance. Finally, cancer cells isolated from salvaged blood lose their ability to proliferate. Our results confirm that cell salvage does not concentrate proliferating cancer cells, and that leucodepletion allows for the reduction of residual nucleated cells, making irradiation unnecessary. Our study gathers pieces of evidence on the feasibility of this procedure in complex cancer surgery. Nevertheless, it highlights the necessity of finding a definitive consensus through prospective trials.

Safety injections of nuclear medicine radiotracers: towards a new modality for a real-time detection of extravasation events and 18F-FDG SUV data correction.

BACKGROUND: 18F-FDG PET/CT imaging allows to study oncological patients and their relative diagnosis through the standardised uptake value (SUV) evaluation. During radiopharmaceutical injection, an extravasation event may occur, making the SUV value less accurate and possibly leading to severe tissue damage. The study aimed to propose a new technique to monitor and manage these events, to provide an early evaluation and correction to the estimated SUV value through a SUV correction coefficient. METHODS: A cohort of 70 patients undergoing 18F- FDG PET/CT examinations was enrolled. Two portable detectors were secured on the patients' arms. The dose-rate (DR) time curves on the injected DRin and contralateral DRcon arm were acquired during the first 10 min of injection. Such data were processed to calculate the parameters ΔpinNOR = (DRinmax- DRinmean)/DRinmax and ΔRt = (DRin(t) - DRcon(t)), where DRinmax is the maximum DR value, DRinmean is the average DR value in the injected arm. OLINDA software allowed dosimetric estimation of the dose in the extravasation region. The estimated residual activity in the extravasation site allowed the evaluation of the SUV's correction value and to define an SUV correction coefficient. RESULTS: Four cases of extravasations were identified for which ΔRt [(390 ± 26) µSv/h], while ΔRt [(150 ± 22) µSv/h] for abnormal and ΔRt [(24 ± 11) µSv/h] for normal cases. The ΔpinNOR showed an average value of (0.44 ± 0.05) for extravasation cases and an average value of (0.91 ± 0.06) and (0.77 ± 0.23) in normal and abnormal classes, respectively. The percentage of SUV reduction (SUV%CR) ranges between 0.3% and 6%. The calculated self-tissue dose values range from 0.027 to 0.573 Gy, according to the segmentation modality. A similar correlation between the inverse of ΔpinNOR and the normalised ΔRt with the SUV correction coefficient was found. CONCLUSIONS: The proposed metrics allowed to characterised the extravasation events in the first few minutes after the injection, providing an early SUV correction when necessary. We also assume that the characterisation of the DR-time curve of the injection arm is sufficient for the detection of extravasation events. Further validation of these hypotheses and key metrics is recommended in larger cohorts.

The Use of Cardiac Stereotactic Radiation Therapy (SBRT) to Manage Ventricular Tachycardia: A Case Report, Review of the Literature and Technical Notes.

BACKGROUND: among cardiac arrhythmias, ventricular tachycardia (VT) is one that can lead to cardiac death, although significant progress has been made in its treatment, including the use of implantable cardioverter-defibrillators (ICD) and radiofrequency catheter ablation. Nevertheless, long-term recurrence rates remain in about half of patients and drastically impact the patient's quality of life. Moreover, recurrent ICD shocks are painful and are associated with higher mortality and worsening of heart failure. Recently, more and more experiences are demonstrating potential efficacy in the use of stereotactic body radiotherapy (SBRT) (also called cardiac radio-ablation) to treat this condition. In this paper, we report our experience in the use of cardiac radio-ablation for the treatment of refractory ventricular tachycardia with a focus on the technique used, along with a review of the literature and technical notes. CASE PRESENTATION: an 81-year-old male patient with a long history of non-ischemic dilated cardiomyopathy and mechanical mitral prosthesis underwent a biventricular cardioverter defibrillator implant after atrial ventricular node ablation. At the end of 2021, the number of tachycardias increased significantly to about 10 episodes per day. After failure of medical treatment and conventional RT catheter ablation, the patient was treated with SBRT for a total dose of 25 Gy in a single session at the site of the ectopic focus. No acute toxicity was recorded. After SBRT (follow-up 7 months) no other VT episodes were recorded. CONCLUSION: SBRT appears to be safe and leads to a rapid reduction in arrhythmic storms as treatment for VT without acute toxicity, representing one of the most promising methods for treating VT storms.

Safety of Inhomogeneous Dose Distribution IMRT for High-Grade Glioma Reirradiation: A Prospective Phase I/II Trial (GLIORAD TRIAL).

Glioblastoma multiforme (GBM) is the most aggressive astrocytic primary brain tumor, and concurrent temozolomide (TMZ) and radiotherapy (RT) followed by maintenance of adjuvant TMZ is the current standard of care. Despite advances in imaging techniques and multi-modal treatment options, the median overall survival (OS) remains poor. As an alternative to surgery, re-irradiation (re-RT) can be a therapeutic option in recurrent GBM. Re-irradiation for brain tumors is increasingly used today, and several studies have demonstrated its feasibility. Besides differing techniques, the published data include a wide range of doses, emphasizing that no standard approach exists. The current study aimed to investigate the safety of moderate-high-voxel-based dose escalation in recurrent GBM. From 2016 to 2019, 12 patients met the inclusion criteria and were enrolled in this prospective single-center study. Retreatment consisted of re-irradiation with a total dose of 30 Gy (up to 50 Gy) over 5 days using the IMRT (arc VMAT) technique. A dose painting by numbers (DPBN)/dose escalation plan were performed, and a continuous relation between the voxel intensity of the functional image set and the risk of recurrence in that voxel were used to define target and dose distribution. Re-irradiation was well tolerated in all treated patients. No toxicities greater than G3 were recorded; only one patient had severe G3 acute toxicity, characterized by muscle weakness and fatigue. Median overall survival (OS2) and progression-free survival (PFS2) from the time of re-irradiation were 10.4 months and 5.7 months, respectively; 3-, 6-, and 12-month OS2 were 92%, 75%, and 42%, respectively; and 3-, 6-, and 12-month PFS2 were 83%, 42%, and 8%, respectively. Our work demonstrated a tolerable tolerance profile of this approach, and the future prospective phase II study will analyze the efficacy in terms of PFS and OS.

Applications of artificial intelligence in stereotactic body radiation therapy.

This topical review focuses on the applications of artificial intelligence (AI) tools to stereotactic body radiation therapy (SBRT). The high dose per fraction and the limited number of fractions in SBRT require stricter accuracy than standard radiation therapy. The intent of this review is to describe the development and evaluate the possible benefit of AI tools integration into the radiation oncology workflow for SBRT automation. The selected papers were subdivided into four sections, representative of the whole radiotherapy process: 'AI in SBRT target and organs at risk contouring', 'AI in SBRT planning', 'AI during the SBRT delivery', and 'AI for outcome prediction after SBRT'. Each section summarises the challenges, as well as limits and needs for improvement to achieve better integration of AI tools in the clinical workflow.

Novel Harmonization Method for Multi-Centric Radiomic Studies in Non-Small Cell Lung Cancer.

The purpose of this multi-centric work was to investigate the relationship between radiomic features extracted from pre-treatment computed tomography (CT), positron emission tomography (PET) imaging, and clinical outcomes for stereotactic body radiation therapy (SBRT) in early-stage non-small cell lung cancer (NSCLC). One-hundred and seventeen patients who received SBRT for early-stage NSCLC were retrospectively identified from seven Italian centers. The tumor was identified on pre-treatment free-breathing CT and PET images, from which we extracted 3004 quantitative radiomic features. The primary outcome was 24-month progression-free-survival (PFS) based on cancer recurrence (local/non-local) following SBRT. A harmonization technique was proposed for CT features considering lesion and contralateral healthy lung tissues using the LASSO algorithm as a feature selector. Models with harmonized CT features (B models) demonstrated better performances compared to the ones using only original CT features (C models). A linear support vector machine (SVM) with harmonized CT and PET features (A1 model) showed an area under the curve (AUC) of 0.77 (0.63-0.85) for predicting the primary outcome in an external validation cohort. The addition of clinical features did not enhance the model performance. This study provided the basis for validating our novel CT data harmonization strategy, involving delta radiomics. The harmonized radiomic models demonstrated the capability to properly predict patient prognosis.

How a very large sarcomatoid lung cancer was efficiently managed with lattice radiation therapy: a case report.

BACKGROUND: The management of large tumors represent a concerning issue in the palliative setting. Since a surgical approach is excluded and systemic therapy has reported limited efficacy, the patients are commonly referred for radiation therapy as last resort. However, to improve quality of life and to avoid excessive toxicity, low doses of palliative radiotherapy (RT) are delivered. In these cases, with limited and short response. Lattice radiation therapy (LRT) represents an innovative technique aiming to increase tumor response without enhancing adjacent organs at risk (OAR) toxicity, by administering inhomogeneous doses with ablative high dose areas inside the tumor and low doses near the OAR. CASE DESCRIPTION: A 69-year-old male patient was admitted to our hospital complaining of sacral pain and mild dyspnea. After a suspicious opacity on X-ray, the chest computed tomography (CT), the positron emission tomography/CT (PET/CT) and the endobronchial ultra sound-guided transbronchial needle aspiration confirmed the diagnosis of a bulky sarcomatoid lung cancer (stage IV: cT4N3M1c). After an effective antalgic RT on the sacral metastasis and three lines of systemic therapy without response, the patient started to have a disabling dyspnea. Thus, we administered LRT on the bulky lesion. The patients experienced no significant toxicity, with a marked lesion response on the 3 month-follow CT and a significant improvement in symptoms and in his daily life. CONCLUSIONS: This is the first LRT treatment done in our Center and it provides another evidence in the efficacy of LRT planning. It shows how LRT could represent an innovative technique to provide durable response in large tumors, without increasing treatment-related toxicity.

Rehabilitation Interventions for Post-Acute COVID-19 Syndrome: A Systematic Review.

Increasing numbers of individuals suffer from post-acute COVID-19 syndrome (PACS), which manifests with persistent symptoms, the most prevalent being dyspnea, fatigue, and musculoskeletal, cognitive, and/or mental health impairments. This systematic review investigated the effectiveness of rehabilitation interventions for individuals with PACS. We searched the MEDLINE, Embase, Cochrane Register of Controlled Trials, CINHAL, Scopus, Prospero, and PEDro databases and the International Clinical Trials Registry Platform for randomized controlled trials (RCTs) up to November 2021. We screened 516 citations for eligibility, i.e., trials that included individuals with PACS exposed to exercise-based rehabilitation interventions. Five RCTs were included, accounting for 512 participants (aged 49.2-69.4 years, 65% males). Based on the revised Cochrane risk-of-bias tool (RoB 2.0), two RCTs had "low risk of bias", and three were in the "some concerns" category. Three RCTs compared experimental rehabilitation interventions with no or minimal rehabilitation, while two compared two active rehabilitation interventions. Rehabilitation seemed to improve dyspnea, anxiety, and kinesiophobia. Results on pulmonary function were inconsistent, while improvements were detected in muscle strength, walking capacity, sit-to-stand performance, and quality of life. Pending further studies based on qualitatively sound designs, these first findings seem to advocate for rehabilitation interventions to lessen disability due to PACS.

Inflammatory burden and persistent CT lung abnormalities in COVID-19 patients.

Inflammatory burden is associated with COVID-19 severity and outcomes. Residual computed tomography (CT) lung abnormalities have been reported after COVID-19. The aim was to evaluate the association between inflammatory burden during COVID-19 and residual lung CT abnormalities collected on follow-up CT scans performed 2-3 and 6-7 months after COVID-19, in severe COVID-19 pneumonia survivors. C-reactive protein (CRP) curves describing inflammatory burden during the clinical course were built, and CRP peaks, velocities of increase, and integrals were calculated. Other putative determinants were age, sex, mechanical ventilation, lowest PaO2/FiO2 ratio, D-dimer peak, and length of hospital stay (LOS). Of the 259 included patients (median age 65 years; 30.5% females), 202 (78%) and 100 (38.6%) had residual, predominantly non-fibrotic, abnormalities at 2-3 and 6-7 months, respectively. In age- and sex-adjusted models, best CRP predictors for residual abnormalities were CRP peak (odds ratio [OR] for one standard deviation [SD] increase = 1.79; 95% confidence interval [CI] = 1.23-2.62) at 2-3 months and CRP integral (OR for one SD increase = 2.24; 95%CI = 1.53-3.28) at 6-7 months. Hence, inflammation is associated with short- and medium-term lung damage in COVID-19. Other severity measures, including mechanical ventilation and LOS, but not D-dimer, were mediators of the relationship between CRP and residual abnormalities.

Enhancing the impact of Artificial Intelligence in Medicine: A joint AIFM-INFN Italian initiative for a dedicated cloud-based computing infrastructure.

Artificial Intelligence (AI) techniques have been implemented in the field of Medical Imaging for more than forty years. Medical Physicists, Clinicians and Computer Scientists have been collaborating since the beginning to realize software solutions to enhance the informative content of medical images, including AI-based support systems for image interpretation. Despite the recent massive progress in this field due to the current emphasis on Radiomics, Machine Learning and Deep Learning, there are still some barriers to overcome before these tools are fully integrated into the clinical workflows to finally enable a precision medicine approach to patients' care. Nowadays, as Medical Imaging has entered the Big Data era, innovative solutions to efficiently deal with huge amounts of data and to exploit large and distributed computing resources are urgently needed. In the framework of a collaboration agreement between the Italian Association of Medical Physicists (AIFM) and the National Institute for Nuclear Physics (INFN), we propose a model of an intensive computing infrastructure, especially suited for training AI models, equipped with secure storage systems, compliant with data protection regulation, which will accelerate the development and extensive validation of AI-based solutions in the Medical Imaging field of research. This solution can be developed and made operational by Physicists and Computer Scientists working on complementary fields of research in Physics, such as High Energy Physics and Medical Physics, who have all the necessary skills to tailor the AI-technology to the needs of the Medical Imaging community and to shorten the pathway towards the clinical applicability of AI-based decision support systems.

Cone beam CT augmented fluoroscopy allows safe and efficient diagnosis of a difficult lung nodule.

BACKGROUND: Detection of small peripheral lung nodules is constantly increasing with the development of low dose computed tomography lung cancer screening programs. A tissue diagnosis is often required to confirm malignity, with endobronchial biopsies being associated with a lower pneumothorax rate than percutaneous approaches. Endoscopic diagnosis of peripheral small size lung nodules is however often challenging using traditional bronchoscopy and endobronchial ultrasound alone. New virtual bronchoscopic navigation techniques such as electromagnetic navigational bronchoscopy (ENB) have developed to improve peripheral navigation, with diagnostic yield however remaining in the 30-50% range for small lesions. Recent studies have shown the benefits of combining Cone beam computed tomography (CBCT) with ENB to improve diagnostic yield to up to 83%. The use of ENB however remains limited by disposable cost, bronchus sign dependency and inaccuracies due to CT to body divergence. CASE PRESENTATION: This case report highlights the feasibility and usefulness of CBCT-guided bronchoscopy for the sampling of lung nodules difficult to reach through traditional bronchoscopy because of nodule size and peripheral position. Procedure was scheduled in a mobile robotic hybrid operating room with patient under general anaesthesia. CBCT acquisition was performed to localize the target lesion and plan the best path to reach it into bronchial tree. A dedicated software was used to segment the lesion and the bronchial path which 3D outlines were automatically fused in real time on the fluoroscopic images to augment live guidance. Navigation to the lesion was guided with bronchoscopy and augmented fluoroscopy alone. Before the sampling, CBCT imaging was repeated to confirm the proper position of the instrument into the lesion. Four transbronchial needle aspirations (TBNA) were performed and the tissue analysis showed a primary lung adenocarcinoma. CONCLUSIONS: CBCT and augmented fluoroscopy technique is a safe and effective and has potential to improve early stage peripheral lesions endobronchial diagnostic yield without ENB. Additional studies are warranted to confirm its safety, efficacy and technical benefits, both for diagnosis of oncological and non-oncological disease and for endobronchial treatment of inoperable patients.

Variations in Head and Neck Treatment Plan Quality Assessment Among Radiation Oncologists and Medical Physicists in a Single Radiotherapy Department.

BACKGROUND: Agreement between planners and treating radiation oncologists (ROs) on plan quality criteria is essential for consistent planning. Differences between ROs and planning medical physicists (MPs) in perceived quality of head and neck cancer plans were assessed. MATERIALS AND METHODS: Five ROs and four MPs scored 65 plans for in total 15 patients. For each patient, the clinical (CLIN) plan and two or four alternative plans, generated with automated multi-criteria optimization (MCO), were included. There was always one MCO plan aiming at maximally adhering to clinical plan requirements, while the other MCO plans had a lower aimed quality. Scores were given as follows: 1-7 and 1-2, not acceptable; 3-5, acceptable if further planning would not resolve perceived weaknesses; and 6-7, straightway acceptable. One MP and one RO repeated plan scoring for intra-observer variation assessment. RESULTS: For the 36 unique observer pairs, the median percentage of plans for which the two observers agreed on a plan score (100% = 65 plans) was 27.7% [6.2, 40.0]. In the repeat scoring, agreements between first and second scoring were 52.3% and 40.0%, respectively. With a binary division between unacceptable (scores 1 and 2) and acceptable (3-7) plans, the median inter-observer agreement percentage was 78.5% [63.1, 86.2], while intra-observer agreements were 96.9% and 86.2%. There were no differences in observed agreements between RO-RO, MP-MP, and RO-MP pairs. Agreements for the highest-quality, automatically generated MCO plans were higher than for the CLIN plans. CONCLUSIONS: Inter-observer differences in plan quality scores were substantial and could result in inconsistencies in generated treatment plans. Agreements among ROs were not better than between ROs and MPs, despite large differences in training and clinical role. High-quality automatically generated plans showed the best score agreements.

Use of knowledge based DVH predictions to enhance automated re-planning strategies in head and neck adaptive radiotherapy.

This study aimed to investigate if a commercial, knowledge-based tool for radiotherapy planning could be used to estimate the amount of sparing in organs at risk (OARs) in the re-planning strategy for adaptive radiotherapy (ART). Eighty head and neck (HN) VMAT Pareto plans from our institute's database were used to train a knowledge-based planning (KBP) model. An evaluation set of another 20 HN patients was randomly selected. For each patient in the evaluation set, the planning computed tomography (CT) and 2 sets of on-board cone-beam CT, corresponding to the middle and second half of the radiotherapy treatment course, were extracted. The original plan was re-calculated on a daily deformed CT (delivered dose-volume histogram (DVH)) and compared with the KBP DVH predictions and with the final KBP DVH after optimisation of the plan, which was performed on the same image sets. To evaluate the feasibility of this method, the range of KBP DVH uncertainties was compared with the gains obtained from re-planning. DVH differences and receiver operating characteristic (ROC) curve analysis were used for this purpose. On average, final KBP uncertainties were smaller than the gain in re-planning. Statistical tests confirmed significant differences between the two groups. ROC analysis showed KBP performance in terms of area under the curve values higher than 0.7, which confirmed a good accuracy in predicted values. Overall, for 48% of cases, KBP predicted a desirable outcome from re-planning, and the final dose confirmed an effective gain in 47% of cases. We have established a systematic workflow to identify effective OAR sparing in re-planning based on KBP predictions that can be implemented in an on-line, ART process.

How direct measurements of worker eyes with a Scheimpflug camera can affect lensdose coefficients in interventional radiology.

The 2013/59/Euratom Directive reduced the occupational exposure limits for the lens. Since it has become crucial to estimate the dose absorbed by the lens, we have studied the individual variability of exposed workers' ocular conformations with respect to the data estimated from their personal dosimetry. The anterior eye conformations of 45 exposed workers were acquired using Scheimpflug imaging and classified according to their sight conditions (emmetropia, myopia or hypermetropia). Three eye models were computed, with two lens reconstructions, and implemented in an interventional radiology scenario using Monte Carlo code. The models were dosimetrically analysed by simulating setup A, a theoretical monoenergetic and isotropic photon source (10-150 keV) and setup B, a more realistic interventional setting with an angiographic x-ray unit (50, 75, 100 kV peak). Scheimpflug imaging provided an average anterior chamber depth of (6.4 ± 0.5) mm and a lens depth of (3.9 ± 0.3) mm, together with a reconstructed equatorial lens length of (7.1-10.1) mm. Using these data for model reconstruction, dose coefficients (DCs) were simulated for all ocular structures. Regardless of the eye model used, the DCs showed a similar trend with radiation energy, which highlighted that for the same energy and setup, no significant dependence on ocular morphology and workers' visual conditions was observed. The maximum difference obtained did not exceed 1% for all eye models or structures analysed. Therefore, the individual variabilities of worker ocular anatomy do not require any additional correction, compared to the personal dosimetry data measured with a dedicated lens dosimeter. To estimate the dose absorbed by the other eye structures, it is, instead, essential to know the spectrum of the source that has generated the irradiation, since there are differences between monoenergetic sources and more realistic angiographic units.

EPID-based 3D dosimetry for pre-treatment FFF VMAT stereotactic body radiotherapy plan verification using dosimetry CheckTM.

PURPOSE: The software Dosimetry Check (DC) reconstructs the 3D dose distribution on CT images data set by using EPID measured signal. This study aimed to evaluate DC for stereotactic body radiotherapy (SBRT) with unflattened photon beams (FFF) for dosimetric independent plan verification in pre-treatment modality. METHODS: DC v.4.1 was configured for Varian TrueBeam STx FFF beams equipped with EPID aS-1200. The DC FFF models were tested using arc open fields (from 1×1 cm2 to 15×15 cm2) and VMAT (Volumetric Modulated Arc Therapy) SBRT plans on phantom and patient CTs. DC dose distributions (DDC) were compared with that calculated by Eclipse with Acuros XB algorithm (DAXB) and one measured by Octavius 1000 SRS detector (DOCT). All differences were quantified in terms of the local 3D gamma passing rate (%GP), DVH and point dose differences. RESULTS: DC was configured for FFF VMAT using an appropriate correction procedure. %GP2%2mm (mean±standard deviation) of DOCT-DDC was 96.3±2.7% for open fields whereas it was 90.1±5.9% for plans on homogeneous phantom CT. However, average %GP3%3mm of DAXB-DDC was 95.0±4.1 for treatments on patient CT. The fraction of plans passing the %GP3%3mm DQA tolerance level [10% (50%) of maximum dose threshold] were 20/20 (14/20) and 18/20 (16/20) for OCT on phantom CT and DC on patient CT, respectively. CONCLUSIONS: DC characterization for FFF beams was performed. For stereotactic VMAT plan verifications DC showed good agreement with TPS whereas underlined discrepancies with Octavius in the high dose regions. A customized tolerance level is required for EPID-based VMAT FFF pre-treatment verification when DC system is applied.

DNA damage in lens epithelial cells exposed to occupationally-relevant X-ray doses and role in cataract formation.

The current framework of radiological protection of occupational exposed medical workers reduced the eye-lens equivalent dose limit from 150 to 20 mSv per year requiring an accurate dosimetric evaluation and an increase understanding of radiation induced effects on Lens cells considering the typical scenario of occupational exposed medical operators. Indeed, it is widely accepted that genomic damage of Lens epithelial cells (LEC) is a key mechanism of cataractogenesis. However, the relationship between apoptosis and cataractogenesis is still controversial. In this study biological and physical data are combined to improve the understanding of radiation induced effects on LEC. To characterize the occupational exposure of medical workers during angiographic procedures an INNOVA 4100 (General Electric Healthcare) equipment was used (scenario A). Additional experiments were conducted using a research tube (scenario B). For both scenarios, the frequencies of binucleated cells, micronuclei, p21-positive cells were assessed with different doses and dose rates. A Monte-Carlo study was conducted using a model for the photon generation with the X-ray tubes and with the Petri dishes considering the two different scenarios (A and B) to reproduce the experimental conditions and validate the irradiation setups to the cells. The simulation results have been tallied using the Monte Carlo code MCNP6. The spectral characteristics of the different X-ray beams have been estimated. All irradiated samples showed frequencies of micronuclei and p21-positive cells higher than the unirradiated controls. Differences in frequencies increased with the delivered dose measured with Gafchromic films XR-RV3. The spectrum incident on eye lens and Petri, as estimated with MCNP6, was in good agreement in the scenario A (confirming the experimental setup), while the mean energy spectrum was higher in the scenario B. Nevertheless, the response of LEC seemed mainly related to the measured absorbed dose. No effects on viability were detected. Our results support the hypothesis that apoptosis is not responsible for cataract induced by low doses of X-ray (i.e. 25 mGy) while the induction of transient p21 may interfere with the disassembly of the nuclear envelop in differentiating LEC, leading to cataract formation. Further studies are needed to better clarify the relationship we suggested between DNA damage, transient p21 induction and the inability of LEC enucleation.