Radiation exposure assessment of nuclear medicine staff administering [177Lu]Lu-DOTA-TATE with active and passive dosimetry.

BACKGROUND: The use of lutetium-177 (177Lu)-based radiopharmaceuticals in peptide receptor nuclear therapy is increasing, but so is the number of nuclear medicine workers exposed to higher levels of radiation. In recent years, [177Lu]Lu-DOTA-TATE has begun to be widely used for the treatment of neuroendocrine tumours. However, there are few studies evaluating the occupational radiation exposure during its administration, and there are still some challenges that can result in higher doses to the staff, such as a lack of trained personnel or fully standardised procedures. In response, this study aims to provide a comprehensive analysis of occupational doses to the staff involved in the administration of [177Lu]Lu-DOTA-TATE. RESULTS: A total of 32 administrations of [177Lu]Lu-DOTA-TATE (7.4 GBq/session) carried out by a physician and a nurse, were studied. In total, two physicians and four nurses were independently monitored with cumulative (passive) and/or real-time (active) dosemeters. Extremity, eye lens and whole-body doses were evaluated in terms of the dosimetric quantities Hp(0.07), Hp(3) and Hp(10), respectively. It was obtained that lead aprons reduced dose rates and whole-body doses by 71% and 69% for the physicians, respectively, and by 56% and 68% for the nurses. On average, normalised Hp(10) values of 0.65 ± 0.18 µSv/GBq were obtained with active dosimetry, which is generally consistent with passive dosemeters. For physicians, the median of the maximum normalised Hp(0.07) values was 41.5 µSv/GBq on the non-dominant hand and 45.2 µSv/GBq on the dominant hand. For nurses 15.4 µSv/GBq on the non-dominant and 13.9 µSv/GBq on the dominant hand. The ratio or correction factor between the maximum dose measured on the hand and the dose measured on the base of the middle/ring finger of the non-dominant hand resulted in a factor of 5/6 for the physicians and 3/4 for the nurses. Finally, maximum normalised Hp(3) doses resulted in 2.02 µSv/GBq for physicians and 1.76 µSv/GBq for nurses. CONCLUSIONS: If appropriate safety measures are taken, the administration of [177Lu]Lu-DOTA-TATE is a safe procedure for workers. However, regular monitoring is recommended to ensure that the annual dose limits are not exceeded.

Predictive value of 99mTc-MAA-based dosimetry in personalized 90Y-SIRT planning for liver malignancies.

BACKGROUND: Selective internal radiation therapy with 90Y radioembolization aims to selectively irradiate liver tumours by administering radioactive microspheres under the theragnostic assumption that the pre-therapy injection of 99mTc labelled macroaggregated albumin (99mTc-MAA) provides an estimation of the 90Y microspheres biodistribution, which is not always the case. Due to the growing interest in theragnostic dosimetry for personalized radionuclide therapy, a robust relationship between the delivered and pre-treatment radiation absorbed doses is required. In this work, we aim to investigate the predictive value of absorbed dose metrics calculated from 99mTc-MAA (simulation) compared to those obtained from 90Y post-therapy SPECT/CT. RESULTS: A total of 79 patients were analysed. Pre- and post-therapy 3D-voxel dosimetry was calculated on 99mTc-MAA and 90Y SPECT/CT, respectively, based on Local Deposition Method. Mean absorbed dose, tumour-to-normal ratio, and absorbed dose distribution in terms of dose-volume histogram (DVH) metrics were obtained and compared for each volume of interest (VOI). Mann-Whitney U-test and Pearson's correlation coefficient were used to assess the correlation between both methods. The effect of the tumoral liver volume on the absorbed dose metrics was also investigated. Strong correlation was found between simulation and therapy mean absorbed doses for all VOIs, although simulation tended to overestimate tumour absorbed doses by 26%. DVH metrics showed good correlation too, but significant differences were found for several metrics, mostly on non-tumoral liver. It was observed that the tumoral liver volume does not significantly affect the differences between simulation and therapy absorbed dose metrics. CONCLUSION: This study supports the strong correlation between absorbed dose metrics from simulation and therapy dosimetry based on 90Y SPECT/CT, highlighting the predictive ability of 99mTc-MAA, not only in terms of mean absorbed dose but also of the dose distribution.

Pilot Study for the Assessment of the Best Radiomic Features for Bosniak Cyst Classification Using Phantom and Radiologist Inter-Observer Selection.

Since the Bosniak cysts classification is highly reader-dependent, automated tools based on radiomics could help in the diagnosis of the lesion. This study is an initial step in the search for radiomic features that may be good classifiers of benign-malignant Bosniak cysts in machine learning models. A CCR phantom was used through five CT scanners. Registration was performed with ARIA software, while Quibim Precision was used for feature extraction. R software was used for the statistical analysis. Robust radiomic features based on repeatability and reproducibility criteria were chosen. Excellent correlation criteria between different radiologists during lesion segmentation were imposed. With the selected features, their classification ability in benignity-malignity terms was assessed. From the phantom study, 25.3% of the features were robust. For the study of inter-observer correlation (ICC) in the segmentation of cystic masses, 82 subjects were prospectively selected, finding 48.4% of the features as excellent regarding concordance. Comparing both datasets, 12 features were established as repeatable, reproducible, and useful for the classification of Bosniak cysts and could serve as initial candidates for the elaboration of a classification model. With those features, the Linear Discriminant Analysis model classified the Bosniak cysts in terms of benignity or malignancy with 88.2% accuracy.

Occupational radiation exposure assessment during the management of [68Ga]Ga-DOTA-TOC.

BACKGROUND: Since it was first approved in Europe in 2016, the gallium-68 (68Ga) radiopharmaceutical [68Ga]Ga-DOTA-TOC has been widely used for imaging of somatostatin receptor (SSTR) positive tumours using positron emission tomography-computed tomography (PET/CT). Significant patient benefits have been reported, so its use is rapidly increasing. However, few studies have been published regarding occupational doses to nuclear medicine personnel handling this radiopharmaceutical, despite its manual usage at low distances from the skin and the beta-emission decay scheme, which may result in an increased absorbed dose to their hands. In this context, this study aims to analyse the occupational exposure during the administration of [68Ga]Ga-DOTA-TOC for PET/CT imaging. For this purpose, extremity, eye lens and whole-body dosimetry in terms of Hp(0.07), Hp(3) and Hp(10), respectively, was conducted on six workers with both thermoluminescent dosimeters, and personal electronic dosimeters. RESULTS: The non-dominant hand is more exposed to radiation than the dominant hand, with the thumb and the index fingertip being the most exposed sites on this hand. Qualitative analysis showed that when no shielding is used during injection, doses increase significantly more in the dominant than in the non-dominant hand, so the use of shielding is strongly recommended. While wrist dosimeters may significantly underestimate doses to the hands, placing a ring dosimeter at the base of the ring or middle finger of the non-dominant hand may give a valuable estimation of maximum doses to the hands if at least a correction factor of 5 is applied. Personal equivalent doses for the eyes did not result in measurable values (i.e., above the lowest detection limit) for almost all workers. The extrapolated annual dose estimations showed that there is compliance with the annual dose limits during management of [68Ga]Ga-DOTA-TOC for diagnostics with PET in the hospital included in this study. CONCLUSIONS: Imaging with [68Ga]Ga-DOTA-TOC is a safe process for the workers performing the administration of the radiopharmaceutical, including intravenous injection to the patient and the pre- and post-activity control, as it is highly unlikely that annual dose limits will be exceeded if good working practices and shielding are used.

The 3rd ESTRO-EFOMP core curriculum for medical physics experts in radiotherapy.

PURPOSE: To update the 2011 ESTRO-EFOMP core curriculum (CC) for education and training of medical physics experts (MPE)s working in radiotherapy (RT), in line with recent EU guidelines, and to provide a framework for European countries to develop their own curriculum. MATERIAL AND METHODS: Since September 2019, 27 European MPEs representing ESTRO, EFOMP and National Societies, with expertise covering all subfields of RT physics, have revised the CC for recent advances in RT. The ESTRO and EFOMP Education Councils, all European National Societies and international stakeholders have been involved in the revision process. RESULTS: A 4-year training period has been proposed, with a total of 240 ECTS (European Credit Transfer and Accumulation System). Training entrance levels have been defined ensuring the necessary physics and mathematics background. The concept of competency-based education has been reinforced by introducing the CanMEDS role framework. The updated CC includes (ablative) stereotactic-, MR-guided- and adaptive RT, particle therapy, advanced automation, complex quantitative data analysis (big data/artificial intelligence), use of biological images, and personalized treatments. Due to the continuously increasing RT complexity, more emphasis has been given to quality management. Clear requirements for a research project ensure a proper preparation of MPE residents for their central role in science and innovation in RT. CONCLUSION: This updated, 3rd edition of the CC provides an MPE training framework for safe and effective practice of modern RT, while acknowledging the significant efforts needed in some countries to reach this level. The CC can contribute to further harmonization of MPE training in Europe.

Early career medical physicist groups in Europe: An EFOMP survey.

INTRODUCTION: Training, educating, and fostering of young professionals are key requisites for the progress of any profession. The young medical physicists (MPs) of today are the medical physics professionals and leaders of tomorrow. It is, therefore, essential that they learn to work collectively and in a coordinated manner at both national and European levels at an early stage in their career. In view of this, EFOMP is planning to create a special interest group (SIG) encompassing early career MPs from across Europe. METHODS: A survey was developed by EFOMP and circulated to all National Member Organisations (NMOs) to gather information on the status of early career groups in their respective societies and on the interest to partake in such group within the Federation. RESULTS: Of the 36 NMOs that are part of EFOMP, 32 responded to the survey. Only 9 NMOs have established early career MPs groups within their NMOs, while the remaining countries are either considering setting up young MPs groups in the future (15 NMOs) or do not show such interest (8 NMOs). Of all responders, 59% expressed interest in the creation of the EFOMP SIG, 34% remained neutral towards this issue by not answering the question and for two NMOs the SIG idea had no appeal. CONCLUSION: Most NMOs showed interest in the creation of an early career MPs group within EFOMP and offered constructive feedbacks on the roles they envisage for the group. EFOMP will use and implement this information when establishing the special interest group.

Towards an updated ESTRO-EFOMP core curriculum for education and training of medical physics experts in radiotherapy - A survey of current education and training practice in Europe.

PURPOSE: ESTRO-EFOMP intend to update the core curriculum (CC) for education and training of medical physicists in radiotherapy in line with the European Commission (EC) guidelines on Medical Physics Experts (MPE), the CanMEDS methodology and recent developments in radiotherapy. As input, a survey of the current structure of radiotherapy MPE national training schemes (NTS) in Europe was carried out. METHODS: A 35-question survey was sent to all European medical physics national societies (NS) with a focus on existence of an NTS, its format and duration, required entry-level education, and financial support for trainees. RESULTS: Twenty-six of 36 NS responded. Twenty had an NTS. Minimum required pre-training education varied from BSc in physics or related sciences (5/2) to MSc in medical physics, physics or related sciences (6/5/2) with 50-210 ECTS in fundamental physics and mathematics. The training period varied from 1 to 5 years (median 3 years with 50% dedicated to radiotherapy). The ratio of time spent on university lectures versus hospital training was most commonly 25%/75%. In 14 of 20 countries with an NTS, a research project was mandatory. Residents were paid in 17 of 20 countries. The recognition was mostly obtained by examination. Medical physics is recognised as a healthcare profession in 19 of 26 countries. CONCLUSIONS: The NTS entrance level, duration and curriculum showed significant variations. This survey serves to inform the design of the updated CC to define a realistic minimum training level for safe and effective practice aiming at further harmonization in line with EC guidelines.

Spanish multicenter real - life registry of retrievable vena cava filters (REFiVeC).

BACKGROUND: The treatment of venous thromboembolic disease the treatment of choice is systemic anticoagulation. However, the interruption of the inferior vena cava with filters has been recommended when anticoagulation fails or there is a contraindication. Due to the rising inferior vena cava filter (IVCF) complications, physicians are encouraged to retrieve them when there is no longer recommended. In daily practice, it may be a difficult close follow-up of these patients. In this study, the primary objective was to evaluate the IVCF retrieval rate of all implanted filters in a Spanish registry. Secondary objectives were to analyze the causes of failed retrieval, procedure-related complications, and outcomes at a 12-month follow-up. RESULTS: Three hundred fifty-six vena cava filters were implanted in 355 patients. The types of filter were: Gunther Tulip (Cook Medical) 160 (44.9%), Optease (Cordis) 77 (21.6%), Celect (Cook Medical) 49 (13, 7%), Aegisy (Lifetech Scientific) 33 (9.2%), Option ELITE (Argon Medical devices) 16 (4.4%), Denali filter (BD Bard) 11 (3.08%), ALN filter (ALN) 10 (2.8%). Removal was achieved in 274/356 (76,9%). eighty-two (23,1%) IVCF were not retrieved due to the following: 41 (11,5%) patients required ongoing filtration, 24 IVCF (6,7%) patients died before retrieval, and 17 (4,7%) impossibility of retrieval because of a tilted and embedded filter apex. There were no major complications observed. CONCLUSIONS: The global retrieval rate of IVCF was achieved in 76.9%, and the adjusted retrieval rate was of 94.15% with no major complications. IVCF tilting was associated with failure of filter removal in less than 5% of cases. This study demonstrates that the retrieval procedure of IVCF is controlled by the clinician and not by the interventional radiologist.

Multimodality functional imaging using DW-MRI and 18F-FDG-PET/CT during radiation therapy for human papillomavirus negative head and neck squamous cell carcinoma: Meixoeiro Hospital of Vigo Experience.

AIM: To noninvasively investigate tumor cellularity measured using diffusion-weighted magnetic resonance imaging (DW-MRI) and glucose metabolism measured by 18F-labeled fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) during radiation therapy (RT) for human papillomavirus negative (HPV-) head and neck squamous cell carcinoma (HNSCC). METHODS: In this prospective study, 6 HPV- HNSCC patients underwent a total of 34 multimodality imaging examinations DW-MRI at 1.5 T Philips MRI scanner [(n = 24) pre-, during- (2-3 wk), and post-treatment (Tx), and 18F-FDG PET/CT pre- and post-Tx (n = 10)]. All patients received RT. Monoexponential modeling of the DW-MRI data yielded the imaging metric apparent diffusion coefficient (ADC) and the mean of standardized uptake value (SUV) was measured from 18F-FDG PET uptake. All patients had a clinical follow-up as the standard of care and survival status was documented at 1 year. RESULTS: There was a strong negative correlation between the mean of pretreatment ADC (ρ = -0.67, P = 0.01) and the pretreatment 18F-FDG PET SUV. The percentage (%) change in delta (∆) ADC for primary tumors and neck nodal metastases between pre- and Wk2-3 Tx were as follows: 75.4% and 61.6%, respectively, for the patient with no evidence of disease, 27.5% and 32.7%, respectively, for those patients who were alive with disease, and 26.9% and 7.31%, respectively, for those who were dead with disease. CONCLUSION: These results are preliminary in nature and are indicative, and not definitive, trends rendered by the imaging metrics due to the small sample size of HPV- HNSCC patients in a Meixoeiro Hospital of Vigo Experience.

Multimodality functional imaging in radiation therapy planning: relationships between dynamic contrast-enhanced MRI, diffusion-weighted MRI, and 18F-FDG PET.

OBJECTIVES: Biologically guided radiotherapy needs an understanding of how different functional imaging techniques interact and link together. We analyse three functional imaging techniques that can be useful tools for achieving this objective. MATERIALS AND METHODS: The three different imaging modalities from one selected patient are ADC maps, DCE-MRI, and 18F-FDG PET/CT, because they are widely used and give a great amount of complementary information. We show the relationship between these three datasets and evaluate them as markers for tumour response or hypoxia marker. Thus, vascularization measured using DCE-MRI parameters can determine tumour hypoxia, and ADC maps can be used for evaluating tumour response. RESULTS: ADC and DCE-MRI include information from 18F-FDG, as glucose metabolism is associated with hypoxia and tumour cell density, although 18F-FDG includes more information about the malignancy of the tumour. The main disadvantage of ADC maps is the distortion, and we used only low distorted regions, and extracellular volume calculated from DCE-MRI can be considered equivalent to ADC in well-vascularized areas. CONCLUSION: A dataset for achieving the biologically guided radiotherapy must include a tumour density study and a hypoxia marker. This information can be achieved using only MRI data or only PET/CT studies or mixing both datasets.

Autophagic marker MAP1LC3B expression levels are associated with carotid atherosclerosis symptomatology.

OBJECTIVES: The mechanism by which atheroma plaque becomes unstable is not completely understood to date but analysis of differentially expressed genes in stable versus unstable plaques may provide clues. This will be crucial toward disclosing the mechanistic basis of plaque instability, and may help to identify prognostic biomarkers for ischaemic events. The objective of our study was to identify differences in expression levels of 59 selected genes between symptomatic patients (unstable plaques) and asymptomatic patients (stable plaques). METHODS: 80 carotid plaques obtained by carotid endarterectomy and classified as symptomatic (>70% stenosis) or asymptomatic (>80% stenosis) were used in this study. The expression levels of 59 genes were quantified by qPCR on RNA extracted from the carotid plaques obtained by endarterectomy and analyzed by means of various bioinformatic tools. RESULTS: Several genes associated with autophagy pathways displayed differential expression levels between asymptomatic and symptomatic (i.e. MAP1LC3B, RAB24, EVA1A). In particular, mRNA levels of MAP1LC3B, an autophagic marker, showed a 5-fold decrease in symptomatic samples, which was confirmed in protein blots. Immune system-related factors and endoplasmic reticulum-associated markers (i.e. ERP27, ITPR1, ERO1LB, TIMP1, IL12B) emerged as differently expressed genes between asymptomatic and symptomatic patients. CONCLUSIONS: Carotid atherosclerotic plaques in which MAP1LC3B is underexpressed would not be able to benefit from MAP1LC3B-associated autophagy. This may lead to accumulation of dead cells at lesion site with subsequent plaque destabilization leading to cerebrovascular events. Identified biomarkers and network interactions may represent novel targets for development of treatments against plaque destabilization and thus for the prevention of cerebrovascular events.

Functional imaging in radiation therapy planning for head and neck cancer.

Functional imaging and its application to radiotherapy (RT) is a rapidly expanding field with new modalities and techniques constantly developing and evolving. As technologies improve, it will be important to pay attention to their implementation. This review describes the main achievements in the field of head and neck cancer (HNC) with particular remarks on the unsolved problems.

Radial scars diagnosed at stereotactic core-needle biopsy: surgical biopsy findings.

We retrospectively reviewed surgical biopsy findings of lesions diagnosed as radial scars (RS) at stereotactic core-needle biopsy (SCNB). RS was diagnosed in 52 of 1415 (3.7%) consecutive mammographically detected lesions that underwent 14-gauge automated SCNB. Subsequent surgical biopsy findings were available for 43 lesions in 41 women constituting the study group. Of these 43 lesions, histopathological analysis of the surgical specimen yielded RS in 27 (63%), RS plus atypical ductal hyperplasia (ADH) in 8 (18%), RS plus carcinoma in five (12%), and only carcinoma in three (7%). Carcinomas underestimated at SCNB (n=8) were two in situ carcinomas, two invasive ductal carcinomas not otherwise specified, and four tubular carcinomas. A statistically significant difference (P=0.02) was found between the mean pathologic size of RS without carcinoma and of RS containing carcinoma. Mammographic features could not be used reliably to predict the presence of carcinoma at excision of lesions diagnosed as RS at SCNB. The results suggest that the diagnosis of RS at 14-gauge SCNB of mammographically detected lesions is an indication for surgical biopsy because of the high prevalence of carcinoma in these lesions.

Characterization of electron contamination in megavoltage photon beams.

The purpose of the present study is to characterize electron contamination in photon beams in different clinical situations. Variations with field size, beam modifier (tray, shaping block) and source-surface distance (SSD) were studied. Percentage depth dose measurements with and without a purging magnet and replacing the air by helium were performed to identify the two electron sources that are clearly differentiated: air and treatment head. Previous analytical methods were used to fit the measured data, exploring the validity of these models. Electrons generated in the treatment head are more energetic and more important for larger field sizes, shorter SSD, and greater depths. This difference is much more noticeable for the 18 MV beam than for the 6 MV beam. If a tray is used as beam modifier, electron contamination increases, but the energy of these electrons is similar to that of electrons coming from the treatment head. Electron contamination could be fitted to a modified exponential curve. For machine modeling in a treatment planning system, setting SSD at 90 cm for input data could reduce errors for most isocentric treatments, because they will be delivered for SSD ranging from 80 to 100 cm. For very small field sizes, air-generated electrons must be considered independently, because of their different energetic spectrum and dosimetric influence.

Comparison between TG-51 and TRS-398: electron contamination effect on photon beam-quality specification.

Two dosimetry protocols based on absorbed dose to water have recently been implemented: TG-51 and TRS-398. These protocols use different beam-quality indices: %dd(10)x and TPR20,10. The effect of electron contamination in measurements of %dd(10)x has been proposed as a disadvantage of the TG-51. For actual measurements of %dd(10)x in five clinical beams (Primus 6-18 MV, SL-75/5 6 MV, SL-18 6-15 MV) a purging magnet was employed to remove the electron contamination. Also, %dd(10)x was measured in the different ways described in TG-51 for high-energy beams: with a lead foil at 50 cm from the phantom surface, at 30 cm, and for open beam. Moreover, TPR20,10 was determined. Also, periodic quality-control measurements were used for comparing both quality indices and variation over time, but D20,10 was used instead of TPR20,10 and measurements in open beam for the %dd(10)x determination. Considering both protocols, S(w,air) and kQ were calculated in order to compare the results with the experimental data. Significant differences (0.3% for kQ) were only found for the two high-energy beams, but when the electron contamination is underestimated by TG-51, the difference in kQ is lower. Differences in the other cases and variations over time were less than 0.1%.

Widespread Horizontal Connections Arising from Layer 5/6 Border Inverted Cells in Rabbit Visual Cortex.

Herein we describe the inverted cells [defined as those projection neurons having a major dendritic shaft abpially oriented (Bueno-López et al., Eur. J. Neurosci., 3, 415, 1991)] originating a unique set of cortical connections characterized by extraordinarily widespread horizontal distribution. Single and multiple injections of wheatgerm agglutinin - horseradish peroxidase were made in areas 17 and 18 and the resulting retrograde labelling in the cortex was analysed. The findings were assessed in independent control experiments in which Fluoro-Gold was used as retrograde tracer. Following single injections in area 17 several separate patches of labelled cells comprising layers 2 - 6 were consistently found in area 18. In addition to these associational cells a number of labelled cells appeared at the layer 5/6 border but were distributed over most of the tangential extent of the visual occipital cortex. This widespread pattern was particularly striking in brains after multiple injections. In these brains a conspicuous band of labelled cells at the 5/6 border radiated from the injection sites, making up an apparently continuous horizontal sheet that intersected the striate - extrastriate boundary and merged with the patches of labelled cells in area 18 and beyond. Most of the cells in the 5/6 border band were inverted cells (82%; n=2081). Injections in area 18 failed to produce such a widespread set of labelled cells in area 17. The functional significance of these connections furnished by the 5/6 border inverted cells remains to be determined, but their distribution would allow for convergent/divergent binding interactions both intra-areally (within area 17) and inter-areally (from area 18 to area 17).

Targets and Laminar Distribution of Projection Neurons with 'Inverted' Morphology in Rabbit Cortex.

This study examines the axonal projections of so-called inverted pyramids and other neurons with their major dendritic shaft oriented in the direction of the white matter ('inverted cells') in the adult rabbit cortex. Single injections of horseradish peroxidase wheat germ agglutinin were made into cortical or subcortical sites. The resulting retrograde labelling in the cortex was analysed and the distribution across areas and layers of inverted cells contributing to each of these projections was estimated. In addition, the radial distribution of inverted cells was independently determined from rapid Golgi-impregnated and Nissl-stained material. All three procedures revealed that inverted cells lay overwhelmingly in infragranular layers, but congregated at the border between layers 5 and 6. Inverted cells, identified by retrograde labelling, seldom furnished non-telencephalic centres; in contrast, these cells constituted a major source for the projections to the ipsi- or the contralateral cortex, the claustrum or the nucleus caudatus. In general, each set of inverted cells (when defined by its specific destination as a group) was located below the typically oriented cells whose axons were aimed at the same target. Thus, the inverted cells of the rabbit cortex are characterized not only by their unique morphology and their corticocortical, corticoclaustral and corticostriatal projections, but also by their distinctive radial locations. These findings suggest that inverted cells, even though possibly composed of different cell types, are a specific class of projection neurons.