GEC-ESTRO survey of 106Ru eye applicator practice for ocular melanoma - Physicist survey.

AIM: 106Ru eye plaque brachytherapy (BT, interventional radiotherapy) is an eye-preserving treatment for uveal melanoma performed in about 100 clinics worldwide. Despite this relatively low number, there is a considerable variation in clinical practice. In 2022, the BRAPHYQS and Head & Neck and Skin GEC-ESTRO working groups conducted a survey to map the current clinical practice. The survey consisted of a physicist and a physician part. This paper describes the physicist results. However, three physician questions with overlapping interest are included here as well. MATERIALS AND METHODS: The survey questions pertained to commissioning and quality control (QC) of the plaques, treatment planning, radiobiological correction, as well as more general questions on practice improvement. The questions overlapping with the physician survey were related to dose prescription and margins. RESULTS: Sixty-five physicist responses were included. A majority of the centres do not perform an independent measurement of the absorbed dose at reference depth, percentage depth dose (PDD) and off-axis data. A lack of calibration services and suitable equipment are the main reasons. About one third of the centres indicated that they do image based treatment planning. The use of margins and dose prescription showed a large variability, despite the availability of guidelines [1]. Many respondents expressed a strong wish for improvement in a wide range of aspects of clinical practice. CONCLUSION: The physics survey showed a wide variability regarding quality control of the 106Ru sources and treatment planning practice.

Robust stochastic optimization of needle configurations for robotic HDR prostate brachytherapy.

BACKGROUND: Ideally, inverse planning for HDR brachytherapy (BT) should include the pose of the needles which define the trajectory of the source. This would be particularly interesting when considering the additional freedom and accuracy in needle pose which robotic needle placement enables. However, needle insertion typically leads to tissue deformation, resulting in uncertainty regarding the actual pose of the needles with respect to the tissue. PURPOSE: To efficiently address uncertainty during inverse planning for HDR BT in order to robustly optimize the pose of the needles before insertion, that is, to facilitate path planning for robotic needle placement. METHODS: We use a form of stochastic linear programming to model the inverse treatment planning problem. To account for uncertainty, we consider random tissue displacements at the needle tip to simulate tissue deformation. Conventionally for stochastic linear programming, each simulated deformation is reflected by an addition to the linear programming problem which increases problem size and computational complexity substantially and leads to impractical runtime. We propose two efficient approaches for stochastic linear programming. First, we consider averaging dose coefficients to reduce the problem size. Second, we study weighting of the slack variables of an adjusted linear problem to approximate the full stochastic linear program. We compare different approaches to optimize the needle configurations and evaluate their robustness with respect to different amounts of tissue deformation. RESULTS: Our results illustrate that stochastic planning can improve the robustness of the treatment with respect to deformation. The proposed approaches approximating stochastic linear programming better conform to the tissue deformation compared to conventional linear programming. They show good correlation with the plans computed after deformation while reducing the runtime by two orders of magnitude compared to the complete stochastic linear program. Robust optimization of needle configurations takes on average 59.42 s. Skew needle configurations lead to mean coverage improvements compared to parallel needles from 0.39 to 2.94 percentage points, when 8 mm tissue deformation is considered. Considering tissue deformations from 4  to 10 mm during planning with weighted stochastic optimization and skew needles generally results in improved mean coverage from 1.77 to 4.21 percentage points. CONCLUSIONS: We show that efficient stochastic optimization allows selecting needle configurations which are more robust with respect to potentially negative effects of target deformation and displacement on the achievable prescription dose coverage. The approach facilitates robust path planning for robotic needle placement.

Geometric accuracy in patient positioning for stereotactic radiotherapy of intracranial tumors.

Background/Purpose: This study determines and compares the geometric setup errors between stereoscopic x-ray and kilo-voltage cone beam CT (CBCT) in phantom tests on a linear accelerator (linac) for image-guided (IG) stereotactic radiotherapy of intracranial tumors. Additionally, dose-volume metrics in the target volumes of the setup errors of CBCT were evaluated. Materials/Methods: A Winston-Lutz- and an anthropomorphic phantom were used. The mean deviation and root mean square error (RMSE) of CBCT and stereoscopic x-ray were compared. Dose-volume metrics of the planning target volume (PTV) and gross target volume (GTV) for CBCT were calculated. Results: The RMSEs in the tests with the Winston-Lutz-Phantom were 0.3 mm, 1.1 mm and 0.3 mm for CBCT and 0.1 mm, 0,1 mm and <0.1 mm for stereoscopic x-ray in the translational dimensions (right-left, anterior-posterior and superior-inferior). The RMSEs in the tests with the anthropomorphic phantom were 0.3 mm, 0.2 mm and 0.1 mm for CBCT and 0.1 mm, 0,1 mm and <0.1 mm for stereoscopic x-ray. The effects on dose-volume metrics of the setup errors of CBCT on the GTV were within 1 % for all considered dose values. The effects on the PTV were within 5 % for all considered dose values. Conclusion: Both IG systems provide high accuracy patient positioning within a submillimeter range. The phantom tests exposed a slightly higher accuracy of stereoscopic x-ray than CBCT. The comparison with other studies with a similar purpose emphasizes the importance of individual IG installation quality assurance.

Multilayer intensity modulated contact interventional radiotherapy (brachytherapy): Stretching the therapeutic window in skin cancer.

Interventional radiotherapy (IRT, brachytherapy) is a highly effective treatment method for non-melanoma skin cancer (NMSC). Traditionally, the maximum depth of NMSC lesions considered eligible for contact IRT was 5 mm; however, following several national surveys and recent recommendations, such cut-off, lesions thicker than 5 mm may be treated by contact IRT. The use of image guidance in defining the actual depth in treating NMSC to correctly identify clinical target volume (CTV) and prevent unnecessary toxicity is of paramount importance. The aim of the paper was to describe a multilayer arrangement of catheters to treat NMSC lesions thicker than 5 mm, thus proposing an example of dynamic intensity modulated IRT, using different catheter-to-skin distance of sources to reach the best CTV coverage and maximally reduce the excess of dose to the skin.

AAPM WGDCAB Report 372: A joint AAPM, ESTRO, ABG, and ABS report on commissioning of model-based dose calculation algorithms in brachytherapy.

The introduction of model-based dose calculation algorithms (MBDCAs) in brachytherapy provides an opportunity for a more accurate dose calculation and opens the possibility for novel, innovative treatment modalities. The joint AAPM, ESTRO, and ABG Task Group 186 (TG-186) report provided guidance to early adopters. However, the commissioning aspect of these algorithms was described only in general terms with no quantitative goals. This report, from the Working Group on Model-Based Dose Calculation Algorithms in Brachytherapy, introduced a field-tested approach to MBDCA commissioning. It is based on a set of well-characterized test cases for which reference Monte Carlo (MC) and vendor-specific MBDCA dose distributions are available in a Digital Imaging and Communications in Medicine-Radiotherapy (DICOM-RT) format to the clinical users. The key elements of the TG-186 commissioning workflow are now described in detail, and quantitative goals are provided. This approach leverages the well-known Brachytherapy Source Registry jointly managed by the AAPM and the Imaging and Radiation Oncology Core (IROC) Houston Quality Assurance Center (with associated links at ESTRO) to provide open access to test cases as well as step-by-step user guides. While the current report is limited to the two most widely commercially available MBDCAs and only for 192 Ir-based afterloading brachytherapy at this time, this report establishes a general framework that can easily be extended to other brachytherapy MBDCAs and brachytherapy sources. The AAPM, ESTRO, ABG, and ABS recommend that clinical medical physicists implement the workflow presented in this report to validate both the basic and the advanced dose calculation features of their commercial MBDCAs. Recommendations are also given to vendors to integrate advanced analysis tools into their brachytherapy treatment planning system to facilitate extensive dose comparisons. The use of the test cases for research and educational purposes is further encouraged.

Radiosurgery for ventricular tachycardia (RAVENTA): interim analysis of a multicenter multiplatform feasibility trial.

BACKGROUND: Single-session cardiac stereotactic radiation therapy (SBRT) has demonstrated promising results for patients with refractory ventricular tachycardia (VT). However, the full safety profile of this novel treatment remains unknown and very limited data from prospective clinical multicenter trials are available. METHODS: The prospective multicenter multiplatform RAVENTA (radiosurgery for ventricular tachycardia) study assesses high-precision image-guided cardiac SBRT with 25 Gy delivered to the VT substrate determined by high-definition endocardial and/or epicardial electrophysiological mapping in patients with refractory VT ineligible for catheter ablation and an implanted cardioverter defibrillator (ICD). Primary endpoint is the feasibility of full-dose application and procedural safety (defined as an incidence of serious [grade ≥ 3] treatment-related complications ≤ 5% within 30 days after therapy). Secondary endpoints comprise VT burden, ICD interventions, treatment-related toxicity, and quality of life. We present the results of a protocol-defined interim analysis. RESULTS: Between 10/2019 and 12/2021, a total of five patients were included at three university medical centers. In all cases, the treatment was carried out without complications. There were no serious potentially treatment-related adverse events and no deterioration of left ventricular ejection fraction upon echocardiography. Three patients had a decrease in VT episodes during follow-up. One patient underwent subsequent catheter ablation for a new VT with different morphology. One patient with local VT recurrence died 6 weeks after treatment in cardiogenic shock. CONCLUSION: The interim analysis of the RAVENTA trial demonstrates early initial feasibility of this new treatment without serious complications within 30 days after treatment in five patients. Recruitment will continue as planned and the study has been expanded to further university medical centers. TRIAL REGISTRATION NUMBER: NCT03867747 (clinicaltrials.gov). Registered March 8, 2019. Study start: October 1, 2019.

Evaluation of sentinel lymph node localization in malignant melanoma by preoperative semiconductor gamma camera and planar lymphoscintigraphy.

INTRODUCTION: Performing lymphoscintigraphy in a separate room, frees up the conventional gamma camera, coupled with the desire to directly localize sentinel lymph nodes (SLN) in the operating theatre has led to the development of high-resolution semiconductor-detector based handheld gamma-cameras, CrystalCam. METHODS: This work consists of phantom and clinical studies. For the first part, a Jaszczak phantom with hollow spheres of various volumes were filled with the 99m Tc and the camera's sensitivity was measured at various distances to assess the possibilities and limitations of the device. The clinical study evaluates the effectiveness of CrystalCam in localizing SLN in 40 consecutive malignant melanoma patients compared to both conventional planar lymphoscintigraphy and hybrid SPECT/CT. SLNs detected by planar lymphoscintigraphy were marked on the patients' skin using a UV-marker. CrystalCam images were acquired in another room by another examiner and the SLNs were marked with a felt pen. The detected nodes by both camera systems were evaluated using UV-lamp and normal light to visualize the UV- and felt pen marks respectively. The concordance rate of the SLNs and higher-echelon nodes localized by both planar scintigraphy and CrystalCam imaging with respect to the total SLNs and higher-echelon nodes detected by SPECT/CT imaging are compared and statistically analyzed. RESULTS: The results of the phantom study show a good correlation between activity and count-rates for all distancesSPECT/CT, CrystalCamm, and planar lymphoscintigraphy detected 69, 58, and 61 SLNs respectively. The concordance rate of 95.65% by the CrystalCam and planar scintigraphy implies both cameras are statistically coequal in preoperative SLN detection of malignant melanoma. For the higher-echelon nodes, SPECT/CT, planar and CrystalCam imaging systems identified 82, 48, and 13 respectively; thus, CrystalCam was statistically inferior to planar imaging. CONCLUSION: The handheld CrystalCam is a reliable instrument for localizing SLNs in surgical centers without an on-site nuclear medicine department.

ATTR- and AFib amyloid - two different types of amyloid in the annular ligament of trigger finger.

INTRODUCTION: Histological examination of tissue specimens obtained during surgical treatment of trigger finger frequently encountered unclassifiable amyloid deposits in the annular ligament. We systematically explored this unknown type by a comprehensive analysis using histology, immunohistochemistry, and quantitative mass spectrometry-based proteomics. METHODS: 205 tissue specimens of annular ligaments were obtained from 172 patients. Each specimen was studied by histology and immunohistochemistry. Tissue specimens obtained from ten patients with histology proven amyloid in annular ligament were analysed by label-free quantitative proteomics. Histological and immunohistochemical findings were correlated with patient demographics. RESULTS: Amyloid was present as band like deposits along the surface of annular ligament, dot like or patchy deposits within the matrix. Immunohistochemistry identified ATTR amyloid in 92 specimens (mostly patchy in the matrix), while the band like deposits of 100 specimens remained unclassifiable. Proteomic profiles identified the unknown amyloid as most likely of fibrinogen origin. The complete cohort was re-examined by immunohistochemistry using a custom-made antibody and confirmed the presence of fibrinogen alpha-chain (FGA) in a hitherto unclassifiable type of amyloid in annular ligament. CONCLUSION: Our study shows that two different types of amyloid affect the annular ligament, ATTR amyloid and AFib amyloid, with distinct demographic patient characteristics and histomorphological deposition patterns.

A MC-based anthropomorphic test case for commissioning model-based dose calculation in interstitial breast 192-Ir HDR brachytherapy.

PURPOSE: To provide the first clinical test case for commissioning of 192 Ir brachytherapy model-based dose calculation algorithms (MBDCAs) according to the AAPM TG-186 report workflow. ACQUISITION AND VALIDATION METHODS: A computational patient phantom model was generated from a clinical multi-catheter 192 Ir HDR breast brachytherapy case. Regions of interest (ROIs) were contoured and digitized on the patient CT images and the model was written to a series of DICOM CT images using MATLAB. The model was imported into two commercial treatment planning systems (TPSs) currently incorporating an MBDCA. Identical treatment plans were prepared using a generic 192 Ir HDR source and the TG-43-based algorithm of each TPS. This was followed by dose to medium in medium calculations using the MBDCA option of each TPS. Monte Carlo (MC) simulation was performed in the model using three different codes and information parsed from the treatment plan exported in DICOM radiation therapy (RT) format. Results were found to agree within statistical uncertainty and the dataset with the lowest uncertainty was assigned as the reference MC dose distribution. DATA FORMAT AND USAGE NOTES: The dataset is available online at http://irochouston.mdanderson.org/rpc/BrachySeeds/BrachySeeds/index.html,https://doi.org/10.52519/00005. Files include the treatment plan for each TPS in DICOM RT format, reference MC dose data in RT Dose format, as well as a guide for database users and all files necessary to repeat the MC simulations. POTENTIAL APPLICATIONS: The dataset facilitates the commissioning of brachytherapy MBDCAs using TPS embedded tools and establishes a methodology for the development of future clinical test cases. It is also useful to non-MBDCA adopters for intercomparing MBDCAs and exploring their benefits and limitations, as well as to brachytherapy researchers in need of a dosimetric and/or a DICOM RT information parsing benchmark. Limitations include specificity in terms of radionuclide, source model, clinical scenario, and MBDCA version used for its preparation.

Errors detected during physics plan review for external beam radiotherapy.

Background and purpose: Risk management in radiotherapy is of high importance. There is not much data published on errors occurring in the treatment planning process of external beam techniques. The aim of this study was to investigate errors occurring during physics plan review in external beam radiotherapy. Materials and methods: Over a period of 14 months errors observed during the physical review process are reported. The errors were grouped and evaluated regarding treatment machine, technique, and treatment site. In addition, a correlation between frequency of errors and staff shortage was analyzed. Results: Subgroups of grave errors (g-errors) and slight errors (s-errors) were defined to consider the different impact on the patient and clinical workflow of the errors. In 1056 plans reviewed, 110 errors (41 g-errors, 69 s-errors) were detected. The most common g-errors and s-errors were "Wrong gantry angle at setup field" (n = 19) and "Wrong field label" (n = 24), respectively. A correlation of number of errors and treatment machine, technique, or anatomical site could not be found. No correlation between staff shortage and number of errors was observed. Conclusions: The process of reviewing treatment plans is a relevant topic to consider in risk analysis of the radiotherapy workflow. The review process could be improved by enhancements in the treatment planning systems, use of digital dose prescription, and treatment planning templates.

GEC-ESTRO ACROP recommendations on calibration and traceability of HE HDR-PDR photon-emitting brachytherapy sources at the hospital level.

The vast majority of radiotherapy departments in Europe using brachytherapy (BT) perform temporary implants of high- or pulsed-dose rate (HDR-PDR) sources with photon energies higher than 50 keV. Such techniques are successfully applied to diverse pathologies and clinical scenarios. These recommendations are the result of Working Package 21 (WP-21) initiated within the BRAchytherapy PHYsics Quality Assurance System (BRAPHYQS) GEC-ESTRO working group with a focus on HDR-PDR source calibration. They provide guidance on the calibration of such sources, including practical aspects and issues not specifically accounted for in well-accepted societal recommendations, complementing the BRAPHYQS WP-18 Report dedicated to low energy BT photon emitting sources (seeds). The aim of this report is to provide a European-wide standard in HDR-PDR BT source calibration at the hospital level to maintain high quality patient treatments.

H&N and Skin (HNS) GEC-ESTRO Working Group critical review of recommendations regarding prescription depth, bolus thickness and maximum dose in skin superficial brachytherapy with flaps and customized moulds.

The aim of this publication is the assessment of the existing guidelines for non-melanoma skin cancer (NMSC) superficial brachytherapy (BT) and make a critical review based on the existing literature about the maximum dose prescription depth, bolus thickness and maximum skin surface dose (Dmax) of the published clinical practice. A systematic review of NMSC superficial BT published articles was carried out by the GEC-ESTRO Head & Neck and Skin (HNS) Working Group (WG). 10 members and 2 external reviewers compared the published clinical procedures with the recommendations in the current guidelines and examined the grade of evidence. Our review verified that there is a large variation among centres with regards to clinical practice in superficial BT and identified studies where published parameters such as maximum dose prescription depth, bolus thickness and Dmax exceed the constraints recommended in the guidelines, while showing excellent results in terms of local control, toxicity and cosmesis. This review confirmed that current recommendations on skin superficial BT do not include published experience on tumours treated with superficial BT that require dose prescription depth beyond the recommended 5 mm under the skin surface and that the existing literature does not provide sufficient evidence to relate dosimetry of superficial BT to patient reported outcome measures. The GEC-ESTRO HNS WG considers acceptable to prescribe superficial BT dose at a depth above 5 mm beyond the skin surface, and modify the bolus thickness to optimize the treatment plan and adjust the acceptable maximum dose on the skin surface, all pending clinical situation.

Evaluation of dosimetric effects of metallic artifact reduction and tissue assignment on Monte Carlo dose calculations for 125 I prostate implants.

PURPOSE: Monte Carlo (MC) simulation studies, aimed at evaluating the magnitude of tissue heterogeneity in 125 I prostate permanent seed implant brachytherapy (BT), customarily use clinical post-implant CT images to generate a virtual representation of a realistic patient model (virtual patient model). Metallic artifact reduction (MAR) techniques and tissue assignment schemes (TAS) are implemented on the post-implant CT images to mollify metallic artifacts due to BT seeds and to assign tissue types to the voxels corresponding to the bright seed spots and streaking artifacts, respectively. The objective of this study is to assess the combined influence of MAR and TAS on MC absorbed dose calculations in post-implant CT-based phantoms. The virtual patient models used for 125 I prostate implant MC absorbed dose calculations in this study are derived from the CT images of an external radiotherapy prostate patient without BT seeds and prostatic calcifications, thus averting the need to implement MAR and TAS. METHODS: The geometry of the IsoSeed I25.S17plus source is validated by comparing the MC calculated results of the TG-43 parameters for the line source approximation with the TG-43U1S2 consensus data. Four MC absorbed dose calculations are performed in two virtual patient models using the egs_brachy MC code: (1) TG-43-based Dw,w-TG 43 , (2) Dw,w-MBDC that accounts for interseed scattering and attenuation (ISA), (3) Dm,m that examines ISA and tissue heterogeneity by scoring absorbed dose in tissue, and (4) Dw,m that unlike Dm,m scores absorbed dose in water. The MC absorbed doses (1) and (2) are simulated in a TG-43 patient phantom derived by assigning the densities of every voxel to 1.00 g cm-3 (water), whereas MC absorbed doses (3) and (4) are scored in the TG-186 patient phantom generated by mapping the mass density of each voxel to tissue according to a CT calibration curve. The MC absorbed doses calculated in this study are compared with VariSeed v8.0 calculated absorbed doses. To evaluate the dosimetric effect of MAR and TAS, the MC absorbed doses of this work (independent of MAR and TAS) are compared to the MC absorbed doses of different 125 I source models from previous studies that were calculated with different MC codes using post-implant CT-based phantoms generated by implementing MAR and TAS on post-implant CT images. RESULTS: The very good agreement of TG-43 parameters of this study and the published consensus data within 3% validates the geometry of the IsoSeed I25.S17plus source. For the clinical studies, the TG-43-based calculations show a D90 overestimation of more than 4% compared to the more realistic MC methods due to ISA and tissue composition. The results of this work generally show few discrepancies with the post-implant CT-based dosimetry studies with respect to the D90 absorbed dose metric parameter. These discrepancies are mainly Type B uncertainties due to the different 125 I source models and MC codes. CONCLUSIONS: The implementation of MAR and TAS on post-implant CT images have no dosimetric effect on the 125 I prostate MC absorbed dose calculation in post-implant CT-based phantoms.

Treatment Planning for Cardiac Radioablation: Multicenter Multiplatform Benchmarking for the RAdiosurgery for VENtricular TAchycardia (RAVENTA) Trial.

PURPOSE: Cardiac radioablation is a novel treatment option for patients with refractory ventricular tachycardia unsuitable for catheter ablation. The quality of treatment planning depends on dose specifications, platform capabilities, and experience of the treating staff. To harmonize the treatment planning, benchmarking of this process is necessary for multicenter clinical studies such as the RAdiosurgery for VENtricular TAchycardia trial. METHODS AND MATERIALS: Planning computed tomography data and consensus structures from 3 patients were sent to 5 academic centers for independent plan development using a variety of platforms and techniques with the RAdiosurgery for VENtricular TAchycardia study protocol serving as guideline. Three-dimensional dose distributions and treatment plan details were collected and analyzed. In addition, an objective relative plan quality ranking system for ventricular tachycardia treatments was established. RESULTS: For each case, 3 coplanar volumetric modulated arc (VMAT) plans for C-arm linear accelerators (LINAC) and 3 noncoplanar treatment plans for robotic arm LINAC were generated. All plans were suitable for clinical applications with minor deviations from study guidelines in most centers. Eleven of 18 treatment plans showed maximal one minor deviation each for target and cardiac substructures. However, dose-volume histograms showed substantial differences: in one case, the planning target volume ≥30 Gy ranged from 0.0% to 79.9% and the ramus interventricularis anterior V14Gy ranged from 4.0% to 45.4%. Overall, the VMAT plans had steeper dose gradients in the high-dose region, while the plans for the robotic arm LINAC had smaller low-dose regions. Thereby, VMAT plans required only about half as many monitor units, resulting in shorter delivery times, possibly an important factor in treatment outcome. CONCLUSIONS: Cardiac radioablation is feasible with robotic arm and C-arm LINAC systems with comparable plan quality. Although cross-center training and best practice guidelines have been provided, further recommendations, especially for cardiac substructures, and ranking of dose guidelines will be helpful to optimize cardiac radioablation outcomes.

GEC-ESTRO ACROP prostate brachytherapy guidelines.

This is an evidence-based guideline for prostate brachytherapy. Throughout levels of evidence quoted are those from the Oxford Centre for Evidence based Medicine (https://www.cebm.ox.ac.uk/resources/levels-of-evidence/oxford-centre-for-evidence-based-medicine-levels-of-evidence-march-2009). Prostate interstitial brachytherapy using either permanent or temporary implantation is an established and evolving treatment technique for non-metastatic prostate cancer. Permanent brachytherapy uses Low Dose Rate (LDR) sources, most commonly I-125, emitting photon radiation over months. Temporary brachytherapy involves first placing catheters within the prostate and, on confirmation of accurate positioning, temporarily introducing the radioactive source, generally High Dose Rate (HDR) radioactive sources of Ir-192 or less commonly Co-60. Pulsed dose rate (PDR) brachytherapy has also been used for prostate cancer [1] but few centres have adopted this approach. Previous GEC ESTRO recommendations have considered LDR and HDR separately [2-4] but as there is considerable overlap, this paper provides updated guidance for both treatment techniques. Prostate brachytherapy allows safe radiation dose escalation beyond that achieved using external beam radiotherapy alone as it has greater conformity around the prostate, sparing surrounding rectum, bladder, and penile bulb. In addition there are fewer issues with changes in prostate position during treatment delivery. Systematic review and randomised trials using both techniques as boost treatments demonstrate improved PSA control when compared to external beam radiotherapy alone [5-7].

Quantitative proteome profiling provides evidence of an activation of the complement cascade in ATTR amyloidosis.

Amyloidosis is a disease group caused by pathological aggregation and deposition of peptides in diverse tissue sites. Apart from the fibril protein, amyloid deposits frequently enclose non-fibrillar constituents. In this study, carpal tunnel tissue sections with ATTR amyloid were analysed by quantitative mass spectrometry-based proteomics. Following manual dissection, tissue samples of equal size and with heterogeneous amyloid load were dissected and forwarded to bottom-up proteome analysis and label-free protein profiling. The amyloid-associated proteins showed significant correlations of label-free intensity profiles. A comprehensive list of 83 proteins specifically enriched in amyloid deposits was discovered. In addition to well-known signature proteins (e.g. apolipoprotein E, apolipoprotein A-IV, and vitronectin), 22 members of the complement system, including all seven components of the membrane attack complex could be associated to the disease. These data lend support to the hypothesis that the complement system is activated in ATTR amyloidosis.

Source strength determination in iridium-192 and cobalt-60 brachytherapy: A European survey on the level of agreement between clinical measurements and manufacturer certificates.

BACKGROUND AND PURPOSE: Brachytherapy treatment outcomes depend on the accuracy of the delivered dose distribution, which is proportional to the reference air-kerma rate (RAKR). Current societal recommendations require the medical physicist to compare the measured RAKR values to the manufacturer source calibration certificate. The purpose of this work was to report agreement observed in current clinical practice in the European Union. MATERIALS AND METHODS: A European survey was performed for high- and pulsed-dose-rate (HDR and PDR) high-energy sources (192Ir and 60Co), to quantify observed RAKR differences. Medical physicists at eighteen hospitals from eight European countries were contacted, providing 1,032 data points from 2001 to 2020. RESULTS: Over the survey period, 77% of the 192Ir measurements used a well chamber instead of the older Krieger phantom method. Mean differences with the manufacturer calibration certificate were 0.01% ± 1.15% for 192Ir and -0.1% ± 1.3% for 60Co. Over 95% of RAKR measurements in the clinic were within 3% of the manufacturer calibration certificate. CONCLUSIONS: This study showed that the agreement level was generally better than that reflected in prior societal recommendations positing 5%. Future recommendations on high-energy HDR and PDR source calibrations in the clinic may consider tightened agreements levels.

Professional practice changes in radiotherapy physics during the COVID-19 pandemic.

BACKGROUND AND PURPOSE: The COVID-19 pandemic has imposed changes in radiotherapy (RT) departments worldwide. Medical physicists (MPs) are key healthcare professionals in maintaining safe and effective RT. This study reports on MPs experience during the first pandemic peak and explores the consequences on their work. METHODS: A 39-question survey on changes in departmental and clinical practice and on the impact for the future was sent to the global MP community. A total of 433 responses were analysed by professional role and by country clustered on the daily infection numbers. RESULTS: The impact of COVID-19 was bigger in countries with high daily infection rate. The majority of MPs worked in alternation at home/on-site. Among practice changes, implementation and/or increased use of hypofractionation was the most common (47% of the respondents). Sixteen percent of respondents modified patient-specific quality assurance (QA), 21% reduced machine QA, and 25% moved machine QA to weekends/evenings. The perception of trust in leadership and team unity was reversed between management MPs (towards increased trust and unity) and clinical MPs (towards a decrease). Changes such as home-working and increased use of hypofractionation were welcomed. However, some MPs were concerned about pressure to keep negative changes (e.g. weekend work). CONCLUSION: COVID-19 affected MPs through changes in practice and QA procedures but also in terms of trust in leadership and team unity. Some changes were welcomed but others caused worries for the future. This report forms the basis, from a medical physics perspective, to evaluate long-lasting changes within a multi-disciplinary setting.

Quality Assurance in Modern Gynecological HDR-Brachytherapy (Interventional Radiotherapy): Clinical Considerations and Comments.

The use of brachytherapy (interventional radiotherapy) in the treatment of gynecological cancers is a crucial element in both definitive and adjuvant settings. The recent developments in high-dose rate remote afterloaders, modern applicators, treatment-planning software, image guidance, and dose monitoring systems have led to improvement in the local control rates and in some cases improved the survival rates. The development of these highly advanced and complicated treatment modalities has been accompanied by challenges, which have made the existence of quality assurance protocols a must to ensure the integrity of the treatment process. Quality assurance aims at standardizing the technical and clinical procedures involved in the treatment of patients, which could eventually decrease the source of uncertainties whether technical (source/equipment related) or clinical. This commentary review sheds light (from a clinical point of view) on some potential sources of uncertainties associated with the use of modern brachytherapy in the treatment of gynecological cancers.

Interdisciplinary Clinical Target Volume Generation for Cardiac Radioablation: Multicenter Benchmarking for the RAdiosurgery for VENtricular TAchycardia (RAVENTA) Trial.

PURPOSE: Cardiac radioablation is a novel treatment option for therapy-refractory ventricular tachycardia (VT) ineligible for catheter ablation. Three-dimensional clinical target volume (CTV) definition is a key step, and this complex interdisciplinary procedure includes VT-substrate identification based on electroanatomical mapping (EAM) and its transfer to the planning computed tomography (PCT). Benchmarking of this process is necessary for multicenter clinical studies such as the RAVENTA trial. METHODS AND MATERIALS: For benchmarking of the RAVENTA trial, patient data (epicrisis, electrocardiogram, high-resolution EAM, contrast-enhanced cardiac computed tomography, PCT) of 3 cases were sent to 5 university centers for independent CTV generation, subsequent structure analysis, and consensus finding. VT substrates were first defined on multiple EAM screenshots/videos and manually transferred to the PCT. The generated structure characteristics were then independently analyzed (volume, localization, surface distance and conformity). After subsequent discussion, consensus structures were defined. RESULTS: VT substrate on the EAM showed visible variability in extent and localization for cases 1 and 2 and only minor variability for case 3. CTVs ranged from 6.7 to 22.9 cm3, 5.9 to 79.9 cm3, and 9.4 to 34.3 cm3; surface area varied from 1087 to 3285 mm2, 1077 to 9500 mm2, and 1620 to 4179 mm2, with a Hausdorff-distance of 15.7 to 39.5 mm, 23.1 to 43.5 mm, and 15.9 to 43.9 mm for cases 1 to 3, respectively. The absolute 3-dimensional center-of-mass difference was 5.8 to 28.0 mm, 8.4 to 26 mm, and 3.8 to 35.1 mm for cases 1 to 3, respectively. The entire process resulted in CTV structures with a conformity index of 0.2 to 0.83, 0.02 to 0.85, and 0.02 to 0.88 (ideal 1) with the consensus CTV as reference. CONCLUSIONS: Multicenter efficacy endpoint assessment of cardiac radioablation for therapy-refractory VT requires consistent CTV transfer methods from the EAM to the PCT. VT substrate definition and CTVs were comparable with current clinical practice. Remarkable differences regarding the degree of agreement of the CTV definition on the EAM and the PCT were noted, indicating a loss of agreement during the transfer process between EAM and PCT. Cardiac radioablation should be performed under well-defined protocols and in clinical trials with benchmarking and consensus forming.