Monte Carlo simulation and analytical calculation methods to investigate the potential of nanoparticles for INTRABEAM® IORT machine.

In the present study, Monte Carlo (MC) simulation and analytical calculation methods were used to investigate the potential of cancer treatment for the combination of IORT with nanoparticles (NPs). The Geant4 MC toolkit was used to simulate ZEISS INTRABEAM® IORT machine and its smallest applicator with 1.5 cm diameter. The dose enhancement effects (DEFs) were obtained for silver (Ag), gold (Au), bismuth (Bi), copper (Cu) and iron (Fe) spherical NPs considering different concentrations. In addition, analytical calculations were performed based on attenuation coefficient formula for sample NPs. Our MC results showed that the use of different NPs led to an increase in DEF up to 40%. Among different NPs, Au had the maximum DEF. In addition, analytical calculations revealed a significant increase, using NPs as well. Our study has suggested that the use of NPs in combination with IORT has the potential to enhance treatment outcomes.

The effect of stereotactic body radiotherapy (SBRT) using flattening filter-free beams on cardiac implantable electronic devices (CIEDs) in clinical situations.

PURPOSE: This study focused on determining risks from stereotactic radiotherapy using flattening filter-free (FFF) beams for patients with cardiac implantable electronic device (CIEDs). Two strategies were employed: a) a retrospective analysis of patients with CIEDs who underwent stereotactic radiosurgery (SRS)/SBRT at the Peter MacCallum Cancer Centre between 2014 and 2018 and b) an experimental study on the impact of FFF beams on CIEDs. METHODS: A retrospective review was performed. Subsequently, a phantom study was performed using 30 fully functional explanted CIEDs from two different manufacturers. Irradiation was carried out in a slab phantom with 6-MV and 10-MV FFF beams. First, a repetition-rate test (RRT) with a range of beam pulse frequencies was conducted. Then, multifraction SBRT (48 Gy/4 Fx) and single-fraction SBRT (28 Gy/1 Fx) treatment plans were used for lung tumors delivered to the phantom. RESULTS: Between 2014 and 2018, 13 cases were treated with an FFF beam (6 MV, 1400 MU/min or 10 MV, 2400 MU/min), and 15 cases were treated with a flattening filter (FF) beam (6 MV, 600 MU/min). All the devices were positioned outside the treatment field at a distance of more than 5 cm, except for one case, and no failures were reported due to SBRT/SRS. In the phantom rep-rate tests, inappropriate sensing occurred, starting at a rep-rate of 1200 MU/min. Cardiac implantable electronic device anomalies during and after delivering VMAT-SBRT with a 10-MV FFF beam were observed. CONCLUSIONS: The study showed that caution should be paid to managing CIED patients when they undergo SBRT using FFF beams, as it is recommended by AAPM TG-203. Correspondingly, it was found that for FFF beams although there is small risk from dose-rate effects, delivering high dose of radiation with beam energy greater than 6 MV and high-dose rate to CIEDs positioned in close vicinity of the PTV may present issues.

Malfunction of cardiac devices after radiotherapy without direct exposure to ionizing radiation: mechanisms and experimental data.

AIMS: Malfunctions of cardiac implantable electronical devices (CIED) have been described after high-energy radiation therapy even in the absence of direct exposure to ionizing radiation, due to diffusion of neutrons (n) causing soft errors in inner circuits. The purpose of the study was to analyse the effect of scattered radiation on different types and models of CIED and the possible sources of malfunctions. METHODS AND RESULTS: Fifty-nine explanted CIED were placed on an anthropomorphous phantom of tissue-equivalent material, and a high-energy photon (15 MV) radiotherapy course (total dose = 70 Gy) for prostate treatment was performed. All devices were interrogated before and after radiation. Radiation dose, the electromagnetic field, and neutron fluence at the CIED site were measured. Thirty-four pacemakers (PM) and 25 implantable cardioverter-defibrillators (ICD) were analysed. No malfunctions were detected before radiation. After radiation a software malfunction was evident in 13 (52%) ICD and 6 (18%) PM; no significant electromagnetic field or photon radiations were detected in the thoracic region. Neutron capture was demonstrated by the presence of the (198)Au((197)Au + n) or (192)Ir((191)Ir + n) isotope activation; it was significantly greater in ICD than in PM and non-significantly greater in damaged devices. A greater effect in St Jude PM (2/2 damaged), Boston (9/11), and St Jude ICD (3/6) and in older ICD models was observed; the year of production was not relevant in PM. CONCLUSION: High-energy radiation can cause different malfunctions on CIED, particularly ICD, even without direct exposure to ionizing radiation due to scattered radiation of neutrons produced by the linear accelerator.

In vivo dosimetry and shielding disk alignment verification by EBT3 GAFCHROMIC film in breast IOERT treatment.

Intraoperative electron radiation therapy (IOERT) cannot usually benefit, as conventional external radiotherapy, from software systems of treatment planning based on computed tomography and from common dose verify procedures. For this reason, in vivo film dosimetry (IVFD) proves to be an effective methodology to evaluate the actual radiation dose delivered to the target. A practical method for IVFD during breast IOERT was carried out to improve information on the dose actually delivered to the tumor target and on the alignment of the shielding disk with respect to the electron beam. Two EBT3 GAFCHROMIC films have been positioned on the two sides of the shielding disk in order to obtain the dose maps at the target and beyond the disk. Moreover the postprocessing analysis of the dose distribution measured on the films provides a quantitative estimate of the misalignment between the collimator and the disk. EBT3 radiochromic films have been demonstrated to be suitable dosimeters for IVD due to their linear dose-optical density response in a narrow range around the prescribed dose, as well as their capability to be fixed to the shielding disk without giving any distortion in the dose distribution. Off-line analysis of the radiochromic film allowed absolute dose measurements and this is indeed a very important verification of the correct exposure to the target organ, as well as an estimate of the dose to the healthy tissue underlying the shielding. These dose maps allow surgeons and radiation oncologists to take advantage of qualitative and quantitative feedback for setting more accurate treatment strategies and further optimized procedures. The proper alignment using elastic bands has improved the absolute dose accuracy and the collimator disk alignment by more than 50%.

Assessment of total annual effective doses to representative person, for authorised and accidental releases from the Nuclear Medicine Department at Cattinara Hospital (Trieste, Italy).

PURPOSE: Clinical procedures in a Nuclear Medicine Department produce radioactive liquid and solid waste. Regarding waste release into the environment from an authorised hospital, it is mandatory to verify the compliance with European Directive 2013/59/EURATOM, adopted by the Italian Government via the Legislative Decree 101/2020. METHODS: Different activity release pathways into the environment from Trieste Nuclear Medicine Department have been analysed: liquid waste from patients' excreta discharged by sewage treatment system into the sea, and atmospheric releases following solid waste incineration. Reference models, provided by NCRP and IAEA guidelines, have been implemented to assess the impact of the discharged radioactivity for coastal waters and atmospheric transport conditions. Finally, an accidental fire event occurring in Radiopharmacy Laboratories has been simulated by HotSpot software. RESULTS: Advanced screening models give an effective dose to population of 5.3 · 10-3 µSv/y and 1.4 · 10-4 µSv/y for introduction by sewage system into coastal waters and atmospheric releases by the incinerator, respectively. Workers involved in the maintenance of the sewage treatment plant receive a total annual effective dose of 3.8 µSv/y, while for incinerator staff the total annual exposure is 5.9 · 10-8 µSv/y. For the accidental fire event the maximum total effective dose to an individual results 3.8 · 10-8 Sv with mild wind, and 4.1 · 10-7 Sv with strong wind. CONCLUSIONS: The total annual effective doses estimated to representative person, due to both Nuclear Medicine authorised clinical practices and in case of an accidental fire event, are in compliance with regulatory stipulations provided by Directives.

State of the art in breast intraoperative electron radiation therapy after intraoperative ultrasound introduction.

BACKGROUND: Breast intraoperative electron radiation therapy (B-IOERT) can be used in clinical practice both as elective irradiation (partial breast irradiation - APBI) in low risk breast cancer patients, and as an anticipated boost. The procedure generally includes the use of a shielding disk between the residual breast and the pectoralis fascia for the protection of the tissues underneath the target volume. The aim of the study was to evaluate the role of intraoperative ultrasound (IOUS) in improving the quality of B-IOERT. PATIENTS AND METHODS: B-IOERT was introduced in Trieste in 2012 and its technique was improved in 2014 with IOUS. Both, needle and IOUS were used to measure target thickness and the latter was used even to check the correct position of the shielding disk. The primary endpoint of the study was the evaluation of the effectiveness of IOUS in reducing the risk of a disk misalignment related to B-IOERT and the secondary endpoint was the analysis of acute and late toxicity, by comparing two groups of patients treated with IOERT as a boost, either measured with IOUS and needle (Group 1) or with needle alone (Group 2). Acute and late toxicity were evaluated by validated scoring systems. RESULTS: From the institutional patients who were treated between June 2012 and October 2019, 109 were eligible for this study (corresponding to 110 cases, as one patients underwent bilateral conservative surgery and bilateral B-IOERT). Of these, 38 were allocated to group 1 and 72 to group 2. The target thickness measured with the IOUS probe and with the needle were similar (mean difference of 0.1 mm, p = 0.38). The percentage of patients in which the shield was perfectly aligned after IOUS introduction increased from 23% to more than 70%. Moreover, patients treated after IOUS guidance had less acute toxicity (36.8% vs. 48.6%, p = 0.33) from radiation therapy, which reached no statistical significance. Late toxicity turned out to be similar regardless of the use of IOUS guidance: 39.5% vs. 37.5% (p = 0.99). CONCLUSIONS: IOUS showed to be accurate in measuring the target depth and decrease the misalignment between collimator and disk. Furthermore there was an absolute decrease in acute toxicity, even though not statistically significant, in the group of women who underwent B-IOERT with IOUS guidance.

Neutron and photon out-of-field doses at cardiac implantable electronic device (CIED) depths.

The accuracy of an out-of-field dose from an Elekta Synergy accelerator calculated using the X-ray Voxel Monte Carlo (XVMC) dose algorithm in the Monaco treatment planning system (TPS) for both low-energy (6 MV) and high-energy (15 MV) photons at cardiac implantable electronic device (CIED) depths was investigated through a comparison between MCNPX simulated out-of-field doses and measured out-of-field doses using three high spatial and sensitive active detectors. In addition, total neutron equivalent dose and fluence at CIED depths of a 15-MV dose from an Elekta Synergy accelerator were calculated, and the corresponding CIED relative neutron damage was quantified. The results showed that for 6-MV photons, the XVMC dose algorithm in Monaco underestimated out-of-field doses in all off-axis distances (average errors: -17% at distances X < 10 cm from the field edge and -31% at distances between 10 < X ≤ 16 cm from the field edge), with an increasing magnitude of underestimation for high-energy (15 MV) photons (up to 11%). According to the results, an out-of-field photon dose at a shallower CIED depth of 1 cm was associated with greater statistical uncertainty in the dose estimate compared to a CIED depth of 2 cm and clinical depth of 10 cm. Our results showed that the relative neutron damage at a CIED depth range for 15 MV photon is 36% less than that reported for 18 MV photon in the literature.

A review and analysis of stereotactic body radiotherapy and radiosurgery of patients with cardiac implantable electronic devices.

The implementation of stereotactic body radiation therapy (SBRT) and stereotactic radiosurgery (SRS) has greatly increased due to its convenience and advantages from perspectives ranging from radiobiology to radio physics. Because SBRT/SRS delivers high doses in few fractions, precise dose delivery to target volumes and sufficient sparing of adjacent organs at risk (OARs) are required. Achieving these conflicting objectives is challenging for all patients receiving SBRT/SRS and may be particularly challenging when SBRT/SRS is adopted for treating patients with cardiac implantable electronic devices (CIEDs) because cumulative doses in CIEDs must be limited. Published research considering the different aspects of stereotactic treatment in patients with CIEDs was reviewed to summarise their findings in the following sections: (I) conventional linear accelerator (linac)-based SBRT and SRS; (II) CyberKnife, Gamma-Knife, VERO and helical tomotherapy SBRT and SRS; and (III) proton therapy. A total of 65 patients who had CIEDs and underwent SRS, SBRT, or SABR treatments were identified in the reviewed studies. The functionality of the CIEDs was assessed for 58 patients. Of those, CIED malfunctions (such as data loss, mode change, and inappropriate shock) were reported in four patients (6.89%). This review highlights the available sparse information in the literature by posing questions for future research.

Evaluation of localized region-based segmentation algorithms for CT-based delineation of organs at risk in radiotherapy.

BACKGROUND AND PURPOSE: In radiation therapy, defining the precise borders of cancerous tissues and adjacent normal organs has a significant effect on the therapy outcome. Deformable models offer a unique and robust approach to medical image segmentation. The objective of this study was to investigate the reliability of segmenting organs-at-risk (OARs) using three well-known local region-based level-set techniques. METHODS AND MATERIALS: A total of 1340 non-enhanced and enhanced planning computed tomography (CT) slices of eight OARs (the bladder, rectum, kidney, clavicle, humeral head, femoral head, spinal cord, and lung) were segmented by using local region-based active contour, local Chan-Vese, and local Gaussian distribution models. Quantitative metrics, namely Hausdorff Distance (HD), Mean Absolute Distance (MAD), Dice coefficient (DC), Percentage Volume Difference (PVD) and Absolute Volumetric Difference (AVD), were adopted to measure the correspondence between detected contours and the manual references drawn by experts. RESULTS: The results showed the feasibility of using local region-based active contour methods for defining six of the OARs (the bladder, kidney, clavicle, humeral head, spinal cord, and lung) when adequate intensity information is available. While the most accurate results were achieved for lung (DC = 0.94) and humeral head (DC = 0.92), a poor level of agreement (DC < 0.7) was obtained for both rectum and femur. CONCLUSION: Incorporating local statistical information in level set methods yields to satisfactory results of OARs delineation when adequate intensity information exists between the organs. However, the complexity of adjacent organs and the lack of distinct boundaries would result in a considerable segmentation error.

A multicenter dosimetry study to evaluate the imaging dose from Elekta XVI and Varian OBI kV-CBCT systems to cardiovascular implantable electronic devices (CIEDs).

The increasing use of daily CBCT in radiotherapy has raised concerns about the additional dose delivered to the patient, and it can also become a concern issue for those patients with cardiovascular implantable electronic devices (CIEDs) (Pacemaker [PM] and Implantable Cardioverter Defibrillator [ICD]). Although guidelines highly recommend that the cumulative dose received by CIEDs should be kept as low as possible, and a safe threshold based on patient risk classification needs to be respected, this additional imaging dose is not usually considered. Four centers with different dosimetry systems and different CBCT imaging protocols participated in this multicenter study to investigate the imaging dose to the CIEDs from Elekta XVI and Varian OBI kV-CBCT systems. It was found that although imaging doses received by CIEDs outside the CBCT field are negligible, special attention should be paid to this value when CIEDs are inside the field because the daily use of CBCT can sometimes contribute considerably to the total dose received by a CIED.

Radiotherapy and risk of implantable cardioverter-defibrillator malfunctions: experimental data from direct exposure at increasing doses.

AIM: During radiotherapy, in patients with implantable cardioverter-defibrillators (ICDs) malfunctions are considered more likely if doses more than 2 Gy reach the ICD site; however, most malfunctions occur with high-energy (>10 MV) radiations, and the risk is less defined using 6-MV linear accelerators. The purpose of the study is to experimentally evaluate the occurrence of malfunctions in ICDs radiated with a 6-MV linear accelerator at increasing photon doses. METHODS: Thirty-two ICDs from all manufacturers (31 explanted and one demo) were evaluated; all devices with a sufficient battery charge underwent multiple radiations with a 6-MV photon beam reaching a cumulative dose at ICD site of 0.5, 1, 2, 3, 5 and 10 Gy and interrogated after every session. All antitachycardia therapies were left enabled; two ICDs were connected to a rhythm simulator (one simulating a complete atrioventricular block without ventricular activity) and visually monitored by external ECG and the ICD programmer during radiation. RESULTS: Thirteen ICDs were excluded before radiation because of battery depletion; after radiation up to the cumulative dose at the cardiac implantable electronic device site of 10 Gy, in the remaining 19 devices, programmation and battery charge remained unchanged and no switch to safety mode was observed; oversensing, pacing inhibition or inappropriate antitachycardia therapy were neither recorded nor visually observed during radiation. CONCLUSION: With a low-energy accelerator, neither malfunctions nor electromagnetic interferences were detected radiating the ICDs at doses usually reaching the ICD pocket during radiotherapy sessions. In this context, magnet application to avoid oversensing and inappropriate therapy seems, therefore, useless.

Management of patients with cardiac implantable electronic devices (CIED) undergoing radiotherapy: A consensus document from Associazione Italiana Aritmologia e Cardiostimolazione (AIAC), Associazione Italiana Radioterapia Oncologica (AIRO), Associazione Italiana Fisica Medica (AIFM).

The management of patients with a cardiac implanted electronic device (CIED) receiving radiotherapy (RT) is challenging and requires a structured multidisciplinary approach. A consensus document is presented as a result of a multidisciplinary working group involving cardiac electrophysiologists, radiation oncologists and physicists in order to stratify the risk of patients with CIED requiring RT and approaching RT sessions appropriately. When high radiation doses and beam energy higher than 6MV are used, CIED malfunctions can occur during treatment. In our document, we reviewed the different types of RT and CIED behavior in the presence of ionizing radiations and electromagnetic interferences, from the cardiologist's, radiation oncologist's and medical physicist's point of view. We also reviewed in vitro and in vivo literature data and other national published guidelines on this issue so far. On the basis of literature data and consensus of experts, a detailed approach based on risk stratification and appropriate management of RT patients with CIEDs is suggested, with important implications for clinical practice.

FMECA Application to Intraoperative Electron Beam Radiotherapy Procedure As a Quality Method to Prevent and Reduce Patient's Risk in Conservative Surgery for Breast Cancer.

INTRODUCTION: Failure Mode Effects and Criticalities Analysis (FMECA) represents a prospective method for risk assessment in complex medical practices. Our objective was to describe the application of FMECA approach to intraoperative electron beam radiotherapy (IOERT), delivered using a mobile linear accelerator, for the treatment of early breast cancer as an anticipated boost. MATERIALS AND METHODS: A multidisciplinary Working Group, including several different professional profiles, was created before the beginning of clinical practice in 2012, with the purpose of writing the Flow Chart and applying the FMECA methodology to IOERT procedure. Several criticalities were identified a priori in the different steps of the procedure and a list of all potential failure modes (FMs) was drafted and ranked using the risk priority number (RPN) scoring system, based on the product of three parameters: severity, occurrence, and detectability (score between 1 and 5). The actions aimed at reducing the risk were then defined by the Working Group and the risk analysis was repeated in 2014 and in 2016, in order to assess the improvement achieved. RESULTS: Fifty-one FMs were identified, which represented the issues prospectively investigated according to the FMECA methodology. Considering a set threshold of 30, the evaluated RPNs show that 33 out of 51 FMs are critical; 6 are included in the moderate risk class (RPN: 31-40); 16 in the intermediate risk class (RPN: 41-50), and 11 in the high risk class (RPN: >50). DISCUSSION: The most critical steps concerned the surgical procedure and IOERT set-up. The introduction of the corrective actions into the clinical practice achieved the reduction of the RPNs in the re-analysis of the FMECA worksheet after 2 and 4 years, respectively. CONCLUSION: FMECA proved to be a useful tool for prospective evaluation of potential failures in IOERT and contributed to optimize patient safety and to improve risk management culture among all the professionals of the Working Group.