PURPOSE:In 2018, the Netherlands Commission on Radiation Dosimetry subcommittee on IORT initiated a limited intercomparison of electron IORT (IOERT) in Belgium and The Netherlands. The participating institutions have enough variability in age, type of equipment, and in dose calibration protocols.METHODS:In this study, three types of IOERT-dedicated mobile accelerators were represented: Mobetron 2000, LIAC HWL and LIAC. Mobetron produces electron beams with energies of 6, 9 and 12 MeV, while LIAC HWL and LIAC can deliver 6, 8, 10 and 12 MeV electron beams. For all energies, the reference beam (10 cm diameter, 0° incidence) and 5 cm diameter beams were measured, as these smaller beams are used more frequently in clinic. The mailed TLD service from the Radiation Dosimetry Services (RDS, Houston, USA) has been used. Following RDS' standard procedures, each beam was irradiated to 300 cGy at dmax with TLDs around dmax and around depth of 50 % dose (R50). Absolute dose at 100 % and beam energy, expressed as R50, could be verified in this way.RESULTS:All absolute doses and energies under reference conditions were well within RDS-stated uncertainties: dose deviations were <5 % and deviations in R50 were <5 mm. For the small 5 cm beams, all results were also within acceptance levels except one absolute dose value. Deviations were not significantly dependent on manufacturer, energy, diameter and calibration protocol.CONCLUSIONS:All absolute dose values, except one of a non-reference beam, and all energy values were well within the measurement accuracy of RDS TLDs.

Purpose Embolization of arteriovenous malformations (AVMs) before radiosurgery has been reported to negatively impact the obliteration rate. This study aims to assess treatment outcomes in a series of 190 patients treated by Gamma Knife radiosurgery (GKRS) for previously embolized AVMs. Methods The institutional database of AVMs was retrospectively reviewed between January 2004 and March 2018. The clinical and radiological data of patients treated with GKRS for previously embolized AVMs were analyzed. Predicting factors of obliteration and hemorrhage following GKRS were assessed with univariate and multivariate regression analyses. Results The mean AVM size was significantly reduced after embolization (p < 0.001). The obliteration rate was 78.4%. Multivariate analyses showed that a lower Spetzler-Martin grade (p = 0.035) and a higher marginal dose (p = 0.007) were associated with obliteration. Post-GKRS hemorrhages occurred in 14 patients (7.4%). A longer time between diagnosis and GKRS was the only factor associated with post-GKRS hemorrhages in multivariate analysis (p = 0.022). Complications related to the combined treatment were responsible for a new permanent neurological disability in 20 patients (10.5%), and a case of death (0.5%). Conclusions This study shows that the embolization of AVMs does not have a negative impact on the obliteration rate after radiosurgery. Embolization reduces the AVM size to a treatable volume by GKRS. However, the combined treatment results in an increased complication rate related to the addition of the risks of each treatment modality.

Background Intraoperative electron radiotherapy (IOERT) can be used to treat early breast cancer during the conservative surgery thus enabling shorter overall treatment times and reduced irradiation of organs at risk. We report on our first 996 patients enrolled prospectively in a registry trial. Methods At Jules Bordet Institute, from February 2010 onwards, patients underwent partial IOERT of the breast. Women with unifocal invasive ductal carcinoma, aged 40 years or older, with a clinical tumour size ≤ 20 mm and tumour-free sentinel lymph node (on frozen section and immunohistochemical analysis). A 21 Gy dose was prescribed on the 90% isodose line in the tumour bed with the energy of 6 to 12 MeV (Mobetron®-IntraOp Medical). Results Thirty-seven ipsilateral tumour relapses occurred. Sixteen of those were in the same breast quadrant. Sixty patients died, and among those, 12 deaths were due to breast cancer. With 71.9 months of median follow-up, the 5-year Kaplan–Meier estimate of local recurrence was 2.7%. Conclusions The rate of breast cancer local recurrence after IOERT is low and comparable to published results for IORT and APBI. IOERT is highly operator-dependent, and appropriate applicator sizing according to tumour size is critical. When used in a selected patient population, IOERT achieves a good balance between tumour control and late radiotherapy-mediated toxicity morbidity and mortality thanks to insignificant irradiation of organs at risk.

Purpose/objective: The objective of this study was to verify the accuracy of treatment plans of stereotactic body radiation therapy (SBRT) and to verify the feasibility of the use of Monte Carlo (MC) as quality control (QC) on a daily basis. Material/methods: Using EGSnrc, a MC model of Agility T linear accelerator was created. Various measurements (Percentage depth dose (PDD), Profiles and Output factors) were done for different fields sizes from 1x1 up to 40x40 (cm(2)). An iterative model optimization was performed to achieve adequate parameters of MC simulation. 40 SBRT patient's dosimetry plans were calculated by Monaco T 3.1.1. CT images, RT-STRUCT and RT-PLAN files from Monaco T being used as input for Moderato MC code. Finally, dose volume histogram (DVH) and paired t-tests for each contour were used for dosimetry comparison of the Monaco T and MC. Results: Validation of MC model was successful, as <2% difference comparing to measurements for all field's sizes. The main energy of electron source incident on the target was 5.8 MeV, and the full width at half maximum (FWHM) of Gaussian electron source were 0.09 and 0.2 (cm) in X and Y directions, respectively. For 40 treatment plan comparisons, the minimum absolute difference of mean dose of planning treatment planning (PTV) was 0.1% while the maximum was 6.3%. The minimum absolute difference of Max dose of PTV was 0.2% while the maximum was 8.1%. Conclusion: SBRT treatment plans of Monaco agreed with MC results. It possible to use MC for treatment plans verifications as independent QC tool.

Radiotherapy (RT) in patients with melanoma historically showed suboptimal results, because the disease is often radioresistant due to various mechanisms such as scavenging free radicals by thiols, pigmentary machinery, or enhanced DNA repair. However, radiotherapy has been utilized as adjuvant therapy after the complete excision of primary melanoma and lymph nodes to reduce the rate of nodal recurrences in high-risk patients. The resistance of melanoma cells to radiotherapy may also be in relation with the constitutive activation of the MAPK pathway and/or with the inactivation of p53 observed in about 90% of melanomas. In this study, we aimed to assess the potential benefit of adding RT to BRAF-mutated melanoma cells under a combined p53 reactivation and MAPK inhibition in vitro and in a preclinical animal model. We found that the combination of BRAF inhibition (vemurafenib, which completely shuts down the MAPK pathway), together with p53 reactivation (PRIMA-1Met) significantly enhanced the radiosensitivity of BRAF-mutant melanoma cells. This was accompanied by an increase in both p53 expression and activity. Of note, we found that radiation alone markedly promoted both ERK and AKT phosphorylation, thus contributing to radioresistance. The combination of vemurafenib and PRIMA-1Met caused the inactivation of both MAPK kinase and PI3K/AKT pathways. Furthermore, when combined with radiotherapy, it was able to significantly enhance melanoma cell radiosensitivity. Interestingly, in nude mice bearing melanoma xenografts, the latter triple combination had not only a synergistic effect on tumor growth inhibition, but also a potent control on tumor regrowth in all animals after finishing the triple combination therapy. RT alone had only a weak effect. In conclusion, we provide a basis for a strategy that may overcome the radioresistance of BRAF-mutated melanoma cells to radiotherapy. Whether this will translate into a rational to use radiotherapy in the curative setting in BRAF-mutated melanoma patients deserves consideration.

Purpose: The current study investigates the usefulness of metabolic positron emission tomography (PET) imaging (in particular with 11C-methionine (MET)), for target definition during gamma knife radiosurgery (GKRS) of locally multirecurrent malignant glioma at inoperable stage. Patients and Methods: We retrospectively evaluated the results of GKRS with MET-PET targeting for 24 adult focally recurrent inoperable malignant gliomas treated at the Erasme Gamma Knife Center between 2007 and 2018. We evaluated the type of tumour progression (local vs remote), progression-free survival (PFS), overall survival (OS) and toxicity after MET-PET targeting of GKRS for these 24 patients. Results: The median PFS after GKRS for the 24 patients with malignant gliomas was 5.5 (2-46) months and 4.5 (3-10), 4.5 (2-8) and 13.5 (2-46) months for glioblastoma, anaplastic glioma and grade II glioma patients, respectively. The median OS from the GKRS procedure for patients with recurrent glioblastomas (n=12) was 18 (6-45) months, 8 (6-184) months for anaplastic gliomas (n=6), and 22 (16-65) months for grade II gliomas (n=6). All patients with grade III and II multirecurrent gliomas (n=12) showed an early favourable local metabolic response, while this response was observed only in 6/12 of the glioblastomas. However, the majority (9/12=75%) of these grade II/III glioma patients further developed new lesions. GKRS treatment was associated with diverse chemotherapies in more than 50% (13/24) of cases. Post-GKRS radio-necrosis was observed in only one patient. Conclusion: Based on a limited series of 24 patients, our study shows, for the first time, the GKRS-induced metabolic response in focally recurrent inoperable malignant gliomas. GKRS could be part of the multidisciplinary approach for multirecurrent malignant gliomas that cannot be anymore treated by surgery.

PurposeThis paper studies the feasibility of using Monte Carlo (MC) for treatment planning of intraoperative electron radiation therapy (IOERT) procedure to get 3D dose by using patient’s CT images.MethodsThe IOERT treatment planning was performed using the following successive steps:I) The Mobetron 1000® machine was modelled with the EGSnrc MC codes. II) The MC model was validated with measurements of percentage depth doses and profiles for three energies (12, 9, 6) MeV. III) CT images were imported as DICOM files. IV) Contouring of the planning target volume (PTV) and the organs at risk was done by the radiation oncologist. V) The medical physicist with the radiation oncologist, had chosen the same parameters of IOERT procedures like energy, applicator (type, size) and using or not bolus. VI) Finally, dose calculation and analysis of 3D maps was carried out.ResultsThe tuning process of the MC model provides good results, as the maximum value of the root mean square deviation (RMSD) was less than 3% between the MC simulated PDDs and the measured PDDs. The contouring and dose analysis review were easy to conduct for the classical treatment planning system. The radiation oncologist had many tools for dose analysis such as DVH and color wash for all the slides. Summation of the 3D dose of IOERT with other radiotherapy plans is possible and helpful for total dose estimation. Archiving and documentation is as good as treatment planning system (TPS).ConclusionsThe method displayed in this paper provides a step forward for IOERT Dosimetry and allows to obtain accurate dosimetry of treated volumes.

PURPOSE:In IOERT breast treatments, a shielding disk is frequently used to protect the underlying healthy structures. The disk is usually composed of two materials, a low-Z material intended to be oriented towards the beam and a high-Z material. As tissues are repositioned around the shield before treatment, the disk is no longer visible and its correct alignment with respect to the beam is guaranteed. This paper studies the dosimetric characteristics of four possible clinical positioning scenarios of the shielding disk. A new alignment method for the shielding disk in the beam is introduced. Finally, it suggests a new design for the shielding disk.METHODS:As the first step, the IOERT machine "Mobetron 1000" was modeled by using Monte Carlo simulation, tuning the MC model until an excellent match with the measured PDDs and profiles was achieved. Four possible shielding disk positioning scenarios were considered, determining the dosimetric impact. Furthermore, in our center, to prevent beam misalignment, we have developed a shielding disk equipped with guiding rods. Having ascertained a correct alignment between the disk and the beam, we can propose a new internal design of the shielding disk that can improve the dose distribution with a better coverage of the treated area.RESULTS:All MC simulations were performed with a 12 MeV beam, the maximum energy of Mobetron 1000 and a 5.5 cm diameter flat tip applicator, this applicator being the most clinically used. The simulations were compared with measurements performed in a water phantom and showed good results within 2.2% of root mean square difference (RMSD). The misplacement positions of the shielding disk have dosimetric impacts in the treatment volume and a small translation could have a significant influence on healthy tissues. The D-scenario is the worst which could happens when the shielding disk is flipped upside down, giving up to 144% dose instead of 90% at the surface of the Pb/Al shielding disk. A new shielding design used, together with our alignment tool, is able to give a more homogeneous dose in the target area.CONCLUSIONS:The accuracy of shielding disk position can still be problematic in IOERT dosimetry. Any method that can ascertain the good alignment between the shielding disk and the beam is beneficial for the dose distribution and is a prerequisite for an optimized shield internal design that could improve the coverage of the treated area and the protection of healthy tissues.

dict the delivered absorbed dose distribution, allowing comparison with the TPS.EPID images were taken during 6MV treatment delivery, with a dose rate of 600 MU/min, from aSi1000 EPID (Varian).Mounted with Exact-arm on a Clinac 23iX equipped with a multi-leaf collimator (120 leaves).The EPID were acquired using the half-resolution mode.2D plane images were calculated in Eclipse TM at the maximum depth dose in a water phantom.Results.Learning was performed using 11 input/output datasets from IMRT treatments.All of the used datasets (both EPID inputs and absorbed dose distribution outputs) consisted of 384 Â 512 pixels.Learning can be time consuming but once the ANN has been fixed, its use during the recognition phase will be instantaneous.The gamma index, c, was used to evaluate the difference between the ANN calculated and planned distributions.c gives the number of pixels (as a percentage) that respect a given objective.c (2% , 2 mm) for Head and Neck cancers was found to be 99.7%, highlighting the ANN capability to predict the absorbed dose distribution based on EPIDs.Conclusions.It was shown that patient-specific quality assurance of IMRT based on EPID can be performed with neural networks algorithms.Next work would be extending algorithms for in vivo dosimetry purpose.

Object. The authors review their experience with the clinical development and routine use of positron emission tomography (PET) during stereotactic procedures, including the use of PET-guided gamma knife radiosurgery (GKS). Methods. Techniques have been developed for the routine use of stercotactic PET, and accumulated experience using PET-guided stereotactic procedures over the past 10 years includes more than 150 stereotactic biopsies, 43 neuronavigation procedures, and 34 cases treated with GKS. Positron emission tomography-guided GKS was performed in 24 patients with primary brain tumors (four pilocytic astrocytomas, five low-grade astrocytomas or oligodendrogliomas, seven anaplastic astrocytomas or ependymomas, five glioblastomas, and three neurocytomas), five patients with metastases (single or multiple lesions), and five patients with pituitary adenomas. Conclusions. Data obtained with PET scanning can be integrated with GKS treatment planning, enabling access to metabolic information with high spatial accuracy. Positron emission tomography data can be successfully combined with magnetic resonance imaging data to provide specific information for defining the target volume for the radiosurgical treatment in patients with recurrent brain tumors, such as glioma, metastasis, and pituitary adenoma. This approach is particularly useful for optimizing target selection for infiltrating or ill-defined brain lesions. The use of PET scanning contributed data in 31 cases (93%) and information that was specifically utilized to adapt the target volume in 25 cases (74%). It would seem that the integration of PET data into GKS treatment planning may represent an important step toward further developments in radiosurgery: this approach provides additional information that may open new perspectives for the optimization of the treatment of brain tumors.

Background: The objective of this study is to study prognostic factors of survival and 3 stratification systems for life expectancy estimation in patients with brain stem metastases treated with radiosurgery.Methods: Between December 1999 and November 2006, 25 patients with 27 brain stem metastases were treated with Gamma Knife radiosurgery. The lesions' mean volume was 0.6 mL (0.013-3.6 mL). The mean marginal dose was 20 Gy (15-24 Gy). Univariate and multivariate studies were done to identify prognostic factors, and 3 patient stratification systems were applied for survival estimation: RPA, SIR, and BSBM.Results: The primary turner location was in the lungs in 12 patients, breast in 8, and other in 5. Fourteen lesions were located in the pons, 9 in the midbrain, and 4 in the medulla. All patients were followed clinically. Radiologic follow-up was available in 21 lesions (78%). Tumor control was achieved in all but one followed lesion (95%). There were no complications related to treatment. Median survival of patients with brain stem metastases was 11.1 months. In multivariate analysis, KPS of 80 or more, control of the primary tumor, absence of radiotherapy, and a marginal dose higher than 18 Gy were associated with better survival., The BSBM in the univariate and multivariate analyses was the strongest predictor of survival (P < .0001).Conclusions: The BSBM was the most useful tool for estimating survival. Rather than the brain stem location of an intracranial metastasis, the patient integral clinical status seems to be more important in determining survival. (C) 2009 Elsevier Inc. All rights reserved.

Beside basic physical notions such as ionizing radiation, beam production and beam characteristics, this chapter will focus on two major principles that should always be considered in a radiosurgery procedure: conformity and selectivity. Those parameters are influenced by different physical beam properties, by the type of beam delivery device and by the way the dose is delivered. Conformity and selectivity should be evaluated for each treatment with the help of some specific indices, i.e. target volume ratio and normal volume ratio based on the dose-volume histograms.

Objective: The purpose of this work is to investigate the extracranial doses in vivo during intracranial treatments comparing the Gamma Knife system with the Novalis system for identical pathologies. The analysis is limited to single fraction stercotactic radiosurgeries. Methods: Measurements were performed with TL dosimeters positioned on the lateral canthus, thyroid, breasts and gonads to obtain the dose received to these anatomical regions. Based on these observations, an estimate of the risk for cancer induction and detriment will be proposed. The measured doses were normalized to 24 Gy, and the influence of target maximum dose, reference isodose volume, equivalent treatment time (which is related to the activity of the "Co sources for the Gamma Knife) and distance on extracranial doses are analyzed. Results: The average extracranial dose with a normalized prescription dose of 24 Gy is comparable for both machines. Gamma Knife: For the lateral canthus, thyroid, breast and gonads the median doses were 435, 103, 48, and 6 mGy, respectively. Novalis: For the lateral canthus, thyroid, breast and gonads the median doses were 234, 79, 45, and 3 mGy, respectively. For the Gamma Knife system as well as the Novalis system no correlation could be found between maximum dose, reference isodose volume and extracranial doses. On the other hand, for the Gamma Knife system the equivalent treatment time and distance have a significant influence on doses received on extracranial sites. For the Novalis system only the distance and the geographical placement of the arcs will influence the extracranial dose. Conclusions: Doses to extracranial sites are small, ranging from 1.4% of the prescribed dose (24 Gy) for the lateral canthus to 0.02% for the gonads for the Gamma Knife and in the range of 0.97% of the prescribed dose (24 Gy) for the lateral canthus, to 0.01% for the gonads for the Novalis. According to ICRP-60, the risk for cancer induction after a radiosurgical treatment is estimated to about 0.2% for both the Gamma Knife and Novalis systems; the risk for detriment is estimated at 0.3% for both systems. Although these risks are very small, they must be kept to a minimum value for long life expectancy patients, by choosing the appropriate treatment strategy. Copyright (c) 2006 S. Karger AG, Basel.