Focused ultrasound therapy in movement disorders: management roadmap toward optimal pathway organization.

MRI-guided focused ultrasound (MRgFUS) lesioning is an innovative, safe and effective treatment which provides an innovative development in the field of minimally invasive stereotactic neurosurgery. Based on the application of focused ultrasound energy under full MR planning and thermal imaging control, unilateral lesioning of the thalamus, subthalamic nucleus, and globus pallidus is indicated for the treatment of movement disorders, including essential tremor, Parkinson's disease, and dystonia. We started to apply this technique in February 2019 for the treatment of patients with movement disorders. The authors developed a diagnostic therapeutic care pathway, which is herewith proposed and applied as an explication of standard clinical practice in use. The project was the result of the application of different methods such as Health Technology Assessment (HTA), Strengths, Weaknesses, Opportunities and Threats analysis (SWOT) and Demin -Plan, Do, Check, Act (PDCA) cycle. The aim of this project was to standardize the MRgFUS diagnostic-therapeutic pathway (DTP), describe its application and the appropriateness of different phases (patient selection, intervention phase and follow-up). Here, we described in detail our experience in the DTP application from 2019 up to now in 610 patients with movement disorders.

On the evaluation of edgeless diode detectors for patient-specific QA in high-dose stereotactic radiosurgery.

PURPOSE: In this work, the potential of an innovative "edgeless" silicon diode was evaluated as a response to the still unmet need of a reliable tool for plan dosimetry verification of very high dose, non-coplanar, patient-specific radiosurgery treatments. In order to prove the effectiveness of the proposed technology, we focused on radiosurgical treatments for functional disease like tremor or pain. METHODS: The edgeless diodes response has been validated with respect to clinical practice standard detectors by reproducing the reference dosimetry data adopted for the Treatment Planning System. In order to evaluate the potential for radiosurgery patient-specific treatment plan verification, the anthropomorphic phantom Alderson RANDO has been adopted along with three edgeless sensors, one placed in the centre of the Planning Target Volume, one superiorly and one inferiorly. RESULTS: The reference dosimetry data obtained from the edgeless detectors are within 2.6% for output factor, off-axis ratio and well within 2% for tissue phantom ratio when compared to PTW 60,018 diode. The edgeless detectors measure a dose discrepancy of approximately 3.6% from the mean value calculated by the TPS. Larger discrepancies are obtained in very steep gradient dose regions when the sensors are placed outside the PTV. CONCLUSIONS: The angular independent edgeless diode is proposed as an innovative dosimeter for patient quality assurance of brain functional disorders and other radiosurgery treatments. The comparison of the diode measurements with TPS calculations confirms that edgeless diodes are suitable candidates for patient-specific dosimetric verification in very high dose ranges delivered by non-isocentric stereotactic radiosurgery modalities.

Additive Fabrication of a Vascular 3D Phantom for Stereotactic Radiosurgery of Arteriovenous Malformations.

In this study, an efficient methodology for manufacturing a realistic three-dimensional (3D) cerebrovascular phantom resembling a brain arteriovenous malformation (AVM) for applications in stereotactic radiosurgery is presented. The AVM vascular structure was 3D reconstructed from brain computed tomography (CT) data acquired from a patient. For the phantom fabrication, stereolithography was used to produce the AVM model and combined with silicone casting to mimic the brain parenchyma surrounding the vascular structure. This model was made with tissues-equivalent materials for radiology. The hollow vascular system of the phantom was filled with a contrast agent usually employed on patients for CT scans. The radiological response of the phantom was tested and compared with the one of the clinical case. The constructed model demonstrated to be a very accurate physical representation of the AVM and its vasculature and good morphological consistency was observed between the model and the patient-specific source anatomy. These results suggest that the proposed method has potential to be used to fabricate patient-specific phantoms for neurovascular radiosurgery applications and medical research.

Sum signal dosimetry: A new approach for high dose quality assurance with Gafchromic EBT3.

Gafchromic EBT3 film dosimetry in radiosurgery (RS) and hypofractionated radiotherapy (HRT) is complicated by the limited film accuracy at high fractional doses. The aim of this study is to develop and evaluate sum signal (SS) film dosimetry to increase dose resolution at high fractional doses, thus allowing for use of EBT3 for dose distribution verification of RS/HRT treatments. To characterize EBT3 dose-response, a calibration was performed in the dose range 0.44-26.43 Gy. Red (RC) and green (GC) channel net optical densities were linearly added to produce the SS. Dose resolution and overall accuracy of the dosimetric protocol were estimated and compared for SS,RC, and GC. A homemade Matlab software was developed to compare, in terms of gamma analysis, dose distributions delivered by a Cyberknife on EBT3 films to dose distributions calculated by the treatment planning system. The new SS and conventional single channel (SC) methods were compared, using 3%/1 and 4%/1 mm acceptance criteria, for 20 patient plans. Our analysis shows that the SS dose-response curve is characterized by a steeper trend in comparison with SC, with SS providing a higher dose resolution in the whole dose range investigated. Gamma analysis confirms that the percentage of points satisfying the agreement criteria is significantly higher for SS compared to SC: 95.03% vs. 88.41% (P = 0.014) for 3%/1 mm acceptance criteria and 97.24% vs. 93.58% (P = 0.048) for 4%/1 mm acceptance criteria. This study demonstrates that the SS approach is a new and effective method to improve dosimetric accuracy in the framework of the RS-HRT patient-specific quality assurance protocol.

CyberKnife beam output factor measurements: A multi-site and multi-detector study.

PURPOSE: New promising detectors are available for measuring small field size output factors (OFs). This study focused on a multicenter evaluation of two new generation detectors for OF measurements on CyberKnife systems. METHODS: PTW-60019 microDiamond and W1 plastic scintillation detector (PSD) were used to measure OFs on eight CyberKnife units of various generations for 5-60mm fixed cones. MicroDiamond and PSD OF were compared to routinely used silicon diodes data corrected applying published Monte Carlo (MC) factors. PSD data were corrected for Cerenkov Light Ratio (CLR). The uncertainties related to CLR determination were estimated. RESULTS: Considering OF values averaged over all centers, the differences between MC corrected diode and the other two detectors were within 1.5%. MicroDiamond exhibited an over-response of 1.3% at 7.5mm and a trend inversion at 5mm with a difference of 0.2%. This behavior was consistent among the different units. OFs measured by PSD slightly under-responded compared to MC corrected diode for the smaller cones and the differences were within 1%. The observed CLR variability was 2.5% and the related variation in OF values was 1.9%. CONCLUSION: This study indicates that CyberKnife microDiamond OF require corrections below 2%. The results are enhanced by the consistency observed among different units. Scintillator shows a good agreement to MC corrected diode but CLR determination remains critical requiring further investigations. The results emphasized the value of a multi-center validation over a single center approach.

Multicenter evaluation of a synthetic single-crystal diamond detector for CyberKnife small field size output factors.

PURPOSE: The aim of the present work was to evaluate small field size output factors (OFs) using the latest diamond detector commercially available, PTW-60019 microDiamond, over different CyberKnife systems. OFs were measured also by silicon detectors routinely used by each center, considered as reference. METHODS: Five Italian CyberKnife centers performed OFs measurements for field sizes ranging from 5 to 60mm, defined by fixed circular collimators (5 centers) and by Iris(™) variable aperture collimator (4 centers). Setup conditions were: 80cm source to detector distance, and 1.5cm depth in water. To speed up measurements two diamond detectors were used and their equivalence was evaluated. MonteCarlo (MC) correction factors for silicon detectors were used for comparing the OF measurements. RESULTS: Considering OFs values averaged over all centers, diamond data resulted lower than uncorrected silicon diode ones. The agreement between diamond and MC corrected silicon values was within 0.6% for all fixed circular collimators. Relative differences between microDiamond and MC corrected silicon diodes data for Iris(™) collimator were lower than 1.0% for all apertures in the totality of centers. The two microDiamond detectors showed similar characteristics, in agreement with the technical specifications. CONCLUSIONS: Excellent agreement between microDiamond and MC corrected silicon diode detectors OFs was obtained for both collimation systems fixed cones and Iris(™), demonstrating the microDiamond could be a suitable detector for CyberKnife commissioning and routine checks. These results obtained in five centers suggest that for CyberKnife systems microDiamond can be used without corrections even at the smallest field size.

Multisession Radiosurgery for Sellar and Parasellar Benign Meningiomas: Long-term Tumor Growth Control and Visual Outcome.

BACKGROUND: Concern about radiation-induced optic neuropathy (RION) has governed recent thinking about the role of radiation therapy in the treatment of meningiomas involving the anterior optic pathways. Despite this concern, during the last few years, the use of radiosurgery for such lesions has increased steadily. OBJECTIVE: To define both the tumor control rate and the risk of RION over a long-term follow-up period in a large cohort of patients treated with multisession radiosurgery. METHODS: The local control and visual outcome of 143 patients who underwent multisession radiosurgery (mRS) were evaluated. Neurological outcome was also analyzed. The data for the present study were obtained from a prospectively maintained database. RESULTS: The mean follow-up was 44 months (range, 12-113 months). All patients underwent mRS. The median prescription dose was 25 Gy delivered in 3 to 5 fractions. The prescription isodose, which typically encompassed at least 95% of the tumor, ranged from 65% to 86% (median, 80%). The mean tumor volume was 11.0 cm (range, 0.1-126.3 cm; median, 8 cm). The progression-free survival at 3, 5, and 8 years was 100%, 93%, and 90%, respectively. Compared with baseline, visual function improved in 36% of patients, whereas 7.4% experienced a worsening in visual function (5.1% excluding the patients with progressive disease). CONCLUSION: Good local control rate and a low risk of RION indicate that mRS is a safe and effective treatment option in cases of large meningiomas.

Multi-institutional application of Failure Mode and Effects Analysis (FMEA) to CyberKnife Stereotactic Body Radiation Therapy (SBRT).

BACKGROUND: A multidisciplinary and multi-institutional working group applied the Failure Mode and Effects Analysis (FMEA) approach to assess the risks for patients undergoing Stereotactic Body Radiation Therapy (SBRT) treatments for lesions located in spine and liver in two CyberKnife® Centres. METHODS: The various sub-processes characterizing the SBRT treatment were identified to generate the process trees of both the treatment planning and delivery phases. This analysis drove to the identification and subsequent scoring of the potential failure modes, together with their causes and effects, using the risk probability number (RPN) scoring system. Novel solutions aimed to increase patient safety were accordingly considered. RESULTS: The process-tree characterising the SBRT treatment planning stage was composed with a total of 48 sub-processes. Similarly, 42 sub-processes were identified in the stage of delivery to liver tumours and 30 in the stage of delivery to spine lesions. All the sub-processes were judged to be potentially prone to one or more failure modes. Nineteen failures (i.e. 5 in treatment planning stage, 5 in the delivery to liver lesions and 9 in the delivery to spine lesions) were considered of high concern in view of the high RPN and/or severity index value. CONCLUSIONS: The analysis of the potential failures, their causes and effects allowed to improve the safety strategies already adopted in the clinical practice with additional measures for optimizing quality management workflow and increasing patient safety.

Evaluation of the peripheral dose in stereotactic radiotherapy and radiosurgery treatments.

PURPOSE: The main purpose of this work was to compare peripheral doses absorbed during stereotactic treatment of a brain lesion delivered using different devices. These data were used to estimate the risk of stochastic effects. METHODS: Treatment plans were created for an anthropomorphic phantom and delivered using a LINAC with stereotactic cones and a multileaf collimator, a CyberKnife system (before and after a supplemental shielding was applied), a TomoTherapy system, and a Gamma Knife unit. For each treatment, 5 Gy were prescribed to the target. Measurements were performed with thermoluminescent dosimeters inserted roughly in the position of the thyroid, sternum, upper lung, lower lung, and gonads. RESULTS: Mean doses ranged from of 4.1 (Gamma Knife) to 62.8 mGy (LINAC with cones) in the thyroid, from 2.3 (TomoTherapy) to 30 mGy (preshielding CyberKnife) in the sternum, from 1.7 (TomoTherapy) to 20 mGy (preshielding CyberKnife) in the upper part of the lungs, from 0.98 (Gamma Knife) to 15 mGy (preshielding CyberKnife) in the lower part of the lungs, and between 0.3 (Gamma Knife) and 10 mGy (preshielding CyberKnife) in the gonads. CONCLUSIONS: The peripheral dose absorbed in the sites of interest with a 5 Gy fraction is low. Although the risk of adverse side effects calculated for 20 Gy delivered in 5 Gy fractions is negligible, in the interest of optimum patient radioprotection, further studies are needed to determine the weight of each contributor to the peripheral dose.