Intracranial Hemorrhage in Patients with Anticoagulant Therapy Undergoing Stereotactic Radiosurgery for Brain Metastases: A Bi-Institutional Analysis

Background: Stereotactic radiosurgery (SRS) is a well-established treatment modality for brain metastases (BM). Given the manifold implications of metastatic cancer on the body, affected patients have an increased risk of comorbidities, such as atrial fibrillation (AF) and venous thromboembolism (VTE), which includes pulmonary embolism (PE) and deep-vein thrombosis (DVT). These may require therapeutic anticoagulant therapy (ACT). Limited data are available on the risk of intracranial hemorrhage (ICH) after SRS for patients with BM who are receiving ACT. This bi-institutional analysis aimed to describe the bleeding risk for this patient subgroup. Methods: Patients with ACT at the time of single-fraction SRS for BM from two institutions were eligible for analysis. The cumulative incidence of ICH with death as a competing event was assessed during follow-up with magnetic resonance imaging or computed tomography. Results: Forty-one patients with 97 BM were included in the analyses. The median follow-up was 8.2 months (range: 1.7-77.5 months). The median and mean BM volumes were 0.47 and 1.19 cubic centimeters, respectively. The most common reasons for ACT were PE (41%), AF (34%), and DVT (7%). The ACT was mostly performed utilizing phenprocoumon (37%), novel oral anticoagulants (32%), or low-molecular-weight heparin (20%). Nine BM from a group of five patients with ICH after SRS were identified: none of them caused neurological or any other deficits. The 6-, 12-, and 18-month cumulative bleeding incidences per metastasis were 2.1%, 12.4%, and 12.4%, respectively. The metastases with previous bleeding events and those originating from malignant melanomas were found to more frequently demonstrate ICH after SRS (p = 0.02, p = 0.01). No surgical or medical intervention was necessary for ICH management, and no observed death was associated with an ICH. Conclusion: Patients receiving an ACT and single-fraction SRS for small- to medium-sized BM did not seem to have a clinically relevant risk of ICH. Previous bleeding and metastases originating from a malignant melanoma may favor bleeding events after SRS. Further studies are needed to validate our reported findings

Meningioma involving the superior sagittal sinus: long-term outcome after robotic radiosurgery in primary and recurrent situation

ObjectiveTreatment for meningiomas involving the superior sagittal sinus (SSS) is challenging and proved to be associated with higher risks compared to other brain locations. Therapeutical strategies may be either microsurgical (sub-)total resection or adjuvant radiation, or a combination of both. Thrombosis or SSS occlusion following resection or radiosurgery needs to be further elucidated to assess whether single or combined treatment is superior. We here present tumor control and side effect data of robotic radiosurgery (RRS) in combination with or without microsurgery.MethodsFrom our prospective database, we identified 137 patients with WHO grade I meningioma involving the SSS consecutively treated between 2005 and 2020. Treatment decisions were interdisciplinary. Patients underwent RRS as initial/solitary treatment (group 1), as adjuvant treatment after subtotal resection (group 2), or due to recurrent tumor growth after preceding microsurgery (group 3). Positive tumor response was assessed by MRI and defined as reduction of more than 50% of volume. Study endpoints were time to recurrence (TTR), time to RRS, risk factors for decreased survival, and side effects. Overall and specific recurrence rates for treatment groups were analyzed. Side effect data included therapy-related morbidity during follow-up (FU).ResultsA total of 137 patients (median age, 58.3 years) with SSS meningiomas WHO grade I were analyzed: 51 patients (37.2%) in group 1, 15 patients (11.0%) in group 2, and 71 patients (51.8%) in group 3. Positive MR (morphological response) to therapy was achieved in 50 patients (36.4%), no response was observed in 25 patients (18.2%), and radiological tumor progression was detected in 8 patients (5.8%). Overall 5-year probability of tumor recurrence was 15.8% (median TTR, 41.6 months). Five-year probabilities of recurrence were 0%, 8.3.%, and 21.5% for groups 1–3 (p = 0.06). In multivariate analysis, tumor volume was significantly associated with extent of SSS occlusion (p = 0.026) and sex (p = 0.011). Tumor volume significantly correlated with TTR (p = 0.0046). Acute sinus venous thrombosis or venous congestion-associated bleedings did not occur in any of the groups.ConclusionRRS for grade I meningiomas with SSS involvement represents a good option as first-line treatment, occasionally also in recurrent and adjuvant scenarios as part of a multimodal treatment strategy

Convolutional Neural Networks to Detect Vestibular Schwannomas on Single MRI Slices: A Feasibility Study.

In this study. we aimed to detect vestibular schwannomas (VSs) in individual magnetic resonance imaging (MRI) slices by using a 2D-CNN. A pretrained CNN (ResNet-34) was retrained and internally validated using contrast-enhanced T1-weighted (T1c) MRI slices from one institution. In a second step, the model was externally validated using T1c- and T1-weighted (T1) slices from a different institution. As a substitute, bisected slices were used with and without tumors originating from whole transversal slices that contained part of the unilateral VS. The model predictions were assessed based on the categorical accuracy and confusion matrices. A total of 539, 94, and 74 patients were included for training, internal validation, and external T1c validation, respectively. This resulted in an accuracy of 0.949 (95% CI 0.935-0.963) for the internal validation and 0.912 (95% CI 0.866-0.958) for the external T1c validation. We suggest that 2D-CNNs might be a promising alternative to 2.5-/3D-CNNs for certain tasks thanks to the decreased demand for computational power and the fact that there is no need for segmentations. However, further research is needed on the difference between 2D-CNNs and more complex architectures

The Role of Stereotactic Radiosurgery in the Management of Foramen Magnum Meningiomas—A Multicenter Analysis and Review of the Literature

Background: Foramen magnum meningiomas (FMMs) represent a considerable neurosurgical challenge given their location and potential morbidity. Stereotactic radiosurgery (SRS) is an established non-invasive treatment modality for various benign and malignant brain tumors. However, reports on single-session or multisession SRS for the management and treatment of FMMs are exceedingly rare. We report the largest FMM SRS series to date and describe our multicenter treatment experience utilizing robotic radiosurgery. Methods: Patients who underwent SRS between 2005 and 2020 as a treatment for a FMM at six different centers were eligible for analysis. Results: Sixty-two patients met the inclusion criteria. The median follow-up was 28.9 months. The median prescription dose and isodose line were 14 Gy and 70%, respectively. Single-session SRS accounted for 81% of treatments. The remaining patients received three to five fractions, with doses ranging from 19.5 to 25 Gy. Ten (16%) patients were treated for a tumor recurrence after surgery, and thirteen (21%) underwent adjuvant treatment. The remaining 39 FMMs (63%) received SRS as their primary treatment. For patients with an upfront surgical resection, histopathological examination revealed 22 World Health Organization grade I tumors and one grade II FMM. The median tumor volume was 2.6 cubic centimeters. No local failures were observed throughout the available follow-up, including patients with a follow-up ≥ five years (16 patients), leading to an overall local control of 100%. Tumor volume significantly decreased after treatment, with a median volume reduction of 21% at the last available follow-up (p < 0.01). The one-, three-, and five-year progression-free survival were 100%, 96.6%, and 93.0%, respectively. Most patients showed stable (47%) or improved (21%) neurological deficits at the last follow-up. No high-grade adverse events were observed. Conclusions: SRS is an effective and safe treatment modality for FMMs. Despite the paucity of available data and previous reports, SRS should be considered for selected patients, especially those with subtotal tumor resections, recurrences, and patients not suitable for surgery

Thermoluminescence dosemeters as biologically relevant detectors

Zsfassung in dt. SpracheDie genaue Messung der absorbierten Strahlendosis und deren Übersetzung in ein potentielles Gesundheitsrisiko bilden die Grundlage für den Strahlenschutz. Durch jüngste Erkenntnisse in der Strahlenbiologie wurde die etablierte makroskopische Betrachtung der Strahlenwirkung um wesentliche Aspekte ergänzt. Dies gilt insbesondere für die Wirkung von niedrigen Dosen hochenergetischer geladener Teilchen, bei denen sich die Energiedeposition im Gewebe weitgehend auf kleine Volumina entlang der Teilchenspuren beschränkt.Die am Atominstitut entwickelte High Temperature Ratio (HTR)-Methode zur Auswertung von LiF:Mg,Ti Thermolumineszenz (TL)-Detektoren erlaubt die gleichzeitige Bestimmung der absorbierten Dosis und des effektiven linearen Energietransfers (LET). Der HTR stellt dabei ein mikrodosimetrisches Maß für die Strahlenqualität dar, was die Möglichkeit einer direkten Beurteilung des biologischen Schadenspotentials aus der Messung in Aussicht stellt.Die Korrelation von TL-Messgrößen mit der zellulären Reaktion auf Strahlung unterschiedlicher Qualität hat ergeben, dass das Ausmaß der unmittelbare strahleninduzierte Effekte ein bemerkenswert ähnliches Verhalten wie HTR(LET) aufweist. Aufgrund des LET-abhängigen Zeitverlaufs der zellulären Reparaturvorgänge weichen allerdings die beobachteten Schadensindikatoren mit zunehmender Dauer immer mehr von HTR(LET) ab. In Proben, die einer Bestrahlung mit hoch-LET Fe-56 Ionen (198 keV/um) unterzogen wurden, gibt es Hinweise darauf, dass die Strahlenwirkung eine größere Zahl an Zellen umfasst als durch einen Teilchentreffer im Zellkern direkt beschädigt werden. Dies deutet auf eine Ausweitung des primären Strahlenschadens auf umliegende Bystander-Zellen hin.Insgesamt konnte durch diesen fächerübergreifenden Ansatz ein wesentliches Argument dafür entwickelt werden, dass LiF:Mg,Ti Detektoren eine geeignete Basis für ein quasi-biologisches Dosimetersystem darstellen. Die vorliegende Arbeit weist damit den Weg zur direkten Vorhersage von biologischen Strahleneffekten mittels physikalischer Messmethoden.Radiation protection relies on the exact determination of absorbed dose and its translation into potential health risks. Recent insights from the field of cellular radiobiology complement common macroscopic views of radiation effects. This is fundamentally important for low doses of high-energy charged particle radiation, where the deposition of radiation energy in tissue is mostly limited to small volumes along the particle tracks.The High Temperature Ratio (HTR) method for evaluation of LiF:Mg,Ti thermoluminescence detectors, which has been developed at the Atomic Institute of the Austrian Universities, allows for parallel assessment of absorbed dose and the effective linear energy transfer (LET). The HTR represents a microdosimetric measure for radiation quality, which hints at the possibility for a direct assessment of the biologic damage potential from measurements.Correlation of measured TL data with the cellular response to radiation of different quality shows that the extent of the initial radiation-induced effects shares a remarkably similar behaviour with HTR(LET). Due to the LET-dependent time course of the cellular repair efforts, the observed damage indicators increasingly deviate from HTR(LET) with time. In samples treated with high-LET Fe-56 ions (198 keV/um), there is strong indication for a spread of the initial radiation damage to bystander cells that have not been subjected to nuclear particle traversals.Overall, this interdisciplinary study has provided evidence that promotes LiF:Mg,Ti dosemeters as a viable option for a quasi-biologic detector system. The presented work highlights a way to a direct prediction of biologic radiation effects based on a physical measurement system.19

Optimizing robot motion for robotic ultrasound-guided radiation therapy

An important aspect of robotic radiation therapy is active compensation of target motion. Recently, ultrasound has been proposed to obtain real-time volumetric images of abdominal organ motion. One approach to realize flexible probe placement throughout the treatment fraction is based on a robotic arm holding the ultrasound probe. However, the probe and the robot holding it may obstruct some of the beams with a potentially adverse effect on the plan quality. This can be mitigated by using a kinematically redundant robot, which allows maintaining a steady pose of the ultrasound probe while moving its elbow in order to minimize beam blocking. Ultimately, the motion of both the beam source carrying and the ultrasound probe holding robot contributes to the overall treatment time, i.e. beam delivery and robot motion. We propose an approach to optimize the motion and coordination of both robots based on a generalized traveling salesman problem. Furthermore, we study an application of the model to a prostate treatment scenario. Because the underlying optimization problem is hard, we compare results from a state-of-the-art heuristic solver and an approximation scheme with low computational effort. Our results show that integration of the robot holding the ultrasound probe is feasible with acceptable overhead in overall treatment time. For clinically realistic velocities of the robots, the overhead is less than 4% which is a small cost for the added benefit of continuous, volumetric, and non-ionizing tracking of organ motion over periodic x-ray-based tracking.Deutsche Forschungsgemeinschaft (DFG

Multicriterial CNN based beam generation for robotic radiosurgery of the prostate

Although robotic radiosurgery offers a flexible arrangement of treatment beams, generating treatment plans is computationally challenging and a time consuming process for the planner. Furthermore, different clinical goals have to be considered during planning and generally different sets of beams correspond to different clinical goals. Typically, candidate beams sampled from a randomized heuristic form the basis for treatment planning. We propose a new approach to generate candidate beams based on deep learning using radiological features as well as the desired constraints. We demonstrate that candidate beams generated for specific clinical goals can improve treatment plan quality. Furthermore, we compare two approaches to include information about constraints in the prediction. Our results show that CNN generated beams can improve treatment plan quality for different clinical goals, increasing coverage from 91.2 to 96.8% for 3,000 candidate beams on average. When including the clinical goal in the training, coverage is improved by 1.1% points

Feasibility and analysis of CNN-based candidate beam generation for robotic radiosurgery

Purpose: Robotic radiosurgery offers the flexibility of a robotic arm to enable high conformity to the target and a steep dose gradient. However, treatment planning becomes a computationally challenging task as the search space for potential beam directions for dose delivery is arbitrarily large. We propose an approach based on deep learning to improve the search for treatment beams. Methods: In clinical practice, a set of candidate beams generated by a randomized heuristic forms the basis for treatment planning. We use a convolutional neural network to identify promising candidate beams. Using radiological features of the patient, we predict the influence of a candidate beam on the delivered dose individually and let this prediction guide the selection of candidate beams. Features are represented as projections of the organ structures which are relevant during planning. Solutions to the inverse planning problem are generated for random and CNN-predicted candidate beams. Results: The coverage increases from 95.35% to 97.67% for 6000 heuristically and CNN-generated candidate beams, respectively. Conversely, a similar coverage can be achieved for treatment plans with half the number of candidate beams. This results in a patient-dependent reduced averaged computation time of 20.28%–45.69%. The number of active treatment beams can be reduced by 11.35% on average, which reduces treatment time. Constraining the maximum number of candidate beams per beam node can further improve the average coverage by 0.75 percentage points for 6000 candidate beams. Conclusions: We show that deep learning based on radiological features can substantially improve treatment plan quality, reduce computation runtime, and treatment time compared to the heuristic approach used in clinics.This work was partially funded by Deutsche Forschungsgemeinschaft (grant SCHL 1844/3-1)

Convolutional Neural Networks for Classifying Laterality of Vestibular Schwannomas on Single MRI Slices-A Feasibility Study.

Introduction: Many proposed algorithms for tumor detection rely on 2.5/3D convolutional neural networks (CNNs) and the input of segmentations for training. The purpose of this study is therefore to assess the performance of tumor detection on single MRI slices containing vestibular schwannomas (VS) as a computationally inexpensive alternative that does not require the creation of segmentations. Methods: A total of 2992 T1-weighted contrast-enhanced axial slices containing VS from the MRIs of 633 patients were labeled according to tumor location, of which 2538 slices from 539 patients were used for training a CNN (ResNet-34) to classify them according to the side of the tumor as a surrogate for detection and 454 slices from 94 patients were used for internal validation. The model was then externally validated on contrast-enhanced and non-contrast-enhanced slices from a different institution. Categorical accuracy was noted, and the results of the predictions for the validation set are provided with confusion matrices. Results: The model achieved an accuracy of 0.928 (95% CI: 0.869-0.987) on contrast-enhanced slices and 0.795 (95% CI: 0.702-0.888) on non-contrast-enhanced slices from the external validation cohorts. The implementation of Gradient-weighted Class Activation Mapping (Grad-CAM) revealed that the focus of the model was not limited to the contrast-enhancing tumor but to a larger area of the cerebellum and the cerebellopontine angle. Conclusions: Single-slice predictions might constitute a computationally inexpensive alternative to training 2.5/3D-CNNs for certain detection tasks in medical imaging even without the use of segmentations. Head-to-head comparisons between 2D and more sophisticated architectures could help to determine the difference in accuracy, especially for more difficult tasks

Intracranial Hemorrhage in Patients with Anticoagulant Therapy Undergoing Stereotactic Radiosurgery for Brain Metastases: A Bi-Institutional Analysis

Background: Stereotactic radiosurgery (SRS) is a well-established treatment modality for brain metastases (BM). Given the manifold implications of metastatic cancer on the body, affected patients have an increased risk of comorbidities, such as atrial fibrillation (AF) and venous thromboembolism (VTE), which includes pulmonary embolism (PE) and deep-vein thrombosis (DVT). These may require therapeutic anticoagulant therapy (ACT). Limited data are available on the risk of intracranial hemorrhage (ICH) after SRS for patients with BM who are receiving ACT. This bi-institutional analysis aimed to describe the bleeding risk for this patient subgroup. Methods: Patients with ACT at the time of single-fraction SRS for BM from two institutions were eligible for analysis. The cumulative incidence of ICH with death as a competing event was assessed during follow-up with magnetic resonance imaging or computed tomography. Results: Forty-one patients with 97 BM were included in the analyses. The median follow-up was 8.2 months (range: 1.7&ndash;77.5 months). The median and mean BM volumes were 0.47 and 1.19 cubic centimeters, respectively. The most common reasons for ACT were PE (41%), AF (34%), and DVT (7%). The ACT was mostly performed utilizing phenprocoumon (37%), novel oral anticoagulants (32%), or low-molecular-weight heparin (20%). Nine BM from a group of five patients with ICH after SRS were identified: none of them caused neurological or any other deficits. The 6-, 12-, and 18-month cumulative bleeding incidences per metastasis were 2.1%, 12.4%, and 12.4%, respectively. The metastases with previous bleeding events and those originating from malignant melanomas were found to more frequently demonstrate ICH after SRS (p = 0.02, p = 0.01). No surgical or medical intervention was necessary for ICH management, and no observed death was associated with an ICH. Conclusion: Patients receiving an ACT and single-fraction SRS for small- to medium-sized BM did not seem to have a clinically relevant risk of ICH. Previous bleeding and metastases originating from a malignant melanoma may favor bleeding events after SRS. Further studies are needed to validate our reported findings