Diffusion tensor imaging in pediatric patients with dystonia.

BACKGROUND: Childhood-onset dystonia is often progressive and severely impairs a child´s life. The pathophysiology is very heterogeneous and treatment responses vary in patients with dystonia. Factors influencing treatment effects remain to be elucidated. We hypothesize that differences in brain connectivity and fiber coherence contribute to the heterogeneity in treatment response among pediatric patients with inherited and acquired dystonia. METHODS: Twenty patients with childhood-onset dystonia were retrospectively recruited including twelve patients with inherited or idiopathic, and eight patients with acquired dystonia (mean age 10 years; 8 female/12 male). Fiber density between the internal part of the globus pallidus and selective target regions, as well as the diffusion measures of fractional anisotropy (FA) and mean diffusivity (MD) were analyzed and compared between different etiologies. RESULTS: Patients with acquired dystonia presented higher fiber density to the premotor cortex and putamen and lower FA values in the thalamus compared to patients with inherited/idiopathic dystonia. MD in the premotor cortex was higher in patients with acquired dystonia, while it was lower in the thalamus. CONCLUSION: Diffusion MRI reveals microstructural and network alterations in patients with dystonia of different etiologies.

General Algorithm Applicability in Determining DBS Lead Orientation: Adapting 2D and 3D X-Ray Techniques for SenSightTM Leads.

INTRODUCTION: With recent advancements in deep brain stimulation (DBS), directional leads featuring segmented contacts have been introduced, allowing for targeted stimulation of specific brain regions. Given that manufacturers employ diverse markers for lead orientation, our investigation focuses on the adaptability of the 2017 techniques proposed by the Cologne research group for lead orientation determination. METHODS: We tailored the two separate 2D and 3D X-ray-based techniques published in 2017 and originally developed for C-shaped markers, to the dual-marker of the Medtronic SenSight™ lead. In a retrospective patient study, we evaluated their feasibility and consistency by comparing the degree of agreement between the two methods. RESULTS: The Bland-Altman plot showed favorable concordance without any noticeable systematic errors. The mean difference was 0.79°, with limits of agreement spanning from 21.4° to -19.8°. The algorithms demonstrated high reliability, evidenced by an intraclass correlation coefficient of 0.99 (p < 0.001). CONCLUSION: The 2D and 3D algorithms, initially formulated for discerning the circular orientation of a C-shaped marker, were adapted to the marker of the Medtronic SenSight™ lead. Statistical analyses revealed a significant level of agreement between the two methods. Our findings highlight the adaptability of these algorithms to different markers, achievable through both low-dose intraoperative 2D X-ray imaging and standard CT imaging.

Automatic Detection of Directional Lead Orientation in Deep Brain Stimulation using Photon-Counting Detector Computed Tomography: A Phantom Study.

INTRODUCTION: Photon-counting detector computed tomography (PCD-CT) represents the next generation of CT technology, offering enhanced capabilities for detecting the orientation of directional leads in deep brain stimulation (DBS). This study aims to refine PCD-CT-based lead orientation determination using an automated method applicable to devices from various manufacturers, addressing current methodological limitations and improving neurosurgical precision. METHODS: An automated method was developed to ascertain the orientation of directional DBS leads using PCD-CT data and grayscale model fitting for devices from Boston Scientific, Medtronic, and Abbott. A phantom study was conducted to evaluate the precision and accuracy of this method, comparing it with the stripe artifact method across different lead alignments relative to the CT gantry axis. RESULTS: Except for the Medtronic Sensight™ lead, where detection was occasionally unfeasible if aligned normal to the z-axis of the CT gantry, a clinically very unlikely alignment, the lead orientation could be automatically determined regardless of its position. The accuracy and precision of this automated method was comparable to those of the stripe artifact method. CONCLUSION: PCD-CT enables the automatic determination of lead orientation from leading manufacturers with an accuracy comparable to the stripe artifact method, and it offers the added benefit of being independent of the clinically occurring orientation of the head and, consequently, the lead relative to the CT gantry axis.

Impact of prescription isodose level and collimator selection on dose homogeneity and plan quality in robotic radiosurgery.

PURPOSE: In stereotactic radiosurgery (SRS), prescription isodoses and resulting dose homogeneities vary widely across different platforms and clinical entities. Our goal was to investigate the physical limitations of generating dose distributions with an intended level of homogeneity in robotic SRS. METHODS: Treatment plans for non-isocentric irradiation of 4 spherical phantom targets (volume 0.27-7.70 ml) and 4 clinical targets (volume 0.50-5.70 ml) were calculated using Sequential (phantom) or VOLOTM (clinical) optimizers (Accuray, Sunnyvale, CA, USA). Dose conformity, volume of 12 Gy isodose (V12Gy) as a measure for dose gradient, and treatment time were recorded for different prescribed isodose levels (PILs) and collimator settings. In addition, isocentric irradiation of phantom targets was examined, with dose homogeneity modified by using different collimator sizes. RESULTS: Dose conformity was generally high (nCI ≤ 1.25) and varied little with PIL. For all targets and collimator sets, V12Gy was highest for PIL ≥ 80% and lowest for PIL ≤ 65%. The impact of PIL on V12Gy was highest for isocentric irradiation and lowest for clinical targets (VOLOTM optimization). The variability of V12Gy as a function of collimator selection was significantly higher than that of PIL. V12Gy and treatment time were negatively correlated. Plans utilizing a single collimator with a diameter in the range of 70-80% of the target diameter were fastest, but showed the strongest dependence on PIL. CONCLUSION: Inhomogeneous dose distributions with PIL ≤ 70% can be used to minimize dose to normal tissue. PIL ≥ 90% is associated with a marked and significant increase in off-target dose exposure. Careful selection of collimators during planning is even more important.

Deviation of the orientation angle of directional deep brain stimulation leads quantified by intraoperative stereotactic X-ray imaging.

Directional deep brain stimulation (dDBS) provides multiple programming options. Knowledge of the spatial lead orientation is useful for time-efficient programming. Recent studies demonstrated deviations of up to 90° from the intended orientation angle. We examined the deviation of dDBS-lead orientation for leads from two different manufacturers using intraoperative stereotactic (STX) X-ray images. Intraoperative 2D-X-ray images were acquired after implantation of the first lead (TP1) and the second lead (TP2) enabling the estimation of the spatial position of the first lead at TP1 and TP2 and of changes of the orientation for a defined time period. Two investigators retrospectively estimated the orientation of the directional marker for 64 patients. The mean deviation from intended spatial orientation was 40.8° ± 46.1° for all examined leads. The spatial orientation of the first lead did not significantly change within a period of approximately 1 h. The degree of deviation did not differ significantly between two lead manufacturers but depended on the lead fixation technique. Our results showed deviations from the intended orientation angle immediately after the insertion of dDBS leads. The initial spatial orientation remained stable for approximately 1 h and was not caused by technical properties of the implanted lead. Hence, it was most probably the result of unintended mechanical torsion during insertion and/or fixation. Because precise determination of the lead orientation is mandatory for target-oriented dDBS programming, the use of additional imaging suitable for precise 3D visualization of lead contacts and/or the positioning marker is recommended.

Sweetspot Mapping in Deep Brain Stimulation: Strengths and Limitations of Current Approaches.

OBJECTIVES: Open questions remain regarding the optimal target, or sweetspot, for deep brain stimulation (DBS) in, for example, Parkinson's disease. Previous studies introduced different methods of mapping DBS effects to determine sweetspots. While having a direct impact on surgical targeting and postoperative programming in DBS, these methods so far have not been compared. MATERIALS AND METHODS: This study investigated five previously published DBS mapping approaches regarding their potential to correctly identify a predefined target. Methods were investigated in silico in eight different use-case scenarios, which incorporated different types of clinical data, noise, and differences in underlying neuroanatomy. Dice coefficients were calculated to determine the overlap between identified sweetspots and the predefined target. Additionally, out-of-sample predictive capabilities were assessed using the amount of explained variance R2. RESULTS: The five investigated methods resulted in highly variable sweetspots. Methods based on voxel-wise statistics against average outcomes showed the best performance overall. While predictive capabilities were high, even in the best of cases Dice coefficients remained limited to values around 0.5, highlighting the overall limitations of sweetspot identification. CONCLUSIONS: This study highlights the strengths and limitations of current approaches to DBS sweetspot mapping. Those limitations need to be taken into account when considering the clinical implications. All future approaches should be investigated in silico before being applied to clinical data.

Temporal Stability of Lead Orientation in Directional Deep Brain Stimulation.

BACKGROUND: Directional deep brain stimulation (DBS) enlarges the therapeutic window by increasing side-effect thresholds and improving clinical benefits. To determine the optimal stimulation settings and interpret clinical observations, knowledge of the lead orientation in relation to the patient's anatomy is required. OBJECTIVE: To determine if directional leads remain in a fixed orientation after implantation or whether orientation changes over time. METHOD: Clinical records of 187 patients with directional DBS electrodes were screened for CT scans in addition to the routine postoperative CT. The orientation angle of each electrode at a specific point in time was reconstructed from CT artifacts using the DiODe algorithm implemented in Lead-DBS. The orientation angles over time were compared with the originally measured orientations from the routine postoperative CT. RESULTS: Multiple CT scans were identified in 18 patients and the constancy of the orientation angle was determined for 29 leads at 48 points in time. The median time difference between the observations and the routine postoperative CT scan was 82 (range 1-811) days. The mean difference of the orientation angles compared to the initial measurement was -1.1 ± 3.9° (range -7.6 to 8.7°). Linear regression showed no relevant drift of the absolute value of the orientation angle over time (0.8°/year, adjusted R2: 0.040, p = 0.093). CONCLUSION: The orientation of directional leads was stable and showed no clinically relevant changes either in the first weeks after implantation or over longer periods of time.

Potentials and Limitations of Directional Deep Brain Stimulation: A Simulation Approach.

BACKGROUND: Directional leads are increasingly used in deep brain stimulation. They allow shaping the electrical field in the axial plane. These new possibilities increase the complexity of programming. Thus, optimized programming approaches are needed to assist clinical testing and to obtain full clinical benefit. OBJECTIVES: This simulation study investigates to what extent the electrical field can be shaped by directional steering to compensate for lead malposition. METHOD: Binary volumes of tissue activated (VTA) were simulated, by using a finite element method approach, for different amplitude distributions on the three directional electrodes. VTAs were shifted from 0 to 2 mm at different shift angles with respect to the lead orientation, to determine the best compensation of a target volume. RESULTS: Malpositions of 1 mm can be compensated with the highest gain of overlap with directional leads. For larger shifts, an improvement of overlap of 10-30% is possible, depending on the stimulation amplitude and shift angle of the lead. Lead orientation and shift determine the amplitude distribution of the electrodes. CONCLUSION: To get full benefit from directional leads, both the shift angle as well as the shift to target volume are required to choose the correct amplitude distribution on the electrodes. Current directional leads have limitations when compensating malpositions >1 mm; however, they still outperform conventional leads in reducing overstimulation. Further, their main advantage probably lies in the reduction of side effects. Databases like the one from this simulation could serve for optimized lead programming algorithms in the future.

Radiomics in radiation oncology-basics, methods, and limitations.

Over the past years, the quantity and complexity of imaging data available for the clinical management of patients with solid tumors has increased substantially. Without the support of methods from the field of artificial intelligence (AI) and machine learning, a complete evaluation of the available image information is hardly feasible in clinical routine. Especially in radiotherapy planning, manual detection and segmentation of lesions is laborious, time consuming, and shows significant variability among observers. Here, AI already offers techniques to support radiation oncologists, whereby ultimately, the productivity and the quality are increased, potentially leading to an improved patient outcome. Besides detection and segmentation of lesions, AI allows the extraction of a vast number of quantitative imaging features from structural or functional imaging data that are typically not accessible by means of human perception. These features can be used alone or in combination with other clinical parameters to generate mathematical models that allow, for example, prediction of the response to radiotherapy. Within the large field of AI, radiomics is the subdiscipline that deals with the extraction of quantitative image features as well as the generation of predictive or prognostic mathematical models. This review gives an overview of the basics, methods, and limitations of radiomics, with a focus on patients with brain tumors treated by radiation therapy.

Radiomic analysis of planning computed tomograms for predicting radiation-induced lung injury and outcome in lung cancer patients treated with robotic stereotactic body radiation therapy.

OBJECTIVES: To predict radiation-induced lung injury and outcome in non-small cell lung cancer (NSCLC) patients treated with robotic stereotactic body radiation therapy (SBRT) from radiomic features of the primary tumor. METHODS: In all, 110 patients with primary stage I/IIa NSCLC were analyzed for local control (LC), disease-free survival (DFS), overall survival (OS) and development of local lung injury up to fibrosis (LF). First-order (histogram), second-order (GLCM, Gray Level Co-occurrence Matrix) and shape-related radiomic features were determined from the unprocessed or filtered planning CT images of the gross tumor volume (GTV), subjected to LASSO (Least Absolute Shrinkage and Selection Operator) regularization and used to construct continuous and dichotomous risk scores for each endpoint. RESULTS: Continuous scores comprising 1-5 histogram or GLCM features had a significant (p = 0.0001-0.032) impact on all endpoints that was preserved in a multifactorial Cox regression analysis comprising additional clinical and dosimetric factors. At 36 months, LC did not differ between the dichotomous risk groups (93% vs. 85%, HR 0.892, 95%CI 0.222-3.590), while DFS (45% vs. 17%, p < 0.05, HR 0.457, 95%CI 0.240-0.868) and OS (80% vs. 37%, p < 0.001, HR 0.190, 95%CI 0.065-0.556) were significantly lower in the high-risk groups. Also, the frequency of LF differed significantly between the two risk groups (63% vs. 20% at 24 months, p < 0.001, HR 0.158, 95%CI 0.054-0.458). CONCLUSION: Radiomic analysis of the gross tumor volume may help to predict DFS and OS and the development of local lung fibrosis in early stage NSCLC patients treated with stereotactic radiotherapy.

DiODe: Directional Orientation Detection of Segmented Deep Brain Stimulation Leads: A Sequential Algorithm Based on CT Imaging.

BACKGROUND: Directional deep brain stimulation (DBS) allows steering the stimulation in an axial direction which offers greater flexibility in programming. However, accurate anatomical visualization of the lead orientation is required for interpreting the observed stimulation effects and to guide programming. OBJECTIVES: In this study we aimed to develop and test an accurate and robust algorithm for determining the orientation of segmented electrodes based on standard postoperative CT imaging used in DBS. METHODS: Orientation angles of directional leads (CartesiaTM; Boston Scientific, Marlborough, MA, USA) were determined using CT imaging. Therefore, a sequential algorithm was developed that quantitatively compares the similarity of the observed CT artifacts with calculated artifact patterns based on the lead's orientation marker and a geometric model of the segmented electrodes. Measurements of seven ground truth phantoms and three leads with 60 different configurations of lead implantation and orientation angles were analyzed for validation. RESULTS: The accuracy of the determined electrode orientation angles was -0.6 ± 1.5° (range: -5.4 to 4.2°). This accuracy proved to be sufficiently high to resolve even subtle differences between individual leads. CONCLUSIONS: The presented algorithm is user independent and provides highly accurate results for the orientation of the segmented electrodes for all angular constellations that typically occur in clinical cases.

Directional DBS increases side-effect thresholds-A prospective, double-blind trial.

OBJECTIVE: The objective of this study was to investigate whether directional deep brain stimulation (DBS) of the subthalamic nucleus in Parkinson's disease (PD) offers increased therapeutic windows, side-effect thresholds, and clinical benefit. METHODS: In 10 patients, 20 monopolar reviews were conducted in a prospective, randomized, double-blind design to identify the best stimulation directions and compare them to conventional circular DBS regarding side-effect thresholds, motor improvement, and therapeutic window. In addition, circular and best-directional DBS were directly compared in a short-term crossover. Motor outcome was also assessed after an open-label follow-up of 3 to 6 months. RESULTS: Stimulation in the individual best direction resulted in significantly larger therapeutic windows, higher side-effect thresholds, and more improvement in hand rotation than circular DBS. Rigidity and finger tapping did not respond differentially to the stimulation conditions. There was no difference in motor efficacy or stimulation amplitudes between directional and circular DBS in the short-term crossover. Follow-up evaluations 3 to 6 months after implantation revealed improvements in motor outcome and medication reduction comparable to other DBS studies with a majority of patients remaining with a directional setting. CONCLUSION: Directional DBS can increase side-effect thresholds while achieving clinical benefit comparable to conventional DBS. Whether directional DBS improves long-term clinical outcome needs to be investigated in the future. © 2017 International Parkinson and Movement Disorder Society.

Stereotactic biopsy in elderly patients: risk assessment and impact on treatment decision.

To evaluate risk profile, diagnostic yield and impact on treatment decision of stereotactic biopsy (SB) in elderly patients with unclear cerebral lesions. In this single center retrospective analysis we identified all patients aged ≥70 years receiving SB between January 2005 and December 2015. Demographic data, Karnofsky Performance Status (KPS), histology, comorbidity (by CHA2DS2-VASc Score) and use of anticoagulation were retrieved. We scrutinized diagnostic yield, procedural complications (mortality, transient and permanent morbidity), hospitalization time and therapeutic consequence. For correlation analysis Chi-Square, Mann-Whitney rank sum test and binary regression were used. Two hundred and thirty patients were included. In 229 patients SB was technically successful. Median age was 74 (70-87) years, 56.1% of patients were male and median preoperative KPS was 80% (30-100). Median CHA2DS2-VASc Score was 4 (1-9), with 29.6% receiving anticoagulation. Median hospital stay was 8 (2-29) days. Pathological diagnosis was conclusive in 97% revealing neoplastic lesions in 91.7% (high-grade glioma 62.6%, lymphoma 18.3%, metastasis 4.8%, low-grade glioma 3.0% and other tumors 3.0%) and non-neoplastic lesions in 5.3% of cases. Procedure-related mortality was 0.4%, transient and permanent morbidity occurred in 19 patients (8.3%) and eight patients (3.5%). Complication rate was not associated with any of the above-mentioned parameters. Adjuvant therapy was initiated in 171 (74.3%) patients. Decision against disease-specific therapy was only influenced by preoperative KPS (p < 0.001). SB in elderly patients is characterized by a favorable risk profile and high diagnostic yield, allowing tissue based therapeutic consequences even in patients with high comorbidity and anticoagulant medication.

Inverse treatment planning for spinal robotic radiosurgery: an international multi-institutional benchmark trial.

Stereotactic radiosurgery (SRS) is the accurate, conformal delivery of high-dose radiation to well-defined targets while minimizing normal structure doses via steep dose gradients. While inverse treatment planning (ITP) with computerized optimization algorithms are routine, many aspects of the planning process remain user-dependent. We performed an international, multi-institutional benchmark trial to study planning variability and to analyze preferable ITP practice for spinal robotic radiosurgery. 10 SRS treatment plans were generated for a complex-shaped spinal metastasis with 21 Gy in 3 fractions and tight constraints for spinal cord (V14Gy < 2 cc, V18Gy < 0.1 cc) and target (coverage > 95%). The resulting plans were rated on a scale from 1 to 4 (excellent-poor) in five categories (constraint compliance, optimization goals, low-dose regions, ITP complexity, and clinical acceptability) by a blinded review panel. Additionally, the plans were mathemati-cally rated based on plan indices (critical structure and target doses, conformity, monitor units, normal tissue complication probability, and treatment time) and compared to the human rankings. The treatment plans and the reviewers' rankings varied substantially among the participating centers. The average mean overall rank was 2.4 (1.2-4.0) and 8/10 plans were rated excellent in at least one category by at least one reviewer. The mathematical rankings agreed with the mean overall human rankings in 9/10 cases pointing toward the possibility for sole mathematical plan quality comparison. The final rankings revealed that a plan with a well-balanced trade-off among all planning objectives was preferred for treatment by most par-ticipants, reviewers, and the mathematical ranking system. Furthermore, this plan was generated with simple planning techniques. Our multi-institutional planning study found wide variability in ITP approaches for spinal robotic radiosurgery. The participants', reviewers', and mathematical match on preferable treatment plans and ITP techniques indicate that agreement on treatment planning and plan quality can be reached for spinal robotic radiosurgery.

Intracranial stereotactic radiosurgery with an adapted linear accelerator vs. robotic radiosurgery: Comparison of dosimetric treatment plan quality.

BACKGROUND AND PURPOSE: Stereotactic radiosurgery with an adapted linear accelerator (linac-SRS) is an established therapy option for brain metastases, benign brain tumors, and arteriovenous malformations. We intended to investigate whether the dosimetric quality of treatment plans achieved with a CyberKnife (CK) is at least equivalent to that for linac-SRS with circular or micromultileaf collimators (microMLC). PATIENTS AND METHODS: A random sample of 16 patients with 23 target volumes, previously treated with linac-SRS, was replanned with CK. Planning constraints were identical dose prescription and clinical applicability. In all cases uniform optimization scripts and inverse planning objectives were used. Plans were compared with respect to coverage, minimal dose within target volume, conformity index, and volume of brain tissue irradiated with ≥ 10 Gy. RESULTS: Generating the CK plan was unproblematic with simple optimization scripts in all cases. With the CK plans, coverage, minimal target volume dosage, and conformity index were significantly better, while no significant improvement could be shown regarding the 10 Gy volume. Multiobjective comparison for the irradiated target volumes was superior in the CK plan in 20 out of 23 cases and equivalent in 3 out of 23 cases. Multiobjective comparison for the treated patients was superior in the CK plan in all 16 cases. CONCLUSION: The results clearly demonstrate the superiority of the irradiation plan for CK compared to classical linac-SRS with circular collimators and microMLC. In particular, the average minimal target volume dose per patient, increased by 1.9 Gy, and at the same time a 14% better conformation index seems to be an improvement with clinical relevance.

Stereotactic radiosurgery for treatment of brain metastases. A report of the DEGRO Working Group on Stereotactic Radiotherapy.

BACKGROUND: This report from the Working Group on Stereotaktische Radiotherapie of the German Society of Radiation Oncology (Deutsche Gesellschaft für Radioonkologie, DEGRO) provides recommendations for the use of stereotactic radiosurgery (SRS) on patients with brain metastases. It considers existing international guidelines and details them where appropriate. RESULTS AND DISCUSSION: The main recommendations are: Patients with solid tumors except germ cell tumors and small-cell lung cancer with a life expectancy of more than 3 months suffering from a single brain metastasis of less than 3 cm in diameter should be considered for SRS. Especially when metastases are not amenable to surgery, are located in the brain stem, and have no mass effect, SRS should be offered to the patient. For multiple (two to four) metastases--all less than 2.5 cm in diameter--in patients with a life expectancy of more than 3 months, SRS should be used rather than whole-brain radiotherapy (WBRT). Adjuvant WBRT after SRS for both single and multiple (two to four) metastases increases local control and reduces the frequency of distant brain metastases, but does not prolong survival when compared with SRS and salvage treatment. As WBRT carries the risk of inducing neurocognitive damage, it seems reasonable to withhold WBRT for as long as possible. CONCLUSION: A single (marginal) dose of 20 Gy is a reasonable choice that balances the effect on the treated lesion (local control, partial remission) against the risk of late side effects (radionecrosis). Higher doses (22-25 Gy) may be used for smaller (< 1 cm) lesions, while a dose reduction to 18 Gy may be necessary for lesions greater than 2.5-3 cm. As the infiltration zone of the brain metastases is usually small, the GTV-CTV (gross tumor volume-clinical target volume) margin should be in the range of 0-1 mm. The CTV-PTV (planning target volume) margin depends on the treatment technique and should lie in the range of 0-2 mm. Distant brain recurrences fulfilling the aforementioned criteria can be treated with SRS irrespective of previous WBRT.

Low-dose rate stereotactic iodine-125 brachytherapy for the treatment of inoperable primary and recurrent glioblastoma: single-center experience with 201 cases.

Treatment options for inoperable glioblastoma are limited. Low-dose-rate stereotactic iodine-125 brachytherapy (SBT) has been reported as an effective and low-risk treatment option for circumscribed low-grade gliomas and brain metastases. The present study evaluates this treatment approach for patients with inoperable glioblastoma. Between 1990 and 2012, 201 patients with histologically proven glioblastoma were treated with SBT (iodine-125 seeds; median cumulative surface dose, 60 Gy; median dose-rate, 6 cGy/h; median gross-tumor-volume, 17 ml) either as primary treatment (n = 103) or at recurrence (n = 98). In addition to SBT, 90.3 % of patients in the primary treatment group received external boost radiotherapy (median dose, 25.2 Gy). Adjuvant chemotherapy was added for 30.8 % of patients following SBT and consisted of temozolomide for the majority of cases (88.7 %). Procedure-related complications, clinical outcome, progression-free and overall survival (PFS, OS) were evaluated. Median follow-up was 9.8 months. The procedure-related mortality was zero. During follow-up, transient and permanent procedure-related morbidity was observed in 7.5 and 2.0 %, respectively. Calculated from the time of SBT, median OS and PFS rates were 10.5 and 6.2 months, with no significant differences among primary and recurrent tumors (11.1 vs.10.4 months for OS and 6.2 vs. 5.9 months for PFS). For OS, multivariate analysis revealed Karnofsky performance score, age, and adjuvant chemotherapy as independent prognostic factors (all p < 0.01). Low-dose-rate SBT is a relatively safe and potentially effective local treatment option for patients with circumscribed inoperable glioblastoma initially or at recurrence. It deserves prospective validation since it may improve the outcome for a subset of patients with inoperable GBM.

Tractography-guided stimulation of somatosensory fibers for thalamic pain relief.

BACKGROUND: The spinothalamocortical tract (STC) is seen as a neural tract responsible for or involved in the generation or transmission of thalamic pain. Either the thalamus itself or the posterior limb of the internal capsule (PLIC) are targets for deep brain stimulation (DBS) in patients with thalamic pain, but due to its low contrast, conventional MRI cannot visualize the STC directly. OBJECTIVES: To show the feasibility of integrating diffusion tensor imaging-based tractography into the stereotactic treatment planning for identification of an object-oriented lead trajectory that allows STC-DBS with multiple electrode contacts. METHODS: Diffusion tensor imaging was performed in 4 patients with thalamic pain. The STC was modeled and integrated into the stereotactic treatment planning for DBS. DBS-lead implantation was done according to trajectory planning along the modeled STC at the level of the PLIC. RESULTS: After implantation, electrode stimulation was possible over a length of more than 20 mm with a tractography-based trajectory along the PLIC part of the STC. After a follow-up of 12 months, pain relief of more than 40% was achieved in 3 of 4 patients with rating on a visual analogue scale. In 1 patient, stimulation failed to reach any long-lasting positive effects. CONCLUSIONS: Integrating tractography data into stereotactic planning of DBS in thalamic pain is technically feasible. It can be used to identify a lead trajectory that allows for multiple contact stimulation along the STC at the level of the PLIC. Due to long-lasting positive stimulation effect, tractography-guided stimulation of sensory fibers seems to be beneficial for thalamic pain relief.

Use of dose-area product to assess plan quality in robotic radiosurgery.

PURPOSE: In robotic stereotactic radiosurgery (SRS), optimal selection of collimators from a set of fixed cones must be determined manually by trial and error. A unique and uniformly scaled metric to characterize plan quality could help identify Pareto-efficient treatment plans. METHODS: The concept of dose-area product (DAP) was used to define a measure (DAPratio) of the targeting efficiency of a set of beams by relating the integral DAP of the beams to the mean dose achieved in the target volume. In a retrospective study of five clinical cases of brain metastases with representative target volumes (range: 0.5-5.68 ml) and 121 treatment plans with all possible collimator choices, the DAPratio was determined along with other plan metrics (conformity index CI, gradient index R50%, treatment time, total number of monitor units TotalMU, radiotoxicity index f12, and energy efficiency index η50%), and the respective Spearman's rank correlation coefficients were calculated. The ability of DAPratio to determine Pareto efficiency for collimator selection at DAPratio < 1 and DAPratio < 0.9 was tested using scatter plots. RESULTS: The DAPratio for all plans was on average 0.95 ±â€¯0.13 (range: 0.61-1.31). Only the variance of the DAPratio was strongly dependent on the number of collimators. For each target, there was a strong or very strong correlation of DAPratio with all other metrics of plan quality. Only for R50% and η50% was there a moderate correlation with DAPratio for the plans of all targets combined, as R50% and η50% strongly depended on target size. Optimal treatment plans with CI, R50%, f12, and η50% close to 1 were clearly associated with DAPratio < 1, and plans with DAPratio < 0.9 were even superior, but at the cost of longer treatment times and higher total monitor units. CONCLUSIONS: The newly defined DAPratio has been demonstrated to be a metric that characterizes the target efficiency of a set of beams in robotic SRS in one single and uniformly scaled number. A DAPratio < 1 indicates Pareto efficiency. The trade-off between plan quality on the one hand and short treatment time or low total monitor units on the other hand is also represented by DAPratio.

Stereotactic iodine-125 brachytherapy for treatment of inoperable focal brainstem gliomas of WHO grades I and II: feasibility and long-term outcome.

Microsurgical resection is the most frequently suggested treatment option for accessible focal brainstem gliomas (F-BSG) of World Health Organization (WHO) grades I and II. Because of their location in the highly eloquent brain, however, resection is associated with permanent postoperative morbidity, ranging from 12 to 33 %. Only a few reports have suggested stereotactic brachytherapy (SBT) with implantation of iodine-125 seeds as a local treatment alternative. Between 1993 and 2010, 47 patients were treated with SBT (iodine-125 seeds; cumulative surface dose 50-65 Gy) for inoperable F-BSG, WHO grades I and II, in one of the largest reported patient series. We evaluated procedure-related complications, clinical outcome, and progression-free and overall survival (PFS, OS). Median follow-up was 81.6 months. Procedure-related mortality was zero. Within 30 days of seed implantation six patients (12.8 %) had transient neurological deficits. Two patients (4.3 %) deteriorated permanently. Space-occupying cysts occurred in six patients (12.8 %) after a median of 28.5 months, and required surgical intervention. Nine patients (19.1 %) presented with tumor relapse after a median of 56.6 months (range 7.9-118.0 months). For the remaining 38 patients complete response was observed for 23.4 %, partial response for 29.8 %, and stable disease for 27.7 %. Actuarial PFS was 97.7 ± 2.2, 92.8 ± 4.0, 81.2 ± 6.5, and 62.0 ± 10.4 % after 1, 2, 5, and 10 years, respectively. Corresponding OS was 100 ± 0.0 % (1 and 2 years), 97.4 ± 2.6 % (5 years), and 87.6 ± 7.0 % (10 years). SBT is a comparatively safe, minimally invasive, and highly effective local treatment option for patients with inoperable F-BSG WHO grades I and II; it merits further evaluation in prospective randomized trials.