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Purpose: Due to its close vicinity to critical structures, especially the spinal cord, standards for safety for spine stereotactic body radiotherapy (SBRT) should be high. This study was conducted, to evaluate intrafractional motion during spine SBRT for patients without individualized immobilization (e.g., vacuum cushions) using high accuracy patient monitoring via orthogonal X-ray imaging. Methods: Intrafractional X-ray data were collected from 29 patients receiving 79 fractions of spine SBRT. No individualized immobilization devices were used during the treatment. Intrafractional motion was monitored using the ExacTrac Dynamic (ETD) System (Brainlab AG, Munich, Germany). Deviations were detected in six degrees of freedom (6 DOF). Tolerances for repositioning were 0.7 mm for translational and 0.5° for rotational deviations. Patients were repositioned when the tolerance levels were exceeded. Results: Out of the 925 pairs of stereoscopic X-ray images examined, 138 (15 %) showed at least one deviation exceeding the predefined tolerance values. In all 6 DOF together, a total of 191 deviations out of tolerance were recorded. The frequency of deviations exceeding the tolerance levels varied among patients but occurred in all but one patient. Deviations out of tolerance could be seen in all 6 DOF. Maximum translational deviations were 2.6 mm, 2.3 mm and 2.8 mm in the lateral, longitudinal and vertical direction. Maximum rotational deviations were 1.8°, 2.6° and 1.6° for pitch, roll and yaw, respectively. Translational deviations were more frequent than rotational ones, and frequency and magnitude of deviations showed an inverse correlation. Conclusion: Intrafractional motion detection and patient repositioning during spine SBRT using X-ray imaging via the ETD System can lead to improved safety during the application of high BED in critical locations. When using intrafractional imaging with low thresholds for re-positioning individualized immobilization devices (e.g. vacuum cushions) may be omitted.

Purpose: To date, no universally accepted technique for the evaluation of the overall dosimetric performance of hybrid integrated magnetic resonance imaging (MR) – linear accelerators (linacs) is available. We report on the suitability and reliability of a novel phantom with modular inserts for combined polymer gel (PG) and ionisation chamber (IC) measurements at a 0.35 T MR-linac. Methods: Three 3D-printed, modular head phantoms, based on real patient anatomy, were used for repeated (2 times) PG irradiations of cranial treatment plans on a 0.35 T MR-linac. The PG readout was performed on two 1.5 T diagnostic MR-scanners to reduce scanning time. The PG dose volumes were normalised to the IC dose (normalised dose N1) and to the median planning target volume dose (normalised dose N2). Linearity of the PG dose response was validated and dose profiles, centres of mass (COM) of the 95% isodoses and dose volume histograms (DVH) were compared between planned and measured dose distributions and a 3D gamma analysis was performed. Results: Dose linearity of the PG was good (R2 > 0.99 for all linear fit functions). High agreement was found between planned and measured dose volumes in the dose profiles and DVHs. The largest dose deviation was found in the intermediate dose region (mean dose deviation 0.2 Gy; 5.6%). A mean COM offset of 1.2 mm indicated high spatial accuracy. Mean 3D gamma passing rates (2%, 2 mm) of 83.3% for N1 and 91.6% for N2 dose distributions were determined. When comparing repeated PG measurements to each other, a mean gamma passing rate of 95.7% was found. Conclusion: The new modular phantom was found practical for use at a 0.35 T MR-linac. In contrast to the high dose region, larger mean deviations were found in the mid dose range. The PG measurements showed high reproducibility. The MR-linac performed well in a non-adaptive setting in terms of spatial and dosimetric accuracy.

Frameless single-isocenter non-coplanar stereotactic radiosurgery (SRS) for patients with multiple brain metastases is a treatment at high geometrical complexity. The goal of this study is to analyze the dosimetric impact of non-coplanar image guidance with stereoscopic X-ray imaging. Such an analysis is meant to provide insights on the adequacy of safety margins, and to evaluate the benefit of imaging at non-coplanar configurations.The ExacTrac® (ET) system (Brainlab AG, Munich, Germany) was used for stereoscopic X-ray imaging in frameless single-isocenter non-coplanar SRS for multiple brain metastases. Sub-millimeter precision was found for the ET-based pre-treatment setup, whereas a degradation was noted for non-coplanar treatment angles. Misalignments without intra-fractional positioning corrections were reconstructed in 6 degrees of freedom (DoF) to resemble the situation without non-coplanar image guidance.Dose recalculation in 20 SRS patients with applied positioning corrections did not reveal any significant differences in D98% for 75 planning target volumes (PTVs) and gross tumor volumes (GTVs). For recalculation without applied positioning corrections, significant differences (p

Background and purpose: Patients receiving cranial radiotherapy are immobilized with a thermoplastic mask to restrict patient motion. Depending on the target volume margins and treatment dose, different mask systems are used. Intrafractional movements can be monitored using stereoscopic X-ray imaging. The aim of the present work was to compare the magnitudes of intrafractional deviation for different mask systems. Material and methods: Four different head mask systems (open face mask, open mask, stereotactic mask, double mask) used in the treatment of 40 patients were investigated. In total 487 treatment fractions and 3708 X-ray images were collected. Deviations were calculated by comparison of the acquired X-ray images with digitally reconstructed radiographs. The results of intrafractional X-ray deviations for translational and rotational axes were compared between the different mask systems. Results: Deviations were below 0.6 mm for translations and below 0.6° for rotations for all mask systems. Along the lateral and longitudinal directions the stereotactic mask was superior, while along the vertical direction the double mask showed the lowest deviations. For low rotational deviations the double mask is the best amongst all other mask systems. Conclusion: As expected, the lowest movement was shown using cranial stereotactic mask systems. The results have shown deviations lower than 0.6 mm and 0.6° using any of the four thermoplastic mask systems.

Abstract Background Hybrid magnetic resonance (MR)-Linac systems have recently been introduced into clinical practice. The systems allow online adaption of the treatment plan with the aim of compensating for interfractional anatomical changes. The aim of this study was to evaluate the dose volume histogram (DVH)-based dosimetric benefits of online adaptive MR-guided radiotherapy (oMRgRT) across different tumor entities and to investigate which subgroup of plans improved the most from adaption. Methods Fifty patients treated with oMRgRT for five different tumor entities (liver, lung, multiple abdominal lymph nodes, pancreas, and prostate) were included in this retrospective analysis. Various target volume (gross tumor volume GTV, clinical target volume CTV, and planning target volume PTV) and organs at risk (OAR) related DVH parameters were compared between the dose distributions before and after plan adaption. Results All subgroups clearly benefited from online plan adaption in terms of improved PTV coverage. For the liver, lung and abdominal lymph nodes cases, a consistent improvement in GTV coverage was found, while many fractions of the prostate subgroup showed acceptable CTV coverage even before plan adaption. The largest median improvements in GTV near-minimum dose (D98%) were found for the liver (6.3%, p

Abstract Background and purpose Chemoradiotherapy (CRT) followed by a brachytherapy (BT) boost is the standard of care for patients with locally advanced or recurrent gynecological cancer (LARGC). However, not every patient is suitable for BT. Therefore, we investigated the feasibility of an MR-guided SBRT boost (MRg-SBRT boost) following CRT of the pelvis. Material and methods Ten patients with LARGC were analyzed retrospectively. The patients were not suitable for BT due to extensive infiltration of the pelvic wall (10%), other adjacent organs (30%), or both (50%), or ineligibility for anesthesia (10%). Online-adaptive treatment planning was performed to control for interfractional anatomical changes. Treatment parameters and toxicity were evaluated to assess the feasibility of MRg-SBRT boost. Results MRg-SBRT boost was delivered to a median total dose of 21.0 Gy in 4 fractions. The median optimized PTV (PTVopt) size was 43.5ccm. The median cumulative dose of 73.6Gy10 was delivered to PTVopt. The cumulative median D2ccm of the rectum was 63.7 Gy; bladder 72.2 Gy; sigmoid 65.8 Gy; bowel 59.9 Gy (EQD23). The median overall treatment time/fraction was 77 min, including the adaptive workflow in 100% of fractions. The median duration of the entire treatment was 50 days. After a median follow-up of 9 months, we observed no CTCAE ≥ °II toxicities. Conclusion These early results report the feasibility of an MRg-SBRT boost approach in patients with LARGC, who were not candidates for BT. When classical BT-OAR constraints are followed, the therapy was well tolerated. Long-term follow-up is needed to validate the results.

Abstract Background The aim of this study was to evaluate and compare the performance of intensity modulated radiation therapy (IMRT) plans, planned for low-field strength magnetic resonance (MR) guided linear accelerator (linac) delivery (labelled IMRT MRL plans), and clinical conventional volumetric modulated arc therapy (VMAT) plans, for the treatment of prostate cancer (PCa). Both plans used the original planning target volume (PTV) margins. Additionally, the potential dosimetric benefits of MR-guidance were estimated, by creating IMRT MRL plans using smaller PTV margins. Materials and methods 20 PCa patients previously treated with conventional VMAT were considered. For each patient, two different IMRT MRL plans using the low-field MR-linac treatment planning system were created: one with original (orig.) PTV margins and the other with reduced (red.) PTV margins. Dose indices related to target coverage, as well as dose-volume histogram (DVH) parameters for the target and organs at risk (OAR) were compared. Additionally, the estimated treatment delivery times and the number of monitor units (MU) of each plan were evaluated. Results The dose distribution in the high dose region and the target volume DVH parameters (D98%, D50%, D2% and V95%) were similar for all three types of treatment plans, with deviations below 1% in most cases. Both IMRT MRL plans (orig. and red. PTV margins) showed similar homogeneity indices (HI), however worse values for the conformity index (CI) were also found when compared to VMAT. The IMRT MRL plans showed similar OAR sparing when the orig. PTV margins were used but a significantly better sparing was feasible when red. PTV margins were applied. Higher number of MU and longer predicted treatment delivery times were seen for both IMRT MRL plans. Conclusions A comparable plan quality between VMAT and IMRT MRL plans was achieved, when applying the same PTV margin. However, online MR-guided adaptive radiotherapy allows for a reduction of PTV margins. With a red. PTV margin, better sparing of the surrounding tissues can be achieved, while maintaining adequate target coverage. Nonetheless, longer treatment delivery times, characteristic for the IMRT technique, have to be expected.

Abstract Background and purpose To report on our clinical experience with a newly implemented workflow for radiotherapy (RT) emergency treatments, which allows for a fast treatment application outside the regular working-hours, and its clinical applicability. Methods Treatment planning of 18 emergency RT patients was carried out using diagnostic computed tomography (CT) without a dedicated RT simulation CT. The cone-beam CT (CBCT) deviations of the first RT treatment were analyzed regarding setup accuracy. Furthermore, feasibility of the “fast-track” workflow was evaluated with respect to dose deviations caused by different Hounsfield unit (HU) to relative electron density (rED) calibrations and RT treatment couch surface shapes via 3D gamma index analysis of exemplary treatment plans. The dosimetric uncertainty introduced by different CT calibrations was quantified. Results Mean patient setup vs. CBCT isocenter deviations were (0.49 ± 0.44) cm (x), (2.68 ± 1.63) cm (y) and (1.80 ± 1.06) cm (z) for lateral, longitudinal and vertical directions, respectively. Three out of four dose comparisons between the emergency RT plan calculated on the diagnostic CT and the same plan calculated on the treatment planning CT showed clinically acceptable gamma passing rates, when correcting for surface artifacts. The maximum difference of rED was 0.054, while most parts of the CT calibration curves coincided well. Conclusion In an emergency RT setting, the use of diagnostic CT data for treatment planning might be time-saving and was shown to be suitable for many cases, considering reproducibility of patient setup, accuracy of initial patient setup and accuracy of dose-calculation.

Abstract The integration of magnetic resonance imaging (MRI) for guidance in external beam radiotherapy has faced significant research and development efforts in recent years. The current availability of linear accelerators with an embedded MRI unit, providing volumetric imaging at excellent soft tissue contrast, is expected to provide novel possibilities in the implementation of image-guided adaptive radiotherapy (IGART) protocols. This study reviews open medical physics issues in MR-guided radiotherapy (MRgRT) implementation, with a focus on current approaches and on the potential for innovation in IGART. Daily imaging in MRgRT provides the ability to visualize the static anatomy, to capture internal tumor motion and to extract quantitative image features for treatment verification and monitoring. Those capabilities enable the use of treatment adaptation, with potential benefits in terms of personalized medicine. The use of online MRI requires dedicated efforts to perform accurate dose measurements and calculations, due to the presence of magnetic fields. Likewise, MRgRT requires dedicated quality assurance (QA) protocols for safe clinical implementation. Reaction to anatomical changes in MRgRT, as visualized on daily images, demands for treatment adaptation concepts, with stringent requirements in terms of fast and accurate validation before the treatment fraction can be delivered. This entails specific challenges in terms of treatment workflow optimization, QA, and verification of the expected delivered dose while the patient is in treatment position. Those challenges require specialized medical physics developments towards the aim of fully exploiting MRI capabilities. Conversely, the use of MRgRT allows for higher confidence in tumor targeting and organs-at-risk (OAR) sparing. The systematic use of MRgRT brings the possibility of leveraging IGART methods for the optimization of tumor targeting and quantitative treatment verification. Although several challenges exist, the intrinsic benefits of MRgRT will provide a deeper understanding of dose delivery effects on an individual basis, with the potential for further treatment personalization.

Abstract Background Volumetric Modulated Arc Therapy (VMAT) techniques have recently been implemented in clinical practice for total-body irradiation (TBI). To date, most techniques still use special couches, translational tables, or other self-made immobilization devices for dose delivery. Aim of the present study was to report the first results of a newly developed rotatable tabletop designed for VMAT-TBI. Methods The VMAT-TBI technique theoretically allows the use of any standard positioning device at the linear accelerator. Nevertheless, the main problem is that patients taller than 120 cm cannot be treated in one position due to the limited cranial-caudal couch shift capacities of the linac. Therefore, patients are usually turned from a head-first supine position (HFS) to a feet-first supine position (FFS) to overcome this limitation. The newly developed rotatable tabletop consists completely of carbon fiber, including the ball bearing within the base plate of the rotation unit. The patient can be turned 180° from a HFS to a FFS position within a few seconds, without the need of repositioning. Results The first 20 patients had a median age of 47 years, and received TBI before bone marrow transplantation for acute myeloid leukemia. Most patients (13/20) received a TBI dose of 4 Gy in 2 fractions, twice daily. The mean number of applied monitor units (MU) was 6476 MU using a multi-arcs and multi-isocenter VMAT-TBI technique. The tabletop has been successfully used in daily clinical practice and helped to keep the treatment times at an acceptable level. During the first treatment fraction, the mean overall treatment time (OTT) was 57 min. Since no additional image guidance was used in fraction 2 of the same day, the OTT was reduced to mean 38 min. Conclusions The easy and reproducible rotation of the patient on the treatment couch using the rotatable tabletop, is time-efficient and overcomes the need of repositioning the patient after turning from a HFS to a FFS position during VMAT TBI. Furthermore, it prevents couch-gantry collisions, incorrect isocenter shifts and beam mix-up due to predicted absolute table coordinates, which are recorded to the R + V system with the corresponding beams.

Abstract Background In this dosimetric study, a dedicated planning tool for single isocenter stereotactic radiosurgery for multiple brain metastases using dynamic conformal arc therapy (DCAT) was compared to standard volumetric modulated arc therapy (VMAT). Methods Twenty patients with a total of 66 lesions who were treated with the DCAT tool were included in this study. Single fraction doses of 15–20 Gy were prescribed to each lesion. Patients were re-planned using non-coplanar VMAT. Number of monitor units as well as V4Gy, V5Gy and V8Gy were extracted for every plan. Using a density-based clustering algorithm, V10Gy and V12Gy and the volume receiving half of the prescribed dose were extracted for every lesion. Gradient indices and conformity indices were calculated. The correlation of the target sphericity, a measure of how closely the shape of the target PTV resembles a sphere, to the difference in V10Gy and V12Gy between the two techniques was assessed using Spearman’s correlation coefficient. Results The automated DCAT planning tool performed significantly better in terms of all investigated metrics (p

Abstract Background Intrafraction motion is particularly problematic in case of small target volumes and narrow margins. Here we simulate the dose coverage of intraprostatic lesions (IPL) by simultaneous integrated boosts (SIB). For this purpose, we use a large sample of actual intrafraction motion data. Methods Fifty-three h of intra-fraction motion of the prostate were recorded in real-time by 4D ultrasound (4DUS) during 720 fractions in 28 patients. We simulate spherical IPLs with 3, 5, and 7 mm radius and matching spherical SIBs with 0, 2, and 5 mm safety margins. The volumetric overlap between IPLs and SIBs is calculated. Dose volume histograms (DVH) are estimated by Monte Carlo simulation. Results On average, the distance of the prostate was 1.3 mm from its initial position over all fractions and patients. Average volumetric overlap was 73, 82, and 87% of IPL volume in case of 3, 5, and 7 mm IPLs and SIBs without safety margins. These improved to 95% or more in case of 2 mm safety margins and 98% or more in case of 5 mm safety margins. DVHs showed that 80% of the IPL volume received 60, 72, and 79% of maximum dose in case of 3, 5, and 7 mm IPLs and SIBs without safety margins. These improved to 94% or more given moderately sized safety margins of 2 mm. Conclusions On average over all fractions and patients, the dose coverage would have been acceptable even for small target volumes such as IPLs of radius 3 to 7 mm and narrow fields. Moderate safety margins of 2 mm could have ensured a delivery of 90% or more of the SIB dose to the IPL. In this case, SIB volume would have been considerably larger than IPL volume, but still considerably smaller than the overall PTV of the prostate.

Building energy code compliance is the crucial link between the actual energy savings and the efficiency prescribed in energy codes. A research project aiming to identify opportunities to reduce energy consumption in new single-family residential construction by increasing compliance with the building energy code was conducted in several states of the United States. The study was comprised of three phases: (1) a baseline study to document typical practice and identify opportunities for improvement based on empirical data gathered from the field; (2) an education and training phase targeting the opportunities identified; and (3) a post-study to assess whether a reduction in average state-wide energy use could be achieved following the education and training phase. We proposed a novel methodology based on large-scale building energy simulation inferred by limited field data to assess the performance of a large population of homes. This paper presents the methodology, findings, and results of this study. The state-wide average energy consumption decreased at Phase III from Phase I for five of the seven states involved in the analysis. The measure-level savings potential analysis shows an overall reduction. Overall, the training and education phase plays a recognizable role in improving compliance with building energy codes.

During the last years, scientists and practitioners have attempted to define and implement the feasible models of building and nurturing e-learning communities in order to continuously activate group dynamics, gain highly interactive learning experiences, and significantly enhance their sense of community. The main objective of this paper is to identify a model for the sense of community behaviour attributes description. The article's sections are: (1) introduction, (2) description of the conceptual model, (3) brief presentation of ECQA, and (4) research on the sense of e-learning communities of ECQA. In the final sectioner, general conclusions and recommendations for future research are presented.

PurposeGlioblastoma is the most common type of primary brain malignancy and has a poor prognosis. The standard treatment strategy is based on maximal safe surgical resection followed by radiotherapy and chemotherapy. Surgical resection can be optimized by using 5-delta-aminolevulinic acid (5-ALA)–induced fluorescence, which is the current mainstay. Although 5-ALA–induced fluorescence has gained general acceptance, it is also limited by inter-observer variability and non-standardized fluorescence parameters. We present a new software for processing images analysis to better recognize the tumor infiltration margins using an intraoperative immediate safety map of 5-ALA–induced fluorescence. We tested this in a brain model using a commercial surgical exoscope.MethodsA dedicated software GLIOVIS (ACQuF-II, Advanced Colorimetry-based Quantification of Fluorescence) was designed for processing analysis of images taken on the Intraoperative Orbital Camera Olympus Orbeye (IOC) to determine the relative quantification of Protoporphyrin IX (5-ALA metabolite) fluorescence. The software allows to superpose the new fluorescence intensity map and the safety margins over the original images. The software was tested on gel-based brain models.ResultsTwo surrogate models were developed: PpIX agarose gel–integrated in gelatin-based brain model at different scales (1:25 and 1:1). The images taken with the IOC were then processed using GLIOVIS. The intensity map and safety margins could be obtained for all available models.ConclusionsGLIOVIS for 5-ALA–guided surgery image processing was validated on various gelatin-based brain models. Different levels of fluorescence could be qualitatively digitalized using this technique. These results need to be further confirmed and corroborated in vivo and validated clinically in order to define a new standard of care for glioblastoma resection.

Glioblastoma multiforme (GBM) is usually treated with surgery followed by adjuvant partial radiotherapy combined with temozolomide (TMZ) chemotherapy. Recent studies demonstrated a better survival and good response to TMZ in methylguanine-DNA methyltransferase (MGMT)-methylated GBM cases. However, approximately 20% of patients with MGMT-unmethylated GBM display an unexpectedly favorable outcome. Therefore, additional mechanisms related to the TMZ response need to be investigated. As such, we decided to investigate the clinical relevance of six miRNAs involved in brain tumorigenesis (miR-181c, miR-181d, miR-21, miR-195, miR-196b, miR-648) as additional markers of response and survival in patients receiving TMZ for GBM. We evaluated miRNA expression and the interplay between miRNAs in 112 IDH wt GBMs by applying commercial assays. Then, we correlated the miRNA expression with patients’ clinical outcomes. Upon bivariate analyses, we found a significant association between the expression levels of the miRNAs analyzed, but, more interestingly, the OS curves show that the combination of low miR-648 and miR-181c or miR-181d expressions is associated with a worse prognosis than cases with other low-expression miRNA pairs. To conclude, we found how specific miRNA pairs can influence survival in GBM cases treated with TMZ.

BackgroundTo detect restenosis after carotid endarterectomy (CEA), long-term monitoring is required. However, non-selective follow-up is controversial and can be limited by costs and logistical considerations.ObjectiveTo examine the value of immediate perioperative vessel flow measurements after CEA using quantitative magnetic resonance angiography (QMRA) to detect patients at risk of long-term restenosis.MethodsA prospective cohort study with long-term sonographic follow-up after CEA for symptomatic internal carotid artery stenosis (ICAs) > 50%. In all patients, vessel flow has been assessed both pre- and postoperatively using QMRA within ±3 days of surgery. Data on QMRA assessment were analyzed to identify patients at risk of restenosis for up to 10 years.ResultsRestenosis was recorded in 4 of 24 patients (17%) at a median follow-up of 6.8 ± 2.6 years. None of them experienced an ischemic event. Perioperative flow differences were significantly greater in patients without long-term restenosis, both for the ipsilateral ICA (p < 0.001) and MCA (p = 0.03), compared to those with restenosis (p = 0.22 and p = 0.3, respectively). The ICA mean flow ratio (p = 0.05) tended to be more effective than the MCA ratio in predicting restenosis over the long term (p = 0.35).ConclusionOur preliminary findings suggest that QMRA-based mean flow increases after CEA may be predictive of restenosis over the long term. Perioperative QMRA assessment could become an operator-independent screening tool to identify a subgroup of patients at risk for restenosis, in whom long-term monitoring is advised.

OBJECTIVE The management of brain tumour patients who would like to resume driving is complex, and needs multidisciplinary input and a consensus among treating physicians. The Swiss Neuro-Oncology Society (SwissNOS) and the Swiss Society for Legal Medicine (SGRM) aim to provide guidance on how to assess “fitness-to-drive” of glioblastoma patients and to harmonise the relevant procedures in Switzerland. METHODS At several meetings, Swiss neuro-oncologists discussed common practices on how to advise patients with a stable, i.e., non-progressive, glioblastoma, who wish to resume driving after the initial standard tumour treatment. All participants of the SwissNOS meetings were invited twice to return a questionnaire (modified Delphi process) on specific tools/procedures they commonly use to assess “fitness-to-drive” of their patients. Answers were analysed to formulate a tentative consensus for a structured and reasonable approach. RESULTS Consensus on minimum requirements for a “fitness-to-drive”programme for glioblastoma patients could be reached among Swiss neuro-oncologists. The recommendations were based on existing guidelines and expert opinions regarding patients with seizures, visual disturbances, cognitive impairment or focal deficits for safe driving. At this point in time, the Swiss neuro-oncologists agreed on the following requirements for glioblastoma patients after the initial standard therapy and without a seizure for at least 12 months: (1) stable cranial magnetic resonance imaging (MRI) according to Response Assessment in Neuro-Oncology (RANO) criteria, to be repeated every 3 months; (2) thorough medical history, including current or new medication, a comprehensive neurological examination at baseline (T0) and every 3 months thereafter, optionally an electrocencephalogram (EEG) at baseline; (3) ophthalmological examination including visual acuity and intact visual fields; and (4) optional neuropsychological assessment with a focus on safe driving. Test results have to be compatible with safe driving at any time-point. Patients should be informed about test results and optionally sign a document. CONCLUSIONS We propose regular thorough clinical neurological examination and brain MRI, optional EEG, neuropsychological and visual assessments to confirm “fitness-to-drive” for glioblastoma patients after initial tumour-directed therapy. The proposed “fitness-to-drive” assessments for glioblastoma patients serves as the basis for a prospective Swiss Pilot Project GLIODRIVE (BASEC ProjectID 2020-00365) to test feasibility, adherence and safety in a structured manner for patients who wish to resume driving. Research will focus on confirming the usefulness of the proposed tools in predicting “fitness-to-drive” and match results with events obtained from the road traffic registry (Strassenverkehrsamt).

Gliomas are intrinsic brain tumours, which are classified by the World Health Organization (WHO) into different grades of malignancy, with glioblastoma being the most frequent and most malignant subtype (WHO grade IV). Mutations in the isocitrate dehydrogenase (IDH) 1 or 2 genes are frequent in lower (WHO II/III) grade tumours but typically absent in classical glioblastoma. IDH mutations are associated with a better prognosis compared with IDH wild-type tumours of the same WHO grade. Following detection of a tumour mass by imaging, maximum safe surgery as feasible is commonly performed to reduce mass effect and to obtain tissue allowing histopathological diagnosis and molecular assessment. Radiotherapy has been the mainstay in the treatment of diffuse gliomas for several decades. It provides improved local control, but is not curative. Furthermore, several randomised trials have shown that the addition of alkylating chemotherapy, either temozolomide or nitrosourea-based regimens, to radiotherapy results in prolonged survival. Tumour-treating fields (TTFields) have emerged as an additional treatment option in combination with maintenance temozolomide treatment for patients with newly diagnosed glioblastoma. Treatment at recurrence is less standardised and depends on the patient’s performance status, symptom burden and prior treatments. Bevacizumab prolongs progression-free survival in newly diagnosed and recurrent glioblastoma, but does not impact overall survival. However, in Switzerland and some other countries, it is still considered a valuable treatment option to reduce clinical symptom burden. Given the generally poor outcome for these patients, various novel treatment approaches are currently being explored within clinical trials including immunotherapeutic strategies such as immune checkpoint inhibition and the brain-penetrant proteasome inhibitor marizomib.

BACKGROUND Plaque vulnerability plays an important role in determining the risk of subsequent cerebrovascular events in patients with carotid stenosis. Plaque morphology magnetic resonance imaging (MRI) can be used to assess plaque vulnerability. We therefore set out to examine the diagnostic accuracy of plaque morphology MRI compared with histopathological findings as gold standard in moderate- to high-grade carotid stenosis at our centre. METHODS A total of 36 patients with moderate- to high-grade carotid stenosis underwent plaque morphology MRI with a multisequence protocol (time of flight sequence, dark blood T1- [native and post-gadolinium] and T2-weighted sequence with fat suppression). The status of the fibrous cap, calcification, lipid-rich necrotic core (LRNC) and intraplaque haemorrhage (IPH) were assessed by means of qualitative MR analysis of plaque characteristics and compared with the histopathological findings. Detection statistics (sensitivity, specificity), chi-squared test, Cohen’s kappa (κ), percentage of agreement and phi coefficient (φ) were determined. RESULTS Carotid stenosis was symptomatic (transient ischaemic attack, amaurosis fugax or ischaemic stroke in the territory of the stenosed carotid artery) in 25 patients (69.5%). Twenty-eight patients (77.8%) had a high-grade and eight patients (12.2%) a moderate-grade stenosis. Significant congruence between MRI and histology was found for plaque calcification (89% histology, 75% MRI, κ = 0.364, p = 0.013), for LRNC (89% histology, 53% MRI, κ = 0.245, p = 0.025) and IPH (75% histology, 53% MRI, κ = 0.314, p = 0.035). In a subgroup of patients with symptomatic stenosis, the agreement for LRNC and IPH was slightly better (LRNC κ = 0.390, p = 0.014; IPH κ = 0.386, p = 0.045). Status of the fibrous cap, essentially ulceration, did not show any significant agreement (κ = 0.032, p = 0.842). There was significant correlation between LRNC on MRI and symptomatic carotid stenosis (φ = 0.339, p = 0.042). CONCLUSION Plaque morphology MRI is capable of identifying the main components of atherosclerotic plaques with moderate to good accuracy as compared with histopathological findings as gold standard. LRNC seems to be a useful marker of plaque vulnerability and warrants its use in clinical decision making.

Object: The treatment of choice in glioblastoma (GBM) is the maximal surgical extent of resection (EOR) followed by adjuvant chemo-radiotherapy. Furthermore, methylguanine-DNA methyltransferase (MGMT) promoter methylation is associated with prolonged overall survival (OS) and progression free survival (PFS). The objective of the present study is correlate the biomolecular aspects in relation with EOR.Materials and methods: We analyzed a series of 116 patients with IDH-1 wild type GBM and different EOR (Gross Total Resection—GTR-, Partial Resection—PR- and Biopsy), treated with adjuvant chemo-radiotherapy. The MGMT status was analyzed in terms of promoter methylation and protein expression.Results: When GTR was possible, OS and PFS were significantly better compared to the other two groups (p = 0.001 and p = 0.035, respectively). MGMT methylation was significantly associated with better OS in the biopsy group (p = 0.022) and better OS and PFS in PR (p = 0.02 and p = 0.012, respectively), but not in the GTR group (p = 0.252 for OS, p = 0.256 for PFS) nor the PFS in the biopsy group (p = 0.259). MGMT protein expression levels do not show any association with OS and PFS, regardless of the type of surgery.Conclusions: Our study confirms the positive association of a safe maximal EOR with better OS and PFS, and indicates a positive prognostic value of MGMT methylation status only in case of the presence of residual tumor tissue. MGMT protein expression seems not to play a clinical role in relation with the type of surgery.

5-Aminolevulinic acid (5-ALA) induced fluorescence to augment surgical resection for high grade glioma has become a standard of care. Protoporphyrin IX (PpIX) visibility is however subject to the variability of the single tumor expression and to the interobserver interpretation. We therefore hypothesized that in different glioma cell lines with variable 5-ALA induced fluorescence, the signal can be pharmacologically increased. We therefore analyzed in three different GBM cell lines, with different expression of epidermal growth factor receptor (EGFR), the variability of 5-ALA induced PpIX fluorescence after the pharmacological blockade at different steps of PpIX breakdown and influencing the outbound transport of PpIX. Using flow cytometry, fluorescence microplate reader, and confocal microscopy the PpIX fluorescence was analyzed after exposure to tin protoporphyrin IX (SnPP), deferoxamine (DFO), and genistein. We furthermore constructed a microscope (Qp9-microscope) being able to measure quantitatively the concentration of PpIX. These values were compared with the extraction of PpIX in tumor biopsy taken during the GBM surgery. Although all three cell lines showed an increase to 5-ALA induced fluorescence their baseline activity was different. Treatment with either SnPP, DFO and genistein was able to increase 5-ALA induced fluorescence. Qp9-microscopy of tumor sample produced a color coded PpIX concentration map which was overlaid on the tumor image. The PpIX extraction from tumor sample analyzed using the plate reader gave lower values of the concentration, as compared to the expected values of the Qp9-microscope, however still in the same decimal range of μg/mL. This may be due to homogenization of the values during extraction and cell disaggregation. In conclusion pharmacological augmentation in GBM cell lines of PpIX signal is possible. A quantitative PpIX map for surgery is feasible and may help refine surgical excision. Further correlations of tumor tissue samples and Qp9-microscopy is needed, prior to develop an intraoperative surgical adjunct to the already existing 5-ALA induced surgery.

PURPOSE: Assessment of the cerebral blood flow (CBF) is crucial in the evaluation of patients with steno-occlusive diseases of the arteries supplying the brain for prediction of stroke risk. Quantitative phase contrast magnetic resonance angiography (PC-MRA) can be utilised for noninvasive quantification of CBF. The aim of this study was to validate in-vivo PC-MRA data by comparing them with colour-coded duplex (CCD) sonography in patients with cerebrovascular disease. METHODS AND MATERIALS: We examined 24 consecutive patients (mean age 63 years) with stenosis of arteries supplying the brain using PC-MRA and CCD. Velocities were measured in a total of 209 stenotic and healthy arterial segments (110 extra- and 99 intracranial). RESULTS: Moderate to good correlation of velocity measurements between both techniques was observed in all six extracranial and five out of seven intracranial segments (p

A common approach to studying the performance of quantum error correcting codes is to assume independent and identically distributed single-qubit errors. However, the available experimental data shows that realistic errors in modern multi-qubit devices are typically neither independent nor identical across qubits. In this work, we develop and investigate the properties of topological surface codes adapted to a known noise structure by Clifford conjugations. We show that the surface code locally tailored to non-uniform single-qubit noise in conjunction with a scalable matching decoder yields an increase in error thresholds and exponential suppression of sub-threshold failure rates when compared to the standard surface code. Furthermore, we study the behaviour of the tailored surface code under local two-qubit noise and show the role that code degeneracy plays in correcting such noise. The proposed methods do not require additional overhead in terms of the number of qubits or gates and use a standard matching decoder, hence come at no extra cost compared to the standard surface-code error correction.

The qubit-mapping problem aims to assign and route qubits of a quantum circuit onto an noisy intermediate-scale quantum (NISQ) device in an optimized fashion, with respect to some cost function. Finding an optimal solution to this problem is known to scale exponentially in computational complexity; as such, it is imperative to investigate scalable qubit-mapping solutions for NISQ computation. In this work, a noise-aware heuristic qubit-assignment algorithm (which assigns initial placements for qubits in a quantum algorithm to qubits on an NISQ device, but does not route qubits during the quantum algorithm’s execution) is presented and compared against the optimal brute-force solution, as well as a trivial qubit assignment, with the aim to quantify the performance of our heuristic qubit-assignment algorithm. We find that for small, connected-graph algorithms, our heuristic-assignment algorithm faithfully lies in between the effective upper and lower bounds given by the brute-force and trivial qubit-assignment algorithms. Additionally, we find that the topological-graph properties of quantum algorithms with over six qubits play an important role in our heuristic qubit-assignment algorithm’s performance on NISQ devices. Finally, we investigate the scaling properties of our heuristic algorithm for quantum processors with up to 100 qubits; here, the algorithm was found to be scalable for quantum-algorithms that admit path-like graphs. Our findings show that as the size of the quantum processor in our simulation grows, so do the benefits from utilizing the heuristic qubit-assignment algorithm, under particular constraints for our heuristic algorithm. This work, thus, characterizes the performance of a heuristic qubit-assignment algorithm with respect to the topological-graph and scaling properties of a quantum algorithm that one may wish to run on a given NISQ device.