High-Grade Glioma Radiation Therapy and Reirradiation Treatment Planning Using Translocator Protein Positron Emission Tomography With 18F-GE-180.

Purpose: Translocator protein (TSPO) positron emission tomography (PET) using 18F-GE-180 shows high tumor-to-brain contrast in high-grade glioma (HGG), even in areas without magnetic resonance imaging (MRI) contrast enhancement. Until now, the benefit of 18F-GE-180 PET in primary radiation therapy (RT) and reirradiation (reRT) treatment planning for patients with HGG has not been assessed. Methods and Materials: The possible benefit of 18F-GE-180 PET in RT and reRT planning was retrospectively evaluated through post hoc spatial correlations of PET-based biological tumor volumes (BTVs) with conventional MRI-based consensus gross tumor volumes (cGTVs). To find the ideal threshold for BTV definition in RT and reRT treatment planning, tumor-to-background activity thresholds of 1.6, 1.8, and 2.0 were applied. Spatial overlap of PET- and MRI-based tumor volumes was measured by the Sørensen-Dice coefficient (SDC) and the conformity index (CI). Additionally, the minimal margin to include the entire BTV into the expanded cGTV was determined. Results: Thirty-five primary RT and 16 reRT cases were examined. BTV1.6, BTV1.8, and BTV2.0 were significantly larger than corresponding cGTV volumes in primary RT (median volumes: 67.4, 50.7, and 39.1, respectively, vs 22.6 cm3; P < .001, P < .001, and P = .017, respectively; Wilcoxon test) and reRT cases (median volumes: 80.5, 55.0, and 41.6, respectively, vs 22.7 cm3; P = .001, P = .005, and P = .144, respectively; Wilcoxon test). BTV1.6, BTV1.8, and BTV2.0 showed low but increasing conformity with cGTVs in the primary RT (SDC: 0.51, 0.55, and 0.58, respectively; CI: 0.35, 0.38, and 0.41, respectively) and reRT setting (SDC: 0.38, 0.40, and 0.40, respectively; CI: 0.24, 0.25, and 0.25, respectively). The minimal margin required to include the BTV within the cGTV was significantly smaller in the RT versus the reRT setting for thresholds 1.6 and 1.8 but not significantly different for threshold 2.0 (median margin: 16, 12, and 10, respectively, vs 21.5, 17.5, and 13 mm, respectively; P = .007, P = .031, and P = .093, respectively; Mann-Whitney U test). Conclusions: 18F-GE-180 PET provides valuable information in RT treatment planning for patients with HGG. 18F-GE-180-based BTVs with a threshold of 2.0 were most consistent in primary and reRT.

Multimodal therapy of cavernous sinus meningioma: Impact of surgery and 68Ga-DOTATATE PET-guided radiation therapy on tumor control and functional outcome.

BACKGROUND: Functional preservation in patients with WHO grade I meningioma involving the cavernous sinus (CSM) is crucial for long-term tumor control. Concise data on the functional outcome of an interdisciplinary, multimodal treatment are scarce. We analyzed functional outcome and tumor control in CSM patients following maximal safe resection (MSR), fractionated stereotactic radiotherapy (FSRT), or combination of them, retrospectively. METHODS: Patients with WHO grade I CSM treated between 2003 and 2017 were included. Prior to FSRT, a 68Ga-DOTATATE PET/CT was performed for radiation planning. Progression-free survival (PFS) was analyzed using Kaplan-Meier method and log-rank test was performed to test differences between groups. Visual function was analyzed at baseline and follow-up. RESULTS: Eighty-five patients were included. MSR alone was performed in 48 patients (group A), MSR followed by FSRT in 25 patients (group B), and FSRT alone in 12 patients (group C). Intracranial tumor volumes were higher in A and B compared to C (median 9.2/10.8/4.3 ccm for A/B/C, P = .023). Median follow-up was 47/46/45 months and PFS at 5 years 55.7%, 100%, and 100% in A/B/C, respectively (P < .001). Optic nerve compression was more common in A (91.7%) and B (84.0%) than C (16.7%), P < .001. Post-therapeutic new onset or deterioration of double vision was observed in 29% (A), 17% (B), and 0% (C). CONCLUSION: Personalized treatment strategies for CSM are essential to control space-occupying or functionally compromising lesions. The additional potential side effect of radiotherapy seems to be justified under the aspect of longer tumor control with low functional risk. Without space-occupying effect of CSM, FSRT alone is reasonably possible.

[F18] FDG-PET/CT for manual or semiautomated GTV delineation of the primary tumor for radiation therapy planning in patients with esophageal cancer: is it useful?

BACKGROUND: Target volume definition of the primary tumor in esophageal cancer is usually based on computed tomography (CT) supported by endoscopy and/or endoscopic ultrasound and can be difficult given the low soft-tissue contrast of CT resulting in large interobserver variability. We evaluated the value of a dedicated planning [F18] FDG-Positron emission tomography/computer tomography (PET/CT) for harmonization of gross tumor volume (GTV) delineation and the feasibility of semiautomated structures for planning purposes in a large cohort. METHODS: Patients receiving a dedicated planning [F18] FDG-PET/CT (06/2011-03/2016) were included. GTV was delineated on CT and on PET/CT (GTVCT and GTVPET/CT, respectively) by three independent radiation oncologists. Interobserver variability was evaluated by comparison of mean GTV and mean tumor lengths, and via Sørensen-Dice coefficients (DSC) for spatial overlap. Semiautomated volumes were constructed based on PET/CT using fixed standardized uptake values (SUV) thresholds (SUV30, 35, and 40) or background- and metabolically corrected PERCIST-TLG and Schaefer algorithms, and compared to manually delineated volumes. RESULTS: 45 cases were evaluated. Mean GTVCT and GTVPET/CT were 59.2/58.0 ml, 65.4/64.1 ml, and 60.4/59.2 ml for observers A-C. No significant difference between CT- and PET/CT-based delineation was found comparing the mean volumes or lengths. Mean Dice coefficients on CT and PET/CT were 0.79/0.77, 0.81/0.78, and 0.8/0.78 for observer pairs AB, AC, and BC, respectively, with no significant differences. Mean GTV volumes delineated semiautomatically with SUV30/SUV35/SUV40/Schaefer's and PERCIST-TLG threshold were 69.1/23.9/18.8/18.6 and 70.9 ml. The best concordance of a semiautomatically delineated structure with the manually delineated GTVCT/GTVPET/CT was observed for PERCIST-TLG. CONCLUSION: We were not able to show that the integration of PET/CT for GTV delineation of the primary tumor resulted in reduced interobserver variability. The PERCIST-TLG algorithm seemed most promising compared to other thresholds for further evaluation of semiautomated delineation of esophageal cancer.

Recurrence pattern analysis after [68Ga]-DOTATATE-PET/CT -planned radiotherapy of high-grade meningiomas.

BACKGROUND: The aim of the present study was to evaluate the influence of the applied safety margins of modern intensity-modulated radiotherapy (IMRT) in patients with high-grade meningiomas on local control and recurrence patterns. METHODS: Twenty patients with a neuropathological diagnosis of a high-grade meningioma (WHO°II or °III) treated with adjuvant or definitive radiotherapy between 2010 and 2015 were included in the present retrospective analysis. All patients were planned PET-based. Recurrence patterns were assessed by means of MRI and/or DOTATATE-PET/computertomography (CT). RESULTS: The median follow-up was 31.0 months [95% confidence interval (CI): 20.1-42.0] and the progression-free survival (PFS) after 24 months was 87.5%. Overall, four patients had a local recurrence of their meningioma. Of these, three were located in field according to the prior radiotherapy treatment region, while only one patient had a distant relapse. There were no independent factors influencing progression-free or overall survival (OS). CONCLUSION: After radiotherapy (RT), patients with atypical or anaplastic meningiomas still have a defined risk of tumor recurrence. The aim of the present study was to examine mono-institutional data concerning target volume definition and recurrence patterns after radiotherapy of high-grade meningiomas as there are limited data available. Our data suggest that extended safety margins are necessary to achieve a favorable local control for high-grade meningiomas.

Stereoscopic X-ray imaging, cone beam CT, and couch positioning in stereotactic radiotherapy of intracranial tumors: preliminary results from a cross-modality pilot installation.

BACKGROUND: To assess the accuracy and precision of a fully integrated pilot installation of stereoscopic X-ray imaging and kV-CBCT for automatic couch positioning in stereotactic radiotherapy of intracranial tumors. Positioning errors as detected by stereoscopic X-ray imaging are compared to those by kV-CBCT (i.e. the accuracy of the new method is verified by the established method), and repeated X-ray images are compared (i.e. the precision of new method is determined intra-modally). METHODS: Preliminary results are reported from a study with 32 patients with intracranial tumors. Patients were treated with stereotactic radiotherapy guided by stereoscopic X-ray imaging and kV-CBCT. Patient positioning was automatically corrected by a robotic couch. Cross-modal discrepancies in position detection were measured (N = 42). Intra-modal improvements after correction and re-verification by stereoscopic X-ray imaging were measured (N = 70). The accuracy and precision of stereoscopic X-ray imaging and the accuracy and precision of CBCT were confirmed in phantom measurements (N = 12 shifts of a ball bearing phantom, N = 24 shifts of a head phantom). RESULTS: After correction based on stereoscopic X-ray imaging 95% of residual mean errors were below 0.4, 0.4, 0.5, and 0.7 mm (lateral, longitudinal, vertical, radial, respectively). Stereoscopic X-ray imaging and CBCT were in close agreement with an average discrepancy of 0.1, 0.5, 0.3 and 0.8 mm, respectively. 95% of discrepancies were below 0.8, 1.2, 1.0, and 1.4 mm, respectively. After correction and re-verification by stereoscopic X-ray imaging, the remaining intra-modal residual error was consistent with zero (p = 0.31, p = 0.48, p = 0.81 in lateral, longitudinal, and vertical direction; p-values from two-tailed t-test). The inherent technical accuracy and precision of stereoscopic X-ray imaging and the accuracy and precision of CBCT were found to be of the order of 0.1 mm in controlled phantom settings. CONCLUSIONS: In a routine clinical setting, both stereoscopic X-ray imaging and CBCT were able to reduce positioning errors by an order of magnitude. The end-to-end precision of the system, measured from the discrepancy (mean) between ExacTrac and CBCT, in a clinical setting seems to be about 0.8 mm radially, including couch positioning. The precision (measured from repeatability of ExacTrac, intra-modal) was found to be about 0.7 mm radially in a clinical setting.

Pharmacases.de - a student-centered e-learning project of clinical pharmacology.

AIM: The aim of the project Pharmacases.de was to develop an innovative concept for creating high-quality e-learning content which integrates and promotes the theoretical and cooperative skills of final-year medical students and is easily adoptable by cooperating institutes and hospitals. METHODS AND RESULTS: A peer-teaching concept was developed in which final-year medical students with the elective pharmacology independently researched and wrote e-learning cases of clinical pharmacology ("pharmacases"). Subject-specific expertise was acquired by consulting a peer network of elective students of other disciplines. The created material was subjected to a multi-step peer review and published on the open-access internet platform http://www.pharmacases.de . At present, the website contains 45 e-learning cases, 27 quizzes, and a student-managed discussion forum. Each month, approximately 1200 students access the e-learning content on the website with above-average evaluation results. SUMMARY AND CONCLUSION: The didactic concept of Pharmacases.de enabled the efficient generation of high-quality e-learning content in a student-centered and interdisciplinary manner and was well received by the students. It will likely facilitate the transfer of theoretical pharmacological knowledge into clinical practice.