Establishment and validation of cyberknife irradiation in a syngeneic glioblastoma mouse model

CyberKnife stereotactic radiosurgery (CK-SRS) precisely delivers radiation to intracranial tumors. However, the underlying radiobiological mechanisms at high single doses are not yet fully understood. Here, we established and evaluated the early radiobiological effects of CK-SRS treatment at a single dose of 20 Gy after 15 days of tumor growth in a syngeneic glioblastoma-mouse model. Exact positioning was ensured using a custom-made, non-invasive, and trackable frame. One superimposed target volume for the CK-SRS planning was created from the fused tumor volumes obtained from MRIs prior to irradiation. Dose calculation and delivery were planned using a single-reference CT scan. Six days after irradiation, tumor volumes were measured using MRI scans, and radiobiological effects were assessed using immunofluorescence staining. We found that CK-SRS treatment reduced tumor volume by approximately 75%, impaired cell proliferation, diminished tumor vasculature, and increased immune response. The accuracy of the delivered dose was demonstrated by staining of DNA double-strand breaks in accordance with the planned dose distribution. Overall, we confirmed that our proposed setup enables the precise irradiation of intracranial tumors in mice using only one reference CT and superimposed MRI volumes. Thus, our proposed mouse model for reproducible CK-SRS can be used to investigate radiobiological effects and develop novel therapeutic approaches

Impact of 68Ga-DOTATOC PET/MRI on robotic radiosurgery treatment planning in meningioma patients: first experiences in a single institution

OBJECTIVEFor stereotactic radiosurgery (SRS) planning, precise contouring of tumor boundaries and organs at risk is of utmost importance. Correct interpretation of standard neuroimaging (i.e., CT and MRI) can be challenging after previous surgeries or in cases of skull base lesions with complex shapes. The aim of this study was to evaluate the impact of 68Ga-DOTATOC PET/MRI on treatment planning for image-guided SRS by CyberKnife.METHODSThe authors retrospectively identified 11 meningioma treatments in 10 patients who received a 68Ga-DOTATOC PET/MRI prior to SRS. The planning target volume (PTV) used for the patients' treatment was defined as the reference standard. This was contoured by a treating radiosurgeon (RS0) using fused planning CT and PET/MRI data sets. The same tumors were then contoured by another experienced radiosurgeon (RS1) and by a less-experienced radiosurgeon (RS2), both blinded to PET data sets. A comparison of target volumes with focus on volume-based metrics and distance to critical structures was performed. RS1 and RS2 also filled in a questionnaire analyzing the confidence level and the subjective need for the implementation of PET data sets for contouring.RESULTSAnalysis showed a subjective personal preference for PET/MRI in all cases for both radiosurgeons, particularly in proximity to critical structures. The analysis of the planning volumes per physician showed significantly smaller RS2-PTV in comparison to RS1-PTV and to RS0-PTV, whereas the median volumes were comparable between RS1-PTV and RS2-PTV (median: RS0: 4.3 cm3 [IQR 3.4-6.5 cm3] and RS1: 4.5 cm3 [IQR 2.7-6 cm3] vs RS2: 2.6 cm3 [IQR 2-5 cm3]; p = 0.003). This was also reflected in the best spatial congruency between the 2 experienced physicians (RS0 and RS1). The percentage of the left-out volume contoured by RS1 and RS2 compared to RS0 with PET/MRI demonstrated a relevant left-out-volume portion in both cases with greater extent for the less-experienced radiosurgeon (RS2) (RS1: 19.1% [IQR 8.5%-22%] vs RS2: 40.2% [IQR 34.2%-53%]). No significant differences were detected regarding investigated critical structures.CONCLUSIONSThis study demonstrated a relevant impact of PET/MRI on target volume delineation of meningiomas. The extent was highly dependent on the experience of the treating physician. This preliminary study supports the relevance of 68Ga-DOTATOC PET/MRI as a tool for radiosurgical treatment planning of meningiomas

Image-Guided Robotic Radiosurgery for Treatment of Recurrent Grade II and III Meningiomas. A Single-Center Study

Objective: Stereotactic radiosurgery (SRS) has been increasingly applied for malignant meningiomas as an alternative to conventionally fractioned radiation therapy. We performed a retrospective analysis of an institutional patient cohort with malignant meningiomas treated by image-guided SRS. Methods: All patients with atypical or anaplastic meningiomas who were treated by SRS using CyberKnife (CK) were identified. Local failure and regional and/or distant recurrences were evaluated together with toxicity and overall survival. Results: We identified 127 treated lesions (105 atypical and 22 anaplastic) in 35 patients. The mean time interval between the last surgery and subsequent CK-SRS was 30.8 \ub1 24.5 months. Most lesions (83.5%) were treated using single-fraction CK-SRS. The median planning target volume of all 127 lesions was 1.71 cm3 (range, 0.06\u201322.5 cm3). The median follow-up period was 23 months (range, 2.1\u201360.3 months). The estimated local control rates were 97%, 77%, and 67% at 12, 36, and 60 months, respectively, in atypical meningiomas and 66% each at 12 and 24 months in anaplastic meningiomas. The regional progression-free survival was 93%, 73%, and 59% at 12, 36, and 60 months, respectively, in atypical lesions and 93% and 46% at 12 and 24 months in anaplastic lesions. The estimated distant tumor progression-free interval in atypical lesions was 80%, 44%, and 44% at 12, 36, and 60 months, respectively, and 49% and 24% at 12 and 24 months, respectively, in anaplastic lesions. Age was identified as a risk factor for local failure. Conclusions: Although the real boundaries of efficacy of SRS have to be further evaluated in a prospective trial, it seems that aggressive treatment by high-dose single or multisession SRS of recurring malignant meningiomas provides satisfactory local control rates

Using chloroplast DNA to trace postglacial migration routes of oaks into Britain

Postglacial migration is a major factor responsible for the patterns of genetic variation we see in natural populations. Fossil pollen data indicate that early postglacial colonists such as oak, were able to take both western and eastern migration routes into Britain. Analysis at a finer level is now permitted by the use of modern molecular techniques. A 13-bp duplication in the chloroplast tRNALeul intron occurs in natural populations of East Anglian oaks, but is not found in other parts of Britain or from mainland Europe. The distribution of this marker suggests that the mutation occurred either in southern England, or during migration from the mainland, and became fixed in a source population from which East Anglia was colonized. Planting of non-native trees for roadside boundaries and in the grounds of old houses and estates, explains the absence of the marker from some East Anglian oaks