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

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

Robotic Stereotactic Radiosurgery in Melanoma Patients with Brain Metastases under Simultaneous Anti-PD-1 Treatment

Combination concepts of radiotherapy and immune checkpoint inhibition are currently of high interest. We examined imaging findings, acute toxicity, and local control in patients with melanoma brain metastases receiving programmed death 1 (PD-1) inhibitors and/or robotic stereotactic radiosurgery (SRS). Twenty-six patients treated with SRS alone (n = 13;20 lesions) or in combination with anti-PD-1 therapy (n = 13;28 lesions) were analyzed. Lesion size was evaluated three and six months after SRS using a volumetric assessment based on cranial magnetic resonance imaging (cMRI) and acute toxicity after 12 weeks according to the Common Terminology Criteria for Adverse Events (CTCAE). Local control after six months was comparable (86%, SRS + anti-PD-1, and 80%, SRS). All toxicities reported were less than or equal to grade 2. One metastasis (5%) in the SRS group and six (21%) in the SRS + anti-PD-1 group increased after three months, whereas four (14%) of the six regressed during further follow-ups. This was rated as pseudoprogression (PsP). Three patients (23%) in the SRS + anti-PD-1 group showed characteristics of PsP. Treatment with SRS and anti-PD-1 antibodies can be combined safely in melanoma patients with cerebral metastases. Early volumetric progression of lesions under simultaneous treatment may be related to PsP;thus, the evaluation of combined radioimmunotherapy remains challenging and requires experienced teams

Iodine-125 brachytherapy for brain tumours - a review

Iodine-125 brachytherapy has been applied to brain tumours since 1979. Even though the physical and biological characteristics make these implants particularly attractive for minimal invasive treatment, the place for stereotactic brachytherapy is still poorly defined

The P323L substitution in the SARS-CoV-2 polymerase (NSP12) confers a selective advantage during infection

Background The mutational landscape of SARS-CoV-2 varies at the dominant viral genome sequence and minor genomic variant population. During the COVID-19 pandemic, an early substitution in the genome was the D614G change in the spike protein, associated with an increase in transmissibility. Genomes with D614G are accompanied by a P323L substitution in the viral polymerase (NSP12). However, P323L is not thought to be under strong selective pressure. Results Investigation of P323L/D614G substitutions in the population shows rapid emergence during the containment phase and early surge phase during the first wave. These substitutions emerge from minor genomic variants which become dominant viral genome sequence. This is investigated in vivo and in vitro using SARS-CoV-2 with P323 and D614 in the dominant genome sequence and L323 and G614 in the minor variant population. During infection, there is rapid selection of L323 into the dominant viral genome sequence but not G614. Reverse genetics is used to create two viruses (either P323 or L323) with the same genetic background. L323 shows greater abundance of viral RNA and proteins and a smaller plaque morphology than P323. Conclusions These data suggest that P323L is an important contribution in the emergence of variants with transmission advantages. Sequence analysis of viral populations suggests it may be possible to predict the emergence of a new variant based on tracking the frequency of minor variant genomes. The ability to predict an emerging variant of SARS-CoV-2 in the global landscape may aid in the evaluation of medical countermeasures and non-pharmaceutical interventions

Deep Brain Stimulation: Current Applications and Future Prospects

Deep Brain Stimulation (DBS) has proven to be an effective and minimally invasive surgical treatment for a variety of neurological and psychiatric diseases such as Parkinson's Disease, essential tremor, dystonia, Tourette's Syndrome and depression. In contrast to early surgical lesioning procedures, DBS has a considerably lower side-effect rate and is usually reversible. Common targets include nuclei involved in the basal ganglia circuitry as well as its efferent and afferent pathways such as the subthalamic nucleus (STN), the globus pallidus internus (GPi) or the ventral striatal region. Despite the increasing application of DBS, the exact mechanism of action is still matter of debates. Current trials focus on establishing alternative targets, exploring new indications as well as on capturing cortical responses during DBS in order to improve individual stimulation parameters

Differentiation of local tumor recurrence from radiation-induced changes after stereotactic radiosurgery for treatment of brain metastasis: case report and review of the literature

BACKGROUND: Structural follow-up magnetic resonance imaging (MRI) after stereotactic radiosurgery (SRS) for brain metastases frequently displays local changes in the area of applied irradiation, which are often difficult to interpret (e.g., local tumor recurrence, radiation-induced changes). The use of stereotactic biopsy for histological assessment of these changes has a high diagnostic accuracy and can be considered as method of choice. In order to solve this relevant clinical problem non-invasively, advanced MRI techniques and amino acid positron-emission-tomography (PET) are increasingly used. CASE PRESENTATION: We report the long-term follow-up of a patient who had been treated with linear accelerator based SRS for cerebral metastases of a lung cancer. Fifty-eight months after SRS, the differentiation of local recurrent brain metastasis from radiation-induced changes using structural MRI was difficult. For further differentiation, perfusion-weighted MRI (PWI), proton magnetic resonance spectroscopy (MRS), and (11)C-methyl-L-methionine (MET) PET was performed. Due to artifacts and technical limitations, PWI MRI and MRS findings were not conclusive. In contrast, MET PET findings were suggestive for radiation-induced changes. Finally, a stereotactic biopsy for histological assessment of these changes demonstrated clearly a radiation-induced necrosis and the absence of vital tumor. CONCLUSION: The use of stereotactic biopsy for histological assessment of indistinguishable lesions on structural MRI after SRS for treatment of brain metastasis represents a highly reliable method to differentiate local tumor recurrence from radiation-induced changes. In this field, results of studies with both advanced MRI techniques and amino acid PET suggest encouraging results. However, artifacts and technical limitations (e.g., lesion size) are still a problem and comparative studies are needed to investigate the relationship, diagnostic performance, and complementary character of advanced MRI techniques and amino acid PET