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Simple Summary: Anatomical variants are traits that differ between individuals. The sphenoid bone has numerous variant features, such as foramina and canals, that may be involved in surgical procedures. This study on CT-scan images describes the foramen meningo-orbitale, the foramen of Vesalius, the canaliculus innominatus and the palatovaginal canal and their relationships. For the first time, a correlation between the foramen of Vesalius and the canaliculus innominatus was found. This topic is especially important in cranial base surgical procedures that may involve tumor treatment. The sphenoid bone presents several anatomical variations, including accessory foramina, such as the foramen meningo-orbitale, the foramen of Vesalius, the canaliculus innominatus and the palatovaginal canal, which may be involved in tumor invasion or surgery of surrounding structures. Therefore, clinicians and surgeons have to consider these variants when planning surgical interventions of the cranial base. The prevalence of each variant is reported in the published literature, but very little information is available on the possible correlation among different variants. Here, 300 CT scans of patients (equally divided among males and females) were retrospectively assessed to investigate the presence of the foramen meningo-orbitale, the foramen of Vesalius, the canaliculus innominatus and the palatovaginal canal. Possible differences in the prevalence of each accessory foramen according to sex were assessed, as well as possible correlations among different variants through the Chi-square test (p < 0.01). Overall, the prevalence of the foramen meningo-orbitale, the foramen of Vesalius, the canaliculus innominatus and the palatovaginal canal was 30.7%, 67.7%, 14.0% and 35.3%, respectively, without any difference according to sex (p > 0.01). A significant positive correlation was found between the foramen of Vesalius and canaliculus innominatus, both in males and in females (p < 0.01). In detail, subjects with canaliculus innominatus in 85.7–100.0% of cases also showed the foramen of Vesalius, independently from sex and side. The present study provided novel data about the prevalence of four accessory foramina of the sphenoid bone in an Italian population, and a correlation between the foramen of Vesalius and the canaliculus innominatus was found for the first time. As these accessory foramina host neurovascular structures, the results of this study are thus useful for appropriate planning surgical procedures that are tailored to the anatomical configuration of the patient and for improving techniques to avoid accidental injuries in cranial base surgery. Knowledge of the topography, frequencies and the presence/absence of these additional foramina are pivotal for a successful procedure. Clinicians and surgeons may benefit from these novel data for appropriate recognition of the variants, decision-making, pre-operative and treatment planning, improvement of the procedures, screening of patients and prevention of misdiagnosis. [ABSTRACT FROM AUTHOR]

Simple Summary: Vestibular schwannomas are benign tumors of the eighth cranial nerve, caused by mutations in the NF2 gene encoding the tumor suppressor, merlin. A standard treatment for vestibular schwannoma is radiation therapy; however, radiation can cause sudden or progressive hearing loss in patients over time. Most commonly, vestibular schwannomas are treated with stereotactic radiation in one or multiple fractions. In this study, we investigated the effect of different radiation fractionation regimens on hearing in rats, loss of auditory hair cells, and control of tumor growth. Our work suggests that hypofractionation may improve the therapeutic ratio by increasing the likelihood of hearing preservation whilst equally reducing proliferation of tumor cells in comparison with single fraction. Further investigations are needed to understand radiation mechanisms and identify new therapeutic options to reduce hearing loss and enhance tumor control in vestibular schwannoma. Background: Vestibular schwannomas (VS) are benign intracranial tumors caused by loss of function of the merlin tumor suppressor. We tested three hypotheses related to radiation, hearing loss (HL), and VS cell survival: (1) radiation causes HL by injuring auditory hair cells (AHC), (2) fractionation reduces radiation-induced HL, and (3) single fraction and equivalent appropriately dosed multi-fractions are equally effective at controlling VS growth. We investigated the effects of single fraction and hypofractionated radiation on hearing thresholds in rats, cell death pathways in rat cochleae, and viability of human merlin-deficient Schwann cells (MD-SC). Methods: Adult rats received cochlear irradiation with single fraction (0 to 18 Gray [Gy]) or hypofractionated radiation. Auditory brainstem response (ABR) testing was performed for 24 weeks. AHC viabilities were determined using immunohistochemistry. Neonatal rat cochleae were harvested after irradiation, and gene- and cell-based assays were conducted. MD-SCs were irradiated, and viability assays and immunofluorescence for DNA damage and cell cycle markers were performed. Results: Radiation caused dose-dependent and progressive HL in rats and AHC losses by promoting expression of apoptosis-associated genes and proteins. When compared to 12 Gy single fraction, hypofractionation caused smaller ABR threshold and pure tone average shifts and was more effective at reducing MD-SC viability. Conclusions: Investigations into the mechanisms of radiation ototoxicity and VS radiobiology will help determine optimal radiation regimens and identify potential therapies to mitigate radiation-induced HL and improve VS tumor control. [ABSTRACT FROM AUTHOR]

Simple Summary: 5-aminolevulinic acid (5-ALA) is administered orally before brain tumor surgery to improve intraoperative visualization of tumor tissue. In comparison to most of the aggressive high-grade gliomas, only a few low-grade gliomas (LGG) demonstrate visible fluorescence during surgery. As the prognosis of these LGG is hard to predict, we aimed to investigate if visible fluorescence might be an intraoperative marker for aggressive tumor behavior in patients with LGG. According to our data, we could demonstrate that intraoperative visible fluorescence is a predictor for early tumor progression, transformation into more aggressive higher-grade tumors, and shorter survival in LGG patients. Therefore, visible 5-ALA fluorescence is an intraoperative marker of unfavorable prognosis during surgery of LGG. The prediction of the individual prognosis of low-grade glioma (LGG) patients is limited in routine clinical practice. Nowadays, 5-aminolevulinic acid (5-ALA) fluorescence is primarily applied for improved intraoperative visualization of high-grade gliomas. However, visible fluorescence is also observed in rare cases despite LGG histopathology and might be an indicator for aggressive tumor behavior. The aim of this study was thus to investigate the value of intraoperative 5-ALA fluorescence for prognosis in LGG patients. We performed a retrospective analysis of patients with newly diagnosed histopathologically confirmed LGG and preoperative 5-ALA administration at two independent specialized centers. In this cohort, we correlated the visible intraoperative fluorescence status with progression-free survival (PFS), malignant transformation-free survival (MTFS) and overall survival (OS). Altogether, visible fluorescence was detected in 7 (12%) of 59 included patients in focal intratumoral areas. At a mean follow-up time of 5.3 ± 2.9 years, patients with fluorescing LGG had significantly shorter PFS (2.3 ± 0.7 vs. 5.0 ± 0.4 years; p = 0.01), MTFS (3.9 ± 0.7 vs. 8.0 ± 0.6 years; p = 0.03), and OS (5.4 ± 1.0 vs. 10.3 ± 0.5 years; p = 0.01) than non-fluorescing tumors. Our data indicate that visible 5-ALA fluorescence during surgery of pure LGG might be an already intraoperatively available marker of unfavorable patient outcome and thus close imaging follow-up might be considered. [ABSTRACT FROM AUTHOR]

Simple Summary: In non-small cell lung cancer patients with brain metastases, combined Gamma Knife radiosurgery and immunotherapy or targeted therapy showed an increase in overall survival. The combination of Gamma Knife radiosurgery and immunotherapy or targeted therapy did not increase complications related to radiosurgery. Therefore, the combined treatment seems to be a safe and powerful treatment option for non-small cell lung cancer patients with brain metastases. The combination of Gamma Knife radiosurgery (GKRS) and systemic immunotherapy (IT) or targeted therapy (TT) is a novel treatment method for brain metastases (BMs) in non-small cell lung cancer (NSCLC). To elucidate the safety and efficacy of concomitant IT or TT on the outcome after GKRS, 496 NSCLC patients with BMs, who were treated with GKRS were retrospectively reviewed. The median time between the initial lung cancer diagnosis and the diagnosis of brain metastases was one month. The survival after the initial BM diagnosis was significantly longer than the survival predicted by prognostic BM scores. After the first Gamma Knife radiosurgery treatment (GKRS1), the estimated median survival was 9.9 months (95% CI = 8.3–11.4). Patients with concurrent IT or TT presented with a significantly longer survival after GKRS1 than patients without IT or TT (p < 0.001). These significant differences in the survival were also apparent among the four treatment groups and remained significant after adjustment for Karnofsky performance status scale (KPS), recursive partitioning analysis (RPA) class, sex, and multiple BMs. About half of all our patients (46%) developed new distant BMs after GKRS1. Of note, no statistically significant differences in the occurrence of radiation reaction, radiation necrosis, or intralesional hemorrhage in association with IT or TT at or after GKRS1 were observed. In NSCLC-BM patients, the concomitant use of GKRS and IT or TT showed an increase in overall survival without increased complications related to GKRS. Therefore, the combined treatment with GKRS and IT or TT seems to be a safe and powerful treatment option and emphasizes the role of radiosurgery in modern BM treatment. [ABSTRACT FROM AUTHOR]