Proton beam radiation therapy for vestibular schwannomas-tumor control and hearing preservation rates: a systematic review and meta-analysis.

OBJECTIVE: Proton beam therapy is considered, by some authors, as having the advantage of delivering dose distributions more conformal to target compared with stereotactic radiosurgery (SRS). Here, we performed a systematic review and meta-analysis of proton beam for VSs, evaluating tumor control and cranial nerve preservation rates, particularly with regard to facial and hearing preservation. METHODS: We reviewed, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) articles published between 1968 and September 30, 2022. We retained 8 studies reporting 587 patients. RESULTS: Overall rate of tumor control (both stability and decrease in volume) was 95.4% (range 93.5-97.2%, p heterogeneity= 0.77, p<0.001). Overall rate of tumor progression was 4.6% (range 2.8-6.5%, p heterogeneity < 0.77, p<0.001). Overall rate of trigeminal nerve preservation (absence of numbness) was 95.6% (range 93.5-97.7%, I2 = 11.44%, p heterogeneity= 0.34, p<0.001). Overall rate of facial nerve preservation was 93.7% (range 89.6-97.7%, I2 = 76.27%, p heterogeneity<0.001, p<0.001). Overall rate of hearing preservation was 40.6% (range 29.4-51.8%, I2 = 43.36%, p heterogeneity= 0.1, p<0.001). CONCLUSION: Proton beam therapy for VSs achieves high tumor control rates, as high as 95.4%. Facial rate preservation overall rates are 93%, which is lower compared to the most SRS series. Compared with most currently reported SRS techniques, proton beam radiation therapy for VSs does not offer an advantage for facial and hearing preservation compared to most of the currently reported SRS series.

Virtual reality-based evaluation of neurovascular conflict for the surgical planning of microvascular decompression in trigeminal neuralgia patients.

OBJECTIVE: Trigeminal neuralgia (TN) is a lightning bolt of violent, electrifying, and stinging pain, often secondary to the neurovascular conflict (NVC). The vessels involved in NVC are mostly arteries and rarely veins. Evaluation of NVC in the deep infratentorial region is inseparably connected with cranial imaging. We retrospectively analyzed the potential influence of three-dimensional (3D) virtual reality (VR) reconstructions compared to conventional magnetic resonance imaging (MRI) scans on the evaluation of NVC for the surgical planning of microvascular decompression in patients with TN. METHODS: Medical files were retrospectively analyzed regarding patient- and disease-related data. Preoperative MRI scans were retrospectively visualized via VR software to detect the characteristics of NVC. A questionnaire of experienced neurosurgeons evaluated the influence of VR visualization technique on identification of anatomical structures involved in NVC and on surgical strategy. RESULTS: Twenty-four patients were included and 480 answer sheets were evaluated. Compared to conventional MRI, image presentation using 3D-VR modality significantly influenced the identification of the affected trigeminal nerve (p = 0.004), the vascular structure involved in the NVC (p = 0.0002), and the affected side of the trigeminal nerve (p = 0.005). CONCLUSIONS: In patients with TN caused by NVC, the reconstruction of conventional preoperative MRI scans and the spatial and anatomical presentation in 3D-VR models offers the possibility of increased understanding of the anatomy and even more the underlying pathology, and thus influences operation planning and strategy.

Load-Bearing Capacity and Design Advantages of a Custom-Made, Thin Pure-Titanium Cranioplasty (CranioTop).

BACKGROUND: Adequate and stable coverage of cranial contour and continuity defects of any origin is a common challenge in neurosurgical clinics. This study presents the results of investigations concerning the mechanical load-bearing capacity and design advantages of custom-made implants made from a thin, pure-titanium sheet (CranioTop) (CLinstruments, Attendorn, Germany) for covering complex cranial defects. METHODS: In 9 test series, the stability of three differently shaped and sized thin titanium sheet implants was tested using vertical, uniaxial compression with 3 different compression stamps, to investigate the behaviour of these implants in relation to punctiform as well as planar forces. RESULTS: All 9 model implants showed elastic behavior in the synchronously recorded force/displacement diagrams at an impression of up to 2 mm. The forces at 2 mm deformation were between 170.1 and 702.7 Newton. CONCLUSION: Cranioplasty using CranioTop is a stable procedure for covering skull defects, even those of large dimensions. An added advantage is the significant reduction in effort required to prepare the area of the bone margins compared to other current techniques of cranioplasty.

Self-Shielding Gyroscopic Radiosurgery for Uveal Melanoma: A First Case Report.

Stereotactic radiosurgery (SRS) is a well-established treatment modality for the management of uveal melanoma, achieving high tumor control and eye retention rates. There are several SRS treatment platforms available, including the recently developed self-shielding gyroscopic radiosurgery (GRS) system. We report the first use of GRS in the treatment of uveal melanoma. We report the treatment of a 63-year-old female patient with a left-sided uveal melanoma. Akinesia of the ocular globe in the orbit was achieved by retrobulbar anesthesia. The treatment plan used six isocenters (three with the 10 mm and three with the 7.5 mm apertures) and 140 beams to cover 99.2% of the planning target volume (PTV) with 21 Gy at the 54% isodose line. Treatment was delivered in a single session with the GRS device. The total workflow time from retrobulbar anesthesia to completion of treatment was 122 minutes. The procedure was flawless, clinically well tolerated by the patient, and reliably performed in an outpatient setting, thus comparable to our published experience with robotic SRS. The evaluation of new radiosurgery treatment platforms is critical to maintaining quality standards and refining future treatments.

Self-Shielding Gyroscopic Radiosurgery: A Prospective Experience and Analysis of the First 100 Patients.

Background Stereotactic radiosurgery is a well-established treatment option for the management of various benign and malignant brain tumors. It can be delivered with several treatment platforms, usually requiring shielded radiation vaults to meet regulatory safety requirements. Recent technical advances have led to the first self-shielding platform enabling the delivery of gyroscopic radiosurgery (GRS). Given the limited number of GRS treatment platforms, the novelty of its characteristics, and the lack of available data, we report our prospective experience with the first 100 patients treated with GRS. Materials and methods Patients undergoing GRS for the treatment of intracranial tumors were enrolled in this prospective study. Patient and treatment characteristics, including patient satisfaction, were collected and analyzed. Results A total of 100 patients with 155 tumors were treated. The most commonly treated tumors comprised brain metastases (BM) (49%), vestibular schwannomas (31%), and meningiomas (14%). The median prescription dose for malignant and benign tumors was 20 and 13 Gy, respectively. The median prescription isodose line was 56%. Gross tumor volumes were small, with a median of 0.37 cc for BM and 0.92 cc for the other entities. The median total treatment time was 40 minutes. Dosimetric performance indices showed median values of 1.20 (conformity index), 1.24 (new conformity index), 1.74 (homogeneity index), and 3.13 (gradient index). Volumetric assessment of the treated tumors showed an overall decrease in size at the first available follow-up. Most patients were satisfied with the treatment experience. Conclusion Our first prospective experience of the use of GRS is favorable. Analyses of the dosimetric performance, treatment times, volumetric assessment, and patient satisfaction demonstrate its suitability for stereotactic treatments of intracranial tumors. Further prospective clinical and dosimetric analyses for GRS are pending.

Revitalizing neurosurgical frontiers: The EANS frontiers in neurosurgery committee's strategic framework.

Introduction: The field of neurosurgery faces challenges with the increasing involvement of other medical specialties in areas traditionally led by neurosurgeons. This paper examines the implications of this development for neurosurgical practice and patient care, with a focus on specialized areas like pain management, peripheral nerve surgery, and stereotactic radiosurgery. Research question: To assess the implications of the expanded scope of other specialties for neurosurgical practice and to consider the response of the EANS Frontiers in Neurosurgery Committee to these challenges. Materials and methods: Analysis of recent trends in neurosurgery, including the shift in various procedures to other specialties, demographic challenges, and the emergence of minimally invasive techniques. This analysis draws on relevant literature and the initiatives of the Frontiers in Neurosurgery Committee. Results: We explore a possible decrease in neurosurgical involvement in certain areas, which may have implications for patient care and access to specialized neurosurgical interventions. The Frontiers in Neurosurgery Committee's role in addressing these concerns is highlighted, particularly in terms of training, education, research, and networking for neurosurgeons, especially those early in their careers. Discussion and conclusion: The potential decrease in neurosurgical involvement in certain specialties warrants attention. This paper emphasizes the importance of carefully considered responses by neurosurgical societies, such as the EANS, to ensure neurosurgeons continue to play a vital role in managing neurological diseases. Emphasis on ongoing education, integration of minimally invasive techniques, and multidisciplinary collaboration is essential for maintaining the field's competence and quality in patient care.

A Case-based Guide for World Health Organization (WHO) Grade 2 Meningioma Radiosurgery and Radiation Therapy from The Radiosurgery Society.

PURPOSE: Meningiomas represent the most common primary tumor of the central nervous system. Current treatment options include surgical resection with or without adjuvant radiation therapy (RT), definitive RT, and observation. However, the radiation dose, fractionation, and margins used to treat patients with WHO grade 2 meningiomas, which account for approximately 20% of all meningiomas, are not clearly defined, and deciding on the optimal treatment modality can be challenging owing to the lack of randomized data. METHODS AND MATERIALS: In this manuscript, 3 cases of patients with WHO grade 2 meningiomas are presented with descriptions of treatment options after gross total resection, subtotal resection, and previous irradiation. Treatment recommendations were compiled from 9 central nervous system radiation oncology and neurosurgery experts from The Radiosurgery Society, and the consensus of treatment recommendations is reported. RESULTS: Both conventional and stereotactic RT are treatment options for WHO grade 2 meningiomas. The majority of prospective data in the setting of WHO grade 2 meningiomas involve larger margins. Stereotactic radiosurgery/hypofractionated stereotactic RT are less appropriate in this setting. Conventionally fractionated RT to at least 59.4 Gy is considered standard of care with utilization of preoperative and postoperative imaging to evaluate the extent of disease and possible osseous involvement. After careful discussion, stereotactic radiosurgery/hypofractionated stereotactic RT may play a role for the subset of patients who are unable to tolerate the standard lengthy conventionally fractionated treatment course, for those with prior RT, or for small residual tumors. However, more studies are needed to determine the optimal approach. CONCLUSIONS: This case-based evaluation of the current literature seeks to provide examples for the management of grade 2 meningiomas and give examples of both conventional and stereotactic RT.

Rescuing Infected Deep Brain Stimulation Therapies in Severely Affected Patients.

(1) Background: Infections in deep brain stimulation (DBS) hardware, while an undesired complication of DBS surgeries, can be effectively addressed. Minor infections are typically treated with wound revision and IV antibiotics. However, when visible hardware infection occurs, most centers opt for complete removal, leaving the patient in a preoperative state and necessitating post-removal care. To avoid the need for such care, a novel technique was developed. (2) Methods: The electrodes are placed at the exact same spot and then led to the contralateral side. new extensions and a new generator contralateral to the infection as well. Subsequently, the infected system is removed. This case series includes six patients. (3) Results: The average duration of DBS system implantation before the second surgery was 272 days. Only one system had to be removed after 18 months due to reoccurring infection; the others remained unaffected. Laboratory alterations and pathogens were identified in only half of the patients. (4) Conclusions: The described surgical technique proves to be safe, well tolerated, and serves as a viable alternative to complete system removal. Importantly, it effectively prevents the need of post-removal care for patients.

Is it a glioblastoma? In dubio pro 5-ALA!

BACKGROUND: Differential diagnosis of unclear contrast-enhancing cerebral lesions includes cerebral metastases as well as malignant glioma. In the majority of cases, a definite preoperative diagnosis by neuroradiological assessment alone cannot be made. Since the introduction of 5-ALA-induced fluorescence-guided resection in the treatment of glioblastoma (GBM), the preoperative putative diagnosis of metastasis vs. GBM triggers a specific preoperative preparation of the patients. We analyzed the patient population with known cancer outside the central nervous system who underwent surgery for an assumed cerebral metastasis and for whom the intraoperative diagnosis was corrected to a malignant glioma. METHODS: Retrospective analysis of patients with a known primary cancer who were operated on for an assumed cerebral metastasis, which turned out to be a GBM. The patients were treated at our center between January 2008 and June 2011. RESULTS: We identified ten patients who underwent surgery for an assumed cerebral metastasis and for whom the diagnosis was corrected intraoperatively to a malignant glioma by frozen section. The median age was 68 years (41-82 years). The female-to-male ratio was 2:8. In all patients, the final histopathological analysis of the intracerbral tumors revealed a glioblastoma, while the patients suffered from diverse primary carcinomas. CONCLUSION: A malignant glioma should always be considered as a differential diagnosis of an unclear contrast-enhancing cerebral lesion even for patients with a known malignancy. Furthermore, we make the case for a more liberal indication for 5-ALA.

Stereotactic Radiosurgery for Benign Cavernous Sinus Meningiomas: A Multicentre Study and Review of the Literature.

Cavernous sinus meningiomas (CSMs) remain a surgical challenge due to the intimate involvement of their contained nerves and blood vessels. Stereotactic radiosurgery (SRS) is a safe and effective minimally invasive alternative for the treatment of small- to medium-sized CSMs. Objective: To assess the medium- to long-term outcomes of SRS for CSMs with respect to tumour growth, prevention of further neurological deterioration and improvement of existing neurological deficits. This multicentric study included data from 15 European institutions. We performed a retrospective observational analysis of 1222 consecutive patients harbouring 1272 benign CSMs. All were treated with Gamma Knife stereotactic radiosurgery (SRS). Clinical and imaging data were retrieved from each centre and entered into a common database. All tumours with imaging follow-up of less than 24 months were excluded. Detailed results from 945 meningiomas (86%) were then analysed. Clinical neurological outcomes were available for 1042 patients (85%). Median imaging follow-up was 67 months (mean 73.4, range 24-233). Median tumour volume was 6.2 cc (+/-7), and the median marginal dose was 14 Gy (+/-3). The post-treatment tumour volume decreased in 549 (58.1%), remained stable in 336 (35.6%) and increased in only 60 lesions (6.3%), yielding a local tumour control rate of 93.7%. Only 27 (2.8%) of the 60 enlarging tumours required further treatment. Five- and ten-year actuarial progression-free survival (PFS) rates were 96.7% and 90.1%, respectively. Tumour control rates were higher for women than men (p = 0.0031), and also for solitary sporadic meningiomas (p = 0.0201). There was no statistically significant difference in outcome for imaging-defined meningiomas when compared with histologically proven WHO Grade-I meningiomas (p = 0.1212). Median clinical follow up was 61 months (mean 64, range 6-233). Permanent morbidity occurred in 5.9% of cases at last follow-up. Stereotactic radiosurgery is a safe and effective method for treating benign CSM in the medium term to long term.

Retrospective Comparison of Minimally Invasive and Open Monosegmental Lumbar Fusion, and Impact of Virtual Reality on Surgical Planning and Strategy.

BACKGROUND AND STUDY AIMS: Spinal fusion for symptomatic lumbar spondylolisthesis can be accomplished using an open or minimally invasive surgical (MIS) technique. Evaluation of segmental spondylolisthesis and instabilities and review of their therapies are inseparably connected with lumbar tomographic imaging. We analyzed a cohort of patients who underwent MIS or open monosegmental dorsal fusion and compared surgical outcomes along with complication rates. We furthermore evaluated the influence of virtual reality (VR) visualization on surgical planning in lumbar fusion. MATERIAL AND METHODS: Patient files were retrospectively analyzed regarding patient- and disease-related data, operative performance, surgical outcomes, and perioperative surgical complications. Preoperative computed tomography (CT) and magnetic resonance imaging (MRI) scans were retrospectively visualized via VR software. A questionnaire evaluated the influence of three-dimensional (3D) VR images versus two-dimensional CT and MRI scans on therapy planning, fusion method, and surgical technique and procedure. RESULTS: Overall, 171 patients were included (MIS/open: 90/81). MIS was associated with less blood loss, shorter surgery time and hospital stay, lower complication rates, equivalent long-term patient-reported outcomes, but lower fusion rates and higher late reoperation rates than open surgery. Image presentation using VR significantly influenced the recommended surgical therapies (decompression only/decompression and fusion; p = 0.02), had no significant influence on the recommended fusion method (rigid/dynamic/stand-alone; p = 0.77), and, in cases of rigid fusion, a significant influence on the recommended technique (MIS/open; p = 0.03) and fusion procedure (p = 0.02). CONCLUSION: In patients with monosegmental degenerative or isthmic spondylolisthesis, MIS fusion was advantageous concerning perioperative complication rates and perioperative surgical outcomes, but disadvantageous regarding fusion and reoperation rates compared to open fusion. 3D-VR-based analysis of sectional images significantly influenced the recommended surgical planning.

Recurrent spinal metastasis of a sporadic medullary carcinoma of the thyroid after radiation therapy: a case report and review of the literature.

Sporadic Medullary Carcinoma of the Thyroid is a relatively uncommon entity and at the time of diagnosis, most already present loco-regional metastasis. Therapy should be aggressive to reduce recurrence and mortality. Follow-up period should continue lifelong and should also include calcium/pentagastrin infusion test, as well as 6-month interval diagnostic imaging.

5-ALA Fluorescence in Native Pituitary Adenoma Cell Lines: Resection Control and Basis for Photodynamic Therapy (PDT)?

OBJECTIVE: Pituitary adenomas (PA), especially invasive ones, are often not completely resectable. Usage of 5-aminolevulinic acid (5-ALA) for fluorescence guided surgery could improve the rate of total resection and, additionally, open the doors for photodynamic therapy (PDT) in case of unresectable or partially resected PAs. The aim of this study was to investigate the uptake of 5-ALA and the effect of 5-ALA based PDT in cell lines. METHODS: GH3 and AtT-20 cell lines were incubated with different concentrations of 5-ALA, protoporphyrin IX (PPIX) fluorescence was measured by flow cytometry and fluorescencespectrometry. WST-1 assays were performed to determine the surviving fraction of cells after PDT. PPIX fluorescence intensities and PDT effect of the pituitary adenoma cells were compared to U373MG, a well-known glioblastoma cell line. RESULTS: Both cell lines showed a 5-ALA dependent intracellular PPIX fluorescence. Significant differences after 24hrs of incubation were observed in AtT-20 cells in comparison to GH3. Regardless of the incubation or metabolism time, there was a proliferation inhibiting effect after PDT, with no statistical significance. CONCLUSION: Since GH3 cells showed a heterogenous uptake of 5-ALA in the flow cytometry profile, but not constantly high concentrations they might have a 5-ALA efflux mechanism, which still needs to be determined. In the case of AtT-20, the cells might need a longer time for the uptake due to their size or slow metabolism. We showed that the different cell lines have different uptake and metabolism mechanisms, which needs to be further investigated. The general uptake of 5-ALA allows the possibility of resection control and PDT for pituitary adenomas. But, the role of PDT for unresectable pituitary adenomas deserves further investigations.

Radiobiology of radiosurgery for the central nervous system.

According to Leksell radiosurgery is defined as "the delivery of a single, high dose of irradiation to a small and critically located intracranial volume through the intact skull." Before its birth in the early 60s and its introduction in clinical therapeutic protocols in late the 80s dose application in radiation therapy of the brain for benign and malignant lesions was based on the administration of cumulative dose into a variable number of fractions. The rationale of dose fractionation is to lessen the risk of injury of normal tissue surrounding the target volume. Radiobiological studies of cell culture lines of malignant tumors and clinical experience with patients treated with conventional fractionated radiotherapy helped establishing this radiobiological principle. Radiosurgery provides a single high dose of radiation which translates into a specific toxic radiobiological response. Radiobiological investigations to study the effect of high dose focused radiation on the central nervous system began in late the 50s. It is well known currently that radiobiological principles applied for dose fractionation are not reproducible when single high dose of ionizing radiation is delivered. A review of the literature about radiobiology of radiosurgery for the central nervous system is presented.

The tumour is not enough or is it? Problems and new concepts in the surgery of cerebral metastases.

Cerebral metastases are the most frequent cerebral tumours. Surgery of cerebral metastases plays an indispensible role in a multimodal therapy concept. Conventional white-light, microscopy assisted microsurgical and circumferential stripping of cerebral metastases is neurosurgical standard therapy, but is associated with an extraordinarily high recurrence rate of more than 50% without subsequent whole-brain radiotherapy. Therefore, neurosurgical standard therapy fails to achieve local tumour control in many patients. The present conceptual paper focuses on this issue and discusses the possible causes of the high recurrence rates such as intraoperative dissemination of tumour cells or the lack of sharp delimitation of metastases from the surrounding brain tissue resulting in incomplete resections. Adjuvant whole-brain radiotherapy reduces the risk of local and distant recurrences, but is associated with a well-documented impairment of neurocognitive function. New surgical strategies, such as supramarginal or fluorescence-guided resection, address the possibility of infiltrating tumour parts to achieve more complete resection of cerebral metastases. Supramarginal resection was shown to significantly reduce the risk of a local recurrence and prolongs two-year survival rates. Furthermore, radiosurgery in combination with surgery represents a promising approach.

Long-term tumor control of benign intracranial meningiomas after radiosurgery in a series of 4565 patients.

BACKGROUND: Radiosurgery is the main alternative to microsurgical resection for benign meningiomas. OBJECTIVE: To assess the long-term efficacy and safety of radiosurgery for meningiomas with respect to tumor growth and prevention of associated neurological deterioration. Medium- to long-term outcomes have been widely reported, but no large multicenter series with long-term follow-up have been published. METHODS: From 15 participating centers, we performed a retrospective observational analysis of 4565 consecutive patients harboring 5300 benign meningiomas. All were treated with Gamma Knife radiosurgery at least 5 years before assessment for this study. Clinical and imaging data were retrieved from each center and uniformly entered into a database by 1 author (A.S.). RESULTS: Median tumor volume was 4.8 cm³, and median dose to tumor margin was 14 Gy. All tumors with imaging follow-up < 24 months were excluded. Detailed results from 3768 meningiomas (71%) were analyzed. Median imaging follow-up was 63 months. The volume of treated tumors decreased in 2187 lesions (58%), remained unchanged in 1300 lesions (34.5%), and increased in 281 lesions (7.5%), giving a control rate of 92.5%. Only 84 (2.2%) enlarging tumors required further treatment. Five- and 10-year progression-free survival rates were 95.2% and 88.6%, respectively. Tumor control was higher for imaging defined tumors vs grade I meningiomas (P < .001), for female vs male patients (P < .001), for sporadic vs multiple meningiomas (P < .001), and for skull base vs convexity tumors (P < .001). Permanent morbidity rate was 6.6% at the last follow-up. CONCLUSION: Radiosurgery is a safe and effective method for treating benign meningiomas even in the medium to long term.