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Ian Paddick and Alexis Dimitriadis

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Sebastian Butscheidt, Marielle Ernst, Tim Rolvien, Jan Hubert, Jozef Zustin, Michael Amling and Tobias Martens

OBJECTIVE

Primary intraosseous meningioma (PIM) is a rare manifestation of meningioma, a benign, neoplastic lesion of the meninges. Its characteristic appearance is hyperostosis, while no or only minimal dural changes can be observed. This study aims to characterize this rare entity from both a clinical and histopathological point of view in order to improve clinical management.

METHODS

In the years 2009–2017, 26 cases of PIM were diagnosed using MRI and CT scans. In 16 cases the indication for resection was given, and specimens were further examined using a multilevel approach, including histological and immunohistochemical analyses. Additionally, the local database was searched for all cases of meningiomas, as well as osteosclerotic differential diagnoses—i.e., fibrous dysplasia, Paget’s disease of bone, and other benign osteosclerotic lesions.

RESULTS

In this study, PIM represented 2.4% of all meningiomas with a predominant occurrence in females (85%). Regarding the initial manifestation, PIMs show a slightly earlier onset than meningiomas. While most PIMs are located in the sphenoid bone, associated calcifications were visible in 58% of the cases on CT scans. Most of the cases were classified as WHO grade I (93%) and meningotheliomatous meningiomas (91%). Tumor growth was associated with an increased bone resorption followed by massive osteoid deposition and consecutive sclerosis. The frequently observed frayed appearance results from multiple bony canals, which contain blood vessels for the blood supply of the highly vascularized tumor tissue.

CONCLUSIONS

PIM is a rare but important differential diagnosis for osteosclerotic lesions of the skull, especially in women. Tumor-induced, cellular-mediated bone resorption and formation may play a central role in the underlying pathogenesis.

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Hardik Sardana, Roshan Sahu and Shweta Kedia

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Brian Appavu, Stephen T. Foldes and P. David Adelson

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in children both in the United States and throughout the world. Despite valiant efforts and multiple clinical trials completed over the last few decades, there are no high-level recommendations for pediatric TBI available in current guidelines. In this review, the authors explore key findings from the major pediatric clinical trials in children with TBI that have shaped present-day recommendations and the insights gained from them. The authors also offer a perspective on potential efforts to improve the efficacy of future clinical trials in children following TBI.

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Current and novel practice of stereotactic radiosurgery

JNSPG 75th Anniversary Invited Review Article

Douglas Kondziolka

Stereotactic radiosurgery emerged as a neurosurgical discipline in order to utilize energy for the manipulation of brain or nerve tissue, with the goal of minimal access and safe and effective care of a spectrum of neurosurgical disorders. Perhaps no other branch of neurosurgery has been so disruptive across the entire discipline of brain tumor care, treatment of vascular disorders, and management of functional problems. Radiosurgery is mainstream, supported by thousands of peer-reviewed outcomes reports. This article reviews current practice with a focus on challenges, emerging trends, and areas of investigation.

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Abhinav K. Reddy, James S. Ryoo, Steven Denyer, Laura S. McGuire and Ankit I. Mehta

OBJECTIVE

The aim of this study was to illustrate the demographic characteristics of meningioma patients and observe the effect of adjuvant radiation therapy on survival by using the Surveillance, Epidemiology, and End Results (SEER) database. More specifically, the authors aimed to answer the question of whether adjuvant radiotherapy following resection of atypical meningioma confers a cause-specific survival benefit. Additionally, they attempted to add to previous characterizations of the epidemiology of primary meningiomas and assess the effectiveness of the standard of care for benign and anaplastic meningiomas. They also sought to characterize the efficacy of various treatment options in atypical and anaplastic meningiomas separately since nearly all other analyses have grouped these two together despite varying treatment regimens for these behavior categories.

METHODS

SEER data from 1973 to 2015 were queried using appropriate ICD-O-3 codes for benign, atypical, and anaplastic meningiomas. Patient demographics, tumor characteristics, and treatment choices were analyzed. The effects of treatment were examined using a multivariate Cox proportional hazards model and Kaplan-Meier survival analysis.

RESULTS

A total of 57,998 patients were included in the analysis of demographic, meningioma, and treatment characteristics. Among this population, cases of unspecified WHO tumor grade were excluded in the multivariate analysis, leaving a total of 12,931 patients to examine outcomes among treatment paradigms. In benign meningiomas, gross-total resection (HR 0.289, p = 0.013) imparted a significant cause-specific survival benefit over no treatment. In anaplastic meningioma cases, adjuvant radiotherapy imparted a significant survival benefit following both subtotal (HR 0.089, p = 0.018) and gross-total (HR 0.162, p = 0.002) resection as compared to gross-total resection alone. In atypical tumors, gross-total resection plus radiotherapy did not significantly change the hazard risk (HR 1.353, p = 0.628) compared to gross-total resection alone. Similarly, it was found that adjuvant radiation did not significantly benefit survival after a subtotal resection (HR 1.440, p = 0.644).

CONCLUSIONS

The results of this study demonstrate that the role of adjuvant radiotherapy, especially after the resection of atypical meningioma, remains somewhat unclear. Thus, given these results, prospective randomized clinical studies are warranted to provide clear information on the effects of adjuvant radiation in meningioma treatment.

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Swathi Chidambaram, Susan C. Pannullo, Michelle Roytman, David J. Pisapia, Benjamin Liechty, Rajiv S. Magge, Rohan Ramakrishna, Philip E. Stieg, Theodore H. Schwartz and Jana Ivanidze

OBJECTIVE

There is a need for advanced imaging biomarkers to improve radiation treatment planning and response assessment. T1-weighted dynamic contrast-enhanced perfusion MRI (DCE MRI) allows quantitative assessment of tissue perfusion and blood-brain barrier dysfunction and has entered clinical practice in the management of primary and secondary brain neoplasms. The authors sought to retrospectively investigate DCE MRI parameters in meningiomas treated with resection and adjuvant radiation therapy using volumetric segmentation.

METHODS

A retrospective review of more than 300 patients with meningiomas resected between January 2015 and December 2018 identified 14 eligible patients with 18 meningiomas who underwent resection and adjuvant radiotherapy. Patients were excluded if they did not undergo adjuvant radiation therapy or DCE MRI. Demographic and clinical characteristics were obtained and compared to DCE perfusion metrics, including mean plasma volume (v p), extracellular volume (v e), volume transfer constant (K trans), rate constant (k ep), and wash-in rate of contrast into the tissue, which were derived from volumetric analysis of the enhancing volumes of interest.

RESULTS

The mean patient age was 64 years (range 49–86 years), and 50% of patients (7/14) were female. The average tumor volume was 8.07 cm3 (range 0.21–27.89 cm3). The median Ki-67 in the cohort was 15%. When stratified by median Ki-67, patients with Ki-67 greater than 15% had lower median v p (0.02 vs 0.10, p = 0.002), and lower median wash-in rate (1.27 vs 4.08 sec−1, p = 0.04) than patients with Ki-67 of 15% or below. Logistic regression analysis demonstrated a statistically significant, moderate positive correlation between v e and time to progression (r = 0.49, p < 0.05). Furthermore, there was a moderate positive correlation between K trans and time to progression, which approached, but did not reach, statistical significance (r = 0.48, p = 0.05).

CONCLUSIONS

This study demonstrates a potential role for DCE MRI in the preoperative characterization and stratification of meningiomas, laying the foundation for future prospective studies incorporating DCE as a biomarker in meningioma diagnosis and treatment planning.

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Adela Wu, Michael C. Jin, Antonio Meola, Hong-nei Wong and Steven D. Chang

OBJECTIVE

Adjuvant radiotherapy has become a common addition to the management of high-grade meningiomas, as immediate treatment with radiation following resection has been associated with significantly improved outcomes. Recent investigations into particle therapy have expanded into the management of high-risk meningiomas. Here, the authors systematically review studies on the efficacy and utility of particle-based radiotherapy in the management of high-grade meningioma.

METHODS

A literature search was developed by first defining the population, intervention, comparison, outcomes, and study design (PICOS). A search strategy was designed for each of three electronic databases: PubMed, Embase, and Scopus. Data extraction was conducted in accordance with the PRISMA guidelines. Outcomes of interest included local disease control, overall survival, and toxicity, which were compared with historical data on photon-based therapies.

RESULTS

Eleven retrospective studies including 240 patients with atypical (WHO grade II) and anaplastic (WHO grade III) meningioma undergoing particle radiation therapy were identified. Five of the 11 studies included in this systematic review focused specifically on WHO grade II and III meningiomas; the others also included WHO grade I meningioma. Across all of the studies, the median follow-up ranged from 6 to 145 months. Local control rates for high-grade meningiomas ranged from 46.7% to 86% by the last follow-up or at 5 years. Overall survival rates ranged from 0% to 100% with better prognoses for atypical than for malignant meningiomas. Radiation necrosis was the most common adverse effect of treatment, occurring in 3.9% of specified cases.

CONCLUSIONS

Despite the lack of randomized prospective trials, this review of existing retrospective studies suggests that particle therapy, whether an adjuvant or a stand-alone treatment, confers survival benefit with a relatively low risk for severe treatment-derived toxicity compared to standard photon-based therapy. However, additional controlled studies are needed.

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Krishna C. Joshi, Alankrita Raghavan, Baha’eddin Muhsen, Jason Hsieh, Hamid Borghei-Razavi, Samuel T. Chao, Gene H. Barnett, John H. Suh, Gennady Neyman, Varun R. Kshettry, Pablo F. Recinos, Alireza M. Mohammadi and Lilyana Angelov

OBJECTIVE

Gamma Knife radiosurgery (GKRS) has been successfully used for the treatment of intracranial meningiomas given its steep dose gradients and high-dose conformality. However, treatment of skull base meningiomas (SBMs) may pose significant risk to adjacent radiation-sensitive structures such as the cranial nerves. Fractionated GKRS (fGKRS) may decrease this risk, but until recently it has not been practical with traditional pin-based systems. This study reports the authors’ experience in treating SBMs with fGKRS, using a relocatable, noninvasive immobilization system.

METHODS

The authors performed a retrospective review of all patients who underwent fGKRS for SBMs between 2013 and 2018 delivered using the Extend relocatable frame system or the Icon system. Patient demographics, pre- and post-GKRS tumor characteristics, perilesional edema, prior treatment details, and clinical symptoms were evaluated. Volumetric analysis of pre-GKRS, post-GKRS, and subsequent follow-up visits was performed.

RESULTS

Twenty-five patients met inclusion criteria. Nineteen patients were treated with the Icon system, and 6 patients were treated with the Extend system. The mean pre-fGKRS tumor volume was 7.62 cm3 (range 4.57–13.07 cm3). The median margin dose was 25 Gy delivered in 4 (8%) or 5 (92%) fractions. The median follow-up time was 12.4 months (range 4.7–17.4 months). Two patients (9%) experienced new-onset cranial neuropathy at the first follow-up. The mean postoperative tumor volume reduction was 15.9% with 6 patients (27%) experiencing improvement of cranial neuropathy at the first follow-up. Median first follow-up scans were obtained at 3.4 months (range 2.8–4.3 months). Three patients (12%) developed asymptomatic, mild perilesional edema by the first follow-up, which remained stable subsequently.

CONCLUSIONS

fGKRS with relocatable, noninvasive immobilization systems is well tolerated in patients with SBMs and demonstrated satisfactory tumor control as well as limited radiation toxicity. Future prospective studies with long-term follow-up and comparison to single-session GKRS or fractionated stereotactic radiotherapy are necessary to validate these findings and determine the efficacy of this approach in the management of SBMs.