George Klironomos

Pure endoscopic expanded endonasal approach for olfactory groove and tuberculum sellae meningiomas

The expanded endoscopic endonasal (EEE) approach for the removal of olfactory groove (OGM) and tuberculum sellae (TSM) meningiomas is currently becoming an acceptable surgical approach in neurosurgical practice, although it is still controversial with respect to its outcomes, indications and limitations. Here we provide a review of the available literature reporting results with use of the EEE approach for these lesions together with our experience with the use of the endoscope as the sole means of visualization in a series of patients with no prior surgical biopsy or resection. Surgical cases between May 2006 and January 2013 were retrospectively reviewed. Twenty-three patients (OGM n=6; TSM n=17) were identified. In our series gross total resection (GTR) was achieved in 4/6 OGM (66.7%) and 11/17 (64.7%) TSM patients. Vision improved in the OGM group (2/2) and 8/11 improved in the TSM group with no change in visual status in the remaining three patients. Post-operative cerebrospinal fluid (CSF) leak occurred in 2/6 (33%) OGM and 2/17 (11.8%) TSM patients. The literature review revealed a total of 19 OGM and 174 TSM cases which were reviewed. GTR rate was 73% for OGM and 56.3% for TSM. Post-operative CSF leak was 30% for OGM and 14% for TSM. With careful patient selection and a clear understanding of its limitations, the EEE technique is both feasible and safe. However, longer follow-ups are necessary to better define the appropriate indications and ideal patient population that will benefit from the use of these newer techniques.

The genomic landscape of schwannoma

Schwannomas are common peripheral nerve sheath tumors that can cause debilitating morbidities. We performed an integrative analysis to determine genomic aberrations common to sporadic schwannomas. Exome sequence analysis with validation by targeted DNA sequencing of 125 samples uncovered, in addition to expected NF2 disruption, recurrent mutations in ARID1A, ARID1B and DDR1. RNA sequencing identified a recurrent in-frame SH3PXD2A-HTRA1 fusion in 12/125 (10%) cases, and genomic analysis demonstrated the mechanism as resulting from a balanced 19-Mb chromosomal inversion on chromosome 10q. The fusion was associated with male gender predominance, occurring in one out of every six men with schwannoma. Methylation profiling identified distinct molecular subgroups of schwannomas that were associated with anatomical location. Expression of the SH3PXD2A-HTRA1 fusion resulted in elevated phosphorylated ERK, increased proliferation, increased invasion and in vivo tumorigenesis. Targeting of the MEK-ERK pathway was effective in fusion-positive Schwann cells, suggesting a possible therapeutic approach for this subset of tumors.

Stereotactic radiosurgery for intracranial meningiomas: current concepts and future perspectives.

Meningiomas are among the most common adult brain tumors. Although the optimal management of meningiomas would provide complete elimination of the lesion, this cannot always be accomplished safely through resection. Therefore, other therapeutic modalities, such as stereotactic radiosurgery (as primary or adjunctive therapy), have emerged. In the current review, we have provided an overview of the historical outcomes of various radiosurgical modalities applied in the management of meningiomas. Furthermore, we provide a discussion on key factors (eg World Health Organization grade, lesion size, and lesion location) that affect tumor control and adverse event rates. We discuss recent changes in our understanding of meningiomas, based on molecular and genetic markers, and how these will change our perspective on the management of meningiomas. We conclude by outlining the areas in which knowledge gaps persist and provide suggestions as to how these can be addressed.

The role of 5‐aminolevulinic acid in enhancing surgery for high‐grade glioma, its current boundaries, and future perspectives: A systematic review

5‐Aminolevulinic acid (5‐ALA) has been approved as an intraoperative adjunct in glioma surgery in Europe, but not North America. A systematic review was conducted to assess the evidence regarding 5‐ALA as a surgical adjunct. The MEDLINE, EMBASE, and CENTRAL databases were searched, using terms relevant to “5‐ALA” and “high‐grade gliomas.” Included studies were based on adults aged ≥18 years who underwent surgical resection/biopsy. No language or date limitations were used. Forty‐three studies (1830 patients) were identified. Thirty‐six were coordinated by European countries, 2 were in the United States, and none were in Canada. One was randomized, 28 were prospective, and 14 were retrospective. Twenty‐six studies assessed the utility of 5‐ALA as a diagnostic tool, 24 assessed its influence on the extent of resection (EOR), 9 assessed survival, and 22 reported adverse events. 5‐ALA had high sensitivity and positive predictive value, whereas its specificity increased with additional adjuncts. The EOR increased with 5‐ALA, but only progression‐free survival was significantly influenced. Reporting of adverse events was not systematic. The use of 5‐ALA improved tumor visualization and thus enabled a greater EOR and perhaps increased survival. However, additional adjuncts may be necessary for maximizing the specificity of resection and patient safety. Additional parameters, such as patient quality of life and health economic analyses, would be informative. Thus, additional systematic collection of prospective evidence may be necessary for the global incorporation of this potentially valuable surgical adjunct into routine practice. Cancer 2016;122:2469–78.

Surgically resected skull base meningiomas demonstrate a divergent postoperative recurrence pattern compared with non–skull base meningiomas

OBJECTIVE The objective of this study was to identify the natural history and clinical predictors of postoperative recurrence of skull base and non-skull base meningiomas. METHODS The authors performed a retrospective hospital-based study of all patients with meningioma referred to their institution from September 1993 to January 2014. The cohort constituted both patients with a first-time presentation and those with evidence of recurrence. Kaplan-Meier curves were constructed for analysis of recurrence and differences were assessed using the log-rank test. Cox proportional hazard regression was used to identify potential predictors of recurrence. RESULTS Overall, 398 intracranial meningiomas were reviewed, including 269 (68%) non-skull base and 129 (32%) skull base meningiomas (median follow-up 30.2 months, interquartile range [IQR] 8.5-76 months). The 10-year recurrence-free survival rates for patients with gross-total resection (GTR) and subtotal resection (STR) were 90% and 43%, respectively. Skull base tumors were associated with a lower proliferation index (0.041 vs 0.062, p = 0.001), higher likelihood of WHO Grade I (85.3% vs 69.1%, p = 0.003), and younger patient age (55.2 vs 58.3 years, p = 0.01). Meningiomas in all locations demonstrated an average recurrence rate of 30% at 100 months of follow-up. Subsequently, the recurrence of skull base meningiomas plateaued whereas non-skull base lesions had an 80% recurrence rate at 230 months follow-up (p = 0.02). On univariate analysis, a prior history of recurrence (p < 0.001), initial WHO grade following resection (p < 0.001), and the inability to obtain GTR (p < 0.001) were predictors of future recurrence. On multivariate analysis a prior history of recurrence (p = 0.02) and an STR (p < 0.01) were independent predictors of a recurrence. Assessing only patients with primary presentations, STR and WHO Grades II and III were independent predictors of recurrence (p < 0.001 for both). CONCLUSIONS Patients with skull base meningiomas present at a younger age and have less aggressive lesions overall. Extent of resection is a key predictor of recurrence and long-term follow-up of meningiomas is necessary, especially for non-skull base tumors. In skull base meningiomas, recurrence risk plateaus approximately 100 months after surgery, suggesting that for this specific cohort, follow-up after 100 months can be less frequent.

Salvage stereotactic radiosurgery for brain metastases

Recurrent or progressive brain metastases after initial treatment represent a common clinical entity mainly due to increased survival of cancer patients. From the various available treatment modalities, salvage stereotactic radiosurgery seems to be the most commonly used. Many clinical studies of class of evidence III have demonstrated satisfied results concerning the local brain control and survival of patients with relapsing brain disease. Also stereotactic radiosurgery is considered a relatively safe modality with low incidence of brain toxicity side effects. It is obvious that well-designed, randomized, prospective studies are necessary for the evaluation of the stereotactic radiosurgery as salvage treatment and for the establishment of guidelines for the selection of patients most suitable for this treatment option. The increasing number of patients with relapsing brain metastatic disease will act as a pressure to this direction.