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Diana A. Roth O’Brien, Sydney M. Kaye, Phillip J. Poppas, Sean S. Mahase, Anjile An, Paul J. Christos, Benjamin Liechty, David Pisapia, Rohan Ramakrishna, AG Wernicke, Jonathan P. S. Knisely, Susan C. Pannullo, and Theodore H. Schwartz

OBJECTIVE

Publications on adjuvant stereotactic radiosurgery (SRS) are largely limited to patients completing SRS within a specified time frame. The authors assessed real-world local recurrence (LR) for all brain metastasis (BM) patients referred for SRS and identified predictors of SRS timing.

METHODS

The authors retrospectively identified BM patients undergoing resection and referred for SRS between 2012 and 2018. Patients were categorized by time to SRS, as follows: 1) ≤ 4 weeks, 2) > 4–8 weeks, 3) > 8 weeks, and 4) never completed. The relationships between timing of SRS and LR, LR-free survival (LRFS), and survival were investigated, as well as predictors of and reasons for specific SRS timing.

RESULTS

In a cohort of 159 patients, the median age at resection was 64.0 years, 56.5% of patients were female, and 57.2% were in recursive partitioning analysis (RPA) class II. The median preoperative tumor diameter was 2.9 cm, and gross-total resection was achieved in 83.0% of patients. All patients were referred for SRS, but 20 (12.6%) did not receive it. The LR rate was 22.6%, and the time to SRS was correlated with the LR rate: 2.3% for patients receiving SRS at ≤ 4 weeks postoperatively, 14.5% for SRS at > 4–8 weeks (p = 0.03), and 48.5% for SRS at > 8 weeks (p < 0.001). No LR difference was seen between patients whose SRS was delayed by > 8 weeks and those who never completed SRS (48.5% vs 50.0%; p = 0.91). A similar relationship emerged between time to SRS and LRFS (p < 0.01). Non–small cell lung cancer pathology (p = 0.04), earlier year of treatment (p < 0.01), and interval from brain MRI to SRS (p < 0.01) were associated with longer intervals to SRS. The rates of receipt of systemic therapy also differed significantly between patients by category of time to SRS (p = 0.02). The most common reasons for intervals of > 4–8 weeks were logistic, whereas longer delays or no SRS were caused by management of systemic disease or comorbidities.

CONCLUSIONS

Available data on LR rates after adjuvant SRS are often obtained from carefully preselected patients receiving timely treatment, whereas significantly less information is available on the efficacy of adjuvant SRS in patients treated under “real-world” conditions. Management of these patients may merit reconsideration, particularly when SRS is not delivered within ≤ 4 weeks of resection. The results of this study indicate that a substantial number of patients referred for SRS either never receive it or are treated > 8 weeks postoperatively, at which time the SRS-treated patients have an LR risk equivalent to that of patients who never received SRS. Increased attention to the reasons for prolonged intervals from surgery to SRS and strategies for reducing them is needed to optimize treatment. For patients likely to experience delays, other radiotherapy techniques may be considered.

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Mark Lee, Hazel T. Rivera-Rosario, Matthew H. Kim, Gregory P. Bewley, Jane Wang, Zellman Warhaft, Bradley Stylman, Angela I. Park, Aoife MacMahon, Ashutosh Kacker, and Theodore H. Schwartz

OBJECTIVE

The authors developed a negative-pressure, patient face-mounted antechamber and tested its efficacy as a tool for sequestering aerated particles and improving the safety of endonasal surgical procedures.

METHODS

Antechamber prototyping was performed with 3D printing and silicone-elastomer molding. The lowest vacuum settings needed to meet specifications for class I biosafety cabinets (flow rate ≥ 0.38 m/sec) were determined using an anemometer. A cross-validation approach with two different techniques, optical particle sizing and high-speed videography/shadowgraphy, was used to identify the minimum pressures required to sequester aerosolized materials. At the minimum vacuum settings identified, physical parameters were quantified, including flow rate, antechamber pressure, and time to clearance.

RESULTS

The minimum tube pressures needed to meet specifications for class I biosafety cabinets were −1.0 and −14.5 mm Hg for the surgical chambers with (“closed face”) and without (“open face”) the silicone diaphragm covering the operative port, respectively. Optical particle sizing did not detect aerosol generation from surgical drilling at these vacuum settings; however, videography estimated higher thresholds required to contain aerosols, at −6 and −35 mm Hg. Simulation of surgical movement disrupted aerosol containment visualized by shadowgraphy in the open-faced but not the closed-faced version of the mask; however, the closed-face version of the mask required increased negative pressure (−15 mm Hg) to contain aerosols during surgical simulation.

CONCLUSIONS

Portable, negative-pressure surgical compartments can contain aerosols from surgical drilling with pressures attainable by standard hospital and clinic vacuums. Future studies are needed to carefully consider the reliability of different techniques for detecting aerosols.

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Theodore H. Schwartz and Michael W. McDermott

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Benjamin I. Rapoport, Michael W. McDermott, and Theodore H. Schwartz

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Michelle Roytman, Andrew B. Tassler, Ashutosh Kacker, Theodore H. Schwartz, Georgiana A. Dobri, Sara B. Strauss, Alyssa M. Capalbo, Rajiv S. Magge, Marissa Barbaro, Eaton Lin, Joseph R. Osborne, and Jana Ivanidze

BACKGROUND

Esthesioneuroblastoma (ENB), also known as olfactory neuroblastoma, is a rare sinonasal neuroectodermal malignancy with a slow onset of symptoms, favorable 5-year survival, and a propensity for delayed locoregional recurrence. Current treatment options include resection, adjuvant radiotherapy, and/or chemotherapy; however, because of its rarity and location, determining the optimal treatment for ENB has been challenging.

OBSERVATIONS

ENBs strongly express somatostatin receptors (SSTRs), particularly SSTR2, providing a molecular target for imaging and therapy.

LESSONs

The authors present a case series of ENBs imaged with [68Ga]-DOTATATE PET/MRI and PET/CT and discuss the emerging role of [68Ga]-DOTATATE PET for ENB diagnosis, staging, and treatment response monitoring.

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Alexander Micko, Benjamin I. Rapoport, Brett E. Youngerman, Reginald P. Fong, Jennifer Kosty, Andrew Brunswick, Shane Shahrestani, Gabriel Zada, and Theodore H. Schwartz

OBJECTIVE

Incomplete resection of skull base pathology may result in local tumor recurrence. This study investigates the utility of 5-aminolevulinic acid (5-ALA) fluorescence during endoscopic endonasal approaches (EEAs) to increase visibility of pathologic tissue.

METHODS

This retrospective multicenter series comprises patients with planned resection of an anterior skull base lesion who received preoperative 5-ALA at two tertiary care centers. Diagnostic use of a blue light endoscope was performed during EEA for all cases. Demographic and tumor characteristics as well as fluorescence status, quality, and homogeneity were assessed for each skull base pathology.

RESULTS

Twenty-eight skull base pathologies underwent blue-light EEA with preoperative 5-ALA, including 15 pituitary adenomas (54%), 4 meningiomas (14%), 3 craniopharyngiomas (11%), 2 Rathke’s cleft cysts (7%), as well as plasmacytoma, esthesioneuroblastoma, and sinonasal squamous cell carcinoma. Of these, 6 (21%) of 28 showed invasive growth into surrounding structures such as dura, bone, or compartments of the cavernous sinus. Tumor fluorescence was detected in 2 cases (7%), with strong fluorescence in 1 tuberculum sellae meningioma and vague fluorescence in 1 pituicytoma. In all other cases fluorescence was absent. Faint fluorescence of the normal pituitary gland was seen in 1 (7%) of 15 cases. A comparison between the particular tumor entities as well as a correlation between invasiveness, WHO grade, Ki-67, and positive fluorescence did not show any significant association.

CONCLUSIONS

With the possible exception of meningiomas, 5-ALA fluorescence has limited utility in the majority of endonasal skull base surgeries, although other pathology may be worth investigating.

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Theodore H. Schwartz and Michael W. McDermott

The Simpson grading scale, developed in 1957 by Donald Simpson, has been considered the gold standard for defining the surgical extent of resection for WHO grade I meningiomas. Since its introduction, the scale and its modifications have generated enormous controversy. The Simpson grade is based on an intraoperative visual assessment of resection, which is subjective and notoriously inaccurate. The majority of studies in which the grading system was used were performed before routine postoperative MRI surveillance was employed, rendering assessments of extent of resection and the definition of recurrence inconsistent. The infiltration and proliferation potential of tumor components such as hyperostotic bone and dural tail vary widely based on tumor location, as does the molecular biology of the tumor, rendering a universal scale for all meningiomas unfeasible. While extent of resection is clearly important at reducing recurrence rates, achieving the highest Simpson grade resection should not always be the goal of surgery.

Donald Simpson’s name and his scale deserve to be recognized and preserved in the historical pantheon of pioneering and transformative neurosurgical concepts. Nevertheless, his eponymous scale is no longer relevant in modern meningioma surgery. While his message of maximizing extent of resection and minimizing morbidity is still germane, a single measure using subjective criteria cannot be applied universally to all meningiomas, regardless of location. Meningioma surgery should be performed with the goal of achieving maximal safe resection, ideally guided by molecularly tagged fluorescent labeling and assessed using objective criteria, including postoperative MRI as well as molecularly tagged scans such as [68Ga]-DOTATATE-PET.

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Rafael Uribe-Cardenas, Andre E. Boyke, Justin T. Schwarz, Peter F. Morgenstern, Jeffrey P. Greenfield, Theodore H. Schwartz, James T. Rutka, James Drake, and Caitlin E. Hoffman

OBJECTIVE

Early surgical intervention for pediatric refractory epilepsy is increasingly advocated as surgery has become safer and data have demonstrated improved outcomes with early seizure control. There is concern that the risks associated with staged invasive electroencephalography (EEG) in very young children outweigh the potential benefits. Here, the authors present a cohort of children with refractory epilepsy who were referred for invasive monitoring, and they evaluate the role and safety of staged invasive EEG in those 3 years old and younger.

METHODS

The authors conducted a retrospective review of children 3 years and younger with epilepsy, who had been managed surgically at two institutions between 2001 and 2015. A cohort of pediatric patients older than 3 years of age was used for comparison. Demographics, seizure etiology, surgical management, surgical complications, and adverse events were recorded. Statistical analysis was completed using Stata version 13. A p < 0.05 was considered statistically significant. Fisher’s exact test was used to compare proportions.

RESULTS

Ninety-four patients (45 patients aged ≤ 3 [47.9%]) and 208 procedures were included for analysis. Eighty-six procedures (41.3%) were performed in children younger than 3 years versus 122 in the older cohort (58.7%). Forty-two patients underwent grid placement (14 patients aged ≤ 3 [33.3%]); 3 of them developed complications associated with the implant (3/42 [7.14%]), none of whom were among the younger cohort. Across all procedures, 11 complications occurred in the younger cohort versus 5 in the older patients (11/86 [12.8%] vs 5/122 [4.1%], p = 0.032). Two adverse events occurred in the younger group versus 1 in the older group (2/86 [2.32%] vs 1/122 [0.82%], p = 0.571). Following grid placement, 13/14 younger patients underwent guided resections compared to 20/28 older patients (92.9% vs 71.4%, p = 0.23).

CONCLUSIONS

While overall complication rates were higher in the younger cohort, subdural grid placement was not associated with an increased risk of surgical complications in that population. Invasive electrocorticography informs management in very young children with refractory, localization-related epilepsy and should therefore be used when clinically indicated.

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Brett E. Youngerman, Matei A. Banu, Mina M. Gerges, Eseosa Odigie, Abtin Tabaee, Ashutosh Kacker, Vijay K. Anand, and Theodore H. Schwartz

OBJECTIVE

The endoscopic endonasal approach (EEA) has gained increasing popularity for the resection of suprasellar meningiomas (SSMs). Appropriate case selection is critical in optimizing patient outcome. Long-term outcome data are lacking. The authors systematically identified preoperative factors associated with extent of resection (EOR) and determined the relationship between EOR and long-term recurrence after EEA for SSMs.

METHODS

In this retrospective cohort study, the authors identified preoperative clinical and imaging characteristics associated with EOR and built on the recently published University of California, San Francisco resectability score to propose a score more specific to the EEA. They then examined the relationship between gross-total resection (GTR; 100%), near-total resection (NTR; 95%–99%), and subtotal resection (STR; < 95%) and recurrence or progression with Kaplan-Meier survival analysis.

RESULTS

A total of 51 patients were identified. Radiographic GTR was achieved in 40 of 47 (85%) patients in whom it was the surgical goal. Significant independent risk factors for incomplete resection were prior surgery (OR 25.94, 95% CI < 2.00 to 336.49, p = 0.013); tumor lateral to the optic nerve (OR 13.41, 95% CI 1.82–98.99, p = 0.011); and complete internal carotid artery (ICA) encasement (OR 15.12, 95% CI 1.17–194.08, p = 0.037). Tumor size and optic canal invasion were not significant risk factors after adjustment for other variables. A resectability score based on the multivariable model successfully predicted the likelihood of GTR; a score of 0 had a positive predictive value of 97% for GTR, whereas a score of 2 had a negative predictive value of 87.5% for incomplete resection. After a mean follow-up of 40.6 ± 32.4 months (mean ± SD), recurrence was 2.7% after GTR (1 patient with atypical histology), 44.4% after NTR, and 80% after STR (p < 0.0001). Vision was stable or improved in 93.5% and improved in 67.4% of patients with a preoperative deficit. There were 5 (9.8%) postoperative CSF leaks, of which 4 were managed with lumbar drains and 1 required a reoperation.

CONCLUSIONS

The EEA is a safe and effective approach to SSMs, with favorable visual outcomes in well-selected cases. The combination of postoperative MRI-based EOR with direct endoscopic inspection can be used in lieu of Simpson grade to predict recurrence. GTR dramatically reduces recurrence and can be achieved regardless of tumor size, proximity or encasement of the anterior cerebral artery, or medial optic canal invasion. Risk factors for incomplete resection include prior surgery, tumor lateral to the optic nerve, and complete ICA encasement.

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Diana A. Julie, Stefanie P. Lazow, Daniel B. Vanderbilt, Shoshana Taube, Menachem Z. Yondorf, Albert Sabbas, Susan Pannullo, Theodore H. Schwartz, and A. Gabriella Wernicke

OBJECTIVE

Adjuvant radiation therapy (RT), such as cesium-131 (Cs-131) brachytherapy or stereotactic radiosurgery (SRS), reduces local recurrence (LR) of brain metastases (BM). However, SRS is less efficacious for large cavities, and the delay between surgery and SRS may permit tumor repopulation. Cs-131 has demonstrated improved local control, with reduced radiation necrosis (RN) compared to SRS. This study represents the first comparison of outcomes between Cs-131 brachytherapy and SRS for resected BM.

METHODS

Patients with BM treated with Cs-131 and SRS following gross-total resection were retrospectively identified. Thirty patients who underwent Cs-131 brachytherapy were compared to 60 controls who received SRS. Controls were selected from a larger cohort to match the patients treated with Cs-131 in a 2:1 ratio according to tumor size, histology, performance status, and recursive partitioning analysis class. Overall survival (OS), LR, regional recurrence, distant recurrence (DR), and RN were compared.

RESULTS

With a median follow-up of 17.5 months for Cs-131–treated and 13.0 months for SRS-treated patients, the LR rate was significantly lower with brachytherapy; 10% for the Cs-131 cohort compared to 28.3% for SRS patients (OR 0.281, 95% CI 0.082–0.949; p = 0.049). Rates of regional recurrence, DR, and OS did not differ significantly between the two cohorts. Kaplan-Meier analysis with log-rank testing showed a significantly higher likelihood of freedom from LR (p = 0.027) as well as DR (p = 0.018) after Cs-131 compared to SRS treatment (p = 0.027), but no difference in likelihood of OS (p = 0.093). Six (10.0%) patients who underwent SRS experienced RN compared to 1 (3.3%) patient who received Cs-131 (p = 0.417).

CONCLUSIONS

Postresection patients with BM treated with Cs-131 brachytherapy were more likely to achieve local control compared to SRS-treated patients. This study provides preliminary evidence of the potential of Cs-131 to reduce LR following gross-total resection of single BM, with minimal toxicity, and suggests the need for a prospective study to address this question.