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Michael W. McDermott, Jason Sheehan and Steve Braunstein

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Yong Xia and Long Yi Chen

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Zoher Ghogawala, Melissa R. Dunbar and Irfan Essa

OBJECTIVE

There are a wide variety of comparative treatment options in neurosurgery that do not lend themselves to traditional randomized controlled trials. The object of this article was to examine how clinical registries might be used to generate new evidence to support a particular treatment option when comparable options exist. Lumbar spondylolisthesis is used as an example.

METHODS

The authors reviewed the literature examining the comparative effectiveness of decompression alone versus decompression with fusion for lumbar stenosis with degenerative spondylolisthesis. Modern data acquisition for the creation of registries was also reviewed with an eye toward how artificial intelligence for the treatment of lumbar spondylolisthesis might be explored.

RESULTS

Current randomized controlled trials differ on the importance of adding fusion when performing decompression for lumbar spondylolisthesis. Standardized approaches to extracting data from the electronic medical record as well as the ability to capture radiographic imaging and incorporate patient-reported outcomes (PROs) will ultimately lead to the development of modern, structured, data-filled registries that will lay the foundation for machine learning.

CONCLUSIONS

There is a growing realization that patient experience, satisfaction, and outcomes are essential to improving the overall quality of spine care. There is a need to use practical, validated PRO tools in the quest to optimize outcomes within spine care. Registries will be designed to contain robust clinical data in which predictive analytics can be generated to develop and guide data-driven personalized spine care.

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Troy Dawley, Zaker Rana, Hussam Abou-Al-Shaar, Anuj Goenka and Michael Schulder

OBJECTIVE

Complications from radiotherapy (RT), in a primary or adjuvant setting, have overall been described as uncommon, with few detailed descriptions of major complications. The authors present two cases involving significant complications and their management in their review of patients undergoing RT for treatment of atypical meningioma.

METHODS

The authors conducted a retrospective review of all patients with pathologically confirmed atypical meningioma (WHO grade II) treated with primary or adjuvant RT from February 2011 through February 2019. They identified two patients with long-term, grade 3 toxicity. The cases of these patients are described in detail.

RESULTS

Two patients had major complications associated with postoperative RT. Patients 1 and 2 both were treated with postoperative RT for pathologically confirmed atypical meningioma. Patient 1 experienced worsening behavioral changes, cognitive decline, and hydrocephalus following treatment. This required cerebrospinal fluid diversion. Patient 2 developed radiation necrosis with mass effect and cognitive decline. Neither patient returned to his/her initial post-RT status after steroid therapy, and each remained in need of supportive care. Both patients remained free of tumor progression at 52 and 38 months following treatment.

CONCLUSIONS

The postoperative management of patients with atypical meningioma continues to be defined, with questions remaining regarding timing of RT, dose, target delineation, and fractionation. Both of the patients in this study received fractionated RT, which included a greater volume of normal brain than more focal treatment options such as would be required by stereotactic radiosurgery (SRS). Further research is needed to compare SRS and fractionated RT for the management of patients with grade II meningiomas. The more focused nature of SRS may make this a preferred option in certain cases of focal recurrence.

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Ahmad Alhourani, Zaid Aljuboori, Mehran Yusuf, Shiao Y. Woo, Eyas M. Hattab, Norberto Andaluz and Brian J. Williams

OBJECTIVE

The purpose of this study was to describe effects of adjuvant radiotherapy (RT) for anaplastic meningiomas (AMs) on long-term survival, and to analyze patient and RT characteristics associated with long-term survival.

METHODS

The authors queried a retrospective cohort of patients with AM from the National Cancer Database (NCDB) diagnosed between 2004 and 2015 to describe treatment trends. For outcome analysis, patients with at least 10 years of follow-up were included, and they were stratified based on adjuvant RT status and propensity matched to controls for covariates. Survival curves were compared. A data-driven approach was used to find a biologically effective dose (BED) of RT with the largest difference between survival curves. Factors associated with long-term survival were quantified.

RESULTS

The authors identified 2170 cases of AM in the NCDB between 2004 and 2015. They observed increased use of adjuvant RT in patients treated with higher doses. A total of 178 cases met the inclusion criteria for outcome analysis. Forty-five percent (n = 80) received adjuvant RT. Patients received a BED of 80.23 ± 16.6 Gy (mean ± IQR). The median survival time was not significantly different (32.8 months for adjuvant RT vs 38.5 months for no RT; p = 0.57, log-rank test). Dichotomizing the patients at a BED of 81 Gy showed maximal difference in survival distribution with a decrease in median survival in favor of no adjuvant RT (31.2 months for adjuvant RT vs 49.7 months for no RT; p = 0.03, log-rank test), but this difference was not significant after false discovery rate correction. Age was a significant predictor for long-term survival.

CONCLUSIONS

AMs are aggressive tumors that carry a poor prognosis. Conventional adjuvant RT improves local control. However, the effect of adjuvant radiation on overall survival is unclear. Further investigation into this area is warranted.

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Nida Fatima, Antonio Meola, Erqi L. Pollom, Scott G. Soltys and Steven D. Chang

OBJECTIVE

Stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) have been used as a primary treatment or adjuvant to resection in the management of intracranial meningiomas (ICMs). The aim of this analysis is to compare the safety and long-term efficacy of SRS and SRT in patients with primary or recurrent ICMs.

METHODS

A systematic review of the literature comparing SRT and SRS in the same study was conducted using PubMed, the Cochrane Library, Google Scholar, and EMBASE from January 1980 to December 2018. Randomized controlled trials, case-control studies, and cohort studies (prospective and retrospective) analyzing SRS versus SRT for the treatment of ICMs in adult patients (age > 16 years) were included. Pooled and subgroup analyses were based on the fixed-effect model.

RESULTS

A total of 1736 patients from 12 retrospective studies were included. The treatment modality used was: 1) SRS (n = 306), including Gamma Knife surgery (n = 36), linear accelerator (n = 261), and CyberKnife (n = 9); or 2) SRT (n = 1430), including hypofractionated SRT (hFSRT, n = 268) and full-fractionated SRT (FSRT, n = 1162). The median age of patients at the time of treatment was 59 years. The median follow-up duration after treatment was 35.5 months. The median tumor volumes at the time of treatment with SRS, hFSRT, and FSRT were 2.84 cm3, 5.45 cm3, and 12.75 cm3, respectively. The radiographic tumor control at last follow-up was significantly worse in patients who underwent SRS than SRT (odds ratio [OR] 0.47, 95% confidence interval [CI] 0.27–0.82, p = 0.007) with 7% less volume of tumor shrinkage (OR 0.93, 95% CI 0.61–1.40, p = 0.72). Compared to SRS, the radiographic tumor control was better achieved by FSRT (OR 0.46, 95% CI 0.26–0.80, p = 0.006) than by hFSRT (OR 0.81, 95% CI 0.21–3.17, p = 0.76). Moreover, SRS leads to a significantly higher risk of clinical neurological worsening during follow-up (OR 2.07, 95% CI 1.06–4.06, p = 0.03) and of immediate symptomatic edema (OR 4.58, 95% CI 1.67–12.56, p = 0.003) with respect to SRT. SRT could produce a better progression-free survival at 4–10 years compared to SRS, but this was not statistically significant (p = 0.29).

CONCLUSIONS

SRS and SRT are both safe options in the management of ICMs. However, SRT carries a better radiographic tumor control rate and a lower incidence of posttreatment symptomatic worsening and symptomatic edema, with respect to SRS. However, further prospective studies are still needed to validate these results.

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Yagiz Ugur Yolcu, Anshit Goyal, Mohammed Ali Alvi, FM Moinuddin and Mohamad Bydon

OBJECTIVE

Recent studies have reported on the utility of radiosurgery for local control and symptom relief in spinal meningioma. The authors sought to evaluate national utilization trends in radiotherapy (including radiosurgery), investigate possible factors associated with its use in patients with spinal meningioma, and its impact on survival for atypical tumors.

METHODS

Using the ICD-O-3 topographical codes C70.1, C72.0, and C72.1 and histological codes 9530–9535 and 9537–9539, the authors queried the National Cancer Database for patients in whom spinal meningioma had been diagnosed between 2004 and 2015. Patients who had undergone radiation in addition to surgery and those who had received radiation as the only treatment were analyzed for factors associated with each treatment.

RESULTS

From among 10,458 patients with spinal meningioma in the database, the authors found a total of 268 patients who had received any type of radiation. The patients were divided into two main groups for the analysis of radiation alone (137 [51.1%]) and radiation plus surgery (131 [48.9%]). An age > 69 years (p < 0.001), male sex (p = 0.03), and tumor size 5 to < 6 cm (p < 0.001) were found to be associated with significantly higher odds of receiving radiation alone, whereas a Charlson-Deyo Comorbidity Index ≥ 2 (p = 0.01) was associated with significantly lower odds of receiving radiation alone. Moreover, a larger tumor size (2 to < 3 cm, p = 0.01; 3 to < 4 cm, p < 0.001; 4 to < 5 cm, p < 0.001; 5 to < 6 cm, p < 0.001; and ≥ 6 cm, p < 0.001; reference = 1 to < 2 cm), as well as borderline (p < 0.001) and malignant (p < 0.001) tumors were found to be associated with increased odds of undergoing radiation in addition to surgery. Receiving adjuvant radiation conferred a significant reduction in overall mortality among patients with borderline or malignant spinal meningiomas (HR 2.12, 95% CI 1.02–4.1, p = 0.02).

CONCLUSIONS

The current analysis of cases from a national cancer database revealed a small increase in the use of radiation for the management of spinal meningioma without a significant increase in overall survival. Larger tumor size and borderline or malignant behavior were found to be associated with increased radiation use. Data in the present analysis failed to show an overall survival benefit in utilizing adjuvant radiation for atypical tumors.

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Vincent Prinz, Simon Bayerl, Nora Renz, Andrej Trampuz, Marcus Czabanka, Johannes Woitzik, Peter Vajkoczy and Tobias Finger

OBJECTIVE

Loosening of pedicle screws is a frequent complication after spinal surgery. Implant colonization with low-virulent microorganisms forming biofilms may cause implant loosening. However, the clinical evidence of this mechanism is lacking. Here, the authors evaluated the potential role of microbial colonization using sonication in patients with clinical pedicle screw loosening but without signs of infection.

METHODS

All consecutive patients undergoing hardware removal between January 2015 and December 2017, including patients with screw loosening but without clinical signs of infection, were evaluated. The removed hardware was investigated using sonication.

RESULTS

A total of 82 patients with a mean (± SD) patient age of 65 ± 13 years were eligible for evaluation. Of the 54 patients with screw loosening, 22 patients (40.7%) had a positive sonication result. None of the 28 patients without screw loosening who served as a control cohort showed a positive sonication result (p < 0.01). In total, 24 microorganisms were detected in those 22 patients. The most common isolated microorganisms were coagulase-negative staphylococci (62.5%) and Cutibacterium acnes (formerly known as Propionibacterium acnes) (25%). When comparing only the patients with screw loosening, the duration of the previous spine surgery was significantly longer in patients with a positive microbiological result (288 ± 147 minutes) than in those with a negative result (201 ± 103 minutes) (p = 0.02).

CONCLUSIONS

The low-virulent microorganisms frequently detected on pedicle screws by using sonication may be an important cause of implant loosening and failure. Longer surgical duration increases the likelihood of implant colonization with subsequent screw loosening. Sonication is a highly sensitive approach to detect biofilm-producing bacteria, and it needs to be integrated into the clinical routine for optimized treatment strategies.

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Damian A. Almiron Bonnin, Matthew C. Havrda, Myung Chang Lee, Linton Evans, Cong Ran, David C. Qian, Lia X. Harrington, Pablo A. Valdes, Chao Cheng, Chris I. Amos, Brent T. Harris, Keith D. Paulsen, David W. Roberts and Mark A. Israel

OBJECTIVE

5-aminolevulinic acid (5-ALA)–induced protoporphyrin IX (PpIX) fluorescence is an effective surgical adjunct for the intraoperative identification of tumor tissue during resection of high-grade gliomas. The use of 5-ALA-induced PpIX fluorescence in glioblastoma (GBM) has been shown to double the extent of gross-total resection and 6-month progression-free survival. The heterogeneity of 5-ALA-induced PpIX fluorescence observed during surgery presents a technical and diagnostic challenge when utilizing this tool intraoperatively. While some regions show bright fluorescence after 5-ALA administration, other regions do not, despite that both regions of the tumor may be histopathologically indistinguishable. The authors examined the biological basis of this heterogeneity using computational methods.

METHODS

The authors collected both fluorescent and nonfluorescent GBM specimens from a total of 14 patients undergoing surgery and examined their gene expression profiles.

RESULTS

In this study, the authors found that the gene expression patterns characterizing fluorescent and nonfluorescent GBM surgical specimens were profoundly different and were associated with distinct cellular functions and different biological pathways. Nonfluorescent tumor tissue tended to resemble the neural subtype of GBM; meanwhile, fluorescent tumor tissue did not exhibit a prominent pattern corresponding to known subtypes of GBM. Consistent with this observation, neural GBM samples from The Cancer Genome Atlas database exhibited a significantly lower fluorescence score than nonneural GBM samples as determined by a fluorescence gene signature developed by the authors.

CONCLUSIONS

These results provide a greater understanding regarding the biological basis of differential fluorescence observed intraoperatively and can provide a basis to identify novel strategies to maximize the effectiveness of fluorescence agents.

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Nícollas Nunes Rabelo, Bruno Braga Sisnando da Costa, Gabriel Reis Sakaya, Manoel Jacobsen Teixeira and Eberval Gadelha Figueiredo