Underrepresentation of racial and ethnic minority groups in gynecologic oncology: An analysis of over 250 trials.

OBJECTIVE: To describe the participation of racial and ethnic minority groups (REMGs) in gynecologic oncology trials. METHODS: Gynecologic oncology studies registered on ClinicalTrials.gov between 2007 and 2020 were identified. Trials with published results were analyzed based on reporting of race/ethnicity in relation to disease site and trial characteristics. Expected enrollment by race/ethnicity was calculated and compared to actual enrollment, adjusted for 2010 US Census population data. RESULTS: 2146 gynecologic oncology trials were identified. Of published trials (n = 252), 99 (39.3%) reported race/ethnicity data. Recent trials were more likely to report these data (36% from 2007 to 2009; 51% 2013-2015; and 53% from 2016 to 2018, p = 0.01). Of all trials, ovarian cancer trials were least likely to report race/ethnicity data (32.1% vs 39.3%, p = 0.011). Population-adjusted under-enrollment for Blacks was 7-fold in ovarian cancer, Latinx 10-fold for ovarian and 6-fold in uterine cancer trials, Asians 2.5-fold in uterine cancer trials, and American Indian and Alaska Native individuals 6-fold in ovarian trials. Trials for most disease sites have enrolled more REMGs in recent years - REMGs made up 19.6% of trial participants in 2007-2009 compared to 38.1% in 2016-2018 (p < 0.0001). CONCLUSION: Less than half of trials that published results reported race/ethnicity data. Available data reveals that enrollment of REMGs is significantly below expected rates based on national census data. These disparities persisted even after additionally adjusting for population size. Despite improvement in recent years, additional recruitment of REMGs is needed to achieve more representative and equitable participation in gynecologic cancer clinical trials.

Pre-operative predictors of post-operative seizure control in low-grade glioma: a systematic review and meta-analysis.

As many as 80% of low-grade gliomas (LGGs) present with seizures, negatively impacting quality of life. While seizures are associated with gliomas regardless of grade, the importance of minimizing impact of seizures for patients with low grade tumors cannot be understated given the prolonged survival period in this population. The objective of this systematic review and meta-analysis was to summarize existing literature and identify factors associated with post-operative seizure control (defined as Engel I classification) in patients with LGGs, with a focus on pre-operative factors. Patient data extracted include tumor location and histology, pre-operative anti-seizure medication use, extent of resection (EOR), adjuvant treatment, pre-operative seizure type, duration, and frequency, and post-operative Engel classification. A random-effects model was used to calculate the effects of EOR, pre-operative seizure duration, adjuvant radiation, and adjuvant chemotherapy on post-operative seizure control. The effect of tumor location and histology on post-operative Engel I classification was determined using contingency analyses. Thirteen studies including 1628 patients with seizures were included in the systematic review. On meta-analyses, Engel I classification was associated with pre-operative seizure type (OR = 0.79 (0.63-0.99), p = 0.0385, focal versus generalized), frontal lobe LGGs (OR = 1.5 (1.1-2.0), p = 0.0195), and EOR (OR (95% CI) = 4.5 (2.3-6.7), p < 0.0001 gross-total versus subtotal). Pre-operative seizure duration less than one year, adjuvant radiation, adjuvant chemotherapy, and tumor histology were not associated with achieving Engel I classification. In addition to the known effects of EOR, Engel I classification is less likely to be achieved in patients with focal pre-operative seizures and more likely to be achieved in patients with frontal lobe LGGs.

Outcomes following surgical resection of trigeminal schwannomas: a systematic review and meta-analysis.

Although typically benign, trigeminal schwannomas (TS) may require surgical resection when large or symptomatic and can cause significant morbidity. This study aims to summarize the literature and synthesize outcomes following surgical resection of TS. A systematic review was performed according to PRISMA guidelines. Data extracted included patient and tumor characteristics, surgical approaches, and postoperative outcomes. Odds ratios (OR) with corresponding 95% confidence intervals (CI) were used for outcome analysis. The initial search yielded 1838 results, of which 26 studies with 974 patients undergoing surgical resection of TS were included. The mean age was 42.9 years and 58.0% were female. The mean tumor diameter was 4.7 cm, with Samii type A, B, C, and D tumors corresponding to 33.4%, 15.8%, 37.2%, and 13.6%, respectively. Over a mean symptom duration of 29 months, patients presented with trigeminal hypesthesia (58.7%), headache (32.8%), trigeminal motor weakness (22.8%), facial pain (21.3%), ataxia (19.4%), diplopia (18.7%), and visual impairment (12.0%). Surgical approaches included supratentorial (61.4%), infratentorial (15.0%), endoscopic (8.6%), combined/staged (5.3%), and anterior (5.7%) or posterior (4.0%) petrosectomy. Postoperative improvement of facial pain (83.9%) was significantly greater than trigeminal motor weakness (33.0%) or hypesthesia (29.4%). The extent of resection (EOR) was reported as gross total (GTR), near total, and subtotal in 77.7%, 7.7%, and 14.6% of cases, respectively. Over a mean follow-up time of 62.6 months, recurrence/progression was noted in 7.4% of patients at a mean time to recurrence of 44.9 months. Patients with GTR had statistically significantly lower odds of recurrence/progression (OR: 0.07; 95% CI: 0.04-0.15) compared to patients with non-GTR. This systematic review and meta-analysis report patient outcomes following surgical resection of TS. EOR was found to be an important predictor of the risk of recurrence. Facial pain was more likely to improve postoperatively than facial hypesthesia. This work reports baseline rates of post-operative complications across studies, establishing benchmarks for neurosurgeons innovating and working to improve surgical outcomes for TS patients.

Characterizing Clinical Trials in Plastic and Reconstructive Surgery: A Systematic Review of ClinicalTrials.gov From 2007 to 2020.

BACKGROUND: Clinical trials form the backbone of evidence-based medicine. ClinicalTrials.gov is the world's largest clinical trial registry, and the state of clinical trials in plastic and reconstructive surgery (PRS) within that database has not been comprehensively studied. To that end, we explored the distribution of therapeutic areas that are under investigation, impact of funding on study design and data reporting, and trends in research patterns of all PRS interventional clinical trials registered with ClinicalTrials.gov. METHODS: Using the ClinicalTrials.gov database, we identified and extracted all clinical trials relevant to PRS that were submitted between 2007 and 2020. Studies were classified based on anatomic locations, therapeutic categories, and specialty topics. Cox proportional hazard was used to calculate adjusted hazard ratios (HRs) for early discontinuation and results reporting. RESULTS: A total of 3224 trials that included 372,095 participants were identified. The PRS trials grew at an annual rate of 7.9%. The therapeutic classes most represented were wound healing (41.3%) and cosmetics (18.1%). Funding for PRS clinical trials is largely provided through academic institutions (72.7%), while industry and US government constituted a minority. Industry-funded studies were more likely to be discontinued early than those funded by academics (HR, 1.89) or government (HR, 1.92) and to be nonblinded and nonrandomized. Academic-funded studies were the least likely to report results data within 3 years of trial completion (odds ratio, 0.87). CONCLUSIONS: A gulf exists in the representation of different PRS specialties among clinical trials. We highlight the role of funding source in trial design and data reporting to identify a potential source of financial waste and to stress the need for continued appropriate oversight.

The role of blood product removal in intraventricular hemorrhage of prematurity: a meta-analysis of the clinical evidence.

INTRODUCTION: Premature neonates have a high risk of intraventricular hemorrhage (IVH) at birth, the blood products of which activate inflammatory cascades that can cause hydrocephalus and long-term neurological morbidities and sequelae. However, there is no consensus for one treatment strategy. While the mainstay of treatment involves CSF diversion to reduce intracranial pressure, a number of interventions focus on blood product removal at various stages including extraventricular drains (EVD), intra-ventricular thrombolytics, drainage-irrigation-fibrinolytic therapy (DRIFT), and neuroendoscopic lavage (NEL). METHODS: We performed a systematic review and meta-analysis to compare the risks and benefits commonly associated with active blood product removal treatment strategies. We searched MEDLINE, Embase, Scopus, Cochrane Library, and CINAHL databases through Dec 2020 for articles reporting on outcomes of EVDs, thrombolytics, DRIFT, and NEL. Outcomes of interest were rate of conversion to ventriculoperitoneal shunt (VPS), infection, mortality, secondary hemorrhage, and cognitive disability. RESULTS: Of the 10,398 articles identified in the search, 23 full-text articles representing 22 cohorts and 530 patients were included for meta-analysis. These articles included retrospective, prospective, and randomized controlled studies on the use of EVDs (n = 7), thrombolytics (n = 8), DRIFT therapy (n = 3), and NEL (n = 5). Pooled rates of reported outcomes for EVD, thrombolytics, DRIFT, and NEL for ventriculoperitoneal shunt (VPS) placement were 51.1%, 43.3%, 34.3%, and 54.8%; for infection, 15.4%, 12.5%, 4.7%, and 11.0%; for mortality, 20.0%, 11.6%, 6.0%, and 4.9%; for secondary hemorrhage, 5.8%, 7.8%, 20.0%, and 6.9%; for cognitive impairment, 52.6%, 50.0%, 53.7%, and 50.9%. Meta-regression using type of treatment as a categorical covariate showed no effect of treatment modality on rate of VPS conversion or cognitive disability. CONCLUSION: There was a significant effect of treatment modality on secondary hemorrhage and mortality; however, mortality was no longer significant after adjusting for year of publication. Re-hemorrhage rate was significantly higher for DRIFT (p < 0.001) but did not differ among the other modalities. NEL also had lower mortality relative to EVD (p < 0.001) and thrombolytics (p = 0.013), which was no longer significant after adjusting for year of publication. Thus, NEL appears to be safer than DRIFT in terms of risk of hemorrhage, and not different than other blood-product removal strategies in terms of mortality. Outcomes-in terms of shunting and cognitive impairment-did not differ. Later year of publication was predictive of lower rates of mortality, but not the other outcome variables. Further prospective and randomized studies will be necessary to directly compare NEL with other temporizing procedures.

Presentation, management and outcome of surgically managed pediatric thoracic outlet syndrome.

PURPOSE: Thoracic outlet syndrome (TOS) is a rare disorder involving compression of the brachial plexus, subclavian artery, and subclavian vein. There is a paucity of data for this pathology's surgical treatment within pediatrics. The objective of this study is to explore the presentation, management, and outcome of pediatric TOS. METHODS: A retrospective chart review was conducted for 44 patients at a single institution undergoing surgery for TOS. Data was collected on demographics, pre- and postoperative factors, and outcomes. RESULTS: Forty-four patients underwent 50 surgeries (8 bilaterally). The average age was 15.5 years with 72% female. The most common symptoms were numbness (72%) and pain (66%), with a normal exam in 58%. The average symptom duration prior to surgery was 35.2 months. A supraclavicular approach was performed in all patients, with anterior scalene section (90%), rib resection (72%), neurolysis (92%), and intraoperative EMG (84%) commonly used. Two patients had a lymphatic leak. All patients reported subjective improvement of preoperative symptoms of numbness (26%), pain (22%), and weakness (6%). Differences between vTOS (n = 9) and nTOS (n = 35) included higher preop swelling (p < 0.012), decreased symptom duration (p < 0.022), higher venogram usage (p < 0.0030), and higher preoperative thrombolytics/angioplasty (p < 0.001) in vTOS compared to nTOS. A comparison of soft tissue and soft tissue with bone decompression did not reveal any outcome differences. CONCLUSION: Pediatric TOS benefits from a multidisciplinary approach, showing good outcomes in postoperative symptom resolution. In our cohort, a supraclavicular approach provided an effective window for decompression with a low complication rate.

The role of surgery in the management of Lennox-Gastaut syndrome: A systematic review and meta-analysis of the clinical evidence.

Lennox-Gastaut syndrome (LGS) is a severe form of childhood onset epilepsy in which patients require multiple medications and may be candidates for palliative surgical intervention. In this meta-analysis, we sought to evaluate the impact of palliative vagus nerve stimulation (VNS), corpus callosotomy (CC), and resective surgery (RS) by analyzing their impact on seizure control, antiepileptic drug (AED) usage, quality of life (QOL), behavior, cognition, prognostic factors, and complications. A systematic search of PubMed MEDLINE, Scopus, and Cochrane Database of Systematic Reviews was performed to find articles that met the following criteria: (1) prospective/retrospective study with original data, (2) at least one LGS surgery patient aged less than 18 years, and (3) information on seizure frequency reduction (measured as percentage, Engel class, or qualitative comment). Seizures were analyzed quantitatively in a meta-analysis of proportions and a random-effects model, whereas other outcomes were analyzed qualitatively. Forty studies with 892 LGS patients met the selection criteria, with 19 reporting on CC, 17 on VNS, four on RS, two on RS + CC, one on CC + VNS, and one on deep brain stimulation. CC seizure reduction rate was 74.1% (95% confidence interval [CI] = 64.5%-83.7%), and VNS was 54.6% (95% CI = 42.9%-66.3%), which was significantly different (p < .001). RS seizure reduction was 88.9% (95% CI = 66.1%-99.7%). Many VNS patients reported alertness improvements, and most had no major complications. VNS was most effective for atonic/tonic seizures; higher stimulation settings correlated with better outcomes. CC patients reported moderate cognitive and QOL improvements; disconnection syndrome, transient weakness, and respiratory complications were noted. Greater callosotomy extent correlated with better outcomes. AED usage most often did not change after surgery. RS showed considerable QOL improvements for patients with localized seizure foci. In the reported literature, CC appeared to be more effective than VNS for seizure reduction. VNS may provide a similar or higher level of QOL improvement with lower aggregate risk of complications. Patient selection, anatomy, and seizure type will inform decision-making.

Vision Outcomes for Pediatric Patients With Optic Pathway Gliomas Associated With Neurofibromatosis Type I: A Systematic Review of the Clinical Evidence.

Children with neurofibromatosis type I (NF1) have a higher predisposition for low-grade astrocytomas of the optic pathway, commonly referred to as optic pathway gliomas (OPGs). OPGs can result in visual deterioration. Treatment outcomes in OPG-NF1 management are often reported around tumor stabilization. We sought to compare vision outcomes associated with different OPG treatment strategies to inform about this important functional metric. A meta-analysis exploring the different modalities to treat children with OPG-NF1 was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using multiple databases. Of the 113 articles identified in the search, 23 full text articles, representing 564 patients, were included for review. These articles included retrospective, prospective, and randomized controlled studies on observation (n=9), chemotherapy (n=19), radiation therapy (n=6), and surgery (n=7). Of the patients undergoing observation, 87% (60/69) demonstrated stable acuity. In the chemotherapy studies, 27.3% (72/264) demonstrated improved acuity/visual field and/or visual-evoked potential amplitudes, 39.4% (104/264) stable acuity, and 33.3% (88/264) deterioration. Both the radiation and surgical treatments reported worsening acuity at 90.9% (10/11) and 73.3% (11/15), respectively. Causal associations are not known. Indications for and timing of treatment choice warrant larger scale study to provide further understanding.

Evaluating outcome associations with race after mechanical thrombectomy: an analysis of the NVQI-QOD acute ischemic stroke registry.

BACKGROUND: Mechanical thrombectomy has become the standard of care for acute ischemic stroke due to large vessel occlusions. Racial differences in outcomes after mechanical thrombectomy for acute ischemic stroke have not been extensively studied. We evaluate the real-world evidence for differences between races in the outcomes of thrombectomy for large vessel occlusions using the NeuroVascular Quality Initiative-Quality Outcomes Database (NVQI-QOD). METHODS: Data from the NVQI-QOD acute ischemic stroke registry were analyzed and compared for racial differences in outcomes after mechanical thrombectomy in 4507 patients from 28 US centers (17 states) between January 2014 and April 2021. Race was dichotomized into non-Hispanic White (NHW, n=3649) and non-Hispanic Black (NHB, n=858). We performed 1:1 propensity score matching resulting in a subsample of matched groups (n=761 each for NHB and NHW) to compare study endpoints using Welch's two-sided t-tests and Χ2 test for continuous and categorical outcomes, respectively. RESULTS: Prior to matching, NHW and NHB patients significantly differed in age, comorbidities, medication use, smoking status, and presenting stroke severity. No significant difference in functional outcomes or mortality, at discharge or follow-up, were revealed. NHB patients had higher average postprocedure length of stay than NHW patients, which persisted following matching (11.2 vs 9.1 days, P=0.004). CONCLUSION: Evidence from the NVQI-QOD acute ischemic stroke registry showed that outcome metrics, such as modified Rankin Scale score and mortality, did not differ significantly between racial groups; however, disparity between NHW and NHB patients in postprocedure length of stay following mechanical thrombectomy was revealed.

Surgical management of spinal metastases from primary thyroid carcinoma: Demographics, clinical characteristics, and treatment outcomes - A retrospective analysis.

Objective: Metastatic spinal tumors represent a rare but concerning complication of primary thyroid carcinoma. We identified demographics, metastatic features, outcomes, and treatment strategies for these tumors in our institutional cohort. Materials and Methods: We retrospectively reviewed patients surgically treated for spinal metastases of primary thyroid carcinoma. Demographics, tumor characteristics, and treatment modalities were collected. The functional outcomes were quantified using Nurik, Modified Rankin, and Karnofsky Scores. Results: Twelve patients were identified who underwent 17 surgeries for resection of spinal metastases. The primary thyroid tumor pathologies included papillary (4/12), follicular (6/12), and Hurthle cell (2/12) subtypes. The average number of spinal metastases was 2.5. Of the primary tumor subtypes, follicular tumors averaged 2.8 metastases at the highest and Hurthle cell tumors averaged 2.0 spinal metastases at the lowest. Five patients (41.7%) underwent preoperative embolization for their spinal metastases. Seven patients (58.3%) received postoperative radiation. There was no significant difference in progression-free survival between patients receiving surgery with adjuvant radiation and surgery alone (P = 0.0773). Five patients (41.7%) experienced postoperative complications. Two patients (16.7%) succumbed to disease progression and two patients (16.7%) experienced tumor recurrence following resection. Postsurgical mean Nurik scores decreased 0.54 points, mean Modified Rankin scores decreased 0.48 points, and mean Karnofsky scores increased 4.8 points. Conclusion: Surgery presents as an important treatment modality in the management of spinal metastases from thyroid cancer. Further work is needed to understand the predictive factors for survival and outcomes following treatment.

The demographic, clinical, and management differences between traumatic dens fracture patients with and without simultaneous atlas fractures.

Introduction: Atlas fractures often accompany traumatic dens fractures, but existing literature on the management of simultaneous atlantoaxial fractures is limited. Methods: We examined all patients with traumatic dens fractures at our institution between 2008 and 2018. We used multivariable logistic regression and ordinal logistic regression to identify factors independently associated with presentation with a simultaneous atlas fracture, as well myelopathy severity, fracture nonunion, and selection for surgery. Results: Two hundred and eighty-two patients with traumatic dens fractures without subaxial fractures were identified, including 65 (22.8%) with simultaneous atlas fractures. The distribution of injury mechanisms differed between groups (χ2 P = 0.0360). On multivariable logistic regression, dens nonunion was positively associated with type II fractures (odds ratio [OR] = 2.00, P = 0.038) and negatively associated with having surgery (OR = 0.52, P = 0.049), but not with having a C1 fracture (P = 0.3673). Worse myelopathy severity on presentation was associated with having a severe injury severity score (OR = 102.3, P < 0.001) and older age (OR = 1.28, P = 0.002), but not with having an atlas fracture (P = 0.2446). Having a simultaneous atlas fracture was associated with older age (OR = 1.29, P = 0.024) and dens fracture angulation (OR = 2.62, P = 0.004). Among patients who underwent surgery, C1/C2 posterior fusion was the most common procedure, and having a simultaneous atlas fracture was associated with selection for occipitocervical fusion (OCF) (OR = 14.35, P = 0.010). Conclusions: Among patients with traumatic dens, patients who have simultaneous atlas fractures are a distinct subpopulation with respect to age, mechanism of injury, fracture morphology, and management. Traumatic dens fractures with simultaneous atlas fractures are independently associated with selection for OCF rather than posterior cervical fusion alone.

Traumatic Dens Fracture Patients Comprise Distinct Subpopulations Distinguished by Differences in Age, Sex, Injury Mechanism and Severity, and Outcome.

BACKGROUND: Dens fractures are an increasingly common injury, yet their epidemiology and its implications remain underexamined. METHODS: We retrospectively analyzed all traumatic dens fracture patients managed at our institution over a 10-year period, examining demographic, clinical, and outcomes data. Patient subsets were compared across these parameters. RESULTS: Among 303 traumatic dens fracture patients, we observed a bimodal age distribution with a strong goodness of fit centered at age 22.3 ± 5.7 (R = 0.8781) and at 77.7 ± 13.9 (R = 0.9686). A population pyramid demonstrated a bimodal distribution among male patients, but not female patients, which was confirmed with a strong goodness of fit for male patient subpopulations age <35 (R = 0.9791) and age ≥35 (R = 0.8843), but a weaker fit for a second female subpopulation age <35. Both age groups were equally likely to undergo surgery. Patients younger than age 35 were more likely to be male (82.4% vs. 46.9%, odds ratio [OR] = 5.29 [1.54, 17.57], P = 0.0052), have motor vehicle collision as their mechanism of injury (64.7% vs. 14.1%, OR = 11.18 [3.77, 31.77], P < 0.0001), and to have a severe trauma injury severity score (17.6% vs. 2.9%, OR = 7.23 [1.88, 28.88], P = 0.0198). Nevertheless, patients age <35 were less likely to have fracture nonunion at follow (18.2% vs. 53.7%, OR = 0.19 [0.041, 0.76], P = 0.0288). CONCLUSIONS: The dens fracture patient population comprises 2 subpopulations, distinguished by differences in age, sex, injury mechanism and severity, and outcome, with male dens fracture patients demonstrating a bimodal age distribution. Young, male patients were more likely to have high-energy injury mechanisms leading to severe trauma, yet were less likely to have fracture nonunion at follow-up.

Odontoid fracture type and angulation affect nonunion risk, but comminution and displacement do not: A propensity score matched analysis of fracture morphology.

OBJECTIVE: Odontoid fractures disproportionately affect older patients who have high surgical risk, but also high rates of fracture nonunion. To guide surgical decision-making, we quantified the effect of fracture morphology on nonunion among nonoperatively managed, traumatic, isolated odontoid fractures. METHODS: We examined all patients with isolated odontoid fractures treated nonoperatively at our institution between 2010 and 2019. Multivariable regression and propensity score matching were used to quantify the effect of fracture type, angulation, comminution, and displacement on bony healing by 26 weeks from injury. RESULTS: 303 consecutive traumatic odontoid fracture patients were identified, of whom 163 (53.8 %) had isolated fractures that were managed nonoperatively. Selection for nonoperative management was more likely with older age (OR=1.31 [1.09, 1.58], p = 0.004), and less likely with higher fracture angle (OR=0.70 [0.55, 0.89], p = 0.004), or higher presenting Nurick scores (OR=0.77 [0.62, 0.94], p = 0.011). Factors associated with nonunion at 26 weeks were fracture angle (OR=5.11 [1.43, 18.26], p = 0.012) and Anderson-D'Alonzo Type II morphology (OR=5.79 [1.88, 17.83], p = 0.002). Propensity score matching to assess the effect of type II fracture, fracture angulation> 10o, displacement≥ 3 mm, and comminution all yielded balanced models (Rubin's B<25.0, 0.5  10o (p = 0.015), and there was an 18.2 % lower rate of bony healing for each 10o increase in fracture angle. Fracture displacement≥ 3 mm and comminution had no significant effect. CONCLUSION: Type II fracture morphology and fracture angle > 10o significantly increase nonunion among nonoperatively managed isolated traumatic odontoid fractures, but fracture comminution and displacement ≥ 3 mm do not.

Recurrent pediatric infratentorial ependymomas: a systematic review and meta-analysis on outcomes and molecular classification.

OBJECTIVE: The aim of this study was to summarize the prognosis of recurrent infratentorial ependymomas based on treatment and molecular characterization. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the authors searched the PubMed, Scopus, Embase, and Ovid databases for studies on recurrent infratentorial ependymomas in patients younger than 25 years of age. Exclusion criteria included case series of fewer than 5 patients and studies that did not provide time-dependent survival data. RESULTS: The authors' database search yielded 482 unique articles, of which 18 were included in the final analysis. There were 479 recurrent infratentorial pediatric ependymomas reported; 53.4% were WHO grade II and 46.6% were WHO grade III tumors. The overall mortality for recurrent infratentorial pediatric ependymomas was 49.1% (226/460). The pooled mean survival was 30.2 months after recurrence (95% CI 22.4-38.0 months). Gross-total resection (GTR) was achieved in 243 (59.0%) patients at initial presentation. The mean survival postrecurrence for those who received initial GTR was 42.3 months (95% CI 35.7-47.6 months) versus 26.0 months (95% CI 9.6-44.6 months) for those who received subtotal resection (STR) (p = 0.032). There was no difference in the mean survival between patients who received GTR (49.3 months, 95% CI 32.3-66.3 months) versus those who received STR (41.4 months, 95% CI 11.6-71.2 months) for their recurrent tumor (p = 0.610). In the studies that included molecular classification data, there were 169 (83.3%) posterior fossa group A (PFA) tumors and 34 (16.7%) posterior fossa group B (PFB) tumors, with 28 tumors harboring a 1q gain. PFA tumors demonstrated worse mean postprogression patient survival (24.7 months, 95% CI 15.3-34.0 months) compared with PFB tumors (48.0 months, 95% CI 32.8-63.2 months) (p = 0.0073). The average postrecurrence survival for patients with 1q+ tumors was 14.7 months. CONCLUSIONS: The overall mortality rate for recurrent infratentorial ependymomas was found to be 49.1%, with a pooled mean survival of 30.2 months in the included sample population. More than 80% of recurrent infratentorial ependymomas were of the PFA molecular subtype, and both PFA tumors and those with 1q gain demonstrated worse prognosis after recurrence.

Surgery Decreases Nonunion, Myelopathy, and Mortality for Patients With Traumatic Odontoid Fractures: A Propensity Score Matched Analysis.

BACKGROUND: Existing literature suggests that surgical intervention for odontoid fractures is beneficial but often does not control for known confounding factors. OBJECTIVE: To examine the effect of surgical fixation on myelopathy, fracture nonunion, and mortality after traumatic odontoid fractures. METHODS: We analyzed all traumatic odontoid fractures managed at our institution between 2010 and 2020. Ordinal multivariable logistic regression was used to identify factors associated with myelopathy severity at follow-up. Propensity score analysis was used to test the treatment effect of surgery on nonunion and mortality. RESULTS: Three hundred and three patients with traumatic odontoid fracture were identified, of whom 21.6% underwent surgical stabilization. After propensity score matching, populations were well balanced across all analyses (Rubin's B < 25.0, 0.5 < Rubin's R < 2.0). Controlling for age and fracture angulation, type, comminution, and displacement, the overall rate of nonunion was lower in the surgical group (39.7% vs 57.3%, average treatment effect [ATE] = -0.153 [-0.279, -0.028], P = .017). Controlling for age, sex, Nurick score, Charlson Comorbidity Index, Injury Severity Score, and selection for intensive care unit admission, the mortality rate was lower for the surgical group at 30 days (1.7% vs 13.8%, ATE = -0.101 [-0.172, -0.030], P = .005) and at 1 year was 7.0% vs 23.7%, ATE = -0.099 [-0.181, -0.017], P = .018. Cox proportional hazards analysis also demonstrated a mortality benefit for surgery (hazard ratio = 0.587 [0.426, 0.799], P = .0009). Patients who underwent surgery were less likely to have worse myelopathy scores at follow-up (odds ratio = 0.48 [0.25, 0.93], P = .029). CONCLUSION: Surgical stabilization is associated with better myelopathy scores at follow-up and causes lower rates of fracture nonunion, 30-day mortality, and 1-year mortality.

Post-Surgical Prognosis of Patients with Pineoblastoma: A Systematic Review and Individual Patient Data Analysis with Trends over Time.

Most of the literature on pineoblastoma consists of case reports and single-institution series. The goal of this systematic review and individual patient data (IPD) analysis was to summarize the existing literature, identify factors associated with overall survival (OS), and provide a contemporary update on prognosis for patients with pineoblastoma. Forty-four studies were identified with 298 patients having IPD. Kaplan-Meier analyses were used to report survival outcomes based on age, tumor metastases, extent of resection (EOR), adjuvant therapy, and publication year. Cox regression was performed to identify independent predictors of time to mortality. Multivariable recursive partitioning analysis was used to identify the most important subgroups associated with mortality. Patients were classified based on publication year before and after the last systematic review on this topic (pre-2012 and 2012 onwards) and compared using univariate and multivariable analyses. This study demonstrates that EOR less-than-gross total resection, metastatic presentation, adjuvant chemotherapy without radiation, and tumor presentation in children less than three years old are associated with poorer prognosis. Since 2012, the 5-year actuarial OS has improved from 32.8% to 56.1%, which remained significant even after accounting for EOR, age, and adjuvant therapy. Pineoblastoma remains a severe rare disease, but survival outcomes are improving.

Analysis of socioeconomic and demographic factors on post-treatment outcomes for metastatic spinal tumors.

OBJECTIVE: Sociodemographic factors may play a role in incidence and treatment of metastatic spinal tumors, as there is a delay in diagnosis and increased incidence of relevant primaries. There has yet to be a detailed analysis of the impact of sociodemographic factors on surgical outcomes for spinal metastases. We sought to examine the influence of socioeconomic factors on outcomes for patients with metastatic spinal tumors. METHODS: Two hundred and sixty-three patients who underwent surgery for metastatic spinal tumors were identified. Sociodemographic characteristics were then collected and assigned to patients based on their ZIP code. The Chi-square test and the Mann-Whitney-U test were used for binary and continuous variables, respectively. Multivariate regression models were also used to control for age, smoking status, body mass index, and Charlson Comorbidity Index. RESULTS: Males had significantly lower rates of post-treatment complication compared to females (22.7 % vs 39.3 %, p = 0.0052), and those in high educational attainment ZIP codes had significantly shorter length of stay (LOS) compared to low educational attainment ZIP codes (9.3 days vs 12.2 days, p = 0.0058). Multivariate regression revealed that living in a high percentage white ZIP code and being male significantly decreased risk of post-treatment complication by 19 % (p = 0.042) and 14 % (p = 0.032), respectively. Living in a high educational attainment ZIP code decreased LOS by 3 days (p = 0.019). CONCLUSIONS: Males had significantly lower rates of post-treatment complication. Patients in high percentage white areas also had decreased rate of post-treatment complications. Patients living in areas with high educational attainment had shorter length of stay.

Impact of Postoperative Stereotactic Body Radiation Therapy on Survival of Patients with Spinal Metastases in the Context of Additional Systemic Adjuvant Therapy.

BACKGROUND: Stereotactic body radiotherapy (SBRT) has been established as a safe and effective treatment modality for control of long-term pain and tumor growth. However, few studies have investigated the efficacy of postoperative SBRT versus conventional external beam radiation therapy (EBRT) in extending survival within the context of systemic therapy. METHODS: A retrospective chart review of patients who underwent surgery for spinal metastasis at our institution was conducted. Demographic, treatment, and outcome data were collected. SBRT was compared with EBRT and non-SBRT, and analyses were stratified by whether patients received systemic therapy. Survival analysis was conducted using propensity score matching. RESULTS: Bivariate analysis in the nonsystemic therapy group revealed longer survival with SBRT compared with EBRT and non-SBRT. Further analysis also showed that primary cancer type and preoperative mRS significantly affected survival. Within patients who received systemic therapy, overall median survival for patients receiving SBRT was 22.7 months (95% confidence interval [CI] 12.1-52.3) versus 16.1 months (95% CI 12.7-44.0; P = 0.28) for patients who received EBRT and 16.1 months (95% CI: 12.2-21.9; P = 0.07) for patients without SBRT. Within patients who did not receive systemic therapy, overall median survival for patients with SBRT was 62.1 months (95% CI 18.1-unknown) versus 5.3 months (95% CI 2.8-unknown; P = 0.08) for patients with EBRT and 6.9 months (95% CI 5.0-45.6; P = 0.02) for patients without SBRT. CONCLUSIONS: In patients who do not receive systemic therapy, treatment with postoperative SBRT may increase survival time compared with patients not receiving SBRT.

Variant allelic frequencies of driver mutations can identify gliomas with potentially false-negative MGMT promoter methylation results.

MGMT promoter methylation testing is required for prognosis and predicting temozolomide response in gliomas. Accurate results depend on sufficient tumor cellularity, but histologic estimates of cellularity are subjective. We sought to determine whether driver mutation variant allelic frequency (VAF) could serve as a more objective metric for cellularity and identify possible false-negative MGMT samples. Among 691 adult-type diffuse gliomas, MGMT promoter methylation was assessed by pyrosequencing (N = 445) or DNA methylation array (N = 246); VAFs of TERT and IDH driver mutations were assessed by next generation sequencing. MGMT results were analyzed in relation to VAF. By pyrosequencing, 56% of all gliomas with driver mutation VAF ≥ 0.325 had MGMT promoter methylation, versus only 37% with VAF < 0.325 (p < 0.0001). The mean MGMT promoter pyrosequencing score was 19.3% for samples with VAF VAF ≥ 0.325, versus 12.7% for samples with VAF < 0.325 (p < 0.0001). Optimal VAF cutoffs differed among glioma subtypes (IDH wildtype glioblastoma: 0.12-0.18, IDH mutant astrocytoma: ~0.33, IDH mutant and 1p/19q co-deleted oligodendroglioma: 0.3-0.4). Methylation array was more sensitive for MGMT promoter methylation at lower VAFs than pyrosequencing. Microscopic examination tended to overestimate tumor cellularity when VAF was low. Re-testing low-VAF cases with methylation array and droplet digital PCR (ddPCR) confirmed that a subset of them had originally been false-negative. We conclude that driver mutation VAF is a useful quality assurance metric when evaluating MGMT promoter methylation tests, as it can help identify possible false-negative cases.

Postoperative risk of IDH-mutant glioma-associated seizures and their potential management with IDH-mutant inhibitors.

Seizures are a frequent complication of adult-type diffuse gliomas, and are often difficult to control with medications. Gliomas with mutations in isocitrate dehydrogenase 1 or 2 (IDHmut) are more likely than IDH-wild type (IDHwt) gliomas to cause seizures as part of their initial clinical presentation. However, whether IDHmut is also associated with seizures during the remaining disease course, and whether IDHmut inhibitors can reduce seizure risk, are unclear. Clinical multivariable analyses showed that preoperative seizures, glioma location, extent of resection, and glioma molecular subtype (including IDHmut status) all contributed to postoperative seizure risk in adult-type diffuse glioma patients, and that postoperative seizures were often associated with tumor recurrence. Experimentally, the metabolic product of IDHmut, d-2-hydroxyglutarate, rapidly synchronized neuronal spike firing in a seizure-like manner, but only when non-neoplastic glial cells were present. In vitro and in vivo models recapitulated IDHmut glioma-associated seizures, and IDHmut inhibitors currently being evaluated in glioma clinical trials inhibited seizures in those models, independent of their effects on glioma growth. These data show that postoperative seizure risk in adult-type diffuse gliomas varies in large part by molecular subtype, and that IDHmut inhibitors could play a key role in mitigating such risk in IDHmut glioma patients.