Is intraoperative MRI use in malignant brain tumor surgery a health care burden? A matched analysis of MarketScan Database.

BACKGROUND: Intraoperative magnetic resonance imaging (iMRI) is a useful adjunct for resection of primary malignant brain tumors (MBTs). The aim of our study is to investigate the impact of iMRI on health care utilization in patients who underwent craniotomy for resection of MBTs. MATERIALS AND METHODS: MarketScan database were queried using the ICD-9/10 and CPT 4th edition, from 2008 to 2020. We included patients ≥ 18 years of age who underwent a craniotomy with at-least one year follow-up. Outcomes were length of stay (LOS), discharge disposition, hospital/emergency room (ER) re-admissions, outpatient services, medication refills and corresponding payments. RESULTS: Of 6,640 patients who underwent craniotomy for MBTs, 465 patients (7%) had iMRI used during the procedure with 0.7% per year increase in iMRI use during the study period. Patients without iMRI use had higher complications at index hospitalization compared to those with iMRI use (19% vs. 14%, p = 0.04). There was no difference in the ER admission rates among the patients who underwent surgery with and without iMRI use at 6-months and 1-year after the index procedure. In terms of post-discharge payments, no significant differences were noted among the patients without and with iMRI use at 6-months ($81,107 vs. $ 81,458, p = 0.26) and 1-year ($132,657 vs. $ 118,113, p = 0.12). CONCLUSION: iMRI use during craniotomy for MBT gradually increased during the study period. iMRI did not result in higher payments at index hospitalization, 6-months, and 1-year after the index procedure.

Preoperative stereotactic radiosurgery for patients with 1-4 brain metastases: A single-arm phase 2 trial outcome analysis (NCT03398694).

Background: Stereotactic radiosurgery (SRS) following surgical resection is the standard of care for patients with symptomatic oligo brain metastasis (BM), however, it is associated with 10-15% local failure. Targeting a resection cavity is imprecise, thus preoperative radiosurgery where the target is well-defined may be superior, however, the efficacy of preoperative SRS has not yet been tested in a clinical trial. Methods: We conducted a phase 2, single-arm trial of preoperative SRS followed by surgical resection in patients with 1-4 symptomatic oligo BMs (NCT03398694) with the primary objective of measuring 6-month local control (LC). SRS was delivered to all patients utilizing a gamma knife or linear accelerator as per RTOG-9005 dosing criteria [Shaw E, Scott C, Souhami L, et al. Single dose radiosurgical treatment of recurrent previously irradiated primary brain tumors and brain metastases: final report of RTOG protocol 90-05. Int J Radiat Oncol Biol Phys. 2000;47(2):291-298] based on tumor diameter with the exception that the largest lesion diameter treated was 5 cm with 15 Gy with all SRS treatment given in single fraction dosing. Results: The trial screened 50 patients, 48 patients were treated under the protocol and 32 patients completed the entire follow-up period. Of all the patients who completed the follow-up period, the primary endpoint of 6-month LC was 100% (95% CI: 0.891-1.000; P = .005). Secondary endpoints, presented as medians, were overall survival (17.6 months), progression-free survival (5.3 months), distant in-brain failure (40.8% at 1 year), leptomeningeal failure (4.8% at 1 year), and radiation necrosis (7.7% at 1 year). Conclusions: Our data confirms superior local control in patients who received preoperative SRS when compared to historical controls. Further study with a larger randomized cohort of patients is warranted to fully understand the benefits of preoperative SRS.

Genomic analysis of human brain metastases treated with stereotactic radiosurgery reveals unique signature based on treatment failure.

Stereotactic radiosurgery (SRS) has been shown to be efficacious for the treatment of limited brain metastasis (BM); however, the effects of SRS on human brain metastases have yet to be studied. We performed genomic analysis on resected brain metastases from patients whose resected lesion was previously treated with SRS. Our analyses demonstrated for the first time that patients possess a distinct genomic signature based on type of treatment failure including local failure, leptomeningeal spread, and radio-necrosis. Examination of the center and peripheral edge of the tumors treated with SRS indicated differential DNA damage distribution and an enrichment for tumor suppressor mutations and DNA damage repair pathways along the peripheral edge. Furthermore, the two clinical modalities used to deliver SRS, LINAC and GK, demonstrated differential effects on the tumor landscape even between controlled primary sites. Our study provides, in human, biological evidence of differential effects of SRS across BM's.

Intraoperative MRI use in transsphenoidal surgery for pituitary tumors: Trends and healthcare utilization.

BACKGROUND: Intraoperative magnetic resonance imaging (iMRI) use in transsphenoidal approach (TSA) for pituitary tumors (PTs) has been reported to improve the extent of resection (EOR). The aim of this study is to report the trends and the impact of iMRI on healthcare utilization in patients who underwent TSA for PTs. MATERIALS AND METHODS: MarketScan database were queried using the ICD-9/10 and CPT-4, from 2004 to 2020. We included patients ≥ 18 years of age PTs with > 1 year follow-up. Outcomes were length of stay (LOS), discharge disposition, hospital/emergency room (ER) re-admissions, outpatient services, medication refills and corresponding payments. RESULTS: A cohort of 10,192 patients were identified from the database, of these 141 patients (1.4%) had iMRI used during the procedure. Use of iMRI for PTs remained stable (2004-2007: 0.85%; 2008-2011: 1.6%; 2012-2015:1.4% and 2016-2019: 1.46%). No differences in LOS (median 3 days each), discharge to home (93% vs. 94%), complication rates (7% vs. 13%) and payments ($34604 vs. $33050) at index hospitalization were noted. Post-discharge payments were not significantly different without and with iMRI use at 6-months ($8315 vs. $ 7577, p = 0.7) and 1-year ($13,654 vs. $ 14,054, p = 0.70), following the index procedure. CONCLUSION: iMRI use during TSA for PTs remained stable with no impact on LOS, complications, discharge disposition and index payments. Also, there was no difference in combined index payments at 6-months, and 1-year after the index procedure in patients with and without iMRI use for PTs.

Facial Nerve Preservation With Inferior Long-Axis Dissection of Large Vestibular Schwannomas.

OBJECTIVE: To describe a tumor resection using the inferior long-axis (ILA) technique for cisternal facial nerve dissection in large vestibular schwannomas (VS). STUDY DESIGN: Retrospective case series from 2018 to 2021. SETTING: Tertiary academic medical center. PATIENTS: Patients who underwent surgical resection with ILA facial nerve dissection of VS (>2.0 cm measured parallel to the petrous ridge) and had at least 3-month follow-up. INTERVENTIONS: Cisternal facial nerve dissection during retrosigmoid or translabyrinthine approach using standardized ILA technique developed by author R.N. MAIN OUTCOME MEASURES: Immediate postoperative and last follow-up facial nerve function with House-Brackmann scores of I to II defined as "good" facial nerve function and House-Brackmann scores III to VI defined as "poor" function. Extent of resection was also assessed. RESULTS: A total of 48 patients underwent large VS resection with ILA dissection of tumor off of the facial nerve from 2018 to 2021. Mean (standard deviation) tumor size was 3.11 (0.76) cm. Mean (standard deviation) follow-up was 9.2 (9.0) months. Gross-total resection or near-total resection were achieved in 75% (radiographic estimate) to 83% (surgeon estimate) of cases. End-of-case facial nerve stimulation at 0.05 mAmp with a response of at least 240 mV was achieved in 80.4% of patients. Good facial nerve function was observed in 72% immediately postoperatively, 70% 1-month postoperatively, and 82% of patients at last follow-up. CONCLUSIONS: The ILA technique is now the method of choice of the senior surgeon (R.N.) when performing microsurgical dissection of the cisternal facial nerve, with which he has achieved high rates of total or near-total resection with excellent facial nerve preservation.

Genomic Analysis of Human Brain Metastases Treated with Stereotactic Radiosurgery Under the Phase-II Clinical Trial (NCT03398694) Reveals DNA Damage Repair at the Peripheral Tumor Edge.

Stereotactic Radiosurgery (SRS) is one of the leading treatment modalities for oligo brain metastasis (BM), however no comprehensive genomic data assessing the effect of radiation on BM in humans exist. Leveraging a unique opportunity, as part of the clinical trial (NCT03398694), we collected post-SRS, delivered via Gamma-knife or LINAC, tumor samples from core and peripheral-edges of the resected tumor to characterize the genomic effects of overall SRS as well as the SRS delivery modality. Using these rare patient samples, we show that SRS results in significant genomic changes at DNA and RNA levels throughout the tumor. Mutations and expression profiles of peripheral tumor samples indicated interaction with surrounding brain tissue as well as elevated DNA damage repair. Central samples show GSEA enrichment for cellular apoptosis while peripheral samples carried an increase in tumor suppressor mutations. There are significant differences in the transcriptomic profile at the periphery between Gamma-knife vs LINAC.

Trends in the Management Paradigms of Intracranial Meningioma.

Objective Intracranial meningiomas are the most common primary brain tumor. Treatment paradigms have evolved over time. There are limited number of population-based studies that examine this modern evolution. Here, we describe the trends of management of intracranial meningiomas using a national database. Methods The data were obtained from the National Cancer Database for the years 2004 to 2015, the collected variables included: patients' age, gender, insurance type, income, comorbidity score, the tumor size and grade, and treatment modality (observation, surgery, radiotherapy, or combination therapy). We performed statistical analyses to detect association between unique variables and outcomes. In addition, we performed mortality analyses for various treatment modalities. Results A total of 199,096 patients with a diagnosis of intracranial meningioma were included, the majority of patients were white females, mean age of 61 years, and half of the tumors were ≤ 3 cm. Observation was the most commonly used management modality followed by surgical resection, radiotherapy, and combination therapy. For the entire time period, there was an increased use of observation as a primary management method. Predictors of mortality included increased age, larger tumor size, higher tumor grade, treatment at a community hospital, and higher comorbidity scores. Conclusion Population-based studies of intracranial meningiomas are uncommon; our study is one of the few reports that examine the changes in the modern management paradigms of meningioma in the United States over time. Additionally, we shed light on the factors that affected survival of patients with this condition.

Symptomatic Cerebral Vasospasm After Transsphenoidal Tumor Resection: Two Case Reports and Systematic Literature Review.

Cerebral vasospasm is a rare life-threatening complication of transsphenoidal surgery (TSS). We report our experience with two cases of symptomatic vasospasm after endoscopic TSS, alongside a systematic review of published cases. Two patients who underwent endoscopic TSS for resection of a tuberculum sella meningioma (case 1) and pituitary adenoma (case 2) developed symptomatic vasospasm. Clinical variables, including demographics, histopathology, the extent of subarachnoid hemorrhage (SAH), diabetes insipidus (DI), day of vasospasm, vasospasm symptoms, vessels involved, management, and clinical outcome, were retrospectively extracted. We subsequently reviewed published cases of symptomatic post-TSS vasospasm. Including our two cases, we identified 34 reported cases of TSS complicated by symptomatic vasospasm. Female patients accounted for 20 (58.8%) of 34 cases. The average age was 48.1 ± 12.9 years. The majority of patients exhibited postoperative SAH (70.6%). The average delay to vasospasm presentation was 8.5 ± 3.6 days. The majority of patients exhibited vasospasm in multiple vessels, typically involving the anterior circulation. Hemodynamic augmentation with hemodilution, hypertension, and hypervolemia was the most common treatment. Death occurred in six (17.6%) of 34 patients. Common deficits included residual extremity weakness (17.6%), pituitary insufficiency (8.8%), and cognitive deficits (8.8%). Symptomatic vasospasm is a rare, potentially fatal complication of TSS. The most consistent risk factor is SAH. Early diagnosis requires a high index of suspicion when confronted with intractable DI, acute mental status change, or focal deficits in the days after TSS. Morbidity and death are significant risks in patients with this complication.

A comparison of endovascular strategies in the treatment of ruptured vertebral artery aneurysms.

BACKGROUND: Contemporary management of ruptured vertebral artery dissecting aneurysms (VADA) has evolved beyond proximal parent artery occlusion (PPAO) to include endovascular trapping (ET) of the diseased segment and vessel preserving stent treatments. The aim of this retrospective cohort study was to assess the outcomes of patients with ruptured VADAs who underwent endovascular management with trapping of the diseased segment as the first-line treatment approach. METHODS: We evaluated an institutional database of patients with ruptured VADAs who were treated at Auckland City Hospital from 1998 to 2017. Baseline and outcomes data were analyzed. High-grade SAH was defined as a World Federation of Neurological Surgeons or a Hunt and Hess grade of IV-V. Favorable outcome was defined as a modified Rankin Scale of 0-2. RESULTS: The study cohort was comprised of 45 ruptured VADA patients with a mean age of 50 years. The mean follow-up duration was 12.9 months. ET of the diseased segment was performed in 32 cases (71.1%), PPAO of the VA was performed in 12 cases (26.7%) and reconstruction using a flow diverting stent was performed in 1 case (2.2%). The overall procedural complication rate was 13%, including procedural neurological morbidity in 4.4%. At last follow-up, no further aneurysm filling was seen in any case, and 77.8% had a favorable outcome. CONCLUSION: ET affords a favorable risk to benefit profile for patients with ruptured VADAs. ET remains a reasonable option for ruptured VADAs in patients with sufficient collateral supply to the vertebrobasilar system.

Three novel missense mutations within the LHX4 gene are associated with variable pituitary hormone deficiencies.

CONTEXT: The LHX4 LIM-homeodomain transcription factor has essential roles in pituitary gland and nervous system development. Heterozygous mutations in LHX4 are associated with combined pituitary hormone deficiency. OBJECTIVES: Our objectives were to determine the nature and frequency of LHX4 mutations in patients with pituitary hormone deficiency and to examine the functional outcomes of observed mutations. DESIGN: The LHX4 gene sequence was determined from patient DNA. The biochemical and gene regulatory properties of aberrant LHX4 proteins were characterized using structural predictions, pituitary gene transcription assays, and DNA binding experiments. PATIENTS: A total of 253 patients from 245 pedigrees with GH deficiency and deficiency of at least one additional pituitary hormone was included in the study. RESULTS: In five patients, three types of heterozygous missense mutations in LHX4 that result in substitution of conserved amino acids were identified. One substitution is between the LIM domains (R84C); the others are in the homeodomain (L190R; A210P). The patients have GH deficiency; some also display reductions in TSH, LH, FSH, or ACTH, and aberrant pituitary morphology. Structural models predict that the aberrant L190R and A210P LHX4 proteins would have impaired DNA binding and gene activation properties. Consistent with these models, EMSAs and transfection experiments using pituitary gene promoters demonstrate that whereas the R84C form has reduced activity, the L190R and A210P proteins are inactive. CONCLUSIONS: LHX4 mutations are a relatively rare cause of combined pituitary hormone deficiency. This report extends the range of phenotypes associated with LHX4 gene mutations and describes three novel exonic mutations in the gene.

Efficacy of pre-operative stereotactic radiosurgery followed by surgical resection and correlative radiobiological analysis for patients with 1-4 brain metastases: study protocol for a phase II trial.

BACKGROUND: Stereotactic radiosurgery (SRS) has emerged as a common adjuvant modality used with surgery for resectable brain metastases (BMs). However, the optimal sequence of the multi-modality therapy has not been established. The goal of the study is to evaluate 6-month local control utilizing pre-operative SRS followed by surgical resection for patients with 1-4 brain metastases. METHODS: This prospective, single arm, phase II trial will recruit patients with up to 4 brain metastases and at least one resectable lesion. All lesions will be treated with SRS and symptomatic lesions will be resected within 1-4 days after SRS. Patients will be monitored for 6-month local control, in-brain progression free survival, distant in-brain failure, rate of leptomeningeal spread, radiation necrosis and overall survival. Additionally, we will also perform correlative radiobiological molecular studies to assess the effect of radiation dosing on the tumor tissue and clinical outcomes. We expect that pre-operative SRS to the gross tumor prior to surgical resection will improve local control and decrease leptomeningeal failure. DISCUSSION: Our study is the second prospective trial to investigate the efficacy of pre-operative SRS in the treatment of multiple BMs. In addition, the correlative molecular studies will be the first to investigate early response of BMs at a cellular and genetic level in response to radiation doses and potentially provide molecular prognostic markers for local control and overall survival. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03398694 (registration date: January 12, 2018).

Endoscopic Endonasal Surgery for the Resection of a Cavernous Hemangioma with a Sellar Extension.

Cavernous hemangiomas with an intrasellar extension are very rare, generally benign lesions that manifest by the compression of nearby structures. The presenting symptoms usually range from visual disturbances to an endocrine imbalance. Occasional extension into the cavernous sinus has been reported, which can cause cranial nerve compression. We present the case of a 69-year-old man presenting with facial pain and decreased libido. On investigation, a lesion was identified and the parasellar region was homogeneously hyper-intense on gadolinium-enhanced magnetic resonance imaging (MRI). Endoscopic endonasal surgery remains one of the favored approaches for the resection of sellar lesions. Such pathology needs to remain on the neurosurgeon's differential diagnosis, making an intraoperative frozen section of these lesions a useful tool in the surgeon's armamentarium, to guide further surgical resection.

Four novel mutations of the LHX3 gene cause combined pituitary hormone deficiencies with or without limited neck rotation.

CONTEXT: The Lhx3 LIM-homeodomain transcription factor gene is required for development of the pituitary and motoneurons in mice. Human LHX3 gene mutations have been reported in five subjects with a phenotype consisting of GH, prolactin, TSH, LH, and FSH deficiency; abnormal pituitary morphology; and limited neck rotation. OBJECTIVE: The objective of the study was to determine the frequency and nature of LHX3 mutations in patients with isolated GH deficiency or combined pituitary hormone deficiency (CPHD) and characterize the molecular consequences of mutations. DESIGN: The LHX3 sequence was determined. The biochemical properties of aberrant LHX3 proteins resulting from observed mutations were characterized using reporter gene and DNA binding experiments. PATIENTS: The study included 366 patients with isolated GH deficiency or CPHD. RESULTS: In seven patients with CPHD from four consanguineous pedigrees, four novel, recessive mutations were identified: a deletion of the entire gene (del/del), mutations causing truncated proteins (E173ter, W224ter), and a mutation causing a substitution in the homeodomain (A210V). The mutations were associated with diminished DNA binding and pituitary gene activation, consistent with observed hormone deficiencies. Whereas subjects with del/del, E173ter, and A210V mutations had limited neck rotation, patients with the W224ter mutation did not. CONCLUSIONS: LHX3 mutations are a rare cause of CPHD involving deficiencies for GH, prolactin, TSH, and LH/FSH in all patients. Whereas most patients have a severe hormone deficiency manifesting after birth, milder forms can be observed, and limited neck rotation is not a universal feature of patients with LHX3 mutations. This study extends the known molecular defects and range of phenotypes found in LHX3-associated diseases.

Mutations in the LHX3 gene cause dysregulation of pituitary and neural target genes that reflect patient phenotypes.

The LHX3 LIM-homeodomain transcription factor is required for correct development of the mammalian pituitary gland and spinal motoneurons. Mutations in the LHX3 gene underlie complex diseases featuring combined anterior pituitary hormone deficiency and, in specific cases, loss of neck rotation considered to result from nervous system abnormalities. The molecular basis for LHX3 protein actions in both normal and aberrant pituitary and nervous system development is poorly understood. In this study, the gene regulatory abilities of mutant LHX3 proteins associated with distinct types of diseases (LHX3a A210V, LHX3a E173Ter, and LHX3a W224Ter) were investigated. The capacity of these proteins to activate pituitary hormone and transcription factor gene promoters, nervous system target genes, and to localize to the nucleus of pituitary cells was measured. Consistent with the symptoms of patients with these mutations, the abnormal proteins displayed diminished capacities to activate the promoters of genes expressed in the pituitary gland. On nervous system promoters, several mutant proteins retained some activity. The ability of the mutant proteins to concentrate in the nucleus of pituitary cells was correlated with the retention of defined nuclear localization signals in the protein sequence, except for the E173Ter protein which unexpectedly localizes to the nucleus, likely due to the insertion of cryptic nuclear localization signals by a frame shift caused by the mutation. This study extends the molecular characterization of the severe neuroendocrine diseases associated with LHX3 gene mutations.

Roles of the LHX3 and LHX4 LIM-homeodomain factors in pituitary development.

The LHX3 and LHX4 LIM-homeodomain transcription factors play essential roles in pituitary gland and nervous system development. Mutations in the genes encoding these regulatory proteins are associated with combined hormone deficiency diseases in humans and animal models. Patients with these diseases have complex syndromes involving short stature, and reproductive and metabolic disorders. Analyses of the features of these diseases and the biochemical properties of the LHX3 and LHX4 proteins will facilitate a better understanding of the molecular pathways that regulate the development of the specialized hormone-secreting cells of the mammalian anterior pituitary gland.

Clinical case seminar: a novel LHX3 mutation presenting as combined pituitary hormonal deficiency.

CONTEXT: LHX3 encodes LIM homeodomain class transcription factors with important roles in pituitary and nervous system development. The only previous report of LHX3 mutations described patients with two types of recessive mutations displaying combined pituitary hormone deficiency coupled with neck rigidity. OBJECTIVE: We report a patient presenting a unique phenotype associated with a novel mutation in the LHX3 gene. PATIENT: We report a 6-yr, 9-month-old boy born from a consanguineous relationship who presented shortly after birth with cyanosis, feeding difficulty, persistent jaundice, micropenis, and poor weight gain and growth rate. Laboratory data, including an undetectable TSH, low free T4, low IGF-I and IGF binding protein-3, prolactin deficiency, and LH and FSH deficiency were consistent with hypopituitarism. A rigid cervical spine leading to limited head rotation was noticed on follow-up examination. Magnetic resonance imaging revealed an apparently structurally normal cervical spine and a postcontrast hypointense lesion in the anterior pituitary. RESULTS: Analysis of the LHX3 gene revealed homozygosity for a novel single-base-pair deletion in exon 2. This mutation leads to a frame shift predicted to result in the production of short, inactive LHX3 proteins. The results of in vitro translation experiments are consistent with this prediction. The parents of the patients are heterozygotes, indicating a recessive mode of action for the deletion allele. CONCLUSIONS: The presence of a hypointense pituitary lesion and other clinical findings broadens the phenotype associated with LHX3 gene mutation.

Regulation of the follicle-stimulating hormone beta gene by the LHX3 LIM-homeodomain transcription factor.

FSH is a critical hormone regulator of gonadal function that is secreted from the pituitary gonadotrope cell. Human patients and animal models with mutations in the LHX3 LIM-homeodomain transcription factor gene exhibit complex endocrine diseases, including reproductive disorders with loss of FSH. We demonstrate that in both heterologous and pituitary gonadotrope cells, specific LHX3 isoforms activate the FSH beta-subunit promoter, but not the proximal LHbeta promoter. The related LHX4 mammalian transcription factor can also induce FSHbeta promoter transcription, but the homologous Drosophila protein LIM3 cannot. The actions of LHX3 are specifically blocked by a dominant negative LHX3 protein containing a Kruppel-associated box domain. Six LHX3-binding sites were characterized within the FSHbeta promoter, including three within a proximal region that also mediates gene regulation by other transcription factors and activin. Mutations of the proximal binding sites demonstrate their importance for LHX3 induction of the FSHbeta promoter and basal promoter activity in gonadotrope cells. Using quantitative methods, we show that the responses of the FSHbeta promoter to activin do not require induction of the LHX3 gene. By comparative genomics using the human FSHbeta promoter, we demonstrate structural and functional conservation of promoter induction by LHX3. We conclude that the LHX3 LIM homeodomain transcription factor is involved in activation of the FSH beta-subunit gene in the pituitary gonadotrope cell.

Transcriptional control during mammalian anterior pituitary development.

The mammalian anterior pituitary gland is a compound endocrine organ that regulates reproductive development and fitness, growth, metabolic homeostasis, the response to stress, and lactation, by actions on target organs such as the gonads, the liver, the thyroid, the adrenals, and the mammary gland. The protein and peptide hormones that control these physiological parameters are secreted by specialized pituitary cell types that derive from a common origin in the early ectoderm. Collectively, the broad physiological importance of the pituitary gland, its intriguing organogenesis, and the clinical and agricultural significance of its actions, have established pituitary development as an excellent model system for the study of the gene-regulatory cascades that guide vertebrate cell determination and differentiation. We review the transcriptional pathways that regulate the commitment of the individual pituitary cell lineages and that subsequently modulate trophic hormone gene activity in the differentiated cells of the mature gland.

Gamma knife surgery of pediatric gliomas.

OBJECT: While some low-grade pediatric gliomas may be cured with resection, many patients harbor tumors that cannot be completely resected safely, are difficult to access via an open surgical approach, or recur. Gamma Knife surgery may be beneficial in the treatment of these tumors. METHODS: The authors reviewed a consecutive series of 24 pediatric patients treated at the authors' institution between 1989 and 2011. All patients harbored tumors that were either surgically inaccessible or had evidence of residual or recurrent growth after resection. Progression-free survival was evaluated and correlated with clinical variables. Additional outcomes evaluated were clinical outcome, imaging response, and overall survival. RESULTS: Between 1989 and 2011, 13 male and 11 female patients (median age 11 years, range 4-18 years) with gliomas were treated. Tumor pathology was pilocytic astrocytoma (WHO Grade I) in 15 patients (63%), WHO Grade II in 4 (17%), and WHO Grade III in 1 (4%). The tumor pathology was not confirmed in 4 patients (17%). The mean tumor volume at the time of treatment was 2.4 cm(3). Lesions were treated with a median maximum dose of 36 Gy, median of 3 isocenters, and median marginal dose of 15 Gy. The median duration of imaging follow-up was 74 months, and the median duration of clinical follow-up was 144 months. The tumors responded with a median decrease in volume of 71%. At last follow up, a decrease in tumor size of at least 50% was demonstrated in 18 patients (75%) and complete tumor resolution was achieved in 5 (21%). Progression-free survival at last follow-up was achieved in 20 patients (83%). Progression was documented in 4 patients (17%), with 3 patients requiring repeat resection and 1 patient dying. The initial tumor volume was significantly greater in patients with disease progression (mean volume 4.25 vs 2.0 cm(3), p < 0.001). Age, tumor pathology, tumor location, previous radiation, Karnofsky Performance Scale score, symptom duration, and target dosage did not differ significantly between the 2 groups. CONCLUSIONS: Gamma Knife surgery can provide good clinical control of residual or recurrent gliomas in pediatric patients. Worse outcomes in the present series were associated with larger tumor volumes at the time of treatment.

Gamma Knife surgery of meningiomas located in the posterior fossa: factors predictive of outcome and remission.

OBJECT: Although numerous studies have analyzed the role of stereotactic radiosurgery for intracranial meningiomas, few studies have assessed outcomes of posterior fossa meningiomas after stereotactic radiosurgery. In this study, the authors evaluate the outcomes of posterior fossa meningiomas treated with Gamma Knife surgery (GKS). The authors also assess factors predictive of new postoperative neurological deficits and tumor progression. METHODS: A retrospective review was performed of a prospectively compiled database documenting the outcomes of 152 patients with posterior fossa meningiomas treated at the University of Virginia from 1990 to 2006. All patients had a minimum follow-up of 24 months. There were 30 males and 122 females, with a median age of 58 years (range 12-82 years). Seventy-five patients were treated with radiosurgery initially, and 77 patients were treated with GKS after resection. Patients were assessed clinically and radiographically at routine intervals following GKS. Factors predictive of new neurological deficit following GKS were assessed via univariate and multivariate analysis, and Kaplan-Meier analysis and Cox multivariate regression analysis were used to assess factors predictive of tumor progression. RESULTS: Patients had meningiomas centered over the tentorium (35 patients, 23%), cerebellopontine angle (43 patients, 28%), petroclival region (28 patients, 18%), petrous region (6 patients, 4%), and clivus (40 patients, 26%). The median follow-up was 7 years (range 2-16 years). The mean preradiosurgical tumor volume was 5.7 cm(3) (range 0.3-33 cm(3)), and mean postradiosurgical tumor volume was 4.9 cm(3) (range 0.1-33 cm(3)). At last follow-up, 55 patients (36%) displayed no change in tumor volume, 78 (51%) displayed a decrease in volume, and 19 (13%) displayed an increase in volume. Kaplan-Meier analysis demonstrated radiographic progression-free survival at 3, 5, and 10 years to be 98%, 96%, and 78%, respectively. In Cox multivariable analysis, pre-GKS covariates associated with tumor progression included age greater than 65 years (hazard ratio [HR] 3.24, 95% CI 1.12-9.37; p = 0.03) and a low dose to the tumor margin (HR 0.76, 95% CI 0.60-0.97; p = 0.03), and post-GKS covariates included shunt-dependent hydrocephalus (HR 25.0, 95% CI 3.72-100.0; p = 0.001). At last clinical follow-up, 139 patients (91%) demonstrated no change or improvement in their neurological condition, and 13 patients showed symptom deterioration (9%). In multivariate analysis, the only factors predictive of new or worsening symptoms were clival or petrous location (OR 4.0, 95% CI 1.1-13.7; p = 0.03). CONCLUSIONS: Gamma Knife surgery offers an acceptable rate of tumor control for posterior fossa meningiomas and accomplishes this with a low incidence of neurological deficits. In patients selected for GKS, tumor progression is associated with age greater than 65 years and decreasing dose to the tumor margin. Clival- or petrous-based locations are predictive of an increased risk of new or worsening neurological deficit following GKS.