Extracranial arteriovenous malformation mimicking a peripheral nerve tumor: illustrative case.

BACKGROUND: Arteriovenous malformations (AVMs) are vascular malformations that are more commonly found intracranially, followed by the head, neck, limbs, and trunk. Extracranially, AVMs can mimic peripheral nerve tumors, leading to misdiagnosis. OBSERVATIONS: A 19-year-old female, who presented with left lateral lower leg pain, was preoperatively thought to have a peripheral nerve tumor; at surgery, however, she was found to have an extracranial AVM. The distinct margins of the tumor on preoperative magnetic resonance imaging suggested that the patient might have a peripheral nerve tumor; however, the clinical symptoms of focal pain at rest and the absence of Tinel's sign should have raised questions about this diagnosis. LESSONS: This case highlights the difficulty in differentiating a peripheral nerve tumor from an extracranial AVM in certain clinical scenarios. It is important to use a multifaceted diagnostic approach to get a correct preoperative diagnosis and plan treatment appropriately.

Autologous cell immunotherapy (IGV-001) with IGF-1R antisense oligonucleotide in newly diagnosed glioblastoma patients.

Standard-of-care first-line therapy for patients with newly diagnosed glioblastoma (ndGBM) is maximal safe surgical resection, then concurrent radiotherapy and temozolomide, followed by maintenance temozolomide. IGV-001, the first product of the Goldspire™ platform, is a first-in-class autologous immunotherapeutic product that combines personalized whole tumor-derived cells with an antisense oligonucleotide (IMV-001) in implantable biodiffusion chambers, with the intent to induce a tumor-specific immune response in patients with ndGBM. Here, we describe the design and rationale of a randomized, double-blind, phase IIb trial evaluating IGV-001 compared with placebo, both followed by standard-of-care treatment in patients with ndGBM. The primary end point is progression-free survival, and key secondary end points include overall survival and safety.

Glioblastoma (GBM) is a fast-growing brain tumor that happens in about half of all gliomas. Surgery is the first treatment for patients with newly diagnosed GBM, followed by the usual radiation and chemotherapy pills named temozolomide. Temozolomide pills are then given as a long-term treatment. The outcome for the patient with newly diagnosed GBM remains poor. IGV-001 is specially made for each patient. The tumor cells are removed during surgery and mixed in the laboratory with a small DNA, IMV-001. This mix is the IGV-001 therapy that is designed to give antitumor immunity against GBM. IGV-001 is put into small biodiffusion chambers that are irradiated to stop the growth of any tumor cells in the chambers. In the phase IIb study, patients with newly diagnosed GBM are chosen and assigned to either the IGV-001 or the placebo group. A placebo does not contain any active ingredients. The small biodiffusion chambers containing either IGV-001 or placebo are surgically placed into the belly for 48 to 52 h and then removed. Patients then receive the usual radiation and chemotherapy treatment. Patients must be adults aged between 18 and 70 years. Patients also should be able to care for themselves overall, but may be unable to work or have lower ability to function. Patients with tumors on both sides of the brain are not eligible. The main point of this study is to see if IGV-001 helps patients live longer without making the illness worse compared with placebo. Clinical Trial Registration: NCT04485949 (ClinicalTrials.gov).

Survival and Radiation Dose Differences Between Single Versus Multi-Session Gamma Knife Stereotactic Radiosurgery in Patients Treated for Multiple (≥10) Brain Metastases.

OBJECTIVE:  To explore whether treatment with multiple Gamma Knife sessions (mGK) resulted in different survival outcomes or cumulative radiation doses compared to single session Gamma Knife (sGK) in patients who have been treated for ≥10 brain metastases (BMs). METHODS:  Thirty-five patients with ≥10 BMs treated with Gamma Knife stereotactic radiosurgery (GK SRS) were identified and separated into sGK vs. mGK cohorts. Survival outcomes and dosimetry data were compared between the two groups. Recursive partitioning analysis (RPA) classes were used to further stratify patients. RESULTS:  mGK patients survived longer from the first GK treatment (p<0.009). By RPA class, patients with class 1 had a prolonged survival from BM diagnosis than those in classes 2 and 3 (p=0.004). However, survival was not significantly different between the classes from the first GK treatment (p=0.089). Stratified by mGK vs. sGK and RPA classes, sGK patients in RPA class 1 had the longest survival from BM diagnosis but the worst survival from GK treatment. mGK patients in any RPA class had the best survival from the first GK treatment. For patients with RPA class 2+3, mGK was associated with longer survival from both BM diagnosis and first treatment. Statistical but not clinical differences between the mGK vs. sGK groups were observed in the max dose to the targets and cochlea, and the V40Gy whole brain dose. CONCLUSIONS:  mGK may be beneficial if GK is initiated early at first BM diagnosis vs. sGK initiated late. Future research is required to confirm these findings and explore additional areas of interest, such as quality-of-life and economic considerations.

Postmortem study of organ-specific toxicity in glioblastoma patients treated with a combination of temozolomide, irinotecan and bevacizumab.

PURPOSE: Systemic chemotherapy including monotherapy with temozolomide (TMZ) or bevacizumab (BEV); two-drug combinations, such as irinotecan (IRI) and BEV, TMZ and BEV and a three-drug combination with TMZ, IRI and BEV (TIB) have been used in treating patients with progressive high-grade gliomas including glioblastoma (GBM). Most patients tolerated these regimens well with known side effects of hypertension, proteinuria, and reversible clinical myelosuppression (CM). However, organ- or system- specific toxicities from chemotherapy agents have never been examined by postmortem study. This is the largest cohort used to address this issue in glioma patients. METHODS: Postmortem tissues (from all major systems and organs) were prospectively collected and examined by standard institution autopsy and neuropathological procedures from 76 subjects, including gliomas (N = 68, 44/M, and 24/F) and brain metastases (N = 8, 5/M, and 3/F) between 2009 and 2019. Standard hematoxylin and eosin (H&E) were performed on all major organs including brain specimens. Electronic microscopic (EM) study was carried out on 14 selected subject's kidney samples per standard EM protocol. Medical records were reviewed with adverse events (AEs) analyzed and graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. A swimmer plot was utilized to visualize the timelines of patient history by treatment group. The binary logistic regression models were performed to explore any associations between treatment strategies and incident myelosuppression. RESULTS: Twenty-four glioma subjects were treated with TIB [median: 5.5 (range: 1-25) cycles] at tumor recurrence. Exposure to IRI significantly increased the frequency of CM (p = 0.05). No unexpected adverse events clinically, or permanent end-organ damage during postmortem examination was identified in glioma subjects who had received standard or prolonged duration of BEV, TMZ or TIB regimen-based chemotherapies except rare events of bone marrow suppression. The most common causes of death (COD) were tumor progression (63.2%, N = 43) followed by aspiration pneumonia (48.5%, N = 33) in glioma subjects. No COD was attributed to acute toxicity from TIB. The study also demonstrated that postmortem kidney specimen is unsuitable for studying renal ultrastructural pathological changes due to autolysis. CONCLUSION: There is no organ or system toxicity by postmortem examinations among glioma subjects who received BEV, TMZ or TIB regimen-based chemotherapies regardless of durations except for occasional bone marrow suppression and reversible myelosuppression clinically. IRI, but not the extended use of TMZ, significantly increased CM in recurrent glioma patients. COD most commonly resulted from glioma tumor progression with infiltration to brain stem and aspiration pneumonia.

Primary Spinal Cord Astrocytomas: Two-Center Clinical Experience of Low- and High-Grade Lesions.

OBJECTIVE: Primary spinal cord astrocytomas are rare, fatal, and poorly studied. METHODS: This study included a 2-center, retrospective analysis of primary spinal cord astrocytoma patients from 1997 to 2020. Patients with drop metastases or without at least one follow-up were excluded. RESULTS: Seven World Health Organization grade I, 6 grade II, 7 grade III, and 4 grade IV astrocytoma patients were included. Older patients had higher grades (median 20 years in grade I vs. 36.5 in grade IV). The median follow-up was 15 months. Thirteen patients were discharged to rehabilitation. Eight patients demonstrated radiographic progression. Adjuvant therapy was utilized more in higher grades (5 of 13 grades III vs. all 11 grades IIIIV). Six patients died (1 death in grades III vs. 5 in grades IIIIV). Ten patients had worsened symptoms at the last follow-up. The median progression-free survival in grade I, II, III, and IV tumors was 116, 36, 8, and 8.5 months, respectively. The median overall survival in grade I, II, III, and IV tumors was 142, 69, 19, and 12 months, respectively. Thrombotic complications occurred in 2 patients, one with isocitrate dehydrogenasewild type glioblastoma. CONCLUSIONS: Outcomes worsen with higher grades and lead to difficult postoperative periods. Clinicians should be vigilant for thromboembolic complications. Further research is needed to understand these rare tumors.

Tufts Medical Center Experience With Long-Term Follow-Up of Vestibular Schwannoma Treated With Gamma Knife Stereotactic Radiosurgery: Novel Finding of Delayed Pseudoprogression.

PURPOSE: Our purpose was to evaluate the long-term outcomes of patients with vestibular schwannoma (VS) treated with Gamma Knife stereotactic radiosurgery (GKSRS) with modern techniques, with attention to posttreatment tumor growth dynamics, dosimetric predictors, and late toxicities. METHODS AND MATERIALS: One hundred twelve patients with VS were treated with GKSRS with a median dose of 12.5 Gy to the 50% isodose line treated between 2004 and 2015, with patients followed up to 15 years. Target and organ-at-risk doses were recorded, and tumor diameter/volume, audiologic decline, and trigeminal/facial nerve preservation were tracked from treatment onward. RESULTS: GKSRS yielded local control of 5, 10, and 15 years at 96.9%, 90.0%, and 87.1% respectively. Pseudoprogression was found in 45%, with a novel pattern detected with peak swelling at 31 months. Pseudoprogression was associated with smaller tumor diameter at treatment and fewer treatment isocenters, but not with the development of any toxicity, nor was it predicted by any dosimetric factor. Median time to hearing loss was 3.4 years with actuarial hearing preservation at 2, 5, and 10 years of 66.5%, 43.1%, and 37.6%, with rate of hearing loss correlating with maximum cochlea and modiolus doses. Trigeminal and facial nerve preservation rates were 92.7% and 97.6%, respectively. Increasing maximum tumor dose was associated with facial paresthesia. CONCLUSIONS: Modern GKSRS is a safe and effective treatment for VS on long-term follow-up, with high levels of facial and trigeminal nerve preservation. A novel pattern of pseudoprogression has been identified suggesting longer imaging follow-up may be needed before initiating salvage in those without symptomatic progression. Several tumor and dosimetric predictors have been suggested for the development of different toxicities, requiring further evaluation.

Primary meningeal melanoma masquerading as neurofibromatosis type 2: illustrative case.

BACKGROUND: Primary meningeal melanocytic neoplasms are exceedingly rare tumors, representing only 0.06% to 0.1% of all primary brain tumors and ranging in spectrum from benign localized tumors to highly aggressive malignant lesions. The diagnosis of these tumors is often challenging from clinical, radiological, and pathologic standpoints. Equally challenging is the distinction between primary meningeal melanocytic neoplasm and metastatic melanoma. OBSERVATIONS: The authors reported the case of a 41-year-old man with imaging findings diagnostic of neurofibromatosis type 2: bilateral internal auditory canal lesions (most consistent with bilateral vestibular schwannomas), two dura-based lesions presumed to be meningiomas, multiple spinal lesions consistent with peripheral nerve sheath tumors, and one intramedullary spinal lesion consistent with an ependymoma. Biopsy of these lesions revealed melanocytic neoplasms with mild to moderate atypia and a mildly elevated proliferation index, which made the distinction between benign and malignant challenging. In addition, the disseminated nature of these tumors made it difficult to determinate whether they arose from the meninges or represented metastases from an occult primary melanoma. LESSONS: This case illustrated the challenges presented by the diagnosis of meningeal melanocytic neoplasms and highlighted the importance of integrating the clinical and radiographic findings with histologic appearance and molecular studies.

Facial nerve outcomes following gamma knife radiosurgery for subtotally resected vestibular schwannomas: Early versus delayed timing of therapy.

OBJECTIVES: Initially treating vestibular schwannomas (VSs) with subtotal resection (STR) followed by Gamma Knife radiosurgery (GKRS) for progression of tumor residual is a strategy that balances maximal tumor resection with preservation of neurological function. The effect of timing of GKRS for residual and recurrent VSs remains poorly defined. We developed a simple and practical treatment algorithm for the timing of GKRS after STR of VSs and reviewed our follow-up results to determine outcomes between patients treated with early vs. late GKRS. PATIENTS AND METHODS: Patients that underwent STR between 1999 and 2017 for a VS at Tufts Medical Center were identified and included in the study cohort. Patients who received GKRS ≤ 12 months after STR were included in the early intervention group. Patients who received GKRS > 12 months after STR or did not have tumor progression on follow-up thus not requiring GKRS were included in the observation/delayed intervention group. RESULTS: STR of VSs was performed on 23 patients. Mean patient age at the time of STR was 53.0 years (range: 20-86.2). The mean follow-up was 4.2 years (range: 1 month-15.5 years). Patients most frequently presented with hearing loss. There were 5 patients (21.7 %) in the early intervention group and 18 (78.3 %) patients in the observation/delayed intervention group. Ten of 23 patients (43.5 %) required GKRS. Thirteen (56.5 %) did not receive GKRS. None of the patients in the early intervention group or the observation/delayed intervention group had changes in House-Brackmann (HB) Grade either after GKRS or at the end of the study period. CONCLUSIONS: GKRS of residual or recurrent tumor is safe following STR of VS and appears to carry a low risk of worsening facial nerve function when performed for progressive tumor growth.

3D extracellular matrix microenvironment in bioengineered tissue models of primary pediatric and adult brain tumors.

Dynamic alterations in the unique brain extracellular matrix (ECM) are involved in malignant brain tumors. Yet studies of brain ECM roles in tumor cell behavior have been difficult due to lack of access to the human brain. We present a tunable 3D bioengineered brain tissue platform by integrating microenvironmental cues of native brain-derived ECMs and live imaging to systematically evaluate patient-derived brain tumor responses. Using pediatric ependymoma and adult glioblastoma as examples, the 3D brain ECM-containing microenvironment with a balance of cell-cell and cell-matrix interactions supports distinctive phenotypes associated with tumor type-specific and ECM-dependent patterns in the tumor cells' transcriptomic and release profiles. Label-free metabolic imaging of the composite model structure identifies metabolically distinct sub-populations within a tumor type and captures extracellular lipid-containing droplets with potential implications in drug response. The versatile bioengineered 3D tumor tissue system sets the stage for mechanistic studies deciphering microenvironmental role in brain tumor progression.

High p16 Expression Is Associated with Malignancy and Shorter Disease-Free Survival Time in Solitary Fibrous Tumor/Hemangiopericytoma.

Objective Solitary fibrous tumors (SFT) and hemangiopericytomas (HPC) are now classified along a single spectrum of fibroblastic mesenchymal tumors with NAB2-STAT6 fusion. This fusion acts as a driver mutation that constitutively activates EGR1, which is known to be involved in the p16 pathway. Overexpression of p16 is associated with malignancy and worse prognosis in multiple mesenchymal tumors. The authors sought to investigate p16 immunoexpression in association with malignancy and prognosis of SFT/HPC tumors. Design Twenty-three SFT/HPC tumors (central nervous system [CNS]: 12, non CNS: 11) diagnosed at our institution from 2002 to 2016 were assigned into 3 grades. Data from microarray immunohistochemistry for STAT6, synaptophysin, CD56, chromogranin, SST2A, EGR1, Ki67, and p16, grade and survival were analyzed. Results CNS SFT/HPCs tend to be malignant (grade 3; 67 vs. 18%, p = 0.036) and more likely to express synaptophysin (33 vs. 0%, p = 0.035) than non CNS tumors. Overexpression of p16 (immunopositivity ≥ 50% tumor cells) was associated with malignant (grade 3) tumors, and has a sensitivity of 70% (7/10), and a specificity of 77% (10/13), as a predictive marker for malignancy. SFT/HPC patients with low p16 expression demonstrated significantly longer disease-free survival time (median survival > 113 months) than those with high p16 expression (median survival = 30 months, p = 0.045). Conclusions SFT/HPCs in the CNS are more likely to be malignant than the tumors in other sites. High p16 expression is also associated with malignancy and shorter disease-free survival time in SFT/HPC tumors in our study cohort. Clinically, p16 overexpression can be used as predictive marker for malignancy and prognosis and a possible therapeutic target.

A Rare Occurrence of Isolated Brain Metastases from Gastric Cancer.

BACKGROUND: Gastric cancer is the fourth most common cancer worldwide and the second most common cause of cancer-related death. The majority of newly diagnosed gastric cancer cases present either as locally advanced tumor growth or with distant metastases. CASE REPORT: Here, we describe a case of isolated brain metastases in a male patient with gastric cancer. Initially, our patient presented with dysphagia and was diagnosed with gastric cancer after a thorough evaluation. One year after chemotherapy and surgical resection of his gastric cancer, he presented with headaches, nausea, dizziness, and photophobia. Further evaluation of these symptoms led to the discovery of three metastatic brain lesions without evidence of extracranial metastases. CONCLUSIONS: Our review of the literature has found that such cases are rare. Additionally, our review of the literature demonstrates the poor outcomes associated with metastatic brain lesions from gastric cancer and highlights the importance of surgical resection in increasing overall survival time.

Case Report: Metastasis of a Trigeminal Malignant Peripheral Nerve Sheath Tumor to the Corpus Callosum.

BACKGROUND AND IMPORTANCE: Malignant peripheral nerve sheath tumors (MPNST) are relatively rare tumors of peripheral nerves that are notable for their locally aggressive nature, ability to metastasize, poor prognosis, and association with Neurofibromatosis type I. We present the case of a patient with a trigeminal nerve MPNST who developed an unusual metastasis to the corpus callosum, in the absence of any other central nervous system or systemic metastatic disease. We review the pathology and presentation of MPNST. CLINICAL PRESENTATION: A 53-yr-old woman presented with a 1-yr history of paroxysmal facial pain and dysesthesias in the right V1 and V2 distributions of the trigeminal nerve. She was initially diagnosed with trigeminal neuralgia although further imaging showed a cavernous sinus mass extending along the trigeminal nerve. She later developed an isolated lesion in the corpus callosum that was biopsied and consistent with MPNST. CONCLUSION: This case reviews the pathology and aggressive nature of MPNST and demonstrates an unusual site of metastasis. Clinicians should remain aware that MPNST can metastasize to sites in the central nervous system as well as systemically. Furthermore, clinicians should have a high index of suspicion for secondary causes of trigeminal neuralgia in cases with atypical features.

A Comparison of the Existing Wellness Programs in Neurosurgery and Institution Champion's Perspectives.

Once the accepted norm during Harvey Cushing's time, the mantra of work to the exclusion of family and lifestyle is now recognized as deleterious to overall well-being. A number of neurosurgical residency training programs have implemented wellness programs to enhance the physical, mental, and emotional well-being of trainees and faculty. This manuscript highlights existing organized wellness education within neurosurgery residency programs in order to describe the motivations behind development, structure, and potential implementation strategies, cost of implementation, and identify successes and barriers in the integration process. This manuscript is designed to serve as a "how-to" guide for other programs who may identify a need in their own trainees and begins the discussion of how to develop wellness, leadership, grit, and resiliency within our future generation of neurosurgeons.

Correction to: First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma.

Following publication of the original article [1], the authors reported an error in the spelling of one of the author names. In this Correction the incorrect and correct author names are indicated and the author name has been updated in the original publication. The authors also reported an error in the Methods section of the original article. In this Correction the incorrect and correct versions of the affected sentence are indicated. The original article has not been updated with regards to the error in the Methods section.

First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma.

BACKGROUND: Standard therapy for glioblastoma includes surgery, radiotherapy, and temozolomide. This Phase 3 trial evaluates the addition of an autologous tumor lysate-pulsed dendritic cell vaccine (DCVax®-L) to standard therapy for newly diagnosed glioblastoma. METHODS: After surgery and chemoradiotherapy, patients were randomized (2:1) to receive temozolomide plus DCVax-L (n = 232) or temozolomide and placebo (n = 99). Following recurrence, all patients were allowed to receive DCVax-L, without unblinding. The primary endpoint was progression free survival (PFS); the secondary endpoint was overall survival (OS). RESULTS: For the intent-to-treat (ITT) population (n = 331), median OS (mOS) was 23.1 months from surgery. Because of the cross-over trial design, nearly 90% of the ITT population received DCVax-L. For patients with methylated MGMT (n = 131), mOS was 34.7 months from surgery, with a 3-year survival of 46.4%. As of this analysis, 223 patients are ≥ 30 months past their surgery date; 67 of these (30.0%) have lived ≥ 30 months and have a Kaplan-Meier (KM)-derived mOS of 46.5 months. 182 patients are ≥ 36 months past surgery; 44 of these (24.2%) have lived ≥ 36 months and have a KM-derived mOS of 88.2 months. A population of extended survivors (n = 100) with mOS of 40.5 months, not explained by known prognostic factors, will be analyzed further. Only 2.1% of ITT patients (n = 7) had a grade 3 or 4 adverse event that was deemed at least possibly related to the vaccine. Overall adverse events with DCVax were comparable to standard therapy alone. CONCLUSIONS: Addition of DCVax-L to standard therapy is feasible and safe in glioblastoma patients, and may extend survival. Trial registration Funded by Northwest Biotherapeutics; Clinicaltrials.gov number: NCT00045968; https://clinicaltrials.gov/ct2/show/NCT00045968?term=NCT00045968&rank=1 ; initially registered 19 September 2002.

Commentary: An Introduction to Leadership Self-Assessment at the Society of Neurological Surgeons Post-Graduate Year 1 Boot Camp: Observations and Commentary.

Recent trends in graduate medical education have emphasized the mastery of nontechnical skills, especially leadership, for neurosurgical trainees. Accordingly, we introduced leadership development and self-awareness training to interns attending the Society of Neurological Surgeons Post-Graduate Year 1 Boot Camp in the Northeast (New England/New York/New Jersey) region in 2015. Feedback about the session was collected from interns. While neurosurgical interns conveyed a desire to receive more information on improving their leadership skills, most indicated that guidance seemed to be lacking in this critical area. We discuss some of the professional development needs uncovered during this process.

Survival following Ommaya reservoir placement for neoplastic meningitis.

The objective of this study was to evaluate the outcomes of patients with neoplastic meningitis (NM) following Ommaya reservoir placement in order to determine whether any patient factors are associated with longer survival. NM is a devastating late manifestation of cancer, and given its dismal prognosis, identifying appropriate patients for Ommaya reservoir placement is difficult. The authors performed a retrospective review of 80 patients who underwent Ommaya reservoir placement at three medical centers from September 2001 through September 2012. The primary outcome was death. Differences in survival were assessed with Kaplan-Meier survival analyses. The Cox proportional hazards and logistic regression modeling were performed to identify factors associated with survival. The primary diagnoses were solid organ, hematologic, and primary central nervous system tumors in 53.8%, 41.3%, and 5%, respectively. The median overall survival was 72.5 days (95% confidence interval 36-122) with 30% expiring within 30 days and only 13.8% surviving more than 1 year. There were no differences in median overall survival between sites (p=0.37) despite differences in time from diagnosis of NM to Ommaya reservoir placement (p<0.001). Diagnosis of hematologic malignancy was inversely associated with death within 90 days (p=0.04; odds ratio 0.34), older age was associated with death within 90 days (p=0.05; odds ratio 1.5, per 10 year increase in age). The prognosis of NM remains poor despite the available treatment with intraventricular chemotherapy. There exists significant variability in treatment algorithms among medical centers and consideration of this variability is crucial when interpreting existing series of Ommaya reservoir use in the treatment of patients with NM.

Local recurrence and survival following stereotactic radiosurgery for brain metastases from small cell lung cancer.

PURPOSE: Stereotactic radiosurgery (SRS) represents a treatment option for patients with brain metastases from small cell lung cancer (SCLC) following prior cranial radiation. Inferior local control has been described. We reviewed our failure patterns following SRS treatment to evaluate this concern. METHODS AND MATERIALS: Individuals with SCLC who received SRS for brain metastases from 2004 to 2011 were identified. Central nervous system (CNS) disease was detected and followed by gadolinium-enhanced, high-resolution magnetic resonance (MR) imaging. SRS dose was prescribed to the tumor periphery. Local recurrence was defined by increasing lesion size or enhancement, MR-spectroscopy, and perfusion changes consistent with recurrent disease or pathologic confirmation. Any new enhancing lesion not identified on the SRS planning scan was considered a regional failure. Overall survival (OS) and CNS control were evaluated using the Kaplan-Meier method. Factors predicted to influence outcome were tested by univariate log-rank analysis and Cox regression. RESULTS: Fifteen males and 25 females (median age of 61 years [range, 36-79]) of which 39 received prior brain irradiation were identified. In all, 132 lesions (3.3 per patient) between 0.4 and 4.7 cm received a median dose of 16 Gy (12-22 Gy). Thirteen metastases (10%) ultimately recurred locally with 6- and 12-month control rates of 81% and 69%, respectively. Only 1 of 110 metastases <2 cm recurred. Local failure was more likely for size >2 cm (P < .001) and dose <16 Gy (P < .001). The median OS was 6.5 months, and the time to regional CNS recurrence was 5.2 months. For patients with single brain metastases, both OS (P = .037) and regional CNS recurrence (P = .003) were improved. CNS control (P = .001), and survival (P = .057), were also longer for patients with controlled systemic disease. CONCLUSIONS: Local control following SRS for SCLC metastases is achievable for lesions <2 cm. For metastases >2 cm, local failure is more common than expected. Patients with controlled systemic disease and limited CNS involvement would benefit most from aggressive treatment.

Development of a sutureless dural substitute from Bombyx mori silk fibroin.

Silk solvent casting, electrospinning, and electrogelation techniques were used to create a biodegradable, biocompatible silk fibroin dural substitute. The all-silk system was designed and produced to improve on currently available materials, grafts and tissue sealants used for dural closure in neurosurgery. The silk biomaterial was successfully fabricated as a dual layer adhesive system designed to seal durotomies while also functioning as a dural regeneration scaffold. The mechanical characteristics, biocompatibility, biodegradability, and hydrodynamic sealing capability of the material were evaluated. Results showed that the biomaterial was biocompatible with neural cells and fibroblasts, had mechanical properties mimicking the natural dura, was biodegradable with controllable degradation, and was able to seal against a hydrodynamic pressure of 205 mmHg, which greatly exceeds the maximum cerebrospinal fluid pressure seen in both cranial and spinal dural closures of 50 mmHg. Based on its design and experimental results, the adhesive silk dual layer composite biomaterial shows potential as a sutureless dural repair system that would improve on current dural closure techniques.