Long-Term Outcomes After Stereotactic Radiosurgery for Spine Metastases: Radiation Dose-Response for Late Toxicity.

PURPOSE: To document the 5- and 10-year rates of late toxicity and vertebral compression fracture (VCF) in long-term survivors after stereotactic radiosurgery for spine metastases. METHODS AND MATERIALS: A retrospective review was performed on 562 patients treated with SRS for spine metastases between April 2001 and July 2011. Selecting those with at least 5-year survival after SRS, included were 43 patients who collectively underwent 84 treatments at 54 spine sites. Most were treated with single-fraction stereotactic radiosurgery to a median dose of 16 Gy (range, 12-24 Gy), and 56% of sites had received prior external beam radiation therapy. Late toxicities and VCFs occurring in the absence of tumor progression were recorded. Binary logistic regression was used to identify predictors of late complications. RESULTS: Nine patients (17% of treatment sites) developed grade ≥2 late toxicities at a median time of 12.8 months (range, 4.2-59.0 months). Actuarial 5- and 10-year rates of grade ≥2 late toxicity were 17% and 17%, respectively. On multivariate analysis, only cumulative biologically effective dose (BED3) > 200 Gy (or EQD22Gy [2-Gy equivalent dose calculated using an α/ß ratio of 2] > 130 Gy) was associated with grade ≥2 late toxicity (P = .036). Maximum point BED3 > 110 Gy (or EQD22Gy > 70 Gy) to spinal cord or cauda equina was associated with grade ≥2 late neuropathy (P = .017). Nine VCFs (18%) occurred at a median time of 10.2 months (range, 3.2-57.2 months), with 5- and 10-year VCF rates of 17% and 17%, respectively. CONCLUSION: Stereotactic radiosurgery for primary treatment and reirradiation of spinal metastases is associated with a moderate risk of late toxicity with 10-year follow-up. Risk of late toxicity significantly increases with cumulative BED3 > 200 Gy and spinal cord or cauda equina point BED3 > 110 Gy. Patients remain at moderate risk of VCF up to 5 years after treatment, with a plateau in incidence thereafter up to 10 years.

Pneumocephalus after resection of a lung cancer with posterior chest wall involvement.

Pneumocephalus after resection of intrathoracic tumors is an extremely rare event. A delayed presentation of iatrogenic subarachnoid pleural fistula resulted in symptomatic pneumocephalus after resection of a locally recurrent T4N0 nonsmall cell lung cancer involving the chest wall, T2 to T4 rib heads, and intercostal vertebral foramina. Progressive neurologic decline was noted 3 weeks after discharge. Computed tomography of the head and chest confirmed the presence of an apical pleural space, thoracic subarachnoid air, and pneumocephalus. Immediate clinical improvement followed chest tube decompression of the pleural space.

Primary intracranial dural-based synovial sarcoma with an unusual SYT fluorescence in situ hybridization pattern.

The authors present the case of an elderly man with a primary dural-based intracranial synovial sarcoma. Histological and immunohistochemical profiles of the lesion were diagnostic for a synovial sarcoma, and molecular studies using fluorescence in situ hybridization were compatible with a synovial sarcoma. A wide array of spindle cell neoplasms has been described as originating in the dura. To the authors' knowledge, however, this is only the second primary dura-based intracranial synovial sarcoma ever reported, emphasizing the importance of a broad differential diagnosis when encountering spindle cell lesions of the meninges.

Autologous glioma cell vaccine admixed with interleukin-4 gene transfected fibroblasts in the treatment of patients with malignant gliomas.

BACKGROUND: The prognosis for malignant gliomas remains dismal. We addressed the safety, feasibility and preliminary clinical activity of the vaccinations using autologous glioma cells and interleukin (IL)-4 gene transfected fibroblasts. METHODS: In University of Pittsburgh Cancer Institute (UPCI) protocol 95-033, adult participants with recurrent glioblastoma multiforme (GBM) or anaplastic astrocytoma (AA) received gross total resection (GTR) of the recurrent tumors, followed by two vaccinations with autologous fibroblasts retrovirally transfected with TFG-IL4-Neo-TK vector admixed with irradiated autologous glioma cells. In UPCI 99-111, adult participants with newly diagnosed GBM or AA, following GTR and radiation therapy, received two intradermal vaccinations with the TFG-IL4-Neo-TK-transfected fibroblasts admixed with type-1 dendritic cells (DC) loaded with autologous tumor lysate. The participants were evaluated for occurrence of adverse events, immune response, and clinical response by radiological imaging. RESULTS AND DISCUSSION: In UPCI 95-033, only 2 of 6 participants received the vaccinations. Four other participants were withdrawn from the trial because of tumor progression prior to production of the cellular vaccine. However, both participants who received two vaccinations demonstrated encouraging immunological and clinical responses. Biopsies from the local vaccine sites from one participant displayed IL-4 dose-dependent infiltration of CD4+ as well as CD8+ T cells. Interferon (IFN)-gamma Enzyme-Linked Immuno-SPOT (ELISPOT) assay in another human leukocyte antigen (HLA)-A2+ participant demonstrated systemic T-cell responses against an HLA-A2-restricted glioma-associated antigen (GAA) epitope EphA2883-891. Moreover, both participants demonstrated clinical and radiological improvement with no evidence of allergic encephalitis, although both participants eventually succumbed with the tumor recurrence. In 99-111, 5 of 6 enrolled participants received scheduled vaccinations with no incidence of major adverse events. Monocyte-derived DCs produced high levels of IL-12 p70. Treatment was well tolerated; however, we were unable to observe detectable IFN-gamma post-vaccine responses or prolonged progression-free survival in these participants. CONCLUSION: Feasibility challenges inherent in the generation of a patient-specific gene transfection-based vaccine strongly suggests the need for more practical formulations that would allow for the timely administration of vaccines. Nevertheless, successful generation of type-1 DCs and preliminary safety in the current study provide a strong rationale for further efforts to develop novel glioma vaccines.

Safety and efficacy of the porcine small intestinal submucosa dural substitute: results of a prospective multicenter study and literature review.

OBJECT: Dural substitutes are often needed after neurosurgical procedures to expand or replace dura mater resected during surgery. A new dural repair material derived from porcine small intestinal submucosa (SIS) was evaluated in a prospective multicenter clinical study. METHODS: Between 2000 and 2003, 59 patients at five different institutions underwent dural reconstruction with the SIS dural substitute, with a minimum follow up of 6 months. The primary goals of the study were to assess the efficacy and safety of the SIS dural substitute according to the rate of cerebrospinal fluid (CSF) leakage, infection, and meningitis. Chiari malformation Type I decompression (32 patients) and tumor resection (18 patients) were the most common procedures performed, with 81% of SIS grafts implanted in the posterior fossa or spine. There was one case of a CSF leak (1.7%), two cases of wound infection (3.4%), and no cases of bacterial meningitis (0%) in the 58 patients available for follow up. In both cases of wound infection, the SIS graft acted as a barrier to infection and was not removed. Intraoperatively, a watertight seal was achieved in all 59 cases. On follow-up imaging available in 27 patients there was no evidence of any adverse reaction to the graft or of cerebral inflammation. CONCLUSIONS: The SIS dural substitute demonstrated substantial efficacy in these patients after a mean follow up of 7.3 +/- 2.2 months. Rates of infection, CSF leakage, and meningitis were comparable to those reported for other dural substitute materials. A lack of adverse reactions to the graft, favorable safety profile, and clinical efficacy all point to the utility of this material as an alternative for dural repair.

Association of the Adult Chiari Malformation and Idiopathic Intracranial Hypertension: more than a coincidence.

There are significant similarities between the Adult Chiari Malformation (ACM) and Idiopathic Intracranial Hypertension (IIH). They include similar demographics, clinical presentation, and response to treatment. There is an eightfold increase in the incidence of significant tonsillar herniation in patients with IIH. Based on these findings and our observation in a subgroup of patients with failed ACM decompression, we suggest that these disorders are interrelated in a group of patients. The physiopathology is that of craniocephalic disproportion, i.e., a disproportion between the skull and the brain, due to a small skull or posterior fossa (like in ACM) and/or an engorged brain (like in IIH). This will occasionally lead to tonsillar ectopia. The craniocephalic disproportion will alter the brain compliance and lead to the symptomatology.

Visual field deficit caused by vascular compression from a suprasellar meningioma: case report.

OBJECTIVE AND IMPORTANCE: Suprasellar meningiomas typically cause bitemporal hemianopsia by direct compression of the chiasm, its blood supply, or both. We report another mechanism for visual loss in suprasellar meningiomas, whereby compression by the suprajacent vascular complex is the offending agent. CLINICAL PRESENTATION: A 78-year-old woman with a suprasellar meningioma was diagnosed incidentally. During the follow-up period, she developed an inferior homonymous wedge defect consistent with superior compression, without any detectable radiological progression. It was decided to resect her tumor. INTERVENTION: The patient underwent a fronto-orbital approach for tumoral excision. Intraoperatively, a groove by the anterior cerebral artery complex was found along the superior surface of the chiasm. Postoperatively, the patient's visual deficit resolved. CONCLUSION: This case illustrates an unusual visual field deficit associated with a suprasellar meningioma. It also emphasizes the importance of frequent and careful visual field monitoring, which can precede radiological and symptomatic progression.