Combined Awake Craniotomy with Endoscopic Port Surgery for Resection of a Deep-Seated Temporal Lobe Glioma: A Case Report

The authors describe the combination of awake craniotomy and minimally invasive endoscopic port surgery to resect a high-grade glioma located near eloquent structures of the temporal lobe. Combined minimally invasive techniques such as these may facilitate deep tumor resection within eloquent regions of the brain, allowing minimum white matter dissection. Technical aspects of this procedure, a case outcome involving this technique, and the direction of further investigations for the utility of these techniques are discussed

Radiotherapy and temozolomide for newly diagnosed glioblastoma and anaplastic astrocytoma: validation of Radiation Therapy Oncology Group-Recursive Partitioning Analysis in the IMRT and temozolomide era

Since the development of the Radiation Therapy Oncology Group-Recursive Partitioning Analysis (RTOG-RPA) risk classes for high-grade glioma, radiation therapy in combination with temozolomide (TMZ) has become standard care. While this combination has improved survival, the prognosis remains poor in the majority of patients. Therefore, strong interest in high-grade gliomas from basic research to clinical trials persists. We sought to evaluate whether the current RTOG-RPA retains prognostic significance in the TMZ era or alternatively, if modifications better prognosticate the optimal selection of patients with similar baseline prognosis for future clinical protocols. The records of 159 patients with newly-diagnosed glioblastoma (GBM, WHO grade IV) or anaplastic astrocytoma (AA, WHO grade III) were reviewed. Patients were treated with intensity-modulated radiation therapy (IMRT) and concurrent followed by adjuvant TMZ (n = 154) or adjuvant TMZ only (n = 5). The primary endpoint was overall survival. Three separate analyses were performed: (1) application of RTOG-RPA to the study cohort and calculation of subsequent survival curves, (2) fit a new tree model with the same predictors in RTOG-RPA, and (3) fit a new tree model with an expanded predictor set. All analyses used a regression tree analysis with a survival outcome fit to formulate new risk classes. Overall median survival was 14.9 months. Using the RTOG-RPA, the six classes retained their relative prognostic significance and overall ordering, with the corresponding survival distributions significantly different from each other (P < 0.01, χ2 statistic = 70). New recursive partitioning limited to the predictors in RTOG-RPA defined four risk groups based on Karnofsky Performance Status (KPS), histology, age, length of neurologic symptoms, and mental status. Analysis across the expanded predictors defined six risk classes, including the same five variables plus tumor location, tobacco use, and hospitalization during radiation therapy. Patients with excellent functional status, AA, and frontal lobe tumors had the best prognosis. For patients with newly-diagnosed high-grade gliomas, RTOG-RPA classes retained prognostic significance in patients treated with TMZ and IMRT. In contrast to RTOG-RPA, in our modified RPA model, KPS rather than age represented the initial split. New recursive partitioning identified potential modifications to RTOG-RPA that should be further explored with a larger data set

Endoscopic Reconstruction of Cranial Base Defects following Endonasal Skull Base Surgery

The expanded endonasal approach provides access to the entire ventral skull base for resection of neoplasms involving the skull base and brain. The creation of large defects of the bone and dura endoscopically presents unique reconstructive challenges. A layered reconstruction of the dura with inlay and onlay fascial grafts covered with fat grafts is an effective technique for repair. An intranasal balloon catheter is used to provide counterpressure in the early phase of healing and a lumbar spinal drain is a useful adjunct in patients at increased risk of a cerebrospinal fluid leak. Vascularized flaps may be necessary in some patients receiving radiation therapy. Continued advances in surgical technology and the introduction of new biomaterials will facilitate the reconstruction of skull base defects following endonasal brain surgery

Prescription dose and fractionation predict improved survival after stereotactic radiotherapy for brainstem metastases

<p>Abstract</p> <p>Background</p> <p>Brainstem metastases represent an uncommon clinical presentation that is associated with a poor prognosis. Treatment options are limited given the unacceptable risks associated with surgical resection in this location. However, without local control, symptoms including progressive cranial nerve dysfunction are frequently observed. The objective of this study was to determine the outcomes associated with linear accelerator-based stereotactic radiotherapy or radiosurgery (SRT/SRS) of brainstem metastases.</p> <p>Methods</p> <p>We retrospectively reviewed 38 tumors in 36 patients treated with SRT/SRS between February 2003 and December 2011. Treatment was delivered with the Cyberknife™ or Trilogy™ radiosurgical systems. The median age of patients was 62 (range: 28–89). Primary pathologies included 14 lung, 7 breast, 4 colon and 11 others. Sixteen patients (44%) had received whole brain radiation therapy (WBRT) prior to SRT/SRS; ten had received prior SRT/SRS at a different site (28%). The median tumor volume was 0.94 cm³ (range: 0.01-4.2) with a median prescription dose of 17 Gy (range: 12–24) delivered in 1–5 fractions.</p> <p>Results</p> <p>Median follow-up for the cohort was 3.2 months (range: 0.4-20.6). Nineteen patients (52%) had an MRI follow-up available for review. Of these, one patient experienced local failure corresponding to an actuarial 6-month local control of 93%. Fifteen of the patients with available follow-up imaging (79%) experienced intracranial failure outside of the treatment volume. The median time to distant intracranial failure was 2.1 months. Six of the 15 patients with distant intracranial failure (40%) had received previous WBRT. The actuarial overall survival rates at 6- and 12-months were 27% and 8%, respectively. Predictors of survival included Graded Prognostic Assessment (GPA) score, greater number of treatment fractions, and higher prescription dose. Three patients experienced acute treatment-related toxicity consisting of nausea (n = 1) and headaches (n = 2) that resolved with a short-course of dexamethasone.</p> <p>Conclusion</p> <p>SRT/SRS for brainstem metastases is safe and achieves a high rate of local control. We found higher GPA as well as greater number of treatment fractions and higher prescription dose to be correlated with improved overall survival. Despite this approach, prognosis remains poor and distant intracranial control remains an issue, even in patients previously treated with WBRT.</p

Fractionated stereotactic radiosurgery for the treatment of meningiomas

Background: Although the vast majority of meningiomas are not malignant, their location within the cranial vault often leads to the development of symptoms. Traditional therapy has included observation, surgical resection, radiation therapy or a multimodality approach. The objective of this study is to review the outcomes in patients with meningioma treated at our institution using stereotactic radiosurgery. Materials and Methods: A total of 73 patients (median age of 59, 15 male and 58 female) with meningioma (median volume of 5.54 cc) underwent Cyber Knife TM stereotactic radiosurgery at our institution. Sixty patients had WHO grade 1 meningioma, eleven patients had WHO grade 2 meningioma, and two patients had WHO grade 3 meningioma. Treatment consisted of a median dose of 17.5 Gy (range, 6 - 27 Gy) delivered over a median of three fractions (range: 1 - 5). The patients were followed by clinical examination as well as serial imaging with magnetic resonance imaging (MRI). Results: The median follow-up was 16.1 months (range, 1.5 - 98.0). Follow-up MRI was available in all 73 patients. Local failure was documented in 11 cases. Actuarial local control at one year was 95, 71, and 0% for WHO grade 1, WHO grade 2, and WHO grade 3, respectively. There was no acute grade 3 or greater toxicity and only one episode of late grade 3 toxicity. A subjective improvement in the existing, tumor-related symptoms was noted in 60% of the patients. Conclusion: Stereotactic radiosurgery is a safe and effective treatment for meningioma. Tumor-related symptoms often improve after treatment

GM-CSF Promotes the Immunosuppressive Activity of Glioma-Infiltrating Myeloid Cells through Interleukin-4 Receptor-α

Malignant gliomas are lethal cancers in the brain and heavily infiltrated by myeloid cells. Interleukin-4 receptor-α (IL-4Rα) mediates the immunosuppressive functions of myeloid cells, and polymorphisms in the IL-4Rα gene are associated with altered glioma risk and prognosis. In this study, we sought to evaluate a hypothesized causal role for IL-4Rα and myeloid suppressor cells in glioma development. In both mouse de novo gliomas and human glioblastoma cases, IL-4Rα was upregulated on glioma-infiltrating myeloid cells but not in the periphery or in normal brain. Mice genetically deficient for IL-4Rα exhibited a slower growth of glioma associated with reduced production in the glioma microenvironment of arginase, a marker of myeloid suppressor cells, which is critical for their T-cell inhibitory function. Supporting this result, investigations using bone marrow-derived myeloid cells showed that IL-4Rα mediates IL-13-induced production of arginase. Furthermore, glioma-derived myeloid cells suppressed T-cell proliferation in an IL-4Rα-dependent manner, consistent with their identification as myeloid-derived suppressor cells (MDSC). Granulocyte macrophage colony-stimulating factor (GM-CSF) plays a central role for the induction of IL-4Rα expression on myeloid cells, and we found that GM-CSF is upregulated in both human and mouse glioma microenvironments compared with normal brain or peripheral blood samples. Together, our findings establish a GM-CSF-induced mechanism of immunosuppression in the glioma microenvironment via upregulation of IL-4Rα on MDSCs

Endoscopic Anterior Skull Base Resection for Esthesioneuroblastoma

Esthesioneuroblastomas (ENB) are relatively rare neoplasms accounting for less than 5% of malignant sinus tumors. The presentation, preoperative evaluation, imaging, and staging are described. The roles of endoscopic endonasal resection and the traditional transcranial subfrontal approach are compared. The endoscopic surgical technique is emphasized including postoperative repair. The early outcomes of patients who have undergone this approach as well as the role of adjunctive treatment including radiation therapy are described. Potential complications from CSF leak to infectious to vascular are reviewed

GM-CSF Promotes the Immunosuppressive Activity of Glioma-Infiltrating Myeloid Cells through Interleukin-4 Receptor-α

Malignant gliomas are lethal cancers in the brain and heavily infiltrated by myeloid cells. Interleukin-4 receptor-α (IL-4Rα) mediates the immunosuppressive functions of myeloid cells, and polymorphisms in the IL-4Rα gene are associated with altered glioma risk and prognosis. In this study, we sought to evaluate an hypothesized causal role for IL-4Rα and myeloid suppressor cells in glioma development. In both mouse de novo gliomas and human glioblastoma cases, IL-4Rα was upregulated on glioma-infiltrating myeloid cells but not in the periphery or in normal brain. Mice genetically deficient for IL-4Rα exhibited a slower growth of glioma associated with reduced production in the glioma microenvironment of arginase, a marker of myeloid suppressor cells which is critical for their T cell inhibitory function. Supporting this result, investigations using bone marrow-derived myeloid cells showed that IL-4Rα mediates IL-13-induced production of arginase. Furthermore, glioma-derived myeloid cells suppressed T cell proliferation in an IL-4Rα-dependent manner, consistent with their identification as myeloid-derived suppressor cells. Granulocyte-macrophage colony-stimulating factor (GM-CSF) plays a central role for the induction of IL-4Rα expression on myeloid cells, and we found that GM-CSF is upregulated in both human and mouse glioma microenvironments compared with normal brain or peripheral blood samples. Together, our findings establish a GM-CSF-induced mechanism of immunosuppression in the glioma microenvironment via upregulation of IL-4Rα on myeloid-derived suppressor cells