Stereotactic radiosurgery to the resection cavity of brain metastases: a retrospective analysis and literature review.

PURPOSE: The aim of this study was to analyze results of stereotactic radiosurgery (SRS) as adjuvant therapy for resected brain metastases. METHODS: Medical records of patients treated at a single institution with SRS to the postoperative cavity of brain metastases were retrospectively reviewed. Patients who completed the prescribed SRS regimen following gross-total resection and had no previous whole brain radiotherapy were included in the study. Kaplan-Meier analyses were used to estimate local (LC) and intracranial control (IC), and overall survival (OS) rates. RESULTS: Between April 2005 and July 2010, 77 patients (median age 63 years) with 89 metastases met the inclusion criteria. The median prescription dose was 18 Gy (12-27 Gy) delivered in 1-3 fractions for a median target volume of 7.6 cm(3) (0.5-59 cm(3)). The 6-month, 1-year, and 2-year LC rates were 76.1, 76.1, and 74.3%, respectively. The 6-month, 1-year, and 2-year IC rates were 75.2, 54, and 43.6%, respectively. With a median follow-up of 13.8 months, the median OS was 14.5 months (1.9-51.4 months) after SRS. The overall 6-month, 1-year, and 2-year OS rates were 91, 62.5, and 43.6%, respectively. Complications included 2 patients with radiation necrosis. CONCLUSION: Adjuvant radiosurgery to the tumor cavity of resected brain metastases is well-tolerated and achieves LC in the majority of patients.

Protection of normal brain cells from γ-irradiation-induced apoptosis by a mitochondria-targeted triphenyl-phosphonium-nitroxide: a possible utility in glioblastoma therapy.

Glioblastoma multiforme is the most frequent and aggressive primary brain tumor. A strong rationale to identify innovative approaches to treat these tumors is required since treatment failures result in local recurrences and median survivals range from 9 to 12 months. Glioma cells are reported to have less mitochondrial content compared to adjacent normal brain cells. Based on this difference, we suggest a new strategy, utilizing protection of normal brain cells by mitochondria-targeted electron scavengers and antioxidants-nitroxides-thus allowing for the escalation of the radiation doses. In this paper, we report that a conjugate of nitroxide with a hydrophobic cation, triphenyl-phosphonium (TPEY-Tempo), significantly protected brain endothelial cells from γ-irradiation-induced apoptosis while radiosensitizing brain tumor cells. Thus, TPEY-Tempo may be a promising adjunct in the treatment of glioblastoma with the potential to not only prolong survival but also to maintain quality of life and reduce treatment toxicity.

Completely endoscopic resection of intraparenchymal brain tumors.

OBJECT: The authors introduce a novel technique of intraparenchymal brain tumor resection using a rod lens endoscope and parallel instrumentation via a transparent conduit. METHODS: Over a 4-year period, 21 patients underwent completely endoscopic removal of a subcortical brain lesion by means of a transparent conduit. Image guidance was used to direct the cannulation and resection of all lesions. Postoperative MR imaging or CT was performed to assess for residual tumor in all patients, and all patients were followed up postoperatively to assess for new neurological deficits or other surgical complications. RESULTS: The histopathological findings were as follows: 12 metastases, 5 glioblastomas, 3 cavernous malformations, and 1 hemangioblastoma. Total radiographically confirmed resection was achieved in 8 cases, near-total in 6 cases, and subtotal in 7 cases. There were no perioperative deaths. Complications included 1 infection and 1 pulmonary embolus. There were no postoperative hematomas, no postoperative seizures, and no worsened neurological deficits in the immediate postoperative period. CONCLUSIONS: Fully endoscopic resection may be a technically feasible method of resection for selected subcortical masses. Further experience with this technique will help to determine its applicability and safety.

Minimal-access technique for distal catheter insertion during ventricular peritoneal shunt procedures: a review of 100 cases.

The authors report the safety and efficacy of using a percutaneous minimal-access insertion technique for distal shunt catheter placement in 100 cases. From June 2007 to March 2008, they attempted 100 minimal-access insertions of distal shunt catheters in 91 patients who required ventriculoperitoneal shunting. Using the minimal-access approach, they avoided utilizing laparoscopic assistance or a mini-laparotomy in 91% of the cases. There were no bowel injuries or misplaced distal catheters. Additional outcomes in terms of operative times, cases that required conversion to open or laparoscopically assisted implantation, and infection rates are presented. They conclude that intraperitoneal shunt catheter placement can be safely and effectively accomplished using a simplified percutaneous minimal-access insertion method that does not require direct laparoscopic visualization.

Expanded endonasal approach, a fully endoscopic transnasal approach for the resection of midline suprasellar craniopharyngiomas: a new classification based on the infundibulum.

OBJECT: Craniopharyngiomas are notoriously difficult to treat. Surgeons must weigh the risks of aggressive resection against the long-term challenges of recurrence. Because of their parasellar location, often extending well beyond the sella, these tumors challenge vision and pituitary and hypothalamic function. New techniques are needed to improve outcomes in patients with these tumors while decreasing treatment morbidity. An endoscopic expanded endonasal approach (EEA) is one such technique that warrants understanding and evaluation. The authors explain the techniques and approach used for the endoscopic endonasal resection of suprasellar craniopharyngiomas and introduce a tumor classification scheme. METHODS: The techniques and approach used for the endoscopic, endonasal resection of suprasellar craniopharyngiomas is explained, including the introduction of a tumor classification scheme. This scheme is helpful for understanding both the appropriate expanded approach as well as relevant involved anatomy. RESULTS: The classification scheme divides tumors according to their suprasellar extension: Type I is preinfundibular; Type II is transinfundibular (extending into the stalk); Type III is retroinfundibular, extending behind the gland and stalk, and has 2 subdivisions (IIIa, extending into the third ventricle; and IIIb, extending into the interpeduncular cistern); and Type IV is isolated to the third ventricle and/or optic recess and is not accessible via an endonasal approach. CONCLUSIONS: The endoscopic EEA requires a thorough understanding of both sinus and skull base anatomy. Moreover, in its application for craniopharyngiomas, an understanding of tumor growth and extension with respect to the optic chiasm and infundibulum is critical to safely approach the lesion via an endonasal route.

The evolution of the endonasal approach for craniopharyngiomas.

Craniopharyngiomas have always been an extremely challenging type of tumor to treat. The transsphenoidal route has been used for resection of these lesions since its introduction. The authors present a historical review of the literature from the introduction of the endonasal route for resection of craniopharyngiomas until the present. Abandoned early due to technological limitations, this approach has been expanded both in its application and in its anatomical boundaries with subsequent progressive improvements in outcomes. This expansion has coincided with advances in visualization devices, imaging guidance techniques, and anatomical understanding. The progression from the use of headlights, to microscopy, to endoscopy and fluoroscopy, and finally to modern intraoperative magnetic resonance-guided techniques, combined with collaboration between otolaryngologists and neurosurgeons, has provided the framework for the development of current techniques for the resection of sellar and suprasellar craniopharyngiomas.

Outcomes following endoscopic, expanded endonasal resection of suprasellar craniopharyngiomas: a case series.

OBJECT: Craniopharyngiomas are challenging tumors that most frequently occur in the sellar or suprasellar regions. Microscopic transsphenoidal resections with various extensions and variations have been performed with good results. The addition of the endoscope as well as the further expansion of the standard and extended transsphenoidal approaches has not been well evaluated for the treatment of this pathological entity. METHODS: The authors performed a retrospective review of all patients who underwent a purely endoscopic, expanded endonasal approach (EEA) for the resection of craniopharyngiomas at their institution between June 1999 and February 2006. Endocrine and ophthalmological outcomes, extent of resection, and complications were evaluated. RESULTS: Sixteen patients underwent endoscopic EEA for the resection of craniopharyngiomas. Five patients (31%) presented with recurrent disease. Complete resection was planned in 11 of the 16 patients. Three elderly patients with vision loss underwent planned debulking, 1 patient with vision loss and a moderate-sized tumor had express wishes for debulking, and 1 patient had a separate, third ventricular nodule that was not resected. Of those in whom complete resection was planned, 91% underwent near-total (2/11) or gross-total (8/11) resection. No patient who underwent gross-total resection suffered a recurrence. The mean follow-up period was 34 months. Of the 14 patients who presented with vision loss, 93% had improvement or complete recovery and 1 patient's condition remained stable. No patient experienced visual worsening. Eighteen percent of patients (without preexisting hypopituitarism) developed panhypopituitarism and 8% developed permanent diabetes insipidus. There were no cases of new obesity. The postoperative cerebrospinal fluid leak rate was 58%. All leaks were resolved, and there were no cases of bacterial meningitis. There was 1 vascular injury (posterior cerebral artery perforator branch) resulting in the only new neurological deficit. No patient died. CONCLUSIONS: Endoscopic EEA for the resection of craniopharyngiomas provides acceptable results and holds the potential to improve outcomes.

Expanded endonasal approach: vidian canal as a landmark to the petrous internal carotid artery.

The purpose of this study was to describe the technique used to safely identify the petrous carotid artery during expanded endonasal approaches to the skull base. A series of 20 cadaveric studies was undertaken to isolate the vidian artery and nerve and to use them as landmarks to the petrous internal carotid artery (ICA). Twenty-five consecutive paraclival endoscopic cases were also reviewed to determine the consistency of the vidian artery in vivo as an intraoperative landmark to the ICA. These data were then correlated with results from a separate study in which computed tomography scans from 44 patients were evaluated to delineate the course of the vidian canal and its relationship to the petrous ICA. In all 20 cadaveric dissections and all 25 surgical cases, the vidian artery was consistently identified and could be reliably used as a landmark to the ICA. The correlation between anatomical and clinical data in this paper supports the consistent use of the vidian artery as an important landmark to the petrous ICA.

Fractionated stereotactic radiosurgery for large brain metastases.

OBJECTIVES: Large brain metastases (>3 cm) present a therapeutic dilemma, as the dose delivered by stereotactic radiosurgery (SRS) in a single fraction is limited by toxicity to adjacent tissues, resulting in suboptimal local control. This study assessed the efficacy and safety of fractionated SRS for the treatment of large brain metastases. MATERIALS AND METHODS: We identified 36 patients with 37 brain metastases treated with fractionated SRS. The median SRS dose was 24 Gy (range, 12 to 27 Gy) in 2 to 5 fractions and the median treatment volume was 15.6 mL (range, 10 to 82.7 mL). Kaplan-Meier analysis was used to estimate local control and overall survival rates. RESULTS: Of the 21 lesions with available radiographic follow-up, 6 lesions (29%) had a documented local failure, yielding an actuarial progression-free survival at 6 and 12 months of 73% and 63%, respectively. The actuarial 6-month and 1-year overall survival rates were 22% and 13%, respectively. No patients in this cohort experienced acute or late complications secondary to SRS. CONCLUSIONS: Fractionated SRS is feasible and safe in patients with large brain metastases. Local control rates appear to be improved when compared with that of single fraction SRS with a relative paucity of treatment-related toxicity.

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.

Simultaneous Muir-Torre and Turcot's syndrome: A case report and review of the literature.

BACKGROUND: Muir-Torre syndrome (MTS) is an autosomal dominant syndrome characterized by neoplasms of the sebaceous gland or keratoacanthomas, in addition to visceral malignancies. Cerebral neoplasms in patients with hereditary nonpolyposis colorectal cancer (HNPCC) or familial adenomatous polyposis suffer from Turcot's syndrome. Genetic mutations in MutS homolog (MSH)-2, MutL homolog (MLH)-1, and MutS homolog (MSH)-6 DNA mismatch repair genes are the most common in MTS with MSH-2 being the most predominant. In HNPCC MLH-1 and MSH-2 mutations are approximately equal in prevalence. CASE DESCRIPTION: We present the case of a 58-year-old male with a prior history of being treated for colonic adenocarcinoma and skin lesions leading to a diagnosis of MTS. The patient later developed a World Health Organization (WHO) grade 4 glioma requiring surgical resection. Pathology revealed mutations in MSH-2 and MSH-6 mismatch repair genes. CONCLUSIONS: This case represents the first report of Turcot's and MTS with extensive molecular testing on the cerebral neoplasm demonstrating a molecular relationship between Turcot's and MTS and only the second published report of simultaneous Turcot's and MTS.

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.

Stereotactic radiosurgery for the treatment and palliation of base of skull metastases.

OBJECTIVES: Patients with skullbase metastases often present with evolving cranial nerve deficits, pain and advanced systemic disease. These factors along with declining performance status limit invasive interventions; yet, a safe, efficient treatment modality that augments palliative efforts is desirable. We herein report the role of stereotactic radiosurgery (SRS) in the management of base of skull metastases. METHODS: This retrospective institutional series reviewed 18 consecutive patients (12 male, 6 female) with of a total of 21 skullbase metastases. Seventy-five percent of patients presented with symptomatic disease most commonly consisting of pain, specific cranial nerve involvement included trigeminal (3), abducens (1), facial (2), and vestibulocochlear (3) nerves. The median prescribed dose was 18 Gy (range 15-40) with eleven of the treatments delivered as a single fraction consisting of 15-21 Gy and the most common fractionated regimen being 24 Gy delivered in 3 fractions. RESULTS: Of the eighteen patients, 10 were transitioned to hospice care and succumbed to extensive metastatic disease prior to the first imaging evaluation. Clinical and imaging follow-up demonstrated local failure in 3/8 of the remaining patients. In regards to palliation of symptoms, 5/6 of the patients with significant cranial nerve deficits reported improvement in symptoms within 1 month. Additionally, 5/5 patients with pre-treatment pain reported improvement. CONCLUSIONS: SRS is a safe, efficient, and potentially effective treatment for skullbase metastases with acceptable rates of local control. SRS leads to improvement in both pain and cranial nerve deficits and should therefore be integrated into the multidisciplinary palliation of this unique patient population.

Extent of perilesional edema differentiates radionecrosis from tumor recurrence following stereotactic radiosurgery for brain metastases.

BACKGROUND: Differentiation of tumor recurrence from radionecrosis is a critical step in the follow-up management of patients treated with stereotactic radiosurgery (SRS) for brain metastases. A method that can reliably differentiate tumor recurrence from radiation necrosis using standard MR sequences would be of significant value. METHODS: We analyzed the records of 49 patients with 52 brain metastases treated with SRS who subsequently underwent surgical resection of the same lesion. Forty-seven of the lesions had preoperative MRI available for review (90%), including T1 postcontrast, T2, and fluid attenuated inversion recovery sequences. Pre-SRS and preoperative lesion and edema volumes were manually contoured and measured in a blinded fashion using radiation treatment planning software. A neuropathologist analyzed samples for the presence of tumor and/or radiation necrosis. RESULTS: Longer time between SRS and resection (P < .001) and a larger edema/lesion volume ratio (high T2/T1c, P = .002) were found to be predictive of radionecrosis as opposed to tumor recurrence. Using a cutoff value of 10 for the edema/lesion volume ratio, we were able to predict the presence of tumor with a positive predictive value of 92%, which increased to 100% when looking only at patients who underwent resection <18 months following SRS. CONCLUSIONS: On follow-up imaging, lesions with a high edema/lesion volume ratio and lesions that progress later after SRS are more likely to contain radionecrosis. These indices may help guide clinical decision making in the context of evolving lesions after SRS for brain metastases and thereby avoid unnecessary interventions.

Clinical outcomes of reirradiation of brain metastases from small cell lung cancer with Cyberknife stereotactic radiosurgery.

PURPOSE: To analyze outcomes of reirradiation with stereotactic radiosurgery (SRS) for patients with brain metastases from small cell lung cancer (SCLC). MATERIALS AND METHODS: We reviewed the clinical outcomes of 27 patients with brain metastases from SCLC treated with CyberKnife® robotic radiosurgery (Accuray Inc., Sunnyvale, CA). Kaplan-Meier analyses were used to estimate local control (LC), intracranial control (IC), and overall survival (OS). The Graded Prognostic Assessment (GPA) prognostic index was determined with a Cox Regression analysis to model predictors of outcome. RESULTS: The median follow-up from SRS was 12 months (2-24 months). Nine patients (32.1%) had Graded Prognostic Assessment (GPA) scores 0-1 and 19 patients (67.9%) had GPA scores 1.5-2.5. 19 patients (70%) received whole brain radiation therapy (WBRT) and 8 patients (30%) received prophylactic cranial irradiation (PCI). The median SRS dose was 20.5 Gy (15-24 Gy) in 1 fraction. Actuarial LC at 6 months and 12 months was 76.5% and 76.5%, respectively. New metastases outside the treated area developed in 60% of assessable patients at a median 3.5 months; 78% received previous WBRT. The median OS was 3 months from SRS with actuarial 6-month and 12-month rates of 25% and 3.6%, respectively. On multivariate analysis no factors were associated with LC, IC, or OS. CONCLUSIONS: SRS for reirradiation of brain metastases from SCLC is safe and achieves local tumor control in the majority of patients. Despite SRS, these patients are at high risk of distant brain failure.

Linear accelerator based stereotactic radiosurgery for melanoma brain metastases.

PURPOSE: Melanoma is one of the most common malignancies to metastasize to the brain. Many patients with this disease will succumb to central nervous system (CNS) disease, highlighting the importance of effective local treatment of brain metastases for both palliation and survival of the disease. Our objective was to evaluate the outcomes associated with stereotactic radiosurgery (SRS) in the treatment of melanoma brain metastases. MATERIALS AND METHODS: We retrospectively reviewed 54 patients with a total of 103 tumors treated with SRS. Twenty patients had prior surgical resection and nine patients underwent prior whole brain radiation therapy (WBRT). 71% of patients had active extracranial disease at the time of SRS. Median number of tumors treated with SRS was 1(range: 1-6) with median radiosurgery tumor volume 2.1 cm 3 (range: 0.05-59.7 cm 3 ). The median dose delivered to the 80% isodose line was 24 Gy in a single fraction. RESULTS: The median follow-up from SRS was five months (range:1-30 months). Sixty-five percent of patients had a follow-up MRI available for review. Actuarial local control at six months and 12 months was 87 and 68%, respectively. Eighty-one percent of patients developed new distant brain metastases at a median time of two months. The six-month and 12-month actuarial overall survival rates were 50 and 25%, respectively. The only significant predictor of overall survival was surgical resection prior to SRS. Post-SRS bleeding occurred in 18% of patients and at a median interval of 1.5 months. There was only one episode of radiation necrosis with no other treatment-related toxicity. CONCLUSION: SRS for brain metastases from melanoma is safe and achieves acceptable local control.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

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.

Induction of CD8+ T-cell responses against novel glioma-associated antigen peptides and clinical activity by vaccinations with {alpha}-type 1 polarized dendritic cells and polyinosinic-polycytidylic acid stabilized by lysine and carboxymethylcellulose in patients with recurrent malignant glioma.

PURPOSE: A phase I/II trial was performed to evaluate the safety and immunogenicity of a novel vaccination with α-type 1 polarized dendritic cells (αDC1) loaded with synthetic peptides for glioma-associated antigen (GAA) epitopes and administration of polyinosinic-polycytidylic acid [poly(I:C)] stabilized by lysine and carboxymethylcellulose (poly-ICLC) in HLA-A2(+) patients with recurrent malignant gliomas. GAAs for these peptides are EphA2, interleukin (IL)-13 receptor-α2, YKL-40, and gp100. PATIENTS AND METHODS: Twenty-two patients (13 with glioblastoma multiforme [GBM], five with anaplastic astrocytoma [AA], three with anaplastic oligodendroglioma [AO], and one with anaplastic oligoastrocytoma [AOA]) received at least one vaccination, and 19 patients received at least four vaccinations at two αDC1 dose levels (1 × or 3 × 10(7)/dose) at 2-week intervals intranodally. Patients also received twice weekly intramuscular injections of 20 µg/kg poly-ICLC. Patients who demonstrated positive radiologic response or stable disease without major adverse events were allowed to receive booster vaccines. T-lymphocyte responses against GAA epitopes were assessed by enzyme-linked immunosorbent spot and HLA-tetramer assays. RESULTS: The regimen was well-tolerated. The first four vaccines induced positive immune responses against at least one of the vaccination-targeted GAAs in peripheral blood mononuclear cells in 58% of patients. Peripheral blood samples demonstrated significant upregulation of type 1 cytokines and chemokines, including interferon-α and CXCL10. Nine (four GBM, two AA, two AO, and one AOA) achieved progression-free status lasting at least 12 months. One patient with recurrent GBM demonstrated sustained complete response. IL-12 production levels by αDC1 positively correlated with time to progression. CONCLUSION: These data support safety, immunogenicity, and preliminary clinical activity of poly-ICLC-boosted αDC1-based vaccines.