Safety and efficacy of surgical treatment for brainstem hemangioblastoma: a meta-analysis.

Brainstem hemangioblastomas are benign, highly vascular tumors located in the mesencephalon, pons, and medulla oblongata. Although surgical resection is currently considered the main therapeutic option for symptomatic lesions, evidence supporting the application of microsurgery has not been systematically assessed. This meta-analysis aims to evaluate the safety and efficacy of surgical treatment for brainstem hemangioblastomas. A comprehensive search of the PubMed, Embase, and Web of Science databases was performed to identify all English language publications reporting the outcomes of surgical treatment for brainstem hemangioblastomas. Studies from January 1990 to July 2019 with ≥ 10 cases were included. We analyzed the surgical outcomes, including gross total resection, mortality, neurological morbidity, and functional outcome according to the McCormick Scale or Karnofsky Performance Scale. Thirteen studies with 473 cases were included. The pooled proportion of gross total resection was 98% (95% confidence interval (CI), 94-100%). Overall mortality and neurological morbidity were 4 (95% CI, 2-6%) and 13% (95% CI, 7-20%), respectively. Favorable functional outcomes at the last follow-up were achieved in 85% (95% CI, 78-92%) of all patients. Improved or stable functional outcomes at long-term follow-up were achieved in 94% (95% CI, 89-97%) of patients. This meta-analysis revealed that surgical treatment for brainstem hemangioblastomas is technically feasible and effective with lasting patient benefits and cure.

Incidence and Prognosis of Spinal Hemangioblastoma: A Surveillance Epidemiology and End Results Study.

OBJECTIVE: Intradural spinal hemangioblastoma are infrequent, vascular, pathologically benign tumors occurring either sporadically or in association with von Hippel-Lindau disease along the neural axis. Described in fewer than 1,000 cases, literature is variable with respect to epidemiological factors associated with spinal hemangioblastoma and their treatment. The objective of this study was to evaluate the epidemiology of intradural spinal hemangioblastoma with the Surveillance, Epidemiology and End Results (SEER) database while also presenting an illustrative case. METHODS: The SEER database was queried for cases of spinal hemangioblastoma between 2000 and 2010 with the use of SEER*Stat software. Incidence was evaluated as a function of age, sex and race. Survival was evaluated with the Cox proportionate hazards ratio using IBM SPSS software evaluating age, sex, location, treatment modality, pathology and number of primaries (p = 0.05). Descriptive statistics of the same factors were also calculated. The case of a 43-year-old patient with a surgical upper cervical intramedullary hemangioblastoma is also presented. RESULTS: In the data set between 2000 and 2010, there were 133 cases with an age-adjusted incidence of 0.014 (0.012-0.017) per 100,000 to the standard USA population. Hemangioblastoma was the tenth most common intradural spinal tumor type representing 2.1% (133 of 6,156) of all spinal tumors. There was no difference in incidence between men and women with an female:male rate ratio of 1.05 (0.73-1.50) with p = 0.86. The average age of patients was 48.0 (45.2-50.9) years, and a lower incidence was noted in patients <15 years compared to all other age groups (p < 0.05). There was no difference in incidence amongst the different races. Treatment included surgical resection in 106 (79.7%) cases, radiation with surgery in 7 (5.3%) cases, and radiation alone was used in only 1 (0.8%) case, and no treatment was performed in 17 (12.8%) cases. Mortality was noted in 12 (9%) cases, and median survival of 27.5 months (range 1-66 months) over the 10-year period. Mortality was attributable to the malignancy in 3 (2%) cases. There was no statistically significant different in Cox hazard ratios for mortality for sex, race, treatment modality, pathology or number of primaries. CONCLUSIONS: Spinal hemangioblastoma represent a small fraction of primary intradural spinal tumors, and this study did not identify any difference in incidence between genders. Surgical treatment alone was the most common treatment modality. Overall prognosis is good, with 9% observed mortality over the 10-year period, with 2% mortality attributable to the malignancy.

Cerebral Hemangioblastoma Without Von Hippel-Lindau Syndrome: A Report of 6 Cases.

Background. Hemangioblastoma occurs mainly in the cerebellum and rarely in the cerebrum. Objective. The present study aimed to analyze the clinical manifestations and radiological and pathological features of cerebral hemangioblastoma, and to improve the recognition of this tumor and avoid misdiagnosis. Methods. The characteristics of 6 patients with cerebral hemangioblastoma were analyzed, and a retrospective review of cerebral hemangioblastoma reported in the literature was performed. Results. All 6 patients were female, aged from 22 to 70 years (55 years on average), and all cases were wild-type sporadic, in which 4 cases occurred in the frontal lobe and 2 cases occurred in the parietal lobe. Imaging revealed a solid tumor in 4 cases, a cystic tumor in 1 case, and a mixed tumor in 1 case. Microscopically, the morphology and immunophenotype of tumor cells were not different from those of classical hemangioblastoma. All 6 patients survived tumor free during the follow-up period. Conclusions. Cerebral hemangioblastoma often simulates the imaging characteristics of meningioma or glioma. Enough attention should be paid to differential diagnosis before the operation, and exact diagnosis relies on the pathological examination.

Central nervous system hemangioblastomas: An age-stratified analysis.

BACKGROUND: Hemangioblastomas (HBs) are rare and understudied. The impact of age on clinical features, optimal treatment, and postoperative outcome in HBs has not been systemically studied. MATERIALS AND METHODS: We performed an institutional study in the West China Hospital, including patients diagnosed with hemangioblastomas between October 2011 and October 2016. Clinical data and surgical outcomes were compared among three different age groups (0-20, 21-59, and ≥ 60 years). We also studied surgical prognostic factors. RESULTS: 187 patients (102 males and 85 females) were identified. HBs in spinal locations were more prevalent in children and adolescents, while the most common site in young and old-age adults was the cerebellum (P = 0.023). Risk of Von Hippel-Lindau syndrome (VHL) was negatively correlated with patient age (P = 0.003). 47.6 % of patients aged 0-20, 23 % of patients aged 21-59, and 6.45 % of patients aged ≥60 years were diagnosed with VHL. Older aged patients had a significantly lower risk of VHL and had a lower tumor recurrence rate. Surgical resection was an adequate and sufficient procedure in all age groups with a favorable surgical outcome (P = 0.823). Solid tumor, VHL disease, and localization in the brainstem were associated with poor outcome in patients with hemangioblastomas. CONCLUSIONS: Our study showed that HBs in elderly patients were mostly included in the cerebellum and had a solid configuration and large size, while HBs in children were mainly localized in the spinal cord. VHL disease was more common in children and adolescents but rare in patients older than 60 years. The present study found no excess surgical mortality and risks for HBs in elderly patients or children than in younger adults.

Assessment of care pattern and outcome in hemangioblastoma.

Due to its rarity, current literature assessing prognostic factors and survival outcomes of hemangioblastoma is limited. Patients with histologically confirmed hemangioblastoma were identified from the US National Cancer Data Base. 1488 patients met inclusion criteria. 644 patients underwent gross total resection (GTR), 220 subtotal resection (STR)/biopsy, 60 stereotactic radiosurgery (SRS), 15 external beam radiotherapy (EBRT), 51 surgery followed by radiotherapy (SR + RT) and 498 no treatment. Independent predictors of shorter OS included age ≥ 40 (HR, 3.897; 95% CI, 2.341-6.487; p < 0.001), Charlson-Deyo score ≥ 1(HR, 1.756; 95% CI, 1.213-2.544; p = 0.003), tumor location in the brainstem (HR, 1.955; 95% CI, 1.129-3. 384; p = 0.017) compared to cerebellum, no treatment (HR, 2530; 95% CI, 1.533-4.177; p < 0.001) and receipt of EBRT (HR, 2.860; 95% CI, 1.073-7.618; p = 0.036) compared to STR/biopsy. GTR was associated with longer OS (HR 0.617; 95% CI, 0.391-0.974; p = 0.038), while SRS had comparable OS to STR/biopsy. The overall trend of OS by treatment modality was consistent after matching to age- and sex-matched US population data. In patients younger than 40 years, treatment was not a significant predictor of OS. In conclusion, GTR remained the optimal treatment for hemangioblastoma. SRS may perform similarly to surgery alone. Treatment was not a significant predictor of survival in younger patients.

Role of fractionated external beam radiotherapy in hemangioblastoma of the central nervous system.

PURPOSE: To assess the clinical outcomes and toxicity in patients receiving fractionated external beam radiotherapy (EBRT) for hemangioblastoma of the central nervous system, treated at two Canadian radiation oncology institutions. METHODS AND MATERIALS: Between January 1980 and December 2004, the data of all patients receiving EBRT for central nervous system hemangioblastoma were retrospectively reviewed. The patient, tumor, and treatment characteristics were collected and overall survival, disease-free survival, and EBRT-related toxicities assessed. RESULTS: A total of 18 cases, 5 associated with von Hippel-Lindau disease (VHL) and 13 sporadic (non-VHL), with a total 31 lesions, were documented. These were located in the cerebellum in 20 and spinal cord in 8 patients. EBRT was delivered for recurrence in 12, adjuvantly for residual disease in 4, and definitively in 2. The EBRT schedules ranged from 50.0 to 55.8 Gy in 1.8-2.0-Gy daily fractions (n = 17), typically with parallel-opposed fields to the cerebellar target volumes and direct posterior fields for spinal disease. At a median follow-up of 5.1 years (range, 0.1-14.5), the 5-year OS rate was 69% (95% confidence interval [CI], 50-96%), decreasing to 30% (95% CI, 10-87%) at 10 years. The disease-free survival rate at 5 and 10 years was 57% (95% CI, 37-87%) and 30% (95% CI, 11-83%), respectively. The outcomes differed according to VHL status. The 5-year OS rate was 100% for those with VHL compared with 55% (95% CI, 32-95%) for those with non-VHL disease (log-rank p = 0.003), and the 5-year disease-free survival rate was 80% (95% CI, 52-100%) with VHL compared with 48% (95% CI, 26-89%) without (log-rank p = 0.036). CONCLUSIONS: Fractionated EBRT has a role in the management of extensive intracranial and/or spinal cord disease, the adjuvant treatment of residual postoperative disease, and the treatment of recurrence. More favorable outcomes were reported for VHL-associated lesions than for sporadic cases.

A non-cell autonomous mouse model of CNS haemangioblastoma mediated by mutant KRAS.

Haemangioblastoma is a rare malignancy of the CNS where vascular proliferation causes lesions due to endothelial propagation. We found that conditionally expressing mutant Kras, using Rag1-Cre, gave rise to CNS haemangioblastoma in the cortex and cerebellum in mice that present with highly vascular tumours with stromal cells similar to human haemangioblastomas. The aberrant haemangioblastoma endothelial cells do not express mutant Kras but rather the mutant oncogene is expressed in CNS interstitial cells, including neuronal cells and progeny. This demonstrates a non-cell autonomous origin of this disease that is unexpectedly induced via Rag1-Cre expression in CNS interstitial cells. This is the first time that mutant RAS has been shown to stimulate non-cell autonomous proliferation in malignancy and suggests that mutant RAS can control endothelial cell proliferation in neo-vascularisation when expressed in certain cells.

Genetic alterations of IDH1 and Vegf in brain tumors.

BACKGROUND: This study evaluates the presence of R132H mutation in isocitrate dehydrogenase (IDH1) gene and the vascular endothelial growth factor (VEGF) +936 C/T polymorphism in brain tumors. The impact of these genetic alterations on overall survival (OS) and progression free survival (PFS) was evaluated. METHODS: A cohort of 80 patients surgically treated at Hospital Clínico San Carlos, Madrid, between March 2004 and November 2012, was analyzed. Tumors were distributed in 73 primary brain tumors (gliomas, meningiomas, hemangiopericytomas and hemangioblastomas) and seven secondary tumors evolved from a low grade glioma, thus providing a mixed sample. RESULTS: IDH1R132H gene mutation was found in 12 patients (15%) and appears more frequently in secondary tumors (5 (71.4%) whereas in 7 (9.7%) primary tumors (p < .001)). The mutation is related to WHO grade II in primary tumors and a supratentorial location in secondary tumors. The OS analysis for IDH1 showed a tendency towards a better prognosis of the tumors containing the mutation (p = .059).The IDH1R132H mutation confers a better PFS (p = .025) on primary tumors. The T allele of VEFG +936 C/T polymorphism was found in 16 patients (20%). No relation was found between this polymorphism and primary or secondary tumor, neither with OS or PFS. CONCLUSIONS: IDH1R132H gene mutation is exclusive in supratentorial tumors and more frequent in secondary ones, with a greater survival trend and better PFS in patients who carry it. The T allele of VEGF +936 C/T polymorphism is more common in primary tumors, although there is no statistical relation with survival.

Safety and outcomes of preoperative embolization of intracranial hemangioblastomas: A systematic review.

INTRODUCTION: While preoperative embolization is often reserved for large and highly vascular tumors in order to minimize blood loss, its safety and efficacy in the treatment of hemangioblastomas (HB) is unclear. We present the largest systematic review focusing on the safety and outcome of preoperative embolization of intracranial HB. MATERIALS AND METHODS: To identify all cases of preoperative embolization for HB, a literature search was conducted via Medline (OVID and PubMed), Scopus, Embase, and Web of Science. Studies that were in English, included intracranial hemangioblastomas treated with preoperative embolization and provided sufficient disaggregated clinical data for each patient were included. Historical control patients with non-embolized intracranial HB undergoing resection were similarly identified. RESULTS: A total of 111 patients that underwent preoperative embolization of HB prior to planned resection were identified. Patient age ranged from 12 to 72 years, with a cohort of 63% males and 36% females. Nine studies comprising 392 non-embolized patients were included as controls. Gross total resection was achieved in 83.7% of embolized and 95.6% of non-embolized patients. Intraoperative blood transfusion was required in 15.3% of embolized and 0.51% of non-embolized controls, while rates of post-operative hemorrhage were 8.4% and 1.6%, respectively. Complication rates from embolization were 11.7% and following consequent surgery were 20.7%. DISCUSSION: Embolization did not increase rates of gross total resection, decrease estimated blood loss, or decrease incidence of complications. Not only does embolization fail to mitigate surgical risks, the embolization procedure itself carries significant risk for complications. Embolization should not be standard of care for intracranial HB.

Gamma knife surgery for hemangioblastomas.

OBJECT: The authors reviewed their 14-year experience using stereotactic radiosurgery for the treatment of hemangioblastomas and define the role and the proper strategy for radiosurgery of this condition. METHODS: This is a retrospective study of 38 hemangioblastomas in 13 patients. Seven patients had von Hippel-Lindau disease. All patients have undergone at least one follow-up visit. The median and mean tumor volumes were 0.23 cm3 and 0.72 cm3 respectively (range 0.004::4.84 cm3). Twenty-eight tumors received 20 Gy to the margin, and the remainder received 18 Gy. The median clinical follow-up period was 36 months (range 3-159 months). No patient died. The survival rate was 84.6% (11 of 13 patients). The actuarial 5- and 10-year survival rates were both 80.8%. The median radiological follow-up period was 35 months (range 7-147 months). Only one tumor increased in volume 24 months after treatment in association with an intratumoral hemorrhage. The tumor control rate was 97.4% (37 of 38 tumors). Actuarial 5- and 10-year control rates were both 96.2%. New lesions and/or those increasing in size outside the irradiated area were discovered in five patients (38.5%). Nine tumors revealed peritumoral contrast enhancement which was seen more frequently in larger tumors with a volume greater than 0.5 cm3 (p = 0.0034). CONCLUSIONS: Gamma knife surgery is a safe and effective method to control hemangioblastomas for as many as 10 years. Higher doses and smaller tumors probably contribute to good outcomes. Recurrence outside the original irradiated area is common. Peritumoral contrast enhancement may be seen in larger tumors. The authors recommend regular imaging follow up and early repeated treatment in the face of new or growing tumors.

The long-term results of gamma knife radiosurgery for hemangioblastomas of the brain.

OBJECT: The authors assessed the long-term result of gamma knife surgery (GKS) for hemangioblastomas of the brain (HABs) and show histopathological findings after GKS. METHODS: Thirty-five patients, 28 men and seven women, with a mean age of 36 years underwent GKS. Eighteen patients presented with multiple tumors and 17 with a solitary tumor. Twenty-one patients had von Hippel-Lindau (VHL) disease. The mean tumor diameter was 13 mm (range 5-55 mm). The mean follow up after GKS was 66 months (range 24-114 months). The mean prescription dose was 17.2 Gy (range 12-24 Gy) at the tumor margin. For tumors close to or within the brainstem a prescription dose of 12 to 13 Gy was used. At the most recent follow up, 29 patients were alive, six were dead, and satisfactory tumor control had been achieved in 29. A stable or improved neurological status was obtained in 21 patients. Eight patients underwent open surgery because of tumor-associated cyst enlargement or the development of new tumors after GKS. Seven patients developed new tumors and five of them required a second GKS. The 1-year tumor control rate was 94%; 2 years, 85%; 3 years, 82%; 4 years, 79%; and 5 years, 71%. Histopathology showed that no tumor cells were found and there was degeneration and necrosis in a tumor nodule 48 months after GKS with a prescription dose of 18 Gy. CONCLUSIONS: Gamma knife surgery was a useful choice for small- or medium-sized, solid HAB in the long term, especially when the tumor margin dose was 18 Gy. Although GKS can treat multiple tumors in a single session, for HABs associated with VHL disease, GKS faces the dual problems of tumor recurrence or development of a new tumor.

Treatment of hemangioblastomas in von Hippel-Lindau disease with linear accelerator-based radiosurgery.

OBJECTIVE: Stereotactic radiosurgery is increasingly being used to treat hemangioblastomas, particularly those that are in surgically inaccessible locations or that are multiple, as is common in von Hippel-Lindau disease. The purpose of this study was to retrospectively evaluate the effectiveness of radiosurgery in the treatment of hemangioblastomas. METHODS: From 1989 to 1996, 29 hemangioblastomas in 13 patients with von Hippel-Lindau disease were treated with linear accelerator-based radiosurgery. The mean patient age was 40 years (range, 31-57 yr). The radiation dose to the tumor periphery averaged 23.2 Gy (range, 18-40 Gy). The mean tumor volume was 1.6 cm3 (range, 0.07-65.4 cm3). Tumor response was evaluated in serial, contrast-enhanced, computed tomographic and magnetic resonance imaging scans. The mean follow-up period was 43 months (range, 11-84 mo). RESULTS: Only one (3%) of the treated hemangioblastomas progressed. Five tumors (17%) disappeared, 16 (55%) regressed, and 7 (24%) remained unchanged in size. Five of nine patients with symptoms referable to treated hemangioblastomas experienced symptomatic improvement. During the follow-up period, one patient died as a result of progression of untreated hemangioblastomas in the cervical spine. Three patients developed radiation necrosis, two of whom were symptomatic. CONCLUSION: Although follow-up monitoring is limited, stereotactic radiosurgery provides a high likelihood of local control of hemangioblastomas and is an attractive alternative to multiple surgical procedures for patients with von Hippel-Lindau disease.

Hypothermic circulatory arrest in neurovascular surgery: evolving indications and predictors of patient outcome.

OBJECTIVE: One of the largest contemporary neurosurgical experiences with hypothermic circulatory arrest was analyzed for trends in patient selection and clinical variables affecting outcome. METHODS: During a 12-year period, 60 patients underwent 62 circulatory arrest procedures: 54 had posterior circulation aneurysms, 4 had anterior circulation aneurysms, and 2 had other lesions (hemangioblastoma and vertebral artery atherosclerosis). RESULTS: The surgical morbidity and mortality rates associated with hypothermic circulatory arrest were 13.3 and 8.3%, respectively. At late follow-up, 76% of the patients had good outcomes (Glasgow Outcome Scale scores of 1 and 2), 5% had poor outcomes (Glasgow Outcome Scale scores of 3 and 4), and 18% had died. After 1992, circulatory arrest was limited to posterior circulation aneurysms and included increasing numbers of basilar trunk aneurysms. Patient outcome correlated with preoperative neurological condition (admission Glasgow Coma Scale score, P < 0.001; Hunt and Hess grade, P = 0.037; and age, P = 0.007). Preservation of perforating arteries was paramount to achieving a good outcome (P = 0.005); duration of circulatory arrest was not. CONCLUSION: Current indications for hypothermic circulatory arrest include only giant and complex posterior circulation aneurysms that cannot be treated using conventional techniques or that recur after endovascular coiling. Surgical morbidity and mortality rates reflect the increasing complexity of the aneurysms treated but are still more favorable than the natural history of these lesions. This experience demonstrates that management in specialized neurovascular centers can minimize the morbidity associated with circulatory arrest so that it remains a viable treatment option for complex posterior circulation aneurysms.

Diagnosis and surgical treatment of posterior fossa solid hemangioblastomas.

OBJECTIVE: To elucidate the diagnosis and surgical treatment of the posterior fossa solid hemangioblastomas (PFSHs). METHODS: The data from 22 patients with PFSHs verified by surgery and pathology were analyzed retrospectively and a review of relevant literature was conducted. RESULTS: The preoperative definitive diagnosis rate was 13/22. Total tumor removal was achieved in 20 patients. Two of the 22 patients died after surgery, one of brain-stem injury and the other from an intracranial hemorrhage. Twenty patients were followed up for 2 months to 8 years (average, 2 years). Kamofsky scale was > or = 80 in 15 patients, 60-70 in 1 patient and not measured in 4 patients who died during follow-up. The causes of death were pneumonia (2 patients) and purulent meningitis (2). CONCLUSION: MRI and DSA (digital subtraction angiography) are major preoperative diagnostic modalities for PFSH, but PFSH remains a challenging benign neoplasm. Special microsurgical techniques and improved operative manipulation can improve surgical efficacy.

Management and outcome in adult intramedullary spinal cord tumours: a 20-year single institution experience.

BACKGROUND: Several uncertainties remain concerning the management of intramedullary spinal cord tumours (IMSCTs). These include the timing and extent of resection, its interrelated functional outcome, and the adequate use and timing of radiation therapy and/or chemotherapy. In this retrospective study we report on all adult cases involving IMSCTs treated from 1987 to 2007 in our institution to validate our treatment strategy for IMSCTs. Pre- and post-operative functional performance was classified according to the McCormick scale. RESULTS: A total of 70 adult cases with IMSCTs consisting of ependymoma (39), astrocytoma (11), carcinoma metastasis (8), haemangioblastoma (5), cavernoma (3) and others (4) were reviewed. Mean age was 46.8 years (range, 18-79 years), and mean follow-up was 4.5 years (range, 1-195 months). The proportion of localisation in descending order was thoracic (36%), cervical (33%), cervicothoracic (19%) and conus region (13%), with 45 gross total resections, 22 partial resections and three biopsies. Surgery-related morbidity with worsening postoperative symptoms occurred immediately in 13 patients (18.6%). The preoperative McCormick grade correlated significantly with the early postoperative grade and the grade at follow-up (χ2-test; p=0.001). None of the patients with preserved intraoperative evoked potentials exhibited significant postoperative deterioration. The degree of resection was correlated with progression-free survival (Duncan test; p=0.05). Most patients with malignant tumours, namely anaplastic ependymoma (3), astrocytoma (2) or metastatic lesions (5), underwent postoperative radiation therapy. Six patients (one anaplastic ependymoma, two anaplastic astrocytomas and three metastatic lesions) received postoperative chemotherapy. CONCLUSIONS: IMSCTs should be operated on when symptoms are mild. We recommend evoked potential-guided microsurgical total resection of ependymomas and other benign lesions; partial resection or biopsy followed by adjuvant therapy should be confined to patients with high-grade astrocytomas, whereas resection or biopsy with adjuvant therapy is the best option for metastatic lesions.

Supratentorial hemangioblastoma: clinical features, prognosis, and predictive value of location for von Hippel-Lindau disease.

Supratentorial hemangioblastoma is a rare form of hemangioblastoma; little information is available regarding prognosis, treatment, and clinical characteristics, because the available literature is primarily composed of case reports and small case series. Therefore, we performed a systematic review of the literature to analyze clinical characteristics, disease progression, and surgical outcomes with respect to survival for supratentorial hemangioblastomas. The rate of progression-free survival (PFS) was determined using Kaplan-Meier analysis. Differences in categorical factors, including location of tumor and diagnosis of von Hippel-Lindau (VHL) disease, were analyzed using the Pearson χ(2) test. A total of 106 articles met the search criteria, which combined for a total of 132 patients. Of the patients with supratentorial tumors, 60% had VHL disease, and 31 (84%) of 37 patients with tumors in the sellar/suprasellar region had associated VHL (χ(2), P < .001). Five-year PFS for gross-total resection and subtotal resection were 100% and 53%, respectively (Log rank, P < .01). On the basis of our analysis of the literature on published cases of supratentorial hemangioblastoma, gross-total resection appears to be superior to other treatment modalities in extending PFS. Von Hippel-Lindau disease is positively correlated with supratentorial hemangioblastoma when compared with non-supratentorial CNS hemangioblastomas, particularly when present in the sellar/suprasellar region.

Prospective evaluation of radiosurgery for hemangioblastomas in von Hippel-Lindau disease.

To determine the effectiveness of stereotactic radiosurgery (SRS) treatment to central nervous system (CNS) hemangioblastomas in von Hippel-Lindau disease (VHL), we analyzed long-term results in VHL patients treated with SRS. Patients were enrolled in a prospective VHL natural history study, undergoing SRS treatment of CNS hemangioblastomas. Treatment regimens, serial clinical evaluations, and longitudinal imaging data were analyzed. Twenty VHL patients (10 males and 10 females) underwent SRS treatment of 44 CNS hemangioblastomas (39 cerebellar and 5 brainstem). Mean (+/-SD) age at treatment was 37.5 +/- 12.0 years (range: 13-67). Mean follow-up was 8.5 +/- 3.2 years (range: 3.0-17.6 years). All patients were alive at last follow-up. Mean treated tumor volume was 0.5 +/- 0.7 cm(3) (range: 0.01-3.6 cm(3)). Mean prescription dose was 18.9 Gy (range: 12-24 Gy) at the tumor margin. Local control rate at 2, 5, 10, and 15 years after SRS treatment was 91%, 83%, 61%, and 51%, respectively. Univariate analysis did not identify variables associated (P > .05) with worse tumor control at last follow-up. Thirty-three percent of SRS-treated small (<1.0 cm diameter), asymptomatic tumors progressed over a long-term follow-up. There were no long-term adverse radiation effects. Although SRS treatment of hemangioblastomas in VHL has a low risk for adverse radiation effects, it is associated with diminishing control over a long-term follow-up. These results indicate that SRS should not be used to prophylactically treat asymptomatic tumors and should be reserved for the treatment of tumors that are not surgically resectable.

Factors associated with progression-free survival and long-term neurological outcome after resection of intramedullary spinal cord tumors: analysis of 101 consecutive cases.

OBJECT: With the introduction of electrophysiological spinal cord monitoring, surgeons have been able to perform radical resection of intramedullary spinal cord tumors (IMSCTs). However, factors associated with tumor resectability, tumor recurrence, and long-term neurological outcome are poorly understood. METHODS: The authors retrospectively reviewed 101 consecutive cases of IMSCT resection in adults and children at a single institution. Neurological function and MR images were evaluated preoperatively, at discharge, 1 month after surgery, and every 6 months thereafter. Factors associated with gross-total resection (GTR), progression-free survival (PFS), and long-term neurological improvement were assessed using multivariate regression analysis. RESULTS: The mean age of the patients was 41 +/- 18 years and 17 (17%) of the patients were pediatric. Pathological type included ependymoma in 51 cases, hemangioblastoma in 15, pilocytic astrocytoma in 16, WHO Grade II astrocytoma in 10, and malignant astrocytoma in 9. A GTR was achieved in 60 cases (59%). Independent of histological tumor type, an intraoperatively identifiable tumor plane (OR 25.3, p < 0.0001) and decreasing tumor size (OR 1.2, p = 0.05) were associated with GTR. Thirty-four patients (34%) experienced acute neurological decline after surgery (associated with increasing age [OR 1.04, p = 0.02] and with intraoperative change in motor evoked potentials [OR 7.4, p = 0.003]); in 14 (41%) of these patients the change returned to preoperative baseline within 1 month. In 31 patients (31%) tumor progression developed by last follow-up (mean 19 months). Tumor histology (p < 0.0001) and the presence of an intraoperatively identified tumor plane (hazard ratio [HR] 0.44, p = 0.027) correlated with improved PFS. A GTR resulted in improved PFS for hemangioblastoma (HR 0.004, p = 0.04) and ependymoma (HR 0.2, p = 0.02), but not astrocytoma. Fifty-five patients (55%) maintained overall neurological improvement by last follow-up. The presence of an identifiable tumor plane (HR 3.1, p = 0.0004) and improvement in neurological symptoms before discharge (HR 2.3, p = 0.004) were associated with overall neurological improvement by last follow-up (mean 19 months). CONCLUSIONS: Gross-total resection can be safely achieved in the vast majority of IMSCTs when an intraoperative plane is identified, independent of pathological type. The incidence of acute perioperative neurological decline increases with patient age but will improve to baseline in nearly half of patients within 1 month. Long-term improvement in motor, sensory, and bladder dysfunction may be achieved in a slight majority of patients and occurs more frequently in patients in whom a surgical plane can be identified. A GTR should be attempted for ependymoma and hemangioblastoma, but it may not affect PFS for astrocytoma. For all tumors, the intraoperative finding of a clear tumor plane of resection carries positive prognostic significance across all pathological types.

The role of stereotactic radiosurgery for intracranial hemangioblastomas.

OBJECTIVE: To evaluate the role of stereotactic radiosurgery (SRS) in the management of recurrent or residual intracranial hemangioblastomas, we assessed tumor control, survival, and complications in 32 consecutive patients. METHODS: We retrospectively reviewed records of 32 consecutive hemangioblastoma patients (74 intracranial tumors) who underwent gamma knife SRS. The median patient age was 43.8 years (range, 21.3-79.4 yr). Thirty-one patients had undergone previous surgical resections. Nineteen patients had sporadic lesions (22 tumors), and 13 patients had von Hippel-Lindau disease-associated hemangioblastomas (52 tumors). The median SRS target volume was 0.72 mL (range, 0.08-16.6 mL), and the median marginal dose was 16.0 Gy (range, 11-20 Gy). RESULTS: At a median of 50.1 months (range, 6.0-165.4 mo), seven patients had died from disease progression, and one patient had died secondary to heart failure. The overall survival after radiosurgery was 100%, 94.4%, and 68.7% at 1, 3, and 7 years, respectively. Follow-up imaging studies demonstrated tumor control in 68 tumors (91.9%). The progression-free survival after SRS at 1, 3, and 5 years was 96.9%, 95.0%, and 89.9%, respectively. Factors associated with an improved progression-free survival included von Hippel-Lindau disease-associated hemangioblastoma, solid tumor, lower tumor volume, and greater marginal dose. CONCLUSION: SRS is an important tool in the management of hemangioblastomas and is associated with a high tumor control rate and a low risk of adverse radiation effects.