A phase II open label, single arm study of hypofractionated stereotactic radiotherapy with chemoradiotherapy using intensity-modulated radiotherapy for newly diagnosed glioblastoma after surgery: the HSCK-010 trial protocol.

BACKGROUND: The most frequently diagnosed primary brain tumor is glioblastoma (GBM). Nearly all patients experience tumor recurrence and up to 90% of which is local recurrence. Thus, increasing the therapeutic ratio of radiotherapy using hypofractionated stereotactic radiotherapy (HSRT) can reduce treatment time and may increase tumor control and improve survival. To evaluate the efficacy and toxicity of the combination of HSRT and intensity-modulated radiotherapy (IMRT) with temozolomide after surgery in GBM patients and provide evidence for further randomized controlled trials. METHODS/DESIGN: HSCK-010 is an open-label, single-arm phase II trial (NCT04547621) which includes newly diagnosed GBM patients who underwent gross total resection. Patients will receive the combination of 30 Gy/5fx HSRT, and 20 Gy/10fx IMRT adjuvant therapy with concurrent temozolomide and adjuvant chemotherapy. The primary endpoint is overall survival (OS). Secondary outcomes include progression-free survival (PFS) rate, objective-response rate (ORR), quality of life (Qol) before and after the treatment, cognitive function before and after the treatment, and rate of treatment-related adverse events (AE). The combination of HSRT and IMRT with temozolomide can benefit the patients after surgery with good survival, acceptable toxicity, and reduced treatment time. TRIAL REGISTRATION: NCT04547621 . Registered on 14 September 2020.

Safety and Efficacy of Hypofractionated Stereotactic Radiotherapy with Anlotinib Targeted Therapy for Glioblastoma at the First Recurrence: A Preliminary Report.

(1) Background: Hypofractionated stereotactic radiotherapy (HSRT) and anti-vascular endothelial growth factor (VEGF) antibodies have been reported to have a promising survival benefit in recent studies. Anlotinib is a new oral VEGF receptor inhibitor. This report describes our experience using HSRT and anlotinib for recurrent glioblastoma (rGBM). (2) Methods: Between December 2019 and June 2020, rGBM patients were retrospectively analysed. Anlotinib was prescribed at 12 mg daily during HSRT. Adjuvant anlotinib was administered d1-14 every 3 weeks. The primary endpoint was the objective response rate (ORR). Secondary endpoints included overall survival (OS), progression-free survival (PFS) after salvage treatment, and toxicity. (3) Results: Five patients were enrolled. The prescribed dose was 25.0 Gy in 5 fractions. The median number of cycles of anlotinib was 21 (14-33). The ORR was 100%. Three (60%) patients had the best outcome of a partial response (PR), and 2 (40%) achieved a complete response (CR). One patient died of tumour progression at the last follow-up. Two patients had grade 2 hand-foot syndrome. (4) Conclusions: Salvage HSRT combined with anlotinib showed a favourable outcome and acceptable toxicity for rGBM. A prospective phase II study (NCT04197492) is ongoing to further investigate the regimen.

Serum Heparanase: A New Clinical Biomarker Involved in Senile Metabolic Inflammatory Syndrome.

AIM: Metabolic inflammation syndrome (MIS) can lead to a series of complications, but its exact inflammatory mechanism is still unclear. The aim of this study was to explore the correlation between heparanase (HPA) and MIS, and the close relationship between HPA and other chronic low-grade inflammation index, such as C-reactive protein (CRP) and interleukin-6 (IL-6). METHODS: A total of 105 patients with MIS in the physical examination population of Huashan Hospital affiliated to Fudan University from May to June 2018 were selected as the MIS group, and 52 patients who were relatively healthy during the same period were used as the control group. The basic clinical data of the selected candidates were collected, the levels of serum HPA, CRP and IL-6 were measured by ELISA, and the levels of blood glucose and blood lipids were also detected. RESULTS: Compared with the control group, the levels of HPA, CRP, IL-6, FBG, HbA1C, and TG of MIS group were all significantly elevated (all P<0.05), and HDL-C levels were considerably reduced (P<0.05). Correlation analysis showed that there was a noticeably positive correlation between serum HPA level and CRP, IL-6 levels (P<0.05). CONCLUSION: Higher HPA levels might play a certain role in the occurrence and development of MIS. There was a certain close correlation between serum HPA level and CRP and IL-6 levels, and which indicated that HPA was involved in the chronic low-grade inflammatory reaction process of MIS.

Safety and efficacy of Hypofractionated stereotactic radiosurgery for high-grade Gliomas at first recurrence: a single-center experience.

BACKGROUND: The optimal treatment for recurrent high-grade gliomas (rHGGs) remains uncertain. This study aimed to investigate the efficacy and safety of hypofractionated stereotactic radiosurgery (HSRS) as a first-line salvage treatment for in-field recurrence of high-grade gliomas. METHODS: Between January 2016 and October 2019, 70 patients with rHGG who underwent HSRS were retrospectively analysed. The primary endpoint was overall survival (OS), and secondary endpoints included both progression-free survival (PFS) and adverse events, which were assessed according to Common Toxicity Criteria Adverse Events (CTCAE) version 5. The prognostic value of key clinical features (age, performance status, planning target volume, dose, use of bevacizumab) was evaluated. RESULTS: A total of 70 patients were included in the study. Forty patients were male and 30 were female. Forty-nine had an initial diagnosis of glioblastoma (GBM), and the rest (21) were confirmed to be WHO grade 3 gliomas. The median planning target volume (PTV) was 16.68 cm3 (0.81-121.96 cm3). The median prescribed dose was 24 Gy (12-30 Gy) in 4 fractions (2-6 fractions). The median baseline of Karnofsky Performance Status (KPS) was 70 (40-90). With a median follow-up of 12.1 months, the median overall survival after salvage treatment was 17.6 months (19.5 and 14.6 months for grade 3 and 4 gliomas, respectively; p = .039). No grade 3 or higher toxicities was recorded. Multivariate analysis showed that concurrent bevacizumab with radiosurgery and KPS > 70 were favourable prognostic factors for grade 4 patients with HGG. CONCLUSIONS: Salvage HSRS showed a favourable outcome and acceptable toxicity for rHGG. A prospective phase II study (NCT04197492) is ongoing to further investigate the value of hypofractionated stereotactic radiosurgery (HSRS) in rHGG.

Cyberknife radiosurgery on the brainstem metastases of non-small cell lung cancer.

OBJECTIVE: Management of brainstem metastatic tumor is challenging. This study aimed to evaluate overall survival and quality-of-life in patients with non-small cell lung cancer (NSCLC) brainstem metastases who were treated with the Cyberknife stereotactic radiosurgery. METHODS: From August 2007 through August 2016, a total of 32 patients with 34 brainstem metastases of NSCLC were consecutively enrolled and treated with the Cyberknife radiosurgery (CKRS) at The Huashan Hospital. The study was limited to patients with NSCLC, which was confirmed by postoperative pathological examination. Patients were treated by CKRS as an initial treatment or a second treatment after whole-brain radiation therapy (WBRT). Quality of life was assessed by the SF-12 score and neurological examination. RESULTS: Four out of the 32 (12.5%) patients received WBRT before or concurrent with CKRS treatment. The mean survival time after CKRS was 10.0 (95%CI: 6.0-14.0) months. Karnofsky performance score was not the independent predictor of survival after radiosurgery as analyzed by log-rank test (p = 0.392). Age, however, was a significant predictor of improved survival as analyzed by multivariate analysis (p = 0.024). SF-12 physical component scores demonstrated no significant change after treatment. CONCLUSIONS: The CKSR is a non-invasive, safe, and effective modality in the treatment of patients with brainstem metastases of NSCLC. Better therapeutic outcomes of CKSR for brainstem metastasis might be achieved in the patients older than 65 years old.

EGb761 improves the cognitive function of elderly db/db-/- diabetic mice by regulating the beclin-1 and NF-κB signaling pathways.

To assess whether EGb761 could protect elderly diabetic mice with cognitive disorders and explore the role of beclin-1-mediated autophagy in these protective effects. Two-month-old male db/db-/- mice and wild-type C57/BL6 mice were randomly divided into six groups: db/db-/- control, db/db-/- 50 mg, db/db-/- 100 mg, wild-type (WT) control, WT 50 mg, and WT 100 mg. EGb761 (50 mg/kg or 100 mg/kg of bodyweight) was given by gavage once a day for 1 month from the age of 6 months. Y-maze and social choice tests were performed at 8th months. The blood pressure was measured. The imaging changes in the brain were measured using magnetic resonance imaging (MRI). The expression and distribution of beclin-1, LC3, and NF-κB were detected using immunohistochemistry staining and western blotting. Ultrastructure alterations in the hippocampus were observed using transmission electron microscopy. Compared with WT mice, the learning ability, memory and overall cognitive function of db/db-/- mice decreased (P < 0.05), and EGb761 could significantly improve the learning and memory function of db/db-/- mice (P < 0.05). EGb761 significantly improved systolic blood pressure in db/db-/- mice (P < 0.01). In addition, fMRI-bold showed a decline in the hippocampus of mice in the db/db-/- group compared with WT. EGb761 could improve these above changes. Immunohistochemistry staining and western blotting confirmed that EGb761 significantly increased beclin-1 and reduced LC3-II/I levels in the brains of db/db-/- mice (P < 0.05). NF-κB levels were obviously higher in the db/db-/- group than that in the WT group, and EGb761 significantly reduced NF-κB levels in db/db-/- mice (P < 0.05). There was a trend of increased autophagosomes in db/db-/- mice, but EGb761 did not change obviously the number of autophagosomes. Compared with normal aged WT mice, aging db/db-/- mice had more common complications of cerebral small vessel disease and cognitive dysfunction. EGb761 could significantly improve the cognitive function of aging db/db-/- mice via a mechanism that may involve the regulation of beclin-1, LC3, and NF-κB.

Radiosurgery reduces plasma levels of angiogenic factors in brain arteriovenous malformation patients.

PURPOSE: Aberrant expression of angiogenic factors has been anecdotally documented in brain arteriovenous malformation (AVM) nidus vessels; however, no data is available on the effect of radiosurgery on the levels of angiogenic factors in AVM patients. We sought to determine the plasma contents of VEGF, TGF-ß, Ang-2 and bFGF in 28 brain AVM patients at baseline and post radiosurgery and further analyzed the relationship between plasma contents of these angiogenic factors with clinicopathologic variables of these patients. METHODS: We enrolled brain AVM patients who underwent Cyberknife radiosurgery at our hospital between January 2014 and December 2015. Brain AVM was confirmed by cerebral angiography and radiosurgery was performed with Cyberknife irradiation. Plasma contents of VEGF, TGF-ß, Ang-2 and bFGF were analyzed using commercially available enzyme-linked immunoassay (ELISA) kits. RESULTS: The baseline plasma VEGF content was 222.63 pg/mL (range 43.25-431.25 pg/mL). At three months post surgery, there was a significant -34.29% decline in plasma VEGF content versus baseline (P = 0.000). Furthermore, the median baseline plasma VEGF levels were higher in brain AVM with a nidus volume ≥ 10 cm3) than those with a nidus volume < 10 cm3 [median(IQR) 293.5 (186.5,359.25) vs. 202 (59.75, 270.75) pg/mL, P = 0.057]. The baseline plasma TGF-ß content was 556.17 pg/mL (range 44.44-1486.11 pg/mL) and there was a significant -27.47% decline in plasma TGF-ß content at 3 months post radiosurgery versus baseline (P = 0.015). Moreover, the baseline plasma ANG-2 content was 214.27 pg/mL (range 77.14-453.76 pg/mL). There was an immediate and significant -12.47% decline in plasma ANG-2 content post surgery versus baseline (P = 0.002). At three months post surgery, the plasma ANG-2 content still remained significantly depressed versus baseline (P = 0.002). In addition, the baseline plasma bFGF content was 9.17 pg/mL (range 3.67-36.78 pg/mL). No significant difference in plasma bFGF content was observed immediately post surgery and 3 months post surgery versus baseline (P = 0.05). CONCLUSIONS: Radiosurgery for brain AVM patients significantly reduced the plasma levels of angiogenic factors. The plasma angiogenic factors may be candidate markers for aberrant agniogenesis of brain AVM and patient response to radiosurgery.

Hypofractionated stereotactic radiosurgery: a new treatment strategy for giant cavernous sinus hemangiomas.

OBJECTIVE Cavernous sinus hemangiomas (CSHs) are rare benign vascular tumors that arise from the dural venous sinuses lateral to the sella. Stereotactic radiosurgery (SRS) has emerged as a principal alternative to microresection for small- and medium-sized CSHs. Resection is a reasonable option for large (3-4 cm in diameter) and giant (> 4 cm in diameter) CSHs. However, management of giant CSHs remains a challenge for neurosurgeons because of the high rates of morbidity and even death that stem from uncontrollable and massive hemorrhage during surgery. The authors report here the results of their study on the use of hypofractionated SRS (H-SRS) to treat giant CSH. METHODS Between January 2008 and April 2014, 31 patients with a giant CSH (tumor volume > 40 cm3, > 4 cm in diameter) treated using CyberKnife radiosurgery were enrolled in a cohort study. Clinical status and targeted reduction of tumor volume were evaluated by means of serial MRI. The diagnosis for 27 patients was determined on the basis of typical imaging features. In 4 patients, the diagnosis of CSH was confirmed histopathologically. The median CSH volume was 64.4 cm3 (range 40.9-145.3 cm3). Three or 4 sessions of CyberKnife radiosurgery were used with a prescription dose based on the intent to cover the entire tumor with a higher dose while ensuring dose limitation to the visual pathways and brainstem. The median marginal dose to the tumor was 21 Gy (range 19.5-21 Gy) in 3 fractions for 11 patients and 22 Gy (range 18-22 Gy) in 4 fractions for 20 patients. RESULTS The median duration of follow-up was 30 months (range 6-78 months) for all patients. Follow-up MRI scans revealed a median tumor volume reduction of 88.1% (62.3%-99.4%) at last examination compared with the pretreatment volume. Ten patients developed new or aggravated temporary headache and 5 experienced vomiting during the treatment; these acute symptoms were relieved completely after steroid administration. Among the 30 patients with symptoms observed before treatment, 19 achieved complete symptomatic remission, and 11 had partial remission. One patient reported seizures, which were controlled after antiepileptic drug administration. No radiation-induced neurological deficits or delayed complications were reported during the follow-up period. CONCLUSIONS Hypofractionated SRS was an effective and safe modality for treating giant CSH. Considering the risks involved with microsurgery, it is possible that H-SRS might be able to serve as a definitive primary treatment option for giant CSH.

Enhanced Neuroprotective Effects of Coadministration of Tetrandrine with Glutathione in Preclinical Model of Parkinson's Disease.

Aim. In this study we examined the influence of tetrandrine (Tet) on the neuroprotective effects of glutathione (GSH) in the 6-hydroxydopamine- (6-OHDA-) lesioned rat model of Parkinson's disease (PD). Methods. Levels in the redox system, dopamine (DA) metabolism, dopaminergic neuronal survival, and apoptosis of the substantia nigra (SN) and striatum, as well as the rotational behavior of animals were examined after a 50-day administration of GSH + Tet (or GSH) and/or L-3,4-dihydroxyphenylalanine (L-dopa) to PD rats. Ethics Committee of Huashan Hospital, Fudan University approved the protocol (number SYXK2009-0082). Results. Administration of GSH or Tet alone did not show any significant effects on the factors evaluated in the PD rats. However, in the GSH + Tet group, we observed markedly decreased oxidative damage, inhibition of DA metabolism and enhanced DA synthesis, increased tyrosine hydroxylase- (TH-) immunopositive neuronal survival, and delayed apoptosis of dopaminergic neurons in the SN. Animal rotational behavior was improved in the GSH + Tet group. Additionally, coadministration of GSH + Tet appeared to offset the possible oxidative neurotoxicity induced by L-dopa. Conclusion. In this study, we demonstrated that tetrandrine allowed occurrence of the neuroprotective effect of glutathione probably due to inhibition of P-glycoprotein on 6-hydroxydopamine-lesioned rat models of Parkinson's disease, including rats undergoing long-term L-dopa treatment.

A new strategy of CyberKnife treatment system based radiosurgery followed by early use of adjuvant bevacizumab treatment for brain metastasis with extensive cerebral edema.

Bevacizumab blocks the effects of vascular endothelial growth factor in leakage-prone capillaries and has been suggested as a new treatment for cerebral radiation edema and necrosis. CyberKnife is a new, frameless stereotactic radiosurgery system. This work investigated the safety and efficacy of CyberKnife followed by early bevacizumab treatment for brain metastasis with extensive cerebral edema. The eligibility criteria of the patients selected for radiosurgery followed by early use of adjuvant bevacizumab treatment were: (1) brain tumors from metastasis with one solitary brain lesion and symptomatic extensive cerebral edema; (2) >18 years of age; (3) the patient refused surgery due to the physical conditions and the risk of surgery; (4) no contraindications for bevacizumab. (5) bevacizumab was applied for a minimum of 2 injections and a maximum of 6 injections with a 2-week interval between treatments, beginning within 2 weeks of the CyberKnife therapy; (6) Karnofsky performance status (KPS) ≥30. Tumor size and edema were monitored by magnetic resonance imaging (MRI). Dexamethasone dosage, KPS, adverse event occurrence and associated clinical outcomes were also recorded. Eight patients were accrued for this new treatment. Radiation dose ranged from 20 to 33 Gy in one to five sessions, prescribed to the 61-71 % isodose line. Bevacizumab therapy was administered 3-10 days after completion of CyberKnife treatment for a minimum of two cycles (5 mg/kg, at 2-week intervals). MRI revealed average reductions of 55.8 % (post-gadolinium) and 63.4 % (T2/FLAIR). Seven patients showed significant clinical neurological improvements. Dexamethasone was reduced in all patients, with five successfully discontinuing dexamethasone treatment 4 weeks after bevacizumab initiation. Hypertension, a bevacizumab-related adverse event, occurred in one patient. After 3-8 months, all patients studied were alive and primary brain metastases were under control, 2 developed new brain metastases and underwent salvage CyberKnife treatment. Recurrent edema and emerging radiation necrosis were not observed. CyberKnife radiosurgery followed by early use of bevacizumab is promising and appears safe for treatment of brain metastases with extensive cerebral edema.

[Cyberknife radiosurgery for cerebral arteriovenous malformations: outlining of the radiosurgical target and obliteration].

OBJECTIVE: To explore the therapeutic outcomes of cyberknife for patients with arteriovenous malformations (AVM) and outline the content of AVM targets. METHODS: Between January 2008 and October 2011, 51 patients underwent cyberknife radiosurgery for cerebral AVMs. The mean age was 27 (8-47) years. The procedures included prior embolization (n = 24), gamma knife before cyberknife (n = 2) and cyberknife initially (n = 25). The delineation of AVM targets was as follows: AVM with prior embolization, radiosurgical targets included AVM nidus, embolization areas and some small draining veins. However, low radiation dose was delivered to embolization parts and draining veins. For 25 patients without embolization, the radiosurgical target was AVM nidus. The mean target volume was 7.8 (1.2-22.0) cm³ and 15 of them were larger than 10.0 cm³. In patients harboring AVM with target volumes < 4 cm³, cyberknife radiation was delivered in a single session. And the remainder had 2 (n = 25) or 3 (n = 19) sessions. The mean marginal dose was 23(18-28) Gy. RESULTS: AVM obliteration was confirmed by magnetic resonance imaging (MRI) or angiography in 40 (78%) patients during a mean follow-up of 46 (36-70) months. Marked size reduction of AVM was obtained in 11 incompletely obliterated patients. Among them, there were second cyberknife treatment (n = 3), third embolization for complex AVM (n = 1), gamma knife (n = 1) and further follow-ups (n = 6). The higher obliteration rate of AVM was correlated with small volume of AVM in noncritical areas, prior embolization and radiation target of embolization areas. Three patients had hemorrhage during the follow-up period and recovered. Brain edema was found in patients with basal ganglion or parietal AVMs. A permanent neurological deficit (paralysis) due to adverse radiation effects developed in 1 patient. CONCLUSION: Cyberknife radiosurgery is particularly effective for patients with smaller AVMs in noncritical areas of brain. In patients with prior embolization, delineation of AVM targets including embolization areas is essential for a higher rate of obliteration.

Intracranial papillary meningioma: a clinicopathologic study of 30 cases at a single institution.

BACKGROUND: Papillary meningioma (PM) is an uncommon meningioma subtype, and the clinical characteristics remain unclear. OBJECTIVE: To determine the clinical characteristics and prognosis of PM. METHODS: The clinical data of 30 PM patients were collected, the samples were reexamined, and the patients' prognoses were based on clinical observations and calculated according to the Kaplan-Meier method. RESULTS: The 30 patients included 16 males and 14 females (median: 34.0 years upon initial diagnosis). Of the 48 intracranial operations in the 30 patients, total removal was attained in 34 surgeries, and subtotal removal in 14 surgeries. Radiotherapy was provided in 20 patients. In 40 specimens with follow-up, 29 attained the positive aggressive factors. Six tumors showed positive progestogen receptor (PR) combined with negative Bcl-2. The median follow-up period was 39.0 months. Tumor recurrence occurred in 18 patients (median: 17.0 months); the recurrence rates following total removal and subtotal removal were 57.1% and 100%, respectively. Fourteen patients died of the recurrence. In the univariate analyses, positive aggressive factors (P = .021), positive PR combined with negative Bcl-2 immunoreactivity (P = .011), the extent of resection (P = .001), and radiotherapy (P = .002) were significantly related to progression-free survival. The MIB-1 labeling index was not significantly related to progression-free survival (P = .88). CONCLUSION: PM is a rare subtype of meningioma with a tendency of recurrence. The extent of resection is an important prognosis factor. The presence of positive histopathological index increases the recurrence risk. Positive PR combined with negative Bcl-2 immunoreaction might predict a good prognosis. Postoperative radiotherapy may play a vital role in prolonging the time to tumor recurrence.

Clinical features and treatment of intracranial chordoid meningioma: a report of 30 cases.

AIMS: To discuss the clinical characteristics and prognosis of chordoid meningioma (CM). METHODS AND RESULTS: Tumour samples of CM from 30 patients were re-examined. The postoperative outcomes were analyzed on the basis of clinical observations. The survival probabilities were calculated using the Kaplan-Meier method. Thirty-two operations were performed in 30 cases, including 27 operations for total removal and five operations for subtotal removal. The median follow-up period was 34.0 months. Tumour recurred in five patients, with a median recurrence time of 32.0 months. No systemic manifestations of Castleman's syndrome were found. The majority (80%) of tumours were found in the supratentorial compartments. The MIB-1 labelling index (MIB-1 LI) varied from 1% to 10%. In univariate analyses, the presence of aggressive factors (P = 0.001) and the extent of resection (P = 0.037) were related to progression-free survival (PFS). The MIB-1 LI (P = 0.50) and postoperative radiotherapy (P = 0.62) were not related to PFS. CONCLUSIONS: Chordoid meningioma is a rare subtype of meningioma, and is often found supratentorially. There is an absence of association with Castleman's syndrome. Aggressive factors and the extent of resection are helpful in predicting recurrence. It might be more pertinent to downgrade CM to grade I, unless it shows aggressive factors.

Phase II study to assess the efficacy of hypofractionated stereotactic radiotherapy in patients with large cavernous sinus hemangiomas.

PURPOSE: Cavernous sinus hemangioma is a rare vascular tumor. The direct microsurgical approach usually results in massive hemorrhage. Although radiosurgery plays an important role in managing cavernous sinus hemangiomas as a treatment alternative to microsurgery, the potential for increased toxicity with single-session treatment of large tumors is a concern. The purpose of this study was to assess the efficacy of hypofractionated stereotactic radiotherapy in patients with large cavernous sinus hemangiomas. METHODS: Fourteen patients with large (volume >20 cm(3)) cavernous sinus hemangiomas were enrolled in a prospective Phase II study between December 2007 and December 2010. The hypofractionated stereotactic radiotherapy dose was 21 Gy delivered in 3 fractions. RESULTS: After a mean follow-up of 15 months (range, 6-36 months), the magnetic resonance images showed a mean of 77% tumor volume reduction (range, 44-99%). Among the 6 patients with cranial nerve impairments before hypofractionated stereotactic radiotherapy, 1 achieved symptomatic complete resolution and 5 had improvement. No radiotherapy-related complications were observed during follow-up. CONCLUSION: Our current experience, though preliminary, substantiates the role of hypofractionated stereotactic radiotherapy for large cavernous sinus hemangiomas. Although a longer and more extensive follow-up is needed, hypofractionated stereotactic radiotherapy of 21 Gy delivered in 3 fractions is effective in reducing the tumor volume without causing any new deficits and can be considered as a treatment modality for large cavernous sinus hemangiomas.

The role of stereotactic radiosurgery in cavernous sinus hemangiomas: a systematic review and meta-analysis.

Cavernous sinus hemangioma is a rare and complex vascular tumor. A direct microsurgical approach usually results in massive hemorrhage. Stereotactic radiosurgery has emerged as a treatment alternative to microsurgery. To conduct a meta-analysis assessing the effect and complications of stereotactic radiosurgery in cavernous sinus hemangioma, a systematic review and meta-analysis of all cases of cavernous hemangioma in the cavernous sinus treated with stereotactic radiosurgery was performed. The search revealed ten papers with a total enrollment of 59 patients. Tumor size ranged from 1.5-51.4 cm(3) (mean 9.6 cm(3)). The mean follow-up period was 49.2 months (range 6-156 months). The most recent MR images demonstrated remarkable tumor shrinkage in 40 patients (67.8%), partial shrinkage in 15 patients (25.4%), and no change in four patients (6.8%). There was no significant correlation between lesion volume and tumor shrinkage. Patients with remarkable tumor shrinkage received higher doses than those with partial or no change tumor shrinkage (P = 0.031). Thirteen patients (22.0%) had no cranial nerve impairments before stereotactic radiosurgery. Among those 46 patients with cranial nerve impairments before stereotactic radiosurgery, complete resolution was achieved in seven patients and improvement in 28, and these impairments remained essentially unchanged in 11 patients. Only one patient had additional trigeminal nerve disturbance. There is no statistical significance in tumor control between patients treated with or without surgery (P = 0.091). The meta-analysis suggests stereotactic radiosurgery avoids the complications associated with attempted microsurgical resection. Stereotactic radiosurgery is an alternative for cavernous sinus hemangiomas confirmed by typical imaging.

[Radiosurgery for cavernous sinus hemangiomas: medium- and long-term results].

OBJECTIVE: To describe the personal experiences of treating cavernous sinus hemangiomas (CSH) with gamma knife or cyberknife and evaluate the medium and long-term outcomes. METHODS: From June 1999 to December 2008, 20 CSH patients were treated by radiosurgery (gamma knife or cyberknife). Among them, 11 had residual tumor after surgery and 9 were diagnosed by neuroradiology. All cases on magnetic resonance imaging (MRI) showed well-defined and homogeneous hyperintensity on T2-weighted images. The mean maximum diameter of tumors was 38.7 ± 9.3 mm (range: 23.0 - 60.6). The volume of tumors ranged between 4.1 - 52.6 cm(3) with a mean of (18.7 ± 12.5) cm(3). The tumor margin dose irradiated by gamma knife ranged from 9 to 16 Gy (mean 12.3 ± 2.3 Gy). The tumor margin dose irradiated by cyberknife was 20 - 21 Gy in 3 fractions. The mean follow-up period was (60 ± 32) months (range: 12 - 120). RESULTS: Follow-up imaging showed tumor volume decreased over 90% (n = 5), tumor regressed over 50% in volume (n = 9) and no change in tumor volume (n = 1). One patient with large tumor (irradiated 10 Gy) was operated by open surgery at 5 months after gamma knife. Four giant tumors decreased over 50% in volume after cyberknife. Neurologically, none of these patients showed any deterioration. And 16 patients demonstrated an obvious improvement after radiosurgery. At the last follow-up, there were no complications related to radiosurgery. CONCLUSION: Radiosurgery (Gamma knife or cyberknife) is a safe and effective modality for small- and medium-sized CSH. Fractionated Cyberknife proves to be an effective treatment for large or giant CSH. Thus radiosurgery will be an alternative option to surgery.

Effect of profound hypothermia on genomics of hippocampus following complete cerebral ischemia in rats.

OBJECTIVE: To determine differential gene expression of hippocampus in rats following complete cerebral ischemia with treatment of profound hypothermia compared to normothermia. METHODS: Six rats got 5 minutes of complete cerebral ischemia with circulatory arrest and randomly divided into two groups: normothermia ischemia group (37 +/- 0.3 degrees C, n = 3) and profound hypothermia ischemia group (18 +/- 0.5 degrees C, n = 3). Affymetrix U34A rat arrays were applied to detect the difference of gene expression profile in hippocampus between the two groups. RESULTS: Expression profiles of a total of 75 transcripts in the profound hypothermia ischemia group were statistically different from those of the normothermia ischemia group, and 33 of them were significantly up-regulated and other 42 were significantly down-regulated (p < 0.07). CONCLUSIONS: Compared with normothermia, profound hypothermia had a significant effect on the gene expression profiles following complete cerebral ischemia, which may be involved in the mechanisms of cerebral protection by profound hypothermia.