Safety evaluation of high-dose BCNU-loaded biodegradable implants in Chinese patients with recurrent malignant gliomas.

OBJECTIVES: Malignant gliomas are common primary brain tumors with dismal prognosis. The blood-brain barrier and unacceptable systemic toxicity limit the employment of chemotherapeutic agents. BCNU-impregnated biodegradable polymers (Gliadel®) have been demonstrated to prolong the survival of patients with malignant gliomas. Until now, no biodegradable drug delivery system has been commercially available in China. In the present study, we evaluated the safety of implants with high-dose BCNU in Chinese patients with recurrent malignant gliomas. PATIENTS AND METHODS: Adults with supratentorial recurrent malignant glioma were eligible. High-dose BCNU-loaded PLGA implants (20mg of BCNU in each implant) were placed in the debulking cavity. The implants were investigated by a classical 3+3 design. Four levels of BCNU, up to 12 implants, were evaluated. Pharmacokinetic sampling was performed. The toxicity of the implants and the survival of patients were recorded. RESULTS: Fifteen recurrent patients were enrolled with 12 glioblastomas and 3 anaplastic gliomas. Among 15 patients, 3 were treated with 3 implants (60 mg of BCNU), 3 with 6 implants (120 mg), 3 with 9 implants (180 mg) and 6 with 12 implants (240 mg). No dose-limiting toxicity was observed in the cohort of patients. Subgaleal effusion was the most common adverse event, presenting in 7 patients (46.7%). The median overall survival (OS) was 322 days (95% CI, 173-471 days). The 6-month, 1-year and 2-year survival rates were 66.7%, 40% and 13.3%, respectively. CONCLUSIONS: The high-dose BCNU-loaded PLGA implants were safe for Chinese patients with recurrent malignant gliomas and further investigation for efficacy is warranted.

[Application of diffusion tensor imaging in preoperation and postoperation patients of glioma with 3.0 Tesla MRI].

OBJECTIVE: To investigate the clinical usefulness of diffusion tensor imaging (DTI) in demonstrating between gliomas and surrounding fibers. METHODS: 24 patients of glioma (WHO grade: grade I - II 16 cases; grade III - IV 8 cases) were examined using DTI and conventional contrast-enhanced MRI of 3.0 T MRI scanner (GE company, America). After the initial data acquisition introduced into workstation, image analysis was performed with the use of functool software. Mean diffusivity (MD) and fractional anisotropy (FA) values were measured in regions of solid tumor, surrounding edema and normal white matter of the high grade cerebral gliomas. Differences in these values among the tissues were assessed on the high grade cerebral gliomas. Anatomic relationship between intracranial tumors and surrounding fibers was analysed on fractional anisotropic (FA) map, color-coded directional map, three-dimensional white matter tractography. All patients' symptoms were evaluated preoperative and postoperative respectively. RESULTS: The DTI patterns altered by the tumor were categorized as follows: displacement, infiltration and destruction. The tractography showed that the main influence in 16 cases of grade I - II glioma on adjacent white matter tracts was displacement, but infiltration and destruction were also revealed. The patients have definite improvement in symptoms. The destruction and infiltration of fiber tracts could be seen in all edema regions around grade III - IV gliomas in 8 cases. The patients have not definite improvement in symptoms. Apparently significant differences of MD were found in solid tumor, surrounding edema, compared with normal white matter regions (P < 0.05). But there was no significant difference among solid tumor and surrounding edema region (P > 0.05). There were significant differences of FA between solid tumor, surrounding edema and normal white matter region (P < 0.05). CONCLUSIONS: The DTI offered the optimal visualization of white matter tracts. DTI plays an important role in demonstrating relationship between gliomas and neighboring fibers. MD and FA values could be used to distinguish normal white matter from solid tumor and surrounding edema region of high grade glioma. The application of DTI in preoperation plays an guidance role in making microsurgery plans and the evaluation of brain functional recovery in postoperation. DTI should be of great value in the microsurgical planning as well as estimation and reduction of potential postoperative neurological deficits for the cerebral gliomas resection.