We tested whether modulation of the CNS-tumor microenvironment by delivery of IFN-α-transduced dendritic cells (DCs: DC-IFN-α) would enhance the therapeutic efficacy of peripheral vaccinations with cytokine-gene transduced tumor cells. Mice bearing intracranial GL261 glioma or MCA205 sarcoma received peripheral immunizations with corresponding irradiated tumor cells engineered to express IL-4 or GM-CSFs, respectively, as well as intratumoral delivery of DC-IFN-α. This regimen prolonged survival of the animals and induced tumor-specific CTLs that expressed TRAIL, which in concert with perforin and Fas ligand (FasL) was involved in the tumor-specific CTL activity of these cells. The in vivo antitumor activity associated with this approach was abrogated by administration of neutralizing mAbs against TRAIL or FasL and was not observed in perforin−/−, IFN-γ−/−, or FasL−/− mice. Transduction of the tumor cells with antiapoptotic protein cellular FLIP rendered the gene-modified cells resistant to TRAIL- or FasL-mediated apoptosis and to CTL killing activity in vitro. Furthermore, the combination therapeutic regimen was ineffective in an intracranial cellular FLIP-transduced MCA205 brain tumor model. These results suggest that the combination of intratumoral delivery of DC-IFN-α and peripheral immunization with cytokine-gene transduced tumor cells may be an effective therapy for brain tumors that are sensitive to apoptotic signaling pathways.

ABSTRACT

Chordoid glioma of the third ventricle is considered to be a benign glial tumor located exclusively in the mid-anterior portion of the third ventricle near the hypothalamus and optic nerves, with the histological features of a chordoma and immuno-labeling for glial fibrillary acidic protein. Unfortunately, the clinical outcome of chordoid glioma has been poor, even in patients receiving gross total or partial removal with or without radiotherapy. Three cases of chordoid glioma of the third ventricle were treated with less invasive microsurgery for pathological diagnosis or partial removal without neuro-endocrinological complication, followed by gamma knife radiosurgery using a lower marginal dose for the optic nerves and hypothalamus. Gamma knife radiosurgery was performed after open biopsy in two patients, and after partial removal in the third patient using a lower marginal dose of 10.5 to 12 Gy. Serial magnetic resonance imaging revealed gradual decrease or at least no change in the tumor size, without significant complication at follow up 70 and 66 months later in two cases. The third patient accidentally died 13 months after gamma knife treatment. We conclude that low dose gamma knife radiosurgery after less invasive microsurgery is both safe and effective for the control of chordoid glioma of the third ventricle over a very long follow-up period.

The latest version of Leksell GammaPlan (LGP) is equipped with Digital Imaging and Communication in Medicine (DICOM) image-processing functions including image co-registration. Diagnostic magnetic resonance imaging (MRI) taken prior to Gamma Knife treatment is available for virtual treatment pre-planning. On the treatment day, actual dose planning is completed on stereotactic MRI or computed tomography (CT) (with a frame) after co-registration with the diagnostic MRI and in association with the virtual dose distributions. This study assesses the accuracy of image co-registration in a phantom study and evaluates its usefulness in clinical cases. Images of three kinds of phantoms and 11 patients are evaluated. In the phantom study, co-registration errors of the 3D coordinates were measured in overall stereotactic space and compared between stereotactic CT and diagnostic CT, stereotactic MRI and diagnostic MRI, stereotactic CT and diagnostic MRI, and stereotactic MRI and diagnostic MRI co-registered with stereotactic CT. In the clinical study, target contours were compared between stereotactic MRI and diagnostic MRI co-registered with stereotactic CT. The mean errors of coordinates between images were < 1 mm in all measurement areas in both the phantom and clinical patient studies. The co-registration function implemented in LGP has sufficient geometrical accuracy to assure appropriate dose planning in clinical use.

Intracranial arteriovenous malformation (AVM) is a rare cause of trigeminal neuralgia (TGN). In this presented case, successful resolution of AVM-related TGN following embolization and gamma knife radiosurgery (GKRS) was obtained. A patient suffered from TGN on the left side, which was thought to be caused by root entry zone compression by dilated superior cerebellar artery (SCA) associated with cerebellar AVM. The cerebellar vermis AVM was embolized in endovascular surgery. The AVM was reduced in size and TGN was partially relieved. The patient subsequently underwent GKRS for the residual nidus. TGN was completely resolved within one year and a half. GKRS following embolization of the nidus improved the flow-related dilation of the SCA and completely relieved TGN.