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Active Therapies for CNS Tumors

Adult CNS Tumors | Pediatric Brain, Spine, and Peripheral Neuroblast Tumors

Therapy for primary and metastatic tumors of the brain, spine, and of peripheral nerves is determined on an individual basis by informed agreement of patient, family, and the members of the Brain Tumor Center. The following treatment protocols are examples of those currently enrolling patients (except where noted) at the MGH. State of the art therapies are also available for tumors of other histologies. These examples are listed by tumor type as follows:

Glioblastoma-Malignant Glioma-Anaplastic Astrocytoma
Oligodendroglioma and Mixed Oligo-Astrocytoma --Benign and malignant
Benign Astrocytoma :--The low grade glioma
Primitive Neuroectodermal Tumors -- Pineoblastoma, medulloblastoma, ependymoblastoma
Meningiomas: Patients with meningiomas are cared for by members of the neurosurgical attending staff. For more information see the MGH Meningioma Homepage .
Other benign brain and spine tumors such as epidermoid, dermoid, hemangioblastoma, colloid cyst, subependymal giant cell astrocytoma, pleomorphic xanthoastrocytoma, and craniopharyngioma.
Acoustic neuromas (trigeminal schwannoma): more information about these tumors and other cranial base lesions can be found at the MGH Cranial Base Center Homepage .
Craniopharyngioma
Subependymal Giant Cell Astrocytoma
Metastatic Cancer to the Brain--All histologies (solitary or multiple)
Metastatic Cancer of the Spinal Fluid--Meningeal cancer-- Carcinomatous meningitis
Primary Lymphoma of the Nervous System
Paraneoplastic Neurologic Syndromes
Complications of Cancer (Pain, radiation necrosis, leukoencephalopathy, neuropathy, myelopathy)
Primary Lymphoma of the Nervous System
High dose methotrexate therapy in the absence of irradiation. Currently more than 25 patients are on-study with 85% complete responses. This approach limits the need for drug administration into the spinal fluid and reduces potential morbidity of radiation therapy. Methotrexate alone provides tumor control within the brain, spinal fluid and covert systemic sites. Drug administration is well tolerated. This single agent approach is under consideration for an NCI study administered through the NABTT brain tumor consortium.
High dose methotrexate induction of response followed by radiation therapy. Thirty five patients have been treated with median duration of response now in excess of 38 months.
Oligodendroglioma and Mixed Oligo-Astrocytoma-benign and malignant
Chemotherapy with PCV (Procarbazine-CCNU-Vincristine) for newly diagnosed and recurrent tumors prior to irradiation therapy. Fifty patients have experienced a 70% partial response rate. Tumors containing as little as 5% oligo component respond to therapy. PCV is well tolerated with minimal risk of immunosuppression. The approach is applicable to oligodendroglioma of both benign and anaplastic histologies in addition to oligo-astrocytomas of benign and malignant histology. This approach also provides the basis for surgical decompression of tumor or definitive radiation therapy to smaller tumor volumes.
Patient with large anaplastic oligodendroglioma or oligo-astrocytoma are provided intensive PCV with peripheral stem cell support.
Benign Astrocytoma:-the low grade glioma
As 40% of "low grade gliomas" harbor malignant foci, we provide diagnosis of growth and identification of malignant degeneration within benign gliomas using echo-planar (Fast) MRI and 18-Fluoro deoxyglucose Positron Emission Tomography (PET). The former provides identification of areas of excessive blood volume - a sign of malignant change. On PET studies these areas of fast growth are visualized as regions of glucose utilization. Over 100 benign astrocytomas tumors have been imaged for the identification of malignant change within benign glioma or necrosis within more malignant tumor.
Low grade gliomas of oligodendroglial origin are provided PCV therapy with attention paid to changes in the above imaging modalities.
Glioblastoma-Malignant Glioma-Anaplastic Astrocytoma
Newly Diagnosed
The Brain Tumor center provides four neurologic surgeons (Drs. Ojemann, Harsh, Chiocca, Barker) whose sole commitment is to tumors of the nervous system. Localization of CT and MRI-based stereotactic biopsy depends on careful evaluation of MRI, echo-planar MRI and PET scans. Decisions regarding the utility of tumor resection reflect the tumor histology and its appearance on scans within the context of preservation of patient functions.
Newly diagnosed anaplastic oligodendroglioma or anaplastic oligo-astrocytoma or glioblastoma of oligo-astrocytoma histology are provided pre-irraidation therapy using PCV.
Tumors that can be completely resected may be provided subsequent proton beam radiosurgery
Adjuvant post-radiation therapy with TNP-770 (NABTT).
Recurrent Therapy
The Brain Tumor Center maintains a commitment to the surgical confirmation of presumed recurrent glioblastoma. As radiation necrosis may be confused with viable tumor we make use of non-invasive echo-planar MRI studies and deoxyglucose-PET scans prior to histologic confirmation of recurrent glioblastoma. Surgical resection is provided when feasible following which is given:
PCV therapy of recurrent oligo-astrocytoma tumors (Massachusetts General Hospital)
Suramin therapy of recurrent tumors (NABTT)
CI-980 therapy of irradiated glioblastoma (NABTT)
Dose - escalation BCNU (to 20% concentrations)(Gliadel) wafer therapy (NABTT)
Proton beam (single dose) therapy of recurrences.
Gene Therapy - is supported by an NCI Program-project grant to the Massachusetts General Hospital (Dr. Hochberg) and by corporate interactions through NABTT.
HSV-TK with ganciclovir therapy of recurrent glioblastoma (with Drs.   Chiocca, Hochberg , Breakefield )
Retroviral cytochrome P-450 - Cytoxan therapy of recurrent glioblastoma (Dr. Chiocca). Likely open for accrual Sept. 1997.
Herpes viral therapy of recurrent glioblastoma (Accrual 1998)(Drs. Chiocca, Harsh, Barker, Hochberg)
Adeno p-53 therapy (Onyx) of recurrent glioblastoma (Dr. Chiocca and Dr. Barker-NABTT).
Primitive Neuroectodermal Tumors - Pineoblastoma, medulloblastoma, ependymoblastoma-adults (over 16 years)

Primary surgical diagnosis is achieved by stereotactic biopsy or surgical operation. Following this, and appropriate examination of bones, cerebrospinal fluid and hormonal status, we provide:

Therapy prior to radiation using VP-16/Cisplatin then Cytoxan/Vincristine.
Craniospinal irradiation.

Protocol and non-protocol therapy for patients under the age of 16-18 with PNETs is described below .

Craniopharyngioma

Treatments available for both pediatric and adult craniopharyngiomas include complete surgical resection (first advocated and performed by Dr. William H. Sweet ), intracyst radiation therapy (with Phosphorus-32), stereotactic radiosurgery, and cerebrospinal fluid shunting procedures.

Treatment for pediatric craniopharyngioma is coordinated through Dr. Dooling's office .
Treatment for adult patients is coordinated through the Neurosurgical Oncology offices.
Subependymal Giant Cell Astrocytoma

Subependymal giant cell astrocytoma can often be successfully cured by a single operation. Members of the Neurosurgical Oncology service have special expertise in treating this rare "benign" brain tumor.

Metastatic Cancer to the Brain-all histologies (solitary or multiple)
Interstitial Photon-radiosurgical (PRS) therapy. Dr. Cosgrove coordinates the localized therapy of these lesions at the time of diagnostic biopsy.
Proton beam (single dose) radiosurgeryof metastases.
"STAR" proton beam radiosurgery of newly diagnosed or recurrent metastases.
For evaluation and treatment of metastatic tumors to the spine or peripheral nerves see the Neurosurgical Oncology section.
Metastatic Cancer of the Spinal Fluid-Meningeal cancer.

Tumors infiltrating the spinal fluid, the coverings of the brain, the ventricles or the nerves roots are diagnosed by careful examination of the appropriate fluid. This examination is achieved by utilization of specific immunohistochemical markers as well as the facilities for Fluorescence-Activated Cell Sorting (FACS) analysis. Following diagnosis we provide:

Intra-thecal administration of methotrexate, cytosine arabinoside, Depotek Ara-C (Dr. Batchelor) through either lumbar or ventricular administration sites, often with the aid of contiguous spinal fluid (Ommaya) reservoirs.
Craniospinal irradiation.
High dose intravenous chemotherapy.
Paraneoplastic Neurologic Syndromes

Remote effects of cancer on the brain- including Cerebellar degeneration, optic neuropathy, brain stem encephalitis, opsoclonus-myoclonus, limbic encephalitis and Eaton-Lambert muscular weakness afflict patients with tumors of the breast, ovary, lung or lymphoma. In general the processes with inflammed tissue (limbic encephalitis, brainstem encephalitis) respond to steroid medications or immune globulin infusions while those of physiologic origins (Lambert Eaton, stiff man, opsoclonus-myoclonus) respond to pheresis or specific physiologic medications (DAP). Thus we provide treatments using:

Appropriate techniques to control the underlying tumor with surgery, irradiation or chemotherapy.
The provision of glucocorticoid medications, intravenous immunoglobulin or plasmapheresis.
Complications of Cancer (Pain, radiation necrosis, leukoencephalopathy, neuropathy, myelopathy)
Localized injection approaches for the control of pain.
Utilization of Echo-planar MRI and PET scanning for the diagnosis of recurrent tumor versus necrosis.
Heparin-fragment therapy of radiation necrosis.

Proton Beam Radiosurgery Homepage at Massachusetts General Hospital

Pediatric Brain, Spine, and Peripheral Neuroblast Tumors

Pediatric brain tumors are treated by a multidisciplinary group including pediatric oncologists, pediatric neurologists, radiation oncologists, and pediatric neurosurgeons . See the MGH Pediatric Neurosurgery Homepage for a listing of MGH neurosurgeons with special expertise in the treatment of pediatric brain tumors. Proton beam stereotactic radiosurgery is also available for the treatment of pediatric brain, and spine tumors.

Appointments may be coordinated through the MGH Pediatric Neurology Service:
Elizabeth Dooling, M.D.
Director, Pediatric Neurology
Vincent-Burnham Kennedy-7
Massachusetts General Hospital
Boston, MA 02114
phone: (617) 726-3877

Experimental treatment protocols including chemotherapy are coordinated through the pediatric oncology service. For more information or to make an appointment contact:

David Ebb, M.D.
Director, Pediatric Oncology
Blake-2
Massachusetts General Hospital
Boston, MA 02114
phone: (617) 726-2737

Protocols therapy is currently available for the following tumor types. Data collection for the majority of these protocols is coordinated by the pediatric oncology group. Non-protocol therapies are available for tumors of any type.

Special protocols are also available for children under 3 years of age with tumors of various histologies.

Low-grade astrocytoma
primary: POG Intergroup protocol
recurrent: idarubicin-based therapy and topotecan -based therapy)
Optic pathway tumors
Ependymomas
Brain stem gliomas
topotecan -based therapy
taxol-based therapy
Craniopharyngioma (see above )
Treatment for pediatric craniopharyngioma is coordinated through Dr. Dooling's office .
Treatment for adult patients is generally coordinated through one of the Neurosurgical Oncology offices.
Supratentorial neoplasms (1. malignant gliomas: anaplastic astrocytoma, glioblastoma multiforme, malignant gliosarcoma, and malignant oligodendrogiomas; malignant small cell neoplasms with glial differentiation are also eligible. 2. Poorly-differentiated embryonal cell tumors (PDETs): undifferentiatied malignant small cell neoplasm, as well as those with pineal (pineoblastomas), ependymal (ependymoblastomas), or neuronal (primary cerebral neuroblastoma) differentiation, including cases diagosed as PNET.)
Topotectan-based therapy
Medulloblastoma (infratentorial PNET)
POG low stage protocol
POG high stage protocol
recurrent: taxol
subquent recurrence: POG salvage protocol
Advancing the Specialized Care of Individuals with Brain Tumors
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APPOINTMENTS & REFERRALS

MGH Brain Tumor Center
Yawkey Building 9th Floor
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Patients & Families with questions about referrals, consultations or appointments may contact:
Telephone: 617.724.8770
Fax: 617.724.8769

PHYSICIANS' INFO SERVICE

Physicians with
questions may contact:
Tracy Batchelor, M.D.
Executive Director,
MGH Brain Tumor Center
 
Harvard Medical School
Mass General Hospital
MassGeneral.org
MGH Cancer Center
NS @ MGHNS Diagnosis @ MGH
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