Table of Contents
General Information
Cellular Classification
Stage Information
Noninfiltrating astrocytomas
Well-differentiated mildly and moderately anaplastic astrocytomas
Anaplastic astrocytomas
Glioblastoma multiforme
Well-differentiated ependymomas
Anaplastic ependymomas
Ependymoblastomas
Well-differentiated oligodendrogliomas
Anaplastic oligodendrogliomas
Meningiomas
Malignant meningiomas
Treatment Option Overview
Adult Noninfiltrating Astrocytoma
Juvenile pilocytic and subependymal astrocytomas 1
Adult Well-Differentiated Mildly and Moderately Anaplastic Astrocytoma
Adult Anaplastic Astrocytoma
Adult Glioblastoma Multiforme
Adult Brain Stem Glioma
Adult Well-Differentiated Ependymoma
Myxopapillary ependymoma and well-differentiated ependymoma
Adult Malignant Ependymoma
Anaplastic ependymoma and ependymoblastoma
Adult Well-Differentiated Oligodendroglioma
Adult Anaplastic Oligodendroglioma
Mixed Gliomas
Mixed astrocytoma-ependymoma, mixed astrocytoma-oligodendroglioma, and mixed astrocytoma-ependymoma-oligodendroglioma
Adult Medulloblastoma
Adult Pineal Parenchymal Tumor
Pineocytoma and pineoblastoma
Pineal astrocytoma
Adult Central Nervous System Germ Cell Tumor
Germinoma, embryonal carcinoma, choriocarcinoma, and teratoma
Adult Craniopharyngioma
Adult Meningioma
Adult Malignant Meningioma
Malignant meningioma, hemangiopericytoma, and papillary meningioma
Recurrent Adult Brain Tumor
General Information
Prognoses of primary brain tumors are determined by histologic type, grade, postoperative size, and extent of the tumor and by the patient's age, the performance status, and the duration of symptoms.1,2 Some primary brain tumors are curable by surgery alone, and some are curable by surgery and radiation therapy; the remainder require surgery, radiation therapy, and chemotherapy. Tumors that require all 3 modalities are infrequently curable.3
Metastases to the brain from a primary tumor that is outside the central nervous system (CNS) are more common than primary tumors of the brain. The most common primary tumors that metastasize to the brain are lung, breast, melanoma, and kidney. Metastases to the brain are usually multiple, but solitary metastases may also occur. Brain involvement can occur with cancers of the nasopharyngeal region by direct extension along the cranial nerves or through the foramina at the base of the skull. Metastatic meningeal involvement can also occur, especially with leukemia, lymphoma, small cell lung cancer, breast cancer, and some primary CNS tumors (such as medulloblastoma and ependymal gliomas).
A lesion in the brain should not be assumed to be a metastasis just because a patient has had a previous cancer; such an assumption could result in overlooking appropriate treatment of a curable tumor. Primary brain tumors rarely spread to other areas of the body, but they can spread to other parts of the brain and to the spinal axis.
References:
1. Levin VA, Leibel SA, Gutin PH: Neoplasms of the central nervous system. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. Philadelphia, Pa: Lippincott-Raven Publishers, 5th ed., 1997, pp 2022-2082.
2. Mahaley MS, Mettlin C, Natarajan N, et al.: National survey of patterns of care for brain-tumor patients. Journal of Neurosurgery 71(6): 826-836, 1989.
3. Surawicz TS, Davis F, Freels S, et al.: Brain tumor survival; results from the National Cancer Data Base. Journal of Neuro-Oncology 40(2): 151-160, 1998.
Cellular Classification
Histological classification for adult brain tumors is as follows:1
Glial tumors:
astrocytic tumors
#noninfiltrating
--juvenile pilocytic subependymal
#infiltrating
--well-differentiated mildly and moderately anaplastic astrocytoma anaplastic astrocytoma glioblastoma multiforme
#ependymal tumors
--myxopapillary and well-differentiated ependymoma anaplastic ependymoma ependymoblastoma
#oligodendroglial tumors
--well-differentiated oligodendroglioma anaplastic oligodendroglioma
#mixed tumors
--mixed astrocytoma-ependymoma mixed astrocytoma-oligodendroglioma mixed astrocytoma-ependymoma-oligodendroglioma
#medulloblastoma
Nonglial tumors:
#pineal parenchymal tumors
--pineocytoma pineoblastoma astrocytoma (see above)
#germ cell tumors
--germinoma embryonal carcinoma choriocarcinoma teratoma
#craniopharyngioma meningiomas
--meningioma malignant meningiomas
----anaplastic meningioma hemangiopericytoma papillary meningioma
#choroid plexus tumors
--choroid plexus papilloma anaplastic choroid plexus papilloma
References:
1. Kleihues P, Burger PC, Scheithauer BW, et al.: Histological typing of tumours of the central nervous system. Berlin: Springer-Verlag, 2nd ed., 1993.
Stage Information
Brain tumors are classified on the basis of tumor cell type and histologic grade. For some tumors, location and metastatic spread within the cerebrospinal fluid are also used in classification.1
Cerebral Astrocytic Gliomas
Gliomas constitute the most common primary central nervous system (CNS) tumors. Of the gliomas, astrocytomas of variable malignancy are the most prevalent. Cerebral astrocytomas are subdivided into categories (grades) based on the degree of tumor anaplasia and the presence or absence of necrosis.
Noninfiltrating astrocytomas
These astrocytomas are relatively slow-growing tumors such as juvenile pilocytic and subependymal astrocytomas, which occur most frequently in children but can occur in adults.
Well-differentiated mildly and moderately anaplastic astrocytomas
These tumors are more infiltrative than the juvenile pilocytic and subependymal astrocytomas but are still relatively slow-growing tumors.
Anaplastic astrocytomas
These tumors are highly anaplastic with obvious vascular abnormalities. This grade III astrocytoma grows more rapidly than the more differentiated astrocytomas.
Glioblastoma multiforme
This grade IV astrocytoma is a poorly differentiated, rapidly growing tumor that occurs most often in adults.
Brain Stem Gliomas
Brain stem gliomas are usually diagnosed on clinical evidence because diagnosis by biopsy might be hazardous. Tumors that diffusely enlarge the brain stem carry a worse prognosis than those that are more focal. Higher grades of malignancy (see above) carry poorer prognoses as well.
Cerebellar Astrocytomas
Although the majority of these tumors are of lower grade and frequently are curable, they vary in grade of malignancy. The higher grade lesions carry a worse prognosis, but prognosis is generally better than for their cerebral counterparts.
Ependymal Tumors
Ependymal tumors are considered to arise from ependymal cells that line the ventricles and from ependymal rests. They vary in grade of malignancy.
Well-differentiated ependymomas
These tumors include myxopapillary ependymoma and well-differentiated ependymoma, and are often curable.
Anaplastic ependymomas
These tumors have more features of anaplasia and appear mitotically more active than the myxopapillary or well-differentiated ependymomas. Although previously considered to do worse than the well-differentiated ependymoma, conflicting evidence suggests that patients treated with surgery and radiation therapy might do nearly as well.
Ependymoblastomas
These are generally tumors of childhood and are considered by some to be primitive neuroectodermal tumors. They are rare.
Oligodendroglial Tumors
Oligodendroglial tumors are gliomas that arise from the oligodendroglia. They vary in grade of malignancy, and prognosis is related to grade.
Well-differentiated oligodendrogliomas
These tumors are usually slow-growing and well circumscribed.
Anaplastic oligodendrogliomas
These tumors are comparable to the highly anaplastic gliomas in prognosis.
Mixed Gliomas
Mixed gliomas can occur with combinations of generally 2, but sometimes 3, different cell types: astrocytoma, ependymoma, and/or oligodendroglioma. Survival statistics are inexact for this group because the cell types and grade of the most malignant-appearing cells influence prognosis. In general, these tumors carry a prognosis that is between the prognoses of well-differentiated and anaplastic astrocytomas.
Medulloblastoma
Medulloblastoma is a rapidly growing tumor arising in the posterior fossa and is found almost exclusively in children and young adults. It has the tendency to spread from the brain to the spinal axis. Prognosis is dependent on the staging following surgical resection.
Pineal Region Tumors
Pineal parenchymal tumors vary in histology and grade of malignancy relative to patient age at occurrence. They can vary from the slow-growing pineocytoma to the more malignant and faster growing pineoblastoma. Astrocytomas can also grow in this location (see above), as can a variety of primary germ cell tumors: germinoma, embryonal carcinoma, choriocarcinoma, and teratoma. These uncommon tumors vary in prognosis. The absence of biopsy specimens in many series make the prognosis for each tumor type difficult to evaluate.
Craniopharyngiomas
Craniopharyngioma is a tumor that arises from the remains of a structure found in the developing embryo in the region of the pituitary gland. This tumor causes symptoms and signs by pressing on vital areas of the brain and the optic nerves; it also causes internal hydrocephalus by obstructing the foramen of Monro in children.
Meningiomas
Meningiomas arise from the meninges surrounding the brain and spinal cord and are generally slow-growing. There are other variants that constitute a group called malignant meningioma and include malignant meningioma, hemangiopericytoma, papillary meningioma, and meningeal sarcoma. Malignant meningiomas are more likely than other meningiomas to metastasize within the craniospinal axis.
Meningiomas
Meningioma is usually curable with surgery if the initial resection is complete. The shape of the tumor is a prognostic factor and should be considered in planning surgery. Incomplete resection associated with lobulated and mushrooming patterns of tumor growth is associated with a higher risk of recurrence.2
Malignant meningiomas
The prognosis for patients with malignant meningioma is worse than for patients with the more well-differentiated meningiomas.
Choroid Plexus Tumors
Choroid plexus tumors are rare tumors arising from choroid plexus epithelial cells. The more benign form is choroid plexus papilloma; the more malignant form is called anaplastic choroid plexus papilloma. These latter tumors are most likely to spread within the craniospinal axis.
References:
1. Levin VA, Leibel SA, Gutin PH: Neoplasms of the central nervous system. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. Philadelphia, Pa: Lippincott-Raven Publishers, 5th ed., 1997, pp 2022-2082.
2. Nakasu S, Nakasu Y, Nakajima M, et al.: Preoperative identification of meningiomas that are highly likely to recur. Journal of Neurosurgery 90(3): 455-462, 1999.
Treatment Option Overview
Surgical removal of brain tumors is recommended for most types and in most locations and should be as complete as possible within the constraints of preservation of neurologic function.1 An exception to this role for surgery is for deep-seated tumors, such as pontine gliomas, which are diagnosed on clinical evidence and are treated without initial surgery approximately 50% of the time. In the majority of cases, however, diagnosis by biopsy is preferred. Stereotaxic biopsy can be used for lesions that are difficult to reach and resect.
Radiation therapy has a major role in the treatment of most tumor types and can increase the cure rate or prolong disease-free survival. Radiation therapy may also be useful in the treatment of recurrences in patients treated initially with surgery alone.
Chemotherapy may prolong survival in some tumor types and has been reported to lengthen disease-free survival in patients with gliomas, medulloblastoma, and some germ cell tumors.2 Local chemotherapy with a nitrosourea applied to a polymer placed directly in the brain during surgery has been shown to be a safe modality and is under clinical evaluation.1,3
Patients who have brain tumors that are either infrequently curable or unresectable should be considered candidates for clinical trials that evaluate radiosensitizers, hyperthermia, or interstitial brachytherapy used in conjunction with external-beam radiation therapy to improve local control of the tumor or for studies that evaluate new drugs and biological response modifiers.
References:
1. Brem H, Piantadosi S, Burger PC, et al.: Placebo-controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas. Lancet 345(8956): 1008-1012, 1995.
2. Cokgor I, Friedman HS, Friedman AH: Chemotherapy for adults with malignant glioma. Cancer Investigation 17(4): 264-272, 1999.
Brem H, Ewend MG, Piantadosi S, et al.: The safety of interstitial chemotherapy with BCNU-loaded polymer followed by radiation therapy in the treatment of newly diagnosed malignant gliomas: phase I trial. Journal of Neuro-Oncology 26(2): 111-123, 1995.
3. Levin VA, Leibel SA, Gutin PH: Neoplasms of the central nervous system. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. Philadelphia, Pa: Lippincott-Raven Publishers, 5th ed., 1997, pp 2022-2082.
Adult Noninfiltrating Astrocytoma
Juvenile pilocytic and subependymal astrocytomas 1
Noninfiltrating astrocytic tumors are often curable.
Treatment options:
Standard:
1. Surgery alone if totally resectable.
2. Surgery followed by radiation therapy to known or suspected residual tumor.2
Under clinical evaluation:
At recurrence following surgery, patients should be considered for reoperation and radiation therapy if not previously given. Patients who have received radiation therapy should be considered candidates for nitrosourea-based chemotherapies and for clinical trials that evaluate new drugs and biological response modifiers.
References:
1. Wallner KE, Gonzales MF, Edwards MS, et al.: Treatment results of juvenile pilocytic astrocytoma. Journal of Neurosurgery 69(2): 171-176, 1988.
2. Shaw EG, Daumas-Duport C, Scheithauer BW, et al.: Radiation therapy in the management of low-grade supratentorial astrocytomas. Journal of Neurosurgery 70(6): 853-861, 1989.
Adult Well-Differentiated Mildly and Moderately Anaplastic Astrocytoma
Well-differentiated mildly and moderately anaplastic astrocytomas are less often curable.
Treatment options:
Standard:
Surgery plus radiation therapy, although some controversy exists and some physicians treat these patients with surgery alone if the patient is younger than 35 years of age and the tumor does not contrast-enhance on a computed tomographic scan.1
Under clinical evaluation:
Clinical trials in progress are evaluating the effect of adding drugs to local therapy, for example, radiation therapy with or without chemotherapy for incompletely resected well-differentiated mildly and moderately anaplastic astrocytomas. Other trials are evaluating the effect of deferring irradiation until the time of tumor progression and of high-dose versus low-dose irradiation.
References:
1. Shaw EG, Daumas-Duport C, Scheithauer BW, et al.: Radiation therapy in the management of low-grade supratentorial astrocytomas. Journal of Neurosurgery 70(6): 853-861, 1989.
Adult Anaplastic Astrocytoma
For anaplastic astrocytomas of higher grade, the cure rate is low with standard local treatment.1 These patients are appropriate candidates for clinical trials designed to improve local control by adding newer forms of treatment to standard treatment.
Treatment options:
Standard:
1. Surgery plus radiation therapy.
2. Surgery plus radiation therapy and chemotherapy.2-6
Under clinical evaluation:
Patients with brain tumors that are either infrequently curable or unresectable should be considered candidates for clinical trials that evaluate hyperfractionated irradiation, accelerated fraction radiation, stereotactic radiosurgery, radiosensitizers, hyperthermia, interstitial brachytherapy, or intraoperative radiation therapy used in conjunction with external-beam radiation therapy to improve local control of the tumor and/or for studies that evaluate new drugs and biological response modifiers following radiation therapy.7-11 Cooperative group trials that evaluate chemoradiotherapy administered with either hyperfractionated irradiation or a combination of brachytherapy and external-beam irradiation are now in progress. Carmustine (BCNU) impregnated polymer may be implanted during surgery.12,13
References:
1. Nelson DF, Nelson JS, Davis DR, et al.: Survival and prognosis of patients with astrocytoma with atypical or anaplastic features. Journal of Neuro-Oncology 3(2): 99-103, 1985.
2. Rodriguez L, Levin V: Does chemotherapy benefit the patient with a central nervous system glioma? Oncology (Huntington NY) 1(9): 29-36, 1987.
3. Chang CH, Horton J, Schoenfeld D, et al.: Comparison of postoperative radiotherapy and combined postoperative radiotherapy and chemotherapy in the multidisciplinary management of malignant gliomas: a joint Radiation Therapy Oncology and Eastern Cooperative Oncology Group Study. Cancer 52(6): 997-1007, 1983.
4. Levin VA, Silver P, Hannigan J, et al.: Superiority of post-radiotherapy adjuvant chemotherapy with CCNU, procarbazine, and vincristine (PCV) over BCNU for anaplastic gliomas: NCOG 6G61 final report. International Journal of Radiation Oncology, Biology, Physics 18(2): 321-324, 1990.
5. Friedman HS, Kerby T, Calvert H: Temozolomide and treatment of malignant glioma. Clinical Cancer Research 6(7): 2585-2597, 2000.
6. Prados MD, Levin V: Biology and treatment of malignant glioma. Seminars in Oncology 27(3 suppl 6): 1-10, 2000.
7. Nelson DF, Urtasun RC, Saunders WM, et al.: Recent and current investigations of radiation therapy of malignant gliomas. Seminars in Oncology 13(1): 46-55, 1986.
8. Levin VA: Chemotherapy of primary brain tumors. Neurologic Clinics 3(4): 855-866, 1985.
9. Shapiro WR: Therapy of adult malignant brain tumors: what have the clinical trials taught us? Seminars in Oncology 13(1): 38-45, 1986.
10. Loeffler JS, Alexander E, Shea WM, et al.: Radiosurgery as part of the initial management of patients with malignant gliomas. Journal of Clinical Oncology 10(9): 1379-1385, 1992.
11. Yung WK, Prados MD, et al., for the Temodal Brain Tumor Group: Multicenter phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse. Journal of Clinical Oncology 17(9): 2762-2771, 1999.
12. Brem H, Piantadosi S, Burger PC, et al.: Placebo-controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas. Lancet 345(8956): 1008-1012, 1995.
13. Brem H, Ewend MG, Piantadosi S, et al.: The safety of interstitial chemotherapy with BCNU-loaded polymer followed by radiation therapy in the treatment of newly diagnosed malignant gliomas: phase I trial. Journal of Neuro-Oncology 26(2): 111-123, 1995.
Adult Glioblastoma Multiforme
For glioblastoma multiforme, the cure rate is very low with standard local treatment. These patients are appropriate candidates for clinical trials designed to improve local control by adding newer forms of treatment to standard treatment.
Treatment options:
Standard:
1. Surgery plus radiation therapy and chemotherapy.1-3
2. Surgery plus radiation therapy.4
Under clinical evaluation:
Patients with brain tumors that are either infrequently curable or unresectable should be considered candidates for clinical trials that evaluate hyperfractionated irradiation, accelerated fraction irradiation, stereotactic radiosurgery, radiosensitizers, hyperthermia, interstitial brachytherapy, or intraoperative radiation therapy used in conjunction with external-beam radiation therapy to improve local control of the tumor and/or for studies that evaluate new drugs and biological response modifiers following radiation therapy.5-8 Cooperative group studies that evaluate hyperfractionated irradiation and interstitial brachytherapy are in progress.9 Carmustine (BCNU) impregnated polymer may be implanted during surgery.10,11
References:
1. Shapiro WR: Therapy of adult malignant brain tumors: what have the clinical trials taught us? Seminars in Oncology 13(1): 38-45, 1986.
2. Rodriguez L, Levin V: Does chemotherapy benefit the patient with a central nervous system glioma? Oncology (Huntington NY) 1(9): 29-36, 1987.
3. Prados MD, Levin V: Biology and treatment of malignant glioma. Seminars in Oncology 27(3 suppl 6): 1-10, 2000.
4. Friedman HS, Kerby T, Calvert H: Temozolomide and treatment of malignant glioma. Clinical Cancer Research 6(7): 2585-2597, 2000.
5. Leibel SA, Gutin PH, Sneed PK, et al.: Interstitial irradiation for the treatment of primary and metastatic brain tumors. Cancer: Principles and Practice of Oncology Updates 3(7): 1-11, 1989.
6. Nelson DF, Urtasun RC, Saunders WM, et al.: Recent and current investigations of radiation therapy of malignant gliomas. Seminars in Oncology 13(1): 46-55, 1986.
7. Loeffler JS, Alexander E, Shea WM, et al.: Radiosurgery as part of the initial management of patients with malignant gliomas. Journal of Clinical Oncology 10(9): 1379-1385, 1992.
8. Fontanesi J, Clark WC, Weir A, et al.: Interstitial iodine 125 and concomitant cisplatin followed by hyperfractionated external beam irradiation for malignant supratentorial glioma. American Journal of Clinical Oncology 16(5): 412-417, 1993.
9. Scharfen CO, Sneed PK, Wara WM, et al.: High activity iodine-125 interstitial implant for gliomas. International Journal of Radiation Oncology, Biology, Physics 24(1): 583-591, 1992.
10. Brem H, Piantadosi S, Burger PC, et al.: Placebo-controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas. Lancet 345(8956): 1008-1012, 1995.
11. Brem H, Ewend MG, Piantadosi S, et al.: The safety of interstitial chemotherapy with BCNU-loaded polymer followed by radiation therapy in the treatment of newly diagnosed malignant gliomas: phase I trial. Journal of Neuro-Oncology 26(2): 111-123, 1995.
Adult Brain Stem Glioma
Brain stem gliomas have a relatively poor prognosis that is correlated with histology (when biopsies are performed), location, and extent of tumor. The overall median survival time of patients in studies has been 44 to 74 weeks.1-5 The best results have been attained with hyperfractionated radiation therapy.5
Treatment options:
Standard:
Radiation therapy.1-5
Under clinical evaluation:
At recurrence, patients should be considered for clinical trials that evaluate new drugs and biological response modifiers.6,7
References:
1. Greenberger JS, Cassady JR, Levene MB: Radiation therapy of thalamic, midbrain and brain stem gliomas. Radiology 122(2): 463-468, 1977.
2. Levin VA, Edwards MS, Wara WM, et al.: 5-Fluorouracil and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) followed by hydroxyurea, misonidazole and irradiation for brain stem gliomas: a pilot study of the Brain Tumor Research Center and the Children's Cancer Study Group. Neurosurgery 14(6): 679-681, 1984.
3. Allen JC, Bloom J, Ertel I, et al.: Brain tumors in children: current cooperative and institutional chemotherapy trials in newly diagnosed and recurrent disease. Seminars in Oncology 13(1): 110-122, 1986.
4. Eifel PJ, Cassady JR, Belli JA: Radiation therapy of tumors of the brainstem and midbrain in children: experience of the Joint Center for Radiation Therapy and Children's Hospital Medical Center (1971-1981). International Journal of Radiation Oncology, Biology, Physics 13(6): 847-852, 1987.
5. Shrieve DC, Wara WM, Edwards MS, et al.: Hyperfractionated radiation therapy for gliomas of the brainstem in children and in adults. International Journal of Radiation Oncology, Biology, Physics 24(1): 599-610, 1992.
6. Fulton DS, Levin VA, Wara WM, et al.: Chemotherapy of pediatric brain-stem tumors. Journal of Neurosurgery 54(6): 721-725, 1981.
7. Rodriguez LA, Prados M, Fulton D, et al.: Treatment of recurrent brain stem gliomas and other central nervous system tumors with 5-fluorouracil, CCNU, hydroxyurea, and 6-mercaptopurine. Neurosurgery 22(4): 691-693, 1988.
Adult Well-Differentiated Ependymoma
Myxopapillary ependymoma and well-differentiated ependymoma
These ependymomas are often curable.
Treatment options:
Standard:
1. Surgery alone if totally resectable.
2. Surgery followed by radiation therapy to known or suspected residual tumor.1,2
Under clinical evaluation:
At recurrence following surgery, patients should be considered for reoperation and radiation therapy if not previously used. Patients who have received radiation therapy should be considered candidates for nitrosourea-based chemotherapies and for clinical trials that evaluate new drugs and biological response modifiers.
References:
1. Wallner KE, Wara WM, Sheline GE, et al.: Intracranial ependymomas: results of treatment with partial or whole brain irradiation without spinal irradiation. International Journal of Radiation Oncology, Biology, Physics 12(11): 1937-1941, 1986.
2. Shaw EG, Evans RG, Scheithauer BW, et al.: Postoperative radiotherapy of intracranial ependymoma in pediatric and adult patients. International Journal of Radiation Oncology, Biology, Physics 13(10): 1457-1462, 1987.
Adult Malignant Ependymoma
Anaplastic ependymoma and ependymoblastoma
Malignant ependymomas have variable prognoses that depend on location and extent of disease. Frequently, but not invariably, anaplastic ependymomas have a worse prognosis than well-differentiated ependymomas. The rare ependymoblastoma has a much worse prognosis.
Treatment options:
Standard:
Surgery plus radiation therapy.1,2
Under clinical evaluation:
Adjuvant chemotherapy before, during, and after radiation are treatment options being evaluated. At recurrence, patients should be considered candidates for nitrosourea-based chemotherapies and for clinical trials that evaluate new drugs and biological response modifiers.
References:
1. Wallner KE, Wara WM, Sheline GE, et al.: Intracranial ependymomas: results of treatment with partial or whole brain irradiation without spinal irradiation. International Journal of Radiation Oncology, Biology, Physics 12(11): 1937-1941, 1986.
2. Shaw EG, Evans RG, Scheithauer BW, et al.: Postoperative radiotherapy of intracranial ependymoma in pediatric and adult patients. International Journal of Radiation Oncology, Biology, Physics 13(10): 1457-1462, 1987.
Adult Well-Differentiated Oligodendroglioma
These tumors behave very similarly to the well-differentiated mildly and moderately anaplastic astrocytomas.
Treatment options:
Standard:
Surgery plus radiation therapy; however, some controversy exists. Some physicians treat these patients with surgery alone if the patient is younger than 45 years of age and the tumor is not contrast-enhanced on a computed tomographic scan.1
Under clinical evaluation:
Clinical trials in progress are evaluating the effect of adding drugs to local therapy, e.g., radiation therapy with or without chemotherapy for incompletely resected well-differentiated mildly or moderately anaplastic astrocytomas.
References:
1. Salazar OM, Castro-Vita H, Van Houtte P, et al.: Improved survival in cases of intracranial ependymoma after radiation therapy: late report and recommendations. Journal of Neurosurgery 59(4): 652-659, 1983.
Adult Anaplastic Oligodendroglioma
For anaplastic oligodendrogliomas of higher grade, the cure rate is low with standard local treatment.1 Such patients are appropriate candidates for clinical trials designed to improve local control by adding newer forms of treatment.
Treatment options:
Standard:
1. Surgery plus radiation therapy.2-5
2. Surgery plus radiation therapy plus chemotherapy.6
Under clinical evaluation:
Patients with brain tumors that are either infrequently curable or unresectable should be considered candidates for clinical trials that evaluate interstitial brachytherapy, radiosensitizers, hyperthermia, or intraoperative radiation therapy in conjunction with external-beam radiation therapy to improve local control of the tumor and/or for studies that evaluate new drugs and biological response modifiers following radiation therapy.
References:
1. Kyritsis AP, Yung WK, Bruner J, et al.: The treatment of anaplastic oligodendrogliomas and mixed gliomas. Neurosurgery 32(3): 365-371, 1993.
2. Bullard DE, Rawlings CE, Phillips BW, et al.: Oligodendroglioma: an analysis of the value of radiation therapy. Cancer 60(9): 2179-2188, 1987.
3. Burger PC, Rawlings CE, Cox EB, et al.: Clinicopathologic correlations in the oligodendroglioma. Cancer 59(7): 1345-1352, 1987.
4. Lindegaard KF, Mork SJ, Eide GE, et al.: Statistical analysis of clinicopathological features, radiotherapy, and survival in 170 cases of oligodendroglioma. Journal of Neurosurgery 67(2): 224-230, 1987.
5. Wallner KE, Gonzales M, Sheline GE: Treatment of oligodendrogliomas with or without postoperative irradiation. Journal of Neurosurgery 68(5): 684-688, 1988.
6. Cairncross JG, Macdonald DR: Successful chemotherapy for recurrent malignant oligodendroglioma. Annals of Neurology 23(4): 360-364, 1988.
Mixed Gliomas
Mixed astrocytoma-ependymoma, mixed astrocytoma-oligodendroglioma, and mixed astrocytoma-ependymoma-oligodendroglioma
These mixed glial tumors have a prognosis similar to that for anaplastic astrocytomas and can be treated as such.
Treatment options:1
Standard:
1. Surgery plus radiation therapy.2
2. Surgery plus radiation therapy plus chemotherapy.
Under clinical evaluation:
Patients with brain tumors that are either infrequently curable or unresectable should be considered candidates for clinical trials that evaluate interstitial brachytherapy, radiosensitizers, hyperthermia, or intraoperative radiation therapy in conjunction with external-beam radiation therapy to improve local control of the tumor and/or for studies that evaluate new drugs and biological response modifiers following radiation therapy.
References:
1. Kyritsis AP, Yung WK, Bruner J, et al.: The treatment of anaplastic oligodendrogliomas and mixed gliomas. Neurosurgery 32(3): 365-371, 1993.
2. Shaw EG, Daumas-Duport C, Scheithauer BW, et al.: Radiation therapy in the management of low-grade supratentorial astrocytomas. Journal of Neurosurgery 70(6): 853-861, 1989.
Adult Medulloblastoma
Treatment options:
Standard:
Surgery plus craniospinal irradiation for good-risk patients.1,2
Under clinical evaluation:
For poor-risk patients, in addition to surgery plus craniospinal irradiation, various chemotherapy programs are being evaluated.3
References:
1. Levin VA, Vestnys PS, Edwards MS, et al.: Improvement in survival produced by sequential therapies in the treatment of recurrent medulloblastoma. Cancer 51(8): 1364-1370, 1983.
2. Carrie C, Lasset C, Alapetite C, et al.: Multivariate analysis of prognostic factors in adult patients with medulloblastoma: retrospective study of 156 patients. Cancer 74(8): 2352-2360, 1994.
3. Allen JC, Bloom J, Ertel I, et al.: Brain tumors in children: current cooperative and institutional chemotherapy trials in newly diagnosed and recurrent disease. Seminars in Oncology 13(1): 110-122, 1986.
Adult Pineal Parenchymal Tumor
Pineocytoma and pineoblastoma
These diverse tumors require special consideration. Pineocytomas are slow growing and carry variable prognoses for cure. Pineoblastomas are more rapidly growing and have a worse prognosis.
Pineal astrocytoma
Depending on the degree of anaplasia, pineal astrocytomas vary in prognosis. Higher grades have a worse prognosis.
Treatment options:
Standard:
1. Surgery plus radiation therapy for pineocytoma and lower grades of astrocytoma.1,2
2. Surgery plus radiation therapy and chemotherapy for pineoblastoma and higher grades of astrocytoma.1,2
Under clinical evaluation:
Patients with brain tumors that are either infrequently curable or unresectable should be considered candidates for clinical trials that evaluate radiosensitizers, hyperthermia, or intraoperative radiation therapy in conjunction with external-beam radiation therapy to improve local control of the tumor and/or for studies that evaluate new drugs and biological response modifiers following radiation therapy.
References:
1. Stein BM, Fetell MR: Therapeutic modalities for pineal region tumors. Clinical Neurosurgery 32: 445-455, 1985.
2. Rich TA, Cassady JR, Strand RD, et al.: Radiation therapy for pineal and suprasellar germ cell tumors. Cancer 55(5): 932-940, 1985.
Adult Central Nervous System Germ Cell Tumor
Germinoma, embryonal carcinoma, choriocarcinoma, and teratoma
The prognosis and treatment of germ cell tumors depends on the histology, location, presence and amount of biological markers, and surgical resectability.1,2
References:
1. Edwards MS, Hudgins RJ, Wilson CB, et al.: Pineal region tumors in children. Journal of Neurosurgery 68(5): 689-697, 1988.
2. Lindstadt D, Wara WM, Edwards MS, et al.: Radiotherapy of primary intracranial germinomas: the case against routine craniospinal irradiation. International Journal of Radiation Oncology, Biology, Physics 15(2): 291-297, 1988.
Adult Craniopharyngioma
Craniopharyngioma is often curable.
Treatment options:
Standard:
1. Surgery alone if totally resectable.1
2. Debulking surgery plus radiation therapy if unresectable.2
References:
1. Baskin DS, Wilson CB: Surgical management of craniopharyngiomas: a review of 74 cases. Journal of Neurosurgery 65(1): 22-27, 1986.
2. Rajan B, Ashley S, Gorman C, et al.: Craniopharyngioma - long-term results following limited surgery and radiotherapy. Radiotherapy and Oncology 26(1): 1-10, 1993.
Adult Meningioma
Meningioma is usually curable when resectable.
Treatment options:
Standard:
1. Surgery.1
2. Surgery plus radiation therapy (in selected cases, such as for patients with known or suspected residual disease or with recurrence after previous surgery).2-4
References:
1. Black PM: Meningiomas. Neurosurgery 32(4): 643-657, 1993.
2. Wara WM, Sheline GE, Newman H, et al.: Radiation therapy of meningiomas. American Journal of Roentgenology, Radium Therapy and Nuclear Medicine 123(3): 453-458, 1975.
3. Barbaro NM, Gutin PH, Wilson CB, et al.: Radiation therapy in the treatment of partially resected meningiomas. Neurosurgery 20(4): 525-528, 1987.
4. Taylor BW, Marcus RB, Friedman WA, et al.: The meningioma controversy: postoperative radiation therapy. International Journal of Radiation Oncology, Biology, Physics 15(2): 299-304, 1988.
Adult Malignant Meningioma
Malignant meningioma, hemangiopericytoma, and papillary meningioma
The prognosis for patients with malignant meningioma is worse than for the more well-differentiated meningiomas because complete resections are less common and the proliferative capacity is greater.1,2
Treatment options:
Standard:
Surgery plus radiation therapy.
Under clinical evaluation:
Patients with brain tumors that are either infrequently curable or unresectable should be considered candidates for clinical trials that evaluate interstitial brachytherapy, radiosensitizers, hyperthermia, or intraoperative radiation therapy in conjunction with external-beam radiation therapy to improve local control of the tumor and/or for studies that evaluate new drugs and biological response modifiers following radiation therapy.
References:
1. Alvarez F, Roda JM, Perez-Romero M, et al.: Malignant and atypical meningiomas: a reappraisal of clinical, histological, and computed tomographic features. Neurosurgery 20(5): 688-694, 1987.
2. Perry A, Scheithauer BW, Stafford SL, et al.: "Malgnancy" in meningiomas: a clinicopathologic study of 116 patients, with grading implications. Cancer 85(9): 2046-2056, 1999.
Recurrent Adult Brain Tumor
Treatment options:
Standard:
1. Surgery alone or in conjunction with chemotherapy.1-3
2. Radiation therapy if not previously used, alone or with chemotherapy.
3. Interstitial irradiation.4
Under clinical evaluation:
Numerous clinical trials (particularly phase II trials) are evaluating the use of newer drugs in the treatment of brain tumors. Carmustine (BCNU) impregnated polymer may be implanted during surgery.5,6
References:
1. Salcman M, Kaplan RS, Ducker TB, et al.: Effect of age and reoperation on survival in the combined modality treatment of malignant astrocytoma. Neurosurgery 10(4): 454-463, 1982.
2. Rodriguez L, Levin V: Does chemotherapy benefit the patient with a central nervous system glioma? Oncology (Huntington NY) 1(9): 29-36, 1987.
3. Young B, Oldfield EH, Markesbery WR, et al.: Reoperation for glioblastoma. Journal of Neurosurgery 55(6): 917-921, 1981.
4. Leibel SA, Gutin PH, Sneed PK, et al.: Interstitial irradiation for the treatment of primary and metastatic brain tumors. Cancer: Principles and Practice of Oncology Updates 3(7): 1-11, 1989.
5. Brem H, Piantadosi S, Burger PC, et al.: Placebo-controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas. Lancet 345(8956): 1008-1012, 1995.
6. Brem H, Ewend MG, Piantadosi S, et al.: The safety of interstitial chemotherapy with BCNU-loaded polymer followed by radiation therapy in the treatment of newly diagnosed malignant gliomas: phase I trial. Journal of Neuro-Oncology 26(2): 111-123, 1995.
General Information
Cellular Classification
Stage Information
Noninfiltrating astrocytomas
Well-differentiated mildly and moderately anaplastic astrocytomas
Anaplastic astrocytomas
Glioblastoma multiforme
Well-differentiated ependymomas
Anaplastic ependymomas
Ependymoblastomas
Well-differentiated oligodendrogliomas
Anaplastic oligodendrogliomas
Meningiomas
Malignant meningiomas
Treatment Option Overview
Adult Noninfiltrating Astrocytoma
Juvenile pilocytic and subependymal astrocytomas 1
Adult Well-Differentiated Mildly and Moderately Anaplastic Astrocytoma
Adult Anaplastic Astrocytoma
Adult Glioblastoma Multiforme
Adult Brain Stem Glioma
Adult Well-Differentiated Ependymoma
Myxopapillary ependymoma and well-differentiated ependymoma
Adult Malignant Ependymoma
Anaplastic ependymoma and ependymoblastoma
Adult Well-Differentiated Oligodendroglioma
Adult Anaplastic Oligodendroglioma
Mixed Gliomas
Mixed astrocytoma-ependymoma, mixed astrocytoma-oligodendroglioma, and mixed astrocytoma-ependymoma-oligodendroglioma
Adult Medulloblastoma
Adult Pineal Parenchymal Tumor
Pineocytoma and pineoblastoma
Pineal astrocytoma
Adult Central Nervous System Germ Cell Tumor
Germinoma, embryonal carcinoma, choriocarcinoma, and teratoma
Adult Craniopharyngioma
Adult Meningioma
Adult Malignant Meningioma
Malignant meningioma, hemangiopericytoma, and papillary meningioma
Recurrent Adult Brain Tumor
General Information
Prognoses of primary brain tumors are determined by histologic type, grade, postoperative size, and extent of the tumor and by the patient's age, the performance status, and the duration of symptoms.1,2 Some primary brain tumors are curable by surgery alone, and some are curable by surgery and radiation therapy; the remainder require surgery, radiation therapy, and chemotherapy. Tumors that require all 3 modalities are infrequently curable.3
Metastases to the brain from a primary tumor that is outside the central nervous system (CNS) are more common than primary tumors of the brain. The most common primary tumors that metastasize to the brain are lung, breast, melanoma, and kidney. Metastases to the brain are usually multiple, but solitary metastases may also occur. Brain involvement can occur with cancers of the nasopharyngeal region by direct extension along the cranial nerves or through the foramina at the base of the skull. Metastatic meningeal involvement can also occur, especially with leukemia, lymphoma, small cell lung cancer, breast cancer, and some primary CNS tumors (such as medulloblastoma and ependymal gliomas).
A lesion in the brain should not be assumed to be a metastasis just because a patient has had a previous cancer; such an assumption could result in overlooking appropriate treatment of a curable tumor. Primary brain tumors rarely spread to other areas of the body, but they can spread to other parts of the brain and to the spinal axis.
References:
1. Levin VA, Leibel SA, Gutin PH: Neoplasms of the central nervous system. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. Philadelphia, Pa: Lippincott-Raven Publishers, 5th ed., 1997, pp 2022-2082.
2. Mahaley MS, Mettlin C, Natarajan N, et al.: National survey of patterns of care for brain-tumor patients. Journal of Neurosurgery 71(6): 826-836, 1989.
3. Surawicz TS, Davis F, Freels S, et al.: Brain tumor survival; results from the National Cancer Data Base. Journal of Neuro-Oncology 40(2): 151-160, 1998.
Cellular Classification
Histological classification for adult brain tumors is as follows:1
Glial tumors:
astrocytic tumors
#noninfiltrating
--juvenile pilocytic subependymal
#infiltrating
--well-differentiated mildly and moderately anaplastic astrocytoma anaplastic astrocytoma glioblastoma multiforme
#ependymal tumors
--myxopapillary and well-differentiated ependymoma anaplastic ependymoma ependymoblastoma
#oligodendroglial tumors
--well-differentiated oligodendroglioma anaplastic oligodendroglioma
#mixed tumors
--mixed astrocytoma-ependymoma mixed astrocytoma-oligodendroglioma mixed astrocytoma-ependymoma-oligodendroglioma
#medulloblastoma
Nonglial tumors:
#pineal parenchymal tumors
--pineocytoma pineoblastoma astrocytoma (see above)
#germ cell tumors
--germinoma embryonal carcinoma choriocarcinoma teratoma
#craniopharyngioma meningiomas
--meningioma malignant meningiomas
----anaplastic meningioma hemangiopericytoma papillary meningioma
#choroid plexus tumors
--choroid plexus papilloma anaplastic choroid plexus papilloma
References:
1. Kleihues P, Burger PC, Scheithauer BW, et al.: Histological typing of tumours of the central nervous system. Berlin: Springer-Verlag, 2nd ed., 1993.
Stage Information
Brain tumors are classified on the basis of tumor cell type and histologic grade. For some tumors, location and metastatic spread within the cerebrospinal fluid are also used in classification.1
Cerebral Astrocytic Gliomas
Gliomas constitute the most common primary central nervous system (CNS) tumors. Of the gliomas, astrocytomas of variable malignancy are the most prevalent. Cerebral astrocytomas are subdivided into categories (grades) based on the degree of tumor anaplasia and the presence or absence of necrosis.
Noninfiltrating astrocytomas
These astrocytomas are relatively slow-growing tumors such as juvenile pilocytic and subependymal astrocytomas, which occur most frequently in children but can occur in adults.
Well-differentiated mildly and moderately anaplastic astrocytomas
These tumors are more infiltrative than the juvenile pilocytic and subependymal astrocytomas but are still relatively slow-growing tumors.
Anaplastic astrocytomas
These tumors are highly anaplastic with obvious vascular abnormalities. This grade III astrocytoma grows more rapidly than the more differentiated astrocytomas.
Glioblastoma multiforme
This grade IV astrocytoma is a poorly differentiated, rapidly growing tumor that occurs most often in adults.
Brain Stem Gliomas
Brain stem gliomas are usually diagnosed on clinical evidence because diagnosis by biopsy might be hazardous. Tumors that diffusely enlarge the brain stem carry a worse prognosis than those that are more focal. Higher grades of malignancy (see above) carry poorer prognoses as well.
Cerebellar Astrocytomas
Although the majority of these tumors are of lower grade and frequently are curable, they vary in grade of malignancy. The higher grade lesions carry a worse prognosis, but prognosis is generally better than for their cerebral counterparts.
Ependymal Tumors
Ependymal tumors are considered to arise from ependymal cells that line the ventricles and from ependymal rests. They vary in grade of malignancy.
Well-differentiated ependymomas
These tumors include myxopapillary ependymoma and well-differentiated ependymoma, and are often curable.
Anaplastic ependymomas
These tumors have more features of anaplasia and appear mitotically more active than the myxopapillary or well-differentiated ependymomas. Although previously considered to do worse than the well-differentiated ependymoma, conflicting evidence suggests that patients treated with surgery and radiation therapy might do nearly as well.
Ependymoblastomas
These are generally tumors of childhood and are considered by some to be primitive neuroectodermal tumors. They are rare.
Oligodendroglial Tumors
Oligodendroglial tumors are gliomas that arise from the oligodendroglia. They vary in grade of malignancy, and prognosis is related to grade.
Well-differentiated oligodendrogliomas
These tumors are usually slow-growing and well circumscribed.
Anaplastic oligodendrogliomas
These tumors are comparable to the highly anaplastic gliomas in prognosis.
Mixed Gliomas
Mixed gliomas can occur with combinations of generally 2, but sometimes 3, different cell types: astrocytoma, ependymoma, and/or oligodendroglioma. Survival statistics are inexact for this group because the cell types and grade of the most malignant-appearing cells influence prognosis. In general, these tumors carry a prognosis that is between the prognoses of well-differentiated and anaplastic astrocytomas.
Medulloblastoma
Medulloblastoma is a rapidly growing tumor arising in the posterior fossa and is found almost exclusively in children and young adults. It has the tendency to spread from the brain to the spinal axis. Prognosis is dependent on the staging following surgical resection.
Pineal Region Tumors
Pineal parenchymal tumors vary in histology and grade of malignancy relative to patient age at occurrence. They can vary from the slow-growing pineocytoma to the more malignant and faster growing pineoblastoma. Astrocytomas can also grow in this location (see above), as can a variety of primary germ cell tumors: germinoma, embryonal carcinoma, choriocarcinoma, and teratoma. These uncommon tumors vary in prognosis. The absence of biopsy specimens in many series make the prognosis for each tumor type difficult to evaluate.
Craniopharyngiomas
Craniopharyngioma is a tumor that arises from the remains of a structure found in the developing embryo in the region of the pituitary gland. This tumor causes symptoms and signs by pressing on vital areas of the brain and the optic nerves; it also causes internal hydrocephalus by obstructing the foramen of Monro in children.
Meningiomas
Meningiomas arise from the meninges surrounding the brain and spinal cord and are generally slow-growing. There are other variants that constitute a group called malignant meningioma and include malignant meningioma, hemangiopericytoma, papillary meningioma, and meningeal sarcoma. Malignant meningiomas are more likely than other meningiomas to metastasize within the craniospinal axis.
Meningiomas
Meningioma is usually curable with surgery if the initial resection is complete. The shape of the tumor is a prognostic factor and should be considered in planning surgery. Incomplete resection associated with lobulated and mushrooming patterns of tumor growth is associated with a higher risk of recurrence.2
Malignant meningiomas
The prognosis for patients with malignant meningioma is worse than for patients with the more well-differentiated meningiomas.
Choroid Plexus Tumors
Choroid plexus tumors are rare tumors arising from choroid plexus epithelial cells. The more benign form is choroid plexus papilloma; the more malignant form is called anaplastic choroid plexus papilloma. These latter tumors are most likely to spread within the craniospinal axis.
References:
1. Levin VA, Leibel SA, Gutin PH: Neoplasms of the central nervous system. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. Philadelphia, Pa: Lippincott-Raven Publishers, 5th ed., 1997, pp 2022-2082.
2. Nakasu S, Nakasu Y, Nakajima M, et al.: Preoperative identification of meningiomas that are highly likely to recur. Journal of Neurosurgery 90(3): 455-462, 1999.
Treatment Option Overview
Surgical removal of brain tumors is recommended for most types and in most locations and should be as complete as possible within the constraints of preservation of neurologic function.1 An exception to this role for surgery is for deep-seated tumors, such as pontine gliomas, which are diagnosed on clinical evidence and are treated without initial surgery approximately 50% of the time. In the majority of cases, however, diagnosis by biopsy is preferred. Stereotaxic biopsy can be used for lesions that are difficult to reach and resect.
Radiation therapy has a major role in the treatment of most tumor types and can increase the cure rate or prolong disease-free survival. Radiation therapy may also be useful in the treatment of recurrences in patients treated initially with surgery alone.
Chemotherapy may prolong survival in some tumor types and has been reported to lengthen disease-free survival in patients with gliomas, medulloblastoma, and some germ cell tumors.2 Local chemotherapy with a nitrosourea applied to a polymer placed directly in the brain during surgery has been shown to be a safe modality and is under clinical evaluation.1,3
Patients who have brain tumors that are either infrequently curable or unresectable should be considered candidates for clinical trials that evaluate radiosensitizers, hyperthermia, or interstitial brachytherapy used in conjunction with external-beam radiation therapy to improve local control of the tumor or for studies that evaluate new drugs and biological response modifiers.
References:
1. Brem H, Piantadosi S, Burger PC, et al.: Placebo-controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas. Lancet 345(8956): 1008-1012, 1995.
2. Cokgor I, Friedman HS, Friedman AH: Chemotherapy for adults with malignant glioma. Cancer Investigation 17(4): 264-272, 1999.
Brem H, Ewend MG, Piantadosi S, et al.: The safety of interstitial chemotherapy with BCNU-loaded polymer followed by radiation therapy in the treatment of newly diagnosed malignant gliomas: phase I trial. Journal of Neuro-Oncology 26(2): 111-123, 1995.
3. Levin VA, Leibel SA, Gutin PH: Neoplasms of the central nervous system. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. Philadelphia, Pa: Lippincott-Raven Publishers, 5th ed., 1997, pp 2022-2082.
Adult Noninfiltrating Astrocytoma
Juvenile pilocytic and subependymal astrocytomas 1
Noninfiltrating astrocytic tumors are often curable.
Treatment options:
Standard:
1. Surgery alone if totally resectable.
2. Surgery followed by radiation therapy to known or suspected residual tumor.2
Under clinical evaluation:
At recurrence following surgery, patients should be considered for reoperation and radiation therapy if not previously given. Patients who have received radiation therapy should be considered candidates for nitrosourea-based chemotherapies and for clinical trials that evaluate new drugs and biological response modifiers.
References:
1. Wallner KE, Gonzales MF, Edwards MS, et al.: Treatment results of juvenile pilocytic astrocytoma. Journal of Neurosurgery 69(2): 171-176, 1988.
2. Shaw EG, Daumas-Duport C, Scheithauer BW, et al.: Radiation therapy in the management of low-grade supratentorial astrocytomas. Journal of Neurosurgery 70(6): 853-861, 1989.
Adult Well-Differentiated Mildly and Moderately Anaplastic Astrocytoma
Well-differentiated mildly and moderately anaplastic astrocytomas are less often curable.
Treatment options:
Standard:
Surgery plus radiation therapy, although some controversy exists and some physicians treat these patients with surgery alone if the patient is younger than 35 years of age and the tumor does not contrast-enhance on a computed tomographic scan.1
Under clinical evaluation:
Clinical trials in progress are evaluating the effect of adding drugs to local therapy, for example, radiation therapy with or without chemotherapy for incompletely resected well-differentiated mildly and moderately anaplastic astrocytomas. Other trials are evaluating the effect of deferring irradiation until the time of tumor progression and of high-dose versus low-dose irradiation.
References:
1. Shaw EG, Daumas-Duport C, Scheithauer BW, et al.: Radiation therapy in the management of low-grade supratentorial astrocytomas. Journal of Neurosurgery 70(6): 853-861, 1989.
Adult Anaplastic Astrocytoma
For anaplastic astrocytomas of higher grade, the cure rate is low with standard local treatment.1 These patients are appropriate candidates for clinical trials designed to improve local control by adding newer forms of treatment to standard treatment.
Treatment options:
Standard:
1. Surgery plus radiation therapy.
2. Surgery plus radiation therapy and chemotherapy.2-6
Under clinical evaluation:
Patients with brain tumors that are either infrequently curable or unresectable should be considered candidates for clinical trials that evaluate hyperfractionated irradiation, accelerated fraction radiation, stereotactic radiosurgery, radiosensitizers, hyperthermia, interstitial brachytherapy, or intraoperative radiation therapy used in conjunction with external-beam radiation therapy to improve local control of the tumor and/or for studies that evaluate new drugs and biological response modifiers following radiation therapy.7-11 Cooperative group trials that evaluate chemoradiotherapy administered with either hyperfractionated irradiation or a combination of brachytherapy and external-beam irradiation are now in progress. Carmustine (BCNU) impregnated polymer may be implanted during surgery.12,13
References:
1. Nelson DF, Nelson JS, Davis DR, et al.: Survival and prognosis of patients with astrocytoma with atypical or anaplastic features. Journal of Neuro-Oncology 3(2): 99-103, 1985.
2. Rodriguez L, Levin V: Does chemotherapy benefit the patient with a central nervous system glioma? Oncology (Huntington NY) 1(9): 29-36, 1987.
3. Chang CH, Horton J, Schoenfeld D, et al.: Comparison of postoperative radiotherapy and combined postoperative radiotherapy and chemotherapy in the multidisciplinary management of malignant gliomas: a joint Radiation Therapy Oncology and Eastern Cooperative Oncology Group Study. Cancer 52(6): 997-1007, 1983.
4. Levin VA, Silver P, Hannigan J, et al.: Superiority of post-radiotherapy adjuvant chemotherapy with CCNU, procarbazine, and vincristine (PCV) over BCNU for anaplastic gliomas: NCOG 6G61 final report. International Journal of Radiation Oncology, Biology, Physics 18(2): 321-324, 1990.
5. Friedman HS, Kerby T, Calvert H: Temozolomide and treatment of malignant glioma. Clinical Cancer Research 6(7): 2585-2597, 2000.
6. Prados MD, Levin V: Biology and treatment of malignant glioma. Seminars in Oncology 27(3 suppl 6): 1-10, 2000.
7. Nelson DF, Urtasun RC, Saunders WM, et al.: Recent and current investigations of radiation therapy of malignant gliomas. Seminars in Oncology 13(1): 46-55, 1986.
8. Levin VA: Chemotherapy of primary brain tumors. Neurologic Clinics 3(4): 855-866, 1985.
9. Shapiro WR: Therapy of adult malignant brain tumors: what have the clinical trials taught us? Seminars in Oncology 13(1): 38-45, 1986.
10. Loeffler JS, Alexander E, Shea WM, et al.: Radiosurgery as part of the initial management of patients with malignant gliomas. Journal of Clinical Oncology 10(9): 1379-1385, 1992.
11. Yung WK, Prados MD, et al., for the Temodal Brain Tumor Group: Multicenter phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse. Journal of Clinical Oncology 17(9): 2762-2771, 1999.
12. Brem H, Piantadosi S, Burger PC, et al.: Placebo-controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas. Lancet 345(8956): 1008-1012, 1995.
13. Brem H, Ewend MG, Piantadosi S, et al.: The safety of interstitial chemotherapy with BCNU-loaded polymer followed by radiation therapy in the treatment of newly diagnosed malignant gliomas: phase I trial. Journal of Neuro-Oncology 26(2): 111-123, 1995.
Adult Glioblastoma Multiforme
For glioblastoma multiforme, the cure rate is very low with standard local treatment. These patients are appropriate candidates for clinical trials designed to improve local control by adding newer forms of treatment to standard treatment.
Treatment options:
Standard:
1. Surgery plus radiation therapy and chemotherapy.1-3
2. Surgery plus radiation therapy.4
Under clinical evaluation:
Patients with brain tumors that are either infrequently curable or unresectable should be considered candidates for clinical trials that evaluate hyperfractionated irradiation, accelerated fraction irradiation, stereotactic radiosurgery, radiosensitizers, hyperthermia, interstitial brachytherapy, or intraoperative radiation therapy used in conjunction with external-beam radiation therapy to improve local control of the tumor and/or for studies that evaluate new drugs and biological response modifiers following radiation therapy.5-8 Cooperative group studies that evaluate hyperfractionated irradiation and interstitial brachytherapy are in progress.9 Carmustine (BCNU) impregnated polymer may be implanted during surgery.10,11
References:
1. Shapiro WR: Therapy of adult malignant brain tumors: what have the clinical trials taught us? Seminars in Oncology 13(1): 38-45, 1986.
2. Rodriguez L, Levin V: Does chemotherapy benefit the patient with a central nervous system glioma? Oncology (Huntington NY) 1(9): 29-36, 1987.
3. Prados MD, Levin V: Biology and treatment of malignant glioma. Seminars in Oncology 27(3 suppl 6): 1-10, 2000.
4. Friedman HS, Kerby T, Calvert H: Temozolomide and treatment of malignant glioma. Clinical Cancer Research 6(7): 2585-2597, 2000.
5. Leibel SA, Gutin PH, Sneed PK, et al.: Interstitial irradiation for the treatment of primary and metastatic brain tumors. Cancer: Principles and Practice of Oncology Updates 3(7): 1-11, 1989.
6. Nelson DF, Urtasun RC, Saunders WM, et al.: Recent and current investigations of radiation therapy of malignant gliomas. Seminars in Oncology 13(1): 46-55, 1986.
7. Loeffler JS, Alexander E, Shea WM, et al.: Radiosurgery as part of the initial management of patients with malignant gliomas. Journal of Clinical Oncology 10(9): 1379-1385, 1992.
8. Fontanesi J, Clark WC, Weir A, et al.: Interstitial iodine 125 and concomitant cisplatin followed by hyperfractionated external beam irradiation for malignant supratentorial glioma. American Journal of Clinical Oncology 16(5): 412-417, 1993.
9. Scharfen CO, Sneed PK, Wara WM, et al.: High activity iodine-125 interstitial implant for gliomas. International Journal of Radiation Oncology, Biology, Physics 24(1): 583-591, 1992.
10. Brem H, Piantadosi S, Burger PC, et al.: Placebo-controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas. Lancet 345(8956): 1008-1012, 1995.
11. Brem H, Ewend MG, Piantadosi S, et al.: The safety of interstitial chemotherapy with BCNU-loaded polymer followed by radiation therapy in the treatment of newly diagnosed malignant gliomas: phase I trial. Journal of Neuro-Oncology 26(2): 111-123, 1995.
Adult Brain Stem Glioma
Brain stem gliomas have a relatively poor prognosis that is correlated with histology (when biopsies are performed), location, and extent of tumor. The overall median survival time of patients in studies has been 44 to 74 weeks.1-5 The best results have been attained with hyperfractionated radiation therapy.5
Treatment options:
Standard:
Radiation therapy.1-5
Under clinical evaluation:
At recurrence, patients should be considered for clinical trials that evaluate new drugs and biological response modifiers.6,7
References:
1. Greenberger JS, Cassady JR, Levene MB: Radiation therapy of thalamic, midbrain and brain stem gliomas. Radiology 122(2): 463-468, 1977.
2. Levin VA, Edwards MS, Wara WM, et al.: 5-Fluorouracil and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) followed by hydroxyurea, misonidazole and irradiation for brain stem gliomas: a pilot study of the Brain Tumor Research Center and the Children's Cancer Study Group. Neurosurgery 14(6): 679-681, 1984.
3. Allen JC, Bloom J, Ertel I, et al.: Brain tumors in children: current cooperative and institutional chemotherapy trials in newly diagnosed and recurrent disease. Seminars in Oncology 13(1): 110-122, 1986.
4. Eifel PJ, Cassady JR, Belli JA: Radiation therapy of tumors of the brainstem and midbrain in children: experience of the Joint Center for Radiation Therapy and Children's Hospital Medical Center (1971-1981). International Journal of Radiation Oncology, Biology, Physics 13(6): 847-852, 1987.
5. Shrieve DC, Wara WM, Edwards MS, et al.: Hyperfractionated radiation therapy for gliomas of the brainstem in children and in adults. International Journal of Radiation Oncology, Biology, Physics 24(1): 599-610, 1992.
6. Fulton DS, Levin VA, Wara WM, et al.: Chemotherapy of pediatric brain-stem tumors. Journal of Neurosurgery 54(6): 721-725, 1981.
7. Rodriguez LA, Prados M, Fulton D, et al.: Treatment of recurrent brain stem gliomas and other central nervous system tumors with 5-fluorouracil, CCNU, hydroxyurea, and 6-mercaptopurine. Neurosurgery 22(4): 691-693, 1988.
Adult Well-Differentiated Ependymoma
Myxopapillary ependymoma and well-differentiated ependymoma
These ependymomas are often curable.
Treatment options:
Standard:
1. Surgery alone if totally resectable.
2. Surgery followed by radiation therapy to known or suspected residual tumor.1,2
Under clinical evaluation:
At recurrence following surgery, patients should be considered for reoperation and radiation therapy if not previously used. Patients who have received radiation therapy should be considered candidates for nitrosourea-based chemotherapies and for clinical trials that evaluate new drugs and biological response modifiers.
References:
1. Wallner KE, Wara WM, Sheline GE, et al.: Intracranial ependymomas: results of treatment with partial or whole brain irradiation without spinal irradiation. International Journal of Radiation Oncology, Biology, Physics 12(11): 1937-1941, 1986.
2. Shaw EG, Evans RG, Scheithauer BW, et al.: Postoperative radiotherapy of intracranial ependymoma in pediatric and adult patients. International Journal of Radiation Oncology, Biology, Physics 13(10): 1457-1462, 1987.
Adult Malignant Ependymoma
Anaplastic ependymoma and ependymoblastoma
Malignant ependymomas have variable prognoses that depend on location and extent of disease. Frequently, but not invariably, anaplastic ependymomas have a worse prognosis than well-differentiated ependymomas. The rare ependymoblastoma has a much worse prognosis.
Treatment options:
Standard:
Surgery plus radiation therapy.1,2
Under clinical evaluation:
Adjuvant chemotherapy before, during, and after radiation are treatment options being evaluated. At recurrence, patients should be considered candidates for nitrosourea-based chemotherapies and for clinical trials that evaluate new drugs and biological response modifiers.
References:
1. Wallner KE, Wara WM, Sheline GE, et al.: Intracranial ependymomas: results of treatment with partial or whole brain irradiation without spinal irradiation. International Journal of Radiation Oncology, Biology, Physics 12(11): 1937-1941, 1986.
2. Shaw EG, Evans RG, Scheithauer BW, et al.: Postoperative radiotherapy of intracranial ependymoma in pediatric and adult patients. International Journal of Radiation Oncology, Biology, Physics 13(10): 1457-1462, 1987.
Adult Well-Differentiated Oligodendroglioma
These tumors behave very similarly to the well-differentiated mildly and moderately anaplastic astrocytomas.
Treatment options:
Standard:
Surgery plus radiation therapy; however, some controversy exists. Some physicians treat these patients with surgery alone if the patient is younger than 45 years of age and the tumor is not contrast-enhanced on a computed tomographic scan.1
Under clinical evaluation:
Clinical trials in progress are evaluating the effect of adding drugs to local therapy, e.g., radiation therapy with or without chemotherapy for incompletely resected well-differentiated mildly or moderately anaplastic astrocytomas.
References:
1. Salazar OM, Castro-Vita H, Van Houtte P, et al.: Improved survival in cases of intracranial ependymoma after radiation therapy: late report and recommendations. Journal of Neurosurgery 59(4): 652-659, 1983.
Adult Anaplastic Oligodendroglioma
For anaplastic oligodendrogliomas of higher grade, the cure rate is low with standard local treatment.1 Such patients are appropriate candidates for clinical trials designed to improve local control by adding newer forms of treatment.
Treatment options:
Standard:
1. Surgery plus radiation therapy.2-5
2. Surgery plus radiation therapy plus chemotherapy.6
Under clinical evaluation:
Patients with brain tumors that are either infrequently curable or unresectable should be considered candidates for clinical trials that evaluate interstitial brachytherapy, radiosensitizers, hyperthermia, or intraoperative radiation therapy in conjunction with external-beam radiation therapy to improve local control of the tumor and/or for studies that evaluate new drugs and biological response modifiers following radiation therapy.
References:
1. Kyritsis AP, Yung WK, Bruner J, et al.: The treatment of anaplastic oligodendrogliomas and mixed gliomas. Neurosurgery 32(3): 365-371, 1993.
2. Bullard DE, Rawlings CE, Phillips BW, et al.: Oligodendroglioma: an analysis of the value of radiation therapy. Cancer 60(9): 2179-2188, 1987.
3. Burger PC, Rawlings CE, Cox EB, et al.: Clinicopathologic correlations in the oligodendroglioma. Cancer 59(7): 1345-1352, 1987.
4. Lindegaard KF, Mork SJ, Eide GE, et al.: Statistical analysis of clinicopathological features, radiotherapy, and survival in 170 cases of oligodendroglioma. Journal of Neurosurgery 67(2): 224-230, 1987.
5. Wallner KE, Gonzales M, Sheline GE: Treatment of oligodendrogliomas with or without postoperative irradiation. Journal of Neurosurgery 68(5): 684-688, 1988.
6. Cairncross JG, Macdonald DR: Successful chemotherapy for recurrent malignant oligodendroglioma. Annals of Neurology 23(4): 360-364, 1988.
Mixed Gliomas
Mixed astrocytoma-ependymoma, mixed astrocytoma-oligodendroglioma, and mixed astrocytoma-ependymoma-oligodendroglioma
These mixed glial tumors have a prognosis similar to that for anaplastic astrocytomas and can be treated as such.
Treatment options:1
Standard:
1. Surgery plus radiation therapy.2
2. Surgery plus radiation therapy plus chemotherapy.
Under clinical evaluation:
Patients with brain tumors that are either infrequently curable or unresectable should be considered candidates for clinical trials that evaluate interstitial brachytherapy, radiosensitizers, hyperthermia, or intraoperative radiation therapy in conjunction with external-beam radiation therapy to improve local control of the tumor and/or for studies that evaluate new drugs and biological response modifiers following radiation therapy.
References:
1. Kyritsis AP, Yung WK, Bruner J, et al.: The treatment of anaplastic oligodendrogliomas and mixed gliomas. Neurosurgery 32(3): 365-371, 1993.
2. Shaw EG, Daumas-Duport C, Scheithauer BW, et al.: Radiation therapy in the management of low-grade supratentorial astrocytomas. Journal of Neurosurgery 70(6): 853-861, 1989.
Adult Medulloblastoma
Treatment options:
Standard:
Surgery plus craniospinal irradiation for good-risk patients.1,2
Under clinical evaluation:
For poor-risk patients, in addition to surgery plus craniospinal irradiation, various chemotherapy programs are being evaluated.3
References:
1. Levin VA, Vestnys PS, Edwards MS, et al.: Improvement in survival produced by sequential therapies in the treatment of recurrent medulloblastoma. Cancer 51(8): 1364-1370, 1983.
2. Carrie C, Lasset C, Alapetite C, et al.: Multivariate analysis of prognostic factors in adult patients with medulloblastoma: retrospective study of 156 patients. Cancer 74(8): 2352-2360, 1994.
3. Allen JC, Bloom J, Ertel I, et al.: Brain tumors in children: current cooperative and institutional chemotherapy trials in newly diagnosed and recurrent disease. Seminars in Oncology 13(1): 110-122, 1986.
Adult Pineal Parenchymal Tumor
Pineocytoma and pineoblastoma
These diverse tumors require special consideration. Pineocytomas are slow growing and carry variable prognoses for cure. Pineoblastomas are more rapidly growing and have a worse prognosis.
Pineal astrocytoma
Depending on the degree of anaplasia, pineal astrocytomas vary in prognosis. Higher grades have a worse prognosis.
Treatment options:
Standard:
1. Surgery plus radiation therapy for pineocytoma and lower grades of astrocytoma.1,2
2. Surgery plus radiation therapy and chemotherapy for pineoblastoma and higher grades of astrocytoma.1,2
Under clinical evaluation:
Patients with brain tumors that are either infrequently curable or unresectable should be considered candidates for clinical trials that evaluate radiosensitizers, hyperthermia, or intraoperative radiation therapy in conjunction with external-beam radiation therapy to improve local control of the tumor and/or for studies that evaluate new drugs and biological response modifiers following radiation therapy.
References:
1. Stein BM, Fetell MR: Therapeutic modalities for pineal region tumors. Clinical Neurosurgery 32: 445-455, 1985.
2. Rich TA, Cassady JR, Strand RD, et al.: Radiation therapy for pineal and suprasellar germ cell tumors. Cancer 55(5): 932-940, 1985.
Adult Central Nervous System Germ Cell Tumor
Germinoma, embryonal carcinoma, choriocarcinoma, and teratoma
The prognosis and treatment of germ cell tumors depends on the histology, location, presence and amount of biological markers, and surgical resectability.1,2
References:
1. Edwards MS, Hudgins RJ, Wilson CB, et al.: Pineal region tumors in children. Journal of Neurosurgery 68(5): 689-697, 1988.
2. Lindstadt D, Wara WM, Edwards MS, et al.: Radiotherapy of primary intracranial germinomas: the case against routine craniospinal irradiation. International Journal of Radiation Oncology, Biology, Physics 15(2): 291-297, 1988.
Adult Craniopharyngioma
Craniopharyngioma is often curable.
Treatment options:
Standard:
1. Surgery alone if totally resectable.1
2. Debulking surgery plus radiation therapy if unresectable.2
References:
1. Baskin DS, Wilson CB: Surgical management of craniopharyngiomas: a review of 74 cases. Journal of Neurosurgery 65(1): 22-27, 1986.
2. Rajan B, Ashley S, Gorman C, et al.: Craniopharyngioma - long-term results following limited surgery and radiotherapy. Radiotherapy and Oncology 26(1): 1-10, 1993.
Adult Meningioma
Meningioma is usually curable when resectable.
Treatment options:
Standard:
1. Surgery.1
2. Surgery plus radiation therapy (in selected cases, such as for patients with known or suspected residual disease or with recurrence after previous surgery).2-4
References:
1. Black PM: Meningiomas. Neurosurgery 32(4): 643-657, 1993.
2. Wara WM, Sheline GE, Newman H, et al.: Radiation therapy of meningiomas. American Journal of Roentgenology, Radium Therapy and Nuclear Medicine 123(3): 453-458, 1975.
3. Barbaro NM, Gutin PH, Wilson CB, et al.: Radiation therapy in the treatment of partially resected meningiomas. Neurosurgery 20(4): 525-528, 1987.
4. Taylor BW, Marcus RB, Friedman WA, et al.: The meningioma controversy: postoperative radiation therapy. International Journal of Radiation Oncology, Biology, Physics 15(2): 299-304, 1988.
Adult Malignant Meningioma
Malignant meningioma, hemangiopericytoma, and papillary meningioma
The prognosis for patients with malignant meningioma is worse than for the more well-differentiated meningiomas because complete resections are less common and the proliferative capacity is greater.1,2
Treatment options:
Standard:
Surgery plus radiation therapy.
Under clinical evaluation:
Patients with brain tumors that are either infrequently curable or unresectable should be considered candidates for clinical trials that evaluate interstitial brachytherapy, radiosensitizers, hyperthermia, or intraoperative radiation therapy in conjunction with external-beam radiation therapy to improve local control of the tumor and/or for studies that evaluate new drugs and biological response modifiers following radiation therapy.
References:
1. Alvarez F, Roda JM, Perez-Romero M, et al.: Malignant and atypical meningiomas: a reappraisal of clinical, histological, and computed tomographic features. Neurosurgery 20(5): 688-694, 1987.
2. Perry A, Scheithauer BW, Stafford SL, et al.: "Malgnancy" in meningiomas: a clinicopathologic study of 116 patients, with grading implications. Cancer 85(9): 2046-2056, 1999.
Recurrent Adult Brain Tumor
Treatment options:
Standard:
1. Surgery alone or in conjunction with chemotherapy.1-3
2. Radiation therapy if not previously used, alone or with chemotherapy.
3. Interstitial irradiation.4
Under clinical evaluation:
Numerous clinical trials (particularly phase II trials) are evaluating the use of newer drugs in the treatment of brain tumors. Carmustine (BCNU) impregnated polymer may be implanted during surgery.5,6
References:
1. Salcman M, Kaplan RS, Ducker TB, et al.: Effect of age and reoperation on survival in the combined modality treatment of malignant astrocytoma. Neurosurgery 10(4): 454-463, 1982.
2. Rodriguez L, Levin V: Does chemotherapy benefit the patient with a central nervous system glioma? Oncology (Huntington NY) 1(9): 29-36, 1987.
3. Young B, Oldfield EH, Markesbery WR, et al.: Reoperation for glioblastoma. Journal of Neurosurgery 55(6): 917-921, 1981.
4. Leibel SA, Gutin PH, Sneed PK, et al.: Interstitial irradiation for the treatment of primary and metastatic brain tumors. Cancer: Principles and Practice of Oncology Updates 3(7): 1-11, 1989.
5. Brem H, Piantadosi S, Burger PC, et al.: Placebo-controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas. Lancet 345(8956): 1008-1012, 1995.
6. Brem H, Ewend MG, Piantadosi S, et al.: The safety of interstitial chemotherapy with BCNU-loaded polymer followed by radiation therapy in the treatment of newly diagnosed malignant gliomas: phase I trial. Journal of Neuro-Oncology 26(2): 111-123, 1995.
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