Management of Specific Tumor Types and Locations

Brain Stem Gliomas
        Current Clinical Trials
Pineal Astrocytic Tumors
Pilocytic Astrocytomas
Diffuse Astrocytomas
Anaplastic Astrocytomas
Glioblastomas
Oligodendroglial Tumors
        Oligodendrogliomas
        Anaplastic oligodendrogliomas
Mixed Gliomas
Ependymal Tumors
        Grade I and II ependymal tumors
        Anaplastic ependymomas
Embryonal Cell Tumors: Medulloblastomas
Pineal Parenchymal Tumors
Meningeal Tumors
        Grade I meningiomas
        Grade II and III meningiomas and hemangiopericytomas
Germ Cell Tumors
Tumors of the Sellar Region: Craniopharyngiomas
Current Clinical Trials

Brain Stem Gliomas

Standard treatment options:

• Radiation therapy.

Brain stem gliomas have relatively poor prognoses that correlate 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.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with adult brain stem glioma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

Pineal Astrocytic Tumors

Standard treatment options:

1. Surgery plus radiation therapy for patients with pilocytic or diffuse astrocytoma.
2. Surgery plus radiation therapy and chemotherapy for patients with higher grade tumors.

Depending on the degree of anaplasia, pineal astrocytomas vary in prognoses. Higher grades have worse prognoses.

Pilocytic Astrocytomas

Standard treatment options:

1. Surgery alone if the tumor is totally resectable.
2. Surgery followed by radiation therapy to known or suspected residual tumor.

This astrocytic tumor is classified as a World Health Organization (WHO) grade I tumor and is often curable.

Diffuse Astrocytomas

Standard treatment options:

• Surgery plus radiation therapy; however, some controversy exists. Some physicians treat these patients with surgery alone if the patient is younger than 35 years and if the tumor does not contrast-enhance on a computed tomographic scan.[1]

This WHO grade II astrocytic tumor is less often curable than pilocytic astrocytoma.

Anaplastic Astrocytomas

Standard treatment options:

1. Surgery plus radiation therapy.
2. Surgery plus radiation therapy and chemotherapy.

Anaplastic astrocytomas (WHO grade III) have a low cure rate with standard local treatment. Because anaplastic astrocytomas represent less than 10% of all central nervous system gliomas, phase III randomized trials restricted to them are not practical. However, because they are aggressive and often included in studies along with glioblastomas, they are generally managed the same way as glioblastomas, with surgery and radiation, and often with chemotherapy even though it is not known whether the improved survival with chemotherapy in glioblastoma can be extrapolated to anaplastic astrocytomas.

Postoperative radiation alone has been compared with postoperative chemotherapy alone in patients with anaplastic gliomas (i.e., 144 astrocytomas, 91 oligoastrocytomas, and 39 oligodendrogliomas) with crossover to the other modality at the time of tumor progression. Of the 139 patients randomly assigned to radiation therapy, 135 were randomly assigned to chemotherapy with a 32-week course of either procarbazine + lomustine + vincristine (PCV) or single-agent temozolomide (2:1:1 randomization). The order of the modalities did not affect time to treatment failure (TTF) or overall survival (OS).[2][Levels of evidence: 1iiA and 1iiD] Neither TTF nor OS differed across the treatment arms.

Patients with anaplastic astrocytomas are appropriate candidates for clinical trials designed to improve local control by adding newer forms of treatment to standard treatment. Information about ongoing clinical trials is available from the NCI Web site.

Glioblastomas

Standard treatment options:

1. Surgery plus radiation therapy.
2. Surgery plus radiation therapy and chemotherapy.
3. Carmustine-impregnated polymer implanted during initial surgery.
4. Radiation therapy and concurrent chemotherapy.

For patients with glioblastoma (WHO grade IV), 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. Information about ongoing clinical trials is available from the NCI Web site.

Oligodendroglial Tumors

Oligodendrogliomas

Standard treatment options:

• Surgery plus radiation therapy; however, some controversy exists concerning the timing of radiation therapy. A study (EORTC-22845) of 300 patients who had surgery and were randomly assigned to either radiation therapy or watch and wait did not show a difference in OS in the two groups.[3][Level of evidence: 1iiA]

Oligodendrogliomas (WHO grade II) behave like diffuse astrocytomas.

Anaplastic oligodendrogliomas

Standard treatment options:

1. Surgery plus radiation therapy.
2. Surgery plus radiation therapy plus chemotherapy.[4]
3. Patients with an allelic loss at 1p and 19q have a higher than average response rate to PCV chemotherapy.

Mature results from the European Organisation for Research and Treatment of Cancer (EORTC) Brain Tumor Group Study 26951 (NCT00002840), a phase III, randomized study with 11.7 years of follow up demonstrated increased OS and progression-free survival in patients with anaplastic oligodendroglial tumors with six cycles of adjuvant PCV chemotherapy after radiation therapy compared with radiation therapy alone.[5] The OS was significantly longer in the radiation therapy and PCV arm (42.3 months vs. 30.6 months; hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.60–0.95). 1p/19q-codeleted tumors derived more benefit from adjuvant PCV chemotherapy compared with non-1p/19q-deleted tumors.[5][Level of evidence: 1iiA]

In contrast, the Radiation Therapy Oncology Group (RTOG) trial (RTOG-9402 [NCT00002569]) demonstrated no differences in median survival by treatment arm between an 8-week, intensive PCV chemotherapy regimen followed by immediate involved-field-plus-radiation therapy and radiation therapy alone.[6] However, in an unplanned subgroup analysis, patients with 1p/19q codeleted anaplastic oligodendroglioma and mixed anaplastic astrocytoma demonstrated a median survival of 14.7 years versus 7.3 years (HR, 0.59; 95% CI, 0.37–0.95; P = .03). For patients with noncodeleted tumors, there was no difference in median survival by treatment arm (2.6 vs. 2.7 years; HR, 0.85; 95% CI, 0.58–1.23; P = .39).[6][Level of evidence: 1iiA]

Based on these data, CODEL, a study that randomly assigned patients to radiation therapy alone (control arm), radiation therapy with temozolomide, and temozolomide alone (exploratory arm), was halted because radiation therapy alone was no longer considered adequate treatment in patients with anaplastic oligodendroglioma with 1p/19q codeletion.[7] A comparison between temozolomide and PCV chemotherapy in anaplastic oligodendroglioma has not been done, although in the setting of grade 3 anaplastic gliomas, no survival difference was seen between PCV chemotherapy and temozolomide.[2,8]

Anaplastic oligodendrogliomas (WHO grade III) have a low cure rate with standard local treatment, but their prognosis is generally better than that of anaplastic astrocytomas. Since anaplastic oligodendrogliomas are uncommon, phase III randomized trials restricted to them are not practical. They are generally managed with the following:

• Postoperative radiation therapy (PORT) alone, with chemotherapy at progression.
• Postoperative chemotherapy with radiation at progression.
• PORT plus chemotherapy, even though the combination of radiation plus chemotherapy is not known to be superior in outcome to sequential modality therapy.

PORT alone has been compared with postoperative chemotherapy alone in patients with anaplastic gliomas (i.e., 144 astrocytomas, 91 oligoastrocytomas, and 39 oligodendrogliomas) with crossover to the other modality at the time of tumor progression. Of the 139 patients randomly assigned to radiation therapy, 135 were randomly assigned to chemotherapy with a 32-week course of either PCV or single-agent temozolomide (2:1:1 randomization). The order of the modalities did not affect TTF or OS.[2][Levels of evidence: 1iiA and 1iiD]. Neither TTF nor OS differed across the treatment arms.

These patients are appropriate candidates for clinical trials designed to improve local control by adding newer forms of treatment. Information about ongoing clinical trials is available from the NCI Web site.

Mixed Gliomas

Standard treatment options:

1. Surgery plus radiation therapy.
2. Surgery plus radiation therapy plus chemotherapy.

Mixed glial tumors, which include oligoastrocytoma (WHO grade II) and anaplastic oligoastrocytoma (WHO grade III), have a prognosis similar to that for astrocytic tumors of corresponding grades and can be treated as such.

Ependymal Tumors

Grade I and II ependymal tumors

Standard treatment options:

1. Surgery alone if the tumor is totally resectable.
2. Surgery followed by radiation therapy to known or suspected residual tumor.

Ependymomas (WHO grade II) and ependymal tumors (WHO grade I), i.e., subependymoma and myxopapillary ependymomas, are often curable.

Anaplastic ependymomas

Standard treatment options:

• Surgery plus radiation therapy.[9]

Anaplastic ependymomas (WHO grade III) have variable prognoses that depend on the location and extent of disease. Frequently, but not invariably, anaplastic ependymomas have worse prognoses than lower grade ependymal tumors.

Embryonal Cell Tumors: Medulloblastomas

Standard treatment options:

• Surgery plus craniospinal radiation therapy for good-risk patients.[10]

Treatment options under clinical evaluation:

• Surgery plus craniospinal radiation therapy and various chemotherapy regimens are being evaluated for poor-risk patients.[10]

Medulloblastoma occurs primarily in children, but it also occurs with some frequency in adults.[11] Other embryonal tumors are pediatric conditions. (Refer to the PDQ summary on Childhood Central Nervous System Embryonal Tumors Treatment for more information.)

Pineal Parenchymal Tumors

Standard treatment options:

1. Surgery plus radiation therapy for pineocytoma.
2. Surgery plus radiation therapy and chemotherapy for pineoblastoma.

Pineocytoma (WHO grade II), pineoblastoma (WHO grade IV), and pineal parenchymal tumors of intermediate differentiation are diverse tumors that require special consideration. Pineocytomas are slow growing and carry variable prognoses for cure. Pineoblastomas are more rapidly growing and have worse prognoses. Pineal parenchymal tumors of intermediate differentiation have unpredictable growth and clinical behavior.

Meningeal Tumors

Grade I meningiomas

Standard treatment options:

1. Active surveillance with deferred treatment, especially for incidentally discovered asymptomatic tumors.[12,13].
2. Surgery.
3. Surgery plus radiation therapy is used in selected cases, such as for patients with known or suspected residual disease or with recurrence after previous surgery.
4. Radiation therapy for patients with unresectable tumors.[14]

WHO grade I meningiomas are usually curable when resectable. With the increasing use of sensitive neuroimaging tools, there has been greater detection of asymptomatic low-grade meningiomas. The majority appear to show minimal growth and can often be safely observed while therapy is deferred until growth or the development of symptoms.[12,13]

Grade II and III meningiomas and hemangiopericytomas

Standard treatment options:

• Surgery plus radiation therapy.

The prognoses for patients with meningiomas (WHO grade II) (i.e., atypical, clear cell, and chordoid), meningiomas (WHO grade III) (i.e., anaplastic/malignant, rhabdoid, and papillary), and hemangiopericytomas are worse than for patients with low-grade meningiomas because complete resections are less commonly feasible, and the proliferative capacity is greater.

Germ Cell Tumors

The prognosis and treatment of patients with germ cell tumors—which include germinoma, embryonal carcinoma, choriocarcinoma, and teratoma—depend on tumor histology, tumor location, presence and amount of biological markers, and surgical resectability.

Tumors of the Sellar Region: Craniopharyngiomas

Standard treatment options:

1. Surgery alone if the tumor is totally resectable.
2. Debulking surgery plus radiation therapy if the tumor is unresectable.

Craniopharyngioma (WHO grade I) is often curable.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with adult brain tumor. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References

1. Kaye AH, Walker DG: Low grade astrocytomas: controversies in management. J Clin Neurosci 7 (6): 475-83, 2000.  [PUBMED Abstract]
   
   
2. Wick W, Hartmann C, Engel C, et al.: NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with procarbazine, lomustine, and vincristine or temozolomide. J Clin Oncol 27 (35): 5874-80, 2009.  [PUBMED Abstract]
   
   
3. van den Bent MJ, Afra D, de Witte O, et al.: Long-term efficacy of early versus delayed radiotherapy for low-grade astrocytoma and oligodendroglioma in adults: the EORTC 22845 randomised trial. Lancet 366 (9490): 985-90, 2005.  [PUBMED Abstract]
   
   
4. van den Bent MJ, Chinot O, Boogerd W, et al.: Second-line chemotherapy with temozolomide in recurrent oligodendroglioma after PCV (procarbazine, lomustine and vincristine) chemotherapy: EORTC Brain Tumor Group phase II study 26972. Ann Oncol 14 (4): 599-602, 2003.  [PUBMED Abstract]
   
   
5. van den Bent MJ, Brandes AA, Taphoorn MJ, et al.: Adjuvant procarbazine, lomustine, and vincristine chemotherapy in newly diagnosed anaplastic oligodendroglioma: long-term follow-up of EORTC brain tumor group study 26951. J Clin Oncol 31 (3): 344-50, 2013.  [PUBMED Abstract]
   
   
6. Cairncross G, Wang M, Shaw E, et al.: Phase III trial of chemoradiotherapy for anaplastic oligodendroglioma: long-term results of RTOG 9402. J Clin Oncol 31 (3): 337-43, 2013.  [PUBMED Abstract]
   
   
7. Gilbert MR: Minding the Ps and Qs: perseverance and quality studies lead to major advances in patients with anaplastic oligodendroglioma. J Clin Oncol 31 (3): 299-300, 2013.  [PUBMED Abstract]
   
   
8. Brada M, Stenning S, Gabe R, et al.: Temozolomide versus procarbazine, lomustine, and vincristine in recurrent high-grade glioma. J Clin Oncol 28 (30): 4601-8, 2010.  [PUBMED Abstract]
   
   
9. Oya N, Shibamoto Y, Nagata Y, et al.: Postoperative radiotherapy for intracranial ependymoma: analysis of prognostic factors and patterns of failure. J Neurooncol 56 (1): 87-94, 2002.  [PUBMED Abstract]
   
   
10. Brandes AA, Franceschi E, Tosoni A, et al.: Long-term results of a prospective study on the treatment of medulloblastoma in adults. Cancer 110 (9): 2035-41, 2007.  [PUBMED Abstract]
    
    
11. Brandes AA, Ermani M, Amista P, et al.: The treatment of adults with medulloblastoma: a prospective study. Int J Radiat Oncol Biol Phys 57 (3): 755-61, 2003.  [PUBMED Abstract]
    
    
12. Nakamura M, Roser F, Michel J, et al.: The natural history of incidental meningiomas. Neurosurgery 53 (1): 62-70; discussion 70-1, 2003.  [PUBMED Abstract]
    
    
13. Yano S, Kuratsu J; Kumamoto Brain Tumor Research Group.: Indications for surgery in patients with asymptomatic meningiomas based on an extensive experience. J Neurosurg 105 (4): 538-43, 2006.  [PUBMED Abstract]
    
    
14. Debus J, Wuendrich M, Pirzkall A, et al.: High efficacy of fractionated stereotactic radiotherapy of large base-of-skull meningiomas: long-term results. J Clin Oncol 19 (15): 3547-53, 2001.  [PUBMED Abstract]