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Adult Brain Tumors Treatment (PDQ®)

  • Last Modified: 02/28/2014

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Management of Specific Tumor Types and Locations

Brain Stem Gliomas
        Current Clinical Trials
Pineal Astrocytic Tumors
Pilocytic Astrocytomas
Diffuse Astrocytomas (WHO grade II)
Anaplastic Astrocytomas (WHO grade III)
Glioblastomas
        O6-methylguanine–DNA methyltransferase (MGMT) promoter DNA methylation
        Dose-dense temozolomide
        Bevacizumab in newly diagnosed glioblastoma
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.

Patients with 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, patients with 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 (WHO grade II)

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 is a pilocytic astrocytoma.

Anaplastic Astrocytomas (WHO grade III)

Standard treatment options:

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

Patients with 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 patients with them are not practical. However, because these tumors are often aggressive, they are frequently 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 for patients with newly diagnosed disease:

  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.

The standard-of-care treatment for patients with newly diagnosed glioblastoma is surgery followed by concurrent radiation therapy and daily temozolomide, and then followed by six cycles of temozolomide. This standard therapy is based on a large, multicenter, randomized trial (NCT00006353) conducted by the European Organization for Research and Treatment of Cancer (EORTC) and National Cancer Institute of Canada (NCIC), which reported a survival benefit with concurrent radiation therapy and temozolomide compared with radiation therapy alone.[3,4][Level of evidence: 1iiA] In that study, 573 patients with glioblastoma were randomly assigned to receive standard radiation to the tumor volume with a 2- to 3-cm margin (60 Gy, 2 Gy per fraction, over 6 weeks) alone or with temozolomide (75 mg/m2 orally per day during radiation therapy for up to 49 days, followed by a 4-week break and then up to six cycles of five daily doses every 28 days at a dose of 150 mg/m2, increasing to 200 mg/m2 after the first cycle). Patients in the combined therapy group were given prophylactic therapy for pneumocystis carinii during the period of concomitant radiation therapy and temozolomide. OS was statistically significantly better in the combined radiation therapy–temozolomide group (hazard ratio [HR]death, 0.6; 95% confidence interval [CI], 0.5–0.7; OS at 3 years was 16.0% vs. 4.4%).

O6-methylguanine–DNA methyltransferase (MGMT) promoter DNA methylation

A companion molecular, correlation subset study to the EORTC-NCIC trial provided strong evidence that epigenetic silencing of the MGMT DNA-repair gene by promoter DNA methylation was associated with increased OS in patients with newly diagnosed glioblastoma.[5] MGMT promoter methylation was an independent favorable prognostic factor (P < .001 by the log-rank test; HR, 0.45; 95% CI, 0.32–0.61). The median OS for MGMT-methylated patients was 18.2 months (95% CI, 15.5–22.0), compared with 12.2 months (95% CI, 11.4–13.5) for MGMT-unmethylated patients.

Dose-dense temozolomide

MGMT DNA-repair activity has been proposed as a major mechanism of resistance to alkylating agents. Intracellular depletion of MGMT has been hypothesized to enhance treatment response, and protracted temozolomide schedules have been shown to deplete intracellular MGMT in peripheral blood mononuclear cells. To test whether protracted temozolomide enhances treatment response in patients with newly diagnosed glioblastoma, a multicenter, randomized, phase III trial conducted by the Radiation Therapy Oncology Group (RTOG), EORTC, and the North Central Cancer Therapy Group, RTOG 0525 (NCT00304031), compared standard adjuvant temozolomide treatment (days 1–5 of a 28-day cycle) with a dose-dense schedule (days 1–21 of a 28-day cycle). All patients were treated with surgery followed by radiation therapy and concurrent daily temozolomide. Patients were then randomly assigned to receive either standard adjuvant temozolomide or dose-dense temozolomide.[6][Level of evidence: 1iiA]

Among 833 randomly assigned patients, no statistically significant difference between standard and dose-dense temozolomide was observed for median OS (16.6 months for standard temozolomide vs. 14.9 months for dose-dense temozolomide; HR, 1.03; P = .63) or median progression-free survival (PFS) (5.5 vs. 6.7 months; HR, 0.87; P = .06). MGMT status was determined in 86% of randomly assigned patients, and no difference in efficacy was observed in either the MGMT-methylated or MGMT-unmethylated subsets. However, this study confirmed the strong prognostic effect of MGMT methylation because the median OS was 21.2 months (95% CI, 17.9–24.8) for methylated patients versus 14 months (95% CI, 12.9–14.7) (HR, 1.74; P < .001) for unmethylated patients.

In summary, there was no survival advantage for the use of dose-dense temozolomide versus standard-dose temozolomide in newly diagnosed glioblastoma patients, regardless of MGMT status. The efficacy of dose-dense temozolomide for patients who have recurrent glioblastoma, however, is yet to be determined.

Bevacizumab in newly diagnosed glioblastoma

In 2013, final data from two multicenter, phase III, randomized, double-blind, placebo-controlled trials of bevacizumab in patients who have newly diagnosed glioblastoma were reported: RTOG 0825 (NCT00884741) and the Roche-sponsored AVAglio (NCT00943826).[7,8][Level of evidence: 1iA] Patients in both studies were randomly assigned to receive standard therapy (chemoradiation with temozolomide) or standard therapy plus bevacizumab. OS and PFS were coprimary endpoints in both trials, and these outcomes were similar. Bevacizumab did not improve OS in either study (median OS was 16–17 months for each arm in both studies); however, it increased median PFS to a similar degree (AVAglio study: 10.6 vs. 6.2 months; HR, 0.64; P < .0001; RTOG 0825 study: 10.7 vs. 7.3 months; HR, 0.79; P = .007). The PFS result in the AVAglio study was statistically significant and associated with clinical benefit because bevacizumab-treated patients remained functionally independent for longer (9.0 months vs. 6.0 months) and went longer before their Karnofsky Performance scale deteriorated (HR, 0.65; P < .0001). Furthermore, bevacizumab-treated patients went longer before corticosteroids were initiated (12.3 vs. 3.7 months; HR, 0.71; P = .002), and a larger proportion of patients was able to discontinue corticosteroids if they were already taking them (66% vs. 47%). However, the PFS result in the RTOG 0825 trial did not meet the prespecified significance level (P = .004). Of note, there was significant crossover in both trials (approximately 40% of RTOG 0825 patients and approximately 30% of AVAglio patients received bevacizumab at the first sign of disease progression).

The two trials had contradictory results in health-related quality of life (HRQoL) and neurocognitive outcomes studies. In the mandatory HRQoL studies in the AVAglio trial, bevacizumab-treated patients experienced improved HRQoL, but bevacizumab-treated patients in the elective RTOG 0825 studies showed more decline in patient-reported HRQoL and neurocognitive function. The reasons for these discrepancies are unclear.

On the basis of these results, there is no definite evidence that the addition of bevacizumab to standard therapy is beneficial for all newly diagnosed glioblastoma patients. It is yet to be determined whether certain subgroups may benefit from the addition of bevacizumab.

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.[9][Level of evidence: 1iiA]

Patients who have oligodendrogliomas (WHO grade II) generally have better prognoses than do patients who have diffuse astrocytomas; however, most of the oligodendrogliomas eventually progress.

Anaplastic oligodendrogliomas

Standard treatment options:

  1. Surgery plus radiation therapy.
  2. Surgery plus radiation therapy plus chemotherapy.[10]
  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.[11] The OS was significantly longer in the radiation therapy and PCV arm (42.3 months vs. 30.6 months; HR, 0.75; 95% CI, 0.60–0.95). 1p/19q-codeleted tumors derived more benefit from adjuvant PCV chemotherapy compared with non-1p/19q-deleted tumors.[11][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.[12] 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).[12][Level of evidence: 1iiA]

On the basis of 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.[13] 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.[2,14]

Patients with anaplastic oligodendrogliomas (WHO grade III) have a low cure rate with standard local treatment, but their prognoses are generally better than are the prognoses of patients with anaplastic astrocytomas. Since anaplastic oligodendrogliomas are uncommon, phase III randomized trials restricted to patients with them are not practical. Patients with these tumors 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.

Patients with mixed glial tumors, which include oligoastrocytoma (WHO grade II) and anaplastic oligoastrocytoma (WHO grade III), have prognoses similar to that for astrocytic tumors of corresponding grades and are often 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.[15]

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

Embryonal Cell Tumors: Medulloblastomas

Standard treatment options:

  • Surgery plus craniospinal radiation therapy for good-risk patients.[16]

Treatment options under clinical evaluation:

  • Surgery plus craniospinal radiation therapy and various chemotherapy regimens are being evaluated for poor-risk patients.[16]

Medulloblastoma occurs primarily in children, but it also occurs with some frequency in adults.[17] 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 tumors, and patients with them carry variable prognoses for cure. Pineoblastomas are more rapidly growing tumors, and patients with them 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.[18,19].
  2. Surgery.
  3. Stereotactic radiosurgery for tumors less than 3 cm.
  4. 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.
  5. Fractionated radiation therapy for patients with unresectable tumors.[20]

WHO grade I meningiomas are usually curable when the mengiomas are 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.[18,19]

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 are those for patients with low-grade meningiomas because complete resections are less commonly feasible, and the proliferative capacity is greater.

Germ Cell Tumors

The prognoses 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.

Craniopharyngiomas (WHO grade I) are 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. Stupp R, Mason WP, van den Bent MJ, et al.: Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352 (10): 987-96, 2005.  [PUBMED Abstract]

  4. Stupp R, Hegi ME, Mason WP, et al.: Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 10 (5): 459-66, 2009.  [PUBMED Abstract]

  5. Hegi ME, Diserens AC, Gorlia T, et al.: MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352 (10): 997-1003, 2005.  [PUBMED Abstract]

  6. Gilbert MR, Wang M, Aldape KD, et al.: Dose-dense temozolomide for newly diagnosed glioblastoma: a randomized phase III clinical trial. J Clin Oncol 31 (32): 4085-91, 2013.  [PUBMED Abstract]

  7. Gilbert MR, Dignam JJ, Armstrong TS, et al.: A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med 370 (8): 699-708, 2014.  [PUBMED Abstract]

  8. Chinot OL, Wick W, Mason W, et al.: Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med 370 (8): 709-22, 2014.  [PUBMED Abstract]

  9. 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]

  10. 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]

  11. 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]

  12. 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]

  13. 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]

  14. 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]

  15. 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]

  16. 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]

  17. 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]

  18. 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]

  19. 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]

  20. 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]