Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Glioblastoma Multiforme Treatment & Management

  • Author: Jeffrey N Bruce, MD; Chief Editor: Jules E Harris, MD, FACP, FRCPC  more...
 
Updated: Dec 11, 2015
 

Medical Care

The treatment of glioblastomas remains difficult in that no contemporary treatments are curative.[23] While overall mortality rates remain high, recent work leading to an understanding of the molecular mechanisms and gene mutations combined with clinical trials are leading to more promising and tailored therapeutic approaches. Multiple challenges remain, including tumor heterogeneity, tumor location in a region where it is beyond the reach of local control, and rapid, aggressive tumor relapse. Therefore, the treatment of patients with malignant gliomas still remains palliative and encompasses surgery, radiotherapy, and chemotherapy. See Brain Cancer Treatment Protocols for summarized information.

Upon initial diagnosis of glioblastoma multiforme (GBM), standard treatment consists of maximal surgical resection, radiotherapy, and concomitant and adjuvant chemotherapy with temozolomide.[24, 25] For patients older than 70 years, less aggressive therapy is sometimes employed, using radiation or temozolomide alone.[26, 27, 28] A study by Scott et al found that elderly patients with glioblastoma who underwent radiotherapy had improved cancer-specific survival and overall survival compared with those who did not undergo radiotherapy treatment.[29]

Recent evidence suggests that in patients over 60 years old, treatment with temozolomide is associated with longer survival than treatment with standard radiotherapy, and for those over 70 years old, temozolomide or hypofractionated radiotherapy is associated with prolonged survival than treatment with standard fractionated radiotherapy. The improvement in survival with temozolomide isenhancedinpatientswithMGMTpromotermethylation.[30]

Stupp et al reported the final results of the randomized phase III trial for patients with glioblastoma who were treated with adjuvant temozolomide and radiation with a median follow-up of more than 5 years. Stupp et al previously reported improved median and 2-year survival when temozolomide was added to radiation therapy in glioblastoma. Survival in the combined therapy group (ie, temozolomide and radiation) continued to exceed that of radiation alone throughout the 5-year follow-up (p< 0.0001). Survival of patients who received adjuvant temozolomide with radiotherapy for glioblastoma is superior to radiotherapy alone across all clinical prognostic subgroups.[45]

Median time to recurrence after standard therapy is 6.9 months.[46] For recurrent glioblastoma multiforme, surgery is appropriate in selected patients, and various radiotherapeutic, chemotherapeutic, biologic, or experimental therapies are also employed.[47, 37] A study by Wernicke et al report that prostate-specific membrane antigen is expressed in the vasculature of GBM vessels and represents a potential novel therapeutic vascular target. Future clinical trials are planned.[48]

Clinical practice guideline

In an evidence-based clinical practice guideline formulated to address the impact of cytotoxic chemotherapy on disease control and survival in adults with progressive glioblastoma, Olson et al make the following recommendations[49] :

  • Temozolomide is recommended over procarbazine in patients who have a first relapse of glioblastoma after treatment with nitrosourea chemotherapy or who had no prior cytotoxic chemotherapy at the time of initial therapy (level II recommendation)
  • Carmustine (BCNU)-impregnated biodegradable polymer wafers are recommended for use as a surgical adjunct when cytoreductive surgery is indicated; the associated toxicities must be taken into account (level II recommendation
  • Various agents of uncertain benefit may be considered for use, depending on the treating clinician's clinical judgment; prior treatment exposure, systemic health, and tolerance must be taken into account; enrollment in clinical trials of these agents is encouraged (level III recommendation)

Radiation therapy [50, 51, 35, 52]

Radiation therapy in addition to surgery or surgery combined with chemotherapy has been shown to prolong survival in patients with glioblastoma multiformes compared to surgery alone. The addition of radiotherapy to surgery has been shown to increase survival from 3-4 months to 7-12 months.[46, 53]

Dose response relationships for glioblastomas demonstrate that a radiation dose of less than 4500 cGy results in a median survival of 13 weeks compared with a median survival of 42 weeks with a dose of 6000 cGy. This is usually administered 5 days per week in doses of 1.8-2.0 Gy.

The responsiveness of glioblastoma multiformes to radiotherapy varies. In many instances, radiotherapy can induce a phase of remission, often marked with stability or regression of neurologic deficits as well as diminution in the size of the contrast-enhancing mass. Unfortunately, any period of response is short-lived because the tumor typically recurs within 1 year, resulting in further clinical deterioration and the appearance of an expansile region of contrast enhancement.[54, 36]

Two studies investigated tumor recurrence after whole-brain radiation therapy and found that the tumor recurred within 2 cm of the original site in 90% and 78% of patients, supporting the use of focal radiation therapy. Multifocal recurrence occurred in 6% of patients in one study and in 5% of patients in a second trial.

Interstitial brachytherapy is of limited use and is rarely used. By implantation of radioactive seeds, a large dose of radiation is delivered to the tumor volume, with rapid fall-off of radiation in surrounding tissue. The tumor must be unilateral and smaller than 5 cm in diameter. In one study, patients treated with interstitial brachytherapy had a significantly better median survival (2 mo) compared with the conventional focal external beam radiation therapy. Following interstitial brachytherapy, up to 40% of patients require another surgery for removal of tissue damaged by radiation necrosis.[55]

Experimental studies are underway in which focal radiation is delivered directly to tumors through an implanted balloon containing interstitial radiation. MRI and MR spectroscopy can be used to monitor therapy. Clinical outcomes from these studies are not yet available.

Radiosensitizers, such as newer chemotherapeutic agents,[56] targeted molecular agents,[41, 42] and antiangiogenic agents[42] may increase the therapeutic effect of radiotherapy.[57]

Radiotherapy for recurrent glioblastoma multiforme is controversial, though some studies have suggested a benefit to stereotactic radiosurgery or fractionated stereotactic reirradiation.[58, 59, 60]  In adult patients with progressive glioblastoma, American Association of Neurological Surgeons/Congress of Neurological Surgeons (AANS/CNS) guidelines recommend that when the target tumor is amenable for additional radiation, re-irradiation should be performed to improve local tumor control. This re-irradiation may take the form of conventional fractionation radiotherapy, fractionated radiosurgery, or single fraction radiosurgery.[61]

Chemotherapy – Antineoplastic agents [62, 63, 64, 65, 66, 67]

Although the optimal chemotherapeutic regimen for glioblastoma is not defined at present, several studies have suggested that more than 25% of patients obtain a significant survival benefit from adjuvant chemotherapy. Meta-analyses have suggested that adjuvant chemotherapy results in a 6-10% increase in 1-year survival rate.[68, 69]

Temozolomide is an orally active alkylating agent that is used for persons newly diagnosed with glioblastoma multiforme. It was approved by the United States Food and Drug Administration (FDA) in March 2005. Studies have shown that the drug was well tolerated and provided a survival benefit. Adjuvant and concomitant temozolomide with radiation was associated with significant improvements in median progression-free survival over radiation alone (6.9 vs 5 mo), overall survival (14.6 vs 12.1 mo), and the likelihood of being alive in 2 years (26% vs 10%).

Nitrosoureas: BCNU (carmustine)-polymer wafers (Gliadel) were approved by the FDA in 2002. Though Gliadel wafers are used by some for initial treatment, they have shown only a modest increase in median survival over placebo (13.8 vs. 11.6 months) in the largest such phase III trial, and are associated with increased rates of CSF leak and increased intracranial pressure secondary to edema and mass effect.[70, 71]

MGMT is a DNA repair enzyme that contributes to temozolomide resistance. Methylation of the MGMT promoter, found in approximately 45% of glioblastoma multiformes, results in an epigenetic silencing of the gene, decreasing the tumor cell's capacity for DNA repair and increasing susceptibility to temozolomide.[72] Note the following:

  • When patients with and without MGMT promoter methylation were treated with temozolomide, the groups had median survivals of 21.7 versus 12.7 months, and 2-year survival rates of 46% versus 13.8%, respectively.
  • Though temozolomide is currently a first-line agent in the treatment of glioblastoma multiforme, unfavorable MGMT methylation status could help select patients appropriate for future therapeutic investigations. [73]
  • O6-benzylguanine and other inhibitors of MGMT as well as RNA interference-mediated silencing of MGMT offer promising avenues to increase the effectiveness of temozolomide and other alkylating antineoplastics, and such agents are under active study. [73, 74, 39]

Carmustine (BCNU) and cis -platinum (cisplatin) have been the primary chemotherapeutic agents used against malignant gliomas. All agents in use have no greater than a 30-40% response rate, and most fall into the range of 10-20%.

Data from the University of California at San Francisco indicate that, for the treatment of glioblastomas, surgery followed by radiation therapy leads to 1-, 3-, and 5-year survival rates of 44%, 6%, and 0%, respectively. By comparison, surgery followed by radiation and chemotherapy using nitrosourea-based regimens resulted in 1-, 3-, and 5-year survival rates of 46%, 18%, and 18%, respectively.

A major hindrance to the use of chemotherapeutic agents for brain tumors is the fact that the blood-brain barrier (BBB) effectively excludes many agents from the CNS. For this reason, novel methods of intracranial drug delivery are being developed to deliver higher concentrations of chemotherapeutic agents to the tumor cells while avoiding the adverse systemic effects of these medications.

Pressure-driven infusion of chemotherapeutic agents through an intracranial catheter, also known as convection-enhanced delivery (CED), has the advantage of delivering drugs along a pressure gradient rather than by simple diffusion. CED has shown promising results in animal models with agents including BCNU and topotecan.[75, 76, 77]

Initial attempts investigated the delivery of chemotherapeutic agents via an intraarterial route rather than intravenously. Unfortunately, no survival advantage was observed.

Chemotherapy for recurrent glioblastoma multiforme provides modest, if any, benefit, and several classes of agents are used. Carmustine wafers increased 6-month survival from 36% to 56% over placebo in one randomized study of 222 patients, though there was a significant association between the treatment group and serious intracranial infections.[78, 79]

Genotyping of brain tumors may have applications in stratifying patients for clinical trials of various novel therapies.

The anti-angiogenic agent bevacizumab was approved by the U.S. Food and Drug Administration for recurrent glioblastoma in May 2009.[80] When used with irinotecan, bevacizumab improved 6-month survival in recurrent glioma patients to 46% compared with 21% in patients treated with temozolomide.[81, 82] This bevacizumab and irinotecan combination for recurrent glioblastoma multiforme has been shown to improve survival over bevacizumab alone.[83] Anti-angiogenic agents also decrease peritumoral edema, potentially reducing the necessary corticosteroid dose.

A small proportion of glioblastomas responds to gefitinib or erlotinib (tyrosine kinase inhibitors). The simultaneous presence in glioblastoma cells of mutant EGFR (EGFRviii) and PTEN was associated with responsiveness to tyrosine kinase inhibitors, whereas increased p-akt predicts a decreased effect.[84, 85, 86] Other targets include PDGFR, VEGFR, mTOR, farnesyltransferase, and PI3K.

Other therapy modalities under investigation include gene therapy, peptide and dendritic cell vaccines, synthetic chlorotoxins, and radiolabeled drugs and antibodies.[87, 88, 89, 90, 91, 92]

A population-based analysis of 5607 adult patients with glioblastoma in the SEER (Surveillance Epidemiology and End Results) database found that bevacizumab therapy may improve survival. In the study, glioblastoma patients who died in 2010 (after the FDA approved bevacizumab for this condition) survived significantly longer than those who died of the disease in 2008. Median survival was 8 months for patients who died in 2006, 7 months in 2008, and 9 months in 2010. This difference in survival was highly significant between 2008 (pre-bevacizumab) and 2010 (post-bevacizumab). This survival difference was unlikely due to improvements in supportive care during this time interval, because there was no significant difference between those who died in 2006 and patients who died 2 years later, in 2008.[93, 94]

Electric-field therapy

The Optune device uses low-intensity, intermediate-frequency, alternating electric fields (tumor- treating fields) to target dividing cells in glioblastoma multiforme while generally not harming normal cells. The tumor-treating fields are generated via electrodes placed directly on the scalp. To target the tumor, array placement is based on the individual patient's magnetic resonance imaging results.[95]

Optune, also known as the NovoTTF-100A System, was initially approved in 2011 for use in glioblastoma multiforme that had recurred or progressed after treatment. In October 2015, the FDA expanded approval to include use of the device in conjunction with temozolomide chemotherapy in the first-line setting. Approval was based on an open-label, randomized phase 3 trial in 700 patients, in which median overall survival was 19.4 months with use of the device plus temozolomide, versus 16.6 months with chemotherapy only.[95]

Next

Surgical Care

The extent of surgery (biopsy vs resection) has been shown in a number of studies to affect length of survival. In a study by Ammirati and colleagues (1987), patients with high-grade gliomas who had a gross total resection had a 2-year survival rate of 19%, while those with a subtotal resection had a 2-year survival rate of 0%.[96]

In another study of 416 patients, gross total resection, defined as >98% on MRI, conferred a survival advantage over subtotal resection (13 vs 8.8 mo).[97]

In another study of 92 patients, a total tumor resection without any residual disease resulted in a median survival of 93 weeks, whereas the smallest percent of resection (< 25%) and greatest volume of residual tumor (>20 cm3) gradually shortened the survival to 31 weeks and 50 weeks, respectively.[98]

An analysis of 28 studies found a mean duration of survival advantage of total over subtotal resection for glioblastoma multiforme (14 vs 11 mo).[99, 100]

Because these tumors cannot be cured with surgery, the surgical goals are to establish a pathological diagnosis, relieve mass effect, and, if possible, achieve a gross total resection to facilitate adjuvant therapy.[101] Most glioblastomas recur in and around the original tumor bed, but contralateral and distant recurrences are not uncommon, especially with lesions near the corpus callosum. The indications for reoperation of malignant astrocytomas after initial treatment with surgery, radiation therapy, and chemotherapy are not firmly established. Reoperation is generally considered in the face of a life-threatening recurrent mass, particularly if radionecrosis rather than recurrent tumor is suspected as the cause of clinical and radiographic deterioration. PET scans and MR spectroscopy have proven useful in discriminating between these 2 entities.

See the images below.

Axial CT scan without intravenous contrast. This i Axial CT scan without intravenous contrast. This image reveals a large right temporal intraaxial mass (glioblastoma multiforme [GBM]). Extensive surrounding edema is present, as demonstrated by the peritumoral hypodensity, and a moderate right-to-left midline shift can be noted. All of the radiologic studies in this article are of the same patient.
A T1-weighted axial MRI without intravenous contra A T1-weighted axial MRI without intravenous contrast. This image demonstrates a hemorrhagic multicentric tumor (glioblastoma multiforme [GBM]) in the right temporal lobe. Effacement of the ventricular system is present on the right, and mild impingement of the right medial temporal lobe can be observed on the midbrain.
A T1-weighted axial MRI with intravenous contrast. A T1-weighted axial MRI with intravenous contrast. Heterogenous enhancement of the lesion is present within the right temporal lobe. The hypointensity circumscribed within the enhancement is suggestive of necrosis. This radiologic appearance is typical of a multicentric glioblastoma multiforme (GBM).
A T1-weighted coronal MRI with intravenous contras A T1-weighted coronal MRI with intravenous contrast. This image demonstrates the lesion (glioblastoma multiforme [GBM]) within the medial temporal lobe and the stereotypical pattern of contrast enhancement.
A T1-weighted sagittal MRI with intravenous contra A T1-weighted sagittal MRI with intravenous contrast in a patient with glioblastoma multiforme (GBM).
A T2-weighted axial MRI. The tumor (glioblastoma m A T2-weighted axial MRI. The tumor (glioblastoma multiforme [GBM]) and surrounding white matter within the right temporal lobe show increased signal intensity compared to a healthy brain, suggesting extensive tumorigenic edema.
A fluid-attenuated inversion recovery (FLAIR) axia A fluid-attenuated inversion recovery (FLAIR) axial MRI. This image is similar to the T2-weighted image and demonstrates extensive edema in a patient with glioblastoma multiforme (GBM).
Histopathologic slide demonstrating a glioblastoma Histopathologic slide demonstrating a glioblastoma multiforme (GBM).

Although no formal studies have been performed, observations indicate that variables, such as young age, prolonged interval between operations, and extent of the second surgical resection, have prognostic significance.[102]

A study by El Hindy et al found that a common regulatory single-nucleotide polymorphism (-938C>A) is a survival prognosticator and a marker for high-risk in patients with glioblastoma multiforme who undergo gross total resection.[103]

Stereotactic biopsy followed by radiation therapy may be considered in certain circumstances. These include patients with a tumor located in an eloquent area of the brain, patients whose tumors have minimal mass effect, and patients in poor medical condition, precluding general anesthesia. Median survival after stereotactic biopsy and radiation therapy is reported to be from 27-47 weeks.[104]

A study by Jakola et al found that surgical procedures may not significantly alter the quality of life (QOL) in the average patient, however, the use of intraoperative ultrasonography may be associated with a preservation of QOL in that it helps avoid introducing new deficits.[105]

Previous
Next

Consultations

Patients with glioblastomas should be evaluated by a team of specialists, including a neurologist, neurosurgeon, neurooncologist, and radiation oncologist, in order to develop a coordinated treatment strategy.

Previous
Next

Diet

No dietary restrictions are necessary.

Previous
Next

Activity

No universal restrictions on activity are necessary for patients with glioblastomas. The patient's activity depends on his or her overall neurologic status. The presence of seizures may prevent the patient from driving. In many circumstances, physical therapy and/or rehabilitation are extremely beneficial. Activity is encouraged to reduce the risk of deep venous thrombosis.

Previous
 
 
Contributor Information and Disclosures
Author

Jeffrey N Bruce, MD Edgar M Housepian Professor of Neurological Surgery Research, Vice-Chairman and Professor of Neurological Surgery, Director of Brain Tumor Tissue Bank, Director of Bartoli Brain Tumor Laboratory, Department of Neurosurgery, Columbia University College of Physicians and Surgeons

Jeffrey N Bruce, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for the Advancement of Science, American Association of Neurological Surgeons, New York Academy of Sciences, North American Skull Base Society, Society of Neurological Surgeons, Society for Neuro-Oncology, American Society of Clinical Oncology, Congress of Neurological Surgeons, Pituitary Society

Disclosure: Received grant/research funds from NIH for other.

Coauthor(s)

Benjamin Kennedy, MD Columbia University College of Physicians and Surgeons

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Jules E Harris, MD, FACP, FRCPC Clinical Professor of Medicine, Section of Hematology/Oncology, University of Arizona College of Medicine, Arizona Cancer Center

Jules E Harris, MD, FACP, FRCPC is a member of the following medical societies: American Association for the Advancement of Science, American Society of Hematology, Central Society for Clinical and Translational Research, American Society of Clinical Oncology

Disclosure: Nothing to disclose.

Additional Contributors

Robert C Shepard, MD, FACP Associate Professor of Medicine in Hematology and Oncology at University of North Carolina at Chapel Hill; Vice President of Scientific Affairs, Therapeutic Expertise, Oncology, at PRA International

Robert C Shepard, MD, FACP is a member of the following medical societies: American Association for Cancer Research, American Association for Physician Leadership, European Society for Medical Oncology, Association of Clinical Research Professionals, American Federation for Clinical Research, Eastern Cooperative Oncology Group, Society for Immunotherapy of Cancer, American Medical Informatics Association, American College of Physicians, American Federation for Medical Research, American Medical Association, American Society of Hematology, Massachusetts Medical Society

Disclosure: Nothing to disclose.

Acknowledgements

We would like to acknowledge previous contributions to this chapter from Katharine Cronk, MD,PhD; Richard C Anderson, MD; Chris E Mandigo, MD; Andrew T Parsa MD, PhD; Patrick B Senatus, MD, PhD; and Allen Waziri, MD.

References
  1. Farrell CJ, Plotkin SR. Genetic causes of brain tumors: neurofibromatosis, tuberous sclerosis, von Hippel-Lindau, and other syndromes. Neurol Clin. 2007 Nov. 25(4):925-46, viii. [Medline].

  2. Hardell L, Carlberg M. Mobile phone and cordless phone use and the risk for glioma - Analysis of pooled case-control studies in Sweden, 1997-2003 and 2007-2009. Pathophysiology. 2015 Mar. 22 (1):1-13. [Medline].

  3. Lahkola A, Auvinen A, Raitanen J, et al. Mobile phone use and risk of glioma in 5 North European countries. Int J Cancer. 2007 Apr 15. 120(8):1769-75. [Medline].

  4. Inskip PD, Tarone RE, Hatch EE, et al. Cellular-telephone use and brain tumors. N Engl J Med. 2001 Jan 11. 344(2):79-86. [Medline].

  5. Weintraub MI. Glioblastoma multiforme and the cellular telephone scare. J Neurosurg. 1994 Jan. 80(1):169-70. [Medline].

  6. Kan P, Simonsen SE, Lyon JL, Kestle JR. Cellular phone use and brain tumor: a meta-analysis. J Neurooncol. 2008 Jan. 86(1):71-8. [Medline].

  7. International Electromagnetic Field (EMF) Collaborative. Cellphones and Brain Tumors: 15 Reasons for Concern. Science, Spin and the Truth Behind Interphone. Available at http://www.radiationresearch.org/pdfs/reasons_us.pdf. Accessed: August 13, 2015.

  8. Mukundan S, Holder C, Olson JJ. Neuroradiological assessment of newly diagnosed glioblastoma. J Neurooncol. 2008 Sep. 89(3):259-69. [Medline].

  9. Piroth MD, Holy R, Pinkawa M, et al. Prognostic impact of postoperative, pre-irradiation (18)F-fluoroethyl-l-tyrosine uptake in glioblastoma patients treated with radiochemotherapy. Radiother Oncol. 2011 May. 99(2):218-24. [Medline].

  10. Russell DS, Rubinstein LJ. Pathology of tumors of the nervous system. 6th ed. London, England: Edward Arnold; 1998. 426-52.

  11. Daumas-Duport C, Scheithauer B, O'Fallon J, Kelly P. Grading of astrocytomas. A simple and reproducible method. Cancer. 1988 Nov 15. 62(10):2152-65. [Medline].

  12. Kim TS, Halliday AL, Hedley-Whyte ET, Convery K. Correlates of survival and the Daumas-Duport grading system for astrocytomas. J Neurosurg. 1991 Jan. 74(1):27-37. [Medline].

  13. Pedersen PH, Rucklidge GJ, Mork SJ, et al. Leptomeningeal tissue: a barrier against brain tumor cell invasion. J Natl Cancer Inst. 1994 Nov 2. 86(21):1593-9. [Medline].

  14. Nagashima G, Suzuki R, Hokaku H, et al. Graphic analysis of microscopic tumor cell infiltration, proliferative potential, and vascular endothelial growth factor expression in an autopsy brain with glioblastoma. Surg Neurol. 1999 Mar. 51(3):292-9. [Medline].

  15. Pompili A, Calvosa F, Caroli F, et al. The transdural extension of gliomas. J Neurooncol. 1993 Jan. 15(1):67-74. [Medline].

  16. Brat DJ, Prayson RA, Ryken TC, Olson JJ. Diagnosis of malignant glioma: role of neuropathology. J Neurooncol. 2008 Sep. 89(3):287-311. [Medline].

  17. Lampl Y, Eshel Y, Gilad R, Sarova-Pinchas I. Glioblastoma multiforme with bone metastase and cauda equina syndrome. J Neurooncol. 1990 Apr. 8(2):167-72. [Medline].

  18. Hulbanni S, Goodman PA. Glioblastoma multiforme with extraneural metastases in the absence of previous surgery. Cancer. 1976 Mar. 37(3):1577-83. [Medline].

  19. Hoffman HJ, Duffner PK. Extraneural metastases of central nervous system tumors. Cancer. 1985 Oct 1. 56(7 Suppl):1778-82. [Medline].

  20. Barnard RO, Geddes JF. The incidence of multifocal cerebral gliomas. A histologic study of large hemisphere sections. Cancer. 1987 Oct 1. 60(7):1519-31. [Medline].

  21. Batzdorf U, Malamud N. The Problem of Multicentric Gliomas. J Neurosurg. 1963 Feb. 20:122-36. [Medline].

  22. Pasquier B, Pasquier D, N'Golet A, Panh MH, Couderc P. Extraneural metastases of astrocytomas and glioblastomas: clinicopathological study of two cases and review of literature. Cancer. 1980 Jan 1. 45(1):112-25. [Medline].

  23. Preusser M, de Ribaupierre S, Wohrer A, et al. Current concepts and management of glioblastoma. Ann Neurol. 2011 Jul. 70(1):9-21. [Medline].

  24. Sathornsumetee S, Reardon DA, Desjardins A, Quinn JA, Vredenburgh JJ, Rich JN. Molecularly targeted therapy for malignant glioma. Cancer. 2007 Jul 1. 110(1):13-24. [Medline].

  25. Furnari FB, Fenton T, Bachoo RM, et al. Malignant astrocytic glioma: genetics, biology, and paths to treatment. Genes Dev. 2007 Nov 1. 21(21):2683-710. [Medline]. [Full Text].

  26. Keime-Guibert F, Chinot O, Taillandier L, et al. Radiotherapy for glioblastoma in the elderly. N Engl J Med. 2007 Apr 12. 356(15):1527-35. [Medline]. [Full Text].

  27. Roa W, Brasher PM, Bauman G, et al. Abbreviated course of radiation therapy in older patients with glioblastoma multiforme: a prospective randomized clinical trial. J Clin Oncol. 2004 May 1. 22(9):1583-8. [Medline]. [Full Text].

  28. Glantz M, Chamberlain M, Liu Q, Litofsky NS, Recht LD. Temozolomide as an alternative to irradiation for elderly patients with newly diagnosed malignant gliomas. Cancer. 2003 May 1. 97(9):2262-6. [Medline].

  29. Scott J, Tsai YY, Chinnaiyan P, Yu HH. Effectiveness of radiotherapy for elderly patients with glioblastoma. Int J Radiat Oncol Biol Phys. 2011 Sep 1. 81(1):206-10. [Medline].

  30. Malmstrom A, Gronberg BH, Marosi C, et al; Nordic Clinical Brain Tumour Study Group (NCBTSG). Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: the Nordic randomised, phase 3 trial. Lancet Oncol. 2012 Sep. 13(9):916-26. [Medline].

  31. Waugh MG. Chromosomal Instability and Phosphoinositide Pathway Gene Signatures in Glioblastoma Multiforme. Mol Neurobiol. 2014 Dec 15. [Medline].

  32. von Deimling A, Louis DN, von Ammon K, et al. Association of epidermal growth factor receptor gene amplification with loss of chromosome 10 in human glioblastoma multiforme. J Neurosurg. 1992 Aug. 77(2):295-301. [Medline].

  33. Ohgaki H, Kleihues P. Genetic pathways to primary and secondary glioblastoma. Am J Pathol. 2007 May. 170(5):1445-53. [Medline]. [Full Text].

  34. Wong AJ, Ruppert JM, Bigner SH, et al. Structural alterations of the epidermal growth factor receptor gene in human gliomas. Proc Natl Acad Sci U S A. 1992 Apr 1. 89(7):2965-9. [Medline]. [Full Text].

  35. Liang BC, Thornton AF Jr, Sandler HM, Greenberg HS. Malignant astrocytomas: focal tumor recurrence after focal external beam radiation therapy. J Neurosurg. 1991 Oct. 75(4):559-63. [Medline].

  36. Hochberg FH, Pruitt A. Assumptions in the radiotherapy of glioblastoma. Neurology. 1980 Sep. 30(9):907-11. [Medline].

  37. Shapiro WR, Green SB, Burger PC, et al. Randomized trial of three chemotherapy regimens and two radiotherapy regimens and two radiotherapy regimens in postoperative treatment of malignant glioma. Brain Tumor Cooperative Group Trial 8001. J Neurosurg. 1989 Jul. 71(1):1-9. [Medline].

  38. Duerr EM, Rollbrocker B, Hayashi Y, et al. PTEN mutations in gliomas and glioneuronal tumors. Oncogene. 1998 Apr 30. 16(17):2259-64. [Medline].

  39. Warren KE, Gururangan S, Geyer JR, McLendon RE, Poussaint TY, Wallace D, et al. A phase II study of O6-benzylguanine and temozolomide in pediatric patients with recurrent or progressive high-grade gliomas and brainstem gliomas: a Pediatric Brain Tumor Consortium study. J Neurooncol. 2012 Feb. 106 (3):643-9. [Medline].

  40. Kleihues P, Burger PC, Cavenee WK. Glioblastoma. WHO Classification: Pathology and genetics of tumors of the nervous system. 1st ed. Lyon, France: International Agency for Research on Cancers; 1997. 16-24.

  41. Chi AS, Wen PY. Inhibiting kinases in malignant gliomas. Expert Opin Ther Targets. 2007 Apr. 11(4):473-96. [Medline].

  42. Duda DG, Jain RK, Willett CG. Antiangiogenics: the potential role of integrating this novel treatment modality with chemoradiation for solid cancers. J Clin Oncol. 2007 Sep 10. 25(26):4033-42. [Medline]. [Full Text].

  43. Fisher JL, Schwartzbaum JA, Wrensch M, Wiemels JL. Epidemiology of brain tumors. Neurol Clin. 2007 Nov. 25(4):867-90, vii. [Medline].

  44. Caccamo DV, Rubenstein LJ. Tumors: Applications of immunohistochemical methods. Neuropathology: The diagnostic approach. St Louis, Mo: Mosby-Year Book; 1997. 193-218.

  45. 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. 2009 May. 10(5):459-66. [Medline].

  46. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005 Mar 10. 352(10):987-96. [Medline]. [Full Text].

  47. Chamberlain MC, Kormanik PA. Practical guidelines for the treatment of malignant gliomas. West J Med. 1998 Feb. 168(2):114-20. [Medline]. [Full Text].

  48. Wernicke AG, Edgar MA, Lavi E, et al. Prostate-specific membrane antigen as a potential novel vascular target for treatment of glioblastoma multiforme. Arch Pathol Lab Med. 2011 Nov. 135(11):1486-9. [Medline].

  49. [Guideline] Olson JJ, Nayak L, Ormond DR, Wen PY, Kalkanis SN, AANS/CNS Joint Guidelines Committee. The role of cytotoxic chemotherapy in the management of progressive glioblastoma : a systematic review and evidence-based clinical practice guideline. J Neurooncol. 2014 Jul. 118 (3):501-55. [Medline].

  50. Barker FG, Prados MD, Chang SM, et al. Radiation response and survival time in patients with glioblastoma multiforme. J Neurosurg. 1996 Mar. 84(3):442-8. [Medline].

  51. Leibel SA, Scott CB, Loeffler JS. Contemporary approaches to the treatment of malignant gliomas with radiation therapy. Semin Oncol. 1994 Apr. 21(2):198-219. [Medline].

  52. Buatti J, Ryken TC, Smith MC, et al. Radiation therapy of pathologically confirmed newly diagnosed glioblastoma in adults. J Neurooncol. 2008 Sep. 89(3):313-37. [Medline].

  53. Walker MD, Alexander E Jr, Hunt WE, et al. Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas. A cooperative clinical trial. J Neurosurg. 1978 Sep. 49(3):333-43. [Medline].

  54. Halperin EC, Bruger PC. Conventional external beam radiotherapy for central nervous system malignancies. Frank BD, ed. Symposium on Neuro-Oncology. 4th ed. New York, NY: Neurologic Clinics; 1985. Vol 3: 867-82.

  55. Waters JD, Rose B, Gonda DD, et al. Immediate post-operative brachytherapy prior to irradiation and temozolomide for newly diagnosed glioblastoma. J Neurooncol. 2013 Jul. 113(3):467-77. [Medline].

  56. Stupp R, Hegi ME, Gilbert MR, Chakravarti A. Chemoradiotherapy in malignant glioma: standard of care and future directions. J Clin Oncol. 2007 Sep 10. 25(26):4127-36. [Medline].

  57. Rodrigus P. Motexafin gadolinium: a possible new radiosensitiser. Expert Opin Investig Drugs. 2003 Jul. 12(7):1205-10. [Medline].

  58. Butowski NA, Sneed PK, Chang SM. Diagnosis and treatment of recurrent high-grade astrocytoma. J Clin Oncol. 2006 Mar 10. 24(8):1273-80. [Medline].

  59. Combs SE, Thilmann C, Edler L, Debus J, Schulz-Ertner D. Efficacy of fractionated stereotactic reirradiation in recurrent gliomas: long-term results in 172 patients treated in a single institution. J Clin Oncol. 2005 Dec 1. 23(34):8863-9. [Medline].

  60. Tsao MN, Mehta MP, Whelan TJ, et al. The American Society for Therapeutic Radiology and Oncology (ASTRO) evidence-based review of the role of radiosurgery for malignant glioma. Int J Radiat Oncol Biol Phys. 2005 Sep 1. 63(1):47-55. [Medline].

  61. [Guideline] Ryu S, Buatti JM, Morris A, Kalkanis SN, Ryken TC, Olson JJ, et al. The role of radiotherapy in the management of progressive glioblastoma : a systematic review and evidence-based clinical practice guideline. J Neurooncol. 2014 Jul. 118 (3):489-99. [Medline].

  62. Kornblith PL. The role of cytotoxic chemotherapy in the treatment of malignant brain tumors. Surg Neurol. 1995 Dec. 44(6):551-2. [Medline].

  63. Kornblith PL, Walker M. Chemotherapy for malignant gliomas [published erratum appears in J Neurosurg 1988 Oct;69(4):645]. J Neurosurg. 1988 Jan. 68(1):1-17. [Medline].

  64. Lesser GJ, Grossman S. The chemotherapy of high-grade astrocytomas. Semin Oncol. 1994 Apr. 21(2):220-35. [Medline].

  65. Levin VA. Chemotherapy of primary brain tumors. Frank BD, ed. Symposium on Neuro-Oncology. 4th ed. New York, NY: Neurologic Clinics; 1985. Vol 3: 855-66.

  66. 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. Int J Radiat Oncol Biol Phys. 1990 Feb. 18(2):321-4. [Medline].

  67. Fadul CE, Wen PY, Kim L, Olson JJ. Cytotoxic chemotherapeutic management of newly diagnosed glioblastoma multiforme. J Neurooncol. 2008 Sep. 89(3):339-57. [Medline].

  68. Fine HA, Dear KB, Loeffler JS, Black PM, Canellos GP. Meta-analysis of radiation therapy with and without adjuvant chemotherapy for malignant gliomas in adults. Cancer. 1993 Apr 15. 71(8):2585-97. [Medline].

  69. Stewart LA. Chemotherapy in adult high-grade glioma: a systematic review and meta-analysis of individual patient data from 12 randomised trials. Lancet. 2002 Mar 23. 359(9311):1011-8. [Medline].

  70. Westphal M, Ram Z, Riddle V, Hilt D, Bortey E. Gliadel wafer in initial surgery for malignant glioma: long-term follow-up of a multicenter controlled trial. Acta Neurochir (Wien). 2006 Mar. 148(3):269-75; discussion 275. [Medline].

  71. Gutenberg A, Bock HC, Bruck W, et al. MGMT promoter methylation status and prognosis of patients with primary or recurrent glioblastoma treated with carmustine wafers. Br J Neurosurg. 2013 Dec. 27(6):772-8. [Medline].

  72. Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005 Mar 10. 352(10):997-1003. [Medline]. [Full Text].

  73. Hegi ME, Liu L, Herman JG, et al. Correlation of O6-methylguanine methyltransferase (MGMT) promoter methylation with clinical outcomes in glioblastoma and clinical strategies to modulate MGMT activity. J Clin Oncol. 2008 Sep 1. 26(25):4189-99. [Medline].

  74. Broniscer A, Gururangan S, MacDonald TJ, et al. Phase I trial of single-dose temozolomide and continuous administration of o6-benzylguanine in children with brain tumors: a pediatric brain tumor consortium report. Clin Cancer Res. 2007 Nov 15. 13(22 Pt 1):6712-8. [Medline]. [Full Text].

  75. Kaiser MG, Parsa AT, Fine RL, Hall JS, Chakrabarti I, Bruce JN. Tissue distribution and antitumor activity of topotecan delivered by intracerebral clysis in a rat glioma model. Neurosurgery. 2000 Dec. 47(6):1391-8; discussion 1398-9. [Medline].

  76. Bruce JN, Falavigna A, Johnson JP, et al. Intracerebral clysis in a rat glioma model. Neurosurgery. 2000 Mar. 46(3):683-91. [Medline].

  77. Lopez KA, Waziri AE, Canoll PD, Bruce JN. Convection-enhanced delivery in the treatment of malignant glioma. Neurol Res. 2006 Jul. 28(5):542-8. [Medline].

  78. 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. The Polymer-brain Tumor Treatment Group. Lancet. 1995 Apr 22. 345(8956):1008-12. [Medline].

  79. Bota DA, Desjardins A, Quinn JA, Affronti ML, Friedman HS. Interstitial chemotherapy with biodegradable BCNU (Gliadel) wafers in the treatment of malignant gliomas. Ther Clin Risk Manag. 2007 Oct. 3(5):707-15. [Medline]. [Full Text].

  80. FDA. Avastin Approval History. U.S. Food and Drug Administration. Available at http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/125085s0169lbl.pdf. Accessed: October 22, 2015.

  81. Vredenburgh JJ, Desjardins A, Herndon JE 2nd, et al. Phase II trial of bevacizumab and irinotecan in recurrent malignant glioma. Clin Cancer Res. 2007 Feb 15. 13(4):1253-9. [Medline]. [Full Text].

  82. Vredenburgh JJ, Desjardins A, Herndon JE 2nd, et al. Bevacizumab plus irinotecan in recurrent glioblastoma multiforme. J Clin Oncol. 2007 Oct 20. 25(30):4722-9. [Medline].

  83. Cloughesy TF, Prados MD, Wen PY. A phase II, randomized, non-comparative clinical trial of the effect of bevacizumab (BV) alone or in combinationwith irinotecan (CPT) on 6-month progressionfree survival (PFS6) in recurrent, treatment-refractory glioblastoma (GBM). J Clin Oncol. 2008. 26:Suppl:91s.

  84. Rich JN, Rasheed BK, Yan H. EGFR mutations and sensitivity to gefitinib. N Engl J Med. 2004 Sep 16. 351(12):1260-1; author reply 1260-1. [Medline].

  85. Rich JN, Reardon DA, Peery T, Dowell JM, Quinn JA, Penne KL. Phase II trial of gefitinib in recurrent glioblastoma. J Clin Oncol. 2004 Jan 1. 22(1):133-42. [Medline]. [Full Text].

  86. Mellinghoff IK, Wang MY, Vivanco I, Haas-Kogan DA, Zhu S, Dia EQ. Molecular determinants of the response of glioblastomas to EGFR kinase inhibitors. N Engl J Med. 2005 Nov 10. 353(19):2012-24. [Medline]. [Full Text].

  87. Fulci G, Chiocca EA. The status of gene therapy for brain tumors. Expert Opin Biol Ther. 2007 Feb. 7(2):197-208. [Medline]. [Full Text].

  88. Reardon DA, Akabani G, Coleman RE, et al. Salvage radioimmunotherapy with murine iodine-131-labeled antitenascin monoclonal antibody 81C6 for patients with recurrent primary and metastatic malignant brain tumors: phase II study results. J Clin Oncol. 2006 Jan 1. 24(1):115-22. [Medline].

  89. Mamelak AN, Rosenfeld S, Bucholz R, et al. Phase I single-dose study of intracavitary-administered iodine-131-TM-601 in adults with recurrent high-grade glioma. J Clin Oncol. 2006 Aug 1. 24(22):3644-50. [Medline].

  90. Ferguson S, Lesniak MS. Convection enhanced drug delivery of novel therapeutic agents to malignant brain tumors. Curr Drug Deliv. 2007 Apr. 4(2):169-80. [Medline].

  91. Quang TS, Brady LW. Radioimmunotherapy as a novel treatment regimen: (125)I-labeled monoclonal antibody 425 in the treatment of high-grade brain gliomas. Int J Radiat Oncol Biol Phys. 2004 Mar 1. 58(3):972-5. [Medline].

  92. Rich JN, Bigner DD. Development of novel targeted therapies in the treatment of malignant glioma. Nat Rev Drug Discov. 2004 May. 3(5):430-46. [Medline]. [Full Text].

  93. Nelson R. Bevacizumab May Boost Survival in Glioblastoma. Medscape Medical News. Available at http://www.medscape.com/viewarticle/809962. Accessed: September 5, 2013.

  94. Johnson DR, Leeper HE, Uhm JH. Glioblastoma survival in the United States improved after Food and Drug Administration approval of bevacizumab: a population-based analysis. Cancer. 2013 Oct 1. 119(19):3489-95. [Medline].

  95. Nelson R. FDA Expands Indication for Optune Device in Glioblastoma. Medscape Medical News. Available at http://www.medscape.com/viewarticle/852196. October 6, 2015; Accessed: December 11, 2015.

  96. Ammirati M, Vick N, Liao YL, et al. Effect of the extent of surgical resection on survival and quality of life in patients with supratentorial glioblastomas and anaplastic astrocytomas. Neurosurgery. 1987 Aug. 21(2):201-6. [Medline].

  97. Lacroix M, Abi-Said D, Fourney DR, et al. A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. J Neurosurg. 2001 Aug. 95(2):190-8. [Medline].

  98. Keles GE, Anderson B, Berger MS. The effect of extent of resection on time to tumor progression and survival in patients with glioblastoma multiforme of the cerebral hemisphere. Surg Neurol. 1999 Oct. 52(4):371-9. [Medline].

  99. Sanai N, Berger MS. Glioma extent of resection and its impact on patient outcome. Neurosurgery. 2008 Apr. 62(4):753-64; discussion 264-6. [Medline].

  100. Fadul C, Wood J, Thaler H, et al. Morbidity and mortality of craniotomy for excision of supratentorial gliomas. Neurology. 1988 Sep. 38(9):1374-9. [Medline].

  101. Ryken TC, Frankel B, Julien T, Olson JJ. Surgical management of newly diagnosed glioblastoma in adults: role of cytoreductive surgery. J Neurooncol. 2008 Sep. 89(3):271-86. [Medline].

  102. Ciric I, Rovin R, Cozzens JW. Role of surgery in the treatment of malignant cerebral gliomas. Malignant Cerebral Glioma. Park Ridge, Ill: American Association of Neurological Surgeons; 1990. 141-53.

  103. El Hindy N, Bachmann HS, Lambertz et al. Association of the CC genotype of the regulatory BCL2 promoter polymorphism (-938C>A) with better 2-year survival in patients with glioblastoma multiforme. J Neurosurg. 2011 Jun. 114(6):1631-9. [Medline].

  104. Coffey RJ, Lunsford LD, Taylor FH. Survival after stereotactic biopsy of malignant gliomas. Neurosurgery. 1988 Mar. 22(3):465-73. [Medline].

  105. Jakola AS, Unsgard G, Solheim O. Quality of life in patients with intracranial gliomas: the impact of modern image-guided surgery. J Neurosurg. 2011 Jun. 114(6):1622-30. [Medline].

  106. Glantz MJ, Cole BF, Forsyth PA, et al. Practice parameter: anticonvulsant prophylaxis in patients with newly diagnosed brain tumors. Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2000 May 23. 54(10):1886-93. [Medline]. [Full Text].

  107. Scott JN, Rewcastle NB, Brasher PM, et al. Long-term glioblastoma multiforme survivors: a population-based study. Can J Neurol Sci. 1998 Aug. 25(3):197-201. [Medline].

  108. Sneed PK, Prados MD, McDermott MW, et al. Large effect of age on the survival of patients with glioblastoma treated with radiotherapy and brachytherapy boost. Neurosurgery. 1995 May. 36(5):898-903; discussion 903-4. [Medline].

  109. Reuters Health Information. Extent of Resection Linked to Glioblastoma Outcome. Medscape [serial online]. Available at http://www.medscape.com/viewarticle/818424. Accessed: January 6, 2014.

  110. Salmon I, Dewitte O, Pasteels JL, et al. Prognostic scoring in adult astrocytic tumors using patient age, histopathological grade, and DNA histogram type. J Neurosurg. 1994 May. 80(5):877-83. [Medline].

  111. Black PM. Brain tumors. Part 1. N Engl J Med. 1991 May 23. 324(21):1471-6. [Medline].

  112. Newcomb EW, Cohen H, Lee SR, et al. Survival of patients with glioblastoma multiforme is not influenced by altered expression of p16, p53, EGFR, MDM2 or Bcl-2 genes. Brain Pathol. 1998 Oct. 8(4):655-67. [Medline].

  113. Kaur G, Bloch O, Jian BJ, et al. A critical evaluation of cystic features in primary glioblastoma as a prognostic factor for survival. J Neurosurg. 2011 Oct. 115(4):754-9. [Medline].

  114. Bouvier-Labit C, Chinot O, Ochi C, Gambarelli D, Dufour H, Figarella-Branger D. Prognostic significance of Ki67, p53 and epidermal growth factor receptor immunostaining in human glioblastomas. Neuropathol Appl Neurobiol. 1998 Oct. 24(5):381-8. [Medline].

  115. Burger PC, Heinz ER, Shibata T, Kleihues P. Topographic anatomy and CT correlations in the untreated glioblastoma multiforme. J Neurosurg. 1988 May. 68(5):698-704. [Medline].

  116. Burger PC, Vogel FS, Green SB, Strike TA. Glioblastoma multiforme and anaplastic astrocytoma. Pathologic criteria and prognostic implications. Cancer. 1985 Sep 1. 56(5):1106-11. [Medline].

  117. Chaichana KL, Jusue-Torres I, Navarro-Ramirez R, et al. Establishing percent resection and residual volume thresholds affecting survival and recurrence for patients with newly diagnosed intracranial glioblastoma. Neuro Oncol. 2014 Jan. 16(1):113-22. [Medline]. [Full Text].

  118. Devaux BC, O'Fallon JR, Kelly PJ. Resection, biopsy, and survival in malignant glial neoplasms. A retrospective study of clinical parameters, therapy, and outcome. J Neurosurg. 1993 May. 78(5):767-75. [Medline].

  119. Dropcho EJ, Soong SJ. The prognostic impact of prior low grade histology in patients with anaplastic gliomas: a case-control study. Neurology. 1996 Sep. 47(3):684-90. [Medline].

  120. Giordana MT, Bradac GB, Pagni CA, et al. Primary diffuse leptomeningeal gliomatosis with anaplastic features. Acta Neurochir (Wien). 1995. 132(1-3):154-9. [Medline].

  121. Glantz MJ, Hoffman JM, Coleman RE, et al. Identification of early recurrence of primary central nervous system tumors by [18F]fluorodeoxyglucose positron emission tomography. Ann Neurol. 1991 Apr. 29(4):347-55. [Medline].

  122. Jafri NF, Clarke JL, Weinberg V, Barani IJ, Cha S. Relationship of glioblastoma multiforme to the subventricular zone is associated with survival. Neuro Oncol. 2013 Jan. 15(1):91-6. [Medline]. [Full Text].

  123. Korkolopoulou P, Christodoulou P, Kouzelis K, et al. MDM2 and p53 expression in gliomas: a multivariate survival analysis including proliferation markers and epidermal growth factor receptor. Br J Cancer. 1997. 75(9):1269-78. [Medline]. [Full Text].

  124. Lang FF, Miller DC, Koslow M, Newcomb EW. Pathways leading to glioblastoma multiforme: a molecular analysis of genetic alterations in 65 astrocytic tumors. J Neurosurg. 1994 Sep. 81(3):427-36. [Medline].

  125. Li J, Wang M, Won M, et al. Validation and simplification of the Radiation Therapy Oncology Group recursive partitioning analysis classification for glioblastoma. Int J Radiat Oncol Biol Phys. 2011 Nov 1. 81(3):623-30. [Medline].

  126. Libermann TA, Nusbaum HR, Razon N, et al. Amplification, enhanced expression and possible rearrangement of EGF receptor gene in primary human brain tumours of glial origin. Nature. 1985 Jan 10-18. 313(5998):144-7. [Medline].

  127. Ohgaki H, Kleihues P. Population-based studies on incidence, survival rates, and genetic alterations in astrocytic and oligodendroglial gliomas. J Neuropathol Exp Neurol. 2005 Jun. 64(6):479-89. [Medline].

  128. Pelloski CE, Ballman KV, Furth AF, et al. Epidermal growth factor receptor variant III status defines clinically distinct subtypes of glioblastoma. J Clin Oncol. 2007 Jun 1. 25(16):2288-94. [Medline]. [Full Text].

  129. Rich JN, Hans C, Jones B, et al. Gene expression profiling and genetic markers in glioblastoma survival. Cancer Res. 2005 May 15. 65(10):4051-8. [Medline]. [Full Text].

  130. Shiras A, Bhosale A, Shepal V, et al. A unique model system for tumor progression in GBM comprising two developed human neuro-epithelial cell lines with differential transforming potential and coexpressing neuronal and glial markers. Neoplasia. 2003 Nov-Dec. 5(6):520-32. [Medline]. [Full Text].

  131. Watanabe K, Tachibana O, Sata K, et al. Overexpression of the EGF receptor and p53 mutations are mutually exclusive in the evolution of primary and secondary glioblastomas. Brain Pathol. 1996 Jul. 6(3):217-23; discussion 23-4. [Medline].

 
Previous
Next
 
Axial CT scan without intravenous contrast. This image reveals a large right temporal intraaxial mass (glioblastoma multiforme [GBM]). Extensive surrounding edema is present, as demonstrated by the peritumoral hypodensity, and a moderate right-to-left midline shift can be noted. All of the radiologic studies in this article are of the same patient.
A T1-weighted axial MRI without intravenous contrast. This image demonstrates a hemorrhagic multicentric tumor (glioblastoma multiforme [GBM]) in the right temporal lobe. Effacement of the ventricular system is present on the right, and mild impingement of the right medial temporal lobe can be observed on the midbrain.
A T1-weighted axial MRI with intravenous contrast. Heterogenous enhancement of the lesion is present within the right temporal lobe. The hypointensity circumscribed within the enhancement is suggestive of necrosis. This radiologic appearance is typical of a multicentric glioblastoma multiforme (GBM).
A T1-weighted coronal MRI with intravenous contrast. This image demonstrates the lesion (glioblastoma multiforme [GBM]) within the medial temporal lobe and the stereotypical pattern of contrast enhancement.
A T1-weighted sagittal MRI with intravenous contrast in a patient with glioblastoma multiforme (GBM).
A T2-weighted axial MRI. The tumor (glioblastoma multiforme [GBM]) and surrounding white matter within the right temporal lobe show increased signal intensity compared to a healthy brain, suggesting extensive tumorigenic edema.
A fluid-attenuated inversion recovery (FLAIR) axial MRI. This image is similar to the T2-weighted image and demonstrates extensive edema in a patient with glioblastoma multiforme (GBM).
Histopathologic slide demonstrating a glioblastoma multiforme (GBM).
Magnetic resonance (MR) spectroscopy is representative of a glioblastoma multiforme (GBM).
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.