Neurologic Manifestations of Glioblastoma Multiforme Follow-up
- Author: ABM Salah Uddin, MD; Chief Editor: Stephen A Berman, MD, PhD, MBA more...
Further Outpatient Care
After the initial successful therapy, observe the patient regularly as an outpatient with neurologic examination and repeat MRI scans every 2 months with the chemotherapy cycles; continue every few months to follow tumor recurrence.
Further Inpatient Care
After the initial definitive treatment (surgical debulking) of glioblastoma multiforme (GBM), the patient may need further inpatient care during the ongoing radiation therapy. Chemotherapy usually is performed on an outpatient basis. Continuing outpatient follow-up care is necessary if the patient develops neurological deterioration such as acute motor weakness or depression of consciousness from the effects of therapy, increased intracranial pressure from vasogenic edema, or acute hydrocephalus from ventricular obstruction. Appropriate intervention depends on the nature of the problem (eg, steroid therapy for edema, shunting for hydrocephalus).
Inpatient & Outpatient Medications
No specific medications are recommended for GBM. However, as mentioned previously, patients may need symptomatic therapy with steroids or anticonvulsants.
Transfer requirements depend on the tumor location and its response to treatment. If the tumor is in a noneloquent area and no neurological deficit is present after treatment, the patient remains fully ambulatory. However, other patients may require assistance, such as a 3-pronged cane or a wheelchair, depending on the residual neurological deficit.
During continuing follow-up care, monitor the patient closely and treat appropriately any complications that may develop. These may be caused by ongoing treatment, such as radiation necrosis and chemotherapy-induced neuropathy, or by progression of the disease, such as recurrence or leptomeningeal spread.
With optimal treatment, the median survival of patients with glioblastoma is about 12 months. However, only 3-5% of patients survive for more than 3 years. The overall prognosis for GBM has changed little since the 1980s, despite major improvements in neuroimaging, neurosurgery, radiotherapy, and chemotherapy techniques. Although histologic grading remains the most important prognostic factor, other important prognostic factors include age at diagnosis and Karnofsky performance status (KPS). Consider the following:
Various studies demonstrated that patients with GBM who are younger than 40 years have an 18-month survival rate of 50%, while those aged 40-60 years have an 18-month survival rate of 20% and those older than 60 years have a rate of only 10%. In some series, age appears to be an even more important prognostic factor than histology.
The survival of patients with GBM decreases as KPS decreases. Patients with a KPS of more than 70 have an 18-month survival rate of 34%, while those with a KPS of less than 70 have an 18-month survival rate of 13%.
Additional factors such as extent of surgical resection, seizures as the initial presentation, and tumor location with superficial tumors have been variably associated with outcome.
A recent animal study in rats investigated the use of monoclonal antibodies 8H9 as interstitial infusion showed significant volumetric response and prolonged survival (54 d for untreated rats vs 120 d for treated rats) as a potential target therapy for high-grade gliomas. 
A study by Wang et al demonstrated that overexpression of EphA7 was predictive of adverse outcomes in patients with primary and recurrent glioblastoma multiforme, independent of microvascular density (MVD) expression. Moreover, high density of both MVD and EphA7 expression predicted the disease outcome more accurately than EphA7 alone. 
A study by Liang et al demonstrated that nuclear FABP7 was preferentially expressed in infiltrative gliomas only and associated with poor prognosis in EGFR-overexpressing glioblastoma. The study suggested that FABP7 immunoreactivity could be used to monitor the EGFR-overexpressed GBM progression. 
Studies are focusing attention on identifying molecular markers similar to anaplastic oligodendroglioma to predict response or resistance to specific treatments. One such interest is the expression of MGMT (O6 -methylguanine–DNA methyltransferase) gene. The protein product of this gene, 06 alkyl guanine DNA-alkyl-transferase (AGAT), is shown to be a major mechanism for tumor resistance to alkylating agents. Recent clinical trials for malignant gliomas now often include determination of MGMT expression status. Several other molecular markers, such as epidermal growth factor receptor, platelet-derived growth factor receptor, vascular endothelial growth factor receptor, loss of chromosome 10, mutation or loss of the p53 gene, expression of the YKL-40 gene, loss or mutation of PTEN gene, are being investigated.
Studies are also focusing on new targets such as receptor blockade. Glutamatergic system alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor-blocker talampanel, may be beneficial in this disease. In a recent study, talampanel was added to the standard radiation and temozolomide in adults with newly diagnosed glioblastoma to estimate the overall survival as well as talampanel toxicity as a secondary measure. The study concluded that talampanel was well tolerated and compared with European Organization for Research and Treatment of Cancer (EORTC) data, median survival seemed superior (20.3 vs 14.6 mo, respectively). Therefore, talampanel can be added to radiation therapy and temozolomide without significant additional toxicity.
During the course of diagnosis, treatment, and follow-up care, educate the patient and family about the course and prognosis of the tumor to help them cope with the physical and emotional burden. Set this goal during discussion with the patient in the presence of family members, nurses, physicians, social services, and spiritual services. In addition, frequent contacts, regular follow-up care, and involvement of support groups are necessary.
Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007 Aug. 114 (2):97-109. [Medline].
Seiz M, Nolte I, Pechlivanis I, et al. Far-distant metastases along the CSF pathway of glioblastoma multiforme during continuous low-dose chemotherapy with temozolomide and celecoxib. Neurosurg Rev. 2010 Jul. 33(3):375-81; discussion 381. [Medline].
Tuettenberg J, Grobholz R, Seiz M, et al. Recurrence pattern in glioblastoma multiforme patients treated with anti-angiogenic chemotherapy. J Cancer Res Clin Oncol. 2009 Sep. 135(9):1239-44. [Medline].
Buhl R, Barth H, Hugo HH, Hutzelmann A, Mehdorn HM. Spinal drop metastases in recurrent glioblastoma multiforme. Acta Neurochir (Wein). 1998;. 140(10):1001-5.
Hess KR, Broglio KR, Bondy ML. Adult glioma incidence trends in the United States, 1977-2000. Cancer. 2004 Nov 15. 101(10):2293-9. [Medline].
Hardell L, Carlberg M, Soderqvist F, Mild KH, Morgan LL. Long-term use of cellular phones and brain tumours: increased risk associated with use for > or =10 years. Occup Environ Med. 2007 Sep. 64(9):626-32. [Medline].
Pichlmeier U, Bink A, Schackert G, Stummer W. ALA Glioma Study Group. Resection and survival in glioblastoma multiforme: an RTOG recursive partitioninganalysis of ALA study patients. Neuro-Oncol. Oct 2008. (6):1025-34.
Preusser M, de Ribaupierre S, Wohrer A, et al. Current concepts and management of glioblastoma. Ann Neurol. 2011 Jul. 70(1):9-21. [Medline].
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].
Hatanaka H. Analysis of clinical results of long surviving brain tumor patients who underwent Boron-neutron-capture therapy with mercapto undeca hydrocarborate. Proceedings of the Xth International Congress of Neurosurgery, Acapulco Mexico. 1993 Oct 17-22.
Westphal M, Hilt DC, Bortey E, et al. A phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma. Neuro-oncol. 2003 Apr. 5(2):79-88. [Medline].
Darakchiev BJ, Albright RE, Breneman JC, Warnick RE. Safety and efficacy of permanent iodine-125 seed implants and carmustine wafers in patients with recurrent glioblastoma multiforme. J Neurosurg. 2008 Feb. 108(2):236-42. [Medline].
Hegi ME, Diserens AC, Gorlia T, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005 Mar 10. 352(10):997-1003. [Medline].
Iwamoto FM, Fine HA. Bevacizumab for malignant gliomas. Arch Neurol. 2010 Mar. 67(3):285-8. [Medline].
Perry JR, Belanger K, Mason WP, et al. Phase II trial of continuous dose-intense temozolomide in recurrent malignant glioma: RESCUE study. J Clin Oncol. 2010 Apr 20. 28(12):2051-7. [Medline].
Burkhardt JK, Riina H, Shin BJ, et al. Intra-arterial delivery of bevacizumab after blood-brain barrier disruption for the treatment of recurrent glioblastoma: progression-free survival and overall survival. World Neurosurg. 2012 Jan. 77(1):130-4. [Medline].
Rosati A, Tomassini A, Pollo B, Ambrosi C, Schwarz A, Padovani A. Epilepsy in cerebral glioma: timing of appearance and histological correlations. J Neurooncol. 2009 Jul. 93(3):395-400. [Medline].
Krex D, Klink B, Hartmann C, et al. Long-term survival with glioblastoma multiforme. Brain. 2007 Oct. 130(Pt 10):2596-606. [Medline].
Luther N, Cheung NK, Souliopoulos EP, et al. Interstitial infusion of glioma-targeted recombinant immunotoxin 8H9scFv-PE38. Mol Cancer Ther. 2010 Apr. 9(4):1039-46. [Medline].
Wang LF, Fokas E, Juricko J, et al. Increased expression of EphA7 correlates with adverse outcome in primary and recurrent glioblastoma multiforme patients. BMC Cancer. 2008 Mar 25. 8:79. [Medline]. [Full Text].
Liang Y, Bollen AW, Aldape KD, Gupta N. Nuclear FABP7 immunoreactivity is preferentially expressed in infiltrative glioma and is associated with poor prognosis in EGFR-overexpressing glioblastoma. BMC Cancer. 2006 Apr 19. 6:97. [Medline].
Wen PY, Fine HA, Black PM, et al. High-grade astrocytomas. Neurol Clin. 1995 Nov. 13(4):875-900. [Medline].
Wallner KE, Galicich JH, Krol G, et al. Patterns of failure following treatment for glioblastoma multiforme and anaplastic astrocytoma. Int J Radiat Oncol Biol Phys. 1989 Jun. 16(6):1405-9. [Medline].
Westermark B, Nister M. Molecular genetics of human glioma. Curr Opin Oncol. 1995 May. 7(3):220-5. [Medline].
Bruner JM. Neuropathology of malignant gliomas. Semin Oncol. 1994 Apr. 21(2):126-38. [Medline].
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].
Byrne TN. Imaging of gliomas. Semin Oncol. 1994 Apr. 21(2):162-71. [Medline].
Clarke J, Butowski N, Chang S. Recent advances in therapy for glioblastoma. Arch Neurol. 2010 Mar. 67(3):279-83. [Medline].
Colombo F, Barzon L, Franchin E, et al. Combined HSV-TK/IL-2 gene therapy in patients with recurrent glioblastoma multiforme: biological and clinical results. Cancer Gene Ther. 2005 Oct. 12(10):835-48. [Medline].
Davis ME, Stoiber AM. Glioblastoma multiforme: enhancing survival and quality of life. Clin J Oncol Nurs. 2011 Jun. 15(3):291-7. [Medline].
Eagan RT, Scott M. Evaluation of prognostic factors in chemotherapy of recurrent brain tumors. J Clin Oncol. 1983 Jan. 1(1):38-44. [Medline].
Gilbert MR, Loghin M. The Treatment of Malignant Gliomas. Curr Treat Options Neurol. 2005 Jul. 7(4):293-303. [Medline].
Green SB, Byar DP, Walker MD, et al. Comparisons of carmustine, procarbazine, and high-dose methylprednisolone as additions to surgery and radiotherapy for the treatment of malignant glioma. Cancer Treat Rep. 1983 Feb. 67(2):121-32. [Medline].
Grossman SA, Ye X, Chamberlain M, et al. Talampanel with standard radiation and temozolomide in patients with newly diagnosed glioblastoma: a multicenter phase II trial. J Clin Oncol. 2009 Sep 1. 27(25):4155-61. [Medline]. [Full Text].
Grossman SA, Ye X, Piantadosi S, et al. Survival of patients with newly diagnosed glioblastoma treated with radiation and temozolomide in research studies in the United States. Clin Cancer Res. 2010 Apr 15. 16(8):2443-9. [Medline]. [Full Text].
Kaye AH, Laws ER Jr. Brain Tumors: An Encyclopedic Approach. New York, NY: Churchill Livingtone; 1995. 449-77.
Kleihus P, Cavenee WK. Pathology and Genetics: Tumors of the Nervous System. Lyon, France: IARC Press; 2000. 56-64.
Lakka SS, Rajan M, Gondi C, et al. Adenovirus-mediated expression of antisense MMP-9 in glioma cells inhibits tumor growth and invasion. Oncogene. 2002 Nov 14. 21(52):8011-9. [Medline].
Leibel SA, Scott CB, Pajak TF. The management of malignant gliomas with radiation therapy: Therapeutic results and research strategies. Semin Radiat Oncol. 1991. 1:32-49.
Loeffler JS, Alexander E, Wen PY, et al. Results of stereotactic brachytherapy used in the initial management of patients with glioblastoma. J Natl Cancer Inst. 1990 Dec 19. 82(24):1918-21. [Medline].
Lu KV, Jong KA, Kim GY, et al. Differential induction of glioblastoma migration and growth by two forms of pleiotrophin. J Biol Chem. 2005 Jul 22. 280(29):26953-64. [Medline].
Macdonald DR. Adjuvant chemotherapy for brain tumor. Semin Radiat Oncol. 1991. 1:54-61.
Pallasch CP, Struss AK, Munnia A, et al. Autoantibodies against GLEA2 and PHF3 in glioblastoma: tumor-associated autoantibodies correlated with prolonged survival. Int J Cancer. 2005 Nov 10. 117(3):456-9. [Medline].
Schold SC, Burger PC, Minna JD, et al. Primary Tumors of the Brain and Spinal Cord. Boston, Mass: Butterworth-Heinemann; 1997. 41-59.
Sipos EP, Brem H. New delivery systems for brain tumor therapy. Neurol Clin. 1995 Nov. 13(4):813-25. [Medline].
Stupp R, Mason WP. Concomitant and adjuvant temozolomide and radiotherapy for newly diagnosed glioblastoma multiforme. Conclusive results of randomized phase III trial by the EORTC brain and RT Groups and NCIC clinical trials group. American Society of Clinical Oncology. 2004. 23(1):
Valk PE, Budinger TF, Levin VA, et al. PET of malignant cerebral tumors after interstitial brachytherapy. Demonstration of metabolic activity and correlation with clinical outcome. J Neurosurg. 1988 Dec. 69(6):830-8. [Medline].
Vile R, Russell SJ. Gene transfer technologies for the gene therapy of cancer. Gene Ther. 1994 Mar. 1(2):88-98. [Medline].