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  • Print publication year: 2008
  • Online publication date: August 2009

11 - High-grade gliomas

Summary

Introduction

After more than 30 years of intensive clinical and laboratory research, high-grade gliomas (HGG) [glioblastoma multiforme (GBM), anaplastic astrocytoma (AAs), anaplastic oligodendroglioma, and anaplastic mixed glioma] retain a well-deserved reputation for poor response to therapy, rapid tumor recurrence, and short overall survival. Currently available treatments, including surgery, cranial irradiation, and chemotherapy, extend survival measurably, but are almost always non-curative, and are associated with substantial toxicity. In this context, maintaining good quality of life has assumed an increasingly prominent role in selecting treatments and in designing clinical trials (Report of the Brain Tumor Progress Review Group, 2005; Taphoorn et al., 2005), and the paradigm of compressing morbidity and “rectangularizing” the survival curve (Fries, 1980) is increasingly seen as the central goal of cancer therapy (Figure 11.1).

Traditionally, myelosuppression and its attendant problems have been the dose-limiting and most important toxicities of radiation and chemotherapy. In the late 1990s and early 2000s, however, the availability of colony stimulating factors, and dramatic improvements in transfusion medicine, antibiotic therapy, and supportive care made the bone marrow more robust. Today, a strong case can be made that the nervous system has replaced the bone marrow as the most important dose-limiting end organ for cancer therapy in general, and for therapy directed at central nervous system tumors in particular. For the large number of children (Bhat et al., 2005; Lannering et al., 1990; Packer et al., 2003) and for the still small but growing number of adult long-term survivors of malignant primary brain tumors, the nervous system rather than the hematopoietic system more frequently affects the quality of survival and the economic productivity of survivors.

REFERENCES
Abdallah, NM-BB, Slomianka, L, Lipp, H-P (2007). Reversible effect of X-irradiation on proliferation, neurogenesis, and cell death in the dentate gyrus of adult mice. Hippocampus 17(12): 1230–1240.
Archibald, YM, Lulnn, D, Ruttan, et al. (1994). Cognitive functioning in long-term survivors of high-grade glioma. J Neurosurg 80: 247–253.
Armstrong, C, Ruffer, J, Corn, B, DeVires, K, Mollman, J (1995). Biphasic patterns of memory deficits following moderate-dose partial-brain irradiation: neuropsychologic outcome and proposed mechanisms. J Clin Oncol 13: 2263–2271.
Bartolomei, F, Bosma, I, Klein, Met al. (2006). How do brain tumors alter functional connectivity? A magnetoencephalography study. Ann Neurol 59: 128–138.
Beck, AT, Steer, RA (1993). Beck Depression Inventory. San Antonio, TX: Psychological Corp.
Beck, AT, Brown, G, Epstein, N, Steer, RA (1990). An inventory for measuring clinical anxiety: psychometric properties. J Consult Clin Psychol 56: 893–897.
Belka, C, Budach, W, Kortmann, RDet al. (2001). Radiation induced CNS toxicity – molecular and cellular mechanisms. Br J Cancer 85: 1233–1239.
Benedict, RHB, Schretlen, D, Groninger, Let al. (1998). Hopkins Verbal Learning Test-Revised: normative data and analysis of inter-form and test-retest reliability. Clin Neuropsychol 12: 43–55.
Benton, AD (1968). Differential behavioral effects in frontal lobe disease. Neuropsychologia 6: 53–60.
Benton, AL, Hamsher, K de S (1989). Multilingual Aphasia Examination. Iowa City, IA: AJA Associates.
Bhat, , Goodwin, TL, Burwinkle, TMet al. (2005). Profile of daily life in children with brain tumors: an assessment of health-related quality of life. J Clin Oncol 23: 5493–5500.
Bosma, I, Vos, MJ, Heimans, JJet al. (2007). The course of neurocognitive functioning in high-grade glioma patients. Neurooncology 9: 53–62.
Brown, PD, Buckner, JC, O'Fallon, JRet al. (2003). Effects of radiotherapy on cognitive function in patients with low-grade glioma measured by the Folstein mini-mental state examination. J Clin Oncol 21: 2519–2524.
Brown, PD, Jensen, AW, Felten, SJet al. (2006). Detrimental effects of tumor progression on cognitive function of patients with high-grade glioma. J Clin Oncol 24: 5427–5433.
Bruera, E, Kuehn, N, Miller, M, Selmser, P, Macmillan, K (1991). The Edmonton Symptom Assessment System (ESAS): a simple method for the assessment of palliative care patients. J Palliative Care 7: 6–9.
Bruera, E, Valero, V, Driver, Let al. (2006). Patient-controlled methylphenidate for cancer fatigue: a double-blind, randomized, placebo-controlled trial. J Clin Oncol 24: 2073–2078.
Bruera, E, Osta, BE, Valero, Vet al. (2007). Donepezil for cancer fatigue: a double-blind, randomized, placebo-controlled trial. J Clin Oncol 25: 3475–3481.
Brunner, R, Schaefer, D, Hess, K, Parzer, P, Resch, F, Schwab, S (2006). Effect of high-dose cortisol on memory functions. Ann N Y Acad Sci 1071: 434–437.
Carson, KA, Grossman, SA, Fisher, JD, Shaw, EG (2007). Prognostic factors for survival in adult patients with recurrent gliomas enrolled onto the new approaches to brain tumor therapy CNS consortium phase I and II clinical trials. J Clin Oncol 25: 2601–2606.
Cavaliere, R, Schiff, D (2006). Neurologic toxicities of cancer therapies. Curr Neurol Neurosci Rep 6: 218–226.
Cella, DF, Tulsky, DS, Gray, Get al. (1993). The functional assessment of cancer therapy scale: development and validation of the general measure. J Clin Oncol 11: 570–577.
,Central Brain Tumor Registry of the United States (2005). Primary Brain Tumors in the United States Statistical Report 1998–2002 (pp. 8–50). Chicago, IL: Central Brain Tumor Registry of the United States.
Crossen, JR, Garwood, D, Glatstein, Eet al. (1994). Neurobehavioral sequelae of cranial irradiation in adults: a review of radiation-induced encephalopathy. J Clin Oncol 12: 627–642.
Cull, A, Hay, C, Love, SBet al. (1996). What do cancer patients mean when they complain of concentration and memory problems?Br J Cancer 74: 1674–1679.
Curran, WJ, Scott, CB, Horton, Jet al. (1993). Recursive partitioning analysis of prognostic factors in three Radiation Therapy Oncology Group malignant gliomas trials. J Natl Cancer Inst 85: 704–710.
Davies, E, Clarke, C (2005). Views of bereaved relatives about quality of survival after radiotherapy for malignant cerebral glioma. J Neurol Neurosurg Psychiatry 76: 555–561.
DeAngelis, LM, Delattre, J-Y, Posner, JB (1989). Radiation-induced dementia in patients cured of brain metastases. Neurology 39: 789–796.
Folstein, MF, Folstein, SE, McHugh, PR (1975). “Mini-mental state”: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12: 189–198.
Fries, JF (1980). Aging, natural death, and the compression of morbidity. N Engl J Med 303: 130–135.
Gill, D, Hatcher, S (2000). Antidepressants for depression in medical illness. Cochrane Database Syst Rev 4: CD001312.
Hamilton, M (1959). The assessment of anxiety state by rating. Br J Med Psychol 32: 50–55.
Hamilton, M (1960). A rating scale for depression. J Neurol Neurosurg Psychiatry 23: 56–62.
Hildebrand, J (2006). Neurological complications of cancer chemotherapy. Curr Opin Oncol 18: 321–324.
Hochberg, FH, Slotnick, B (1980). Neuropsychologic impairment in astrocytoma survivors. Neurology 30: 172–177.
Imperato, JP, Palelogos, NA, Vick, NA (1990). Effects of treatment on long-term survivors with malignant astrocytomas. Ann Neurol 28: 818–822.
Jagaroo, V, Rogers, MP, Black, PM (2000). Allocentric visuospatial processing in patients with cerebral gliomas: a neurocognitive assessment. J Neurooncol 49: 235–248.
Jemal, A, Siegel, R, Ward, et al. (2007). Cancer statistics, 2008. CA Cancer J Clin 58: 71–96.
Johnson, MR, Hageboutros, A, Wand, K, High, L, Smith, JB, Diasio, RB (1999). Life-threatening toxicity in a dihydropyrimidine dehydrogenase-deficient patient after treatment with topical 5-fluorouracil. Clin Cancer Res 5: 2006–2011.
Kaleita, TA, Wellich, DK, Graham, CAet al. (2006). Pilot study of modafinil for treatment of neurobehavioral dysfunction and fatigue in adult patients with brain tumors. Proc ASCO 24(18S): 58S, [abstract 1503].
Karnofsky, DA, Abelmann, WH, Craver, LF (1948). The use of nitrogen mustards in the palliative treatment of carcinoma. Cancer 1: 634–656.
Kayl, AE, Meyers, CA (2003). Does brain tumor histology influence cognitive function?Neurooncology 5: 255–260.
Klein, M, Heimans, JJ (2004). The measurement of cognitive functioning in low-grade glioma patients after radiotherapy [Letter]. J Clin Oncol 22: 966–967.
Klein, M, Taphoorn, MJB, Heimans, JJet al. (2001). Neurobehavioral status and health-related quality of life in newly diagnosed high-grade glioma patients. J Clin Oncol 19: 4037–4047.
Klein, M, Engelberts, NHJ, Ploeg, HMet al. (2003a). Epilepsy in low-grade gliomas: the impact on cognitive function and quality of life. Ann Neurol 54: 514–520.
Klein, M, Postma, TJ, Taphoorn, MJBet al. (2003b). The prognostic value of cognitive functioning in the survival of patients with high-grade glioma. Neurology 61: 1796–1798.
Lannering, B, Marky, I, Lundberg, Aet al. (1990). Long-term sequelae after pediatric brain tumors: their effect on disability and quality of life. Med Pediatr Oncol 18: 304–310.
Lezak, MD. (1995). Neuropsychological Assessment (3rd edn.). New York: Academic Press.
Lezak, MD, Howieson, DB, Loring, DW (1994). Neuropsychological Assessment. New York: Oxford University Press.
Levin, VA, Yung, WK, Bruner, Jet al. (2002). Phase II study of accelerated fractionation radiation therapy with carboplatin followed by PCV chemotherapy for the treatment of anaplastic gliomas. Int J Radiat Oncol Biol Phys 53: 58–66.
Levine, DW, Kripke, DF, Kaplan, RMet al. (2003). Reliability and validity of the Women's Health Initiative Insomnia Rating Scale. Psychol Assess 15: 137–148.
Lilja, A, Brun, A, Salford, LGet al. (1992). Neuropsychological indexes of a partial frontal syndrome in patients with nonfrontal gliomas. Neuropsychology 6: 315–326.
Lupien, SJ, Gillin, CJ, Hauger, RL (1999). Working memory is more sensitive than declarative memory to the acute effects of corticosteroids: a dose-response study in humans. Behav Neurosci 113: 420–430.
Maldjian, JA, Detre, JA, Killgore, WESet al. (2001). Neuropsychologic performance after resection of an activation cluster involved in cognitive memory function. AJR Am J Roentgenol 176: 541–544.
Marin, RS (1991). Apathy: a neuropsychiatric syndrome. J Neuropsychiatry Clin Neurosci 3: 243–254.
Marin, RS (1996). Apathy: concept, syndrome, neural mechanisms, and treatment. Semin Clin Neuropsychiatry 1: 304–314.
Mattson, RH (2004). Cognitive, affective, and behavioral side events in adults secondary to antiepileptic drug use. Rev Neurol Dis 1 [Suppl 1]: S10–S17.
Mauer, M, Stupp, R, Taphoorn, MJet al. (2007). The prognostic value of health-related quality-of-life data in predicting survival in glioblastoma cancer patients: results from an international randomised phase III EORTC Brain Tumour and Radiation Oncology Groups, and NCIC Clinical Trials Group study. Br J Cancer 97: 302–307.
McNair, DM, Lorr, M, Droppleman, LF (1992). Profile of Mood States Manual. San Diego, CA: Educational and Industrial Testing Service.
Mendoza, TR, Wang, XS, Cleeland, CSet al. (1999). The rapid assessment of fatigue severity in cancer patients: use of the Brief Fatigue Inventory. Cancer 85: 1186–1196.
Mesulam, M (2000). Attentional networks, confusional states, and neglect syndromes. In Mesulam, M (ed.) Principles of Behavioral and Cognitive Neurology (pp. 174–256). New York: Oxford University Press.
Meyers, CA, Boake, C (1993). Neurobehavioral disorders in brain tumor patients: rehabilitation strategies. Cancer Bull 45: 362–364.
Meyers, CA, Brown, PD (2006). Role and relevance of neurocognitive assessment in clinical trials of patients with CNS tumors. J Clin Oncol 24: 1305–1309.
Meyers, CA, Wefel, JS (2003). The use of the mini-mental state examination to assess cognitive functioning in cancer trials: no ifs, ands, buts, or sensitivity. J Clin Oncol 21: 3357–3358.
Meyers, CA, Kudelka, AP, Conrad, CAet al. (1997). Neurotoxicity of CI-980, a novel mitotic inhibitor. Clin Cancer Res 3: 419–422.
Meyers, CA, Weitzner, MA, Valentine, AD, Levin, VA (1998). Methylphenidate therapy improves cognition, mood, and function of brain tumor patients. J Clin Oncol 16: 2522–2527.
Meyers, CA, Hess, KR, Yung, WKA, Levin, VA (2000). Cognitive function as a predictor of survival in patients with recurrent malignant glioma. J Clin Oncol 18: 646–650.
Meyers, CA, Smith, JA, Bezjak, Aet al. (2004). Neurocognitive function and progression in patients with brain metastases treated with whole-brain radiation and motexafin gadolinium: results of a randomized phase III trial. J Clin Oncol 22: 157–165.
Monje, ML, Mizumatsu, S, Fike, JR, Palmer, TD (2002). Irradiation induces neural precursor-cell dysfunction. Nat Med 8: 955–962.
Monje, ML, Toda, H, Palmer, TD (2003). Inflammatory blockade restores adult hippocampal neurogenesis. Science 302: 1760–1765.
Monje, ML, Vogel, H, Masek, M, Ligon, KL, Fisher, PG, Palmer, TD (2007). Impaired human hippocampal neurogenesis after treatment for central nervous system malignancies. Ann Neurol 62(5): 515–520.
Moulder, JE, Robbins, ME, Cohen, EPet al. (1998). Pharmacologic modification of radiation-induced late normal tissue injury. Cancer Treat Res 93: 129–151.
Mulhern, RK, Khan, RB, Kaplan, Set al. (2004). Short-term efficacy of methylphenidate: a randomized, double-blind, placebo-controlled trial among survivors of childhood cancer. J Clin Oncol 22: 4795–4803.
Murphy, GM, Kremer, C, Rodrigues, HE, Schatzberg, AF (2003). Pharmacogenetics of antidepressant medication intolerance. Am J Psychiatry 160: 1830–1835.
Murray, KJ, Scott, C, Zachariah, Bet al. (2000). Importance of the mini-mental status examination in the treatment of patients with brain metastases: a report from the Radiation Therapy Oncology Group protocol 91–04. Int J Radiat Oncol Biol Phys 48: 59–64.
O'Connor, NM, Mayberrg, MR (2000). Effects of radiation on cerebral vasculature: a review. Neurosurgery 46: 138–151.
O'Dwyer, JP, Clabby, C, Crown, J, Barton, , Hutchinson, M (2005). Fragile X-associated tremor/ataxia syndrome presenting in a woman after chemotherapy. Neurology 65: 331–332.
Oken, MM, Creech, RH, Tormey, DCet al. (1982). Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 5: 649–655.
Okuyama, T, Akechi, T, Kugaya, Aet al. (2000). Development and validation of the cancer fatigue scale: a brief, three-dimensional, self-rating scale for assessment of fatigue in cancer patients. J Pain Symptom Manage 19: 5–14.
Packer, RJ, Gurney, JG, Punyko, JAet al. (2003). Long-term neurologic and neurosensory sequelae in adult survivors of a childhood brain tumor: childhood cancer survivor study. J Clin Oncol 21: 3255–3261.
Patchell, RA, Tibbs, PA, Regine, WFet al. (1998). Postoperative radiotherapy in the treatment of single metastases to the brain: a randomized trial. J Am Med Assoc 280: 1485–1489.
Raida, M, Schwabe, W, Hausler, Pet al. (2001). Prevalence of a common point mutation in the dihydropyrimidine dehydrogenase (DPD) gene within the 5′-splice donor site of intron 14 in patients with severe 5-fluorouracil (5-FU)-related toxicity compared with controls. Clin Cancer Res 7: 2832–2839.
,Report of the Brain Tumor Progress Review Group (2005). National Institute of Neurologic Disorders and Stroke. Accessed 27 March, 2008 from http://www.ninds.nih.gov/find_people/groups/brain_tumor_prg/btprgreport.htm.
Rozental, JMLevine, RL, Nickles, RJ, Dobkin, JA, Hanson, JM (1990). Cerebral diaschisis in patients with malignant glioma. J Neurooncol 8: 153–161.
Salander, P, Karlsson, T, Bergenheim, Tet al. (1995). Long-term memory deficits in patients with malignant gliomas. J Neurooncol 25: 227–238.
Scheibel, RS, Meyers, CA, Levin, VA (1996). Cognitive dysfunction following surgery for intracerebral glioma: influence of histopathology, lesion location, and treatment. J Neurooncol 30: 61–69.
Shaw, E, Arusell, R, Scheithauer, Bet al. (2002). Prospective randomized trial of low- versus high-dose radiation therapy in adults with supratentorial low-grade glioma: initial report of a North Central Cancer Treatment Group/ Radiation Therapy Oncology Group/Eastern Cooperative Oncology Group study. J Clin Oncol 20: 2267–2276.
Shaw, EG, Rosdhal, R, D'Agostino, RBet al. (2006). Phase II study of donepezil in irradiated brain tumor patients: effect on cognitive function, mood, and quality of life. J Clin Oncol 24: 1415–1420.
Shehata, N, Pater, A, Tang, SC (1999). Prolonged severe 5-fluorouracil-associated neurotoxicity in a patient with dihydropyrimidine dehydrogenase deficiency. Cancer Invest 17: 201–205.
Sherer, M, Meyers, CA, Bergloff, P (1997). Efficacy of postacute brain injury rehabilitation for patients with primary malignant brain tumors. Cancer 80: 250–257.
Sherman, AM, Jaeckle, K, Meyers, CA (2002). Pre-treatment cognitive performance predicts survival in patients with leptomeningeal disease. Cancer 95: 1311–1316.
Sohlberg, MM, Maateer, CA (1989). Introduction to Cognitive Rehabilitation. New York: Guilford.
Spielberger, C, Gorsuch, R, Lushene, R (1970). State-Trait Anxiety Inventory. Palo Alto, CA: Consulting Psychologists.
Steinbach, JP, Blaicher, H-P, Herrlinger, Uet al. (2006). Surviving glioblastoma for more than 5 years: the patient's perspective. Neurology 66: 239–242.
Stupp, R, Mason, WP, Bent, MJet al. (2005). Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. New Engl J Med 352: 987–996.
Taphoorn, MJ, Klein, M (2004). Cognitive deficits in adult patients with brain tumours. Lancet Neurol 3: 159–168.
Taphoorn, MJ, Heimans, JJ, Snoek, FLet al. (1992). Assessment of quality of life in patients treated for low-grade glioma: a preliminary report. J Neurol Neurosurg Psychiatry 55: 372–376.
Taphoorn, MJ, Stupp, R, Coens, Cet al. (2005). Health-related quality of life in patients with glioblastoma: a randomized controlled trial. Lancet Oncol 6: 937–944.
Taylor, BV, Buckner, JC, Cascino, TLet al. (1998). Effects of radiation and chemotherapy on cognitive function in patients with high-grade glioma. J Clin Oncol 16: 2195–2201.
Tofilon, PJ, Fike, JR (2000). The radioresponse of the central nervous system: a dynamic process. Radiat Res 153: 357–370.
Torres, IJ, Mundt, AJ, Sweeney, PJet al. (2003). A longitudinal neuropsychological study of partial brain radiation in adults with brain tumors. Neurology 60: 1113–1118.
Ulrich, CM, Yasui, Y, Storb, Ret al. (2001). Pharmacogenetics of methotrexate: toxicity among marrow transplantation patients varies with the methylenetetrahydrofolate reductase C677T polymorphism. Blood 98: 231–234.
Ulrich, CM, Robien, K, Sparks, R (2003). Pharmacogenetics and folate metabolism – a promising direction. Pharmacogenomics 3: 299–313.
Varni, JW, Limbers, CA, Burnwinkle, TM (2007). How young can children reliably and validly self-report their health-related quality of life? An analysis of 8,591 children across age subgroups with the PedsQL 4.0 Generic Core Scales. Health Qual Life Outcomes 5: 1–13.
Wade, DT, Collin, C (1988). The Barthel ADL Index: a standard measure of physical disability. Int Disabil Stud 10: 64–67.
Ware, JE, Sherbourne, CD (1992). The MOS 36-item short-form health survey (SF-36): I. Conceptual framework and item selection. Med Care 30: 473–483.
Wechsler, D (1981). Wechsler Adult Intelligence Scale-Revised. San Antonio, TX: The Psychological Corporation.
Wei, CW, Gui, G, Mikulis, DJ (2007). Tumor effects on cerebral white matter as characterized by diffusion tensor tractography. Can J Neurol Sci 34: 62–68.
Weitzner, MA, Meyers, CA, Gelke, CKet al. (1995). The Functional Assessment of Cancer Therapy (FACT) scale: development of a brain subscale and revalidation of the general version (FACT-G) in patients with primary brain tumors. Cancer 75: 1151–1161.
Wellisch, DK, Kaleita, TA, Freeman, D, Cloughesy, T, Goldman, J (2002). Predicting major depression in brain tumor patients. Psychooncology 11: 230–238.
Wen, PY, Schiff, D, Kesari, S, Drappatz, J, Gigas, DC, Doherty, L (2006). Medical management of patients with brain tumors. J Neurooncol 80: 313–332.
Young, AH, Sahakian, BJ, Robbns, TWet al. (1999). The effects of chronic administration of hydrocortisone on cognitive functioning normal male volunteers. Psychopharmacology 145: 260–266.
Young, GS (2007). Advanced MRI of adult brain tumors. Neurol Clin N Am 25: 947–973.