Detrimental effects of tumor progression on cognitive function of patients with high-grade glioma.

PURPOSE There is growing recognition that the primary cause of cognitive deficits in adult patients with primary brain tumors is the tumor itself and more significantly, tumor progression. To assess the cognitive performance of high-grade glioma patients, prospectively collected cognitive performance data were analyzed. PATIENTS AND METHODS We studied 1,244 high-grade brain tumor patients entered onto eight consecutive North Central Cancer Treatment Group treatment trials that used radiation and nitrosourea-based chemotherapy. Imaging studies and Folstein Mini-Mental State Examination (MMSE) scores recorded at baseline, 6, 12, 18, and 24 months were analyzed to assess tumor status and cognitive function over time. RESULTS The proportion of patients without tumor progression who experienced clinically significant cognitive deterioration compared with baseline was stable at 6, 12, 18, and 24 months (18%, 16%, 14%, and 13%, respectively). In patients without radiographic evidence of progression, clinically significant deterioration in MMSE scores was a strong predictor of a more rapid time to tumor progression and death. At evaluations preceding interval radiographic evidence of progression, there was significant deterioration in MMSE scores for patients who were to experience progression, whereas the scores remained stable for the patients who did not have tumor progression. CONCLUSION The proportion of high-grade glioma patients with cognitive deterioration over time is stable, most consistent with the constant pressure of tumor progression over time. Although other factors may contribute to cognitive decline, the predominant cause of cognitive decline seems to be subclinical tumor progression that precedes radiographic changes.

[1]  M. Taphoorn,et al.  The course of neurocognitive functioning in high-grade glioma patients. , 2007, Neuro-oncology.

[2]  Martin J. van den Bent,et al.  Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. , 2005, The New England journal of medicine.

[3]  P. Brown,et al.  Cognitive sequelae of brain radiation in adults. , 2004, Seminars in oncology.

[4]  R. Scheibel,et al.  Cognitive dysfunction following surgery for intracerebral glioma: influence of histopathology, lesion location, and treatment , 1996, Journal of Neuro-Oncology.

[5]  W. Curran,et al.  Neurocognitive function and progression in patients with brain metastases treated with whole-brain radiation and motexafin gadolinium: results of a randomized phase III trial. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[6]  B. Scheithauer,et al.  Effects of radiotherapy on cognitive function in patients with low-grade glioma measured by the folstein mini-mental state examination. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[7]  M. Castillo,et al.  A longitudinal neuropsychological study of partial brain radiation in adults with brain tumors , 2003, Neurology.

[8]  K. Hess,et al.  Multifaceted end points in brain tumor clinical trials: cognitive deterioration precedes MRI progression. , 2003, Neuro-oncology.

[9]  J. Jolles,et al.  Effect of radiotherapy and other treatment-related factors on mid-term to long-term cognitive sequelae in low-grade gliomas: a comparative study , 2002, The Lancet.

[10]  J. Hunter,et al.  Late cognitive and radiographic changes related to radiotherapy: Initial prospective findings , 2002, Neurology.

[11]  M. Mehta,et al.  A multi-institutional review of radiosurgery alone vs. radiosurgery with whole brain radiotherapy as the initial management of brain metastases. , 2002, International journal of radiation oncology, biology, physics.

[12]  J. O'fallon,et al.  Safety of thrice-daily hyperfractionated radiation and BCNU for high-grade gliomas. , 2002, International journal of radiation oncology, biology, physics.

[13]  A. Young,et al.  Risk of symptomatic brain tumor recurrence and neurologic deficit after radiosurgery alone in patients with newly diagnosed brain metastases: results and implications. , 2002, International journal of radiation oncology, biology, physics.

[14]  M. Taphoorn,et al.  Neurobehavioral status and health-related quality of life in newly diagnosed high-grade glioma patients. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[15]  B. Scheithauer,et al.  A phase III study of radiation therapy plus carmustine with or without recombinant interferon‐α in the treatment of patients with newly diagnosed high‐grade glioma , 2001 .

[16]  A. Paetau,et al.  Adverse long-term effects of brain radiotherapy in adult low-grade glioma patients , 2001, Neurology.

[17]  T. Cascino,et al.  Phase I evaluation of preirradiation chemotherapy with carmustine and cisplatin and accelerated radiation therapy in patients with high-grade gliomas. , 1999, Neurosurgery.

[18]  T. Cascino,et al.  Phase I and pharmacokinetic study of preirradiation chemotherapy with BCNU, cisplatin, etoposide, and accelerated radiation therapy in patients with high-grade glioma. , 1998, International journal of radiation oncology, biology, physics.

[19]  W R Markesbery,et al.  Postoperative radiotherapy in the treatment of single metastases to the brain: a randomized trial. , 1998, JAMA.

[20]  J. O'fallon,et al.  Effects of radiation and chemotherapy on cognitive function in patients with high-grade glioma. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[21]  R. Dinapoli,et al.  Phase I evaluation of radiation combined with recombinant interferon alpha-2a and BCNU for patients with high-grade glioma. , 1998, International journal of radiation oncology, biology, physics.

[22]  E G Tangalos,et al.  The Mini-Mental State Examination in general medical practice: clinical utility and acceptance. , 1996, Mayo Clinic proceedings.

[23]  A. Gregor,et al.  Neuropsychometric evaluation of long-term survivors of adult brain tumours: relationship with tumour and treatment parameters. , 1996, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[24]  E. Neuwelt,et al.  Neurobehavioral sequelae of cranial irradiation in adults: a review of radiation-induced encephalopathy. , 1994, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[25]  Y. Archibald,et al.  Cognitive functioning in long-term survivors of high-grade glioma. , 1994, Journal of neurosurgery.

[26]  B. Scheithauer,et al.  Phase III comparative evaluation of PCNU and carmustine combined with radiation therapy for high-grade glioma. , 1993, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[27]  K. Wallner,et al.  Erratum: Good performance status of long-term disease-free survivors of intracranial gliomas (International Journal of Radiation Oncology Biology (1993) 26 (129-133)) , 1993 .

[28]  K. Wallner,et al.  Good performance status of long-term disease-free survivors of intracranial gliomas. , 1993, International journal of radiation oncology, biology, physics.

[29]  T. Tombaugh,et al.  The Mini‐Mental State Examination: A Comprehensive Review , 1992, Journal of the American Geriatrics Society.

[30]  N. Vick,et al.  Effects of treatment on long‐term survivors with malignant astrocytomas , 1990, Annals of neurology.

[31]  L. Thal,et al.  Longitudinal evaluation of dementia of the Alzheimer type , 1990, Neurology.

[32]  D P Salmon,et al.  The Mini-Mental State Examination in the early diagnosis of Alzheimer's disease. , 1990, Archives of neurology.

[33]  L. Deangelis,et al.  Radiation‐induced dementia in patients cured of brain metastases , 1989, Neurology.

[34]  J. Guérin,et al.  Neuropsychologic Impairment in Adults with Brain Tumors , 1987, American journal of clinical oncology.

[35]  D. Moody,et al.  MRI of radiation injury to the brain. , 1986, AJR. American journal of roentgenology.

[36]  R. Hatlevoll,et al.  Combined modality therapy of operated astrocytomas grade III and IV. Confirmation of the value of postoperative irradiation and lack of potentiation of bleomycin on survival time: A prospective multicenter trial of the scandinavian glioblastoma study group , 1981, Cancer.

[37]  E. Alexander,et al.  Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas. A cooperative clinical trial. , 1978, Journal of neurosurgery.

[38]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.

[39]  N. Mantel Evaluation of survival data and two new rank order statistics arising in its consideration. , 1966, Cancer chemotherapy reports.

[40]  E. Kaplan,et al.  Nonparametric Estimation from Incomplete Observations , 1958 .