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脑癌化疗手册Handbook of Brain Tumor Chemotherapy(2006)（英文）.pdf Dr Psyxo Contributors Lauren E. Abrey (395) Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA Till Acker (219) Karolinska Institute, CMB, Stockholm, Sweden Eric Amundson (274) Department of Neurological Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA Kaveh Asadi-Moghaddam (332) Department of Neurological Surgery, The Ohio State University Medical Center, Columbus, OH, USA Michael E. Berens (115) TGen, The Translational Genomics Research Institute, Phoenix, AZ, USA Henry Brem (274) Departments of Neurological Surgery, Oncology, and Opthalmology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA William C. Broaddus (295) Department of Neuro- surgery, Medical College of Virginia Hospitals, Richmond, VA, USA Anna Butturini (305) Children’s Hospital Los Angeles and the Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA Nicholas Butowski (105) Department of Neuro- Oncology, University of California, San Francisco, San Francisco, CA, USA Matthew Carabasi (305) Children’s Hospital Los Angeles and the Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA Marc C. Chamberlain (316) Department of Inter- disciplinary Oncology, University of South Florida, Tampa, FL, USA Susan Chang (105) Department of Neuro-Oncology, University of California, San Francisco, San Francisco, CA, USA Mike Yue Chen (295) Department of Neurosurgery, Medical College of Virginia Hospitals, Richmond, VA, USA Zhi-jian Chen (295) Department of Neurosurgery, Medical College of Virginia Hospitals, Richmond, VA, USA Antonio E. Chiocca (332) Department of Neurolo- gical Surgery, The Ohio State University Medical Center, Columbus, OH, USA Tim Demuth (115) TGen, The Translational Genomics Research Institute, Phoenix, AZ, USA Nancy D. Doolittle (262) Department of Neurology, Oregon Health & Science University, Portland, OR, USA Michael Dorsi (274) Department of Neurological Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA Patricia K. Duffner (490) Departments of Pediatrics and Neurology, State University of New York at Buffalo School of Medicine and The Women and Children’s Hospital of Buffalo, Buffalo, NY, USA Francois G. El Kamar (395) Department of Neu- rology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA Herbert H. Engelhard (236) Departments of Neuro- surgery and Pathology, The University of Illinois at Chicago, Chicago, IL, USA Christopher Fahey (371) Department of Neurology, Northwestern University, Evanston, IL, USA Jonathan L. Finlay (305) Children’s Hospital Los Angeles and the Norris Comprehensive Cancer Dr Psyxo Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA Karen L. Fink (44) Baylor University Medical Center, Dallas, TX, USA Lorna K. Fitzpatrick (490) Departments of Pediatrics and Neurology, State University of New York at Buffalo School of Medicine and The Women and Children’s Hospital of Buffalo, Buffalo, NY, USA George T. Gillies (295) Department of Neuro- surgery, Medical College of Virginia Hospitals, Richmond, VA, USA Abhijit Guha (173) Division of Neurosurgery and the Arthur and Sonia Labatts Brain Tumor Research Center, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada Peter J. Haar (295) Department of Neurosurgery, Medical College of Virginia Hospitals, Richmond, VA, USA Daphne A. Haas-Kogan (185) Department of Radiation Oncology, University of California, San Francisco, CA, USA Raqeeb M. Haque (274) Department of Neurolo- gical Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA Stacey M. Ivanchuk (123) The Division of Neuro- surgery and The Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, Toronto, ON, Canada Mark T. Jennings (448) Department of Pediatrics and Neurology, University of Illinois College of Medicine, Peoria, IL, USA Mark G. Malkin (364, 426) Department of Neu- rology, Medical College of Wisconsin, Milwaukee, WI, USA Tom Mikkelsen (193) Department of Neurosurgery, Henry Ford Hospital, Detroit, MI, USA Nimish Mohile (432) Department of Neurology, Northwestern Univesity, Chicago, IL, USA Joydeep Mukherjee (173) Arthur and Sonia Labatts Brain Tumor Center, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada Tulio P. Murillo (262) Departments of Neurology and Neurosurgery, Oregon Health & Science University, Portland, OR, USA Jean L. Nakamura (185) Department of Radiation Oncology, University of California, San Francisco, CA, USA Edward A. Neuwelt (262) Departments of Neu- rology and Neurosurgery, Oregon Health & Science University, Portland, OR, USA Herbert B. Newton (3, 21, 247, 347, 407, 439, 463, 475) Division of Neuro-Oncology, Dardinger Neuro-Oncology Center, The Ohio State University Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, OH, USA Nina A. Paleologos (371, 382) Evanston North- western Healthcare and Feinberg School of Medi- cine, Northwestern University, Evanston, IL, USA Karl H. Plate (219) Institute of Neurology (Edinger Institute), Johann-Wolfgang Goethe University, Frankfurt, Germany Ian F. Pollack (155) Department of Neurosurgery, Children’s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Scott L. Pomeroy (74) Department of Neurology, Children’s Hospital Boston, Boston, MA, USA Jeffrey J. Raizer (432) Department of Neurology, Northwestern University, Chicago, IL, USA Abhik Ray-Chaudhury (3) Department of Pathology, The Ohio State University Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, OH, USA Sandra A. Rempel (193) Department of Neurosur- gery, Henry Ford Hospital, Detroit, MI, USA James T. Rutka (123) The Division of Neurosurgery and The Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, Toronto, ON, Canada Adrienne C. Scheck (89) Ina Levine Brain Tumor Center, Neuro-Oncology and Neurosurgery Research, Barrow Neurological Institute of SJHMC, Phoenix, AZ, USA Joachim P. Steinbach (141) Department of General Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany Beverly A. Teicher (58) Genzyme Corporation, Framingham, MA, USA Nicole J. Ullrich (74) Department of Neurology, Children’s Hospital Boston, Boston, MA, USA Tibor Valyi-Nagy (236) Departments of Neurosur- gery and Pathology, The University of Illinois at Chicago, Chicago, IL, USA Allison L. Weathers (382) Department of Neuro- logical Sciences, Rush University, Chicago, IL, USA Michael Weller (141) Department of General Neuro- logy, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany xvi CONTRIBUTORS Dr Psyxo C H A P T E R 1 Overview of Brain Tumor Epidemiology and Histopathology Herbert B. Newton and Abhik Ray-Chaudhury ABSTRACT: Primary brain tumors (PBT) comprise a diverse group of neoplasms that are often malignant and refractory to treatment. Between 30 000 and 35 000 new PBT are diagnosed each year in the USA (approximately 14 per 100 000). Tumors of neuroe- pithelial origin are the largest histological class of PBT and include the glioma sub-group (e.g., glioblastoma multiforme, anaplastic astrocytoma, oligodendroglio- ma), which represent the most frequently diagnosed tumors in adults. Other important tumors in adults include meningiomas, primary brain lymphoma, and oligoastrocytoma. Commonly diagnosed tumors in children include medulloblastoma, cerebellar astro- cytoma, and optic pathway glioma. This chapter will review the microscopic and molecular pathology of PBT that are most likely to require treatment with chemotherapy, utilizing the classification system of the World Health Organization. EPIDEMIOLOGY OF BRAIN TUMORS Brain tumors remain a significant health problem in the USA and worldwide. Overall, they comprise some of the most malignant tumors known to affect humans and are generally refractory to all modalities of treatment. It is estimated that between 30 000 and 35 000 new cases of primary brain tumors (PBT) will be diagnosed in the upcoming year in the USA (1–2 per cent of newly diagnosed cancers overall) [1–6]. Metastatic brain tumors (MBT) are even more common and affect between 100 000 and 150 000 new patients each year in this country [7]. Most studies suggest that approximately 14 per 100 000 people in the USA will be diagnosed with a PBT each year. Among this cohort with newly diagnosed tumors, 6 to 8 per 100 000 will have a high-grade neoplasm. Recent epidemiological studies suggest an increasing inci- dence rate for development of PBT in children less than 14 years of age and in patients 70 years or older [8]. For people in the 15- to 44-year-old age group, the overall incidence rates have remained fairly stable. The cause of the increased incidence of PBT in some age groups remains unclear, but may be due to improvements in diagnostic neuro-imaging such as magnetic resonance imaging (MRI), greater availabil- ity of neurosurgeons, improved patterns of access to medical care for children and elderly patients, and more aggressive approaches to health care for elderly patients [5,8]. The prognosis and survival of patients with brain tumors remains poor [1–7]. Although an uncommon neoplasm, PBT are among the top 10 causes of cancer- related deaths in the USA and account for 2.4 per cent of all yearly cancer-related deaths [9]. The median survival for a patient with glioblastoma multiforme (GBM) is approximately 12–14 months, and has not improved substantially over the past 30 years. For patients with a low-grade astrocytoma or oligoden- droglioma, the median survival is still significantly curtailed and is about 6–10 years. For PBT patients in the USA as a whole, across all age groups and tumor types, the 5-year survival rate is 20 per cent [3]. If a patient with a PBT survives for an initial 2 years, the probability of surviving another 3 years is 76.2 per cent. In general, for any given tumor type, survival is better for younger patients than for older patients. The only exception to this generalization Copyright � 2006, Elsevier Inc. Handbook of Brain Tumor Chemotherapy 3 All rights reserved. Dr Psyxo 4 1. OVERVIEW OF BRAIN TUMOR EPIDEMIOLOGY AND HISTOPATHOLOGY is for children with medulloblastoma and embryonal tumors, in which patients under three years of age have poorer survival rates than children between 3 and 14 years of age [10]. The 5-year survival rate for all children less than 14 years of age with a malignant PBT is 72 per cent. The median age for diagnosis of PBT is between 54 and 58 years [1–6]. Among different histological varieties of PBT, there is significant variability in the age of onset. A small secondary peak is also present in the pediatric age group, in children between the ages of 4 and 9. Overall, PBT are more common in males than females, with the exception of meningiomas, which are almost twice as common in females. Tumors of the sellar region, and of the cranial and spinal nerves, are almost equally represented among males and females. In the USA, gliomas are more commonly diagnosed in Whites than Blacks, while the incidence of meningiomas is relatively equal between the two groups. Numerous epidemiological studies have been performed in an attempt to define risk factors involved in the development of brain tumors (see Table 1.1) [2–6]. The vast majority of these potential risk factors have not been associated with any TABLE 1.1 Risk Factors that have been Investigated in Epidemiological Studies of Primary Brain Tumors Hereditary syndromes (proven): tuberous sclerosis, neurofibro- matosis types 1 and 2, nevoid basal cell carcinoma syndrome, Turcot’s syndrome, and Li-Fraumeni syndrome Family History of brain tumors Constitutive polymorphisms: glutathione transferases, cytochrome P-450 2D6 and 1A1, N-acetyltransferase, and other carcinogen metabolizing, DNA repair, and immune function genes History of prior cancer Exposure to infectious agents Allergies (possible reduced risk) Head trauma Drugs and medications Dietary history: N-nitroso compounds, oxidants, antioxidants Tobacco usage Alcohol consumption Ionizing radiation exposure (proven) Occupational and industrial chemical exposures: pesticides, vinyl chloride, synthetic rubber manufacturing, petroleum refining and production, agricultural workers, lubricating oils, organic solvents, formaldehyde, acrylonitrile, phenols, polycyclic aromatic hydrocarbons Cellular telephones Power frequency electromagnetic field exposure Data adapted from references [2–6,11–23] significant predisposition to brain tumors. One risk factor that has proven to be important is the presence of a hereditary syndrome with a genetic predisposition for developing tumors, some of which can affect the nervous system [4,5,11]. Several heredi- tary syndromes are associated with PBT, including tuberous sclerosis, neurofibromatosis types 1 and 2, nevoid basal cell carcinoma syndrome, Li-Fraumeni syndrome, and Turcot’s syndrome. However, it is estimated that hereditary genetic predisposition may be involved in only 2–8 per cent of all cases of PBT. Familial aggregation of brain tumors has also been studied, with conflicting results [5,11]. The relative risk for developing a tumor among family members of a patient with a PBT are quite variable and range from 1 to 10. One study that performed a segregation analysis of families of more than 600 adult glioma patients showed that a polygenic model most accu- rately explained the inheritance pattern [12]. A similar analysis of 2141 first-degree relatives of 297 glioma families did not reject a multifactorial model, but concluded that an autosomal recessive model fit the inheritance pattern more accurately [13]. Critics of these studies suggest that the common exposure of a family to a similar pattern of environmental agents could lead to a similar clustering of tumors. Other investigators have focused on genetic polymorphisms that might influence genetic and environmental factors to increase the risk for a brain tumor [4,5]. Alterations in genes involved in oxidative metabo- lism, detoxification of carcinogens, DNA stability and repair, and immune responses might confer a genetic predisposition to tumors. For example, Elexpuru- Camiruaga and colleagues demonstrated that cyto- chrome P-4502D6 and glutathione transferase theta were associated with an increased risk for brain tumors [14]. Other studies have not supported these results, but have found an increased risk for rapid N-acetyltransferase acetylation and intermediate acetylation [15]. In general, further studies with larger cohorts of patients will be necessary to deter- mine if genetic polymorphisms of key metabolic enzyme systems play a significant role in the risk for developing a brain tumor. Cranial exposure to therapeutic ionizing radiation is a potent risk factor for subsequent development of a brain tumor, and is known to occur after a wide range of exposures [1–6]. Application of low doses of irradiation (1000 to 2000 cGy), such as for children with tinea capitis or skin hemangiomas, have been associated with relative risks of 18 for nerve sheath tumors, 10 for meningiomas, and 3 for gliomas [5,16]. Gliomas and other PBT are also known to occur after radiotherapy for diseases such as leukemia, Dr Psyxo ...