Site-Specific Cancer Series: Central Nervous System Cancers
Cancers of the central nervous system (CNS) are considered to be among the most devastating of all cancers. The brain and spinal cord are complex organs that control the CNS, the peripheral nervous system, and many of the voluntary and involuntary systems of the body. The effects can be devastating for the patient and the family when cancer attacks the CNS. It has been found that 20%–40% of all cancers metastasize to the brain (Cairncross, Kim, & Posner, 1980; Gavrilovic & Posner, 2005; Nathoo, Chahlavi, Barnett, & Toms, 2005; Posner, 1992).
The diagnosis and death of Senator Edward Kennedy in 2009 brought public awareness to this disease state. Many families have experienced the effects of a CNS cancer. All patients will have some change in personality, memory, motor skills, or executive functioning during the illness trajectory that compromises their quality of life. Care of those living with a brain and spinal tumor requires a broad knowledge base in neuro-oncology and a sensitive and realistic approach that optimizes quality of life and permits a sense of hopefulness to prevail. Care of informal caregivers also is an area of ongoing study.
The brain being the domicile for all the mysteries of the body has been suspected for ages. Dating back to the middle Stone Age period, archeologists found skulls with holes bored into them, a procedure called trepanation. The healed holes reveal that the surgeries had been successful and the patients had survived. Trepanation was carried out until the beginning of the 20th century. This treatment was believed to permit evil spirits to be removed and to treat seizures, headaches, and blindness. The first experiential physiologists, Galen, Vesalius, and Willis, whose work dated back to 130–200 AD, described on parchment paper the anatomy of the brain. Galen’s view of human anatomy dominated European medicine for 1,500 years (Kaye & Laws, 1995).
Modern brain surgery was first reported by Rickman Godlee in 1884. He operated on a 25-year-old Scottish farmer who suffered from epilepsy and progressive hemiparesis. He was found to have an oligodendroglioma and subsequently died from an infection (Kaye & Laws, 1995). The discoveries in the 19th century of asepsis, anesthesia, and neurologic localization of the brain tumor allowed modern brain surgery to flourish. The 20th century found a surge of technologic advances mostly focused on diagnostic and surgical techniques. Treatment choices have remained few with no grand slams, but the discovery of temozolomide provided hope.
The 21stcentury has just begun to reveal advances. Personalized treatments based on tumor typing may be on the horizon. MGMT (chemically known as O-6-methylguanine DNA methyltransferase) status of the tumor was found to differentiate those patients who may be more receptive to temozolomide (Hegi et al., 2005) (see Chapters 5 and 8 for discussions regarding MGMT). Scientists are working to find the genomic makeup of tumors and to work on effective treatments to possibly cure them. Thus far, CNS cancer death rates have not declined. Oncology nurses are also more sensitive to the overall psychosocial needs of patients and family caregivers.
Low-grade (grade 2) tumors, including low-grade oligodendrogliomas, astrocytomas, and mixed oligoastrocytomas, have been found over time to progress to grade 3 or 4 tumors. The time may vary depending on the genetic makeup of the tumor, which can only be determined if a surgical pathology specimen is obtained and analyzed (Whittle, 2004). Despite the surgical and oncologic advances in technology, the prognosis remains poor for high-grade tumors. The diagnosis of CNS cancer, with the daunting statistics on median survival of patients with high-grade tumors being less than 12 months, leaves little hope for the patient. Current knowledge reveals that most low-grade tumors will progress to high-grade tumors (van den Bent et al., 2005).
The National Cancer Institute (NCI, n.d.) estimated that 22,070 new cases of brain and other CNS cancers would be diagnosed in the United States in 2009. The American Brain Tumor Association (ABTA, 2010) clarifies this statistic further by estimating that 62,930 new cases of primary brain tumors would be diagnosed in 2010. Of this total, 23,720 are malignant and 39,210 are nonmalignant (ABTA, 2010).The death toll from cancers of the CNS is estimated to reach approximately 13,000 (NCI, n.d.).
An estimated 12,920 deaths were attributed to primary CNS cancers in 2009 (Central Brain Tumor Registry of the United States, 2010). The incidence of CNS tumors is highest in developed, industrialized countries where approximately 6–11 new cases are diagnosed annually per 100,000 population; mortality rates for all types of primary CNS tumors are 3–7 per 100,000 (Feraly, Bray, Pisani, & Parkin, 2000; Parkin, Whelan, Feraly, Teppo, & Thomas, 2002). Gliomas comprise 70% of all brain tumors with the most common type, glioblastoma multiforme, also being the most lethal (Ohgaki, 2009). From 2003 to 2007, the median age of patients at the time of a brain cancer diagnosis was 56 years old (NCI Surveillance, Epidemiology, and End Results, 2009).
Some controversy exists regarding a possible increase in the incidence of brain tumors, particularly in older adults. This may be due to improvements in neuroimaging access and technology (Christensen, Kosteljanetz, & Johansen, 2003; Legler et al., 1999). Population-based incidence data from the Netherlands Cancer Registry showed a stable incidence of adult and childhood gliomas (Houben et al., 2006). In this study, an increase in incidence of high-grade astrocytomas in adults was balanced by a decrease in low-grade astrocytomas.
Although the exact incidence of metastatic brain tumors is unknown, estimates range from double to 10 times the number of primary brain tumors, with at least 20%–40% of patients with cancer developing brain metastases at some point in their disease (Cairncross et al., 1980; Gavrilovic & Posner, 2005; Nathoo et al., 2004; Posner, 1992).
Little consensus exists regarding the risk factors for developing primary brain tumors. The general principles of tumorigenesis implicate an accumulation of inherited and acquired genetic alterations that allow cells to evade normal regulatory mechanisms and divide abnormally. The relationship between chromosome instability and cancer susceptibility is well established, as is the association of defective DNA repair mechanisms in individuals harboring chromosomal alterations (Busch, 1994; Wei et al., 1996). Heritable factors are implicated in a few rare autosomal dominant tumor syndromes (only one mutant gene is required to express the disease), including Li-Fraumeni syndrome, neurofibromatosis types 1 and 2, and Turcot syndrome (Ohgaki, 2009).
Environmental factors associated with this malignant transformation have been difficult to positively identify. Exposure to ionizing radiation has been established as a risk factor for CNS tumors through studies on atomic bomb survivors, as well as children treated with radiation for tinea capitis (ringworm of the scalp) (Hodges, Smith, Garrett, & Tate, 1992; Preston et al., 2002; Socié et al., 2000).
The observation that brain tumor incidence is increased in certain occupations, including firefighters, physicians, farmers, embalmers, and pathologists, has prompted studies of the effects of industrial and occupational chemical exposure, but no definitive causative agent has been found (Mazumdar et al., 2008). Studies on diet, alcohol consumption, tobacco, electromagnetic fields, and cell phone use have similarly resulted in conflicting and inconclusive findings about risk factors (Parascandola, 2001). Some viruses have been implicated in brain tumor development in animal models, but only HIV has been causally linked to brain cancer in humans (Brittain, 2002; McLaughlin-Drubin & Munger, 2008).
Clinical Practice Implications
The brain tumor diagnosis continues to provoke fear and anxiety in patients. Because of the brief median overall survival of less than 12 months for patients with glioblastoma multiforme, specialists in neuro-oncology have systematically researched the natural history of brain tumors. Through the tireless effort of those committed to improve outcomes, advances have been made in the initial surgical management of brain tumors, with a reduction in the morbidity while achieving the surgical objectives. For decades, radiation therapy has been shown to be an effective postsurgical adjuvant therapy, and the current fractionated regimen maximizes the efficacy while minimizing the toxicity of this therapy. Only recently have definitive results shown a benefit from chemotherapy drugs, particularly alkylating agents (Hegi et al., 2005).
With these therapeutic advances, the median survival today has increased several months compared to earlier last century. This is thought to be a result of both the aggressive and resistant biology of brain tumors and the difficulty with which promising agents can be delivered to the brain. To circumvent these barriers, innovations in the form of surgical bed polymer-based therapeutics delivery and positive-pressure interstitial therapy delivery have been tested in the surgical arena. Although the polymer-based therapeutics delivery methods, such as chemotherapy-impregnated wafers, have shown modest activity (Lassman & Holland, 2005), trials investigating the utility of positive-pressure interstitial therapy delivery used to deliver chemotherapeutic agents directly into the tumor have not yet yielded positive results (Debinski, 2002).
Scientists have embraced the challenge of advancing care by dissecting the molecular biologic basis of brain tumor formation and the molecular signatures that dictate tumors’ behavior. By identifying unique molecules that appear to play important roles in brain tumor biology, the field of neuro-oncology has moved forward with a tailored approach to targeting and modifying treatment. Through these efforts, the U.S. Food and Drug Administration has approved promising new agents for use against brain tumors, with the most recent approval for bevacizumab, which targets the activity of vascular endothelial growth factor. Interestingly, as the fight against these tumors advances, the use of newer agents has rewritten what is known about the radiographic changes that occur when treating brain tumors, necessitating reevaluation of previous knowledge.
Today, tools and methods to analyze tumors and their behavior are becoming more prevalent. Clearly, efforts over the past century have yielded real advances; however, we have also come to realize that gains in survival must be balanced with the maintenance of quality of life. Recognizing that what is more important to patients is the length of their good quality of life, more and more researchers have incorporated measures into clinical trials that follow quality of life. Although we have yet to cure brain tumors, clear steps forward have been taken toward reaching this ultimate goal. Each advance injects hope to the team of caregivers and, more importantly, to those who live with this diagnosis.
This book will explore the current treatment for cancers of the CNS. Nurses are trying to make a difference in the outcomes of our patients in survival and quality of life. Our future endeavors will focus on not only basic science questions but also on quality of life for patients, caregivers, and families.
The author wishes to acknowledge Kenji Muro, MD, and Rosemary Cashman, RN, MA, MSc(A), ACNP, for their contributions to this chapter.
American Brain Tumor Association. (2010). Facts and statistics, 2010. Retrieved from http://www.abta.org/sitefiles/pdflibrary/ABTA-FactsandStatistics2010.pdf
Brittain, D. (2002). Management of cancer in patients with HIV. Southern African Journal of HIV Medicine, 3, 24–28. Retrieved from http://ajol.info/index.php/sajhivm/article/viewFile/
Busch, D. (1994). Genetic susceptibility to radiation and chemotherapy injury: Diagnosis and management. International Journal of Radiation Oncology, Biology, Physics, 30, 997–1002.
Cairncross, J.G., Kim, J.H., & Posner, J.B. (1980). Radiotherapy for brain metastases. Annals of Neurology, 7, 529–541. doi:10.1002/ana.410070606
Central Brain Tumor Registry of the United States. (2010). CBTRUS statistical report:Primary brain and central nervous system tumors diagnosed in the United States in 2004–2006. Retrieved from http://www.cbtrus.org/2010-NPCR-SEER/CBTRUS
Christensen, H.C., Kosteljanetz, M., & Johansen, C. (2003). Incidences of gliomas and meningiomas in Denmark, 1943 to 1997. Neurosurgery, 52, 1327–1333. doi:10.1227/01.NEU.0000064802.46759.53
Debinski, W. (2002). Local treatment of brain tumours with targeted chimera cytotoxic proteins. Cancer Investigation, 20, 801–809.
Feraly, J., Bray, F., Pisani, P., & Parkin, D.M. (2000). Globocan 2000: Cancer incidence, mortality and prevalence worldwide. Lyon, France: International Agency for Research on Cancer.
Gavrilovic, I.T., & Posner, J.B. (2005). Brain metastases: Epidemiology and pathophysiology. Journal of Neuro-Oncology, 75, 5–14. doi:10.1007/s11060-004-8093-6
Hegi, M.E., Diserens, A.C., Gorlia, T., Hamou, M.F., de Tribolet, N., Weller, M., … Stupp, R. (2005). MGMT silencing and benefit from temozolomide in glioblastoma. New England Journal of Medicine, 352, 997–1003. doi:10.1056/NEJMoa043331
Hodges, L.C., Smith, J.L., Garrett, A., & Tate, S. (1992). Prevalence of glioblastoma multiforme in subjects with prior therapeutic radiation. Journal of Neuroscience Nursing, 24, 79–83.
Houben, M.P., Aben, K.K., Teepen, J.L., Schouten-Van Meeteren, A.Y., Tijsen, C.C., Van Dujin, C.M., & Coebergh, J.W. (2006). Stable incidence of childhood and adult glioma in the Netherlands, 1989–2003. Acta Oncologica, 45, 272–279. doi:10.1080/02841860500543190
Kaye, A.H., & Laws, E.R. (1995). Historical perspective. In A.H. Kaye & E.R. Laws (Eds.), Brain tumors: An encyclopedic approach (pp. 3–8). New York, NY: Churchill Livingstone.
Lassman, A., & Holland, E. (2005, October). Glioblastoma multiforme—past, present and future. US Neurology Review, pp. 1–6. Retrieved from http://www.touchneurology.com/files/article_pdfs/neuro_1887
Legler, J.M., Ries, L.A.G., Smith, M.A., Warren, J.L., Heineman, E.F., Kaplan, R.S., & Linet, M.S. (1999). Brain and other central nervous system cancers: Recent trends in incidence and mortality. Journal of the National Cancer Institute, 91, 1382–1390. doi:10.1093/jnci/91.16.1382
Mazumdar, M., Liu, C.-Y., Wang, S.-F., Pan, P.-C., Wu, M.-T., Christiani, D.C., & Kaohsiung Brain Tumor Research Group. (2008). No association between parental or subject occupation and brain tumor risk. Cancer Epidemiology, Biomarkers and Prevention, 17, 1835–1837. doi:10.1158/1055-9965.EPI-08-0035
McLaughlin-Drubin, M.E., & Munger, K. (2008). Viruses associated with human cancer. Biochimica et Biophysica Acta, 1782, 127–150. doi:10.1016/j.bbadis.2007.12.005
Nathoo, N., Chahlavi, A., Barnett, G.H., & Toms, S.A. (2005). Pathobiology of brain metastases. Journal of Clinical Pathology, 58, 237–242. doi:10.1136/jcp.2003.013623
National Cancer Institute. (n.d.). Brain tumor. Retrieved from http://www.cancer.gov/cancertopics/types/brain
National Cancer Institute Surveillance, Epidemiology, and End Results. (2009, November). SEER stat fact sheets: Brain and other nervous system. Retrieved from http://seer.cancer.gov/statfacts/html/brain.html
Ohgaki, H. (2009). Epidemiology of brain tumors. Methods in Molecular Biology, 472, 323–342. doi:10.1007/978-1-60327-492-0_14
Parascandola, M. (2001, January). Cell phones, aluminum, Agent Orange: No? Yes? Maybe? Retrieved from http://www.dana.org/news/cerebrum/detail.aspx?id=3034
Parkin, D.M., Whelan, S.L., Feraly, J., Teppo, L., & Thomas, D.B. (Eds.). (2002). Cancer incidence in five continents (Vol. VIII). Lyon, France: International Agency for Research on Cancer.
Posner, J.B. (1992). Management of brain metastases. Revue Neurologique, 148, 477–487.
Preston, D.L., Ron, E., Yonehara, S., Toshihiro, K., Hideharu, F., Kishikawa, M., … Mabuchi, K. (2002). Tumors of the nervous system and pituitary gland associated with atomic bomb radiation exposure. Journal of the National Cancer Institute, 94, 1555–1563.
Socié, G., Curtis, R.E., Deeg, H.J., Sobocinski, K.A., Filipovich, A.H., Travis, L.B., … Horowitz, M.M. (2000). New malignant diseases after allogeneic marrow transplantation for childhood acute leukemia. Journal of Clinical Oncology, 18, 348–357.
van den Bent, M.J., Afra, D., de Witte, O., Ben Hassel, M., Schraub, S., Hoang-Huan, K., … UK Medical Research Council. (2005). Long-term efficacy of early versus delayed radiotherapy for low-grade astrocytoma and oligodendroglioma in adults: The EORTC 22845 randomised trial. Lancet, 366, 985–990. doi:10.1016/S0140-6736(05)67070-5
Wei, Q., Spitz, M.R., Gu, J., Cheng, L., Xu, X., Strom, S.S., … Hsu, T.C. (1996). DNA repair capacity correlates with mutagen sensitivity in lymphoblastoid cell lines. Cancer Epidemiology, Biomarkers and Prevention, 5, 199–204. Retrieved from http://cebp.aacrjournals.org/content/5/3/199.full.pdf
Whittle, I.R. (2004). The dilemma of low grade glioma. Journal of Neurology, Neurosurgery and Psychiatry With Practical Neurology, 75, 31–36. doi:10.1136/jnnp.2004.040501