Neuroblastoma
Neuroblastoma
Definition
Neuroblastoma is a type of cancer that usually originates either in the tissues of the adrenal gland or in the ganglia of the abdomen or in the ganglia of the nervous system. (Ganglia are masses of nerve tissue or groups of nerve cells.) Tumors develop in the nerve tissue in the neck, chest, abdomen, or pelvis.
Description
Neuroblastoma is one of the few cancer types known to secrete hormones. It occurs most often in children, and it is the third most common cancer that occurs in children. Approximately 7.5% of the childhood cancers diagnosed in 2001 were neuroblastomas, affecting one in 80,000 to 100,000 children in the United States. Close to 50% of cases of neuroblastoma occur in children younger than two years old. The disease is sometimes present at birth, but is usually not noticed until later. By the time the disease is diagnosed, it has often spread to the lymph nodes, liver, lungs, bones, or bone marrow. Approximately one-third of neuroblastomas start in the adrenal glands.
Demographics
According to some reports, African-American children develop the disease at a slightly higher rate than Caucasian children (8.7 per million compared to 8.0 per million cases diagnosed).
Causes and symptoms
The causes of neuroblastoma are not precisely known. Current research holds that neuroblastomas develop when cells produced by the fetus (neuroblast cells) fail to mature into normal nerve or adrenal cells and keep growing and proliferating. The first symptom of a neuroblastoma is usually an unusual growth or lump, found in most cases in the abdomen of the child, causing discomfort or a sensation of fullness and pain. Other symptoms such as numbness and fatigue, arise because of pressure caused by the tumor. Bone pain also occurs if the cancer has spread to the bone. If it has spread to the area behind the eye, the cancer may cause protruding eyes and dark circles around the eyes; in a few cases, blindness may be the presenting symptom. Or paralysis may result from compression of the spinal cord. Fever is also reported in one case out of four. High blood pressure, persistent diarrhea, rapid heartbeat, reddening of the skin and sweating occur occasionally. Some children may also have uncoordinated or jerky muscle movements, or uncontrollable eye movements, but these symptoms are rare. If the disease spreads to the skin, blue or purple patches are observed.
Diagnosis
A diagnosis of neuroblastoma usually requires blood and urine tests to investigate the nature and quantity of chemicals (neurotransmitters) released by the nerve cells. These are broken down by the body and released in urine. Additionally, scanning techniques are used to confirm the diagnosis of neuroblastoma. These techniques produce images or pictures of the inside of the body and they include computed tomography scan (CT scan) and magnetic resonance imaging (MRI). To confirm the diagnosis, the physician will surgically remove some of the tissue from the tumor or bone marrow (biopsy), and examine the cells under the microscope.
Treatment
The treatment team usually consists of an oncologist specialized in the treatment of neuroblastoma, a surgeon to perform biopsies and possibly attempt surgical removal of the tumor, a radiation therapy team and, if indicated, a bone marrow transplantation team.
Staging
Once neuroblastoma has been diagnosed, the physician will perform more tests to determine if the cancer has spread to other tissues in the body. This process, called staging, is important for the physician to determine how to treat the cancer and check liver and kidney function. The staging system for neuroblastoma is based on how far the disease has spread from its original site to other tissues in the body.
Localized resectable (able to be cut out) neuroblastoma is confined to the site of origin, with no evidence that it has spread to other tissues, and the cancer can be surgically removed. Localized unresectable neuroblastoma is confined to the site of origin, but the cancer cannot be completely removed surgically. Regional neuroblastoma has extended beyond its original site, to regional lymph nodes, and/or surrounding organs or tissues, but has not spread to distant sites in the body. Disseminated neuroblastoma has spread to distant lymph nodes, bone, liver, skin, bone marrow, and/or other organs. Stage 4S (or IVS, or "special") neuroblastoma has spread only to liver, skin, and/or, to a very limited extent, bone marrow. Recurrent neuroblastoma means that the cancer has come back, or continued to spread after it has been treated. It may come back in the original site or in another part of the body.
Treatments are available for children with all stages of neuroblastoma. More than one of these treatments may be used, depending on the stage of the disease. The four types of treatment used are:
- surgery (removing the tumor in an operation)
- radiation therapy (using high-energy x-rays to kill cancer cells)
- chemotherapy (using drugs to kill cancer cells)
- bone marrow transplantation (replacing the patient's bone marrow cells with those from a healthy person)
Surgery is used whenever possible, to remove as much of the cancer as possible, and can generally cure the disease if the cancer has not spread to other areas of the body. Before surgery, chemotherapy may be used to shrink the tumor so that it can be more easily removed during surgery; this is called neoadjuvant chemotherapy. Radiation therapy is often used after surgery; high-energy rays (radiation) are used to kill as many of the remaining cancer cells as possible. Chemotherapy (called adjuvant chemotherapy) may also be used after surgery to kill remaining cells. Bone marrow transplantation is used to replace bone marrow cells killed by radiation or chemotherapy. In some cases the patient's own bone marrow is removed prior to treatment and saved for transplantation later. Other times the bone marrow comes from a "matched" donor, such as a sibling.
One novel approach to treatment of neuroblastomas is therapy with desferoxamine (DFO), which is ordinarily used to treat iron poisoning. DFO has been shown to have antitumor activity in neuroblastomas and other cancers of the central nervous system. It is thought that the drug works by lowering the increased iron levels in the body associated with cancer.
As of 2004, there are significant differences in treatment protocols for neuroblastoma between the major North American study group (Children's Oncology Group) and its European counterpart, the Société Internationale d'Oncologie Pédiatrique (SIOP). These differences include biopsy techniques, the timing and extent of surgery, chemotherapy dosages, and the types of salvage therapy employed.
Alternative treatment
No alternative therapy has yet been reported to substitute for conventional neuroblastoma treatment. Complementary therapies—such as retinoic acid therapy—have been shown to be beneficial to patients when administered after a conventional course of chemotherapy or transplantation.
Prognosis
The chances of recovery from neuroblastoma depend on the stage of the cancer, the age of the child at diagnosis, the location of the tumor, and the state and nature of the tumor cells evaluated under the microscope. Infants have a higher rate of cure than do children over one year of age, even when the disease has spread. In general, the prognosis for a young child with neuroblastoma is good: the predicted five-year survival rate is approximately 85% for children who had the onset of the disease in infancy, and 35% for those whose disease developed later.
Prevention
Neuroblastoma may be a genetic disease passed down from the parents. In 2004, a group of German researchers reported that a series of neuroblastomas demonstrated a consistent pattern of deletions and overrepresentations on chromosomes 3, 10, 17q, and 20. There is currently no known method for its prevention.
Special concerns
After completion of a course of treatment for neuroblastoma, physicians sometimes recommend that the child undergo an investigative operation. This procedure allows the treatment team to evaluate how effective treatment has been, and may offer an opportunity to remove more of the tumor if it is still present.
KEY TERMS
Adjuvant chemotherapy— Treatment of the tumor with drugs after surgery to kill as many of the remaining cancer cells as possible.
Adrenal gland— Gland located above each kidney consisting of an outer wall (cortex) that produces steroid hormones and an inner section (medulla) that produces other important hormones, such as adrenaline and noradrenaline.
Alternative therapy— A therapy is generally called alternative when it is used instead of conventional cancer treatments.
Biopsy— A small sample of tissue removed from the site of the tumor to be examined under a microscope.
Conventional therapy— Treatments that are widely accepted and practiced by the mainstream medical community.
Complementary therapy— A therapy is called complementary when it is used in addition to conventional cancer treatments.
Disseminated— Spread to other tissues.
Hormone— A substance produced by specialized cells that affects the way the body carries out the biochemical and energy-producing processes required to maintain health (metabolism.
Localized— Confined to a small area.
Neoadjuvant chemotherapy— Treatment of the tumor with drugs before surgery to reduce the size of the tumor.
Neuroblast cells— Cells produced by the fetus which mature into nerve cells and adrenal medulla cells.
Monoclonal antibody— A protein substance which is produced in the laboratory by a single population of cells. They are being tested as a possible form of cancer treatment.
Resectable cancer— A tumor that can be surgically removed.
Salvage therapy— Treatment measures taken late in the course of a disease after other therapies have failed. It is also known as rescue therapy.
Staging system— A system based on how far the cancer has spread from its original site, developed to help the physician determine how best to treat the disease.
Unresectable cancer— A tumor that cannot be completely removed by surgery.
Resources
BOOKS
Alexander, F. "Neuroblastoma." Urol. Clin. North. Am. 27, August 2000, pp. 383-92.
Beers, Mark H., MD, and Robert Berkow, MD., editors. "Neuroblastoma." Section 19, Chapter 266 In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2004.
PERIODICALS
Alexander, F. "Neuroblastoma." Urol. Clin. North. Am. 27 (August 2000): 383-392.
Berthold, F., and B. Hero. "Neuroblastoma: current drug therapy recommendations as part of the total treatment approach." Drugs 59 (June 2000): 1261-1277.
Bockmuhl, U., X. You, M. Pacyna-Gengelbach, et al. "CGH Pattern of Esthesioneuroblastoma and Their Metastases." Brain Pathology 14 (April 2004): 158-163.
Dayani, P. N., M. C. Bishop, K. Plack, and P. M. Zeltzer. "Desferoxamine (DFO)—Mediated Iron Chelation: Rationale for a Novel Approach to Therapy for Brain Cancer." Journal of Neurooncology 67 (May 2004): 367-377.
Grosfeld, J. L. "Risk-based management of solid tumors in children." American Journal of Surgery 180 (November 2000):322-327.
Lau, J. J., J. D. Trobe, R. E. Ruiz, et al. "Metastatic Neuroblastoma Presenting with Binocular Blindness from Intracranial Compression of the Optic Nerves." Journal of Neuroophthalmology 24 (June 2004): 119-124.
Morgenstern, B. Z., A. P. Krivoshik, V. Rodriguez, and P. M. Anderson. "Wilms' Tumor and Neuroblastoma." Acta Paediatrica Supplementum 93 (May 2004): 78-84.
Pinkerton, C., R. Blanc, M. P. Vincent, C. Bergeron, B. Fervers, and T. Philip. "Induction chemotherapy in metastatic neuroblastoma—does dose influence response? A critical review of published data standards, options and recommendations (SOR) project of the National Federation of French Cancer Centres (FNCLCC)." European Journal of Cancer 36 (September 2000): 1808-1815.
ORGANIZATIONS
The American Cancer Society. "After Diagnosis: A Guide for Patients and Families." "Caring for the Patient with Cancer at Home." "Understanding Chemotherapy: A Guide for Patients and Families." "Understanding Radiation Therapy: A Guide for Patients and Families."
National Cancer Institute. Office of Cancer Communications, 31 Center Drive, MSC 2580, Bethesda, MD 20892-2580. 800-422-6237. 〈http://cancernet.nci.nih.gov/clinpdq/pif/Neuroblastoma_Patient.html〉.
National Institutes of Health & National Cancer Institute. Young People With Cancer: A Handbook for Parents. 〈http://www.cancernet.nci.nih.gov/young_people/yngconts.html〉.
Neuroblastoma
Neuroblastoma
Definition
Neuroblastoma is a type of cancer that usually originates either in the tissues of the adrenal gland or in the ganglia of the abdomen or in the ganglia of the nervous system. (Ganglia are masses of nerve tissue or groups of nerve cells.) Tumors develop in the nerve tissue in the neck, chest, abdomen, or pelvis.
Description
Neuroblastoma is one of the few cancer types known to secrete hormones. It occurs most often in children, and it is the third most common cancer that occurs in children. Approximately 7.5% of the childhood cancers diagnosed in 2001 were neuroblastomas, affecting one in 80, 000 to 100, 000 children in the United States. Close to 50% of cases of neuroblastoma occur in children younger than two years old. The disease is sometimes present at birth, but is usually not noticed until later. By the time the disease is diagnosed, it has often spread to the lymph nodes, liver, lungs, bones, or bone marrow. Approximately one-third of neuroblastomas start in the adrenal glands.
Demographics
According to some reports, African-American children develop the disease at a slightly higher rate than Caucasian children (8.7 per million compared to 8.0 per million cases diagnosed).
Causes and symptoms
The causes of neuroblastoma are not precisely known. Current research holds that neuroblastomas develop when cells produced by the fetus (neuroblast cells) fail to mature into normal nerve or adrenal cells and keep growing and proliferating. The first symptom of a neuroblastoma is usually an unusual growth or lump, found in most cases in the abdomen of the child, causing discomfort or a sensation of fullness and pain. Other symptoms such as numbness and fatigue , arise because of pressure caused by the tumor. Bone pain also occurs if the cancer has spread to the bone. If it has spread to the area behind the eye, the cancer may cause protruding eyes and dark circles around the eyes. Or paralysis may result from compression of the spinal cord. Fever is also reported in one case out of four. High blood pressure, persistent diarrhea , rapid heartbeat, reddening of the skin and sweating occur occasionally. Some children may also have uncoordinated or jerky muscle movements, or uncontrollable eye movements, but these symptoms are rare. If the disease spreads to the skin, blue or purple patches are observed.
Diagnosis
A diagnosis of neuroblastoma usually requires blood and urine tests to investigate the nature and quantity of chemicals (neurotransmitters) released by the nerve cells. These are broken down by the body and released in urine. Additionally, scanning techniques are used to confirm the diagnosis of neuroblastoma. These techniques produce images or pictures of the inside of the body and they include computed tomography scan (CT scan) and magnetic resonance imaging (MRI). To confirm the diagnosis, the physician will surgically remove some of the tissue from the tumor or bone marrow (biopsy ), and examine the cells under the microscope.
Treatment team
The treatment team usually consists of an oncologist specialized in the treatment of neuroblastoma, a surgeon to perform biopsies and possibly attempt surgical removal of the tumor, a radiation therapy team and, if indicated, a bone marrow transplantation team.
Clinical staging, treatments, and prognosis
Staging
Once neuroblastoma has been diagnosed, the physician will perform more tests to determine if the cancer has spread to other tissues in the body. This process, called staging, is important for the physician to determine how to treat the cancer and check liver and kidney function. The staging system for neuroblastoma is based on how far the disease has spread from its original site to other tissues in the body.
Localized resectable (able to be cut out) neuroblastoma is confined to the site of origin, with no evidence that it has spread to other tissues, and the cancer can be surgically removed. Localized unresectable neuroblastoma is confined to the site of origin, but the cancer cannot be completely removed surgically. Regional neuroblastoma has extended beyond its original site, to regional lymph nodes, and/or surrounding organs or tissues, but has not spread to distant sites in the body. Disseminated neuroblastoma has spread to distant lymph nodes, bone, liver, skin, bone marrow, and/or other organs. Stage 4S (or IVS, or "special") neuroblastoma has spread only to liver, skin, and/or, to a very limited extent, bone marrow. Recurrent neuroblastoma means that the cancer has come back, or continued to spread after it has been treated. It may come back in the original site or in another part of the body.
Treatments
Treatments are available for children with all stages of neuroblastoma. More than one of these treatments may be used, depending on the stage of the disease. The four types of treatment used are:
- Surgery (removing the tumor in an operation)
- Radiation therapy (using high-energy x-rays to kill cancer cells)
- Chemotherapy (using drugs to kill cancer cells)
- Bone marrow transplantation (replacing the patient's bone marrow cells with those from a healthy person).
Surgery is used whenever possible, to remove as much of the cancer as possible, and can generally cure the disease if the cancer has not spread to other areas of the body. Before surgery, chemotherapy may be used to shrink the tumor so that it can be more easily removed during surgery; this is called neoadjuvant chemotherapy. Radiation therapy is often used after surgery; high-energy rays (radiation) are used to kill as many of the remaining cancer cells as possible. Chemotherapy (called adjuvant chemotherapy) may also be used after surgery to kill remaining cells. Bone marrow transplantation is used to replace bone marrow cells killed by radiation or chemotherapy. In some cases the patient's own bone marrow is removed prior to treatment and saved for transplantation later. Other times the bone marrow comes from a "matched" donor, such as a sibling.
Prognosis
The chances of recovery from neuroblastoma depend on the stage of the cancer, the age of the child at diagnosis, the location of the tumor, and the state and nature of the tumor cells evaluated under the microscope. Infants have a higher rate of cure than do children over one year of age, even when the disease has spread. In general, the prognosis for a young child with neuroblastoma is good: the predicted five-year survival rate is approximately 85% for children who had the onset of the disease in infancy, and 35% for those whose disease developed later.
Alternative and complementary therapies
No alternative therapy has yet been reported to substitute for conventional neuroblastoma treatment. Complementary therapies—such as retinoic acid therapy— have been shown to be beneficial to patients when administered after a conventional course of chemotherapy or transplantation.
Coping with cancer treatment
Neuroblastoma is a childhood cancer and it must be recognized that children, adolescents and their families have very special needs. These are best met at cancer centers for children working in close contact with the treatment team and the primary care physician. These centers have experience in recognizing the unique needs of children having to cope with cancer and they are staffed by pediatric support professionals other than the oncology treatment team while being associated with a children's hospital.
Clinical trials
In 2001, the National Cancer Institute supported over 39 neuroblastoma clinical trials to evaluate a variety of anti-cancer drugs either combined to other drugs or to other treatments. Clinical trials are being carried out to investigate the use of a drug called topotecan , alone and in combination with another drug called cyclophosphamide . It is hoped that this drug will allow less intense doses of chemotherapy drugs to be used for treatment of neuroblastoma. Other clinical trials have shown that long-term retinoid therapy following high-dose chemotherapy lowers the risk of recurrence for children with certain types of neuroblastoma. Research is presently aimed at developing more effective retinoids and at understanding the possible benefits of retinoids in the treatment of neuroblastoma. Trials on treatments based on the use of monoclonal antibodies also show that approximately 40% of children with neuroblastoma show some response to some types of monoclonal antibodies.
Prevention
Neuroblastoma may be a genetic disease passed down from the parents. There is currently no known method for its prevention.
Special concerns
After completion of a course of treatment for neuroblastoma, physicians sometimes recommend that the child undergo an investigative operation. This procedure allows the treatment team to evaluate how effective treatment has been, and may offer an opportunity to remove more of the tumor if it is still present.
See Also Bone marrow aspiration and biopsy
Resources
BOOKS
Raghaven, Derek, et al, eds. Principles and Practice of Geni tourinary Oncology. Philadelphia: Lippincott-Raven Pub lishers, 1997.
PERIODICALS
Alexander, F. "Neuroblastoma." Urol. Clin. North. Am. 27 (August 2000):383-92.
Berthold, F., B. Hero. "Neuroblastoma: current drug therapy recommendations as part of the total treatment approach." Drugs 59 (June 2000):1261-77.
Grosfeld, J. L. "Risk-based management of solid tumors in children." American Journal of Surgery 180 (November 2000):322-7.
Herrera, J. M., A. Krebs, P. Harris, F. Barriga. "Childhood tumors." Surg. Clin. North. Am. 80 (April 2000):747-60.
Hoefnagel, C. A. "Nuclear medicine therapy of neuroblas toma." Quartely Journal of Nuclear Medicine 43 (Decem ber 1999):336-43.
Pinkerton, C., R. Blanc, M. P. Vincent, C. Bergeron, B. Fervers, T. Philip. "Induction chemotherapy in metastatic neurob lastoma—does dose influence response? A critical review of published data standards, options and recommenda tions (SOR) project of the National Federation of French Cancer Centres (FNCLCC)." European Journal of Cancer 36 (September 2000):1808-15.
ORGANIZATIONS
The American Cancer Society (1-800-ACS-2345) provides information on specific types of cancer and a variety of cancer-related subjects. Additionally, it distributes book lets which can help cope with cancer treatment. Examples are: After Diagnosis: A Guide for Patients and Families (Booklet, Code #9440); Caring for the Patient with Can cer at Home (Booklet, Code #4656); Understanding Chemotherapy: A Guide for Patients and Families (Book let, Code #9458); Understanding Radiation Therapy: A Guide for Patients and Families (Booklet, Code #9459).
National Cancer Institute. Office of Cancer Communications, 31 Center Drive, MSC 2580, Bethesda, MD 20892-2580. 800-422-6237. <http://cancernet.nci.nih.gov/clinpdq/pif/Neuroblastoma_Patient.html.>
National Institutes of Health & National Cancer Institute. Young People With Cancer: A Handbook for Parents <http://www.cancernet.nci.nih.gov/young_people/yngconts.html>
Lisa Christenson
Monique Laberge, PhD
KEY TERMS
Adjuvant chemotherapy
—Treatment of the tumor with drugs after surgery to kill as many of the remaining cancer cells as possible.
Adrenal gland
—Gland located above each kidney consisting of an outer wall (cortex) that produces steroid hormones and an inner section (medulla) that produces other important hormones, such as adrenaline and noradrenaline.
Alternative therapy
—A therapy is generally called alternative when it is used instead of conventional cancer treatments.
Biopsy
—A small sample of tissue removed from the site of the tumor to be examined under a microscope.
Conventional therapy
—Treatments that are widely accepted and practiced by the mainstream medical community.
Complementary therapy
—A therapy is called complementary when it is used in addition to conventional cancer treatments.
Disseminated
—Spread to other tissues.
Hormone
—A substance produced by specialized cells that affects the way the body carries out the biochemical and energy-producing processes required to maintain health (metabolism).
Localized
—Confined to a small area.
Neoadjuvant chemotherapy
—Treatment of the tumor with drugs before surgery to reduce the size of the tumor.
Neuroblast cells
—Cells produced by the fetus which mature into nerve cells and adrenal medulla cells.
Monoclonal antibody
—A protein substance which is produced in the laboratory by a single population of cells. They are being tested as a possible form of cancer treatment.
Resectable cancer
—A tumor that can be surgically removed.
Staging system
—A system based on how far the cancer has spread from its original site, developed to help the physician determine how best to treat the disease.
Unresectable cancer
—A tumor that cannot be completely removed by surgery.
QUESTIONS TO ASK THE DOCTOR
- What treatment choices do we have?
- Has the neuroblastoma spread to other parts of the body?
- What is the stage of the cancer?
- Based on your experience in treating neuroblastoma, how long do you think my child will survive if there is no response to treatment or the cancer comes back?
- How long will it take to recover from treatment?
- Will my child develop any long-term risks or complications from the cancer or its treatment?
- Can you recommend a support group in my town for people who are coping with neuroblastoma?