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KANSAS CITY, MO—As cancer treatment advances, the prevalence of childhood cancer survivors increases; as a result, physicians see more neurologic complications of surgery, chemotherapy, and radiation, according to an overview presented at the 46th Annual Meeting of the Child Neurology Society.
“There is an increasing impact of neurologic and neuropsychological toxicity that underscores the need for intervention and follow-up over the lifespan,” said Nicole Ullrich, MD, PhD, Director of Neurologic Neuro-Oncology at the Dana-Farber/Boston Children's Cancer and Blood Disorders Center.
Lifelong Effects
The prevalence of adult survivors of childhood cancer is one in 250 people, and there are more than 270,000 childhood cancer survivors in the United States. These cancer survivors “experience long-term toxicities affecting their respiratory system, cardiovascular system, cerebrovascular system, reproductive system, and a gamut of other late effects of treatment that we need to think about as they continue to advance into adulthood,” said Dr. Ullrich.
“Ninety-five percent of all cancer survivors will have a chronic health problem by the age of 45, and 80% will have a severe or life-threatening condition,” she said. The risk is greater for patients with CNS malignancies.
Childhood cancer survivors may develop physical, cognitive, and psychological issues later in life. These late effects have a significant impact on their quality and quantity of life. Neurologic issues can include headache, seizures, and stroke.
Headache and Seizures
Patients with elevated intracranial pressure or large tumors have an increased risk of headache. Nontumor causes of headache may include medications, such as antiemetic drugs and chemotherapy. Radiation therapy may cause acute radiation necrosis and long-term vascular issues. Supportive therapies, including steroids, antacids, and antinausea regimens, can cause headaches as well as sleep disruption, said Dr. Ullrich.
Approximately 15% to 25% of children with a brain tumor present with a seizure. Seizures are more often associated with low-grade tumors. Children with solid tumors or leukemia often have seizures without clinical or radiologic signs of a structural lesion. When a surgeon removes the tumor, there may be associated areas of dysplasia that surround the tumor, said Dr. Ullrich. Strategies such as electrocorticography or intraoperative monitoring can help identify epileptic zones for removal during surgery.
Potential causes of seizures include the tumor itself, surrounding edema, areas of cortical dysplasia, hyperexcitability related to neurotransmitters and glutamate levels, and scar formation that occurs after tumor resection. Individuals who have had cortically based or temporal lobe tumors or who have had incomplete resection or preexisting seizures before diagnosis have the highest risk of developing seizures, even years after completion of therapy.
EEG can help confirm seizures and distinguish between seizure types. It also can aid in the choice of an anticonvulsant. “We tend to lean more towards non-enzyme-inducing anticonvulsants in order to not interfere with concurrent chemotherapy,” said Dr. Ullrich. If seizures are acutely related to a drug or infection, Dr. Ullrich aims to withdraw anticonvulsants as soon as possible.
Surgery and Chemotherapy
Children who have had a gross total resection of the primary tumor may still be at risk for acute neurologic, neurosensory, and neuromotor issues, endocrine dysfunction, cerebellar mutism, and other neuropsychological deficits, said Dr. Ullrich.
Deficits and long-term effects of brain tumor treatment mainly depend on tumor location. Maximal tumor resection may cause hypopituitarism, vascular issues, and vision issues. Image-guided therapy can help surgeons remove most, if not all, of the tumor during the initial resection.
Chemotherapy-related neurologic effects are common, said Dr. Ullrich. One of the main side effects is chemotherapy-induced peripheral neuropathy (ie, any injury or inflammation to the peripheral nerve due to administration of a chemotherapeutic drug). Patients with peripheral neuropathy may exhibit changes in their gait, loss of reflexes, and sensory changes. Pediatric patients with Charcot-Marie-Tooth disease or other hereditary neuropathies have a greater risk of chemotherapy-induced peripheral neuropathy.
Radiation
Age at the time of radiation, radiation field, genetic predisposition, and total dose are all risk factors for radiation-induced cognitive injury. One study found that children younger than 7 had the most significant decline in overall IQ after radiation. This research led to a shift in the development of treatment protocols and inspired physicians to strive to decrease and eliminate the use of radiation in the youngest patients, said Dr. Ullrich.
Another consequence of radiation may be the development of secondary neoplasms. The mean interval between the time of radiation and the development of secondary tumors is around eight years. These secondary neoplasms resulting from radiation often have anaplastic features. Childhood cancer survivors should see a dermatologist to monitor radiated areas for skin cancer.
Stroke and SMART Syndrome
Stroke is increasingly recognized as a late consequence of cancer treatment, especially in patients who have been treated for leukemia and brain tumors. Studies have found that prior radiation is an independent predictor of stroke. Mueller et al found that pediatric cancer survivors with hypertension had a fourfold increased risk of stroke, compared with sibling controls.
“Screen for correctable risk factors such as hypertension, hypercholesterolemia, hyperlipidemia, obesity, and sedentary lifestyle,” said Dr. Ullrich.
SMART syndrome (stroke-like migraine attacks after radiation therapy) is another potential complication that can occur years after radiation therapy. The syndrome can present like a transient ischemic attack, and symptoms can last hours to days. This syndrome can be treated with aggressive preventive headache care.
Mitigation and Prevention
Neurologists can take steps to help prevent or ameliorate some of these late effects. The Children's Oncology Group has created Passport for Care, a tool that allows patients to share a summary of their cancer treatments and follow-up recommendations with their primary care providers. The Children's Oncology Group also has created long-term follow-up guidelines for survivors of childhood, adolescent, and young adult cancers.
In addition, new and refined surgical techniques help detect and remove residual tumor after surgery. Proton beam radiation, intensity-modulated radiation therapy, and other approaches can help reduce doses of radiation, potentially reducing cognitive risks. “The goal is to shift the paradigm from just categorizing the late effects to mitigating them and actually preventing them in the first place,” said Dr. Ullrich.
—Erica Tricarico
Suggested Reading
Mueller S, Fullerton HJ, Stratton K, et al. Radiation, atherosclerotic risk factors and stroke risk in survivors of pediatric cancer: a report from the Childhood Cancer Survivor Study. Int J Radiat Oncol Biol Phys. 2013;86(4):649-655.
KANSAS CITY, MO—As cancer treatment advances, the prevalence of childhood cancer survivors increases; as a result, physicians see more neurologic complications of surgery, chemotherapy, and radiation, according to an overview presented at the 46th Annual Meeting of the Child Neurology Society.
“There is an increasing impact of neurologic and neuropsychological toxicity that underscores the need for intervention and follow-up over the lifespan,” said Nicole Ullrich, MD, PhD, Director of Neurologic Neuro-Oncology at the Dana-Farber/Boston Children's Cancer and Blood Disorders Center.
Lifelong Effects
The prevalence of adult survivors of childhood cancer is one in 250 people, and there are more than 270,000 childhood cancer survivors in the United States. These cancer survivors “experience long-term toxicities affecting their respiratory system, cardiovascular system, cerebrovascular system, reproductive system, and a gamut of other late effects of treatment that we need to think about as they continue to advance into adulthood,” said Dr. Ullrich.
“Ninety-five percent of all cancer survivors will have a chronic health problem by the age of 45, and 80% will have a severe or life-threatening condition,” she said. The risk is greater for patients with CNS malignancies.
Childhood cancer survivors may develop physical, cognitive, and psychological issues later in life. These late effects have a significant impact on their quality and quantity of life. Neurologic issues can include headache, seizures, and stroke.
Headache and Seizures
Patients with elevated intracranial pressure or large tumors have an increased risk of headache. Nontumor causes of headache may include medications, such as antiemetic drugs and chemotherapy. Radiation therapy may cause acute radiation necrosis and long-term vascular issues. Supportive therapies, including steroids, antacids, and antinausea regimens, can cause headaches as well as sleep disruption, said Dr. Ullrich.
Approximately 15% to 25% of children with a brain tumor present with a seizure. Seizures are more often associated with low-grade tumors. Children with solid tumors or leukemia often have seizures without clinical or radiologic signs of a structural lesion. When a surgeon removes the tumor, there may be associated areas of dysplasia that surround the tumor, said Dr. Ullrich. Strategies such as electrocorticography or intraoperative monitoring can help identify epileptic zones for removal during surgery.
Potential causes of seizures include the tumor itself, surrounding edema, areas of cortical dysplasia, hyperexcitability related to neurotransmitters and glutamate levels, and scar formation that occurs after tumor resection. Individuals who have had cortically based or temporal lobe tumors or who have had incomplete resection or preexisting seizures before diagnosis have the highest risk of developing seizures, even years after completion of therapy.
EEG can help confirm seizures and distinguish between seizure types. It also can aid in the choice of an anticonvulsant. “We tend to lean more towards non-enzyme-inducing anticonvulsants in order to not interfere with concurrent chemotherapy,” said Dr. Ullrich. If seizures are acutely related to a drug or infection, Dr. Ullrich aims to withdraw anticonvulsants as soon as possible.
Surgery and Chemotherapy
Children who have had a gross total resection of the primary tumor may still be at risk for acute neurologic, neurosensory, and neuromotor issues, endocrine dysfunction, cerebellar mutism, and other neuropsychological deficits, said Dr. Ullrich.
Deficits and long-term effects of brain tumor treatment mainly depend on tumor location. Maximal tumor resection may cause hypopituitarism, vascular issues, and vision issues. Image-guided therapy can help surgeons remove most, if not all, of the tumor during the initial resection.
Chemotherapy-related neurologic effects are common, said Dr. Ullrich. One of the main side effects is chemotherapy-induced peripheral neuropathy (ie, any injury or inflammation to the peripheral nerve due to administration of a chemotherapeutic drug). Patients with peripheral neuropathy may exhibit changes in their gait, loss of reflexes, and sensory changes. Pediatric patients with Charcot-Marie-Tooth disease or other hereditary neuropathies have a greater risk of chemotherapy-induced peripheral neuropathy.
Radiation
Age at the time of radiation, radiation field, genetic predisposition, and total dose are all risk factors for radiation-induced cognitive injury. One study found that children younger than 7 had the most significant decline in overall IQ after radiation. This research led to a shift in the development of treatment protocols and inspired physicians to strive to decrease and eliminate the use of radiation in the youngest patients, said Dr. Ullrich.
Another consequence of radiation may be the development of secondary neoplasms. The mean interval between the time of radiation and the development of secondary tumors is around eight years. These secondary neoplasms resulting from radiation often have anaplastic features. Childhood cancer survivors should see a dermatologist to monitor radiated areas for skin cancer.
Stroke and SMART Syndrome
Stroke is increasingly recognized as a late consequence of cancer treatment, especially in patients who have been treated for leukemia and brain tumors. Studies have found that prior radiation is an independent predictor of stroke. Mueller et al found that pediatric cancer survivors with hypertension had a fourfold increased risk of stroke, compared with sibling controls.
“Screen for correctable risk factors such as hypertension, hypercholesterolemia, hyperlipidemia, obesity, and sedentary lifestyle,” said Dr. Ullrich.
SMART syndrome (stroke-like migraine attacks after radiation therapy) is another potential complication that can occur years after radiation therapy. The syndrome can present like a transient ischemic attack, and symptoms can last hours to days. This syndrome can be treated with aggressive preventive headache care.
Mitigation and Prevention
Neurologists can take steps to help prevent or ameliorate some of these late effects. The Children's Oncology Group has created Passport for Care, a tool that allows patients to share a summary of their cancer treatments and follow-up recommendations with their primary care providers. The Children's Oncology Group also has created long-term follow-up guidelines for survivors of childhood, adolescent, and young adult cancers.
In addition, new and refined surgical techniques help detect and remove residual tumor after surgery. Proton beam radiation, intensity-modulated radiation therapy, and other approaches can help reduce doses of radiation, potentially reducing cognitive risks. “The goal is to shift the paradigm from just categorizing the late effects to mitigating them and actually preventing them in the first place,” said Dr. Ullrich.
—Erica Tricarico
Suggested Reading
Mueller S, Fullerton HJ, Stratton K, et al. Radiation, atherosclerotic risk factors and stroke risk in survivors of pediatric cancer: a report from the Childhood Cancer Survivor Study. Int J Radiat Oncol Biol Phys. 2013;86(4):649-655.
KANSAS CITY, MO—As cancer treatment advances, the prevalence of childhood cancer survivors increases; as a result, physicians see more neurologic complications of surgery, chemotherapy, and radiation, according to an overview presented at the 46th Annual Meeting of the Child Neurology Society.
“There is an increasing impact of neurologic and neuropsychological toxicity that underscores the need for intervention and follow-up over the lifespan,” said Nicole Ullrich, MD, PhD, Director of Neurologic Neuro-Oncology at the Dana-Farber/Boston Children's Cancer and Blood Disorders Center.
Lifelong Effects
The prevalence of adult survivors of childhood cancer is one in 250 people, and there are more than 270,000 childhood cancer survivors in the United States. These cancer survivors “experience long-term toxicities affecting their respiratory system, cardiovascular system, cerebrovascular system, reproductive system, and a gamut of other late effects of treatment that we need to think about as they continue to advance into adulthood,” said Dr. Ullrich.
“Ninety-five percent of all cancer survivors will have a chronic health problem by the age of 45, and 80% will have a severe or life-threatening condition,” she said. The risk is greater for patients with CNS malignancies.
Childhood cancer survivors may develop physical, cognitive, and psychological issues later in life. These late effects have a significant impact on their quality and quantity of life. Neurologic issues can include headache, seizures, and stroke.
Headache and Seizures
Patients with elevated intracranial pressure or large tumors have an increased risk of headache. Nontumor causes of headache may include medications, such as antiemetic drugs and chemotherapy. Radiation therapy may cause acute radiation necrosis and long-term vascular issues. Supportive therapies, including steroids, antacids, and antinausea regimens, can cause headaches as well as sleep disruption, said Dr. Ullrich.
Approximately 15% to 25% of children with a brain tumor present with a seizure. Seizures are more often associated with low-grade tumors. Children with solid tumors or leukemia often have seizures without clinical or radiologic signs of a structural lesion. When a surgeon removes the tumor, there may be associated areas of dysplasia that surround the tumor, said Dr. Ullrich. Strategies such as electrocorticography or intraoperative monitoring can help identify epileptic zones for removal during surgery.
Potential causes of seizures include the tumor itself, surrounding edema, areas of cortical dysplasia, hyperexcitability related to neurotransmitters and glutamate levels, and scar formation that occurs after tumor resection. Individuals who have had cortically based or temporal lobe tumors or who have had incomplete resection or preexisting seizures before diagnosis have the highest risk of developing seizures, even years after completion of therapy.
EEG can help confirm seizures and distinguish between seizure types. It also can aid in the choice of an anticonvulsant. “We tend to lean more towards non-enzyme-inducing anticonvulsants in order to not interfere with concurrent chemotherapy,” said Dr. Ullrich. If seizures are acutely related to a drug or infection, Dr. Ullrich aims to withdraw anticonvulsants as soon as possible.
Surgery and Chemotherapy
Children who have had a gross total resection of the primary tumor may still be at risk for acute neurologic, neurosensory, and neuromotor issues, endocrine dysfunction, cerebellar mutism, and other neuropsychological deficits, said Dr. Ullrich.
Deficits and long-term effects of brain tumor treatment mainly depend on tumor location. Maximal tumor resection may cause hypopituitarism, vascular issues, and vision issues. Image-guided therapy can help surgeons remove most, if not all, of the tumor during the initial resection.
Chemotherapy-related neurologic effects are common, said Dr. Ullrich. One of the main side effects is chemotherapy-induced peripheral neuropathy (ie, any injury or inflammation to the peripheral nerve due to administration of a chemotherapeutic drug). Patients with peripheral neuropathy may exhibit changes in their gait, loss of reflexes, and sensory changes. Pediatric patients with Charcot-Marie-Tooth disease or other hereditary neuropathies have a greater risk of chemotherapy-induced peripheral neuropathy.
Radiation
Age at the time of radiation, radiation field, genetic predisposition, and total dose are all risk factors for radiation-induced cognitive injury. One study found that children younger than 7 had the most significant decline in overall IQ after radiation. This research led to a shift in the development of treatment protocols and inspired physicians to strive to decrease and eliminate the use of radiation in the youngest patients, said Dr. Ullrich.
Another consequence of radiation may be the development of secondary neoplasms. The mean interval between the time of radiation and the development of secondary tumors is around eight years. These secondary neoplasms resulting from radiation often have anaplastic features. Childhood cancer survivors should see a dermatologist to monitor radiated areas for skin cancer.
Stroke and SMART Syndrome
Stroke is increasingly recognized as a late consequence of cancer treatment, especially in patients who have been treated for leukemia and brain tumors. Studies have found that prior radiation is an independent predictor of stroke. Mueller et al found that pediatric cancer survivors with hypertension had a fourfold increased risk of stroke, compared with sibling controls.
“Screen for correctable risk factors such as hypertension, hypercholesterolemia, hyperlipidemia, obesity, and sedentary lifestyle,” said Dr. Ullrich.
SMART syndrome (stroke-like migraine attacks after radiation therapy) is another potential complication that can occur years after radiation therapy. The syndrome can present like a transient ischemic attack, and symptoms can last hours to days. This syndrome can be treated with aggressive preventive headache care.
Mitigation and Prevention
Neurologists can take steps to help prevent or ameliorate some of these late effects. The Children's Oncology Group has created Passport for Care, a tool that allows patients to share a summary of their cancer treatments and follow-up recommendations with their primary care providers. The Children's Oncology Group also has created long-term follow-up guidelines for survivors of childhood, adolescent, and young adult cancers.
In addition, new and refined surgical techniques help detect and remove residual tumor after surgery. Proton beam radiation, intensity-modulated radiation therapy, and other approaches can help reduce doses of radiation, potentially reducing cognitive risks. “The goal is to shift the paradigm from just categorizing the late effects to mitigating them and actually preventing them in the first place,” said Dr. Ullrich.
—Erica Tricarico
Suggested Reading
Mueller S, Fullerton HJ, Stratton K, et al. Radiation, atherosclerotic risk factors and stroke risk in survivors of pediatric cancer: a report from the Childhood Cancer Survivor Study. Int J Radiat Oncol Biol Phys. 2013;86(4):649-655.