Eight patients with recurrent medulloblastoma were treated with a chemotherapy regimen consisting... more Eight patients with recurrent medulloblastoma were treated with a chemotherapy regimen consisting of vincristine, BCNU, dexamethasone and intrathecal and intermediate dose intravenous methotrexate (500 mg/m/sup 2/). Five also received local low dose radiotherapy (RT). All 8 patients responded to treatment; 6 completely and 2 partially. These latter 2 were in their second and third recurrences. Three remain in remission. The median duration of response was 18.8 months, and median time from start of chemotherapy to death was 32 months using the Kaplan-Meier technique. In addition, 9 other patients with newly diagnosed medulloblastoma were treated with craniospinal radiation and the same adjuvant chemotherapy as above. The first 5 patients also received intraventricular methotrexate and/or intravenous BCNU during radiotherapy. The toxicity in the 5 patients was very severe. There were three toxic deaths, one death from cancer; one patient survives disease-free, but he is demented. With...
This article reviews the current approach to the treatment of childhood brain tumors. Common chil... more This article reviews the current approach to the treatment of childhood brain tumors. Common childhood brain tumors are profiled in separate sections, and the conclusion includes a discussion of the long-term clinical effects of radiation and chemotherapy.
Survivals of children with brain tumors have increased over the past 20 years owing to advances i... more Survivals of children with brain tumors have increased over the past 20 years owing to advances in surgery, radiation, and, most recently, chemotherapy. Unfortunately, central nervous system therapy, particularly radiation, may be associated with the development of dementia and learning disabilities, leukoencephalopathy, endocrinopathies, and oncogenesis. Recognition of these long-term effects of therapy is important as some are amenable to treatment and others may be prevented by modification of current treatment regimens.
Overall, the majority of patients with optic pathway tumors will have stable disease regardless i... more Overall, the majority of patients with optic pathway tumors will have stable disease regardless if they are radiated or receive chemotherapy. This is a very indolent tumor system and, for the most part, not a threat to life. Because of this, issues regarding appropriate therapeutic approaches have yet to be resolved. Most agree that in patients with progressive visual loss and tumor limited to the orbit, surgery can be associated with a cure. The downside is the loss of vision associated with surgical extirpation. Radiation rather than surgery has been the mainstay of treatment for intracranial tumors of the optic pathway. To eliminate side effects associated with radiotherapy in the young child, chemotherapy may be the more considered choice. However, on escape of control, i.e., conversion of stable disease to progressive disease, radiotherapy should be considered.
Publisher Summary This chapter discusses the meaning of cure in childhood central nervous system ... more Publisher Summary This chapter discusses the meaning of cure in childhood central nervous system malignancies. Of all malignancies in childhood, the tumors of the central nervous system are second in frequency only to leukemia. The success of treatment in childhood leukemia has resulted in a correspondingly aggressive approach to CNS neoplasia in children. The burgeoning number of child neurologists, the increasing availability of sophisticated technology, and an ever expanding therapeutic armamentarium has led to more involvement of child neurologists in the management of CNS tumors and their complications. Depending upon the biological behavior of the particular tumor following surgery, craniospinal radiation is recommended with a large boost to the tumor bed. It is found that although a great deal is known about radiation biology and the effects of ionizing radiation on normal as well as abnormal tissue, radiation dosage schedules have been developed in an empirical fashion. Side-effects are not only dependent on the total dose but also on the radiation given per unit dose. It is found that because of radiation complications, it has been recommended that the amount of radiation per unit dose be reduced.
Approximately 13% of brain tumors in childhood occur in children less than 2 years of age. Althou... more Approximately 13% of brain tumors in childhood occur in children less than 2 years of age. Although the survivals of older children with certain forms of brain tumors have increased over the past 20 years, this treatment has been least effective in very young children with brain tumors. These poor survival rates may be due in part to the highly malignant nature of the neoplasms; the delay in diagnosis because of low index of suspicion; the large bulk of tumor found at presentation, and the reduction in radiation dosage to the central nervous system. Since standard treatment has produced both poor results and severe neurotoxicity, new approaches have been sought. A conservative approach is recommended in some children with optic gliomas and low-grade supratentorial astrocytomas. Radiation is deferred until the child reaches 3–4 years of age when he can better tolerate its effects on the CNS. Current therapy of malignant brain tumors of infancy is not only toxic, but inadequate. There...
Gliomas of the optic pathway are considered to be slowly growing, potentially benign neoplasms. A... more Gliomas of the optic pathway are considered to be slowly growing, potentially benign neoplasms. Association of this tumor with neurofibromatosis has been well established. We have recently evaluated 7 children with putative evidence of optic glioma, 6 of whom had additional evidence of neurofibromatosis. All children had CT scans and visual-evoked responses. CT scan allows anatomic assessmant of the optic nerve mass while evoked responses offer the possibility of identifying functional abnormalities in the optic pathway. It is felt that both these modalities will add in the early diagnosis of optic gliomas and help to further establish the true natural history of this tumor.
Survival of children with brain tumors has improved over the past 20 years due in part to advance... more Survival of children with brain tumors has improved over the past 20 years due in part to advances in surgery, radiation, and most recently chemotherapy. The long-term adverse effects of radiation and chemotherapy on these children is the subject of this report. In Part I, we reviewed the pathologic consequences of radiation, including leukoencephalopathy, radiation necrosis, and radiation myelopathy as well as the oncogenic effects of both radiation and chemotherapy. Part II addresses the long-term consequences of radiation and chemotherapy on intellectual and endocrine function. Risk factors for the development of both endocrinopathies and intellectual dysfunction include age at the time of radiation, volume and dose of radiation, site of tumor, and use of adjuvant chemotherapy, in particular methotrexate. Early recognition of these complications and treatment, where indicated, will measurably improve the quality-of-life of children treated for brain tumors. The national cancer groups are currently attempting to limit these long-term adverse effects by taking risk factors into account when formulating new treatment regimens.
A case of infantile spasms associated with histidinemia is presented. Histidinemia was well-docum... more A case of infantile spasms associated with histidinemia is presented. Histidinemia was well-documented through biochemical assays. The patient was treated with the standard anticonvulsant regimen for infantile spasms, as well as an elimination diet for histidinemia. Despite low levels of histidine and adequate anticonvulsant therapy, the child continues to have seizures and is markedly retarded. The natural history of infantile spasms and its possible association with histidinemia is discussed.
We prospectively evaluated 47 children with neurofibromatosis to determine whether the previously... more We prospectively evaluated 47 children with neurofibromatosis to determine whether the previously reported high signals on magnetic resonance imaging (MRI) (prolonged T2) correlated with CT, brainstem auditory evoked responses (BAER), EEG, clinical examinations, cognitive abilities, or seizure disorder. Thirty percent of children had a history of seizures and 70% had either learning disabilities or mental retardation. Overall, 74% had an abnormal MRI examination. Sixty-two percent had high signals (prolonged T2) on T2-weighted images. Abnormal signals were located primarily in the basal ganglia, brainstem, and cerebellum. Twenty-five percent of patients had abnormal EEGs, 28% had abnormal CTs, and 27% had abnormal BAER examinations. The abnormal signals on MRI did not consistently relate to findings on CT, BAER, EEG, school placement, or clinical examination. The abnormal signals presumably reflect areas of abnormal brain parenchyma, either hamartomas, heterotopias, or local areas of brain dysplasia.
Although brainstem gliomas carry the worst prognosis of any brain tumor in children, with median ... more Although brainstem gliomas carry the worst prognosis of any brain tumor in children, with median survivals of 9 to 12 months, there may be a subgroup of long-term survivors. We have identified 12 children with brainstem gliomas, 5 of whom have survived greater than 6 years and 6 less than or equal to 12 months. Another child, alive and well 3 years following diagnosis, was considered in the long-term survivor group. Favorable prognostic factors included neurofibromatosis, symptoms greater than or equal to 12 months before diagnosis, calcification on CT, exophytic location, and pathology suggesting a low-grade tumor. Recognition that certain patients with brainstem gliomas may have prolonged survivals even in the absence of definitive treatment must be taken into consideration when new treatment regimens are being formulated.
Eight hundred eighty-seven children with brain tumors were identified by the SEER registries (197... more Eight hundred eighty-seven children with brain tumors were identified by the SEER registries (1973-1980). Twenty-five percent were low-grade supratentorial astrocytomas, medulloblastomas were 23%, cerebellar astrocytomas 12%, high-grade supratentorial astrocytomas 11%, brainstem gliomas 9%, and ependymomas 8%. The worst survivals were in children less than 2 years of age, and the best were in those aged 10 to 14 years. Five-year survivals of children with cerebellar astrocytomas were 91%, low-grade supratentorial astrocytomas 71%, high-grade supratentorial astrocytomas 35%, medulloblastomas 39%, ependymomas 28%, and brainstem gliomas 18%.
Seventeen children with CNS leukemia treated with chemotherapy and 5 children treated with both c... more Seventeen children with CNS leukemia treated with chemotherapy and 5 children treated with both cranial radiation (CRT) and chemotherapy were evaluated. Eighty-eight percent of patients treated with chemotherapy alone had CT abnormalities, and all treated with CRT and chemotherapy had abnormal CT. The severity of CT abnormality paralleled intraventricular methotrexate levels and clinical signs of leukoencephalopathy. Children who receive chemotherapy for CNS leukemia, even without cranial irradiation, are more likely to have leukoencephalopathy than children without CNS leukemia. Moreover, patients with CNS leukemia may have abnormalities of CSF clearance of intraventricularly administered drugs.
Example 1. A 10-iiioritti-old lt~liar3 gut was brought to the hospital with the complaint that sh... more Example 1. A 10-iiioritti-old lt~liar3 gut was brought to the hospital with the complaint that she had srrddenly lost her vision. Her eyes &dquo;began ~wllin~ about,&dquo; and thereafter she appeared blind. The parents were certain that previously she had been able to see w°ell: she had reached tor and grasped small objects and had recognized her parents’ faces. There was 110 history of drug ingestion or recent infection. She had had varicella at three months of age and she had sustained several episodes of minor head trauma. Birth history was unnen ~rarkable. Development was within normal lirllits. She sat at six months and at 10 months walked with assistance. Family history was noncontributory. ~ ‘
Eight patients with recurrent medulloblastoma were treated with a chemotherapy regimen consisting... more Eight patients with recurrent medulloblastoma were treated with a chemotherapy regimen consisting of vincristine, BCNU, dexamethasone and intrathecal and intermediate dose intravenous methotrexate (500 mg/m/sup 2/). Five also received local low dose radiotherapy (RT). All 8 patients responded to treatment; 6 completely and 2 partially. These latter 2 were in their second and third recurrences. Three remain in remission. The median duration of response was 18.8 months, and median time from start of chemotherapy to death was 32 months using the Kaplan-Meier technique. In addition, 9 other patients with newly diagnosed medulloblastoma were treated with craniospinal radiation and the same adjuvant chemotherapy as above. The first 5 patients also received intraventricular methotrexate and/or intravenous BCNU during radiotherapy. The toxicity in the 5 patients was very severe. There were three toxic deaths, one death from cancer; one patient survives disease-free, but he is demented. With...
This article reviews the current approach to the treatment of childhood brain tumors. Common chil... more This article reviews the current approach to the treatment of childhood brain tumors. Common childhood brain tumors are profiled in separate sections, and the conclusion includes a discussion of the long-term clinical effects of radiation and chemotherapy.
Survivals of children with brain tumors have increased over the past 20 years owing to advances i... more Survivals of children with brain tumors have increased over the past 20 years owing to advances in surgery, radiation, and, most recently, chemotherapy. Unfortunately, central nervous system therapy, particularly radiation, may be associated with the development of dementia and learning disabilities, leukoencephalopathy, endocrinopathies, and oncogenesis. Recognition of these long-term effects of therapy is important as some are amenable to treatment and others may be prevented by modification of current treatment regimens.
Overall, the majority of patients with optic pathway tumors will have stable disease regardless i... more Overall, the majority of patients with optic pathway tumors will have stable disease regardless if they are radiated or receive chemotherapy. This is a very indolent tumor system and, for the most part, not a threat to life. Because of this, issues regarding appropriate therapeutic approaches have yet to be resolved. Most agree that in patients with progressive visual loss and tumor limited to the orbit, surgery can be associated with a cure. The downside is the loss of vision associated with surgical extirpation. Radiation rather than surgery has been the mainstay of treatment for intracranial tumors of the optic pathway. To eliminate side effects associated with radiotherapy in the young child, chemotherapy may be the more considered choice. However, on escape of control, i.e., conversion of stable disease to progressive disease, radiotherapy should be considered.
Publisher Summary This chapter discusses the meaning of cure in childhood central nervous system ... more Publisher Summary This chapter discusses the meaning of cure in childhood central nervous system malignancies. Of all malignancies in childhood, the tumors of the central nervous system are second in frequency only to leukemia. The success of treatment in childhood leukemia has resulted in a correspondingly aggressive approach to CNS neoplasia in children. The burgeoning number of child neurologists, the increasing availability of sophisticated technology, and an ever expanding therapeutic armamentarium has led to more involvement of child neurologists in the management of CNS tumors and their complications. Depending upon the biological behavior of the particular tumor following surgery, craniospinal radiation is recommended with a large boost to the tumor bed. It is found that although a great deal is known about radiation biology and the effects of ionizing radiation on normal as well as abnormal tissue, radiation dosage schedules have been developed in an empirical fashion. Side-effects are not only dependent on the total dose but also on the radiation given per unit dose. It is found that because of radiation complications, it has been recommended that the amount of radiation per unit dose be reduced.
Approximately 13% of brain tumors in childhood occur in children less than 2 years of age. Althou... more Approximately 13% of brain tumors in childhood occur in children less than 2 years of age. Although the survivals of older children with certain forms of brain tumors have increased over the past 20 years, this treatment has been least effective in very young children with brain tumors. These poor survival rates may be due in part to the highly malignant nature of the neoplasms; the delay in diagnosis because of low index of suspicion; the large bulk of tumor found at presentation, and the reduction in radiation dosage to the central nervous system. Since standard treatment has produced both poor results and severe neurotoxicity, new approaches have been sought. A conservative approach is recommended in some children with optic gliomas and low-grade supratentorial astrocytomas. Radiation is deferred until the child reaches 3–4 years of age when he can better tolerate its effects on the CNS. Current therapy of malignant brain tumors of infancy is not only toxic, but inadequate. There...
Gliomas of the optic pathway are considered to be slowly growing, potentially benign neoplasms. A... more Gliomas of the optic pathway are considered to be slowly growing, potentially benign neoplasms. Association of this tumor with neurofibromatosis has been well established. We have recently evaluated 7 children with putative evidence of optic glioma, 6 of whom had additional evidence of neurofibromatosis. All children had CT scans and visual-evoked responses. CT scan allows anatomic assessmant of the optic nerve mass while evoked responses offer the possibility of identifying functional abnormalities in the optic pathway. It is felt that both these modalities will add in the early diagnosis of optic gliomas and help to further establish the true natural history of this tumor.
Survival of children with brain tumors has improved over the past 20 years due in part to advance... more Survival of children with brain tumors has improved over the past 20 years due in part to advances in surgery, radiation, and most recently chemotherapy. The long-term adverse effects of radiation and chemotherapy on these children is the subject of this report. In Part I, we reviewed the pathologic consequences of radiation, including leukoencephalopathy, radiation necrosis, and radiation myelopathy as well as the oncogenic effects of both radiation and chemotherapy. Part II addresses the long-term consequences of radiation and chemotherapy on intellectual and endocrine function. Risk factors for the development of both endocrinopathies and intellectual dysfunction include age at the time of radiation, volume and dose of radiation, site of tumor, and use of adjuvant chemotherapy, in particular methotrexate. Early recognition of these complications and treatment, where indicated, will measurably improve the quality-of-life of children treated for brain tumors. The national cancer groups are currently attempting to limit these long-term adverse effects by taking risk factors into account when formulating new treatment regimens.
A case of infantile spasms associated with histidinemia is presented. Histidinemia was well-docum... more A case of infantile spasms associated with histidinemia is presented. Histidinemia was well-documented through biochemical assays. The patient was treated with the standard anticonvulsant regimen for infantile spasms, as well as an elimination diet for histidinemia. Despite low levels of histidine and adequate anticonvulsant therapy, the child continues to have seizures and is markedly retarded. The natural history of infantile spasms and its possible association with histidinemia is discussed.
We prospectively evaluated 47 children with neurofibromatosis to determine whether the previously... more We prospectively evaluated 47 children with neurofibromatosis to determine whether the previously reported high signals on magnetic resonance imaging (MRI) (prolonged T2) correlated with CT, brainstem auditory evoked responses (BAER), EEG, clinical examinations, cognitive abilities, or seizure disorder. Thirty percent of children had a history of seizures and 70% had either learning disabilities or mental retardation. Overall, 74% had an abnormal MRI examination. Sixty-two percent had high signals (prolonged T2) on T2-weighted images. Abnormal signals were located primarily in the basal ganglia, brainstem, and cerebellum. Twenty-five percent of patients had abnormal EEGs, 28% had abnormal CTs, and 27% had abnormal BAER examinations. The abnormal signals on MRI did not consistently relate to findings on CT, BAER, EEG, school placement, or clinical examination. The abnormal signals presumably reflect areas of abnormal brain parenchyma, either hamartomas, heterotopias, or local areas of brain dysplasia.
Although brainstem gliomas carry the worst prognosis of any brain tumor in children, with median ... more Although brainstem gliomas carry the worst prognosis of any brain tumor in children, with median survivals of 9 to 12 months, there may be a subgroup of long-term survivors. We have identified 12 children with brainstem gliomas, 5 of whom have survived greater than 6 years and 6 less than or equal to 12 months. Another child, alive and well 3 years following diagnosis, was considered in the long-term survivor group. Favorable prognostic factors included neurofibromatosis, symptoms greater than or equal to 12 months before diagnosis, calcification on CT, exophytic location, and pathology suggesting a low-grade tumor. Recognition that certain patients with brainstem gliomas may have prolonged survivals even in the absence of definitive treatment must be taken into consideration when new treatment regimens are being formulated.
Eight hundred eighty-seven children with brain tumors were identified by the SEER registries (197... more Eight hundred eighty-seven children with brain tumors were identified by the SEER registries (1973-1980). Twenty-five percent were low-grade supratentorial astrocytomas, medulloblastomas were 23%, cerebellar astrocytomas 12%, high-grade supratentorial astrocytomas 11%, brainstem gliomas 9%, and ependymomas 8%. The worst survivals were in children less than 2 years of age, and the best were in those aged 10 to 14 years. Five-year survivals of children with cerebellar astrocytomas were 91%, low-grade supratentorial astrocytomas 71%, high-grade supratentorial astrocytomas 35%, medulloblastomas 39%, ependymomas 28%, and brainstem gliomas 18%.
Seventeen children with CNS leukemia treated with chemotherapy and 5 children treated with both c... more Seventeen children with CNS leukemia treated with chemotherapy and 5 children treated with both cranial radiation (CRT) and chemotherapy were evaluated. Eighty-eight percent of patients treated with chemotherapy alone had CT abnormalities, and all treated with CRT and chemotherapy had abnormal CT. The severity of CT abnormality paralleled intraventricular methotrexate levels and clinical signs of leukoencephalopathy. Children who receive chemotherapy for CNS leukemia, even without cranial irradiation, are more likely to have leukoencephalopathy than children without CNS leukemia. Moreover, patients with CNS leukemia may have abnormalities of CSF clearance of intraventricularly administered drugs.
Example 1. A 10-iiioritti-old lt~liar3 gut was brought to the hospital with the complaint that sh... more Example 1. A 10-iiioritti-old lt~liar3 gut was brought to the hospital with the complaint that she had srrddenly lost her vision. Her eyes &dquo;began ~wllin~ about,&dquo; and thereafter she appeared blind. The parents were certain that previously she had been able to see w°ell: she had reached tor and grasped small objects and had recognized her parents’ faces. There was 110 history of drug ingestion or recent infection. She had had varicella at three months of age and she had sustained several episodes of minor head trauma. Birth history was unnen ~rarkable. Development was within normal lirllits. She sat at six months and at 10 months walked with assistance. Family history was noncontributory. ~ ‘
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