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Biomedical subjects

H S Nicholson

Publications and source records attributed to H S Nicholson.

32 records · Page 2Linked to original sources

'Complicated migraine-like episodes' in children following cranial irradiation and chemotherapy.

Neurologic sequelae may occur months to years after cranial irradiation. The site of primary damage is probably the vascular endothelium. Over a 2.8-year period, four children with brain tumors, a mean of 11 years of age at diagnosis (range, 6.5 to 15.5 years), had new onset of severe intermittent unilateral headaches associated with nausea, episodic visual loss, hemiparesis, aphasia, or hemisensory loss. The headaches lasted 2 to 24 hours. All patients had previously received whole-brain (2,400 to 3,600 cGy) and additional local boost (1,800 to 3,100 cGy) cranial irradiation, as well as cisplatin-, lomustine-, and vincristine-containing chemotherapy regimens. Symptoms began 1.2 to 2.8 years after the diagnosis, when all had stable disease and were off treatment. MRI studies were unchanged, and CSF cytology, EEGs, echocardiograms, and magnetic resonance angiograms were normal in all. Cerebral angiograms, performed in three children, were normal but led to severe headaches and neurologic deficits (hemiparesis in one and visual loss in two) that resolved after 24 to 48 hours. Response to antimigraine and antiplatelet medications was variable. We conclude that (1) "complicated migraine-like episodes" may occur in children after cranial irradiation and chemotherapy as a sequela of therapy; (2) these headaches may not be the harbinger of impending strokes, severe intracranial vasculitis, or tumor recurrence; and (3) while cerebral angiography may be useful in differential diagnosis, it may cause transient worsening of symptoms.

Adolescent↗

Educational attainment in long-term survivors of childhood acute lymphoblastic leukemia.

OBJECTIVE: To determine the impact of treatment on scholastic performance in the first cohort of survivors of childhood acute lymphoblastic leukemia who are old enough to have completed their educational experience. DESIGN: Retrospective cohort study. SETTING: Twenty-three institutions in the Childrens Cancer Group. SUBJECTS: A total of 593 adult survivors of childhood acute lymphoblastic leukemia and 409 sibling controls. OUTCOME MEASURES: Enrollment in special programs, grades during high school, graduation from high school, college admission, and college graduation. RESULTS: After diagnosis, survivors were more likely than their sibling controls to enter a special education (relative risk [RR] = 3.4; P < .01) or a learning disabled (RR = 3.6; P < .01) program, while just as likely to enter gifted and talented programs (RR = 1.0). The risk associated with special education and learning disabled programs increased with increasing dose of cranial radiotherapy. Despite these problems, survivors generally had the same probability as their siblings of finishing high school, entering college, and earning a bachelor's degree. However, survivors treated with 24 Gy and those diagnosed before 6 years of age were less likely to enter college (RR = 0.67 and 0.6, respectively; P < .01). CONCLUSIONS: This large study demonstrates that childhood acute lymphoblastic leukemia survivors have a greater likelihood of being placed in special education or learning disabled programs than their siblings, but that most are able to overcome these problems. Dose of cranial radiotherapy and age at diagnosis are the most important education-related risk factors.

Adolescent↗

Death during adulthood in survivors of childhood and adolescent cancer.

BACKGROUND: Therapeutic advances have extended survival for most children and adolescents with cancer beyond 5 years from diagnosis. However, excess mortality continues beyond 5 years, and a significant portion results from causes other than the primary cancer. Risk factors for these deaths are not currently known. Thus, the authors studied mortality in a cohort of adult survivors of childhood and adolescent cancer to determine whether survivor characteristics were associated with increased relative risk of death from other causes. METHODS: Using 3255 siblings as control subjects, the authors studied survival in a retrospective cohort study of 2319 adults who were at least 5-year survivors of cancer diagnosed before reaching 20 years of age and between 1945 and 1974 (the NCI Five Center Study). Follow-up occurred between 1980 and 1983 at a mean survivor age of 32 years (range, 21-55 years). RESULTS: Between cohort entry and follow-up, 292 (13%) survivors and 50 (2%) controls died. One-third of the deaths in survivors were from causes other than the primary malignancy. Compared with control subjects, between ages 21 and 40 years, survivors had a more than threefold risk of death from other causes. The relative risk (RR) for death from other causes was greatest for survivors treated with radiation and alkylating agents (RR = 6.1; 95% confidence interval [CI], 3.0-12.4) and for those treated with radiation alone (RR = 3.8; 95% CI, 2.3-6.2; Cox regression analysis containing terms for treatment and cancer diagnosis). CONCLUSIONS: Adult survivors of childhood and adolescent cancer had a higher death rate than their siblings, even after removing the effect of primary cancer as the direct cause. Moreover, death from other causes was most strongly associated with increasing intensity of therapy, and this excess risk did not diminish with increasing age and duration of cancer survival. Because contemporary anticancer therapy is, in general, even more intensive than that received by the survivors described in this study, medical surveillance of cancer survivors is increasingly important to diagnose and treat potentially life-threatening complications that may occur decades after therapy has ceased.

Adolescent↗

LCH-I: a randomized trial of etoposide vs. vinblastine in disseminated Langerhans cell histiocytosis. The Histiocyte Society.

An international randomized trial in Langerhans cell histiocytosis (LCH) has been initiated by the Histiocyte Society. This report reviews the rationale, design, and progress of LCH-I, which compares etoposide (VP-16) and vinblastine in the treatment of disseminated LCH. Data on the risk of etoposide-associated (therapy-induced) malignancy, in the setting of histiocytosis, are reviewed. The available evidence leads to the recommendation that the study of etoposide in LCH should be continued.

Drug Administration Schedule↗

Quality of long-term survival in young children with medulloblastoma.

The reported success of treatment for children with medulloblastoma must be balanced against the effect that treatment has on the quality of life of long-term survivors. The outcome of long-term survivors reported in previous studies has been conflicting. The authors evaluate the mental and behavioral skills of a group of medulloblastoma survivors from their institution, all of whom had survived for more than 5 years postdiagnosis. A review of the institutional records yielded 32 patients. Twenty-three families were interviewed by telephone and, of these, 13 subjects came to the hospital for detailed neuropsychological and neurological evaluations. Intelligence quotient (IQ) was less than 90 for all participants tested, and patients diagnosed before the age of 3 years had lower IQ scores on average than those diagnosed later. Mean IQ and achievement test scores in reading, spelling, and mathematics were all higher in survivors who had undergone shunting. Achievement test results were often not in accord with intellectual potential, and individual intellectual skills varied widely. Perceptual-motor task performance was below average in more than 50% of the participants, but motor dexterity was more severely affected than perception. Problems in learning and a delay in both physical growth and development were seen in a majority of participants. This study directs attention to the serious difficulties faced by long-term survivors of medulloblastoma and their families, and underscores the importance of routine neuropsychological testing. Moreover, the study provides further impetus to seek alternatives to irradiation in the treatment of malignant brain tumors.

Adolescent↗

Outcome for children with medulloblastoma treated with radiation and cisplatin, CCNU, and vincristine chemotherapy.

It has previously been reported in a single-institution trial that progression-free survival of children with medulloblastoma treated with radiotherapy and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), cisplatin, and vincristine chemotherapy during and after radiotherapy was better than the outcome in children treated with radiotherapy alone. To better characterize long-term outcome and duration of disease control, this treatment approach was used for 10 years and expanded to three institutions. Sixty-three children with posterior fossa medulloblastomas were treated with craniospinal local-boost radiotherapy and adjuvant chemotherapy with vincristine weekly during radiotherapy followed by eight 6-week cycles of cisplatin, CCNU, and vincristine. To be eligible for study entry, patients had to be older than 18 months of age at diagnosis and have a subtotal resection, evidence of metastatic disease, and/or brainstem involvement. Patients younger than 5 years of age and without these poor risk factors who received reduced-dose craniospinal radiotherapy (2400 cGy) were also eligible for entry into the study. Sixty-three of 66 eligible patients (95%) were entered and placed on this treatment regimen. Forty-two patients had brainstem involvement, 15 had metastatic disease at the time of diagnosis, and 19 had received a subtotal resection. Progression-free survival for the entire group at 5 years is 85% +/- 6%. Three children have succumbed to a second malignancy, and overall 5-year event-free survival is 83% +/- 6%. Progression-free survival was not adversely affected by younger age at diagnosis, brainstem involvement, or subtotal resection. Five-year actuarial progression-free survival for patients who received reduced-dose radiotherapy was similar to that for patients receiving conventional-dose radiotherapy. Patients with metastatic disease at the time of diagnosis had a 5-year progression-free survival rate of 67% +/- 15%, as compared to 90% +/- 6% for those patients with localized disease at the time of diagnosis (p = 0.037). The authors conclude that overall progression-free survival remains excellent for children with posterior fossa medulloblastomas treated with this drug regimen. Chemotherapy has a definite role in the management of children with medulloblastoma. Further studies are indicated to define which subpopulations of children with medulloblastoma benefit from chemotherapy and what regimens are optimum in increasing disease control and, possibly, in reducing the amount of radiotherapy required.

Adolescent↗

Fertility and pregnancy after treatment for cancer during childhood or adolescence.

Because most children and adolescents with cancer now survive, issues regarding the late effects of therapy, including fertility and the health of offspring, are increasingly important. This article summarizes the literature regarding issues related to fertility in survivors of cancer, including actual fertility, gonadal function, menarche, menopause, and birth defects and cancer in the offspring. Radiation therapy to the gonads and alkylating agent chemotherapy, either alone or in combination, impair actual fertility in survivors of childhood and adolescent cancer. Males are particularly affected by alkylating agents, and females who have had radiation therapy to the abdomen have decreased fertility and an increased risk of adverse pregnancy outcomes. Consequently, these women should be followed up as high-risk obstetrical patients. Offspring of survivors of cancer appear to have little risk of childhood cancer or birth defects. Thus, in most instances, survivors of cancer should not be discouraged from having children and can expect a good outcome of pregnancy. This article concludes with advice to survivors and clinicians who counsel survivors.

Adolescent↗

Late effects of therapy in survivors of childhood and adolescent osteosarcoma.

Adult survivors of childhood or adolescent osteosarcoma require ongoing medical follow-up in order to monitor for potentially life-threatening consequences of therapy, including second cancers and anthracycline cardiotoxicity. In the future, additional knowledge of tumor biology will likely change staging methods and allow intensive therapy to be given only to those most likely to benefit from it [25]; those with less risk of relapse may require less toxic therapy and still achieve acceptable levels of survival.

Adolescent↗

Carboplatin and vincristine for recurrent and newly diagnosed low-grade gliomas of childhood.

PURPOSE: This study investigates the response rate to and toxicity of carboplatin and vincristine in children with recurrent low-grade gliomas (LGGs) or patients younger than 60 months with newly diagnosed LGGs. PATIENTS AND METHODS: Twenty-three children with recurrent and 37 children with newly diagnosed LGGs were treated with a 10-week induction cycle of carboplatin and vincristine, followed by maintenance treatment with the same drugs. Patients were evaluated for response to treatment and toxicity. RESULTS: Twelve of 23 (52% +/- 10%; 95% confidence interval [CI], 0.32 to 0.72) assessable children with recurrent disease had an objective response to treatment, which included a greater than 50% reduction in tumor size in seven of 23 (30% +/- 10%; 95% CI, 0.10 to 0.50). Twenty-three of 37 (62% +/- .08; 95% CI, 0.46 to 0.78) of newly diagnosed patients had an objective response, 16 of 37 (43% +/- 0.08%; 95% CI, 0.27 to 0.59) with greater than 50% reduction in tumor size. The majority of those with an objective response had diencephalic tumors (n = 29), but children with thalamic (n = 2), cortical (n = 1), and brain stem (n = 2) LGGs also responded to treatment. Of the 35 patients with objective response to treatment, the maximum response was seen in 25 after completion of induction and in the remaining 10 after two to six cycles of maintenance treatment. Forty-nine of 53 (92% +/- .04%) patients who were stable or improved after induction remain without progressive disease (PD). Hematologic toxicity was common, but resulted in cessation of therapy in only one patient. Six children have been removed from the study because of allergic reactions, which were considered to be carboplatin-associated. CONCLUSION: Carboplatin and vincristine have activity in children with recurrent and newly diagnosed progressive LGGs. Objective responses to treatment after chemotherapy can be seen. This drug regimen is relatively well tolerated, and further studies are indicated to define the role of this combination of drugs in children with newly diagnosed LGGs.

Adolescent↗

Late effects of therapy in adult survivors of osteosarcoma and Ewing's sarcoma.

To study the late consequences of primary bone cancer, we interviewed 82 osteosarcoma and 29 Ewing's sarcoma survivors regarding their health, fertility and offspring, employment, annual income, and activities of daily living. All subjects had been diagnosed before age 20 (mean age, 14.6 years), had survived at least 5 years from diagnosis, and were at least 21 years of age. On average, they were 32.5 years of age at interview. As controls, 151 siblings were interviewed. During the follow-up period, eight survivors had died, and eight survivors had been diagnosed with a second malignancy (7.2%; P = .002). No other health condition distinguished survivors from controls. Although the survivors were more likely than controls to have some difficulty climbing stairs and to have had employment disability, employment status and annual income at follow-up were similar. Deficits in marriage and fertility were not significant. Adult survivors of primary bone tumors diagnosed during childhood or adolescence are at high risk for second malignancies and premature death, making continued medical follow-up of utmost importance. Despite the physical impairment following limb amputation for many, the majority of outcomes we measured did not differ from controls, suggesting few adverse psychosocial outcomes in this group of cancer survivors.

Adult↗

Brainstem gliomas.

Brainstem gliomas, a relatively common form of childhood brain tumor, are highly resistant to therapy. With computed tomography and magnetic resonance imaging, these lesions can be diagnosed with a high degree of reliability. The indications for surgery are unclear. Focal lesions may be amenable to partial resections. Stereotactic approaches can be used for diffuse lesions, but it has not been shown that the information obtained changes the approach to treatment or outcome. Higher dose radiotherapy has been recently used but has not improved survival for most patients. Patients with brainstem gliomas must be stratified into risk groups, and new means of treatment are needed.

Brain Neoplasms↗

Dilemmas in the management of childhood brain tumors: brainstem gliomas.

Brainstem glioma is a malignant childhood brain tumor for which the 'best' treatment approach has not been defined. Many issues concerning the management of these lesions require clarification, including the following. (1) Can patients be reliably separated into risk groups? (2) Is surgery indicated; if so, for which patients? (3) How effective are new radiotherapy regimens? (4) What other forms of treatment are available? This article will attempt to address these management issues.

Brain Neoplasms↗