Late-occurring neurologic sequelae in adult survivors of childhood acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study.

Purpose: Children with acute lymphoblastic leukemia (ALL) are often cured, but the therapies they receive may be neurotoxic. Little is known about the incidence and severity of late-occurring neurologic sequelae in ALL survivors. Data were analyzed to determine the incidence of adverse long-term neurologic outcomes and treatment-related risk factors.

Neurocognitive status in long-term survivors of childhood CNS malignancies: a report from the Childhood Cancer Survivor Study.

To assess neurocognitive functioning in adult survivors of childhood Central Nervous System (CNS) malignancy, a large group of CNS malignancy survivors were compared to survivors of non-CNS malignancy and siblings without cancer on a self-report instrument (CCSS-NCQ) assessing four factors, Task Efficiency, Emotional Regulation, Organization and Memory. Additional multiple linear regressions were used to assess the contribution of demographic, illness, and treatment variables to reported neurocognitive functioning in CNS malignancy survivors and the relationship of reported neurocognitive functioning to socioeconomic indicators. Survivors of CNS malignancy reported significantly greater neurocognitive impairment on all CCSS-NCQ factors than non-CNS cancer survivors or siblings (p < .

Ocular late effects in childhood and adolescent cancer survivors: a report from the childhood cancer survivor study.

Introduction: Approximately 80% of children currently survive 5 years following diagnosis of their cancer. Studies based on limited data have implicated certain cancer therapies in the development of ocular sequelae in these survivors.

Procedure: The Childhood Cancer Survivor Study (CCSS) is a retrospective cohort study investigating health outcomes of 5+ year survivors diagnosed and treated between 1970 and 1986 compared to a sibling cohort.

Consensus recommendations to accelerate clinical trials for neurofibromatosis type 2.

Purpose: Neurofibromatosis type 2 (NF2) is a rare autosomal dominant disorder associated primarily with bilateral schwannomas seen on the superior vestibular branches of the eighth cranial nerves. Significant morbidity can result from surgical treatment of these tumors. Meningiomas, ependymomas, and other benign central nervous system tumors are also common in NF2.

Long-term outcomes among adult survivors of childhood central nervous system malignancies in the Childhood Cancer Survivor Study.

Background: Adult survivors of childhood central nervous system (CNS) malignancies are at high risk for long-term morbidity and late mortality. However, patterns of late mortality, the long-term risks of subsequent neoplasms and debilitating medical conditions, and sociodemographic outcomes have not been comprehensively characterized for individual diagnostic and treatment groups.

Methods: We collected information on treatment, mortality, chronic medical conditions, and neurocognitive functioning of adult 5-year survivors of CNS malignancies diagnosed between 1970 and 1986 within the Childhood Cancer Survivor Study.

Primary spinal cord tumors of childhood: effects of clinical presentation, radiographic features, and pathology on survival.

To determine the relationship between clinical presentation, radiographic features, pathology, and treatment on overall survival of newly diagnosed pediatric primary spinal cord tumors (PSCT). Retrospective analysis of all previously healthy children with newly diagnosed PSCT at a single institution from 1995 to present was performed. Twenty-five pediatric patients (15 boys, average 7.

The Childhood Cancer Survivor Study: a National Cancer Institute-supported resource for outcome and intervention research.

Survival for childhood cancer has increased dramatically over the last 40 years with 5-year survival rates now approaching 80%. For many diagnostic groups, rapid increases in survival began in the 1970s with the broader introduction of multimodality approaches, often including combination chemotherapy with or without radiation therapy. With this increase in rates of survivorship has come the recognition that survivors are at risk for adverse health and quality-of-life outcomes, with risk being influenced by host-, disease-, and treatment-related factors.

Objective response of multiply recurrent low-grade gliomas to bevacizumab and irinotecan.

Background: Chemotherapy has taken on a prominent role in the treatment of pediatric low-grade gliomas not amenable to gross total resections; however, there are few proven effective options for children with multiply recurrent tumors. Bevacizumab, a humanized immunoglobulin, monoclonal antibody that inhibits the activity of vascular endothelial growth factor and irinotecan have been used with some success in adults with malignant gliomas.

Methods: Ten children with multiply recurrent low-grade gliomas were treated with the combination of bevacizumab and irinotecan.

Phase I study of SU5416, a small molecule inhibitor of the vascular endothelial growth factor receptor (VEGFR) in refractory pediatric central nervous system tumors.

SU5416 is a novel small molecule tyrosine kinase inhibitor of the VEGF receptors 1 and 2. A phase I dose escalation study stratified by concurrent use (stratum II) or absence (stratum I) of enzyme-inducing anticonvulsant drugs was undertaken to estimate the maximum-tolerated dose (MTD) and to describe the toxicity profile of SU5416 in pediatric patients with refractory brain tumors. Dose escalations were conducted independently for stratum I starting at 110 mg/m(2) while stratum II started at 48 mg/m(2).

Management of and prognosis with medulloblastoma: therapy at a crossroads.

Medulloblastoma is the most common malignant childhood brain tumor and, although relatively uncommon in older patients, poses a therapeutic challenge in adults. With current means of therapy, children with nondisseminated medulloblastoma have a high likelihood of long-term survival; 80% or more will be alive 5 years after diagnosis and treatment, with many free of the disease. Even in children with disseminated disease, intensified therapy has been associated with improved survival rates, although some of this improvement may be more apparent than real.

Childhood brain tumors: accomplishments and ongoing challenges.

The management of childhood brain tumors, which consist of many different histological subtypes, continues to be a challenge. Outcome, measured not only by survival rates but also by the effects of disease and therapy on quality of life, has improved over the past two decades for some tumor types, most notably medulloblastomas. For others, however, there has been little progress, and quality of life for long-term survivors remains suboptimal.

Tumors of the central nervous system: clinical aspects, molecular mechanisms, unanswered questions, and future research directions.

Central nervous system tumors are the most common solid tumors in children. Many histological subtypes and biological variants exist. The 2007 Neurobiology of Disease in Children Symposium, held in conjunction with the 36th annual meeting of the Child Neurology Society, aimed to define current knowledge in the field and to develop specific aims for future clinical, translational, and fundamental science.

The cerebellar mutism syndrome and its relation to cerebellar cognitive function and the cerebellar cognitive affective disorder.

The postoperative cerebellar mutism syndrome (CMS), consisting of diminished speech output, hypotonia, ataxia, and emotional lability, occurs after surgery in up to 25% of patients with medulloblastoma and occasionally after removal of other posterior fossa tumors. Although the mutism is transient, speech rarely normalizes and the syndrome is associated with long-term adverse neurological, cognitive, and psychological sequelae. The clinical, neuroradiographic, and neuropsychological findings associated with CMS as well as possible mechanisms of injury are reviewed.

Myeloablative chemotherapy with autologous bone marrow rescue in children and adolescents with recurrent malignant astrocytoma: outcome compared with conventional chemotherapy: a report from the Children's Oncology Group.

Purpose: Children and adolescents with malignant astrocytomas recurring after initial treatment have a dismal prognosis, with only rare patients surviving 1-year beyond recurrence. The purpose of this study was to attempt to improve their survival.

Methods: Twenty-seven children and adolescents with malignant astrocytomas [17 glioblastoma multiforme and 10 anaplastic astrocytoma (AA)] following initial tumor progression, received myeloablative chemotherapy followed by autologous marrow rescue with one of three thiotepa and etoposide-based chemotherapy regimens, administered alone (n = 11) or combined with carmustine (n = 5) or carboplatin (n = 11).

Biological background of pediatric medulloblastoma and ependymoma: a review from a translational research perspective.

Survival rates of pediatric brain tumor patients have significantly improved over the years due to developments in diagnostic techniques, neurosurgery, chemotherapy, radiotherapy, and supportive care. However, brain tumors are still an important cause of cancer-related deaths in children. Prognosis is still highly dependent on clinical characteristics, such as the age of the patient, tumor type, stage, and localization, but increased knowledge about the genetic and biological features of these tumors is being obtained and might be useful to further improve outcome for these patients.

Neurotoxicity of chemotherapeutic and biologic agents in children with cancer.

The sequelae of treatment modalities used to treat childhood cancer are of increasing clinical importance. In children with pediatric malignancies, the full impact of such sequelae may not be apparent until years after treatment. The earlier recognition of these neurotoxicities could possibly alter the course of a treatment or facilitate interventions to improve quality of life.

Phase I trial of VNP40101M (Cloretazine) in children with recurrent brain tumors: a pediatric brain tumor consortium study.

Purpose: VNP40101M (Cloretazine), a novel DNA alkylating agent, was evaluated in a phase I study in children with recurrent brain tumors.

Experimental Design: VNP40101M was given i.v.

Central nervous system tumors.

Central nervous system (CNS) tumors comprise 15% to 20% of all malignancies occurring in childhood and adolescence. They may present in a myriad of ways, often delaying diagnosis. Symptoms and signs depend on the growth rate of the tumor, its location in the central nervous system (CNS), and the age of the child.

Medulloblastoma in childhood: new biological advances.

Medulloblastoma is the most common embryonal tumour in children. Patients with medulloblastoma are currently staged as average-risk or poor-risk on the basis of clinical findings. With current multimodality therapy, nearly 90% of children with average-risk, non-disseminated medulloblastoma have 5-year event-free survival, and those with high-risk disease have a 60-65% survival rate; however, the outcome for younger children, particularly infants, is worse.

Phase I trial of single-dose temozolomide and continuous administration of o6-benzylguanine in children with brain tumors: a pediatric brain tumor consortium report.

Purpose: To estimate the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of escalating doses of temozolomide combined with O(6)-benzylguanine in patients < or =21 years with recurrent brain tumors.

Experimental Design: Treatment strata consisted of patients who had previously received no or local radiotherapy (Str1) and patients who had undergone craniospinal radiotherapy or myeloablative chemotherapy (Str2). One-hour i.

Feasibility of metronomic maintenance chemotherapy following high-dose chemotherapy for malignant central nervous system tumors.

Background: Children less than 5 years of age with malignant central nervous system (CNS) tumors, continue to have a high rate of morbidity and mortality following administration of conventional therapy. In an attempt to avoid the neurologic sequelae associated with craniospinal radiation, strategies such as high-dose chemotherapy (HDCT) followed by peripheral stem cell rescue have been used successfully. Metronomic chemotherapy has also been reported as a potential new treatment strategy in solid tumors, particularly in adults.

Phase I and pharmacokinetic study of the oral farnesyltransferase inhibitor lonafarnib administered twice daily to pediatric patients with advanced central nervous system tumors using a modified continuous reassessment method: a Pediatric Brain Tumor Consortium Study.

Purpose: A dose-escalation phase I and pharmacokinetic study of the farnesyltransferase inhibitor lonafarnib (SCH66336) was conducted in children with recurrent or progressive CNS tumors. Primary objectives were to estimate the maximum-tolerated dose (MTD) and to describe the dose-limiting toxicities (DLTs) and pharmacokinetics of lonafarnib. Farnesylation inhibition of HDJ-2 in peripheral blood was also measured.