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R J Packer

Publications and source records attributed to R J Packer.

At least 37 records · Page 2Linked to original sources
PubMed1999

Chemotherapy for low-grade gliomas.

Low-grade gliomas are the most common histological type of pediatric brain tumor. They can arise in any part of the nervous system. Although low-grade gliomas are slow growing, they often recur or progress, especially in areas such as the diencephalon or brain stem, where resection is limited by proximity to vital and eloquent structures. Radiation has been used to treat progressive low-grade gliomas, but it is not clear that it improves long-term outcome. Radiotherapy also has potential significant cognitive, endocrine, and vascular side- effects. There is a growing body of evidence to suggest that chemotherapy can delay and may obviate the need for radiation therapy or aggressive surgery. This chapter reviews the published chemotherapeutic trials. Chemotherapy appears to have a major role in the management of children with progressive low-grade gliomas.

Antineoplastic Agents↗
PubMed1999

Prothrombin G20210A mutation in a child with spinal cord infarction.

Prothrombin G20210A is a newly described common mutation that is associated with an increased risk of arterial and venous thrombosis. We describe a healthy child heterozygous for this prothrombin mutation who had a spinal cord infarct with no other prothrombotic risk factors.

Family↗
PubMed1999

Childhood medulloblastoma: progress and future challenges.

Medulloblastoma and other primitive neuroectodermal tumors are the most common malignant tumors of childhood. Progress has been slowly made in the management of such tumors. Long-term neurocognitive sequelae of treatment in children with medulloblastoma are common and recent treatment trials have attempted to reduce the amount of craniospinal radiation therapy or delay radiation therapy in attempts to reduce such sequelae. Surgery remains a critical component of treatment, although there is increasing concern about surgically-related complications, including the cerebellar mutism syndrome. For older children, craniospinal radiation remains an integral part of management. However, recent studies have suggested an excellent outcome after reduced-dose craniospinal radiation therapy and adjuvant chemotherapy. The role of chemotherapy is expanding for children with medulloblastoma and is now presently a component of protocols for children with average-risk and poor-risk disease. For children with poor-risk disease, intensifications of chemotherapy both during and after radiation therapy are presently being explored. Treatment of infants and young children with medulloblastoma remains problematic and a variety of different approaches are being investigated with the aims of both improving outcome and reducing long-term sequelae.

Cerebellar Neoplasms↗
PubMed1999

Etoposide with or without mannitol for the treatment of recurrent or primarily unresponsive brain tumors: a Children's Cancer Group Study, CCG-9881.

PURPOSE: This study was undertaken to evaluate the response of recurrent brain tumors to intravenous etoposide and to evaluate the efficacy of mannitol in augmenting etoposide's tumoricidal effect. PATIENTS AND METHODS: Ninety-nine children between one and 21 years of age with recurrent brain tumors were randomly assigned to treatment with intravenous etoposide 150 mg/M2, with or without mannitol 15 gm/M2, daily for five days every three weeks for one year or until disease progression or death. Computerized tomographic (CT) or magnetic resonance image (MRI) scans, obtained after three cycles of therapy, were compared with pre-therapy scans. Scans were centrally reviewed. RESULTS: Of 87 evaluable patients, 12 (13.8%) were determined to have had an objective response by the institutional radiologist. On central review, 7/66 (10.6%) responses were documented. Responses in centrally reviewed patients were observed in 2/12 (16.7%) low grade astrocytomas, 4/26 (15.4%) medulloblastoma or primitive neuroectodermal tumors (PNET), 1/13 (7.7%) high grade astrocytomas and 0/15 (0%) brain stem gliomas. Survival at one year was 53% (SE 12%) for low grade astrocytomas, 38% (SE 7%) for medulloblastoma or PNET, 28% (SE 10%) for high grade astrocytomas and 9% (SE 5%) for brain stem gliomas. An effect of mannitol was not observed. CONCLUSION: Intravenous etoposide has a low level of activity in the treatment of recurrent low grade astrocytomas and medulloblastoma or PNET. The efficacy of this agent was not enhanced by the coincident intravenous administration of mannitol.

Adolescent↗
PubMed1999

Medulloblastoma: clinical and biologic aspects.

Medulloblastoma is the most common childhood primary CNS tumor, and treatment approaches have evolved over the past three decades. The biologic underpinnings of medulloblastoma are not fully characterized, but recent work has identified new, important directions for research. Stratification of patients with medulloblastoma into risk groups is the backbone of most ongoing therapeutic studies. Patients are usually characterized as being either average risk or poor risk, although an intermediate risk group may exist. Standard treatment for older children with medulloblastoma consists of radiation and, for most, chemotherapy. Children with nondisseminated disease at the time of diagnosis have been reported to have as high as an 80% five-year disease-free survival rate after treatment with reduced dose (2340 cGy) craniospinal irradiation, local boost radiation therapy (5500 cGy), and chemotherapy, given during and after radiation therapy. Preradiation chemotherapy has yet to be shown to be of benefit for children with medulloblastoma. Children with disseminated disease are a highly problematic subgroup of patients to treat. A variety of new approaches are being studied, most of which are intensifying chemotherapy either prior to or after radiation. Long-term survivors of medulloblastoma are at significant risk for permanent endocrinologic, cognitive, and psychological sequelae. Infants and very young children with medulloblastoma remain a difficult therapeutic challenge because they have the most virulent form of the disease and are at highest risk for treatment-related sequelae.

Adult↗
PubMed1999

Quality of life of adult survivors of germinomas treated with craniospinal irradiation.

OBJECTIVE: To assess the quality of life (QOL) of a group of patients treated for intracranial germinoma with biopsy followed by prophylactic whole-neuraxis radiation therapy. METHODS: The Short-form-36 and Functional Assessment of Cancer Therapy QOL questionnaires were completed by 22 of 27 eligible adults treated with whole-neuraxis irradiation for biopsy-proven, marker-negative intracranial germinomas between 1976 and 1996. In addition, data were obtained regarding height and weight, medications, ability to work, and educational achievement. RESULTS: The patients' QOL was generally good. All of the patients are in or have completed high school; nine are in or have completed college, and five have advanced degrees. Patients rated themselves lower on the physical composite scale of the Short-form-36 (average, 46 versus 54 in a normal population). On the mental composite scale, patients rated themselves more favorably than the normal population (average, 54 versus 49 in a normal population). Patients were normally proportioned for height and weight, but female patients tended to be short. Age at radiation did not correlate with QOL. CONCLUSION: The QOL of adults treated for marker-negative germinoma with prophylactic whole-neuraxis irradiation is generally good. These data should serve as a benchmark for newer treatment protocols eliminating or reducing radiation.

Achievement↗
PubMed1999

Medulloblastoma.

The utilization of multi-modal therapy in the treatment of medulloblastoma has improved survival rates and overall outcome. Recent large clinical trials have supported the use of radiation and chemotherapy as adjuvant treatment. Treatment advances have been made despite a poor understanding of the biological underpinnings of medulloblastoma. Current laboratory investigations are shedding light on the oncogenesis of medulloblastoma and may lead to improved treatments.

Cerebellar Neoplasms↗
PubMed1999

Metastasis stage, adjuvant treatment, and residual tumor are prognostic factors for medulloblastoma in children: conclusions from the Children's Cancer Group 921 randomized phase III study.

PURPOSE: From 1986 to 1992, "eight-drugs-in-one-day" (8-in-1) chemotherapy both before and after radiation therapy (XRT) (54 Gy tumor/36 Gy neuraxis) was compared with vincristine, lomustine (CCNU), and prednisone (VCP) after XRT in children with untreated, high-stage medulloblastoma (MB). PATIENTS AND METHODS: Two hundred three eligible patients with an institutional diagnosis of MB were stratified by local invasion and metastatic stage (Chang T/M) and randomized to therapy. Median time at risk from study entry was 7.0 years. RESULTS: Survival and progression-free survival (PFS) +/- SE at 7 years were 55%+/-5% and 54%+/-5%, respectively. VCP was superior to 8-in-1 chemotherapy, with 5-year PFS rates of 63%+/-5% versus 45%+/-5%, respectively (P = .006). Upon central neuropathology review, 188 patients were confirmed as having MB and were the subjects for analyses of prognostic factors. Children aged 1.5 to younger than 3 years had inferior 5-year estimates of PFS, compared with children 3 years old or older (P = .0014; 32%+/-10% v 58%+/-4%, respectively). For MB patients 3 years of age or older, the prognostic effect of tumor spread (MO v M1 v M2+) on PFS was powerful (P = .0006); 5-year PFS rates were 70%+/-5%, 57%+/-10%, and 40%+/-8%, respectively. PFS distributions at 5 years for patients with M0 tumors with less than 1.5 cm2 of residual tumor, versus > or = 1.5 cm2 of residual tumor by scan, were significantly different (P = .023; 78%+/-6% v 54%+/-11%, respectively). CONCLUSION: VCP plus XRT is a superior adjuvant combination compared with 8-in-1 chemotherapy plus XRT. For patients with M0 tumors, residual tumor bulk (not extent of resection) is a predictor for PFS. Patients with M0 tumors, > or = 3 years with < or = 1.5 cm2 residual tumor, had a 78%+/-6% 5-year PFS rate. Children younger than 3 years old who received a reduced XRT dosage had the lowest survival rate.

Adolescent↗
PubMed1999

Treatment of children with medulloblastomas with reduced-dose craniospinal radiation therapy and adjuvant chemotherapy: A Children's Cancer Group Study.

PURPOSE: Medulloblastoma is the most common malignant brain tumor of childhood. After treatment with surgery and radiation therapy, approximately 60% of children with medulloblastoma are alive and free of progressive disease 5 years after diagnosis, but many have significant neurocognitive sequelae. This study was undertaken to determine the feasibility and efficacy of treating children with nondisseminated medulloblastoma with reduced-dose craniospinal radiotherapy plus adjuvant chemotherapy. PATIENTS AND METHODS: Over a 3-year period, 65 children between 3 and 10 years of age with nondisseminated medulloblastoma were treated with postoperative, reduced-dose craniospinal radiation therapy (23.4 Gy) and 55.8 Gy of local radiation therapy. Adjuvant vincristine chemotherapy was administered during radiotherapy, and lomustine, vincristine, and cisplatin chemotherapy was administered during and after radiation. RESULTS: Progression-free survival was 86% +/- 4% at 3 years and 79% +/- 7% at 5 years. Sites of relapse for the 14 patients who developed progressive disease included the local tumor site alone in two patients, local tumor site and disseminated disease in nine, and nonprimary sites in three. Brainstem involvement did not adversely affect outcome. Therapy was relatively well tolerated; however, the dose of cisplatin had to be modified in more than 50% of patients before the completion of treatment. One child died of pneumonitis and sepsis during treatment. CONCLUSION: These overall survival rates compare favorably to those obtained in studies using full-dose radiation therapy alone or radiation therapy plus chemotherapy. The results suggest that reduced-dose craniospinal radiation therapy and adjuvant chemotherapy during and after radiation is a feasible approach for children with nondisseminated medulloblastoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Treatment of diencephalic syndrome with chemotherapy: growth, tumor response, and long term control.

BACKGROUND: The diencephalic syndrome (DS), which is manifested by progressive emaciation and failure to thrive in an apparently alert, cheerful infant, usually is due to a low grade hypothalamic glioma. Treatment with aggressive surgery and/or radiotherapy is variably successful in controlling disease and may result in severe neurologic sequelae. Chemotherapy recently has been shown to be effective in patients with low grade gliomas of childhood, but it is used infrequently in those with DS. METHODS: The authors evaluated the efficacy of a regimen of carboplatin and vincristine on improving weight, causing tumor shrinkage, and delaying the need for alternative therapies in seven children (ages 9-20 months; median age, 11 months) with DS. Five patients weighed less than the 5th percentile for their age at the start of the study, one weighed within the 10th percentile, and one weighed within the 25th percentile. RESULTS: At follow-up (range, 6-54 months; median, 28 months), the patients' weights had increased by 66-95% (median, 80%). On magnetic resonance imaging, four patients had a >50% reduction in tumor mass, one had a 25-50% reduction, and two had stable disease. In those patients with radiographic response to treatment, weight gain was accomplished with oral feedings in four of five patients, whereas those with stable disease required nasogastric, nasojejunal, or gastrostomy tube supplementation to maintain weight. Disease progression occurred at a median of 24 months after initiation of chemotherapy, and two patients remained free of progressive disease at last follow-up. Five patients were alive a median of 59 months from diagnosis. The need for radiation or other therapies was delayed in six of seven children. Therapy was tolerated without significant toxicities. CONCLUSION: The authors conclude that treatment of DS with a carboplatin and vincristine regimen results in demonstrable weight gain, may result in tumor shrinkage, and in some cases, significantly delays the need for alternative therapies.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Pediatric central nervous system tumors.

Much of the recent change in the management of brain tumors in children has centered on the expanded use of chemotherapy. The addition of chemotherapy has resulted in better survival rates for children with medulloblastoma and altered the management for those with low-grade gliomas. For other tumor types, therapeutic advances have been slower. High-dose chemotherapy increasingly is being employed to treat malignant childhood tumors, with variable results.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Survival and prognostic factors following radiation therapy and chemotherapy for ependymomas in children: a report of the Children's Cancer Group.

OBJECT: Ependymomas in children continue to generate controversy regarding their histological diagnosis and grading. optimal management, and possible prognostic factors. To increase our knowledge of these tumors the authors addressed these issues in a cohort of children with prospectively staged ependymomas treated with radiotherapy and chemotherapy. METHODS: Children between the ages of 2 and 17.3 years harboring an intracranial ependymoma confirmed by a central review of the tumor's pathological characteristics were treated according to Children's Cancer Group Protocol 921 from 1986 to 1992. Treatment following surgery and postoperative tumor staging (including brain computerized tomography or magnetic resonance [MR] imaging, spinal MR imaging or myelography, and cerebrospinal fluid cytological investigation) included craniospinal irradiation with a local boost to the primary tumor and patient randomization to receive adjuvant chemotherapy with either 1) CCNU, vincristine, and prednisone, or 2) the eight-drugs-in-1-day regimen. Centralized review of the tumor pathological characteristics revealed 20 ependymomas and 12 anaplastic ependymomas in the 32 children included in the study. Diagnoses made at the individual institutions included anaplastic (malignant) ependymoma (15 patients), ependymoma (four patients), ependymoblastoma (nine patients), ependymoastrocytoma (one patient), and primitive neuroectodermal tumor (three patients), which were discordant with the centralized review diagnosis in 22 of 32 cases. Only three of the 32 patients had metastatic disease (two with M and one with M3 stages). At surgery, 47% of tumors were estimated to be totally resected. Among the 14 of 17 patients who suffered a relapse and were evaluated for site of relapse, 10 (71%) had an isolated local relapse, three (21%) had concurrent local and metastatic relapse, and only one (7%) had an isolated metastatic relapse. Kaplan-Meier estimates of 5-year progression-free survival (PFS) and overall survival rates were 50 +/- 10% and 64 +/- 9%, respectively. CONCLUSIONS: Predictors of PFS duration included an estimate of the extent of resection made at surgery (total compared with less than total, p = 0.0001) and the amount of residual tumor on postoperative imaging as verified by centralized radiological review (< or = 1.5 cm2 compared with > 1.5 cm2, p < 0.0001). No other factors, including centrally reviewed tumor histopathological type, location, metastasis and tumor (M and T) stages, patient age, race, gender, or chemotherapy treatment regimen significantly correlated with PFS duration. The pattern of predominantly local relapse and the important influence of residual tumor or the extent of resection on PFS duration confirms a prevailing impression that local disease control is the major factor in the prediction of outcome of ependymoma. Survival rates were comparable with those reported by other investigators who have treated patients with similar doses of radiation and no chemotherapy.

Adolescent↗
PubMed1998

Current neurosurgical management and the impact of the extent of resection in the treatment of malignant gliomas of childhood: a report of the Children's Cancer Group trial no. CCG-945.

OBJECT: One hundred seventy-two children with high-grade astrocytomas were treated by members of the Children's Cancer Group in a prospective randomized trial designed to evaluate the role of two chemotherapy regimens. Seventy-six percent of the patients (131 children) in whom a diagnosis of either anaplastic astrocytoma or glioblastoma multiforme was confirmed by central pathological review are the subject of this report. METHODS: Patients were stratified according to the extent of tumor resection (biopsy [< 10%], partial resection [10-50%], subtotal resection [51-90%], near-total resection [> 90%], and total resection) as determined by surgical observation and postoperative computerized tomography scanning. Information on contemporary neurosurgical management was obtained from the patient's operative records and standardized neurosurgical report forms. The vast majority of tumors were supratentorial: 63% (83 tumors) in the superficial cerebral hemisphere, 28% (37 tumors) in the deep or midline cerebrum, and only 8% (11 tumors) in the posterior fossa. A significant association was detected between the primary tumor site and the extent of resection (p < 0.0001). A radical resection (> 90%) was performed in 37% of the children: 49% of the tumors in the superficial hemisphere and 45% of tumors in the posterior fossa compared with 8% of midline tumors. Tumor location could also be used to predict the need for both temporary and permanent cerebrospinal fluid (CSF) diversion. Half of the deep tumors and 8% of the hemispheric astrocytomas ultimately required a permanent CSF shunt. Improvement in preoperative neurological deficits and level of consciousness was seen in 36% and 34% of the children, respectively. New or increased deficits were present in 14% of the children, with 6% experiencing a diminished sensorium after surgery. Postoperative nonneurological complications were rare: infection, hematoma, and CSF fistula each occurred in 1.7% of the children. Univariate and multivariate analyses demonstrated that radical tumor resection (> 90%) was the only therapeutic variable that significantly improved progression-free survival (PFS) rates. For all patients with malignant astrocytomas, the distributions of PFS rates were significantly different (p = 0.006) following radical resection compared with less extensive (< or = 90%) resection. The 5-year PFS rates were 35 +/- 7% and 17 +/- 4%, respectively. The differences in the distribution of PFS rate were significant for the subsets of patients with anaplastic astrocytoma (p = 0.055) and glioblastoma multiforme (p = 0.046). The 5-year PFS rates for anaplastic astrocytoma were 44 +/- 11% and 22 +/- 6% for cases in which the tumor was radically resected and less than radically resected, respectively; whereas the 5-year PFS rates for glioblastoma multiforme were 26 +/- 9% and 4 +/- 3% for cases in which the tumor was radically resected and less than radically resected, respectively. CONCLUSIONS: The demonstration of a survival advantage provided by radical resection should prompt neurosurgeons to treat malignant pediatric astrocytomas with aggressive surgical resection prior to initiation of radiotherapy or adjuvant chemotherapy.

Adolescent↗
PubMed1997

Pediatric congenital bilateral perisylvian syndrome: clinical and MRI features in 12 patients.

In 1926, Foix, Chavany and Marie described an acquired syndrome of fasciopharyngoglossomasticatory diplegia resulting from bilateral infarction of the anterior operculum. Clinical features consisted of facial diplegia, dysarthria, pseudobulbar palsy, mild to severe mental retardation, and seizures. A developmental form, similar in presentation in adults with MRI findings consisting of bilateral perisylvian cortical malformation consistent with polymicrogyria involving the sylvian fissure and opercular cortex, has been recognized; but few pediatric cases of congenital bilateral perisylvian syndrome (CBPS) have been reported. Over the past four years, we have encountered 12 cases of CBPS presenting in childhood. Age ranges were from 1 week to 11 years with a median of 2.25 years; six were less than two years of age. Seven were male and five female. Ten had bilateral perisylvian polymicrogyria on MRI; two had unilateral perisylvian schizencephaly with contralateral perisylvian polymicrogyria. Clinical manifestations included developmental delay in 7; poor palatal function in 5; hypotonia in 4; arthrogryposis in 4; hemiparesis in 3; apnea in 3; paraparesis in 2; micrognathia in 2; pectus excavatum in 2; quadriparesis in 1; and hearing loss in 1. Seizures occurred in seven (58%) and consisted of infantile spasms (n = 1), generalized tonic-clonic (n = 1), complex partial (n = 2), partial motor (n = 2; 1 with secondary generalization), and febrile convulsions (n = 1). CBPS has different manifestations in the pediatric population than in adults. CBPS is more common than previously thought, is recognizable by MRI and should be suspected clinically in any infant or child presenting with oromotor dysfunction/pseudobulbar signs and developmental delay, especially if there are associated congenital malformations. Epilepsy is not a constant feature in the pediatric presentation and is variable in type and severity.

Abnormalities, Multiple↗
PubMed1997

Childhood tumors.

Advances are slowly being made in the understanding and treatment of primary childhood brain tumors. The addition of chemotherapy has resulted in better survival for children with medulloblastoma. For other tumor types, therapeutic advances have been slower. High-dose chemotherapy is increasingly being employed to treat malignant childhood tumors, with variable results. Chemotherapy has been effective in low-grade glial tumors.

Antineoplastic Agents↗