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R J Packer

Publications and source records attributed to R J Packer.

At least 145 records · Page 8Linked to original sources
PubMed1988

Results of the treatment of children with recurrent gliomas with lomustine and vincristine.

Gliomas comprise over 50% of all childhood brain tumors. Treatment of recurrent childhood gliomas has been disappointing and the effectiveness of therapy has been difficult to judge because of the variable natural history of the disease. Information gathered recently has suggested that treatment with [1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea)] (CCNU) and vincristine (VCR) after radiotherapy is effective in prolonging survival in children with newly diagnosed anaplastic gliomas. The authors have used these same drugs--CCNU (100 mg/m2) and VCR (1.5 mg/m2 up to a maximum dose of 2 mg)--in 6-week cycles for a maximum of eight cycles in children with recurrent gliomas. To date, 15 patients have been treated; five patients had malignant gliomas and ten low-grade gliomas. Three children showed improvement, five had stable disease, and seven had progressive disease. Of the five patients with malignant gliomas, four progressed within two cycles of treatment and one had stable disease for 7 months on treatment and then relapsed. Seven of ten children with low-grade gliomas benefitted from treatment and six remain in continuous remission a median of 16 months after initiation of therapy. Three of these children are off all therapy 21, 30, and 30 months after treatment, respectively. Therapy was well tolerated and toxicity consisted primarily of reversible bone marrow suppression. The authors conclude that CCNU and VCR chemotherapy is effective in children with recurrent low-grade gliomas and can result in relatively long-term disease stabilization. In limited experience of the authors, it is not of benefit in children with recurrent anaplastic lesions.

Adolescent↗
PubMed1988

Chromosome abnormalities in pediatric brain tumors.

Recurrent, site-specific chromosome translocations and other cytogenetic abnormalities are being described in ever-increasing numbers and types of human tumors. Primary brain tumors are the most common pediatric solid tumor and differ from those of adults in both histology and clinical behavior. We examined chromosomes from 21 primary pediatric brain neoplasms grown in short-term tissue culture, including 6 astrocytomas, 10 primitive neuroectodermal tumors, and 5 other tumors. Karyotypes from 3 of 5 astrocytomas were abnormal, as were those of 9 of 10 primitive neuroectodermal tumors. Numerical abnormalities were found in 6 tumors and structural aberrations in 12 tumors. Deletions, additions, and translocations involving the short arm of chromosome 1 were observed in 5 tumors, with chromosome breakpoints ranging from 1p1 to 1p3. An isochromosome of the long arm of 17, i(17q) was the most frequent site-specific structural abnormality, found in 1 anaplastic astrocytoma and 2 recurrent cerebellar primitive neuroectodermal tumors, one with islands of anaplastic astrocytoma. These results differ from reported chromosome studies of adult brain tumors, suggesting that pediatric brain tumors may differ from those of adults when examined at the genetic level. Additional chromosomal and molecular studies of brain tumors from children are warranted to define these differences.

Adolescent↗
PubMed1988

Treatment of chiasmatic/hypothalamic gliomas of childhood with chemotherapy: an update.

Chiasmatic/hypothalamic gliomas (CHG) of childhood may cause progressive neurological and visual deterioration. Radiotherapy results in at least transient stabilization of tumor growth in most patients but may also have adverse long-term effects, especially in young children. Since 1977, children with progressive CHG under 5 years of age at diagnosis have been treated with combination chemotherapy (actinomycin D and vincristine) without radiotherapy. Twenty-four patients, a median of 1.6 years of age at diagnosis, have been treated and followed for a median of 4.3 years (range, 0.3-10 years). All patients are alive. Nine have developed radiographic or clinical progression, occurring a median of 3 years (range, 2-6.5 years) after initiation of treatment. Fifteen of 24 (62.5%) have remained free of progressive disease and have received no other therapy. Tumor shrinkage was documented in 9 of 24 patients but did not clearly relate to long-term outcome. Full-scale intelligence quotient (IQ) obtained a median of 3.5 years after diagnosis in patients who received only chemotherapy was a mean of 103 (range 84-133). We conclude that chemotherapy can significantly delay the need for radiotherapy in children with CHG and such a delay may be beneficial regarding long-term outcome.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Efficacy of adjuvant chemotherapy for patients with poor-risk medulloblastoma: a preliminary report.

Recent studies have demonstrated that preoperative and postoperative factors can broadly stratify patients with medulloblastoma/primitive neuroectodermal tumors (MB/PNET) into risk groups. For children with factors that suggest poor outcome after treatment with surgery and radiotherapy, the addition of chemotherapy can improve survival. Since 1983, 26 children with poor-risk posterior fossa MB/PNET have been treated at our institution with craniospinal radiation therapy and adjuvant chemotherapy. Chemotherapy consisted of vincristine during radiotherapy and eight 6-week cycles of vincristine, cis-platinum, and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU). Twenty-five of 26 patients (96%) who have been entered on this protocol remain alive and free of disease at a median of 24 months from diagnosis (range 6 to 50 months). Twenty patients have completed all therapy and are at a median of 32 months from initial diagnosis with no evidence of disease. These patients were compared to a group of children with similar prognostic features treated at our institution between 1975 and 1983. Actuarial disease-free survival was statistically significantly better for protocol patients than for historical control subjects (p less than 0.002). This difference was most marked in patients who had received radiation therapy alone (p less than 0.0003). Actuarial 2-year disease-free survival was 96% for patients on protocol as compared to 59% for historical control patients who had been treated with radiotherapy alone. The chemotherapy given in this protocol was well tolerated. The results of this study, although preliminary, suggest that adjuvant chemotherapy is at least transiently effective in improving the rate of disease-free survival for children with poor-risk MB/PNET.

Adolescent↗
PubMed1988

Cis-platinum ototoxicity after radiation treatment: an animal model.

The chemotherapeutic agent cis-platinum has been used effectively as a treatment for many tumors. One of the most common toxic effects caused by this treatment is ototoxicity. More severe hearing loss has been reported in patients who had received cranial radiation prior to chemotherapy with cis-platinum. The present laboratory study was undertaken with chinchillas to determine whether ototoxicity is potentiated by cis-platinum administration after cochlear irradiation. Results support the clinical observation that cranial radiation prior to administration of an ototoxic chemotherapeutic agent can have a synergistic effect of increased susceptibility to the ototoxic potential of the agent.

Acoustic Stimulation↗
PubMed1988

Significance of basal ganglia calcification on computed tomography in children.

We reviewed 6,428 head computed tomography (CT) scans performed on 4,283 children at our institution over a 3-year period and found basal ganglia calcification (BGC) in 48 (1.1%) of the patients. Their mean age at the time of detection was 5.3 years (range: 0.5-20 years); 16 (33%) patients had cancer, 14 (29%) had tuberous sclerosis or congenital infection and 18 (38%) had other medical conditions. All patients with cancer had been treated with radiation therapy, receiving a mean dose of 4,583 cGy (range: 1,800-5,500 cGy) to the diencephalon, and calcifications first became apparent at a median of 10 months after treatment. Other medical conditions included neonatal asphyxia (3), metabolic disease (3) (Kearns Sayre, MELAS, Krabbe's), congenital anomalies (3), meningitis (2), Fahr's disease (1) and others (6). Neurologic symptoms were common in children of all groups, but could not be correlated to BGC changes. Calcium and phosphorus metabolism was evaluated in 19 patients and was abnormal in 1. We conclude that BGC on CT in childhood occur primarily as an aftermath of the cancer treatment or in children with generalized neurologic dysfunction. Many children with BGC are delayed in their development, but calcifications are not directly related to specific forms of neurologic dysfunction. Rather, ther appear to serve as markers for more extensive brain damage.

Adolescent↗
PubMed1988

Leptomeningeal dissemination of low-grade gliomas in childhood.

Although leptomeningeal spread (LMS) of primary CNS tumors in children has been well documented in the literature, it has rarely been reported in children with low-grade gliomas. Between 1975 and 1985, 6 of 162 children (3.7%) with low-grade gliomas treated at Children's Hospital of Philadelphia had LMS. LMS was present at diagnosis of the original tumor in one patient, was the first sign of relapse in one patient, occurred simultaneously with local relapse in two patients, and after local relapse in two patients. Pathology of the original tumor was low-grade astrocytoma in five and low-grade oligodendroglioma in one. Primary tumor site was cervical cord in three, chiasm in one, frontal lobe in one, and cerebellum in one. All of the children with LMS had undergone surgical treatment at the time of diagnosis of the primary tumor; four had total resections at some point in their course. Three of the six patients died; three are still alive after treatment with radiation therapy and/or chemotherapy. The longest survival to date has been 3 1/2 years after diagnosis of LMS. We compared clinical characteristics of these six patients with 131 children with low-grade tumors without dissemination treated at our institution during the same time period. LMS, although relatively infrequent, does occur in children with low-grade gliomas, especially spinal cord tumors. LMS may occur at any time during illness and diagnosis may be difficult unless LMS is suspected. Treatment, at times, results in clinical improvement and considerable disease control.

Adolescent↗
PubMed1988

Leptomeningeal spread of intramedullary spinal cord tumors. Report of three cases.

Three patients with intramedullary spinal cord tumors and secondary leptomeningeal spread of their tumors are presented. Two patients had astrocytomas and one had a ganglioglioma. Two tumors were located in the cervical spinal cord and one within the thoracic spinal cord. Review of the past and recent literature shows leptomeningeal dissemination of spinal cord tumors to be relatively rare, but it should be suspected and investigated in any patient whose condition deteriorates following removal of a spinal cord neoplasm.

Adolescent↗
PubMed1988

Intracranial visual pathway gliomas in children with neurofibromatosis.

The association between neurofibromatosis and visual pathway gliomas is well documented. The introduction of computed tomography and magnetic resonance imaging has heralded a new era in the understanding of visual pathway gliomas. Both of these noninvasive neuroinvestigative techniques have demonstrated extensive abnormalities throughout the visual pathway in children with visual pathway gliomas, especially in those with neurofibromatosis. The clinical significance of these abnormal areas of brain, especially in asymptomatic patients, is unknown. In an attempt to clarify the incidence, natural history, and clinical course of patients with neurofibromatosis and visual pathway lesions, we reviewed our experience with 24 patients managed consecutively at Children's Hospital of Philadelphia over the past 12 years. The patients in this series were compared to 29 children with visual pathway gliomas without neurofibromatosis who were evaluated at our institution over the same period of time. Visual pathway gliomas in children with neurofibromatosis differ from those in children without neurofibromatosis. In general, lesions tended to be more extensive in patients with neurofibromatosis and the clinical course of these patients is more variable. Twelve of the 24 patients with neurofibromatosis in our series had symptoms of progressive disease at the time of diagnosis and underwent treatment with variable results. Twelve children with neurofibromatosis and visual pathway lesions had static lesions at the time of diagnosis and, to date, 3 have developed progressive disease. From our review we can make some recommendations concerning the management of children with neurofibromatosis and visual pathway gliomas, but many questions remain unanswered. Sequential follow-up of a large cohort of both asymptomatic and symptomatic children with neurofibromatosis and visual pathway lesions is needed to more definitively outline the best management approach for these patients.

Adolescent↗
PubMed1988

Medulloblastoma: presentation, diagnosis and management.

Primitive neuroectodermal tumor or medulloblastoma (PNET/MB) is the most common malignant tumor of the brain in children. Recent progress in the management of this once almost uniformly fatal disease is illustrative of both the advances which have been made in the management of childhood brain tumors and the gaps in our understanding of childhood central nervous system malignancies. Using aggressive surgery and radiotherapy, more than 50% of children with this tumor can be expected to be alive and free of disease five years later. With detailed postoperative evaluation, children with PNET/MB can be stratified into two major subgroups: Those with an average prognosis and those with a poor prognosis. The addition of chemotherapy for children at the highest risk of relapse after treatment with radiotherapy results in an improved duration and rate of survival. However, treatment often results in significant endocrinological and intellectual sequelae.

Adolescent↗
PubMed1987

Pineocytomas of childhood. A reappraisal of natural history and response to therapy.

Pineocytomas are pineal parenchymal tumors composed of differentiated cells histologically similar to those of the mature pineal gland. Little is known about the incidence, pattern of growth, or response to treatment of pineocytomas. Between 1975 and 1985, six children with pineocytomas were treated at our institution, and pineocytomas constituted 11% of all newly diagnosed pineal region tumors. The clinical, radiographic, and pathologic features of these six patients with pineocytomas are presented. Initial treatment for these children included craniospinal plus supplemental local radiotherapy (three), local radiotherapy alone (one), or radiation therapy plus adjuvant chemotherapy (two). Four of six patients had tumor recurrence a median of two years after diagnosis. Three patients had leptomeningeal dissemination, one at the time of diagnosis and two following therapy. Our findings suggest that: biopsy is necessary to distinguish pineocytomas from other pineal region tumors; radiation therapy alone is inadequate; and these tumors are aggressive in the pediatric population, with a high propensity for leptomeningeal dissemination.

Adolescent↗
PubMed1987

Long-term sequelae of cancer treatment on the central nervous system in childhood.

Increasing numbers of children with cancer, including those with acute lymphocytic leukemia and medulloblastoma, are experiencing long-term disease control. As survival increases, so does the recognition that the treatment used to prolong survival may have significant detrimental effects on the central nervous system (CNS). Because of the slow replication rate of most constituents of the CNS, these effects tend to be delayed. Radiotherapy, and to a lesser extent, chemotherapy (primarily methotrexate) have been implicated in the causation of such sequelae. The pathogenesis of CNS damage is only partially understood and evidence suggests that direct effects on intracranial endothelial cells and brain white matter and immunologic mechanism play a role. A spectrum of clinical syndromes may occur, including radionecrosis, necrotizing leukoencephalopathy, mineralizing microangiopathy with dystrophic calcification, cerebellar sclerosis and spinal cord dysfunction. The two most common forms of sequelae are neuropsychological and neuroendocrinologic damage. The frequency, degree of and etiology of neurocognitive dysfunction is less than completely elucidated. Radiotherapy has been implicated as the major cause of damage, but the relationship between radiotherapy and the type of damage caused and the volume and dose of radiotherapy and degree of cognitive damage is unclear. Cognitive deficits are progressive in nature. Younger children are more likely to suffer the severest damage; but no patient of any age is free of risk of damage. Growth hormone impairment is the most common form of neuroendocrinologic dysfunction. There is increasing evidence that children with cancer who are long-term survivors are at increased risk for the development of secondary CNS tumors; possibly due, in part, to previous treatment. Much work needs to be done to characterize the sequelae which may occur, develop means of earlier detection, investigate ways to ameliorate sequelae and devise less toxic treatment.

Antineoplastic Agents↗
PubMed1987

Cerebellar sclerosis in pediatric cancer patients.

Cerebral cortical sclerosis is an acquired condition that has rarely been described in cancer patients. We reviewed necropsy findings in all children with cancer who died at the Children's Hospital of Philadelphia during the 20 year period 1963-1982 and found cerebellar sclerosis in 14 children with cancer (12 with acute lymphoblastic leukemia, 1 each with neuroblastoma and osteogenic sarcoma). The lesions were focal (3), multifocal (9) or diffuse (2). They occurred more frequently in children with acute lymphoblastic leukemia who had received intravenous methotrexate therapy. Ten of these 12 children had also received whole brain irradiation. The pathogenesis of the cerebellar sclerosis is unknown, but it is possible that extrinsic cerebellar compression by tumor or chronically increased intracranial pressure may have played a role in 6, ischemia/hypoxia in 3, and methotrexate toxicity in 2. No clear associations could be ascertained in 3. Methotrexate may be a previously unrecognized cause of cerebellar cortical injury. In addition, oncologic treatment regimens that include other central nervous system-penetrating drugs and irradiation may sensitize cerebellar cortex and make it more susceptible to other cerebellar sclerosis-causative factors.

Cerebellum↗
PubMed1987

Outcome of children with primary intramedullary spinal cord tumors.

The influence of clinical and treatment factors on the outcome of children with primary intramedullary spinal cord tumors (PST) was evaluated by reviewing the records of 26 children diagnosed during the 15-year period 1970-1984. Five-year survival was 39%, but 5-year event-free survival (EFS) was only 14%. Eighteen-month EFS was 53% (9/17) among children with low-grade astrocytoma. 100% (2/2) with ependymoma, and 0 of 7 with anaplastic astrocytoma or ganglioglioma. There was no significant difference in the 18-month EFS by location of tumor, duration of symptoms, or extent of surgical removal. Five of 9 children with locally recurrent PST had a second operation, and 4 were alive a median of 56 months later. PST disseminated to the leptomeninges or the III ventricle in 5 children: 2 at diagnosis, 2 as the first sign of disease relapse, and 1 after local recurrence. Given the poor outcome of our children, different methods of treatment for children with tumors in this location should be evaluated.

Adolescent↗
PubMed1987

Magnetic resonance imaging determination of gliomatosis cerebri.

Gliomatosis cerebri is a rare condition characterized by diffuse overgrowth of large portions of the brain and spinal cord by glial cells in varying stages of differentiation. The tumor process is primarily an infiltrative, rather than a destructive one. Hence, pre-operative diagnosis by traditional imaging studies, including computed tomography (CT), has been difficult. Magnetic resonance imaging (MRI), with its unique sensitivity for cerebral pathology, is an ideal modality for demonstrating this lesion. We present three cases of gliomatosis cerebri in which high-field MRI clearly delineates the extent of the pathologic process.

Adolescent↗
PubMed1987

Magnetic resonance imaging diagnosis of disseminated necrotizing leukoencephalopathy.

Disseminated necrotizing leukoencephalopathy is a rare syndrome of progressive neurologic deterioration seen most often in patients who have received central nervous system irradiation combined with intrathecal or systemic chemotherapy in the treatment or prophylaxis of various malignancies. Magnetic resonance imaging was more sensitive than computed tomography in detecting white matter abnormalities in the case of disseminated necrotizing leukoencephalopathy reported here. Magnetic resonance imaging may be useful in diagnosing incipient white matter changes in disseminated necrotizing leukoencephalopathy, thus permitting early, appropriate therapeutic modifications.

Child↗
PubMed1987

Results of a pilot study of hyperfractionated radiation therapy for children with brain stem gliomas.

The majority of children with brain stem gliomas develop progressive disease within 18 months of diagnosis and treatment. Radiotherapy (RT) is of transient benefit in most patients and higher total doses of RT have been related to improved survival. The amount of RT which can be given is limited by the tolerance of the surrounding brain. Hyperfractionated RT theoretically allows higher doses of RT to be tolerated by the brain. Sixteen children with brain stem gliomas were treated on a hyperfractionated RT schedule, receiving 120 cGy of RT twice daily, to a total dose of 6480 cGy. All patients tolerated treatment well. Eleven of 15 (73%) evaluable patients had a response to treatment and two (13%) others had stable disease. One patient developed progressive disease during treatment. All patients were tapered off steroids by the completion of treatment. Thirteen of 16 (81%) patients developed progressive disease at a median of 7 months after diagnosis and three remain in remission 8, 12, and 15 months following diagnosis. These results were similar to those of historical controls. Two patients were surgically explored at time of relapse and 5 have had an autopsy. No acute or subacute neurologic toxicity was seen; but long-term detrimental effects on brain could not be assessed. The implications of this study are that escalations of the dose of hyperfractionated RT can be entertained for children with brain stem gliomas.

Adolescent↗