Biomedical subjects

R J Packer

Publications and source records attributed to R J Packer.

At least 19 recordsLinked to original sources

PubMed1992

The effects of adjuvant chemotherapy on growth in children with medulloblastoma.

BACKGROUND: Current therapy for children with medulloblastoma includes craniospinal radiation therapy (CSRT) with or without adjuvant chemotherapy. The difference in growth of children after the two different therapeutic modalities is unknown. METHODS: The growth of 38 prepubertal children who survived medulloblastoma was reviewed retrospectively. Fifteen of these patients received CSRT alone; 23 received chemotherapy in addition to the radiation therapy. RESULTS: The average growth velocity of all patients with medulloblastoma during the 4 years of the study was below the mean for age and sex in all patients except one. Most patients grew at velocities more than two standard deviations below the mean. The overall growth of children who received chemotherapy in conjunction with CSRT was significantly worse than the growth of those who received only CSRT. The children who received chemotherapy showed little or no improvement in growth velocity by year 4; those who did not receive chemotherapy had some improvement. CONCLUSIONS: These findings suggest that chemotherapy potentiates the deleterious effects of radiation on growth.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1992

Vascular malformation with radiation vasculopathy after treatment of chiasmatic/hypothalamic glioma.

Chiasmatic/hypothalamic gliomas usually are histologically benign astrocytomas that may recur many years after diagnosis and treatment. Three children with chiasmatic/hypothalamic gliomas who were treated at the authors' institution returned 9.5, 11.5, and 2 years, respectively, after radiation therapy (RT) because visual and neurologic deterioration developed. Neuroradiographic studies, including arteriography in two of the patients, showed large mass lesions. These were presumed to be recurrence of tumor, and chemotherapy was administered. Pathologic examination of two children who died and of the third who had a biopsy revealed only a minimal amount of residual, histologically benign astrocytoma, whereas the bulk of the specimen consisted of numerous vessels of variable size. These probably represented incorporation of the rich vasculature in the chiasmal region into the tumor, which underwent degeneration secondary to RT. Radiographic methods did not distinguish progressive tumor growth from the vasculopathy and led to inappropriate clinical diagnoses and treatment.

Adolescent↗

PubMed1992

Spinal cord compression in widely metastatic Wilms' tumor. Paraplegia in two children with anaplastic Wilms' tumor.

Spinal cord compression in Wilms' tumor is a rare event, generally caused by invasion of the canal by paraspinal lesions or metastatically involved vertebral bodies. This case report reviews the clinical presentation, radiologic evaluation, and emergent therapy in two cases of spinal cord compromise involving patients with widely metastatic Wilms' tumor. One of these is the only known report of intradural metastasis in a child with this malignancy. Both cases illustrate the importance of anticipating and rapidly responding to neurologic complications that may arise in patients with aggressively metastatic Wilms' tumor.

Child, Preschool↗

PubMed1992

Choroid plexus carcinoma of childhood.

The presentation, growth patterns, and response to therapy of 11 consecutive children with choroid plexus carcinomas were analyzed, and the results were compared with the outcome reported in other series. Patients were a median of 26 months of age at diagnosis. Two patients had thalamic tumors, one had a posterior fossa primary, and the rest had ventricular lesions. Five of 11 (45%) children remain in continuous progression-free remission a median of 48 months from diagnosis. Four of the five in continuous remission had a "gross total" surgical resection, and only one received radiation therapy. Five of six patients with subtotal resections relapsed despite postoperative treatment with radiation therapy (three) and chemotherapy (one). The response to treatment with radiation therapy or chemotherapy at relapse was disappointing, with only one child (treated with etoposide) responding. In combination with other series, 11 of 14 children had prolonged progression-free survival after gross total resection (only two of whom received adjuvant therapy) compared with two of 20 after less than total resections, independent of the type of adjuvant therapy given. Adjuvant therapy for children with choroid plexus carcinomas is of unproven benefit, and this must be considered when analyzing innovative treatment trials for such children, especially for those with totally resected tumors. Patients with partially resected lesions fare poorly with present forms of treatment.

Child↗

PubMed1992

Three- and four-year cognitive outcome in children with noncortical brain tumors treated with whole-brain radiotherapy.

Cognitive function and school achievement were studied prospectively over 3 to 4 years in 19 children treated for brain tumors with whole-brain radiotherapy; 14 of 19 also received adjuvant chemotherapy. For the group as a whole, mean IQ fell from a baseline of 104 to 92 at follow-up (p < 0.01). Age was inversely correlated with change in IQ over time (r = 0.71; p < 0.001). Children younger than 7 years at diagnosis had a mean IQ loss of 27 points, while children over 7 years at diagnosis showed no significant decrease in IQ. Decline in IQ occurred between baseline and year 2 of follow-up; none could be documented between years 2 and 4. All children younger than 7 years at diagnosis were receiving special education at follow-up; 50% of the children over 7 years at diagnosis were receiving supplemental educational services.

Adolescent↗

PubMed1992

Chemotherapy with vincristine (VCR) and etoposide (VP-16) in children with low-grade astrocytoma.

Twenty patients, aged 6 months to 20 years, with low-grade astrocytoma (LGA) participated in a chemotherapy trial of vincristine (VCR) and etoposide (VP-16). Fourteen children had recurrent progressive disease at entry on study. Prior treatment consisted of surgical resection alone (6), surgical resection and irradiation (4), surgical resection, irradiation and chemotherapy (2), surgery and chemotherapy (1), and irradiation and chemotherapy (1). Six patients were treated at initial diagnosis of LGA because they were less than 5 years old (5) or for a second primary tumor (1). Four recurrent patients and 3 newly diagnosed patients underwent surgical debulking of their tumors immediately prior to study entry. Tumors were located in the optic nerve/chiasm/hypothalamus (8), brain stem/cerebellum (4), cerebral hemispheres (3), midline structures (3), and spinal cord (2). The treatment plan administered in an out-patient setting consisted of weekly VCR 1.5 mg/m2 for 7 to 8 weeks and VP-16 100 mg/m2 for 5 days repeated every 6 weeks for a total of 18 months of therapy. Responses were evaluated by computerized tomography or magnetic resonance imaging. Of the 20 patients, 1 exhibited a partial response maintained for 12+ months, 3 exhibited minor responses maintained for a period of 10+ to 35 months, and 11 maintained stable disease for 10 to 42 months. Of the 11 patients with stable disease, 2 were withdrawn early from the study without further therapy. Five of the 20 patients developed progressive disease; for 4 of these 5, this occurred during the first course of therapy. Subsequently, these 5 died due to tumor.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1992

Chemotherapy of malignant brain tumors in children.

Chemotherapy has become an important modality in the management of children with brain tumors. Factors that impede improved effectiveness of anti-neoplastic drugs are being identified and addressed. Specific agents have emerged that show anti-brain tumor activity alone or in combination therapy. Use of these agents requires facility regarding their dosing, routes of delivery, mechanisms of action, metabolism and toxicities. Multi-institution cooperative group trials provide the optimum means by which to evaluate the effectiveness of chemotherapy in children with brain tumors.

Adolescent↗

PubMed1992

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↗

PubMed1991

Is craniospinal irradiation required to cure children with malignant (anaplastic) intracranial ependymomas?

Between 1970 and 1989, 17 children with histologically malignant intracranial ependymomas received treatment at the University of Pennsylvania (Philadelphia, PA). Eleven were treated with prophylactic cranial or craniospinal irradiation plus a local boost (CS-XRT), five with local (L-XRT) irradiation only, and one was treated without (NRT) irradiation. With a median survival of 2 years and a median follow-up time for long-term survivors of 6.0 years, five of 11 patients who received CS-XRT are alive compared with none treated with L-XRT and none treated with NRT. Two-year actuarial survival rates are 40% (L-XRT) and 52% (CS-XRT). When examined for other factors, age and local radiation dose remain the most significant prognostic indicators of survival. The 2-year actuarial survival for children younger than 4 years at diagnosis is 20% compared with 83% for their older counterparts. Likewise, the 2-year survival for patients treated with local radiation doses over 4500 cGy was 55% compared with 0% for patients treated with lesser doses. To date there are a total of 28 recurrences. All have occurred with local components except for six (unknown) who died before the exact site(s) could be determined. There is no significant difference in the failure rates outside the original tumor bed in the three groups. These data suggest that local relapse remains the most significant component of failure. Because intrinsic and extrinsic factors such as age and radiation dose seem to be interrelated and at least as important as the use of craniospinal irradiation, the need for prophylactic treatment for children with anaplastic ependymoma could neither be substantiated nor refuted. The use of local radiation alone, however, should be restricted to carefully designed clinical trials in which meticulous pretreatment evaluation is performed, and vigilant posttreatment evaluation of the spine and brain is mandatory.

Brain Neoplasms↗

PubMed1991

Cognitive deficits in long-term survivors of childhood brain tumors.

Improvements in survival for patients who had childhood brain tumors has led to an increasing emphasis on the quality of life for these long-term survivors. Initial survival studies relied on global descriptions of functional abilities to assess cognitive deficits and reported that from 20% to 40% of long-term survivors had obvious partial disability and less than 10% were severely disabled. Formal neuropsychological testing has revealed that from 40% to 100% of long-term survivors have some form of cognitive deficit in various intelligence quotients, visual/perceptual skills, learning abilities, and adaptive behavior. Prospective, controlled studies have found a younger age at diagnosis, radiotherapy, methotrexate chemotherapy, tumor location and time interval to testing to be important (alone or in combination) and related to a high risk of subsequent cognitive deficits. Some variables play an as yet unresolved role. However, despite the progress of the last decade, future prospective studies are needed to define the role of certain variables in the development of cognitive deficits that maximize survival while minimizing cognitive deficits.

Brain Neoplasms↗

PubMed1991

Comparison of myelography with CT follow-up versus gadolinium MRI for subarachnoid metastatic disease in children.

We evaluated 17 children with primary intracranial neoplasms for subarachnoid metastatic disease (SAMD) using myelography with computed tomographic follow-up (Myelo + CT) and cerebrospinal fluid (CSF) histopathologic examination, as well as magnetic resonance imaging with gadolinium DTPA (MRI + Gd), between December 1988 and December 1989. There were 12 boys, and the median age was 5.7 years (range, 0.8 to 21.8 years). Tumor histology included 8 primitive neuroectodermal tumors (PNETs), 3 ependymomas, 2 low-grade astrocytomas, 1 anaplastic astrocytoma, 1 glioblastoma multiforme, 1 atypical rhabdoid tumor, and 1 malignant fibrous histiocytoma. Thirteen tumors originated in the posterior fossa, 2 were supratentorial, and 2 were in the spinal cord. The median interval between the 2 diagnostic tests was 2 days. MRI + Gd was positive in 11 (65%), Myelo + CT in 8 (47%), and CSF in 5 (29%) cases. MRI + Gd was superior in delineating spinal cord nodules and "sugar coating" whereas Myelo + CT more readily revealed nerve root sleeve filling defects. There was no case in which Myelo + CT was positive that MRI + Gd did not reveal SAMD. MRI + Gd is a safe, noninvasive test that should be used as the initial imaging modality for the presence of SAMD.

Adolescent↗

PubMed1991

Improved survival with the use of adjuvant chemotherapy in the treatment of medulloblastoma.

Between 1975 and 1989, 108 children with newly diagnosed medulloblastoma/primitive neuroectodermal tumor (MB/PNET) of the posterior fossa were treated at the authors' institution. The patients were managed uniformly, and treatment included aggressive surgical resections, postoperative staging evaluations for extent of disease, and craniospinal radiation therapy with a local boost. Beginning in 1983, children with MB/PNET were prospectively assigned to risk groups; those with "standard-risk" MB/PNET were treated with radiation therapy alone, while those in the "poor-risk" group received similar radiation therapy plus adjuvant chemotherapy with 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), vincristine, and cisplatin. The 5-year actuarial disease-free survival rate for all patients treated between 1975 and 1982 was 68%, and 73% when patients who died within 2 weeks after operation were excluded. This survival rate was statistically better for patients treated after 1982 (82%) compared to those treated between 1975 and 1982 (49%) (p less than 0.004). There was no difference in disease-free survival rates over time for children with standard-risk factors; however, there was a significant difference in the 5-year survival rate for poor-risk patients treated prior to 1982 (35%) compared to those treated later (87%) (p less than 0.001). For the group as a whole, a younger age at diagnosis correlated with a poorer survival rate; however, this relationship between age and outcome was significant only for children treated before 1983 (p less than 0.001). These results demonstrated an encouraging survival rate for children with MB/PNET, especially those treated with aggressive surgical resection followed by both radiation therapy and chemotherapy. The results strongly suggest that chemotherapy has a role for some, and possibly all, children with MB/PNET.

Adolescent↗

PubMed1991

Fusiform dilatations of the carotid artery following radical surgery of childhood craniopharyngiomas.

Between 1982 and 1990, a series of 31 children with craniopharyngiomas underwent initial surgery at the Children's Hospital of Philadelphia with an attempt at total tumor removal. Nine (29%) of them were found to have fusiform dilatation of the supraclinoid carotid artery either at the time of surgery for recurrence (one patient) or on routine surveillance with enhanced computerized tomography 6 to 18 months postoperatively (eight patients). The finding of carotid enlargement was confirmed in seven cases with magnetic resonance angiography and in one case with a formal arteriogram. Eight of the nine patients remain alive at a mean of 3.7 years after diagnosis. None have experienced hemorrhage or other symptoms referrable to fusiform dilatation of the carotid artery, which is believed to result from surgical manipulation of the carotid artery.

Adolescent↗

PubMed1991

Nerve growth factor receptor expression in peripheral and central neuroectodermal tumors, other pediatric brain tumors, and during development of the adrenal gland.

Nerve growth factor (NGF) is important to the survival, development, and differentiation of neurons. Its action is mediated by a specific cell surface transmembrane glycoprotein, nerve growth factor receptor (NGFR). In this study, NGFR expression by human fetal and adult adrenal medullary tissue, peripheral nervous system (PNS) neuroectodermal tumors (neuroblastoma, ganglioneuroblastoma, ganglioneuroma), pediatric primitive neuroectodermal tumors (PNETs) of the central nervous system (CNS), and CNS gliomas was examined by an immunohistochemical technique. Sixty-nine tumors in total were probed in this manner. Nerve growth factor receptor immunoreactivity was confined to nerve fibers and clusters of primitive-appearing cells in the fetal adrenal, and to nerve fibers and ganglion cells of the adult adrenal medulla; adrenal chromaffin cells were negative. In PNS neuroectodermal tumors, there was NGFR expression in tumor cells of 6 of 11 neuroblastomas and 6 of 6 ganglioneuroblastomas or ganglioneuromas. Thirteen of thirty-five CNS PNETs showed NGFR positivity. In most CNS PNETs, NGFR was restricted to scattered single or small groups of cells, but two tumors with astroglial differentiation showed much more extensive immunoreactivity. Most astrocytomas (11 of 14) and all ependymomas (3 of 3) were intensely NGFR positive.

Adolescent↗

PubMed1991

Biologic and immune modulating agents in the treatment of childhood brain tumors.

The data on the utility of biologic response modifiers are quite sketchy. Although no true home-runs have been hit, there is evidence that some patients will benefit from these immunologic agents. The majority of studies for central nervous system tumors have been done in adults with highly aggressive anaplastic gliomas. Many of these patients had extensive disease at the time of treatment and determination of benefit is difficult. Few pediatric trials have been attempted. The evidence for efficacy for most agents is lacking, although there are encouraging responses in children with isolated leptomeningeal spread to radiolabeled monoclonal antibodies and for patients with progressive intracranial mass lesions to one form of beta-interferon. Given the limited alternatives for many of these patients, and the neurotoxicity of other means of therapy, future studies are clearly indicated in children with malignant brain tumors. The lack of evidence of efficacy in adult glioblastoma trials cannot be used as direct evidence for the nonutility of these agents for childhood brain tumors. By and large, children tend to tolerate higher doses of biologic response modifiers than adults, again raising the hope of greater utility of these drugs for pediatric patients. From the information available, it seems unlikely that these immunomodulating agents, in themselves, will be effective in the treatment of the majority of patients with brain tumors. But in combination with aggressive surgery, radiation, and possibly chemotherapy, these agents may in time add to the armamentarium available for the treatment of childhood brain tumors.

Adjuvants, Immunologic↗

PubMed1990

Recurrent intracranial ependymomas in children. Survival, patterns of failure, and prognostic factors.

Thirty-six pediatric patients (ages 0.8-16.8 years) with recurrent intracranial ependymoma were treated for a total of 52 separate cases of relapse from 1970 to 1989. Therapy consisted of surgery in 33 cases and chemotherapy in 38 cases. Twelve patients received radiation at the time of first relapse, and five of these 12 who had initially been treated with surgery and chemotherapy alone were irradiated to full dose. The 2-year actuarial survival and progression-free survival (PFS) rates are 29% and 23%, respectively. Two-year survival after treatment of first relapse is 39%. Of the 52 cases, there have been 44 subsequent relapses (and one septic death), three of which have occurred in the five patients treated with definitive radiation. Twenty-seven relapses have occurred exclusively with local disease. Eight patients failed with disease outside as well as in the primary site. Survival was better for patients who had histologically benign lesions at relapse (53% versus 9%, P less than 0.02), and for patients in first versus subsequent relapse (p less than 0.005). Cisplatin and etoposide (VP-16) appeared to be the most active chemotherapeutic agents. The authors conclude that some patients with histologically benign ependymoma at first relapse may benefit from aggressive therapy, with occasional long-term, progression-free survival possible. Patients with malignant lesions, or patients who relapse a second time, are less likely to benefit from conventional therapy for a significant period of time.

Actuarial Analysis↗

PubMed1990

Results of treatment of children with recurrent medulloblastoma/primitive neuroectodermal tumors with lomustine, cisplatin, and vincristine.

Primitive neuroectodermal tumors/medulloblastoma (PNET/MB) are the most common posterior fossa tumors in childhood. Despite surgery and radiation therapy, 40% to 50% of children with PNET/MB will have recurrent disease. Various chemotherapeutic agents are transiently effective in recurrent PNET/MB, but long-lasting responses are rarely attainable. To increase the rate and duration of response in children with recurrent PNET/MB, the authors treated seven patients (ages 2-18 years; median, 10 years) with lomustine (CCNU) (100 mg/m2), cisplatin (CPDD) (90 mg/m2) and vincristine (VCR) (1.5 mg/m2; maximum, 2 mg) in a 6-week cycle for a maximum of eight cycles. Six of six evaluable patients responded to chemotherapy. Four patients had a complete response; three with complete disappearance of tumor by imaging studies; and one with eradication of extraneural disease for a median of 24 months from relapse (13-29 months). Overall disease-free survival was 18.5 months. All six patients have subsequently died of recurrent tumor. Major toxicities consisted of reversible bone marrow suppression (six of six), high frequency hearing loss (six of six) and decreased renal function (three of six). All patients required dosage modification for toxicity. A regimen of CCNU, VCR, and CPDD is effective therapy in children with relapsed PNET/MB and can produce relatively long-term disease control with good quality of life. Further investigation into the efficacy of this combination as adjuvant chemotherapy in newly diagnosed high-risk PNET/MB is now being performed.

Adolescent↗

PubMed1990

Microphthalmia and chorioretinal lesions in a girl with an Xp22.2-pter deletion and partial 3p trisomy: clinical observations relevant to Aicardi syndrome gene localization.

We present a 4-year-old girl with a maternally derived, unbalanced X;3 translocation resulting in partial Xp monosomy and partial 3p trisomy. She had chorioretinal defects, developmental delay, infantile seizures, and microphthalmia. These findings initially suggested a diagnosis of Aicardi syndrome. However, she had a normal-appearing corpus callosum on CT and magnetic resonance imaging scans of the brain and her retinal findings were not typical for Aicardi syndrome. This represents the 6th reported example of microphthalmia associated with an Xp22 chromosome abnormality. Four of these individuals also had features suggestive of focal dermal hypoplasia (FDH), which was not evident in our patient. The available evidence supports the hypothesis that gene disruption at Xp22 may lead to findings similar to those seen in Aicardi syndrome and FDH, both of which are believed to be X-linked dominant male lethal conditions.

Child, Preschool↗