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R J Packer

Publications and source records attributed to R J Packer.

At least 73 records · Page 4Linked to original sources
PubMed1996

Pilot study of high-dose thiotepa and etoposide with autologous bone marrow rescue in children and young adults with recurrent CNS tumors. The Children's Cancer Group.

PURPOSE: This study was designed to determine the toxicity, radiographic response rate, and outcome following high-dose thiotepa, etoposide, and autologous bone marrow rescue (ABMR) for young patients with recurrent malignant brain tumors. METHODS: Eligibility criteria required adequate renal, hepatic, and pulmonary function, and no bone marrow infiltration. Thiotepa 300 mg/m2 and etoposide 500 mg/ m2 were infused on 3 consecutive days, and autologous bone marrow was infused 72 hours following chemotherapy. RESULTS: Forty-five patients with recurrent high-grade brain tumors, aged 8 months to 36 years (median, 8 years), were treated. Seven patients (16%) died of treatment-related toxicities within 56 days of marrow reinfusion. Delayed platelet engraftment occurred in 44% of patients who survived beyond day 56. Of 35 patients with radiographically measurable disease who survived at least 28 days following ABMR, there were two complete responses (CRs) and six partial responses (PRs), for an overall response (CRs plus PRs) rate of 23% (SE = 7%). Objective responses were observed in four of 14 assessable patients with high-grade glioma and in two of six with primitive neuroectodermal tumors (PNETs)/ medulloblastoma. Survival was significantly improved in patients treated with minimal residual disease (P < .0005). Five of 18 patients (28%) with high-grade gliomas remain free of disease at 39+, 44+, 49+, 52+, and 59+ months post-ABMR. CONCLUSION: The combination of high-dose thiotepa and etoposide has activity against a variety of recurrent childhood brain tumors. These results merit further evaluation in children and young adults with both recurrent and newly diagnosed high-grade brain tumors.

Adolescent↗
PubMed1996

Central nervous system atypical teratoid/rhabdoid tumors of infancy and childhood: definition of an entity.

Clinical and pathological features of 52 infants and children with atypical teratoid/rhabdoid tumor (ATT/RhT) of the central nervous system are defined. This tumor is typically misdiagnosed as a primitive neuroectodermal tumor (PNET) primarily because 70% of ATT/RhTs contain fields indistinguishable from classic PNETs. Separation of these two tumor types is crucial because the prognosis for ATT/RhT is given even when treatment includes surgery with or without radio and/or chemotherapy. These tumors are most common in infants less than 2 years of age. The cases described in this study arose in intracranially in all but one instance, although one-third had already spread throughout the subarachnoid space at presentation. Clinical signs and symptoms and radiological features do not distinguish ATT/RhTs from PNETs. The tumors are composed entirely (13%) or partly (77%) or rhabdoid cells. Seventy percent contains fields of typical PNET alone or in combinations with mesenchymal and/r epithelial elements. The immunohistochemical profile is unique: epithelial membrane antigen, vimentin, and smooth-muscle actin are positive in the majority of tumors and markers for germ-cell tumors are consistently negative. Abnormalities of chromosome 22 distinguish ATT/RhTs from PNETs, which typically display an i(17q) abnormality.

Antibodies↗
PubMed1995

Survival of infants with malignant astrocytomas. A Report from the Childrens Cancer Group.

BACKGROUND: Very young children with central nervous system malignant brain tumors have a poor prognosis. As compared with older children, survival is less likely, and those children who do survive frequently have severe impairment of growth and cognitive abilities, resulting partly from treatment with radiotherapy. Therefore, an intensive chemotherapeutic regimen was used to treat children younger than 2 years of age with a diagnosis of malignant astrocytomas. PATIENTS AND METHODS: Thirty-nine children younger than 24 months of age who were diagnosed with malignant astrocytoma were treated on a Childrens Cancer Group protocol with an eight-drug chemotherapeutic regimen (vincristine, carmustine, procarbazine, hydroxyurea, cisplatin, cytosine arabinoside, prednisone, and dimethyl-triazenoimidazole-carboxamide) after surgery and postoperative staging. Radiation therapy was to be deferred until the completion of chemotherapy. RESULTS: The objective response rate after two cycles of chemotherapy was 24%. Most patients did not receive radiotherapy. Progression-free survival (PFS) and survival at 3 years was 36% (standard error, 8%) and 51% (8%), respectively. The PFS of those children with anaplastic astrocytoma was 44% (11%), significantly better than that of glioblastoma multiforme (GBM) (0%). Extent of resection was not associated significantly with PFS, but tumors within the cerebral hemispheres were associated with a more favorable prognosis. Tumor progression occurred locally in almost all cases and early in treatment (median PFS, 8 months). CONCLUSION: Chemotherapy appears to be effective primary adjuvant treatment for some very young children with anaplastic astrocytomas. Overall, however, survival remains poor, especially for children with GBM. Strategies to improve outcome require early intervention, because tumor progression occurs soon after diagnosis in the majority of patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Optic pathway and hypothalamic/chiasmatic gliomas in children younger than age 5 years with a 6-year follow-up.

BACKGROUND: Gliomas of the hypothalamus and optic pathways (H/OPG) comprise 5% of pediatric intracranial tumors, present most frequently in patients younger than age 5 years, and may have a more aggressive course in younger children. This study examined clinical characteristics and consequences of treatment of young children diagnosed with H/OPG: METHODS: The authors reviewed the course, treatment, and outcomes of 46 children diagnosed with H/OPG younger than age 5 years; the median follow-up was 72 months. The median age at diagnosis was 27 months. RESULTS: Fifteen (33%) of 46 patients had neurofibromatosis-1 (NF-1). Forty children (87%) had tumor progression in the follow-up period, and tumor growth was less common in children with NF-1. Initial therapy was limited to surgical resection in three and radiation in five children. To postpone radiation until after the age of 5 years, initial therapy was limited to chemotherapy in 32 patients. Radiation was not required in 9 of these patients and was postponed for 40 months (mean) in 17. Of the 46 children, 5 died of tumor progression, 4 became blind, and 20 of 34 evaluable patients had endocrine abnormalities. Endocrinopathy did not correlate with therapy. Ten of 17 children evaluated by questionnaire required special education. There was a trend for educational problems to occur in children who were irradiated before the age of 5 years. CONCLUSIONS: Gliomas of the hypothalamus and optic pathways and their treatment cause long term morbidity in young children. Chemotherapy postpones radiation effectively, and this delay may reduce neurologic morbidity; however, 60% of children eventually relapse. By contrast, patients with NF-1 have indolent disease.

Child Behavior Disorders↗
PubMed1995

Encephalopathy with parkinsonian features in children following bone marrow transplantations and high-dose amphotericin B.

Encephalopathy, leukoencephalopathy, and secondary parkinsonism occurred in 3 children with refractory leukemia undergoing allogenic bone marrow transplantation (BMT) who were treated with high-dose amphotericin B for pulmonary aspergillosis or sinus aspergillosis that did not involve the nervous system. Treatment included high-dose cytosine arabinoside, cyclophosphamide, and total body irradiation prior to the BMT. The children developed a progressively worsening encephalopathy and parkinsonian features, characterized by resting tremor, cogwheel rigidity, and masklike facies. Neuroimaging studies showed cerebellar, cerebral, and basal ganglia atrophy, as well as frontal and temporal lobe white matter involvement. Two of the 3 patients recovered, although 1 has residual intellectual impairment. The third succumbed to non-central nervous system Epstein-Barr virus-lymphoproliferative disease and had autopsy-confirmed leukoenephalopathy.

Adolescent↗
PubMed1995

Brain tumors in children.

Brain tumors are the most common form of solid neoplasm of childhood. Progress in the treatment of childhood brain tumors has been frustratingly slow, especially in comparison with other pediatric malignancies. The biology of primary pediatric brain tumors of childhood is just being unraveled. Chemotherapy is a major component of the treatment of many forms of childhood primary central nervous system tumors and is being used in attempts to improve survival and to delay or decrease the amount of radiotherapy needed. Despite the use of more aggressive radiotherapy approaches and intensified chemotherapy approaches, outcome remains dismal for brain stem gliomas and high-grade cortical gliomas. Many unsettled issues exist concerning the treatment of childhood low-grade gliomas.

Brain Neoplasms↗
PubMed1995

A phase I and II trial of dose-intensified cyclophosphamide and GM-CSF in pediatric malignant brain tumors.

PURPOSE: Cyclophosphamide is commonly used in the treatment of children with malignant brain tumors. The purpose of this study was to develop a multicycle, high-dose intensity cyclophosphamide regimen with granulocyte-macrophage colony-stimulating factor (GM-CSF) and to assess its activity against malignant glioma and primitive neuroectodermal tumor (PNET). METHODS: Twenty-three patients with brain tumors, including 15 with malignant glioma and six with PNET, were enrolled. Cyclophosphamide (1.8-2.25 g/m2/day for 2 days i.v.; total dose 3.6-4.5 g/m2) was administered and was followed by recombinant human GM-CSF (5 micrograms/kg/day s.c.) on days 3-11 or until the absolute granulocyte count reached 1.5 x 10(9)/L. RESULTS: With a total of 83 cycles administered, the mean dose intensity of cyclophosphamide ranged from 1.5 g/m2/week through cycle 2 (22 patients) to 0.8 g/m2/week through cycle 8 (two patients). No activity was seen against malignant glioma, and five of six patients with PNET had partial responses. The mean duration of a neutrophil count of < 0.5 x 10(9)/L was only 8 days; the platelet recovery was substantially longer. Fever during neutropenia occurred in 54 of 83 cycles. One patient died from transfusion-related graft-versus-host disease. CONCLUSIONS: A cyclophosphamide regimen equal to twice the dose intensity of that used in conventional therapy was administered. The regimen was active against PNET but inactive against malignant glioma.

Adolescent↗
PubMed1995

'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↗
PubMed1995

Long-term outcome of hypothalamic/chiasmatic astrocytomas in children treated with conservative surgery.

The feasibility of radical surgery for astrocytomas of the optic chiasm/hypothalamus has been reported by several groups. Such surgery carries significant risks, however, including permanent damage to the pituitary gland, optic apparatus, hypothalamic structures, and carotid arteries. The benefits of radical surgery, both in terms of efficacy and toxicity, should, therefore, be evaluated against standard therapy, as is usually done for new chemotherapeutic protocols. To this end, a retrospective review was performed of 33 patients treated at Children's Hospital of Philadelphia between 1976 and 1991 who met criteria that would have made them eligible for radical surgery in many centers today, but were treated with either no surgery or conservative surgery (< 50% resection) or biopsy followed by adjuvant therapy with local radiation therapy (29 patients) and/or chemotherapy with actinomycin-D and vincristine (18 patients). The review encompassed all children with a globular enhancing mass of at least 2 cm in the hypothalamic/chiasmatic region, no evidence of optic nerve involvement or involvement of the optic radiations by computerized tomography or magnetic resonance imaging, and follow up of at least 3 years. All but one patient had tissue confirmation of a low-grade or pilocytic astrocytoma. Thirteen of the patients were 2 years of age or younger at diagnosis. Five individuals died: three of tumor progression, one of acute shunt malfunction, and one of intercurrent infection. The remaining 28 were alive at last follow up, a mean of 10.9 years from diagnosis. Twenty-three surviving patients have functional vision in at least one eye, 12 require no endocrine replacement, and 16 are in or have completed schooling with regular academic requirements. If radical surgery is to become standard care for children with low-grade astrocytomas of the hypothalamic/chiasmatic region, long-term survival and functional outcome will have to equal or surpass those of historical controls who were treated conservatively.

Adolescent↗
PubMed1994

Outcome of children with brain stem gliomas after treatment with 7800 cGy of hyperfractionated radiotherapy. A Childrens Cancer Group Phase I/II Trial.

BACKGROUND: Brain stem gliomas remain the childhood brain tumors most resistant to treatment. Treatments with hyperfractionated radiotherapy at doses as high as 7560 cGy have been fairly well tolerated. This study was undertaken to determine the toxicity and possible efficacy of hyperfractionated radiotherapy in children with brain stem gliomas using 100 cGy of radiation twice daily, to a total dose of 7800 cGy. METHODS: Sixty-six children (mean age at diagnosis, 7.5 years) with diffuse intrinsic brain stem gliomas were treated. Patients were evaluated for potential toxicity of treatment, progression-free survival, survival, and response to treatment. RESULTS: Objective response to treatment was documented in 20 of 58 (34%) evaluable patients, with 8 (14%) patients having a greater than 50% reduction in tumor size. Overall survival was 35% plus or minus 6% at 1 year and 11% plus or minus 6% at 3 years. Intralesional cystic/necrotic radiographic changes developed in nine patients 6 weeks after radiation, and three of these patients subsequently improved without antitumor intervention. Six of 14 autopsied patients had evidence of probable radiation-induced intralesional necrotic damage, and in 1, necrosis may have played a role in death. Thirty-three of 66 patients were treated with steroids for prolonged periods. CONCLUSIONS: The results of this treatment regimen demonstrate that hyperfractionated radiotherapy, as delivered in this study to a total dose of 7800 cGy, is relatively well tolerated, but may result in prolonged steroid-use dependency and possible radiation-associated damage. Objective responses to treatment were seen in 34% of patients, but these results were not better than those seen at lower doses of hyperfractionated radiotherapy. There is no evidence that radiation to 7800 cGy results in improved survival for patients with diffuse intrinsic brain stem gliomas.

Adolescent↗
PubMed1994

Pre-irradiation chemotherapy in children with high-grade astrocytoma: tumor response to two cycles of the '8-drugs-in-1-day' regimen. A Childrens Cancer Group study, CCG-945.

PURPOSE: This study was undertaken to evaluate the radiographic response to two cycles of chemotherapy prior to irradiation in newly diagnosed children with high-grade astrocytomas. PATIENTS AND METHODS: One hundred and thirty children less than 21 years of age with newly-diagnosed high-grade astrocytoma were treated with the 'eight-drugs-in-one-day' chemotherapy regimen as part of a phase III multi-institutional Childrens Cancer Group (CCG) trial. Computerized Tomographic (CT) or Magnetic Resonance Image (MRI) scans, obtained after two cycles of chemotherapy had been administered, were compared with post-operative scans to determine treatment response. Scans were evaluated by institutional radiologists, and were reviewed centrally by a single neuroradiologist. RESULTS: Of 79 patients with evaluable post-operative residual tumor on CT or MRI scans, 26 (33%) were determined on institutional evaluation to have had an objective response. However, central review of scans documented responses on only 14/79 (18%). A significantly higher response rate on central review was observed for those children 36 months of age or less at study entry than for older children (33% v 11%; p < 0.001). However, a higher disease progression rate was also observed for those children 36 months of age or less than for older children (21% v 2.6%; p < 0.001). CONCLUSION: In this study, the largest yet reported in newly-diagnosed children with high-grade astrocytomas, the chemotherapy regimen has activity in younger children. The differences in response rates reported by institutional and central review highlight the difficulties inherent in assessing response to brain tumor therapy. However, the study does demonstrate the consistent ability of radiologists to identify disease progression within the institutional and central reviews.

Adolescent↗
PubMed1994

Diagnosis, treatment, and outcome of primary central nervous system tumors of childhood.

Significant work has been published over the past year on the management of childhood primary central nervous system tumors. Chemotherapy is taking on an increased role in the treatment of children with medulloblastoma and low-grade gliomas and infants with malignant tumors. Although survival remains poor for children with brain stem gliomas, even after treatment with high-dose radiotherapy regimens, subsets of patients have been identified who have a more favorable prognosis. Neurocognitive dysfunction remains a significant treatment outcome in children surviving brain tumors.

Brain Neoplasms↗
PubMed1994

Diagnosis and treatment of pediatric brain tumors.

Brain tumors are the most common form of solid neoplasm of childhood. Progress is clearly being made in the understanding and management of childhood brain tumors. There are possible biologic differences between histologically similar childhood and adult brain tumors. Chemotherapy is a major component of the treatment of many forms of childhood primary central nervous system tumors and is being used in attempts to improve survival and to delay or decrease the amount of radiotherapy needed. Despite the use of more aggressive radiotherapy approaches or intensified chemotherapy approaches, the outcome remains dismal for some forms of brain cancer. Many unsettled issues exist concerning the management of childhood low-grade gliomas.

Adolescent↗
PubMed1994

Staging and surveillance of children with central nervous system neoplasms: recommendations of the Neurology and Tumor Imaging Committees of the Children's Cancer Group.

Standardization of the baseline and surveillance evaluation of children with central nervous system (CNS) tumors could contribute to understanding tumor behavior, establishing prognoses, directing treatment, and interpreting multi-institutional cooperative study data. A tumor categorization schedule, based on recognized patterns of CNS tumor behavior involving 'aggressiveness' as assessed by the likelihood for neuraxis dissemination, relative time to progression and pattern of disease recurrence is presented. Included are the most common histologic subtypes of pediatric CNS neoplasms. No attempt has been made to include all histologic subtypes of pediatric CNS neoplasms. Using this categorization as a framework, recommendations are suggested for baseline evaluation at diagnosis and in surveillance.

Adolescent↗
PubMed1994

Seizure control following tumor surgery for childhood cortical low-grade gliomas.

Detailed preoperative electroencephalographic (EEG) studies are now recommended for children with seizures and cortical tumors to define seizure foci prior to surgery. To develop a historical perspective for better evaluation of results from series reporting tumor removal combined with resection of seizure foci, the authors reviewed seizure outcome in 60 children with seizures and low-grade neoplasms treated consecutively since 1981 by surgical resection without concomitant EEG monitoring or electrocortical mapping. Forty-seven of the 60 tumors were totally or near-totally resected; 45 patients were seizure-free and two were significantly improved 1 year following surgery. Of the 50 children in this series with more than five seizures prior to surgery, 36 were seizure-free, two were significantly improved, and 12 were not improved. Factors associated with poor seizure control included a parietal tumor location, a partial tumor resection, and a history of seizures for more than 1 year prior to surgery. The children at highest risk for poor seizure control at 2 years had experienced seizures for more than 1 year prior to surgery and had undergone partial resection of their parietal low-grade glial tumors or gangliogliomas. In contradistinction, the best seizure control was seen in patients with totally resected low-grade gliomas or gangliogliomas who had experienced seizures for less than 1 year (concordance rates for being seizure-free ranged from 78% to 86%). Long-term seizure control remained excellent. These results suggest that seizure control can be obtained 2 years following tumor surgery in the majority of children with presumed tumors after extensive tumor resection without concomitant EEG monitoring or electrocortical mapping.

Adolescent↗
PubMed1994

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↗
PubMed1994

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↗