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G J D'Angio

Publications and source records attributed to G J D'Angio.

At least 19 recordsLinked to original sources
PubMed1996

Updated results of a pilot study of low dose craniospinal irradiation plus chemotherapy for children under five with cerebellar primitive neuroectodermal tumors (medulloblastoma).

PURPOSE: Children under 5 years old with medulloblastoma (MB) have a poor prognosis. They are more susceptible to the deleterious effects of craniospinal irradiation (CSART) and have a higher relapse rate when treated with low-dose CSART alone. We, thus, embarked on a prospective trial testing the usefulness of very low dose CSART and adjuvant chemotherapy. This is an update of a previous report on these patients. METHODS AND MATERIALS: Between January 1988 and March 1990, 10 patients with medulloblastoma were treated using 18 Gy radiation therapy (RT) to the craniospinal axis, a posterior fossa (PF) boost to 50.4-55.8 Gy and chemotherapy consisting of vincristine (VCR) weekly during RT. This was followed by VCR, cis-diamminedichloroplatinum (CDDP), and lomustine (CCNU) for eight, 6-week cycles. Patients between 18 and 60 months of age without evidence of tumor dissemination were eligible for study. Follow-up was available until September 1994 with a median follow-up for living patients of 6.3 years from diagnosis. RESULTS: Actuarial survival at over 6 years is 70 +/- 20%. Three of the 10 patients relapsed and died. In one patient, the relapse developed in the spine and brain outside the posterior fossa, in the second, concurrently in the posterior fossa, brain and spine, and the third, only in the spine. One surviving child developed a brain stem infarct 4.8 years after diagnosis and has since almost fully recovered. A mean intelligence quotient (IQ) score of 103 in six patients surviving at least 1 year is unchanged from the baseline group score of 107. Five children tested at baseline and 2 years following treatment had IQ scores of 101 and 102, respectively. Six children tested at baseline and at 3 years had IQ scores of 106 and 96, respectively. Excluding the child tested shortly after his brain stem infarct, baseline and 3 year IQ scores were 103 and 97, respectively. Five of the seven long-term survivors grew at rates significantly below their expected velocities during the follow-up period, while the others grew normally. Three patients have received growth hormone, and none have required thyroid replacement. CONCLUSIONS: These data suggest that medulloblastoma patients can be cured with chemotherapy and reduced doses of craniospinal irradiation. The low doses of CSART given by us in conjunction with cis-platin-based chemotherapy produce minimal neurocognitive damage. Growth velocities in very young children so treated are, however, dramatically reduced. Better means of improving the therapeutic ratio are still needed.

Age Factors↗
PubMed1996

Treatment of children with stage IV favorable histology Wilms tumor: a report from the National Wilms Tumor Study Group.

The purpose of this study was to evaluate the effect of the sequential addition of doxorubicin and cyclophosphamide to the combination of vincristine and actinomycin D on the relapse-free survival of children with stage IV/favorable histology Wilms tumor. We reviewed the clinical courses of all randomized patients from National Wilms Tumor Study (NWTS)-2 and 3 with stage IV/favorable histology (FH) Wilms tumor. We determined the four-year relapse-free survival percentage for patients treated on NWTS-2 with the combination of vincristine (VCR) and actinomycin D (AMD) with (regimen D) or without (regimen C) doxorubicin (DOX), and for patients treated on NWTS-3 with the combination of VCR+AMD+DOX with (regimen J) or without (regimen DD-RT) cyclophosphamide (CTX). All children received whole lung radiation therapy. The four-year relapse-free survival percentage for children with stage IV/FH Wilms tumor treated with regimen C was 53.3%, compared to 57.7% for those treated with regimen D (P = 0.63). The four-year relapse-free survival percentage for children with stage IV/FH Wilms tumor treated with regimen DD-RT was 79.0%, compared to 80.9% for those treated on regimen J (P = 0.79). The four-year relapse-free survival for children with lung metastases only treated with regimen D on NWTS-2 was significantly lower than that of children treated with the related regimen DD-RT on NWTS-3 (P = 0.03). We conclude that the addition of doxorubicin to the combination of vincristine and actinomycin D and pulmonary irradiation did not clearly improve the four-year relapse-free survival percentage of children with stage IV/FH Wilms tumor, although the benefit may have been masked by the greater frequency of death due to toxicity in NWTS-2. There was no evidence that the addition of CTX to the three-drug treatment regimen improved the four-year relapse-free survival percentage of children with stage IV/FH Wilms tumor. The data with only two drugs derived from NWTS-2 suggest that there is a population of children with stage IV/FH Wilms tumor who can be successfully treated without an anthracycline. The goal of future research will be to identify this subgroup at the time of initial diagnosis.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Hepatomegaly in neuroblastoma stage 4s: criteria for treatment of the vulnerable neonate.

Infants with neuroblastoma (NBL) frequently present as stage 4s and overall, such patients have a good prognosis. However, not all survive, and neonates with hepatomegaly are particularly at risk. We therefore reviewed our 4s experience, the objective being to identify lethal patterns of disease progression. The specific aims of this work were (1) to develop a semiquantitative scoring system based on the severity of signs and symptoms that alone or in combination presaged a fatal outcome, and (2) to determine if early intervention could reverse life-threatening disease. Thirty-five patients were seen over a period of 50 years. The signs and symptoms of organ distress caused by hepatomegaly occurred in the lungs, kidneys, gastrointestinal tract (GI), the inferior vena cava (IVC), and the liver. A scoring scale reflecting organ compromise was developed, the scores ranging from 0 (0 compromise) to 10 (all 5 systems showing evidence of impairment). Scores were derived for 32 of 35 patients; 13 were 4 weeks old or under (neonates) when first seen, and 19 were aged 1-12 months (infants). Neonates were more likely than infants to develop increasing symptomatology (50% versus 25%) and were more likely to die when a score of 2 or more developed. None of the 6 neonates who did so survived despite treatment, compared with three of four infants. Early intervention is recommended: (1) for 4s neonates who develop a score of 1 and (2) for older infants with a score > or = 2.

Hepatomegaly↗
PubMed1996

Successful management of low-stage neuroblastoma without adjuvant therapies: a comparison of two decades, 1972 through 1981 and 1982 through 1992, in a single institution.

PURPOSE: A review was undertaken of 119 children seen at the Children's Hospital of Philadelphia between 1972 and 1992 to assess the impact of adjuvant therapies for patients with low-stage neuroblastoma (NBL). PATIENTS AND METHODS: Twenty-one of 119 International Neuroblastoma Staging System (INSS) stage 1, 2a, 2b, and 4s patients seen received initial adjuvant treatment postoperatively and 98 did not. The patients were further subdivided according to decade, age, presence of residual disease, and lymph node status. Outcomes were then compared. RESULTS: The event-free survival (EFS) rate for those who received adjuvant therapy was 52% versus 86% for those who did not. The 5-year survival rate was 68% and 94%, respectively. Age (< or > 12 months), extent of residual disease, and status of lymph nodes did not influence survival. Over the two decades, the reasons for selecting treatment changed as new and powerful additional prognostic factors were identified; 71% of patients received no adjuvant treatment in the first decade, compared with 90% in the second. EFS rates for untreated patients by decade were 79% and 89%, and 5-year survival rates were 85% and 98%, respectively. CONCLUSION: It is possible to define most low-stage NBL as favorable-even in patients with positive lymph nodes and gross residual disease-and to omit initial adjuvant treatments successfully.

Child↗
PubMed1995

Fractionated total-body irradiation preceding high-dose cytosine arabinoside as a preparative regimen for bone marrow transplantation in children with acute leukemia.

Twenty children with acute leukemia between 3 and 19 years of age underwent allogeneic bone marrow transplantation from HLA-matched sibling donors after conditioning with total-body irradiation (1,200 cGy in six fractions of 200 cGy twice daily for 3 days) and high dose cytosine arabinoside (3 g/m2 given every 12 hours for 12 doses). Three patients died with acute toxicity. Six patients developed grade II acute graft versus host disease. With a median follow-up of 68 months (range 26-96 months), thirteen children (65%) are alive and in remission with Karnofsky scores of 90-100%. A patient with AML in resistant relapse went into remission but relapsed and died 5 months post-transplantation. Three other patients relapsed, 8, 12, and 16 months post BMT. Our results suggest that this conditioning regimen is associated with high but manageable acute toxicity and may be highly effective in controlling leukemia resistant to conventional chemotherapy.

Adolescent↗
PubMed1995

Langerhans cell histiocytosis.

The first major stride toward understanding LCH was taken when ultrastructural studies identified the proliferating cells as part of the Langerhans (dendritic) cell system. Another step forward was the definition of the morphologic, immunohistochemical, and clinical criteria needed for the diagnosis of LCH. Meanwhile, modern imaging studies have disclosed lesions that were not previously visible, especially those in the brain and the pituitary gland. These advantages have had a major impact on clinical management by making it possible to compare data from different institutions and to centralize coherent clinical and therapeutic data. Moreover, the agreement concerning diagnostic criteria provides a solid foundation for current clinical trials and for laboratory research regarding the possible roles of the immune system, clonality, and cytokines in the etiology of LCH.

Bone Marrow↗
PubMed1995

Langerhans cell histiocytosis: presentation and evolution of radiologic findings with clinical correlation.

Radiologic images and medical records of 42 children with Langerhans cell histiocytosis (LCH) (histiocytosis X) were reviewed to evaluate the presentation of the disease and the evolution of the radiologic findings. There were 26 male and 16 female patients aged 3 months to 18 years. Twenty-two patients presented with localized disease; 20 presented with multifocal disease. Four patients developed diabetes insipidus. Two patients had organ dysfunction. The radiologic findings were largely due to destructive bone lesions; 83% of the patients had at least one affected bone. Isolated soft-tissue masses, interstitial lung disease, and central nervous system abnormalities were also seen. Of patients in whom results of appropriate follow-up were available, 91% showed improvement in their lesions, 43% developed new lesions, and 92% had good clinical outcomes. LCH is usually a self-limited disease with a varied clinical and radiologic presentation. The prognosis is generally poor in children with organ dysfunction. In the absence of organ dysfunction, children with either localized or multifocal LCH have an excellent prognosis.

Adolescent↗
PubMed1995

Second malignant neoplasms following treatment for Wilm's tumor: a report from the National Wilms' Tumor Study Group.

PURPOSE: The study was undertaken to determine the incidence of second malignant neoplasms (SMNs) in patients treated for Wilms' tumor and demonstrate how the incidence varied with the initial treatment protocol. PATIENTS AND METHODS: Between October 1969 and December 1991, 5,278 assessable patients were enrolled onto the National Wilms' Tumor Study (NWTS) and by the end of 1993 had contributed 39,461 person-years to a follow-up study. Expected numbers of second cancers were calculated by applying national incidence rates to person-years classified by age, sex, and calendar year. RESULTS: Forty-three SMNs were observed, whereas only 5.1 were expected (standardized incidence ratio [SIR], 8.4; 95% confidence interval [CI], 6.1 to 11.4). Fifteen years after the Wilms' tumor diagnosis, the cumulative incidence of a SMN was 1.6% and increasing steadily. Abdominal irradiation received as part of the initial therapy increased the risk of a SMN (SIR, 1.43/10 Gy; 95% CI, 1.13 to 1.81). Doxorubicin potentiated the radiation effect. Among 234 patients who received doxorubicin and greater than 35 Gy of abdominal radiation, eight SMNs were observed, whereas only 0.22 were expected (SIR, 36; 95% CI, 16 to 72). Treatment for relapse further increased the SMN risk by a factor of 4 to 5. CONCLUSION: These results demonstrate the importance of current efforts to limit the use of intensive chemotherapy and radiation therapy, which are now applied only to patients with the most aggressive disease. Continuing close surveillance of the great majority of Wilms' tumor patients who become long-term survivors is essential for early diagnosis of SMNs and other late sequelae of therapy.

Adolescent↗
PubMed1995

Relationship between dose schedule and charges for treatment on National Wilms' Tumor Study-4. A report from the National Wilms' Tumor Study Group.

National Wilms' Tumor Study-4 was designed to evaluate the efficacy, toxicity, and cost of administration of different regimens for the treatment of Wilms' tumor. The charges for treatment with dactinomycin and doxorubicin administered by two different schedules were calculated using current charges in Buffalo, N.Y. An annual savings of approximately $779,259 could be achieved by the use of the short, pulse-intensive (i.e., single-dose) treatment regimens for all children with Wilms' tumor of stages I-IV/favorable histology. The pulse-intensive administration schedule for the treatment of children with Wilms' tumor permits administration of chemotherapy at a substantially lower total treatment cost.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Imaging patients with Wilms tumor.

Imaging plays a significant role in the management of Wilms tumor. Appropriate imaging continually must undergo refinement related to improvements in therapy and imaging modalities. We must recognize the need to demonstrate effectiveness in all phases of patient management and address the contentious issue of maximizing yield and minimizing cost.

Follow-Up Studies↗
PubMed1995

Late effects of treatment for Wilms tumor.

Successfully treated patients may be at risk for a variety of organ-specific complications, depending upon the treatment administered. Former patients should be carefully screened for such complications to facilitate early intervention. Additional research is necessary to define more accurately the frequency of these complications, to identify techniques for screening of childhood cancer survivors, and to develop therapeutic regimens of equal efficacy but lower potential for long-term morbidity.

Antineoplastic Agents↗
PubMed1994

The relationship between microsubstaging variables, age at diagnosis, and tumor weight of children with stage I/favorable histology Wilms' tumor. A report from the National Wilms' Tumor study.

BACKGROUND: The purpose of this study was to determine the relationship between histologic microsubstaging variables, patient age, and tumor specimen weight in patients with Stage I/favorable histology Wilms' tumors. METHODS: The authors reviewed all randomized patients from the Fourth National Wilms' Tumor Study, who had Stage I/favorable histology Wilms' tumors evaluated for one or more of the microsubstaging variables: (1) the presence of an inflammatory pseudocapsule, (2) renal sinus invasion, (3) tumor in the intrarenal vessels, and (4) tumor capsule invasion. The authors determined the correlation between microsubstaging variables and age at diagnosis or tumor specimen weight. RESULTS: Patients who were younger than 2 years of age at diagnosis were significantly more likely to have all negative microsubstaging variables. Patients who had tumors weighing less than 550 g were more likely to have all negative microsubstaging variables. However, neither renal sinus invasion nor tumor in the intrarenal vessels was more frequent in tumors weighing more than 550 g. CONCLUSIONS: An age at diagnosis of younger than 2 years and a tumor specimen weight of less than 550 g are highly correlated with the absence of adverse microsubstaging variables. The clinical variables of age at diagnosis and tumor specimen weight, compared with the assessment of microsubstaging variables, have the practical advantage of being more objectively determined and not requiring a central pathologic review for confirmation.

Adolescent↗
PubMed1994

Bone marrow transplantation for high risk neuroblastoma at the Children's Hospital of Philadelphia: an update.

A bone marrow transplant (BMT) protocol including surgical excision, local and total body irradiation, and high dose multiagent chemotherapy based on melphalan and bone marrow rescue has been in effect for children with high risk or relapsed neuroblastoma at the Children's Hospital of Philadelphia since 1979. The initial results were reported in 1984 [August et al.: J Clin Oncol 2:609-616, 1984]. This report updates the initial results and those that followed changes in the original conditioning regimen. Forty-two patients were treated between may 1979 and November 1987, and included 27 whose disease had relapsed and 15 who received BMT as part of primary treatment. Allogeneic marrow was given to 12 and autologous marrow to 30; in 7 of these 30, the marrow was purged with monoclonal antibodies and magnetic beads. The 4-year actuarial survival rate is 29%. Ten patients died of early treatment-related complications, 18 died of progressive disease, and 2 died of late complications (1 AIDS and 1 acute myelogenous leukemia). Censoring the two late complications the actuarial 4-year relapse-free survival rate becomes 32%. The longest interval after BMT to relapse was 20 months. There was no significant difference in the survival for patients transplanted following relapse or in first remission. The better survival for patients rescued with autologous marrow (30%) is not statistically significantly different from the result with allogeneic marrow (17%).

Adult↗
PubMed1994

The effect of chemotherapy dose intensity on the hematological toxicity of the treatment for Wilms' tumor. A report from the National Wilms' Tumor Study.

PURPOSE: To determine the relationship between hematological toxicity and actual dose intensity of treatment of patients randomized to therapy during the first 28 months of the National Wilms' Tumor Study-4. METHODS: The mean minimum white blood cell count (WBC), platelet count (PLT), hemoglobin, and absolute neutrophil count (ANC) during the first two courses of chemotherapy and the mean number of days of hospitalization for toxicity were compared between standard and "pulse-intensive" regimens for all randomized patients entered on National Wilms' Tumor Study-4 between August 6, 1986 and December 31, 1988. The mean dose intensity of dactinomycin, vincristine, and doxorubicin received during the first two courses and the entire course of treatment was compared between standard and "pulse-intensive" regimens. RESULTS: The mean minimum WBC, PLT, and ANC were all significantly lower during the first two courses of chemotherapy for stage I patients treated with the standard regimen, compared with the "pulse-intensive" regimen. The mean dose intensity of dactinomycin and doxorubicin was significantly higher for patients treated with the "pulse-intensive" regimens, compared with the appropriate standard regimen. CONCLUSIONS: The "pulse-intensive" administration schedule for the treatment of children with Wilms' tumor permits administration of chemotherapy at a higher dose intensity without an increase in hematological toxicity.

Adolescent↗