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R Sposto

Publications and source records attributed to R Sposto.

45 records · Page 3Linked to original sources

Quality of life in children with primitive neuroectodermal tumors (medulloblastoma) of the posterior fossa.

We reviewed our experience in 43 consecutive patients with primitive neuroectodermal tumors (medulloblastoma), PNET (MB), treated between 1975 and 1984, to characterize their quality of life and identify factors which impacted on long-term function. Twenty-four of forty-three (56%) of children are alive and free of disease, a median of 4.5 years after diagnosis. The quality of life was analyzed for the 24 long-term survivors. 79% (19 of 24) were functioning well in everyday activities. The median full-scale intelligence quotient (FSIQ), obtained a median of 3.5 years after diagnosis for those tested (n = 17) was 97, with all but 3 (12%) of the patients functioning in the normal range. Specific learning, memory and fine-motor disabilities were found in over one half of patients. Factors associated with poorer performance and lower FSIQ included preoperative obtundation, the need for a permanent shunt, younger age at diagnosis, and a complicated postoperative course. It is concluded that (1) the majority of long-term survivors have 'normal' intellectual function, but may have specific intellectual and academic disabilities, and (2) preoperative and postoperative factors strongly impact on the quality of life of survivors.

Adolescent↗

Brain-stem tumors in childhood: a prospective randomized trial of irradiation with and without adjuvant CCNU, VCR, and prednisone. A report of the Childrens Cancer Study Group.

Seventy-four children with a brain-stem tumor diagnosed between 1977 and 1980 were entered into a prospective study in which exploration and assessment for resection were optional, radiation treatment using standard methods was required, and randomization occurred with regard to the use of adjuvant chemotherapy (1-(2-chloroethyl)-1-nitrosourea, vincristine, and prednisone) or no further treatment. The overall 5-year survival rate was 20% and was not improved by the adjuvant chemotherapy program. An increased risk of infection was associated with the adjuvant therapy.

Adolescent↗

Determining the duration of comparative clinical trials while allowing for cure.

Rubinstein et al. provide a technique for estimating the required length of accrual in a two treatment group randomized survival trial. An important parameter in this approach is the expected number of events as estimated by assuming exponential failure. When the underlying distribution of failure times displays a distinct plateau, as in many children's cancers (i.e. there is a "cure"), the assumption of exponential failure could be misleading. In this situation we propose the use of the general formulation in [1], but with the expected number of failures based on failure models with hazard functions which may decrease to zero. We suggest two such models and show that they provide a good fit in an example from Childrens Cancer Study Group (CCSG) trials, and that the determination of required trial duration depends strongly upon which model is assumed.

Child↗

The treatment of localized non-Hodgkin's lymphoma in children: a report from the Children's Cancer Study Group.

Investigators of the Children's Cancer Study Group entered 73 children with previously untreated localized non-Hodgkin's lymphoma on a prospective randomized trial of systemic treatment with either a four-drug program (cyclophosphamide, vincristine, methotrexate, prednisone [COMP]) or a 10-drug (LSA2-L2 modified) program of 18 months duration. All patients received central nervous system prophylaxis with intrathecal methotrexate and most received local or regional radiation treatment. The three-year relapse-free survival rate for all patients (N = 73) was 84%; for COMP (N = 42) was 85%, and for LSA2-L2 (N = 31) was 84%. Of the 12 patients who suffered adverse events eight relapsed and four died of toxicity. Histopathology was reviewed centrally. Of 32 patients with nonlymphoblastic disease treated with COMP only one relapsed. Of 26 patients treated with LSA2-L2, four relapsed. Patients with localized lymphoblastic disease were uncommon. None of three patients treated with LSA2-L2 relapsed compared with three of nine treated with COMP. COMP is an excellent treatment for patients with localized disease of nonlymphoblastic type, but the relative value of the two regimens for patients with localized lymphoblastic disease is uncertain.

Adolescent↗

Prognostic importance of cellular differentiation in medulloblastoma of childhood.

Medulloblastoma is the most common intracranial primitive neuroectodermal malignancy of childhood. Certain parameters are predictive of survival in children with medulloblastoma; however, tumor histology is of unclear prognostic value. A classification system, proposed by Rorke for all central nervous system (CNS) neoplasms composed of primitive neuroepithelial cells, was utilized in a review of 38 consecutive patients with newly diagnosed medulloblastoma. The classification is based on the concept that medulloblastoma is not unique to the cerebellum but is similar to tumors that may arise elsewhere in the CNS consequent to neoplastic transformation of primitive neuroepithelial cells. Cells forming the tumors may remain in the undifferentiated state or they may exhibit differentiation along glial, and/or ependymal, and/or neuronal lines. For purposes of simplification, the cases were divided into two major groups: those primitive neuroectodermal tumors (PNET's) which showed no evidence of cellular differentiation (PNET-U) and those that were differentiated (PNET-D). There were 20 cases in the PNET-U group and 18 in the PNET-D group. The 4-year survival rate was 70% for PNET-U, compared to 32% for PNET-D (p = 0.004). Only one of 10 children with PNET-D with differentiation along more than one cell line survived. Other factors, including age at diagnosis, tumor metastasis (TM) stage, and extent of surgical resection, were analyzed and were of prognostic importance; but histological features remained statistically significant within each subgroup.

Adolescent↗

Monitoring clinical research. A report from the Childrens Cancer Study Group.

This report describes an evaluative approach in assessing study quality in clinical trials. The size of the data set required is defined using decision analysis methods. Assuming entry of eligible patients, the minimum data set required in determining study quality includes: the treatment agent, the protocol stipulated treatment time, and the actual time of administration. While toxicity, complication and response data are primary for the resolution of the scientific issues, they are secondary for study performance questions. Separation of study performance and scientific questions simplifies the design and execution of complex, multimodal, multidisciplinary clinical trials. Application of separate criteria for study performance and scientific questions enhances understanding of protocol requirements by data managers, physicians, and nurses. Once study performance issues are resolved, the scientific issues addressed by the protocol can be considered in detail. The usual practice of focusing on science and study performance simultaneously precludes efficient consideration of either data set. The distinction between analyses of study performance and of scientific questions is illustrated using data from Childrens Cancer Study Group protocol CCG-551. This study is a controlled trial of therapies for non-Hodgkin's lymphoma. The protocol provides an example of modern diagnostic and therapeutic management complexities.

Antineoplastic Combined Chemotherapy Protocols↗

Suicide potential and behavior in children ages 4 to 12.

From a population of 662 children 12 years of age and under, seen at the UCLA Neuropsychiatric Institute, during the years 1970 to 1974, 34 severely depressed children were identified who were also self-abusive and/or suicidal. Case study revealed fragmented, pathological homes, where the children's affect disorders and behaviors were symptomatic of acute family breakdown, marital disharmony, and observed and experienced violence, both verbal and physical. Follow-up on all available children, at least three years posttreatment, revealed that no child had committed suicide. Treatment evaluation by the parents was highly positive, with the great majority of children showing fair to good recovery and adjustment.

Behavior Therapy↗

A novel snake venom disintegrin that inhibits human ovarian cancer dissemination and angiogenesis in an orthotopic nude mouse model.

OVCAR-5 is a human epithelial carcinoma cell line of the ovary, established from the ascitic fluid of a patient with progressive ovarian adenocarcinoma without prior cytotoxic treatment. The unique growth pattern of ovarian carcinoma makes it an ideal model for examining the anticancer activity of contortrostatin (CN), a homodimeric disintegrin from southern copperhead venom. FACS analysis revealed that OVCAR-5 is integrin alphavbeta3 negative, but alphavbeta5 positive. CN effectively blocks the adhesion of OVCAR-5 cells to several extracellular matrix proteins and inhibits tumor cell invasion through an artificial basement membrane. In a xenograft nude mouse model with intraperitoneal introduction of OVCAR-5 cells, intraperitoneal injection of CN was used for therapy. Tumor dissemination in CN-treated versus control groups was studied by gross examination, and antiangiogenic potential was examined by factor VIII immunohistochemistry and image analysis. CN not only significantly inhibited ovarian cancer dissemination in the nude mouse model, but it also dramatically prevented the recruitment of blood vessels to tumors at secondary sites.

Agkistrodon↗