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Solid tumors account for approximately 70% of malignant neoplasms in children younger than 15 years of age. The 5-year survival of children with solid tumors increased from 27% to 70% between 1960 and 1990. The slope of the curve that describes the change in survival over this period is remarkably constant, reflecting the nature of progress made through clinical trials. In addition to providing data important for the refinement of treatment for specific tumors, clinical trials have made numerous important, global contributions for the practice of oncology. The development of uniform response criteria, for example, was necessitated by clinical trials. The identification of histologic subtypes and the recognition of prognostic variables have permitted refinements in diagnosis and staging. By exploring novel strategies for the integration of different therapeutic modalities, clinical trials have identified indications for the use of presurgical chemotherapy, preradiation chemotherapy, and second-look and delayed primary surgeries. Refinements in the utilization of chemotherapy have been made possible by the evaluation of new agents, the study of dose intensity, and the use of the 'window of opportunity' to identify active agents for tumors for which there is no effective treatment. Clinical trials have been instrumental in defining the late effects of treatment, investigating the causes of childhood cancer through epidemiologic studies, and supporting cancer biology research. The close collaboration of basic and clinical investigators offers the best opportunity for realizing the rewards of transitional research. Cancer 1994;74:2710-8.

Background: Neuroblastoma is the most common pediatric extra-cranial solid cancer. Using conventional therapies, children older than 1 year of age with advanced neuroblastoma have a poor prognosis. The development of new approaches for treating such children with neuroblastoma continues to be one of the most important goals today in pediatric oncology. Despite numerous anecdotal reports of human tumor regression during viral infections, the use of viruses to directly lyse neuroblastoma cells has never been reported as a potential therapy. New-castle disease virus (NDV) has been shown to replicate in and kill cultured human and rat neuroblastoma cells but not normal human fibroblasts. Purpose: Our purpose was to determine if this selective killing of human neuroblastoma (IMR-32) cells is maintained during the in vivo treatment of established tumors. Methods: Two experiments were performed using NDV strain 73-T. Athymic mice with subcutaneous IMR-32 human neuroblastoma xenografts (6-12 mm) were treated intralesionally with live NDV, UV-inactivated NDV, or phosphatebuffered saline (PBS). To study virus replication in situ, mice were given intratumoral or intramuscular injections of NDV. These mice were then killed at various times, and the amount of infectious virus present in tumor or muscle was determined. Results: After one injection of live NDV, 17 of 18 tumors regressed completely, whereas rapid tumor growth occurred in all 18 mice treated with PBS and in all nine mice treated with UV-inactivated NDV (P

Background. Melanocytic proliferations affecting the central nervous system (CNS) of children may be classified as meningeal melanocytosis, primary melanoma, or metastatic melanoma. Meningeal melanocytosis often is associated with giant congenital pigmented nevi preferentially involving the midline, the head and neck) representing the lethal condition neurocutaneous melanocytosis. Primary or metastatic melanomas, although extremely rare in children, can occur in the brain and its coverings and are associated with a poor prognosis. Methods. A retrospective study of five patients with nevomelanocytic proliferations of the CNS was performed. Results. There was characteristic enhancement in the magnetic resonance imaging (MRI) with gadolinium contrast, abnormal cerebral spinal fluid (CSF) cytology with neoplastic cells showing cytoplasmic prolongations, and nevomelanocytic proliferation in the meninges expressing HMB45 positivity and exhibiting ultrastructural features of melanocytes. Conclusions. Because of the rarity of these lesions, awareness of their existence is crucial for their recognition. Clinical, radiologic, and cytologic, correlation may allow an opportune diagnosis, which would allow avoidance of brain biopsy. Melanin production is not restricted to melanocytic neoplasms, and other CNS tumoral lesions occasionally may feature melanin as part of their histologic findings. Cancer 1993; 72:2277-85.

The authors presented the cases of two children with inflammatory myofibroblastic (IMF) tumor and reviewed the literature to facilitate the preoperative recognition, delineate the clinical features, and describe the natural history of this entity. The first child had IMF tumor arising from the mesentery of the small intestine. He presented with an abdominal mass associated with severe inflammatory response manifested by fever, impaired growth, thrombocytosis, and microcytic, hypochromic anemia. After surgical resection, his fever resolved and his growth rate and the laboratory abnormalities normalized. Five months after initial diagnosis, the fever, anemia, and thrombocytosis recurred along with two tumors arising from the omentum and the abdominal soft tissue. After the second surgery, he remains free of recurrent disease for 30 months. The second child presented with a lung mass that was radiologically indistinguishable from pulmonary sequestration. After surgical resection, she remains free of recurrent disease for 18 months. IMF tumor should be considered in any solid tumor that occurs in association with a chronic inflammatory response. IMF tumor should also be considered in the differential diagnosis of pulmonary sequestration. Cancer 1993; 72:2042-8.

Background. Although flow cytometry (FCM) has become a widely used technique for the measurement of DNA content in solid tumors, the correlation of ploidy analysis by FCM with cytogenetic analysis (CGA) is not well described. The sensitivities of G-banded CGA and FCM were compared to determine the accuracy of the DNA index value (DI) as a measurement of chromosome number. Methods. Tumor specimens from 56 pediatric cases were analyzed for DNA content by both FCM and CGA. Nuclei for FCM were prepared from archival tissue in 53 specimens using a modification of the Hedley technique and from fresh tissue in 3 specimens. Metaphase chromosomes for CGA were prepared from standard solid tumor harvests and Giemsa-trypsin banding procedures. Ploidy status for this study was defined as (1) diploid--DI between 0.97 and 1.03 by FCM or chromosome number [+ or -] 2 from normal by CGA (44-48); and (2) aneuploid--DI < 0.97 or > 1.03 by FCM or total chromosomes < 44 or > 48 by CGA. Results. Forty-nine of the 56 pediatric specimens were evaluable by both techniques. Concordance was observed in 34 cases (69%) between the two techniques in assigning similar ploidy status to a tumor (22 diploid and 12 aneuploid). It also was observed that among the aneuploid concordant cases, the actual DI obtained from archival material could predict total chromosome number with 95% accuracy. The 15 discordant cases showed a distinct aneuploid population by FCM, but were diploid by CGA. Conclusions. A correlation of 69% was obtained between both techniques to assign a similar pleidy status (diploid versus aneuploid) in 56 pediatric solid tumors. These results support the combined use of CGA and FCM to obtain the most complete analysis of DNA content and chromosome abnormalities in pediatric solid tumors. FCM on formalin-fixed, paraffin-embedded tissue can be used to measure total DNA content. Cancer 1993; 72:2033-41.

Background. Gestational trophoblastic neoplasms comprise the neoplastic spectrum of nonmalignant hydatidiform mole, invasive hydatidiform mole, and truly malignant choriocarcinoma. Increasing evidence indicates that epidermal growth factor (EGF) acts as an enhancer of trophoblast function to produce human chorionic gonadotropin and that EGF and its receptor may provide a growth advantage to certain carcinoma cells. The current study was undertaken to evaluate a possible link between malignant transformation of trophoblast and expression of EGF and EGF receptor. Methods. Cytologic localization and cellular levels of expression of EGF and EGF receptor in hydatidiform mole, invasive hydatidiform mole, and choriocarcinoma tissue specimens were examined by the avidin-biotin immunoperoxidase techniques with monoclonal antibodies against EGF and EGF receptor. Results. EGF in hydatidiform mole and invasive mole was localized in syncytiotrophoblasts, whereas cytologic localization of EGF receptor in hydatidiform mole and invasive mole was observed in both cytotrophoblasts and syncytiotrophoblasts. By contrast, EGF and EGF receptor in choriocarcinoma were exhibited in cytotrophoblastic and syncytiotrophoblastic elements. Most (72%) hydatidiform moles immunostained intensely for EGF and EGF receptor, whereas most (78%) choriocarcinomas immunostained slightly for EGF and EGF receptor. Invasive mole occupied the middle position in the staining intensity for EGF and EGF receptor, between hydatidiform mole and choriocarcinoma, with 50% of the cases exhibiting moderate staining. Conclusions. The simultaneous expression of EGF and EGF receptor in the neoplastic trophoblasts implies that EGF may act in an autocrine-paracrine manner in trophoblastic neoplasms. Furthermore, the results obtained suggest that cytologic expression of EGF and EGF receptor in trophoblastic neoplasms decreases in the malignant transformation of trophoblast.

Background. Synovial sarcoma is the third most common pediatric soft tissue tumor. It requires an aggressive approach to achieve a cure. However, optimal treatment modalities adapted to disease extension and histologic variants have not been determined because there is little information about prospectively treated patients. Methods. A multicenter trial for soft tissue sarcomas (Protocol CWS 81) was conducted in West Germany between 1981-1985, and 31 patients with synovial sarcoma were registered. Treatment included multiagent chemotherapy and irradiation after initial tumor excision or biopsy. The male-female ratio in this group was 1:1.6 with a median age of 14 years (range, 1-19 years). The median follow-up time after diagnosis was 101 months (range, 77-131 months). Results. The overall event-free survival (EFS) for patients with synovial sarcoma was 74.2% at 5 years. Group I-II tumors had a significantly better prognosis than those in Group lll-IV (EFS at 5 years 84.4% and 58.3%, respectively; P = 0.024). Small tumors ( < 5 cm) responded better than larger tumors [is greater than or equal to] 5 cm; EFS, 93% versus 58%; P = 0.029). Synovial sarcoma involved the extremities in 28 patients who had a better outcome compared with those with extremity rhabdomyosarcoma in this study (EFS for Group I-IV was 82% versus 24%, P = 0.001). Conclusions. The results appeared superior to previous experience using radical surgery alone and suggested that after initial, nonmutilating surgery, adjuvant chemotherapy, and irradiation contributed to the improved long-term survival.

Background. Malignant rhabdoid tumor (MRT), originally described as a rare renal sarcoma in childhood, has been known to express phenotypic diversity. In this study, unique characteristics of the MRT cells were investigated by using established cell lines. Methods. Immunocytochemical, ultrastructural, cytogenetic, and molecular (by polymerase chain reaction, PCR) analyses were done for two MRT cell lines, one of renal and one of extrarenal origin, before and after differentiation-induction with either 12-0-tetradecanoyl phorbol-13-acetate (TPA) or transretinoic acid (RA). Results. The proliferating cells in the original tumor tissues as well as in the established cell lines demonstrated neural, epithelial, and mesenchymal markers morphologically. Both cell lines had karyotypic abnormalities including chromosome 22q11.2. The cell line from the extrarenal MRT, Tm87-16, demonstrated distinct morphologic changes with neuroblastic differentiation and produced numerous neuritic processes after treatment with either TPA or RA. The cell line from the renal MRT, STM91-01, suggested schwannian differentiation but did not change morphologically after chemical induction. Both cell lines expressed c-myc, but did not express N-myc, MyoD1, tyrosine hydroxylase, or neural cell adhesion molecule (N-CAM). With PCR and immunocytochemical study, a high level of chromogranin expression was detected by the cells of TM87-16 only after TPA induced differentiation. Conclusions. MRT cells demonstrated diverse phenotype of neuro-ecto-mesenchymal differentiation. The results of this study suggest that MRT may be derived from a primitive pluripotential cell, such as neural crest or equivalent. MRT, therefore, might be categorized as one of the subsets of primitive neuroectodermal tumor. Cancer 1993; 71:2862-72.

Background. Children and adolescents with unresectable rhabdomyosarcoma fare poorly when treated with contemporary chemotherapeutic regimens. Evaluation of newly developed agents in these patients is important to improve their outcome. Based on a preclinical rhabdomyosarcoma xenograft model that accurately predicted the activity of new agents, the safety and efficacy of ifosfamide was evaluated as part of a Phase II clinical trial in previously untreated children with unresectable rhabdomyosarcoma. Methods. Twenty-two children and adolescents (median age, 9 years) with newly diagnosed unresectable rhabdomyosarcoma (Intergroup Rhabdomyosarcoma Study Group III [n = 15] or IV [n = 7]) received two courses of ifosfamide at a dose of 1.6 g/[m.sup.2] intravenously for 5 days over a 6-week period. Then the patients were evaluated for response, and additional treatment with surgery, radiation therapy, and multiagent chemotherapy (vincristine, cyclophosphamide, dactinomycin, and doxorubicin) was administered. Results. Nineteen of 22 patients (86%) had a partial response to ifosfamide given as a single agent. No complete responses to this agent alone were observed. After administration of additional chemotherapy and local control measures (radiation therapy and surgery), the estimated proportion of patients surviving progression-free at 2 years was 63% (95% confidence interval, 37-80%). Ifosfamide was tolerated well; the most frequent toxicity was nondose-limiting myelosuppression. Transient mild renal toxicity infrequently was observed, and no central nervous system toxicity occurred in this group of patients. Conclusions. Ifosfamide appears to have significant clinical activity in untreated patients with unresectable rhabdomyosarcomas. These findings provide an accurate estimate of the response rate to single-agent ifosfamide in this group of previously untreated patients and thus provide a foundation for its rational incorporation into multiagent clinical trials. In addition, the potential benefits of this type of new drug development were demonstrated. Cancer 1993; 71:2119-25.

The study aims to document data on the patterns of childhood malignant tumors diagnosed in children in a teaching hospital in south-western Nigeria. The results indicate that Burkitt's lymphoma is the most common and generally found malignant tumor among children in the region and suggest more resource allocation keeping in mind the increasing incidence of such tumors.

Hemangiomas are the most common tumors seen in infants. Despite their rapid growth early in life, often the only action required of the physician is to reassure the parents that [...]

A parent's loss The Colleen Giblin Foundation for Children's Neurological & Cancer-Related Research was formed in 1985 after Paul and Vickie Giblin experienced the painful loss of their 4-year-old daughter, [...]