Disparate Outcomes, Biologic and Therapeutic Differences in Pediatric versus Adult Patients with Ewing Sarcoma.

INTRODUCTION: Ewing sarcoma (ES) is a small blue round cell sarcoma affecting a wide age spectrum. Clinical advances predominately stem from pediatric research consortia clinical trials. In most series, adults have poorer outcomes when compared to children. The aim of this study was to perform a detailed evaluation of factors potentially accounting for this difference. METHODS: A single institution retrospective chart review was conducted on patients with ES diagnosed from 2005 to 2015, identified using a free-text search engine with the keywords "Ewing sarcoma" as well as a corresponding pathologic database. Data were analyzed based on age, pediatric (age <18) and adult (age >18 years), using a multivariate analysis model. RESULTS: Eighty-eight ES patients (34 pediatric, 54 adult) were identified with a median age of 13 (range 3-18) and 31 (range 19-70) in their respective cohorts. Five-year overall survival (OS) was higher in pediatric patients (73.5% vs. 48.1%, p = 0.0213). By stage, 5-year OS in pediatric versus adult patients was 65% versus 20% (p = 0.0530) in metastatic (n = 32) and 68.1% versus 58.8% (p = 0.278) in localized (n = 56) patients. Lung-only metastases were present in 83% of metastatic pediatric patients versus 35% of adult metastatic patients. Pediatric patients received more cycles of first-line chemotherapy (13.8 vs. 11.4, p = 0.001), independent of stage. More cycles of chemotherapy correlated with improved OS (HR: 0.864, CI: 0.773-0.967) and progression-free survival (HR: 0.897, CI: 0.808-0.996). CONCLUSIONS: Outcome differences were most notable in patients with metastatic disease, although not statistically significant. Our series found differences in presentation between pediatric and adult populations with adult patients receiving fewer cycles of chemotherapy. This may suggest that both variations in underlying disease biology and potentially differences in treatment may account for outcome disparities.

Multiple Cavitary Lung Lesions in an Adolescent: Case Report of a Rare Presentation of Nodular Lymphocyte Predominant Hodgkin Lymphoma.

A 14-year-old male patient presented with a nonproductive cough, weight loss, fatigue, and malaise. A chest radiograph showed large bilateral cavitary lung lesions in both upper and lower lobes that failed to improve with antibiotics and anti-inflammatory medications. Infectious and rheumatologic work-ups were negative. Thoracoscopic lung biopsies were diagnostic for nodular lymphocyte predominant Hodgkin lymphoma (NLPHL). The patient received combination chemotherapy and immunotherapy based on current treatment standards with an excellent clinical response. NLPHL is a rare B-cell lymphoma that typically presents as peripheral lymph nodal disease, clinically distinct from classical Hodgkin lymphoma. The prognosis of NLPHL in children is favorable, although relapse rates are high. This case details several unique features of NLPHL and describes the presentation, diagnosis, and treatment of an adolescent male with a rare pulmonary and cervical NLPHL, the first such case described in a pediatric patient.

Outcome of young children with high-grade glioma treated with irradiation-avoiding intensive chemotherapy regimens: Final report of the Head Start II and III trials.

PURPOSE: To report the final analysis of survival outcomes for children with newly diagnosed high-grade glioma (HGG) treated on the "Head Start" (HS) II and III protocols with chemotherapy and intent to avoid irradiation in children <6 years old. PATIENTS AND METHODS: Between 1997 and 2009, 32 eligible children were enrolled in HS II and III with anaplastic astrocytoma (AA, n = 19), glioblastoma multiforme (GBM, n = 11), or other HGG (n = 2). Central pathology review was completed on 78% of patients. Patients with predominantly brainstem tumors were excluded. Patients were to be treated with single induction chemotherapy regimen C, comprising four cycles of vincristine, carboplatin, and temozolomide. Following induction, patients underwent marrow-ablative chemotherapy and autologous hematopoietic cell rescue. Irradiation was used for patients with residual tumor after consolidation or >6 years old or at the time of tumor progression. RESULTS: The 5-year event-free survival (EFS) and overall survival (OS) for all HGG patients were 25 ± 8% and 36 ± 9%, respectively. The EFS at 5 years for patients with AA and GBM were 24 ± 11% and 30 ± 16%, respectively (P = 0.65). The OS at 5 years for patients with AA and GBM was 34 ± 12% and 35 ± 16%, respectively (P = 0.83). Children <36 months old experienced improved 5-year EFS and OS of 44 ± 17% and 63 ± 17%, compared with children 36-71 months old (31 ± 13% and 38 ± 14%) and children >72 months old (0% and 13 ± 12%). CONCLUSIONS: Irradiation-avoiding treatment strategies should be evaluated further in young children with HGG given similar survival rates to older children receiving standard irradiation-containing therapies.

A report of renal artery embolization for hematuria facilitating neoadjuvant chemotherapy in an unresectable malignant renal rhabdoid tumor.

Malignant rhabdoid tumor (MRT) of the kidney is a rare pediatric tumor characterized by its aggressive nature and chemoresistance. Our patient had MRT of the right kidney with tumor thrombus in the renal vein, inferior vena cava, and right atrium. He developed transfusion-resistant hematuria. This was successfully controlled with right renal artery embolization allowing completion of his neoadjuvant chemotherapy. He then underwent complete resection of the tumor and thrombus avoiding cardiopulmonary bypass.

A phase II study of amifostine in children with myelodysplastic syndrome: a report from the Children's Oncology Group study (AAML0121).

Based on its potential role in adult myelodysplastic syndrome (MDS), the Children's Oncology Group (COG) embarked on a phase II study using amifostine in pediatric MDS (WHO 2001 criteria) patients. Responses were evaluated after two cycles. Ten patients were enrolled; five were deemed ineligible, and four withdrew after the first course. Only one patient completed two courses, and was found to be in complete remission. The study was closed after being open for 2 years due to slow accrual. Studying a rare disease like MDS may pose insurmountable obstacles even in a large clinical trials group such as COG, in part because of the changing definitions of MDS and the rarity of adult type MDS in children. The role of amifostine in pediatric MDS was not known at the time of study.

Impact of clinical pathway on quality of care in sickle cell patients.

Clinical pathways are disease specific and are designed to standardize care. They are intended to serve the purpose of improving quality of care and decreasing healthcare and societal costs. A retrospective cross-sectional study was conducted comparing sickle cell patients admitted to Mercy Children's Hospital (MCH) from June 1999 to November 2001 before the implementation of the clinical care pathway (n=66), to a similar group of patients admitted from December 2001 to July 2004 after pathway (n=121) implementation. The χ2 tests were used to compare categoric variables and independent t-tests for continuous variables. The results indicate improvement in compliance postpathway with specific care elements: incentive spirometry, pulse oximetry, ordering comfort measures, right dosage of pain medications, and achieving excellent nursing compliance in documenting pain scores. There was a significant decrease in the number of blood transfusions in postpathway patients. Though limited by sample size, the results suggest that clinical pathways are good tools for standardization of care in certain care elements and help to improve quality of care in sickle cell patients.

N-myc modulates expression of p73 in neuroblastoma.

The human p73 gene is a homolog of p53, which has been localized to chromosome 1p36 in a region that is frequently deleted in neuroblastoma. Transfection of the p73 gene into neuroblastoma cells that lack detectable p73 protein has been shown to result in growth suppression and to induce neuronal differentiation. In this study, we have identified by means of restriction landmark genome scanning (RLGS) a genomic fragment that was frequently reduced in intensity in neuroblastomas. The cloned fragment contained exon 1 of p73 as well as intronic and promoter sequences. We investigated the genomic and expression status of p73 and N-myc in 34 neuroblastoma tumors and 12 neuroblastoma cell lines. Approximately a third of neuroblastomas in our series exhibited deletion of p73. Most tumors analyzed exhibited reduced expression of p73, as determined by quantitative RT-PCR, in the absence of detectable p73 gene deletion. The reduced expression of p73 correlated with overexpression of N-myc in a statistically significant manner. The N-myc gene was transfected into two neuroblastoma cell lines that lacked N-myc amplification to determine its effect on p73 RNA levels. p73 was detectable at low level by RT-PCR in untransfected SK-N-AS cells and became undetectable following N-myc transfection, whereas in SH-EP1 cells, p73 levels were substantially reduced following transfection but remained detectable. Our data suggest that the N-myc gene modulates expression of p73, allowing neuroblastoma cells to escape the growth suppressing properties of p73.

Successful management of rhabdoid tumor of the liver.

A 3-year-old male was referred because of fever, abdominal pain, and enlarged abdomen. Magnetic resonance imaging showed a very large lobulated mass involving predominantly the right lobe of liver. Tumor histology was consistent with rhabdoid tumor of the liver. The patient received 3 cycles of chemotherapy consisting of ifosfamide, carboplatin, and etoposide alternating with vincristine, adriamycin, and cyclophosphamide, at 3-week intervals. Follow-up magnetic resonance imaging revealed approximately 84% decrease in size of tumor after 2 cycles of chemotherapy. Patient underwent liver transplantation, as the tumor was unresectable. Six weeks posttransplant, the patient received 4 more cycles of chemotherapy. The patient is free of disease at evaluation 3 years posttransplant.

Immunophenotype of blood lymphocytes in neuroblastoma-associated opsoclonus-myoclonus.

OBJECTIVE: To determine whether the distribution of peripheral blood mononuclear cells (PBMCs) is altered in paraneoplastic opsoclonus-myoclonus (POM). METHODS: PBMCs from 17 children with POM, 17 children with OM but no tumor, and 17 controls were immunophenotyped using a comprehensive panel of surface markers by dual-laser flow cytometry. All groups were matched for age and gender; POM and OM patients were matched for treatment. RESULTS: In the POM patients, the CD4+ T-cell subset was smaller in both relative size (-18%, P = 0.02) and absolute size (-41%, P = 0.03) compared with controls. The CD4/CD8 ratio also was less (-29% to -44%) and was related to POM duration (P = 0.03). The absolute but not relative size of the gammadelta T-cell subset was reduced (-44%, P = 0.02). There were no significant abnormalities of CD19+ B-cells, CD3- or CD3+ NK cells, HLA-DR+ or CD25+ T-cells, or CD45RA+ or CD45RO+ T-cells. Prior tumor chemotherapy, which was associated with a higher percentage but not number of CD8+ T-cells, did not restore the CD4+ T-cell subset. When the POM and OM groups, which were not significantly different, were combined, chemotherapy decreased both the relative and absolute size of the CD19+ B-cell pool and had small effects on other lymphocyte subsets. CONCLUSIONS: POM is characterized by T-cell abnormalities of PBMCs, the most robust of which is reduction of the CD4+ T-cell subset and the CD4/CD8 ratio. Although this reduction was found previously in cerebrospinal fluid in POM patients, PBMC subsets did not otherwise reflect cerebrospinal fluid abnormalities. Longitudinal studies will be necessary to determine whether PBMC abnormalities could serve as treatment markers.