Outcomes of children with well-differentiated fetal hepatoblastoma treated with surgery only: Report from Children's Oncology Group Trial, AHEP0731.

Background: Hepatoblastoma (HB) requires surgical resection for cure, but only 20-30% of patients have resectable disease at diagnosis. Patients who undergo partial hepatectomy at diagnosis have historically received 4-6 cycles of adjuvant chemotherapy; however, those with 100% well-differentiated fetal histology (WDF) have been observed to have excellent outcomes when treated with surgery alone.

Patients And Methods: Patients on the Children's Oncology Group non randomized, multicenter phase III study, AHEP0731, were stratified based on Evan's stage, tumor histology, and serum alpha-fetoprotein level at diagnosis.

Management of Hypertrophic Cardiomyopathy: JACC State-of-the-Art Review.

Hypertrophic cardiomyopathy (HCM), a relatively common, globally distributed, and often inherited primary cardiac disease, has now transformed into a contemporary highly treatable condition with effective options that alter natural history along specific personalized adverse pathways at all ages. HCM patients with disease-related complications benefit from: matured risk stratification in which major markers reliably select patients for prophylactic defibrillators and prevention of arrhythmic sudden death; low risk to high benefit surgical myectomy (with percutaneous alcohol ablation a selective alternative) that reverses progressive heart failure caused by outflow obstruction; anticoagulation prophylaxis that prevents atrial fibrillation-related embolic stroke and ablation techniques that decrease the frequency of paroxysmal episodes; and occasionally, heart transplant for end-stage nonobstructive patients. Those innovations have substantially improved outcomes by significantly reducing morbidity and HCM-related mortality to 0.

Primary Mediastinal B Cell Lymphoma in the Positron-Emission Tomography Era Executive Summary of the American Radium Society Appropriate Use Criteria.

Purpose: Primary mediastinal B cell lymphoma (PMBCL) is a highly curable subtype of non-Hodgkin lymphoma that is diagnosed predominantly in adolescents and young adults. Consequently, long-term treatment-related morbidity is critical to consider when devising treatment strategies that include different chemoimmunotherapy strategies with or without radiation therapy. Furthermore, adaptive approaches using the end-of-chemotherapy (EOC) positron emission tomography (PET)/computed tomography (CT) scanning may help to determine which patients may benefit from additional therapies.

Irinotecan, Temozolomide, and Dinutuximab With GM-CSF in Children With Refractory or Relapsed Neuroblastoma: A Report From the Children's Oncology Group.

Purpose: The combination of irinotecan, temozolomide, dintuximab, and granulocyte-macrophage colony-stimulating factor (I/T/DIN/GM-CSF) demonstrated activity in patients with relapsed/refractory neuroblastoma in the randomized Children's Oncology Group ANBL1221 trial. To more accurately assess response rate and toxicity, an expanded cohort was nonrandomly assigned to I/T/DIN/GM-CSF.

Patients And Methods: Patients were eligible at first relapse or first designation of refractory disease.

Outcome of Children With Hypodiploid Acute Lymphoblastic Leukemia: A Retrospective Multinational Study.

Purpose: We determined the prognostic factors and utility of allogeneic hematopoietic cell transplantation among children with newly diagnosed hypodiploid acute lymphoblastic leukemia (ALL) treated in contemporary clinical trials.

Patients And Methods: This retrospective study collected data on 306 patients with hypodiploid ALL who were enrolled in the protocols of 16 cooperative study groups or institutions between 1997 and 2013. The clinical and biologic characteristics, early therapeutic responses as determined by minimal residual disease (MRD) assessment, treatment with or without MRD-stratified protocols, and allogeneic transplantation were analyzed for their impact on outcome.

Local control for vaginal botryoid rhabdomyosarcoma with pre-rectal transperineal surgical resection and autologous buccal graft vaginal replacement: A novel, minimally invasive, radiation-sparing approach.

Purpose: Localized vaginal rhabdomyosarcoma (RMS) is associated with a favorable prognosis, but strategies for local control remain controversial. The use of radiotherapy (RT) can have important long-term sequelae, while traditional resection involves major reconstructive surgery. We describe a new surgical approach employing a minimally-invasive resection and immediate reconstruction.

Influence of Cranial Radiotherapy on Outcome in Children With Acute Lymphoblastic Leukemia Treated With Contemporary Therapy.

Purpose: We sought to determine whether cranial radiotherapy (CRT) is necessary to prevent relapse in any subgroup of children with acute lymphoblastic leukemia (ALL).

Patients And Methods: We obtained aggregate data on relapse and survival outcomes for 16,623 patients age 1 to 18 years old with newly diagnosed ALL treated between 1996 and 2007 by 10 cooperative study groups from around the world. The proportion of patients eligible for prophylactic CRT varied from 0% to 33% by trial and was not related to the proportion eligible for allogeneic stem-cell transplantation in first complete remission.

Non-Hodgkin Lymphoma in Children and Adolescents: Progress Through Effective Collaboration, Current Knowledge, and Challenges Ahead.

Non-Hodgkin lymphoma is the fourth most common malignancy in children, has an even higher incidence in adolescents, and is primarily represented by only a few histologic subtypes. Dramatic progress has been achieved, with survival rates exceeding 80%, in large part because of a better understanding of the biology of the different subtypes and national and international collaborations. Most patients with Burkitt lymphoma and diffuse large B-cell lymphoma are cured with short intensive pulse chemotherapy containing cyclophosphamide, cytarabine, and high-dose methotrexate.

YM155 potently kills acute lymphoblastic leukemia cells through activation of the DNA damage pathway.

Background: Novel-targeted therapies are in rapid development for the treatment of acute lymphoblastic leukemia (ALL) to overcome resistance and decrease toxicity. Survivin, a member of the inhibitor of apoptosis gene family and chromosome passenger complex, is critical in a variety of human cancers, including ALL. A well-established suppressor of survivin has been the small molecule, YM155.

Acute lymphoblastic leukaemia.

Acute lymphoblastic leukaemia occurs in both children and adults but its incidence peaks between 2 and 5 years of age. Causation is multifactorial and exogenous or endogenous exposures, genetic susceptibility, and chance have roles. Survival in paediatric acute lymphoblastic leukaemia has improved to roughly 90% in trials with risk stratification by biological features of leukaemic cells and response to treatment, treatment modification based on patients' pharmacodynamics and pharmacogenomics, and improved supportive care.

Recent research advances in childhood acute lymphoblastic leukemia.

Recent progress in risk-adapted treatment for childhood acute lymphoblastic leukemia has secured 5-year event-free survival rates of approximately 80% and 5-year survival rates approaching 90%. With improved systemic and intrathecal chemotherapy, it is now feasible to omit safely in all patients prophylactic cranial irradiation, which was once a standard treatment. As high-resolution, genome-wide analyses of leukemic and normal host cells continue to identify novel subtypes of lymphoblastic leukemia and provide new insights into leukemogenesis, we can look forward to the time when all cases of this disease will be classified according to specific genetic abnormalities, some of which will yield "druggable" targets for more effective and less toxic treatments.

Acute lymphoblastic leukaemia.

Acute lymphoblastic leukaemia, a malignant disorder of lymphoid progenitor cells, affects both children and adults, with peak prevalence between the ages of 2 and 5 years. Steady progress in development of effective treatments has led to a cure rate of more than 80% in children, creating opportunities for innovative approaches that would preserve past gains in leukaemia-free survival while reducing the toxic side-effects of current intensive regimens. Advances in our understanding of the pathobiology of acute lymphoblastic leukaemia, fuelled by emerging molecular technologies, suggest that drugs specifically targeting the genetic defects of leukaemic cells could revolutionise management of this disease.

Adeno-associated virus vector-mediated delivery of pigment epithelium-derived factor restricts neuroblastoma angiogenesis and growth.

Purpose: The purpose of this study was to evaluate the ability of adeno-associated virus (AAV) vector-mediated delivery of pigment epithelium-derived factor (PEDF) to inhibit neuroblastoma (NB) xenograft growth. Pigment epithelium-derived factor was chosen for this study because, in addition to being a potent inhibitor of angiogenesis, it is capable of inducing neuronal differentiation.

Methods: Cohorts of mice received either recombinant AAV encoding human PEDF (rAAV-hPEDF) at a range of doses or control vector via tail vein.

Recombinant urate oxidase (rasburicase) in the prophylaxis and treatment of tumor lysis syndrome.

Spontaneous or treatment-induced tumor lysis syndrome (TLS) can cause significant morbidity and potential mortality. Vigorous hydration, alkalinization and inhibition of uric acid synthesis are the most frequently used methods for prevention of TLS. However, this approach requires hospitalization and tedious nursing care, and fails to prevent renal insufficiency in up to 25% of high-risk patients.

Cyclophosphamide dose intensification during induction therapy for intermediate-risk pediatric rhabdomyosarcoma is feasible but does not improve outcome: a report from the soft tissue sarcoma committee of the children's oncology group.

Purpose: More than half of pediatric rhabdomyosarcoma cases have intermediate-risk features and suboptimal outcome (3-year failure-free survival estimates, 55 to 76%). Dose intensification of known active agents may improve outcome.

Experimental Design: This pilot study evaluated the feasibility of dose intensification of cyclophosphamide in previously untreated patients ages < 21 years with intermediate-risk rhabdomyosarcoma.

Pharmacogenetics of thiopurine S-methyltransferase and thiopurine therapy.

Most medications exhibit wide interpatient variability in their efficacy and toxicity. For many medications, these interindividual differences result in part from polymorphisms in genes encoding drug-metabolizing enzymes, drug transporters, and/or drug targets (eg, receptors, enzymes). Pharmacogenomics is a burgeoning field aimed at elucidating the genetic basis of differences in drug efficacy and toxicity, using genome-wide approaches to identify the network of genes that govern an individual's response to drug therapy.

Endostatin-mediated concomitant resistance in neuroblastoma.

Purpose: Concomitant resistance, the phenomenon whereby a primary malignancy inhibits the growth of metastatic lesions, is likely caused by the production of endogenous anti-angiogenic factors. The purpose of this study was to evaluate the influence of the angiogenesis inhibitor, endostatin, expressed by primary sites of neuroblastoma, on synchronous disease.

Methods: Two neuroblastoma models were used.

De novo purine synthesis inhibition and antileukemic effects of mercaptopurine alone or in combination with methotrexate in vivo.

Methotrexate (MTX) and mercaptopurine (MP) are widely used antileukemic agents that inhibit de novo purine synthesis (DNPS) as a mechanism of their antileukemic effects. To elucidate pharmacodynamic differences among children with acute lymphoblastic leukemia (ALL), DNPS was measured in leukemic blasts from newly diagnosed patients before and after therapy with these agents. Patients were randomized to receive low-dose MTX (LDMTX: 6 oral doses of 30 mg/m(2)) or high-dose MTX (HDMTX: intravenous 1 g/m(2)) followed by intravenous MP; or intravenous MP alone (1 g/m(2)), as initial therapy.

Perianal rhabdomyosarcoma presenting as a perirectal abscess: A report of 11 cases.

Background Purpose: The organs and soft tissues of the pelvis are some of the most common primary sites for rhabdomyosarcoma (RMS) in children and adolescents. In most cases a mass is detectable on clinical examination, and the initial concern is focused on the possibility of a neoplasm. The current report concerns 11 patients, each presented with a painful perineal-perianal mass suggesting an abscess to the extent that each one of these patients was treated initially with antibiotics or incision and drainage for several weeks to months before the pathologic diagnosis of RMS was established.

Autocrine expression of both endostatin and green fluorescent protein provides a synergistic antitumor effect in a murine neuroblastoma model.

Modalities that act through different mechanisms can often provide synergistic antitumor activity for the treatment of refractory tumors when used in combination. Here we report a gene therapy approach in which the genes for the angiogenesis inhibitor, endostatin, and the marker protein and potent immunogen, green fluorescent protein (GFP), were delivered to murine neuroblastoma cells prior to inoculation of the tumor cells into syngeneic immunocompetent mice. Although the effect of either angiogenesis inhibition or immunomodulation alone resulted in only a modest delay in tumor growth, when these approaches were used in combination, prevention of the formation of appreciable tumors was effected in 15 of 24 (63%) mice.