Phase 1 study of high-dose DFMO, celecoxib, cyclophosphamide and topotecan for patients with relapsed neuroblastoma: a New Approaches to Neuroblastoma Therapy trial.

Background: MYC genes regulate ornithine decarboxylase (Odc) to increase intratumoral polyamines. We conducted a Phase I trial [NCT02030964] to determine the maximum tolerated dose (MTD) of DFMO, an Odc inhibitor, with celecoxib, cyclophosphamide and topotecan.

Methods: Patients 2-30 years of age with relapsed/refractory high-risk neuroblastoma received oral DFMO at doses up to 9000 mg/m/day, with celecoxib (500 mg/m daily), cyclophosphamide (250 mg/m/day) and topotecan (0.

Altered Peripheral Blood Gene Expression in Childhood Cancer Survivors With Anthracycline-Induced Cardiomyopathy - A COG-ALTE03N1 Report.

Background Anthracycline-induced cardiomyopathy is a leading cause of premature death in childhood cancer survivors, presenting a need to understand the underlying pathogenesis. We sought to examine differential blood-based mRNA expression profiles in anthracycline-exposed childhood cancer survivors with and without cardiomyopathy. Methods and Results We designed a matched case-control study (Children's Oncology Group-ALTE03N1) with mRNA sequencing on total RNA from peripheral blood in 40 anthracycline-exposed survivors with cardiomyopathy (cases) and 64 matched survivors without (controls).

Identification of novel hypermethylated or hypomethylated CpG sites and genes associated with anthracycline-induced cardiomyopathy.

Anthracycline-induced cardiomyopathy is a leading cause of late morbidity in childhood cancer survivors. Aberrant DNA methylation plays a role in de novo cardiovascular disease. Epigenetic processes could play a role in anthracycline-induced cardiomyopathy but remain unstudied.

Utilizing RENAL nephrometry in pediatric patients undergoing nephron-sparing surgery for renal tumors: A single-institutional cohort.

Introduction: RENAL Nephrometry is a complexity score validated in adults with renal tumors and describes the likelihood of complication after partial nephrectomy (PN). Utilization in pediatrics has been limited. Thus, our goal is to quantify inter-rater agreement as well as determine how scores correlate with outcomes.

Haptoglobin Gene Expression and Anthracycline-Related Cardiomyopathy in Childhood Cancer Survivors: A COG-ALTE03N1 Report.

Background: Anthracycline-related cardiomyopathy is a leading cause of premature death in childhood cancer survivors. The high interindividual variability in risk suggests the need to understand the underlying pathogenesis.

Objectives: The authors interrogated differentially expressed genes (DEGs) to identify genetic variants serving regulatory functions or genetic variants not easily identified when using genomewide array platforms.

An enhanced recovery after surgery protocol in children who undergo nephrectomy for Wilms tumor safely shortens hospital stay.

Background: Pediatric unilateral renal tumors in the US are treated with upfront nephrectomy and surgical staging. We applied enhanced recovery after surgery (ERAS) principles in care of children after Wilms nephrectomy.

Methods: We reviewed records of pediatric unilateral nephrectomies for Wilms tumors, and analyzed tumor stage, surgical approach, length of operation, use of anesthesia adjuncts and catheters, diet advancement, hospital length of stay (LOS), and complications.

Pharmacokinetics of the disialoganglioside, G, a circulating tumor biomarker for neuroblastoma, in nonhuman primates.

Background:: The ganglioside G is a potential circulating tumor biomarker for the childhood cancer neuroblastoma. Interpreting the levels of a circulating tumor biomarker depends in part on a knowledge of the biomarker’s clinical pharmacology.

Methods:: We studied the plasma and cerebrospinal fluid (CSF) pharmacokinetics of the C lipoform of G in two nonhuman primates with indwelling subcutaneous CSF lateral ventricular reservoir systems.

Activity of Crizotinib in Patients with ALK-Aberrant Relapsed/Refractory Neuroblastoma: A Children's Oncology Group Study (ADVL0912).

Purpose: Anaplastic lymphoma kinase (ALK) aberrations are a promising target for patients with neuroblastoma. We assessed the activity of first-generation ALK inhibitor crizotinib in patients with no known curative treatments and whose tumors harbored an activating ALK alteration.

Patients And Methods: Twenty patients with relapsed/refractory ALK-positive neuroblastoma received crizotinib at the recommended phase II dose of 280 mg/m/dose.

The ganglioside G as a circulating tumor biomarker for neuroblastoma.

Background: G is a ganglioside that is ubiquitously expressed in the plasma membrane of neuroblastoma and is shed into the circulation.

Procedure: G was measured with a high-pressure liquid chromatography/tandem mass spectrometry assay in serum or plasma from 40 children without cancer (controls) and in biobanked samples from 128 (73 high-risk) children with neuroblastic tumors at diagnosis, 56 children with relapsed neuroblastoma, 14 children with high-risk neuroblastoma after treatment, and 8 to 12 children each with 10 other common childhood cancers at diagnosis.

Results: The C (18 carbon fatty acid) lipoform was the predominant circulating form of G in controls and in patients with neuroblastoma.

Exceptional Response to Nivolumab in a 13-Year-Old Female with Metastatic HPV-Negative Cervical Carcinoma.

Cervical carcinoma is associated with high-risk human papillomavirus (HPV) DNA integration and usually occurs after age 21 (peak 45 years), as reflected in screening guidelines. Between 1999 and 2008, cervical carcinoma rate in adolescents aged 15-19 years was 0.15 per 100,000.

Fundamental problems with pediatric adaptive dosing of carboplatin using nuclear-medicine-based estimates of renal function.

Background: Carboplatin is often adaptively dosed based on glomerular filtration rate (GFR), usually estimated by nuclear medicine tests. At least five pediatric adaptive dosing formulas have been developed. In an effort to standardize dosing in Children's Oncology Group protocols, we explored methodologic variation in GFR estimation and adaptive-dosing formula performance.

Diagnosis of Beckwith-Wiedemann syndrome in children presenting with Wilms tumor.

Beckwith-Wiedemann syndrome (BWS) is a genetic syndrome associated with overgrowth and cancer predisposition, including predisposition to Wilms tumor (WT). Patients with BWS and BWS spectrum are screened from birth to age 7 years for BWS-associated cancers. However, in some cases a BWS-associated cancer may be the first recognized manifestation of the syndrome.

Case Report: Nephron-sparing Surgery in a Patient With Bilateral Multifocal Wilms Tumor.

We present a case of bilateral multifocal Wilms tumor in a nonsyndromic 12-month-old male. Our management approach included 12 weeks of preoperative chemotherapy for maximal tumor shrinkage and, despite the central location of the tumors, successful staged bilateral nephron-sparing surgery. We advocate for a broader application of nephron-sparing surgery in Wilms tumor cases with the goal of preserving renal function without compromising oncologic outcomes.

Outcomes of Children and Adolescents with Advanced Hereditary Medullary Thyroid Carcinoma Treated with Vandetanib.

Vandetanib is well-tolerated in patients with advanced medullary thyroid carcinoma (MTC). Long-term outcomes and mechanisms of MTC progression have not been reported previously. We monitored toxicities and disease status in patients taking vandetanib for hereditary, advanced MTC.

Consensus Guideline for Use of Glucarpidase in Patients with High-Dose Methotrexate Induced Acute Kidney Injury and Delayed Methotrexate Clearance.

Unlabelled: Acute kidney injury due to high-dose methotrexate (HDMTX) is a serious, life-threatening toxicity that can occur in pediatric and adult patients. Glucarpidase is a treatment approved by the Food and Drug Administration for high methotrexate concentrations in the context of kidney dysfunction, but the guidelines for when to use it are unclear. An expert panel was convened to provide specific, expert consensus guidelines for the use of glucarpidase in patients who develop HDMTX-induced nephrotoxicity and delayed methotrexate excretion.

Modernizing Clinical Trial Eligibility: Recommendations of the American Society of Clinical Oncology-Friends of Cancer Research Minimum Age Working Group.

Purpose Children have historically been excluded from first-in-human studies of promising new cancer drugs and later phase adult clinical trials. Delays in evaluation may result in off-label use without dosing information as the only access to new drugs. A multistakeholder workshop was convened in May 2016 by ASCO and Friends of Cancer Research to identify opportunities for when it would be scientifically appropriate to expand trial eligibility to include children younger than age 18 years in first-in-human and other adult cancer clinical trials.

Dosing anticancer drugs in infants: Current approach and recommendations from the Children's Oncology Group's Chemotherapy Standardization Task Force.

An analysis of dose modifications for infants in 29 Children's Oncology Group protocols across 10 cancer types revealed 11 sets of criteria defining the infant population using age, weight, body surface area (BSA), or a combination of these parameters and eight dose modification methods. A new method of dosing anticancer drugs in infants was developed based on the rationale that prior modifications were implemented to reduce toxicity, which is not cancer-specific. The new method uses BSA dose banding in dosing tables for infants and children with a BSA <0.

First-dose and steady-state pharmacokinetics of orally administered crizotinib in children with solid tumors: a report on ADVL0912 from the Children's Oncology Group Phase 1/Pilot Consortium.

Purpose: Characterize the pharmacokinetics of oral crizotinib in children with cancer.

Methods: Sixty-four children with solid tumors or anaplastic large-cell lymphoma (ALCL) enrolled on a phase 1/2 trial of the ALK, MET and ROS1 inhibitor, crizotinib, had pharmacokinetic sampling after the first dose (n = 15) or at steady state (n = 49). Dose levels studied were 100, 130, 165, 215, 280 and 365 mg/m/dose administered twice daily.

Pharmacokinetic and pharmacodynamic study of tariquidar (XR9576), a P-glycoprotein inhibitor, in combination with doxorubicin, vinorelbine, or docetaxel in children and adolescents with refractory solid tumors.

Purpose: P-glycoprotein (Pgp), an ATP-dependent transport protein, confers multidrug resistance in cancer cells. Tariquidar binds and inhibits Pgp. To assess the toxicity, pharmacokinetics (PK), and pharmacodynamics of tariquidar, we conducted a phase I trial of tariquidar in combination with doxorubicin, docetaxel, or vinorelbine in children and adolescents with recurrent or refractory solid tumors.

Phase II/III trial of a pre-transplant farnesyl transferase inhibitor in juvenile myelomonocytic leukemia: a report from the Children's Oncology Group.

Background: Juvenile myelomonocytic leukemia (JMML) is not durably responsive to chemotherapy, and approximately 50% of patients relapse after hematopoietic stem cell transplant (HSCT). Here we report the activity and acute toxicity of the farnesyl transferase inhibitor tipifarnib, the response rate to 13-cis retinoic acid (CRA) in combination with cytoreductive chemotherapy, and survival following HSCT in children with JMML.

Procedure: Eighty-five patients with newly diagnosed JMML were enrolled on AAML0122 between 2001 and 2006.

Pharmacokinetics of the chimeric anti-GD2 antibody, ch14.18, in children with high-risk neuroblastoma.

Purpose: Ch14.18 improves survival in children with high-risk neuroblastoma but is associated with substantial toxicity. Ch14.