BackgroundRhabdomyosarcoma (RMS) is a small round blue cell malignant tumor, representing 7% of childhood malignancies, and over 50% of all soft tissue sarcomas. Cyclophosphamide (CPA) is a prodrug and is the mainstay of RMS treatment. CYP2B6 is a highly polymorphic drug metabolizing enzyme involved in CPA bioactivation. The influence of CYP2B6 single nucleotide polymorphisms (SNPs) on the survival of RMS is still unknown.MethodsWe genotyped CYP2B6SNPs rs2279343, rs3745274, and rs3211371 by restriction fragment polymorphism (RFLP) after PCR amplification in a cohort of 73 pediatric RMS patients treated with CPA-based first line treatment. We then analyzed the association between those genotypes and survival outcome of RMS.ResultsThe frequencies of CYP2B6 rs2279343, rs3745274, and rs3211371 were 63%, 45.2%, and 5.5%, respectively. There was no association between rs3745274, rs3211371 genotypes and survival outcomes of RMS. However, the carriers of at least one mutant allele CYP2B6rs2279343 had significantly longer event-free survival (p-value = 0.03).ConclusionOur results demonstrated that CYP2B6 rs2279343 may predict EFS in RMS patients and warrants future studies to clarify the pharmacogenetics of CPA in pediatrics. If validated, integration of genetic factors with clinical and molecular characteristics could be used for a composite algorithm to better stratify risk prior to treatment.

Background: Rhabdomyosarcoma (RMS) in the head and neck especially orbit represents a major anatomic site for this tumor in pediatrics. Orbital RMS is the most common primary orbital malignancy in children with approximately 35 new cases per year. Objectives:The aim of this work is to study cases of orbital RMS and assess epidemiology, clinical and pathological characteristics as well as survival outcomes.Methods: Patients diagnosed with orbital RMS between July 2007 and July 2012 follow-up till July 2014. They were treated according to IRS-IV and IRS V protocols. Case report forms were analyzed and treatment outcome, OS and FFS for patients were analyzed.Results: Seventeen orbital RMS patients were diagnosed at the mentioned period. Complete remission was identified in 7 (41.2%) cases, Partial remission in 4 (23.5%) cases and progressive disease in 4 (23.5%) cases while 2 cases died before evaluation. Three patients had experienced different management-related ophthalmic sequelae. Only one patient died due to chemotherapy-associated toxicity. The 4-years OS and 4-years FFS were 94.1 ± 5.7% and 65.4 ± 1.5% respectively. Conclusion:The current study demonstrated that RMS cases that present with orbit involvement are associated with better clinical outcome. Future treatment of patients with non-metastatic orbital RMS will focus on adjustments in therapy to reduce acute and late adverse effects while maintaining their excellent treatment outcome. New therapeutic approaches are required for the patients whose present outcome is less than optimal.

Objectives: Osteosarcoma (OS) is one of the aggressive bone tumors commonly diagnosed in adolescents and young adults. The study investigated the effect of 9 single nucleotide polymorphisms (SNPs) in 5 genes on methotrexate (MTX) plasma level and its impact on the patients’ clinical outcomes. Methods: One hundred and thirty-three patients with OS (68 boys and 65 girls with age range 4.00-17.86 years) were enrolled and treated with four weeks of high-dose methotrexate (HDMTX) as neo-adjuvant therapy in children’s cancer hospital (CCHE-57357). Blood samples were collected and genotyped for the studied SNPs (MTHFR rs1801133, SLCO1B1 rs11045879, rs4149081, rs2306283, ABCC3 rs4793665, rs4148412, rs733392 ABCG2 rs2231142, and ABCC2 rs717620 using Taqman® (RT-PCR) assay. Plasma concentrations of MTX were measured using the enzyme multiple immunoassay technique (EMIT®). The clinical outcomes included toxicities that were evaluated based on the common terminology criteria for adverse events - version 5 (CTCAEv5.0.), besides the studying of survival analysis and tumor necrosis (TN %). Results: Older patients experienced increased risk of delayed MTX elimination at 72-hour, OR=1.19 (95% CI=1.09-1.29, p=0.00059). The studied SNPs weren’t associated with MTX elimination. Patients with ABCC2 HW (Homozygous wild) genotype group showed a high statistically significant association with higher grade hyperbilirubinemia, OR= 2.05(95% CI=1.05-4.01, p=0.037). Moreover, the patients with ABCC3 (rs4793665) HV and HT (Homozygous variant and Heterozygous) genotypes had a significant association with severe nephrotoxicity, OR= 0.34(95% CI=1.6-0.72, p=0.005). Conclusions: ABCC2 (rs717620), ABCC3 (rs4793665) genotyping with age and gender could help in predicting patients at risk of toxicities due to HDMTX.

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