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In children with cancer, the heterogeneity in ototoxicity occurrence after similar treatment suggests a role for genetic susceptibility. Using a genome-wide association study (GWAS) approach, we identified a genetic variant in TCERG1L (rs893507) to be associated with hearing loss in 390 non-cranial irradiated, cisplatin-treated children with cancer. These results were replicated in two independent, similarly treated cohorts (n = 192 and 188, respectively) (combined cohort: P = 5.3 × 10−10, OR 3.11, 95% CI 2.2–4.5). Modulating TCERG1L expression in cultured human cells revealed significantly altered cellular responses to cisplatin-induced cytokine secretion and toxicity. These results contribute to insights into the genetic and pathophysiological basis of cisplatin-induced ototoxicity. [ABSTRACT FROM AUTHOR]

Background: To enhance risk stratification for Wilms tumour (WT) in a pre-operative chemotherapy setting, we explored the prognostic significance and optimal age cutoffs in patients treated according to International Society of Paediatric Oncology Renal Tumour Study Group (SIOP-RTSG) protocols. Methods: Patients(6 months-18 years) with unilateral WT were selected from prospective SIOP 93–01 and 2001 studies(1993–2016). Martingale residual analysis was used to explore optimal age cutoffs. Outcome according to age was analyzed by uni- and multivariable analysis, adjusted for sex, biopsy(yes/no), stage, histology and tumour volume at surgery. Results: 5631 patients were included; median age was 3.4 years(IQR: 2–5.1). Estimated 5-year event-free survival (EFS) and overall survival (OS) were 85%(95%CI 83.5–85.5) and 93%(95%CI 92.0–93.4). Martingale residual plots detected no optimal age cutoffs. Multivariable analysis showed lower EFS with increasing age(linear trend P<0.001). Using previously described age categories, EFS was lower for patients aged 2-4(HR 1.34, P = 0.02), 4-10(HR 1.83, P<0.0001) and 10–18 years(HR 1.74, P = 0.01) as compared to patients aged 6 months-2 years. OS was lower for patients 4–10 years(HR 1.67, P = 0.01) and 10–18 years(HR 1.87, P = 0.04), but not for 2–4 years(HR 1.29, P = 0.23). Higher stage, histological risk group and tumour volume were independent adverse prognostic factors. Conclusion: Although optimal age cutoffs could not be identified, we demonstrated the prognostic significance of age as well as previously described cutoffs for EFS (2 and 4 years) and OS (4 years) in children with WT treated with pre-operative chemotherapy. These findings encourage the consideration of age in the design of future SIOP-RTSG protocols. [ABSTRACT FROM AUTHOR]

Childhood cancer patients treated with platinums often develop hearing loss and the degree is classified according to different scales globally. Our objective was to compare concordance between five well-known ototoxicity scales used for childhood cancer patients. Audiometric test results (n = 654) were evaluated longitudinally and graded according Brock, Chang, International Society of Pediatric Oncology (SIOP) Boston, Muenster scales and the U.S. National Cancer Institute Common Technology Criteria for Adverse Events (CTCAE) version 4.03. Adverse effects of grade 2, 3 and 4 are considered to reflect a degree of hearing loss sufficient to interfere with day-to-day communication (> = Chang grade 2a; > = Muenster grade 2b). We term this “deleterious hearing loss”. A total number of 3,799 audiograms were evaluated. The prevalence of deleterious hearing loss according to the last available audiogram of each patient was 59.3% (388/654) according to Muenster, 48.2% (315/653) according to SIOP, 40.5% (265/652) according to Brock, 40.3% (263/652) according to Chang, and 57.5% (300/522) according to CTCAEv4.03. Overall concordance between the scales ranged from ĸ = 0.636 (Muenster vs. Chang) to ĸ = 0.975 (Brock vs. Chang). Muenster detected hearing loss the earliest in time, followed by Chang, SIOP and Brock. Generally good concordance between the scales was observed but there is still diversity in definitions of functional outcomes, such as differences in distribution levels of severity of hearing loss, and additional intermediate scales taking into account losses <40 dB as well. Regardless of the scale used, hearing function decreases over time and therefore, close monitoring of hearing function at baseline and with each cycle of platinum therapy should be conducted. [ABSTRACT FROM AUTHOR]

Introduction To further optimize survival rates as well as quality of cure for pediatric kidney tumors, attention for treatment related morbidity and mortality has become increasingly important. Intussusception is a rare but important complication after tumornephrectomy in children, causing morbidity, mortality and prolonged hospitalization. In this study, we describe two recent cases in our institute and provide a comprehensive review of the literature. Methods For our narrative review, we searched for all reported cases of post tumor nephrectomy intussusception published until November 2016, using Pubmed and Embase libraries. Results A total of 52 pediatric renal tumor cases who developed intussusception after tumor nephrectomy were identified. Median age was 23 months (range 3–84). Median time of onset was postoperative day 6 (range 1–18). Of 41 patients described in detail, only 4/41 were ileocolic, the others suffered from a small bowel intussusception. Most frequent presenting symptom was bilious vomiting. Preceding treatment approach was documented in 47 cases; i.e. preoperative chemotherapy had been administered to 10/47 patients. In 29 of 30 well documented cases, successful manually reduction during re-laparotomy was described and only 1 patient needed resection. All patients survived without recurrence of intussusception. Conclusion In pediatric renal tumor patients, small bowel obstruction seems to reflect mostly post nephrectomy intussusception cases in contrast to the ileocolic idiopathic intussusceptions that are observed in healthy children. Symptoms of intussusception mimic chemotherapy related toxicity and general post-surgical symptoms, thereby initiating a significant delay in diagnosis. Awareness of intussusception after renal tumor surgery is warranted. [ABSTRACT FROM AUTHOR]