Background: Neuroblastoma is a highly aggressive pediatric cancer, particularly in children with refractory or relapsed disease, where survival outcomes remain poor despite advancements in treatment. Combining anti-GD2 antibodies, such as dinutixumab beta, dinutixumab, and naxitanab, with conventional chemotherapy has emerged as a promising approach to improve clinical outcomes in this high-risk population. This chemo-immunotherapy regimen meta-analysis aimed to investigate the efficacy of these combination regimens by analyzing objective response rate (ORR), overall survival (OS), and event-free survival (EFS) outcomes across multiple studies. Methods: A systematic review and meta-analysis were conducted following PRISMA guidelines. PubMed, Web of Science, and Scopus databases were searched, yielding studies comprising the related reports. Both randomized controlled trials and non-randomized studies were included. The primary outcome of interest was ORR, and the secondary outcome of interest was EFS. A random-effects model using the DerSimonian–Laird method and Knapp–Hartung–Sidik–Jonkman adjustments was employed to pool effect sizes, and heterogeneity was assessed using I² statistics. Results: A total of ten reports from eight studies were deemed eligible and included in the meta-analysis. The pooled ORR across the studies was 0.45 (95% CI: 0.35–0.54, p < 0.001), indicating that approximately 45% of patients showed a favorable treatment response, with moderate heterogeneity (I² = 52.78%). The pooled analysis showed an OS of 75% (95% CI: 53–96, p < 0.001), and the pooled EFS effect size was 0.59 (95% CI: 0.45–0.73, p < 0.001), despite substantial heterogeneity (I² = 60.54%). Conclusions: anti-GD2 antibodies combined with conventional chemotherapy may significantly improve response rates and event-free survival in children with refractory or relapsed neuroblastoma. Future research should focus on identifying predictive biomarkers to tailor therapies to individual patients, enhancing both efficacy and safety in this vulnerable population.

OBJECTIVE: Cisplatin (CDDP) is an anti-neoplastic agent that has been used in treatments of both pediatric and adult cancers. It has many side effects, such as ototoxicity, nephrotoxicity, and neurotoxicity. Lipoplatin (LIPO) is a nanomolecule with 110 nm diameter and composed of lipids and CDDP. In this study, we aimed to compare the toxic effects of LIPO with CDDP in the cochlear cells with anti-tumoral doses determined in neuroblastoma cells. MATERIALS and METHODS: House Ear Institute Organ Corti 1 (HEI-OC1), MYC-N amplified KELLY, and MYC-N non-amplified SH-SY5Y human neuroblastoma cells were used in this study. Firstly, anti-tumoral lethal dose 50 (LD50) of LIPO and CDDP were determined using the WST-1 assay in both neuroblastoma cells. Then anti-tumoral doses of CDDP and LIPO were applied on HEI-OC1 cells for evaluating the toxic effects. The apoptotic cell death was measured using flow cytometric analysis of annexin-V/7-amino-actinomycin (7-AAD) and cell cycle tests. RESULTS: LIPO or CDDP inhibited cell viability in a dose- and time-dependent manner in both neuroblastoma and HEI-OC1 cells. LD50 values were selected as 20 mM for CDDP and 750 mM for LIPO in neuroblastoma cells. After the 48-hour incubation, KELLY cells treated with 20 mM CDDP and 750 mM LIPO had a 53% viability; SH-SY5Y cells treated 20 mM CDDP and 750 mM LIPO had a 45% and 58% viability, respectively; and HEI-OC1 cells treated with 20 mM CDDP and 750 mM LIPO had a 65% and 82% viability, respectively. CONCLUSION: LIPO showed less toxic effects in the HEI-OC1 cells compared to CDDP at anti-tumoral doses. Cite this article as: Serinan E, Atun Z, Aktaş S, Çeçen E, Olgun N. Comparison of Cisplatin with Lipoplatin in Terms of Ototoxicity. J Int Adv Otol 2018; 14(2): 211-5.

Background: There is considerable interest in the molecular evaluation of solid tumors in pediatric cases. Although clinical trials are in progress for targeted therapies against neuroblastoma (NB), novel therapeutic strategies are needed for high-risk cases that are resistant to therapy. The aim of the present study was to document the specific gene mutations related to targeted therapy in relapsed or refractory NB patients by using next generation sequencing (NGS). Methods: The study included 57 NB patients from amongst 1965 neuroblastic cases in Turkey who experienced a recurrence after multi-model therapy. The cases were diagnosed, risk-stratified, and treated according to the classification system from the International Neuroblastoma Risk Group. Single nucleotide variations in 60 genes were investigated using the Pillar Onco/Reveal Multicancer v4 panel and Pillar RNA fusion panel on the Illumina Miniseq platform. Results: ERBB2 I655V was the most frequent mutation and was found in 39.65% of cases. Anaplastic Lymphoma Kinase (ALK) mutations (F1174L, R1275Q, and rare mutations in the tyrosine kinase domain) were detected in 29.3% of cases. Fusion mutations in NTRK1, NTRK3, ROS1, RET, FGFR3, ALK and BRAF were observed in 19.6% of cases. Conclusions: This study presents valuable mutation data for relapsed and refractory NB patients. The high frequency of the ERBB2 I655V mutation may allow further exploration of this mutation as a potential therapeutic target. Rare BRAF mutations may also provide opportunities for targeted therapy. The role of ABL1 mutations in NB should also be explored further.