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1 Minimally Invasive Surgery for Neurogenic Tumors of The 1 Minimally Invasive Surgery for Neurogenic Tumors of The Posterior Mediastinum in Children Diana Rybakova1, Anatoly Kazanchzev1, Polad Kerimov1 1FGBU "NMIC Oncologists Them. N.n. Blokhin »moscow, Ministry of Health of The Russian Federation, Moscow, Moscow, Russian Federation Actuality: Neurogenic tumors of the mediastinum in children occur in 15% of all tumors of the nervous system. The main method of treatment of this pathology is surgery, including minimally invasive surgery. Objectives: To determine the possibility of minimally invasive surgery in the treatment of neurogenic tumors of the posterior mediastinum in children. Materials and methods: From 2007 to 2016, 47 patients underwent thoracoscopic operations of the neurogenic tumor of the mediastinum. The age of the patients varied from 5 months to 16 years. The largest number of children entered the group from 1 year to 3 years - 18 people (38.3%). The sex ratio was approximately equal to: boys were 24 (51%), girls - 23 (49%).The duration of the operations was, on average, 49 minutes. In 85% of cases, the operation time was less than 60 minutes, and only 15% more than 1 hour. The blood loss during thoracoscopic operations averaged 14.3 ml. In 36 cases, blood loss was not observed. No intraoperative complications were noted. All patients within the first 24 hours after the operation were transferred to the profile department from the intensive care unit. Postoperative complications arose in 4 patients - Horner's syndrome, in connection with the localization of the tumor process in the apical part of the chest. 43 patients after surgery were in the surgical clinic for no more than 3 days, and 4 patients were detained in the hospital for up to 7 days to assess the neurological status due to manifestations of Horner's syndrome. All neoplasms were represented by neurogenic tumors: neuroblastoma-23 (49%), ganglioneuroblastoma-14 (30%) and geglioneuroma-10 (21%). Conclusion: The advantages of using minimally invasive surgery for the treatment of neurogenic mediastinal tumors are: low traumatism, minimal blood loss, low number of complications, early activation of the patient and shortening of time in hospital, good cosmetic effect. Performing endosurgical operations in children with mediastinal tumors can be at the age of several months, while the oncological principles of performing surgical intervention are not violated, and the age of the child is not a limiting factor for performing endosurgical operations. 2 Histone Demethylases Are Novel Therapeutic Targets of Neuroblastoma Jun Yang1, Andrew Davidoff1 1St Jude Children's Research Hospital, Memphis, United States Neuroblastoma is the most common type of cancer in infants and causes as much as 15% of cancer-related deaths in children. Although the outcomes of children with low- or intermediate-risk disease are excellent, those of children with high-risk disease remain dismal. Thus, the need to identify novel therapeutic targets and develop more effective treatments for high-risk neuroblastoma is urgent. The genetic abnormalities that drive tumorigenesis are usually coupled with epigenetic alterations, such as aberrant histone modification, which may help oncogenic drivers accelerate cancer progression, metastasis, and therapy resistance. Oncogenic MYCN amplification is the most important biological feature of high-risk neuroblastoma. Histone lysine demethylases appear to be involved in facilitating the activity of oncogenic transcription factors such as Myc. Therefore, targeting histone demethylases may block Myc signaling central to tumorigenesis. Here we present that genetic or pharmacologic inhibition with novel inhibitors of histone demethylases is able to inhibit proliferation of neuroblastoma. Our findings provide new insight into the epigenetic regulation of Myc function via histone demethylation and indicate that pharmacologic inhibition of histone demethylases may be an effective approach for cancer therapy through Myc pathway inhibition. 3 Prognostic Value of Minimal Residual Disease in High-Risk Neuroblastoma Group: Protocol NB 2004m, End of Induction Inna Praliaskouskaya1, Irina Pakhomava1, Alexandra Romantsova1, Oleg Budanov1, Olga Aleinikova1 1Belarusian Research Center for Pediatric Oncology, Hematology and Immunology, Minsk, Belarus Background: To establish the prognostic value of the presence of a minimal residual disease (MRD) in bone marrow (BM) in the high-risk neuroblastoma group at the end of induction. Methods: The study of MRD in BM on protocol NB2004m, end of induction, performed by flow cytometry (Syto16+CD45-CD56+CD81+ phenotype), immunocytochemistry (GD2-positive cells), molecular biology (semiquantitative evaluation of TH and PHOX2B gene expression using RT-PCR). Results: For flow cytometry and immunocytochemistry, we used cut-off positivity and negativity. Overall survival (OS) flow cytometry (n = 5) 100% vs (n=31) 52%±11% (р=0,16); event-free survival (EFS) 50%±25% vs 37%±10%, (р=0,4). OS immunocytochemistry (n = 1) 100% vs (n = 20) 86% ± 9% (p = 0,8); EFS 0% vs 40% ± 19%, (p=0,34). The presence of MRD in BM, determined by both methods, didn’t influence OS and EFS on patients with neuroblastoma. Сut-off, determined for the level of expression of TH and PHOX2B genes, allows to classify a part of patients as ultra-high risk: for expression of TH gene - log10> 0.0018, for PHOX2B gene - positive expression in BM. In case of expression of TH gene higher than cut–off OS (n=11) 30%±15% vs (n=34) 67%±10% (р = 0,0032); EFS 11% ± 9% vs 53% ± 10%, (p = 0,0004). Positive expression of PHOX2B gene OS (n = 9) 35% ± 18% vs (n = 31) 59% ± 11% (p = 0,0032), EFS 0% vs 55% ± 15%, (p = 0,0002). In Cox regression analysis, we used the following risk factors: age, stage, MYC-N amplification, the expression level of TH and PHOX2B genes in BM, end of induction. Two regression models for OS and EFS were constructed. In the model for EFS, the expression of PHOX2B gene had significance (p = 0,0087) with RR 3.02. Conclusion: the presence of MRD in BM, revealed by the evaluation of the expression of TH and PHOX2B genes, in our patients at the end of induction strongly negatively influences the prognosis of the disease. For this cohort of patients, the approaches to therapy should be changed, since the standard therapy is not effective for them. 4 Outcomes and Complications of Surgery in Patients with Intermediate- Risk Neuroblastoma: Experience from an Indian Tertiary Cancer Centre Sajid Qureshi1, Girish Chinnaswamy1, Tushar Vora1, Seema Medhi1, Maya Prasad1, Mukta Ramadwar1, Omshree Shetty1, Siddharth Laskar1 1Tata Memorial Hospital, Mumbai, India Background: The treatment of intermediate risk (IR) neuroblastoma has evolved with the focus now on reducing the drugs, dosage, and duration of chemotherapy. The aim of this study is to present the outcomes of treatment and the complications of surgery in patients with IR neuroblastoma treated at a tertiary cancer center in India. Procedure: All eligible patients with IR neuroblastoma treated between April 2005 and August 2016 were identified. The presence and number of image-defined risk factors (IDRF) before and after neoadjuvant chemotherapy were retrospectively analyzed as were the extent of surgery, complications, and outcomes. Results: Of 282 neuroblastoma patients treated during the study period, 54 had IR neuroblastoma. A median of 3 IDRF's were identified at presentation which reduced to 2 after preoperative chemotherapy; however, complete disappearance of IDRF was not seen in any patient. Complete excision was achieved in 25 patients. There were 28 surgical complications in 22 patients with a similar incidence in patients with complete (n=14) or incomplete (n=13) resection (p=0.6). The most common complication was postoperative chylous leakage. There was no perioperative mortality. After a median follow-up of 47 months, the 4-year overall and event-free survival was 91.5% and 75% respectively. There was no difference in survival between patients who underwent complete resection versus those with incomplete resection (p=0.78). Conclusion: Outcomes of IR neuroblastoma are favorable. IDRFs do not predict the extent of resection or survival. The extent of resection does not affect the survival and complications can occur even when the resection is incomplete. 5 A Kinome-Wide RNAi Screen Identifies ALK As a Target to Sensitize Neuroblastoma Cells for HDAC8-Inhibitor Treatment Jing Shen1, Sara Najafi1,2, Sina Stäble1, Johannes Fabian1, Emily Koeneke1,2, Fiona R. Kolbinger1,2, Tino Heimburg3, Wolfgang Sippl3, Manfred Jung4, Heike Peterziel1,2, Dominique Kranz5, Michael Boutros5, Frank Westermann6, Olaf Witt1,2,7, Ina Oehme1,2 1Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany, 2Translational Program, Hopp Children’s Cancer Center at NCT Heidelberg (KiTZ), Heidelberg, Germany, 3Institute of Pharmacy, Martin-Luther University of Halle-Wittenberg, Halle/Saale, Germany, 4Institute of Pharmaceutical Sciences, University of Freiburg, Freiburg, Germany, 5Division of Signaling and Functional Genomics, German Cancer Research Center and Heidelberg University, Department for Cell and Molecular Biology, Medical Faculty Mannheim, Heidelberg, Germany, 6Research Group Neuroblastoma Genomics, German Cancer Research Center (DKFZ), Heidelberg, Germany, 7Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg Medical Center, Heidelberg, Germany The prognosis of advanced stage neuroblastoma patients
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