Treatment of patients with high-risk neuroblastoma (NB) is a complex challenge, and it is based on response to certain elements of therapy. The development and introduction of new treatment approaches, such as GD2-targeted immunotherapy (IT), leads to improved survival in this cohort of patients. The aim of the study was to retrospectively assess the effectiveness of therapy in patients with high-risk NB before the introduction of IT into clinical practice. We retrospectively analyzed the data of 151 NB patients stratified into a high-risk group who had received treatment in accordance with the modified NB2004 protocol of the German Society for Pediatric Oncology and Hematology (GPOH) at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology from 01.2012 to 12.2017. This study was approved by the Independent Ethics Committee and the Academic Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. All the study subjects (or their legal representatives) signed a voluntary informed consent form indicating their agreement to treatment and use of their data for research purposes. Overall survival (OS), event-free survival (EFS), and risk factors were analyzed in the patients with high-risk NB including those who had completed multimodal therapy with autologous hematopoietic stem cell transplantation and post-consolidation therapy with isotretinoin and had achieved a satisfactory response to induction therapy (complete response (CR), very good partial response (VGPR), partial response (PR)) (population of special interest). The main unfavorable prognostic clinical and molecular genetic factors affecting survival in the high-risk NB patients were older age, MYCN gene amplification, and stage 4 of the disease. The use of the modified GPOH NB2004 protocol resulted in a satisfactory response (CR/VGPR/PR) to the induction therapy in most patients: 124/151 (82.1 %). Surgery (other than primary tumor biopsy) led to improved survival, with no statistical difference between macroscopic radical surgery and macroscopic residual tumor. At the same time, radiation therapy (RT), as the second element of local control, had a significant impact on EFS in the group of the patients with stage 4 disease: the 3-year EFS was 39.4 % (95 % confidence interval (CI) 23.1–55.4) in the patients with RT versus 25.7 % (95 % CI 17.5–34.7) in the patients without RT (p = 0.0295). The introduction of a new high-dose TreoMel chemotherapy regimen did not result in worse survival rates but led to a decrease in transplant-related toxicity. The 5-year OS and 5-year EFS were 49.4 % (95 % CI 40.9–57.3 %) and 33.3 % (95 % CI 25.9–40.9) respectively for all the study subjects, and 81.6 % (95 % CI 70.3–88.9) and 55.1 % (95 % CI 43.1–65.5) respectively for the patients from the population of special interest. The analysis of the results of therapy in the high-risk NB patients who had received treatment at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, yielded results comparable to those of the original GPOH NB2004 protocol. The patients with CR/VGPR/PR to the induction therapy who had completed the protocol treatment with autologous hematopoietic stem cell transplantation and isotretinoin post-consolidation therapy demonstrated higher 5-year EFS rates. However, there remains a need to develop more effective treatment regimens for high-risk NB.

Amaranthus L. includes valuable and promising crops of multi-purpose use, having high morphological diversity and complicated taxonomy. Their karyotypes and genomic relationships remain insufficiently studied. For the first time, a comparative repeatome analysis of Amaranthus tricolor L., Amaranthus cruentus L., and Amaranthus hypochondriacus L. was performed based on the high-throughput sequencing data obtained via bioinformatic analyses using the RepeatExplorer2/TAREAN/DANTE_LTR pipelines. Interspecific variations in the abundance of Ty1 Copia and Ty3 Gypsy retroelements, DNA transposons, and ribosomal and satellite DNA (satDNA) were detected. Based on fluorescence in situ hybridization (FISH), chromosome mapping of 45S rDNA, 5S rDNA, and satDNAs AmC9 and AmC70, and unique karyograms of A. tricolor, A. cruentus, Amaranthus paniculatus L., and A. hypochondriacus were constructed. The analysis of the interspecies genome diversity/similarity in DNA repeat contents, sequences of the identified satDNAs, and chromosome distribution patterns of the studied molecular markers indicated that these species might also share a common evolutionary ancestor. However, the genomes of A. cruentus, A. paniculatus, and A. hypochondriacus were more similar compared to A. tricolor, which aligns with the previous phylogenetic data. Our results demonstrate that cytogenomic studies might provide important data on Amaranthus species relationships elucidating taxonomy and evolution of these valuable crops.

INTRODUCTION: Extracranial neurogenic tumors in children are represented by neoplasms of the sympathetic nervous system and adrenal medulla: ganglioneuromas, ganglioneuroblastomas and neuroblastomas. The main prognostic factors used to stratify patients into risk groups and, in many ways, determine the effectiveness of treatment are the histological type of the tumor and the presence of MYCN gene amplification.OBJECTIVE: To evaluate the capabilities of quantitative MRI to determine the histological variant of neurogenic tumors and predict the presence of MYCN gene amplification in children.MATERIALS AND METHODS: We retrospectively analyzed the data of 110 patients with primary peripheral neurogenic tumors who underwent therapy or received an advisory opinion at the D.Rogachev National Medical Research Center for Pediatric Orthopedics and Pediatric Orthopedics in the period from 2012 to 2022. with diagnoses of ganglioneuroma — 12, mixed ganglioneuroblastoma — 10, neuroblastoma — 88. The age of patients at the time of diagnosis ranged from 15 days to 16 years, median age — 17 months. Before surgery and therapeutic interventions, all patients underwent diffusion-weighted MRI and a tumor biopsy to determine MYCN gene amplification using FISH.Statistics: To determine the threshold values of the apparent diffusion coefficient (ADC) of neurogenic tumors of various histological structures, as well as with the presence and absence of MYCN gene amplification, ROC analysis (receiver operating characteristic) was used. Differences in qualitative parameters in the studied groups of patients were analyzed using the χ2 test, and quantitative ones — using the Mann-Whitney and Kruskal-Wallis tests.RESULTS: Threshold values of the ADC index were determined to reliably differentiate neurogenic tumors rich in Schwann stroma (ganglioneuromas and ganglioneuroblastomas, ADC≥1.25 mm²/s) and neuroblastomas, as well as neuroblastomas without MYCN gene amplification (0.78<ADC <1.25 mm²/s) and with the presence of amplification (ADC≤0.78 mm²/s). In the first case, sensitivity was 0.95, specificity — 0.94; in the second — 0.94 and 0.75, respectively.DISCUSSION: Our data indicate the possibility of separating histological types of neurogenic tumors on the basis of quantitative MRI; the ADC value makes it possible to differentiate ganglioneuromas and ganglioneuroblastomas from neuroblastoma, as well as to distinguish neuroblastoma with the presence of MYCN gene amplification and without this genetic event. Non-invasive quantitative MRI makes it possible to assess the entire tumor volume at the diagnostic stage, and an extremely low ADC value radiogenomic sing for the presence of MYCN gene amplification in neuroblastoma.CONCLUSION: Quantitative MRI with determination of ADC of neurogenic tumors allows not only to separate the histological variants of neurogenic tumors, but also to predict the presence of MYCN gene amplification as the most unfavorable genetic marker of neuroblastomas.