MYCN-amplified stage 1 neuroblastoma: results of a retrospective multicenter study

Neuroblastoma (NB) is considered as a model of risk-adapted therapy for malignant neoplasms in children. The use of a combination of prognostic factors, such as age, stage of the tumor process, histological variant, and molecular genetic profile of a tumor, makes it possible to identify three risk groups characterized by different intensity of therapy and prognosis. However, the stratification of patients with MYCN-amplified stage 1 NB into a certain risk group and, consequently, the choice of therapeutic tactics for patients in this group vary significantly in the protocols of large cooperative NB study groups. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation. Clinical data were collected on patients with stage 1 NB according to the INSS system and the presence of the MYCN gene amplification, who received treatment in the period from 2013 to 2021, by sending requests and questionnaires to 77 specialized (oncological) medical institutions in the Russian Federation. At the time of information collection, we made an assessement of the extent of therapy and the status of the disease. A total of 7 patients were registered: 3 boys and 4 girls. The median age at diagnosis was 4.8 months (range 1.5–53.7 months). The primary tumor in all patients was located in the adrenal gland. In 4/7 (57.2%) patients, the 1p deletion was detected, in 6/7 (85.7%) patients who underwent an assessment of the 11q status, no deletion was detected. The therapy was carried out according to the modified NB2004 protocol. Induction therapy, high-dose chemotherapy and autologous hematopoietic stem cell transplantation (auto-HSCT) were received by 6/7 (85.7%) patients. Immunotherapy with anti-GD2 monoclonal antibodies was performed in 1 patient (14.2%). At the time of the manuscript preparation, all patients remained alive without events. One patient with severe congenital heart disease (single ventricle, transposition of the great vessels) has not received systemic therapy and is alive without events at the time of the analysis. Patients with MYCN-amplified stage 1 NB included in this study and stratified into the high-risk group according to the NB2004 protocol, had high survival rates without any adverse events during intensive multimodal therapy. However, given the literature data of international cooperative groups on a decrease in the intensity of therapy in this cohort of patients, for example, refusal of auto-HSCT, as well as a high risk of developing long-term side effects of therapy, including secondary malignant tumors, in patients receiving therapy according to protocols for high-risk groups, it is possible to revise the concept of therapy in this category of patients. This requires a complete registration of all cases of NB in the Russian Federation, the implementation of a diagnostic algorithm, including scintigraphy with ¹²³I-metaiodobenzylguanidine, review of imaging data, histology and molecular cytogenetic studies in national/federal oncological institutions. With the accumulation of more representative data, auto-HSCT is likely to be omitted in patients with MYCN-amplified stage 1 NB with the absence of other unfavorable biological markers of the disease.