КОСТНАЯ И ВНЕСКЕЛЕТНАЯ САРКОМА ЮИНГА: СРАВНИТЕЛЬНАЯ ХАРАКТЕРИСТИКА ОСОБЕННОСТЕЙ ТЕЧЕНИЯ И ИСХОДОВ ЗАБОЛЕВАНИЯ (ОПЫТ НИИ ДЕТСКОЙ ОНКОЛОГИИ И ГЕМАТОЛОГИИ им. Л.А. ДУРНОВА)

Abstract

Ewing's sarcoma (ES) is a highly malignant tumor of children and adolescents that affects bones and soft tissues with the same frequency. The origins of ES are the subject to many discussions. Differential diagnosis is complicated and requires a full range of immunohistochemical and molecular genetic studies. The prognostic value for extraskeletal and bone ES under current chemotherapy protocols is unknown and requires further analysis. The purposes of this research were a comparative analysis of clinical characteristics, therapeutic approaches and outcomes of the disease in patients with extraskeletal and bone localizations of ES. Materials and methods used: a single-center retrospective cohort study was conducted, which included 330 patients (237 (71.8%) boys/93 (28.2%) girls) aged 0 to 18 y/o (median 11 [7; 14] y/o) with confirmed diagnosis of ES who received treatment in 2008-2022, of which 280 (84.85%) with primary bone localization (group of bone ES - BES), and 50 (15.15%) with soft tissue localization (group of extraskeletal ES - ESES). Comparative analysis of survival rates for primary tumor localization in the area of bones and soft tissues was performed. The median follow-up time for all patients was 35.5 [18.2; 68.5] months, 37.0 [18.0; 71.0] months with BES, and 29.5 [16.8; 65.5] months with ESES. All patients received treatment according to the protocols adopted at the Research Institute of Pediatric Oncology and Hematology named after Academician L.A. Durnov with the N.N. Blokhin Russian Cancer Research Center (Moscow, Russia): MMES-99, ES-2017. Overall survival (OS) was calculated with the Kaplan-Meier estimator. Results: the selected groups differed statistically significantly by gender (74% of boys in the BES group, and 60% of boys the ESES group, p=0.035) and age (10.5 [8; 15] years in the BES group, and 8.5 [4; 12] y/o in the ESES group, p=0.001). BES was diagnosed statistically significantly more often in older age groups than ESES (p=0.004). Compared with BES, in ESES the tumor was statistically significantly more often located in the region of the axial skeleton and visceral organs (24.0% vs. 56%, p<0.001). Disseminated form of the disease in the BES group was recorded in 110 (39.3%) patients, and in 15 (30.0%) in the ESES group. Authors did not find statistically significant differences in overall 5-year OS for localized forms of BES and ESES (79% and 78.5%, respectively), the median OS in these groups was not reached. The OS of patients with disseminated stages of BES and ESES was statistically significantly lower than in the group of localized forms. At the same time, the 5-year OS was 41.2% and 40.6%, the median OS was 46.9 and 28.4 months (p=0.001, respectively). Differences in 5-year progression-free survival (PFS) for localized forms were 71.6% for BES and 75.6% for ESES (p=0.001), for disseminated forms - 32.4% vs. 44.9% (p=0.036, respectively). In the disseminated stage of BES, progression/relapse was detected in 50% of cases after 21.1 months, and after 20.3 months for ESES. Conclusions: Authors have identified the following unfavorable prognostic factors. As for BES these were: older age, disease stage, primary tumor volume over 200 cm3 and length over 8 cm, radiation therapy in the treatment program or combined treatment. As for ESES, the unfavorable PFS factors were the stage of the disease, the volume of the primary tumor and the process dissemination. In this regard additional analysis of key genomic characteristics is required in order to further determine the risk group stratification and prognosis.