Experience of like-SJMB03 protocolin treatment of children with medulloblastomain the age group over 3 years:results of an intercenter pilot study
Authors: Levashov Andrey  S. , Zagidullina Svetlana R. , Valiev Timur T. , Stroganova Anna M. , Khochenkov Dmitry A. , Grigorenko Vasiliy  A. , Mikhaylova Elena V. , Tyurina Elizaveta V. , Ryzhova Marina V. , Horielyshev Serhii K. , Kadyrov Shavkat  U. , Polyakov Vladimir G. 
Published: April 2024

Background. The experience of using the like-SJMB03 therapeutic program is presented. The aim of this study was to assess the potential possibility of reducing the dose of craniospinal and local radiation therapy in the standard and high-risk group patients, and to identify clinical, therapeutic, morphological and molecular-biological factors that determine disease prognosis.
Materials and methods. From 2008 till 2016 years 48 patients with newly diagnosed medulloblastoma were included in the study. In most cases (85%), localization of the primary tumor site was presented by a lesion of the cerebellar vermis with spread into the 4-th ventricle cavity. Gross total or near gross total resection of the primary tumor focus (R0 status) was achieved in 32 (66.7%) cases. The presence of a metastatic disease was established in 15 (31.2%) patients. Molecular biological characteristics of tumor samples were assessed using fluorescent hybridization in situ (FISH), Sanger PCR sequencing, and Illumina Infinium Human Methylation 450/850K BeadChip. Risk group stratification was according to SJMB03 (standard risk group was defined as: R0, M0 status; high-risk group: R1M0 or R0/1M+). A distinctive feature of this protocol was a reduction of the craniospinal irradiation dose down to 36 Gy for patients with M2/M3 status (without additional irradiation of metastatic foci) and the local irradiation dose down to 54 Gy (regardless of R status).
Results. In the standard risk group (R0M0), 5-year and 10-year EFS were 84.0±7.3% and 67.2±9.6%, 5-year and 10-year OS were 92.0±5.4% and 76.4±9.9%, in the high-risk group (R1M0): 5-year and 10-year EFS – 62.5±17.1% and 62.5±17.1%, 5-year and 10-year OS – 75.0±15.3% and 62.5±17.1%, in the high-risk group (R0/1M+): 5-year and 10-year EFS – 33.3±12.2% and 33.3±12.2%, 5-year and 10-year OS – 60.0±12.6% and 33.3±12.2%. Structure of events was presented by 15 disease recurrences (7 localized – 2 early, 5 late; 8 disseminated – 3 early, 5 late), 2 cases of disease progression, 2 cases of secondary tumors (in the first – osteosarcoma, in the second – glioblastoma) and 2 episodes of fatal septic complications. Most of the events were found in patients with a Group 4 tumor. Two peaks of the events were established in standard risk group (the first peak was within 2 years after the end of treatment program, mainly in the age group of 8 years and older, the second peak was within 3 years after the fifth year of observation, predominantly in the group from 3 to 7 years). CSI dose reduction down to 36 Gy for patients with M2/M3 status (without additional irradiation of metastatic foci) in the high-risk group led to a dramatic decrease of 5-year EFS. There was a trend towards a decrease in 5-year EFS and OS in patients aged 8 years and older, as well as in the presence of the C-MYC, N-MYC genes amplification, isochromosome 17q in tumor cells.
Conclusion. Despite the accumulated experience, it is necessary to continue studying the relationship between age groups and the molecular biology of tumor cells in medulloblastoma.