P10.17.B IMPACT OF SOMATIC TP53 MUTATION ON SURVIVAL OF PATIENTS WITH MEDULLOBLASTOMA OF THE WNT MOLECULAR GROUP

Abstract RELEVANCE The WNT molecular group (MB-WNT) constitutes only 10% of medulloblastoma cases. This group is characterized by a favorable prognosis. Considering the aggressive schemes used in the treatment for medulloblastoma, it seems appropriate to attempt a reduction of the therapy intensity for prognostically favorable tumors. MATERIAL AND METHODS From 1993 to 2021, a total of 85patients with MB-WNT aged under 1 were included in this study. After tumor resection, these patients got radiotherapy (CSI with a boost on the posterior fossa and parallel chemotherapy) and 6 to 8 chemotherapy courses according to the HIT-MED protocol. The presence of CTNNB1, АРС and TP53 mutations in the tumor tissue was evaluated using polymerase chain reaction, Sanger’s method. The median patients’ age at diagnosis was 10 years old. All the patients had classic variant of medulloblastoma. 18 patients had metastases at diagnosis and 32 had a residual tumor; 6 patients had stage M1, 2 had stage M2 and 10had stage M3. Somatic mutations in gene TP53 were found in 10 patients; in gene CTNNB1 in 79 patients; in gene APC in 5patients. Monosomy 6 was found in 76 children. The risk group distribution was as follows: low risk 58.8%, standard risk 15.3%, high risk 25.9%. Among the patients, 28 got reduced CSI (23.4 Gy) with a boost on the posterior fossa. The number of the cycles of postradiation maintenance chemotherapy was reduced (less than 8) in 24 patients. RESULTS 774 patients were alive by the moment of analysis, 11 patients had died, 6 patients had a tumor recurrence; among the latter, five died of progressive disease, and one patient is alive in the second remission. The 10-year PFS was 0.92,the 10-year OS was 0.86. The median OS was 112 months. The PFS was statistically higher for the absence of somatic ТР53 mutations compared to their presence in the tumor tissue (0.98 and 0.50, p=0.00000); for stage М0 compared to М+ (0.97 and 0.74, p=0.00437); for total tumor removal compared to the presence of a residual tumor (0.96 and 0.85, p=0.03090); for low-risk patients compared to standard- and high-risk groups (0.98, 0.92 and 0.78, respectively, Р=0.03579); for females compared to males (0.98 and 0.81, respectively, p=0.02036). OS is statistically significantly higher without somatic mutations in gene ТР53, for females, for patients with a total resection of the primary tumor, without metastases, in the low-risk group. CONCLUSION For patients with MB-WNT, the use of the reduced dose of CSI (23.4 Gy) and the reduced number of chemotherapy cycles (6) may be recommended without somatic mutations in gene ТР53, for female patients, those with stage M0, for patients with a total tumor resection, within the low-risk group. According to univariate and multivariate analysis, the presence of somatic mutations in gene TP53 is determined as the predictor that statistically significantly increases the risk of relapse and/or fatal outcome.