CMV Infection degree in Medulloblastoma patients: a novel predictor of survival. A single-center study in Germany.

Introduction: Medulloblastoma represents the most common malignant childhood tumor. Despite multimodal treatment [Surgery, QT/RT) overall survival (OS) remains 60-70% at 5 years. The presence of CMV has been previously reported in medulloblastoma tumor tissue. However, the association between the grade of CMV-infection and survival is still unknown. The objective of our study is to evaluate the correlation between CMV-infection-degree on medulloblastoma survival.

Methods: A retrospective study in medulloblastoma patients treated at the Tübingen University Hospital between 1991-2023 was made. TMA from tumoral tissue FFPE of medulloblastoma patients was analyzed by immunochemistry (IHC) for CMV (IE and LA). CMV infection was classified as a high (more than 25% of tumoral positive cells) and low-grade CMV infection (less than 25%). Bivariate analysis (X2-test) was performed to evaluate the association between medulloblastoma molecular subtypes and clinical data. Univariate and multivariate survival analyses were performed to determine the risk, p< 0.05 was considered statistically significant.

Results: 77 medulloblastoma patients were included. The mean age was 17-years (range0-64). Forty-nine cases were children. 47%(n=33) of samples from first surgery (n=70) were positive for CMV-LA and 49% (n=16) presented a high-grade CMV infection. The mean of PFS was 23 months and the mean OS was 75 months. Mortality rate was 9.1%. Survival analysis reported a significant correlation between positive-CMV and non-WNT/non-SHH compared to other subgroups (WNT, SHH)(p=0.019). High-grade CMV-infection presented a poor OS compared with Low-grade CMV infection (46vs.229 months, p=0.006). Children with CMV-positive and non-WNT/non-SHH group (p=0.055), and subgroup 3 (11 vs.105 months, p=0.384) presented a poor OS compared with CMV-negative. Furthermore, pediatric cases with high-grade CMV-infection presented significantly poor survival in contrast with low-grade CMV infection (26 vs.197 months, p=0.026). A high-grade CMV infection was also a significant independent risk factor in COX analysis (HR=8.983,CI95% 1.245-64.815,p=0.029).

Conclusion : This study represents the first survival analysis in medulloblastoma patients in relation to CMV-infection-degree. Medulloblastoma cases with a high-grade of CMV-infection presented a significantly poor survival. These results could represent a new therapeutic strategy for these patients.