ID #1154 Is the Brazilian TP53 R337H Variant a Distinct Clinical Entity? Survival Analysis in Choroid Plexus Carcinoma
Jessica Rodrigues, Nasjla Silva, Diana Osorio, Natalia Dassi, Sergio Cavalheiro, Patricia Dastoli, Marcos Costa, Fernanda Lima, Andrea CappellanoAbstract
Background
Choroid plexus carcinoma (CPC) is a rare pediatric brain tumor frequently associated with germline TP53 mutations. In Brazil, the R337H founder variant is particularly prevalent and may influence disease behavior and outcomes.
Methods
A retrospective review was conducted including 21 patients with CPC, between 2004 – 2024, treated at a single center in Brazil.
Results
This study analyzed 21 patients with choroid plexus carcinoma (median age: 1.0 year; 57% male). Tumors were predominantly located in the right lateral ventricle (62%). At diagnosis, 71% of cases were localized and 29% metastatic. Complete surgical resection was achieved in 71% (n = 15). Li-Fraumeni Syndrome (LFS) was confirmed in 71% of the cohort (n = 15); the TP53 R337H variant was the most common 43% (n = 9), while other variants (H179R, R248W, R110C, R158H) were less frequent. Regarding treatment, only three patients received upfront high-dose chemotherapy with autologous stem cell transplantation (AuSCT), while 18 received conventional chemotherapy, primarily the CPT-SIOP-2000 protocol. No patient received radiation at first treatment. For the entire cohort, the 2-year and 5-year Event-Free Survival (EFS) were 45.8% and 12.0%, respectively, while Overall Survival (OS) was 89.7% and 67.6%. In a comparative analysis, R337H carriers (n = 9) exhibited a median OS of 134.3 months and EFS of 19.4 months. In contrast, patients with other TP53 variants (n = 4) achieved 100% 5-year OS and EFS. Although R337H carriers showed a trend toward inferior outcomes, this was not statistically significant (OS p = 0.091; EFS p = 0.352). Among LFS patients who did not undergo upfront AuSCT (n = 13), the 2-year EFS and OS were 50.8% and 91.7%, respectively. Second malignancies occurred in three patients (thymic carcinoma, osteosarcoma, and high-grade glioma).
Conclusions
The TP53 R337H mutation is a distinct driver of CPC in Brazil, showing a tendency for worse prognosis than other TP53 variants. Improving long-term EFS remains a critical challenge.