Alpha/beta values in pediatric medulloblastoma: implications for tailored approaches in radiation oncology

Medulloblastoma is the most common malignant pediatric brain tumor, typically treated with normofractionated craniospinal irradiation (CSI) with an additional boost over about 6 weeks in children older than 3 years. This study investigates the sensitivity of pediatric medulloblastoma cell lines to different radiation fractionation schedules. While extensively studied in adult tumors, these ratios remain unknown in pediatric cases due to the rarity of the disease.

Five distinct medulloblastoma cell lines (ONS76, UW228-3, DAOY, D283, D425) were exposed to varying radiation doses and fractionation schemes. In addition, ONS76 and UW228-3 stably overexpressing MYC were analyzed. Alpha/beta values, representing fractionation sensitivity, were quantified using the linear-quadratic model of radiation survival.

The study unveiled elevated alpha/beta ratios across diverse medulloblastoma cell lines, with a weighted mean alpha/beta value of 11.01 Gy (CI: 5.23-16.79 Gy). Neither TP53 status nor the levels of MYC expression influenced fractionated radiosensitivity. Furthermore, differences in alpha/beta values cannot be correlated with molecular subgroups (p = 0.07) or radiosensitivity (SF2).

These in vitro findings strongly recommend normofractionated or hyperfractionated radiotherapy for paediatric medulloblastoma cases due to consistently high alpha/beta values across subgroups. Conversely, hypofractionated radiotherapy is not advisable within a curative approach. This study presents significant potential by enabling the estimation of radiobiological fractionations and dose effects in young, vulnerable patients, highlighting its importance for advancing patient-specific therapeutic strategies.