Purpose: The first clinical biology-guided radiation therapy (BgRT) system – RefleXion ^TM X1 - was installed and commissioned for clinical use at our institution. This study aims at evaluating X1 treatment planning feasibility of complex craniospinal targets for pediatric medulloblastoma patients and comparing plan quality to multi-isocenter linac-based VMAT plans. Methods: Five pediatric patients treated with multi-isocenter craniospinal irradiation (CSI), planned using Eclipse VMAT and delivered using Varian Trilogy C-arm linac, were selected for this retrospective study. All PTV targets had a craniocaudal length<50cm (current X1 TPS limit) and received 36 Gy in 20 fractions. The target volumes and organs-at-risk (OARs) used for VMAT plans were used to generate plans using RefleXion X1. The near maximum dose to PTV (PTV D2%), OARs Dmean and Dmax, and treatment times were collected for analysis. A paired-sample t-test was performed to detect significance at p <0.05. Results: All five RefleXion X1 CSI plans were successfully generated and were clinically acceptable for treatment. PTV D2% was higher for X1 compared to VMAT plans at 41.3 Gy and 39.2 Gy, respectively, (p = 0.08). For the X1 plans, the average Dmean to the bowel, cochleas, heart, kidneys, lungs, and oral cavity were 10.4 Gy, 38.5 Gy, 12.5 Gy, 18.2 Gy, 13.7 Gy, and 16.0 Gy, respectively. The difference was not found to be statistically significant (p>0.05) compared to VMAT plans which showed Dmean to the bowel, heart, kidneys, lungs, and oral cavity at 11.7 Gy, 38.4 Gy, 11.6 Gy, 15.6 Gy, 13.3 Gy, and 15.0 Gy, respectively. The average treatment beam-on time for X1 plans was 16.7 min versus 3.6 min for VMAT plans (p<0.01). However, RefleXion X1 platform enabling one-isocenter treatment and 90 cm long kVCT scan has a potential to decrease the setup/imaging time, and thus the total treatment time compared to multi-isocenter linac-based VMAT where the total treatment time up to 43.5 min was observed. Conclusion: Apart from a higher maximum dose to PTV, X1 plans showed comparable dosimetry to multi-isocenter VMAT plans. Although the average beam-on time with X1 was longer, there is a potential for a more streamlined setup and IGRT using a single-isocenter plans.