Active bone marrow–sparing IMRT guided by SPECT/CT functional imaging to reduce hematologic toxicity in pediatric pelvic/craniospinal irradiation: A randomized controlled trial.

75

Background: Pediatric patients receiving pelvic radiotherapy or craniospinal irradiation (CSI) are at high risk for severe hematologic toxicity due to the inevitable irradiation of large bone marrow volumes. This study investigated whether intensity-modulated radiotherapy (IMRT) plans incorporating sparing of functionally active bone marrow (ABM), as defined by ^99mTc-sulfur colloid SPECT/CT, could reduce this toxicity without compromising target coverage. Methods: In this prospective, randomized controlled trial, 20 pediatric patients (aged 5–18 years) scheduled for pelvic radiotherapy or CSI were assigned 1:1 to standard IMRT or ABM-sparing IMRT. All patients underwent baseline SPECT/CT fused with the planning CT. High-activity ABM within the pelvic bones was defined using an individualized threshold (≥40% maximum counts). For the ABM-sparing arm, specific dose-volume constraints (V10<90%, V20<75%, V30<50%, D_mean<22 Gy) were applied as secondary optimization objectives. The primary endpoint was the incidence of grade ≥3 neutropenia during radiotherapy. Results: ABM-sparing IMRT significantly reduced the radiation dose to high-activity ABM (e.g., V20: 64.3% vs. 89.1%, P<0.001) while maintaining target coverage. The incidence of grade ≥3 neutropenia was significantly lower in the ABM-sparing arm (20.0% vs. 70.0%, P=0.041). Hematopoietic recovery was faster (median 4.5 vs. 7.8 weeks, P=0.032), and functional marrow recovery at 12 months assessed by SPECT/CT was superior (83.5% vs. 64.8% uptake recovery, P=0.002) in the ABM-sparing group. Conclusions: SPECT/CT-guided ABM-sparing IMRT is feasible and significantly reduces the incidence of severe neutropenia and accelerates hematopoietic recovery in pediatric patients undergoing pelvic or CSI radiotherapy. These results support the integration of functional bone marrow imaging into treatment planning to mitigate hematologic toxicity.