Influence of Setup Uncertainties: Optimizing Clinical Target Volume-to-planning Target Volume Margins in Total Marrow...

Total Marrow and Lymphoid Irradiation (TMLI) is an advanced alternative to traditional Total Body Irradiation, aiming to reduce toxicities while maintaining treatment efficacy.

This study evaluates setup uncertainties and their impact on clinical target volume (CTV) to planning target volume (PTV) in patients undergoing Total Marrow and Lymphoid Irradiation using a linear accelerator-based volumetric modulated arc therapy (VMAT).

Setup deviations were analyzed for 15 patients using cone-beam CT image guidance across multiple isocenters. Systematic and random errors were computed for each anatomical region, and CTV-to-PTV margins were estimated using ICRU 62, Stroom's, and van Herk's formulas. Average shifts and 3D displacement vectors were quantified across the skull, thorax, abdomen, pelvis, and extremities.

Setup uncertainties were site dependent, with the thorax showing the largest systematic error (3.9 mm) and the leg the largest random error (2.6 mm). The mean 3D displacement vector ranged from 3.3 mm (pelvis) to 6.8 mm (leg). Based on systematic and random error analysis, differential PTV margins of 3 mm, for skull, 5 mm for thorax, abdomen and pelvis, and 10 mm for extremities were determined to maintain adequate dose coverage.

VMAT-based TMLI requires region-specific margins to account for setup uncertainties, particularly in extremities. Image-guided adaptive strategies can optimize target coverage while minimizing normal tissue exposure. Precise image guidance and tailored margins are crucial for maximizing treatment efficacy and minimizing side effects in TMLI.