Incorporating Intensity Modulated Total Body Irradiation (IMRT-TBI) Into Future Cooperative Group Clinical Trials: An NRG Hematologic Malignancies Working Group-Led Report From the National Clinical Trials Network.

Abstract

Intensity modulated radiation therapy (IMRT) is increasingly used for total body irradiation (TBI) due to its ability to deliver myeloablative doses while sparing radiosensitive organs. To enable consistent evaluation in future National Clinical Trials Network (NCTN) studies, the NRG Hematologic Malignancies Working Group (HMWG) convened IMRT-TBI experts and NCTN leaders to develop consensus recommendations for standardized multi-institutional implementation. A 47-question survey was distributed to NRG institutions utilizing total body irradiation treated with intensity modulated radiation therapy (IMRT-TBI) to characterize current planning and delivery practices. Responses were analyzed for commonalities and variations. A multidisciplinary working group reviewed survey findings, developed consensus-based technical and clinical recommendations, and created a standardized template for IMRT-TBI integration into NCTN protocols. Topics included simulation, contouring, planning, organ-at-risk (OAR) constraints, quality assurance (QA), image guided radiation therapy, commissioning, credentialing, and safeguards for clinical trial conduct. Eight institutions with collective experience treating more than 750 patients with IMRT-TBI responded. Most centers used volumetric modulated arc therapy (VMAT) to the upper body with anteroposterior/posteroanterior fields to the lower body, 3 to 9 isocenters, lower dose rates for lung fields (100-200 MU/min), and no physical bolus. Common OAR constraints included lungs mean dose <8 Gy, kidneys mean dose <6 to 8 Gy, and lenses maximum dose <90% of prescription. All respondents used auto-segmentation; 50% used auto-planning. QA practices varied, but patient-specific QA passing rates were high (>95% with 3%/2 mm gamma). Consensus recommendations for clinical trial use were established, including standardized planning target volume definitions, OAR sparing goals, dosimetric constraints, QA requirements, and credentialing processes. IMRT-TBI offers the potential for reduced toxicity and improved dose precision compared with total body irradiation treated with a 2-dimensional technique, but its complexity requires careful standardization in multi-institutional trials. The NRG HMWG and collaborating NCTN experts developed the consensus-based technical and clinical framework for incorporating IMRT-TBI into cooperative group protocols. Adoption of these recommendations will facilitate consistent implementation and enable rigorous evaluation of outcomes.