TU-C-BRA-03: Dose-Mapping to Determine Anatomically Sensitive Bone Marrow Regions

Abstract

Multiple studies have established associations between increased bone marrow (BM) radiation dose and hematologic toxicity, which is an important barrier to optimal delivery of chemoradiotherapy. Generalized linear toxicity models have been validated, using metrics derived from dose-volume histograms (DVHs), but these models are limited by low predictive power. One reason may be that DVH-based metrics disregard spatial information regarding the 3D BM dose distribution. For example, it is known that BM is comprised of subregions of heterogeneous functionality, which cannot be distinguished on traditional computed tomography (CT) simulation scans. BM-sparing radiation techniques could be optimized by specifically sparing functional BM subregions, but the precise location of active BM subregions and relationship between toxicity and radiation dose to these subregions remains unclear. We have analyzed two approaches to identifying critical BM subregions: (1) a “bottom-up” approach, using functional imaging to map hematopoietically active BM, and (2) a “top-down” approach, using deformable image registration and high dimensional data analysis to statistically map BM subregions in which radiation dose is associated with toxicity. An advantage of the latter approach is that if active BM exists in consistent locations within the pelvis, a class solution for active BM-sparing IMRT would be feasible, obviating the need for expensive functional imaging in every patient. Validation of the models and hypotheses underlying both approaches is still needed. This lecture will review the contemporary literature on BM-sparing radiotherapy techniques, particularly functional BM-sparing using the aforementioned approaches. Special attention will be given to toxicity modeling techniques that move beyond DVH-based metrics to capture information about the spatial relationship between BM dose and toxicity. Learning Objectives: 1. Understand techniques used to locate heterogeneously functioning subregions within an organ, particularly bone marrow 2. Understand techniques used to quantify and model relationships between hematologic toxicity and radiation dose to functional bone marrow 3. Critically evaluate strengths and limitations of existing approaches and literature pertaining to this subject matter