A Multi-atlas Approach for Active Bone Marrow Sparing Radiation Therapy: Implementation in the NRG-GY006 Trial

Abstract

Purpose: Sparing active bone marrow (ABM) can reduce acute hematologic toxicity in patients undergoing chemoradiotherapy for cervical cancer, but ABM segmentation based on positron emission tomography/computed tomography (PET/CT) is costly. We sought to develop an atlas-based ABM segmentation method for implementation in a prospective clinical trial.

Methods and materials: A multiatlas was built on a training set of 144 patients and validated in 32 patients from the NRG-GY006 clinical trial. ABM for individual patients was defined as the subvolume of pelvic bone greater than the individual mean standardized uptake value on registered ¹⁸F-fluorodeoxyglucose PET/CT images. Atlas-based and custom ABM segmentations were compared using the Dice similarity coefficient and mean distance to agreement and used to generate ABM-sparing intensity modulated radiation therapy plans. Dose-volume metrics and normal tissue complication probabilities of the two approaches were compared using linear regression.

Results: Atlas-based ABM volumes (mean [standard deviation], 548.4 [88.3] cm³) were slightly larger than custom ABM volumes (535.1 [93.2] cm³), with a Dice similarity coefficient of 0.73. Total pelvic bone marrow V₂₀ and D_mean were systematically higher and custom ABM V₁₀ was systematically lower with custom-based plans (slope: 1.021 [95% confidence interval (CI), 1.005-1.037], 1.014 [95% CI, 1.006-1.022], and 0.98 [95% CI, 0.97-0.99], respectively). We found no significant differences between atlas-based and custom-based plans in bowel, rectum, bladder, femoral heads, or target dose-volume metrics.

Conclusions: Atlas-based ABM segmentation can reduce pelvic bone marrow dose while achieving comparable target and other normal tissue dosimetry. This approach may allow ABM sparing in settings where PET/CT is unavailable.

Fig. 1.

Flow diagram showing exclusion criteria applied to the training sample used to construct and validate an active bone marrow atlas. Abbreviations: CT = computed tomography; PET = positron emission tomography.

Fig. 2.

Canonical distribution of metabolically “active” bone marrow subregions in a patient with cervical cancer, with “active” marrow defined either by custom (A) positron emission tomography–based segmentation or (B) multiatlas-based segmentation.

Fig. 3.

Averaged dose-volume histogram (DVH) comparison for custom plans designed to spare active bone marrow (ABM) defined by positron emission tomography (PET) (dashed lines) versus ABM-sparing plans based on the atlas (solid lines), indicating similar results using either approach. Note the DVHs for ABM (left) depict results for the ABM that is defined by PET, indicating that atlas-based plans, on average, result in good sparing of the custom ABM. Abbreviation: PTV = planning target volume.

Fig. 4.

The custom-based active bone marrow (purple) may include outliers, such as seen in the left femur in this patient. The atlas-based method (blue), by virtue of averaging, removes outliers, consequently avoiding unnecessarily restrictive planning constraints that potentially compromise sparing of the overall pelvic bone volume.