Potential for Early Fracture Risk Assessment in Patients with Metastatic Bone Disease using Parametric Response Mapping of CT Images.

Benjamin A Hoff,Corrie Yablon,Brian D Ross,Gary D Luker,Michael Toole,Craig J Galbán,Catherine Van Poznak

doi:10.18383/j.tom.2015.00154

Benjamin A Hoff, Corrie Yablon + Show 5 more

Open Access

https://doi.org/10.18383/j.tom.2015.00154

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Abstract

Pathologic vertebral compression fractures (PVCFs) cause significant morbidity in patients with metastatic bone disease. Limitations in existing clinical biomarkers leave clinicians without reliable metrics for predicting PVCF, thus impeding efforts to prevent this severe complication. To establish the feasibility of a new method for defining the risk of a PVCF, we retrospectively analyzed serial computed tomography (CT) scans from 5 breast cancer patients using parametric response mapping (PRM) to quantify dynamic bone miniral density (BMD) changes that preceded an event. Vertebrae segmented from each scan were registered to the same spatial frame and voxel classification was accomplished using a predetermined threshold of change in Hounsfield units (HU), resulting in relative volumes of increased (PRMHU+), decreased (PRMHU−), or unchanged (PRMHU0) attenuation. A total of 7 PVCFs were compared to undiseased vertebrae in each patient serving as controls. A receiver operator curve (ROC) analysis identified optimal imaging times for group stratification. BMD changes were apparent by an elevated PRMHU+ as early as 1 year before fracture. ROC analysis showed poor performance of PRMHU− in stratifying PVCFs versus controls. As early as 6 months before PVCF, PRMHU+ was significantly larger (12.9 ± 11.6%) than control vertebrae (2.3 ± 2.5%), with an area under the curve of 0.918 from an ROC analysis. Mean HU changes were also significant between PVCF (26.8 ± 26.9%) and control (−2.2 ± 22.0%) over the same period. A PRM analysis of BMD changes using standard CT imaging was sensitive for spatially resolving changes that preceded structural failure in these patients.

Highlights

Bone metastases occur in approximately 70% of patients with metastatic breast cancer, and bone is the most common site of metastasis for patients with estrogen receptor-positive (ERϩ) disease [1]
parametric response mapping (PRM) for Predicting Fracture Longitudinal monitoring of bone density changes relative to the first available scan using PRM was performed using ␰ ϭ 100 Hounsfield units (HU) to reveal localized changes in bone miniral density (BMD) and to quantify dynamic changes in vertebral structure caused by metastatic disease (Figure 1)
PRM revealed temporal changes in BMD localized around the tumor mass beginning between 12 and 24 months from when computed tomography (CT) scans were initiated

Summary

Introduction

Bone metastases occur in approximately 70% of patients with metastatic breast cancer, and bone is the most common site of metastasis for patients with estrogen receptor-positive (ERϩ) disease [1]. Without bone-directed therapies, the estimated yearly incidence of skeletal-related events (SREs) is 3.5 [3], with a median incidence of 1.3 for pathologic vertebral compression fractures (PVCFs) [4]. Breast cancer metastases to vertebral bodies present devastating complications, including vertebral collapse with spinal cord compression [5,6,7]. Therapies for breast cancer metastases to vertebrae and other bones cost an estimated $4.2 billion in 1998 US dollars, emphasizing the tremendous burden to society and potential impact of new biomarkers for impending pathologic vertebral compression fractures [9]

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