Metastatic Cancer to the Spine Noninvasive Prediction of Fracture Risk in Patients with Updated

Purpose: Skeletal metastases affect up to 85% of breast cancer patients by the time of their death. This prospective in vivo study evaluated the diagnostic performance of computed tomography–based structural rigidity analysis (CTRA) to predict vertebral fracture risk in breast cancer patients with skeletal metastasis and in comparison with the current standard of care. Experimental Design: Torso CT scans of 94 women with vertebral metastatic breast cancer were obtained as part of routine screening for lung and liver metastases. The load-bearing capacity (LBC) and axial (EA) and bending (EI) rigidities of vertebrae T8 to L5 were calculated from CT images. The LBC was normalized by patient body mass index (BMI) to account for height and mass variations. Vertebral fracture risk was also calculated using the current radiographic-based criteria based on lesion size and location. The actual occurrence of a new vertebral fracture was assessed radiographically over the ensuing 4 months. Results: Eleven vertebral fractures occurred in 10 patients. The structural parameters EA, EI, LBC, and LBC/BMI were all 100% sensitive and 55%, 53%, 44%, and 70% specific to predict fracture risk, respectively. Although radiographic criteria correctly predicted all fracture cases (100% sensitive), only 48 of the 236 spinal segments that did not have a fracture were correctly predicted not to fracture (20% specific). Conclusions: CTRA, using CT scans as part of routine screening for lung and liver metastasis, is shown to be as sensitive as, and significantly more specific than, the current radiographic criteria for predicting vertebral fracture in breast cancer patients with skeletal metastasis. (Clin Cancer Res 2009;15(24):7676–83) Skeletal metastases occur in 65% of patients with breast cancer due to the overall high incidence and the relatively long clinical course of the disease (1). The spine is the most common site for skeletal metastasis in breast cancer patients (2). Of these patients, 17% to 50% sustain a vertebral fracture, resulting in pain, deformity, loss of mobility, and/or paralysis (3, 4). Although much has been learned about the mechanisms of metastasis of cancer to the spine, little headway has been made in the past 25 years to establish guidelines to estimate fracture risk associated with spinal metastasis or monitor the response of a specific bone defect to treatment (5). Currently, clinicians make subjective assessments about fracture risk on plain radiographs using guidelines now recognized to be inaccurate (6). Systemic treatment with cytotoxic agents, hormone manipulation, bisphosphonates, and/or local treatment with radiation and/or surgical stabilization constitutes the range of therapies available to breast cancer patients with skeletal metastases (7– 10). However, there are no objective methods for selecting which treatment will best reduce the patient's risk for sustaining a pathologic fracture and for monitoring the patient's response to therapy. Our goal is to establish objective criteria for evaluating the load-bearing capacity (LBC) of involved vertebrae that can be used both to monitor changes in the bone structure that reflect the interaction of the tumor with the host bone and to guide treatment for fracture prevention. Anatomic site, lesion type (lytic, blastic, or mixed), size, geometry, presence of pain, patient age, and activity level have all been shown to be predictors of fracture risk in retrospective clinical studies (11–13). However, although pain is the most common presenting symptom of a skeletal metastasis, it is not always present (14), may be unrelated to the metastatic cancer (e.g., degenerative disc disease and facet arthropathy), and is not a reliable indicator of imminent vertebral fracture (15). Skeletal metastases are most often diagnosed using plain radiographs of the spine. Investigators have estimated vertebral Authors' Affiliations: Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Departments of Anesthesia and Orthopaedic Surgery, Boston Children's Hospital, and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts Received 2/20/09; revised 9/14/09; accepted 9/15/09; published OnlineFirst 12/8/09. Grant support: NIH grant CA40211 and Susan Komen Foundation. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Requests for reprints: Brian D. Snyder, Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, RN115, Boston, MA 02215. Phone: 617-667-2940; Fax: 617-667-7175; E-mail: bsnyder@bidmc.harvard. edu. F 2009 American Association for Cancer Research. doi:10.1158/1078-0432.CCR-09-0420 7676 Clin Cancer Res 2009;15(24) December 15, 2009 www.aacrjournals. org American Association for Cancer Research Copyright © 2009 on March 13, 2012 clincancerres.aacrjournals. org Downloaded from Published OnlineFirst December 8, 2009; DOI:10.1158/1078-0432.CCR-09-0420