Fracture Risk Assessment Software for Skeletal Metastasis

 描述(申请人提供)：骨骼是转移性癌症的第三大常见部位，近一半的癌症转移到骨。由于新的积极治疗方法，癌症患者的寿命延长，但在骨骼转移部位，高达35%的受影响骨骼在微创后发生骨折，严重影响患者的功能和生活质量。预防骨转移导致的骨折取决于反映肿瘤与宿主骨相互作用的客观标准。虽然对骨转移的机制已经了解很多，但临床医生仍在根据目前公认的不准确的平片和临床症状，对患者的骨折风险和治疗反应进行主观评估。转移性癌症改变了骨骼的材料和几何特性；未能考虑到这两个参数的变化限制了当前骨折预测方法/评分的准确性。由于它是贯穿骨骼的最薄弱的部分，决定了整个结构的承载能力，我们开发了一个软件包，称为基于计算机断层扫描的刚性分析(CTRA)，用于计算包含肿瘤性病变的骨骼的最小刚性。这种方法使用受影响骨骼的计算机断层扫描(CT)图像来计算其结构刚性，作为一种反映肿瘤过程中骨组织材料和几何形状变化的机械测试。这种方法在估计负荷能力和预测病理性骨折方面的准确性已经在体外、临床前和体内研究中得到验证，包括最近发表在临床癌症研究上的一篇论文。这项研究由肌肉骨骼肿瘤协会资助，该协会支持该软件的商业化(请参阅支持函)。该软件目前正在波士顿儿童医院用于评估良性病变儿童的骨折风险。在过去的两年中，CHB使用CTRA对50多个病例进行了分析，分析结果已提交给保险公司并得到保险公司的补偿。此外，商业化产品还可用于其他领域，如脆性骨折预测、代谢和发育性肌肉骨骼疾病以及骨折不愈合。对于这一直接的第二阶段SBIR提交，我们建议将该软件平台商业化，使临床医生可以使用CTRA分析。这项工作包括建立一个标准的附件骨骼数据库，作为解释患者数据的参考；并进一步完善我们现有的轴向、弯曲和扭转刚度指数的骨折阈值，为我们的分析方法提供额外的敏感性。因此，这项研究的目的是：为附件骨骼建立一个标准化的结构刚性数据库，作为解释患者特定数据的参考；优化刚性指数降低的阈值，以最大限度地敏感性和特异性确定骨折与非骨折；以及开发CTRA软件来简化和优化CTRA分析程序。

 DESCRIPTION (provided by applicant): The skeleton is the third most common site of metastatic cancer, and nearly half of all cancers metastasize to bone. As a result of new and aggressive treatments, cancer patients are living longer, but at sites of skeletal metastasis, fractures occur in up to 35% of affected bones after minimal trauma, significantly impacting patient function and quality of life. Preventing fractures due to skeletal metastases depends on objective criteria that reflect the interaction of the tumor with the host bone. While much has been learned about the mechanisms of skeletal metastasis, clinicians continue to make subjective assessments regarding a patient's fracture risk and response to treatment based on plain radiographs and clinical symptoms now recognized to be inaccurate. Metastatic cancer alters both the material and geometric properties of the bone; failure to account for changes in both of these parameters limits the accuracy of current fracture prediction methodologies/scores. As it is the weakest segment through the bone that dictates the load capacity of the entire structure, we have developed a software package, called Computed Tomography-based Rigidity Analysis (CTRA), to calculate the minimal rigidity of a bone containing a neoplastic lesion. This method uses computed tomography (CT) images of the affected bone to calculate its structural rigidity, as a mechanical assay representing changes in bone tissue material and geometry induced by the neoplastic process. The accuracy of this approach for estimating load capacity and predicating pathologic fractures has been validated in ex-vivo, pre- clinical, and in-vivo studies, including a recent paper published in Clinical Cancer Research. This study was funded by the Musculoskeletal Tumor Society, which supports the commercialization of the software (please see letter of support).The software is currently being using at Boston Children's Hospital to assess fracture risk in children with benign lesions. Over the past 2 years, over 50 cases have been analyzed using CTRA at CHB, and the analysis results have been submitted to and reimbursed by insurance companies. Moreover, the commercialized product can be used in other areas such as fragility fracture prediction, metabolic and developmental musculoskeletal diseases and fracture non-unions. For this Direct Phase II SBIR submission, we propose to commercialize the software platform to make CTRA analysis available to clinicians. This work involves the establishment of a normative database of appendicular skeleton as a reference to interpret patient data; and to further refine our existing fracture threshold values for axial, bending and torsional rigidity indices to provide additional sensitivity for our analysis method. Therefore, the aims of the study are to: Develop a normative structural rigidity database for the appendicular skeleton as a reference for interpreting patient specific data; Optimize the threshold for reduction in rigidity indices that will determine fracturs from non-fractures with maximal sensitivity and specificity; and Develop the CTRA software to streamline and optimize the CTRA analysis procedure.