Quantification of Osteosarcoma Mineralization on Plain Radiographs - Novel Software Applications to Assess Response to Chemotherapy

摘要

Osteosarcoma is the most common primary malignant bone tumor in children. Patient survival with osteosarcoma isheavily influenced by the response to chemotherapy, measured by tumor necrosis upon histological analysis.Unfortunately, response is not measurable until the time of surgery and therefore modifications to chemotherapyprotocol are only made after several weeks of treatment and surgery. Osteosarcoma tumors often demonstrateincreased mineralization following the onset of chemotherapy. Furthermore, it has been hypothesized that thismineralization—apparent on radiographs—may correlate with chemotherapy response, however, this has not beendemonstrated with qualitative visual evaluation. The ability to non-invasively measure a patient’s response tochemotherapy using plain radiographs, which is currently included in the normal clinical workflow, would guide themedical oncologists to tailor treatment for patients with osteosarcoma. After obtaining appropriate multi-centerinstitutional review board approvals, we identified 31 patients that possess a pair of pre- and post-chemotherapyradiograph along with the necrosis measure. The images were digitized scans of physical radiographs between 1999and 2013. Software was designed to measure the signal intensities in the tumor, a region of the soft tissue, air, andhealthy bone. The tumor signals were normalized based on the random combination of air, soft tissue or bone, bysubtraction or division. The differences in tumor signal between pre- and post-image were plotted against the percentnecrosis determined by histological analysis. Different combinations of the normalization methods were comparedbased on the slope, coefficient of determination (R~2) and Pearson correlation coefficient (ρ).