Objective The development and evaluation of a computer-aided bone scan analysis technique to quantify changes in tumor burden and assess treatment effects in prostate cancer clinical trials. Methods We have developed and report on a commercial fully automated computer-aided detection system. Using this system, scan images were intensity normalized, then lesions identified and segmented by anatomic region-specific intensity thresholding. Detected lesions were compared against expert markings to assess the accuracy of the computer-aided detection system. The metrics Bone Scan Lesion Area, Bone Scan Lesion Intensity, and Bone Scan Lesion Count were calculated from identified lesions, and their utility in assessing treatment effects was evaluated by analyzing before and after scans from metastatic castration-resistant prostate cancer patients: 10 treated and 10 untreated. In this study, patients were treated with cabozantinib, a MET/VEGF inhibitor resulting in high rates of resolution of bone scan abnormalities. Results Our automated computer-aided detection system identified bone lesion pixels with 94% sensitivity, 89% specificity, and 89% accuracy. Significant differences in changes from baseline were found between treated and untreated groups in all assessed measurements derived by our system. The most significant measure, Bone Scan Lesion Area, showed a median (interquartile range) change from baseline at week 6 of 7.13% (27.61) in the untreated group compared with −73.76% (45.38) in the cabozantinib-treated group (P = 0.0003). Conclusions Our system accurately and objectively identified and quantified metastases in bone scans, allowing for interpatient and intrapatient comparison. It demonstrates potential as an objective measurement of treatment effects, laying the foundation for validation against other clinically relevant outcome measures.

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"Quantitative bone scan lesion area as an early surrogate outcome measure indicative of overall survival in metastatic prostate cancer," J. Med. Imag. 5(1), 011017 (2018), doi: 10.1117/1.JMI.5.1.011017. Abstract. A clinical validation of the bone scan lesion area (BSLA) as a quantitative imaging biomarker was performed in metastatic castration-resistant prostate cancer (mCRPC). BSLA was computed from whole-body bone scintigraphy at baseline and week 12 posttreatment in a cohort of 198 mCRPC subjects (127 treated and 71 placebo) from a clinical trial involving a different drug from the initial biomarker development. BSLA computation involved automated image normalization, lesion segmentation, and summation of the total area of segmented lesions on bone scan AP and PA views as a measure of tumor burden. As a predictive biomarker, treated subjects with baseline BSLA <200 cm 2 had longer survival than those with higher BSLA (HR ¼ 0.4 and p < 0.001). As a surrogate outcome biomarker, subjects were categorized as progressive disease (PD) if the BSLA increased by a prespecified 30% or more from baseline to week 12 and non-PD otherwise. Overall survival rates between PD and non-PD groups were statistically different (HR ¼ 0.64 and p ¼ 0.007). Subjects without PD at week 12 had longer survival than subjects with PD: median 398 days versus 280 days. BSLA has now been demonstrated to be an early surrogate outcome for overall survival in different prostate cancer drug treatments. © The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.