Computer-aided quantitative bone scan assessment of prostate cancer treatment response

Abstract

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.

Analytic Validation of the Automated Bone Scan Index as an Imaging Biomarker to Standardize Quantitative Changes in Bone Scans of Patients with Metastatic Prostate Cancer

“…One of the most serious limitations in the effort to analytically validate an imaging biomarker has been the difficulty in procuring a true analytic standard: histologic confirmation of abnormal hotspots as metastatic lesions. Previous studies have circumvented the issue of the lack of an analytic standard by using a reference interpreter for the bone scan analysis (13). Using a manual assessment as a true analytic benchmark limits the analytic validation to the skills of the reference individual.…”

Dynamic Bone Imaging with99mTc-Labeled Diphosphonates and18F-NaF: Mechanisms and Applications

“…Consequently, even after successful systemic treatment of bone metastases, bone scans are known to improve very slowly, if at all (63). Other notable problems are false-negative results, a flare response leading to worsening of the scan appearance despite a clinical response to therapy, poor interobserver agreement, subjective interpretation, and inability to grade changes in intensity and extent (63,64). Also, certain chemotherapeutic approaches may directly interfere with bone remodeling.…”

“…This index aims to quantify tumor burden as a percentage of the total skeletal mass of a reference man (63). Bone scan index and bone scan index doubling time measurements have been shown to correlate with outcome in clinical trials for castration-resistant prostate cancer (63,64). Computer-aided quantitative intensity normalization and segmentation of bone uptake compared with healthy controls has also been proposed to assess therapy response after cabozantinib treatment (measuring lesion area and numbers as well as radiotracer uptake per lesion) (64).…”

Prognostic Utility of PET in Prostate Cancer

“…Bone scintigraphy is typically analyzed visually. Computer-assisted quantitative assessment (bone scan index) has been attempted which can diminish inter-observer variability and aid with more robust longitudinal comparative studies (65, 66). Bone scan index captures the burden of osseous metastatic disease that has been shown to relate to outcome.…”