There are growing expectations that imaging biomarkers for tumor therapeutic drug response assessment will speed up preclinical testing of anticancer drugs in rodent models. The only imaging biomarker presently approved by the U.S. Food and Drug Administration is tumor size measurement based on either World Health Organization (WHO) criteria or Response Evaluation Criteria in Solid Tumors (RECIST). Frequently, preclinical data are accumulated from multiple research centers on multiple continents using scanners from different manufacturers and sometimes even using different imaging modalities. Very expensive cancer drug response studies can be compromised by inadequate controls to assure precision and accuracy of tumor size measurements. This project was undertaken to develop standardized quality assurance (QA) procedures using a multimodality preclinical tumor response phantom to validate the accuracy of tumor size measurements based on WHO criteria, RECIST, or global tumor volume criteria for evaluation of cytostatic drugs.Methods:
A tumor response phantom containing five low contrast test objects designed to simulate animal tumor models was made of tissue-mimicking materials. Imaging of the phantom was performed using three modalities in two institutions to evaluate size measurement of tumor-simulating test objects.Results:
Evaluation of tumormeasurements from the three commonly used imaging devices in two different institutions for monitoring tumor size changes showed that a single phantom for multiple modalities was feasible. The tumor response phantom validated precision and accuracy of tumor response data input from ultrasound, computed tomography, and/or magnetic resonance imaging devices.Conclusions:
Measurement results show that the standardized QA procedures using the tumor response phantom can provide a rationale check of data that excludes input from poorly maintained instruments, inadequate measurement protocols, or random operator error that frequently introduce unacceptable variability or systematic error in multiple institutions trials.
The authors are grateful to Dr. Kelly Ambler, Dr. Natalie Serkova, Mark Brown, and Kendra Hasebroock in University of Colorado Denver for help in acquiring U.S., CT, and MR images, and measurements of the multimodality phantom. The authors are also grateful to Dr. Ernest L. Madsen at the University of Wisconsin Madison and Cristel Baiu at Gammex Inc. for providing advice on making TM materials, and Dr. Malcolm David Murray at UTHSCSA for providing a good idea on making the multimodality tumor response phantom.
II.A.1. Design of phantom
II.A.2. Phantom materials
II.A.3. Construction of phantom
II.B. Evaluation of size measurement
II.B.1. Evaluation in UTHSCSA
II.B.2. Evaluation in UC Denver
II.C. Development of QA worksheet for tumor size measurement
III.A.1. Evaluation of size measurement
III.B. RECIST, WHO, and volume analysis
IV.A.1. Phantom materials and contrast
IV.A.2. Phantom dehydration
IV.A.3. Phantom size
IV.B. Size measurement
IV.B.1. Size measurement in UTHSCSA
IV.B.2. Size measurement in UC Denver
IV.C. RECIST, WHO and volume analysis in UTHSCSA and UC Denver
IV.C.1. RECIST and WHO analysis
IV.C.2. Volume analysis
IV.D. Feasibility of this study and future work
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