A pilot study of volume measurement as a method of tumor response evaluation to aid biomarker development

Abstract

Purpose: Tissue biomarker discovery is potentially limited by conventional tumor measurement techniques, which have an uncertain ability to accurately distinguish sensitive and resistant tumors. Semi-automated volumetric measurement of computed tomography imaging has the potential to more accurately capture tumor growth dynamics, allowing for more exact separation of sensitive and resistant tumors and a more accurate comparison of tissue characteristics. Experimental Design: Forty-eight patients with early stage non-small cell lung cancer and clinical characteristics of sensitivity to gefitinib were studied. High-resolution computed tomography was done at baseline and after 3 weeks of gefitinib. Tumors were then resected and molecularly profiled. Unidimensional and volumetric measurements were done using a semiautomated algorithm. Measurement changes were evaluated for their ability to differentiate tumors with and without sensitizing mutations. Results: Forty-four percent of tumors had epidermal growth factor receptor-sensitizing mutations. Receiver operating characteristic curve analysis showed that volumetric measurement had a higher area under the curve than unidimensional measurement for identifying tumors harboring sensitizing mutations (P = 0.009). Tumor volume decrease of >24.9% was the imaging criteria best able to classify tumors with and without sensitizing mutations (sensitivity, 90%; specificity, 89%). Conclusions: Volumetric tumor measurement was better than unidimensional tumor measurement at distinguishing tumors based on presence or absence of a sensitizing mutation. Use of volume-based response assessment for the development of tissue biomarkers could reduce contamination between sensitive and resistant tumor populations, improving our ability to identify meaningful predictors of sensitivity. ©2010 AACR.