Impact of Variability in Portal Venous Phase Acquisition Timing in Tumor Density Measurement and Treatment Response Assessment: Metastatic Colorectal Cancer as a Paradigm

Laurent Dercle, Lin Lu, Philip Lichtenstein, Hao Yang, Deling Wang, Jianguo Zhu, Feiyun Wu, Hubert Piessevaux, Lawrence H Schwartz, Binsheng Zhao, Laurent Dercle, Lin Lu, Philip Lichtenstein, Hao Yang, Deling Wang, Jianguo Zhu, Feiyun Wu, Hubert Piessevaux, Lawrence H Schwartz, Binsheng Zhao

Abstract

Purpose: New response patterns to anticancer drugs have led tumor size-based response criteria to shift to also include density measurements. Choi criteria, for instance, categorize antiangiogenic therapy response as a decrease in tumor density > 15% at the portal venous phase (PVP). We studied the effect that PVP timing has on measurement of the density of liver metastases (LM) from colorectal cancer (CRC).

Methods: Pretreatment PVP computed tomography images from 291 patients with LM-CRC from the CRYSTAL trial (Cetuximab Combined With Irinotecan in First-Line Therapy for Metastatic Colorectal Cancer; ClinicalTrials.gov identifier: NCT00154102) were included. Four radiologists independently scored the scans' timing according to a three-point scoring system: early, optimal, late PVP. Using this, we developed, by machine learning, a proprietary computer-aided quality-control algorithm to grade PVP timing. The reference standard was a computer-refined consensus. For each patient, we contoured target liver lesions and calculated their mean density.

Results: Contrast-product administration data were not recorded in the digital imaging and communications in medicine headers for injection volume (94%), type (93%), and route (76%). The PVP timing was early, optimal, and late in 52, 194, and 45 patients, respectively. The mean (95% CI) accuracy of the radiologists for detection of optimal PVP timing was 81.7% (78.3 to 85.2) and was outperformed by the 88.6% (84.8 to 92.4) computer accuracy. The mean ± standard deviation of LM-CRC density was 68 ± 15 Hounsfield units (HU) overall and 59.5 ± 14.9 HU, 71.4 ± 14.1 HU, 62.4 ± 12.5 HU at early, optimal, and late PVP timing, respectively. LM-CRC density was thus decreased at nonoptimal PVP timing by 14.8%: 16.7% at early PVP ( P < .001) and 12.6% at late PVP ( P < .001).

Conclusion: Nonoptimal PVP timing should be identified because it significantly decreased tumor density by 14.8%. Our computer-aided quality-control system outperformed the accuracy, reproducibility, and speed of radiologists' visual scoring. PVP-timing scoring could improve the extraction of tumor quantitative imaging biomarkers and the monitoring of anticancer therapy efficacy at the patient and clinical trial levels.