Pitfalls in RECIST Data Extraction for Clinical Trials: Beyond the Basics

Abstract

Response Evaluation Criteria in Solid Tumors (RECIST) is a standardized methodology for determining therapeutic response to anticancer therapy using changes in lesion appearance on imaging studies. Many radiologists are now using RECIST in their routine clinical workflow, as part of consultative arrangements, or within dedicated imaging core laboratories. Although basic RECIST methodology is well described in published articles and online resources, inexperienced readers may encounter difficulties with certain nuances and subtleties of RECIST. This article illustrates a set of pitfalls in RECIST assessment considered to be "beyond the basics." These pitfalls were uncovered during a quality improvement review of a recently established cancer imaging core laboratory staffed by radiologists with limited prior RECIST experience. Pitfalls are presented in four categories: (1) baseline selection of lesions, (2) reassessment of target lesions, (3) reassessment of nontarget lesions, and (4) identification of new lesions. Educational and operational strategies for addressing these pitfalls are suggested. Attention to these pitfalls and strategies may improve the overall quality of RECIST assessments performed by radiologists.

Keywords: Oncology; RECIST; antitumor efficacy; solid malignancies; tumor response assessment.

Figure 1

Selection of a target lesion when not unequivocally a metastasis (61-year-old female with breast cancer). Contrast-enhanced computed tomography at baseline (a) depicts a low-attenuation lesion in the right breast that was designated as a target lesion, yet represented postsurgical granulation tissue/scarring rather than a metastasis. Lesion shrinkage on 8-week (time point #2) follow-up imaging (b) therefore represented a false-positive “response.”

Figure 2

Inappropriate selection of a target lesion from within a radiation field (53-year-old female with non-small cell lung cancer). Baseline contrast-enhanced computed tomography of the chest viewed at soft tissue window settings (a) reveals a lesion in the left lung that was designated as a target lesion. However, the same slice viewed at lung window settings (b) demonstrates surrounding linear parenchymal fibrosis characteristic of previous radiation. The previous radiation would disqualify this lesion as a target lesion, unless unequivocal progression after radiation had been previously demonstrated.

Figure 3

Lesion remeasurement in a different phase of contrast than baseline (50-year-old female with breast cancer). Baseline contrast-enhanced computed tomography of the abdomen acquired in the portal venous phase (a) demonstrates an 18 mm metastasis in the right hemi-liver. Portal venous phase computed tomography at 8-week (time point #2) follow-up imaging (b) shows that lesion size has decreased to 8 mm. At 16 weeks (time point #3), the lesion was incorrectly evaluated in the arterial phase (c), leading to a measurement of 14 mm and a false assessment of progressive disease. Reevaluation in the portal venous phase (d) yielded a measurement of 6 mm.

Figure 4

Failure to change measurement axis with changes in lesion orientation (51-year-old male with metastatic adenoid cystic carcinoma of the tongue base). Baseline contrast-enhanced computed tomography of the chest viewed at lung window settings (a) demonstrates a mass in the right lung, correctly measured along its axis. At 8-week (time point #2) follow-up imaging (b), the original measurement axis was incorrectly maintained, resulting in the underestimation of true lesion size. Shifting the measurement to the new long axis (c) correctly captures the interval lesion growth.

Figure 5

Incorrect assignment of progressive disease for a nontarget lesion (60-year-old female with breast cancer). Contrast-enhanced computed tomography of the chest viewed at bone window settings demonstrates a vertebral body metastasis becoming more sclerotic at baseline (a), 8 weeks (time point #1) (b), and 16 weeks (time point #2) (c). Because this could represent a treatment response rather than worsening disease, it would be inappropriate to assign progressive disease to this lesion.

Figure 6

Equivocal progressive disease for a nontarget lesion (60-year-old female with non-small cell lung cancer). Contrast-enhanced computed tomography of the chest reveals a cluster of left subpectoral lymph nodes that are slowly growing over time (a–c). According to Response Evaluation Criteria in Solid Tumors, an assignment of progressive disease for these nodes must be considered with reference to overall disease burden on the rest of the scan.

Figure 7

Comparison to the incorrect prior scan (46-year-old female with non-small cell lung cancer). Baseline contrast-enhanced computed tomography of the chest viewed at lung window settings (a) reveals a small pleural-parenchymal nodule at the left lung apex. The lesion steadily grew at successive follow-up time points (b, c) but was repeatedly designated as stable because comparisons were made to the most recent prior. The worsening disease is more evident when comparison is made to the baseline scan. (Measurements provided for reference.)

Figure 8

Premature assessment of new disease before it is unequivocal (79-year-old male with metastatic melanoma). Baseline contrast-enhanced computed tomography of the chest viewed at lung windows (a) reveals no suspicious finding. At follow-up imaging (b), there is a small right lower lobe pulmonary nodule (arrow). Given only these two images, it is unclear whether the nodule is a new metastasis or a lesion that was present at baseline and not visualized because of slice placement. As such, this lesion should not yet be designated as progressive disease, but rather flagged for close attention at the next time point. (On subsequent imaging, not shown, the lesion did continue to grow; a designation of progressive disease was therefore applied retroactively to the time point at which the nodule was first visualized.)

Figure 9

Standard CISL tumor measurement form for Response Evaluation Criteria in Solid Tumor data extractions.