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Pitfalls in RECIST Data Extraction for Clinical Trials

Posted May 31, 2015 Updated Apr 10, 2023
By Richard G. Abramson MD , Carrie R. McGhee RT(R)(CT) , Nikita Lakomkin , Carlos L. Arteaga MD
10 min read

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.

The Response Evaluation Criteria in Solid Tumors (RECIST) have become broadly accepted by the oncology community, industry sponsors, and regulatory bodies for assessing the therapeutic efficacy of new anticancer agents. Most clinical trials for solid malignancies use RECIST for response assessment. RECIST guidelines, maintained by the European Organization for Research and Treatment of Cancer (EORTC), specify how to identify and measure lesions, how to evaluate disease burden at follow-up imaging, and how to place patients into response categories at successive time points during a trial. Trial-level composite end points derived from RECIST, including overall response rate, time to progression, and progression-free survival (PFS), form the basic vocabulary for reporting the efficacy of investigational new agents and for comparing the efficacy of different treatment regimens.

Although RECIST was developed in the oncology community, many radiologists are now involved with performing RECIST assessments, especially in the academic setting . Radiologists may use RECIST in different contexts, including within their routine clinical workflow, as part of consultative arrangements with local research colleagues or industry sponsors, or within dedicated imaging core laboratories. A key objective when using RECIST is to apply the technique in a standardized fashion, adhering as closely as possible to established methodology and thus minimizing interreader variability that can lead to suboptimal reproducibility of results.

Although basic RECIST methodology is described in published articles and online resources , certain nuances and subtleties of the technique may be problematic for inexperienced readers. The purpose of this article is to illustrate a set of RECIST pitfalls considered to be “beyond the basics.” Examples were drawn from a 6-month quality improvement review of a cancer imaging core laboratory established at our institution in 2012; the radiologists staffing this new core laboratory were board-certified and subspecialty trained, but had little to no prior dedicated experience with RECIST methodology. (Please see Appendix for a description of our core laboratory, an overview of our quality improvement review methods, and a downloadable version of our educational materials.) Pitfalls are presented in four categories: (1) baseline selection of lesions, (2) reassessment of target lesions, (3) reassessment of nontarget lesions, and (4) reassessment of new lesions. These categories are intended to replicate the major evaluative steps established by RECIST for an individual patient on a clinical trial. For each pitfall, we suggest educational or operational support strategies for minimizing or preventing errors.

Baseline selection of lesions

Pitfalls in this category include (1) inappropriate selection of a target lesion when it is not unequivocally a metastasis, (2) selection of too many target lesions at baseline, (3) inappropriate selection of a small lesion as a target lesion, and (4) inappropriate selection of a target lesion from within a radiation field.

Inappropriate Selection of Target Lesion When Not Unequivocally a Metastasis

Because inadvertently selecting a benign lesion as a target lesion can lead to a false assessment of response or stability over time, it is crucial that only unequivocally metastatic lesions be chosen as target lesions ( Fig 1 ). Educational materials presented to new RECIST readers should emphasize this point. Prior studies may be useful to confirm prior growth of an otherwise indeterminate lesion, although these may not always be available (especially in a centralized review setting). Review of clinic notes, operative reports, or surgical pathology reports may be useful to confirm sites of recent biopsy or surgery, thus preventing the inadvertent selection of a postoperative seroma or granulation tissue as a target lesion.

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.”

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Selection of Too Many Target Lesions at Baseline

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Inappropriate Selection of Small Lesions as Target Lesions

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Inappropriate Selection of Target Lesion from within a Radiation Field

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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.

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Reassessment of target lesions

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Remeasurement of Lesions in a Different Phase of Contrast than Baseline

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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 hemiliver. 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.

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Failure to Change Measurement Axis with Changes in Lesion Orientation

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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 long axis. At 8-week (time point #2) follow-up imaging (b) , the original measurement axis was incorrectly maintained, resulting in an underestimation of true lesion size. Shifting the measurement to the new long axis (c) correctly captures the interval lesion growth.

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Reassessment of nontarget lesions

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Premature Assignment of PD for Nontarget Lesions

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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.

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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 RECIST 1.1 guidelines an assignment of progressive disease for these nodes must be considered with reference to overall disease burden on the rest of the scan.

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Incorrect Designation of PR for Nontarget Lesions

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Comparison to the Incorrect Prior Scan

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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.)

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Failure to Assign CR for Nontarget Lymph Nodes Falling Less than 10 mm

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Identification of new lesions

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Premature Assessment of New Disease on Anatomic Imaging

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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.)

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Premature Assessment of New Disease on FDG-PET Studies

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Discussion

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Table 1

Response Evaluation Criteria in Solid Tumor Data Extraction “Pearls”

Baseline selection of lesions

Reassessment of target lesions

Reassessment of nontarget lesions

Identification of new lesions

CR, complete response; CT, computed tomography; FDG-PET, 18-F-fluorodeoxyglucose positron emission tomography; PD, progressive disease; PR, partial response.

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Supplementary data

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Appendix

Table 2

Figure

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References

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Academic Radiology, Volume 22, Issue 6
Journals General Radiology
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