Variability of lung tumor measurements on repeat computed tomography scans taken within 15 minutes

Abstract

Purpose: We use changes in tumor measurements to assess response and progression, both in routine care and as the primary objective of clinical trials. However, the variability of computed tomography (CT) -based tumor measurement has not been comprehensively evaluated. In this study, we assess the variability of lung tumor measurement using repeat CT scans performed within 15 minutes of each other and discuss the implications of this variability in a clinical context.

Patients and methods: Patients with non-small-cell lung cancer and a target lung lesion ≥ 1 cm consented to undergo two CT scans within a period of minutes. Three experienced radiologists measured the diameter of the target lesion on the two scans in a side-by-side fashion, and differences were compared.

Results: Fifty-seven percent of changes exceeded 1 mm in magnitude, and 33% of changes exceeded 2 mm. Median increase and decrease in tumor measurements were +4.3% and -4.2%, respectively, and ranged from 23% shrinkage to 31% growth. Measurement changes were within ± 10% for 84% of measurements, whereas 3% met criteria for progression according to Response Evaluation Criteria in Solid Tumors (RECIST; ≥ 20% increase). Smaller lesions had greater variability of percent measurement change (P = .005).

Conclusion: Apparent changes in tumor diameter exceeding 1 to 2 mm are common on immediate reimaging. Increases and decreases less than 10% can be a result of the inherent variability of reimaging. Caution should be exercised in interpreting the significance of small changes in lesion size in the care of individual patients and in the interpretation of clinical trial results.

Trial registration: ClinicalTrials.gov NCT00579852.

Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.

(A) Distribution of measurement changes found on repeat computed tomography scans performed within 15 minutes of each other, in millimeters; there was a greater than 1-mm magnitude of change in the majority of lesions (57%). (B) A plot of relative change of longest dimension of indicator lesion (waterfall plot) is also shown; 3% of changes met Response Evaluation Criteria in Solid Tumors for progression, but none met criteria for partial response (dashed lines).

Fig 2.

Correlation between measurement change and lesion size, in millimeters (left) and as a percentage (right). There is a trend toward greater measurement variability in larger tumors using absolute measurement differences (P = .06), whereas there is significantly more measurement variability in smaller tumors using percent measurement difference (P = .005). Most of those increases exceeding 20% were from tumors smaller than 30 mm.

Fig 3.

Relative change of longest dimension of indicator lesions, using data from a recently completed phase II study of targeted therapy in non–small-cell lung cancer. The gray zone demarcates changes of less than 10%, highlighting the fact that changes in this range may be a result of variability alone.

Fig A1.

During the minutes between the repeat computed tomography scans, changes to the appearance of the tumor or surrounding parenchyma may exacerbate measurement variability, such as changes in the surrounding lung parenchyma leading to development of pleural contact (top); slight changes to the tumor orientation in the chest cavity (middle); and collapse of esophagus changing mediastinal contour (bottom).