Rationale and Objectives
Determine inter- and intraobserver variability of computed tomography (CT) tumor volume measurements in advanced non-small-cell lung cancer (NSCLC) patients treated in a Phase II clinical trial using chest CT.
Materials and Methods
Twenty-three advanced NSCLC patients with a total of 53 measurable lung lesions enrolled in a Phase II, multicenter, open-label clinical trial of erlotinib were retrospectively studied with institutional review board approval. Two radiologists independently measured the tumor size, volume, and CT attenuation coefficient using commercially available volume analysis software. Concordance correlation coefficients (CCCs) and Bland-Altman plots were used to assess inter- and intraobserver agreement.
Results
High CCCs (0.949–0.990) were observed in all types of measurements for interobserver agreement. The 95% limits of agreements for volume, unidimensional, and bidimensional measurements were (−26.0%, 18.6%), (−23.1%, 24.4%), and (−34.0%, 48.6%), respectively. Volume measurement had slightly higher CCC and narrower 95% limits of agreement compared to uni- and bidimensional measurements. CCCs for intraobserver agreement were high (range, 0.946–0.996) with CCC for volume being slightly higher than CCCs of uni- and bidimensional measurements. The smaller the tumor volume was, the larger the interobserver difference of CT attenuation. Location, morphology, or adjacent atelectasis had no significant impact on inter- or intraobserver variability.
Conclusion
CT tumor volume measurement in advanced NSCLC patients using clinical chest CT and commercially available software demonstrated high inter- and intraobserver agreement, indicating that the method may be used routinely in clinical practice.
Lung cancer is a leading cause of death from cancer in the United States as well as worldwide, resulting in more than 160,000 deaths per year in the United States . Non-small-cell lung cancer (NSCLC), accounting for approximately 85% of lung cancer cases, has a 5-year survival rate of only 15%. Given the increasing availability of newer targeted therapeutic options against NSCLC, such as the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, gefitinib and erlotinib, accurate assessment of response to a given therapy is of utmost importance . In addition, accurate tumor assessment to document time to progression has become a critical determinant because it is used as a primary end point in lung cancer clinical trials using targeted agents.
Two widely accepted and conventional guidelines for objective response assessment to therapy in patients with solid tumors include the World Health Organization (WHO) guideline that uses bidimensional tumor measurements and the Response Evaluation Criteria in Solid Tumors (RECIST) that uses unidimensional measurements of the longest diameter of the tumor . Recent advancement of computed tomography (CT) and multidetector-row CT (MDCT) imaging technology has enabled volumetric measurements of tumors . To use the tumor volume measurement as a method of response assessment to therapy, it is necessary to determine the reproducibility of this volume measurement. However, only a few reports have been published regarding the reproducibility of CT volume measurement of lung lesions in advanced NSCLC patients participating in prospective clinical trials . To answer questions of CT measurement reproducibility and repeatability, Zhao et al evaluated the variability in tumor measurements from same-day repeat CT scans using thin-section CT images in 32 NSCLC patients . In their study, the patients were recruited to a specific imaging trial, and their own semiautomated three-dimensional algorithm was used for determining tumor volume measurements . To widely apply CT volume measurements in response assessment of NSCLC in clinical practice, it is important to assess reproducibility of the measurements in NSCLC patients who were actually treated in a prospective clinical trial of therapeutic agents. CT volume measurement is gradually becoming a clinically available tool for assessing tumor burden. However, radiologists should accurately assess the performance characteristics of these volumetric tools including inter- and intraobserver reproducibility.
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Materials and methods
Patients
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CT Examinations
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Tumor Size and Volume Measurement
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Statistical Analysis
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Results
Interobserver Agreement
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Table 1
Interobserver Agreement Between Two Radiologists for Volume, Uni- and Bidimensional, and CT Attenuation Coefficient Measurements
Types of Measurement Concordance Correlation Coefficient ∗ Mean Relative Difference (%) 95% limits of Agreement (%) Percentage of Observations Inside the Limits (%) Standard Deviation ‡ Volume 0.990 (0.983–0.994) −3.7 −26.0, 18.6 90.5 0.112 (0.058) Longest diameter 0.969 (0.949–0.982) 0.6 −23.1, 24.4 94.3 0.119 (0.098) Longest perpendicular diameter 0.949 (0.914–0.970) 7.1 −23.9, 38.0 94.3 0.155 (0.105) Bidimensional 0.966 (0.942–0.980) 7.3 −34.0, 48.6 92.4 0.207 (0.156) CT attenuation coefficient 0.985 (0.975–0.991) −0.7 −55.1, 53.7 † 92.4 27.2 † (18.9)
CCC: concordance correlation coefficients; CT: computed tomography.
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Intraobserver Agreement
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Table 2
Intraobserver Agreement for Volume, Uni- and Bidimensional, and CT Attenuation Coefficient Measurements
Types of Measurement Average Concordance Correlation Coefficient ∗ Average Mean Relative Difference (%) ∗ Average Standard Deviation ∗ Average Trimmed Standard Deviation ∗ Average Percentage of Observations Inside the Limits (%) ∗ Volume 0.992 (0.985–0.996) −5.4 (−9.3, −0.2) 0.148 (0.104–0.220) 0.008 (0.064–0.113) 95.0 (90.5, 98.1) Longest diameter 0.977 (0.971–0.984) −3.2 (−6.0, −0.7) 0.110 (0.098–0.117) 0.086 (0.071–0.095) 94.7 (90.5, 98.1) Longest perpendicular diameter 0.959 (0.946–0.971) −1.7 (−5.2, 21.3) 0.160 (0.138–0.197) 0.117 (0.100–0.130) 94.3 (90.5, 96.2) Bidimensional 0.975 (0.959–0.989) −5.1 (−8.4, 0.3) 0.210 (0.186–0.234) 0.165 (0.141–0.187) 94.7 (92.4, 98.1) CT attenuation coefficient 0.984 (0.974–0.996) 6.6 † (−3.1, 13.7) 26.2 † (12.6–33.4) 16.4 † (10.1–21.6) 94.5 (90.5, 96.2)
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Impact of Lesion Characteristics on CT Measurement Variability
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Table 3
The Summary of the Lesion Characteristics
Lesion Characteristics Number of Lesions Location Intraparenchymal 25 Pleura/fissure 18 Juxtavascular 10 Morphology Smooth 7 Lobulated 14 Irregular 32 Adjacent atelectasis Present 17 Absent 36
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Discussion
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