Variability of tumor area measurements for response assessment in malignant pleural mesothelioma

The measurement of malignant pleural mesothelioma is critical to the assessment of tumor response to therapy. Current response assessment standards utilize summed linear measurements acquired on three computed tomography (CT) sections. The purpose of this study was to evaluate manual area measurements as an alternate response assessment metric, specifically through the study of measurement interobserver variability.

Two CT scans from each of 31 patients were collected. Using a computer interface, five observers contoured tumor on three selected CT sections from each baseline scan. Four observers also constructed matched follow-up scan tumor contours for the same 31 patients. Area measurements extracted from these contours were compared using a random effects analysis of variance model to assess relative interobserver variability. The sums of section area measurements were also analyzed, since these area sums are more clinically relevant for response assessment.

When each observer's measurements were compared with those of the other four observers, strong correlation was observed. The 95% confidence interval for relative interobserver variability of baseline scan summed area measurements was [-71%, +240%], spanning 311%. For the follow-up scan summed area measurements, the 95% confidence interval for relative interobserver variability was [-41%, +70%], spanning 111%. At both baseline and follow-up, the variability among observers was a significant component of the total variability in both per-section and summed area measurements (p<0.0001).

Despite the ability of tumor area measurements to capture tumor burden with greater fidelity than linear tumor thickness measurements, manual area measurements may not be a robust means of response assessment in mesothelioma patients.