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

Our plain-English summary of Variability of tumor area measurements for response assessment in malignant pleural mesothelioma, by Z.E. Labby, C. Straus, P. Caligiuri, et al (Medical Physics, 2013).

The study

• Authors: Z.E. Labby, C. Straus, P. Caligiuri, H. MacMahon, P. Li, A. Funaki, H.L. Kindler, S.G. Armato
• Journal: Medical Physics
• Published: 2013;40(8):081916
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Purpose: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

In plain English

This study tested how consistently radiologists measure malignant pleural mesothelioma on CT scans when they outline the tumor's area. Tumor area was being considered as an alternative to the current method, which adds up linear measurements of tumor thickness. The study used two CT scans from each of 31 patients with biopsy-proven malignant pleural mesothelioma in a phase II chemotherapy trial: one before treatment and one after two cycles of chemotherapy. Five attending thoracic radiologists outlined tumor on three preselected sections of each first scan. Four of them then outlined the matching sections on the follow-up scan. The observers' measurements were strongly correlated, but they still differed widely. For the summed first-scan areas, the 95% confidence interval for relative differences between observers ran from minus 71% to plus 240%. At follow-up it ran from minus 41% to plus 70%. Using World Health Organization response criteria, the four observers classified tumor response inconsistently for 9 of the 31 patients. The authors concluded that manual area measurements may not be a robust way to assess treatment response in mesothelioma patients. The study did not examine asbestos exposure.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Measurement variability (interobserver) study using existing CT scans from a clinical trial, analyzed with a random effects analysis of variance model
• Who was studied: 31 patients (27 males, 4 females) with biopsy-proven malignant pleural mesothelioma, median age 68 (range 49 to 81), all in a phase II chemotherapy trial; scans read by five attending thoracic radiologists at the baseline step and four of them at follow-up
• Exposure: No asbestos exposure was studied or reported. The patients were receiving a chemotherapy regimen of cisplatin, pemetrexed and bevacizumab; the study examined manual CT tumor area measurements, not exposures.
• Main results:
  • Observers' measurements were strongly correlated with each other. On the first (baseline) scans, the average rank correlation between pairs of observers was 0.898 for summed areas and 0.885 for per-section areas.
  • On the baseline scans, the 95% confidence interval for relative interobserver variability of summed area measurements was minus 71% to plus 240%, a span of 311%.
  • On the follow-up scans, measured with reference to existing baseline outlines, the 95% confidence interval for relative interobserver variability of summed area measurements was minus 41% to plus 70%, a span of 111%.
  • Differences among observers accounted for 8.7% of the total variability in baseline summed area measurements and 1.6% in follow-up summed area measurements. Both shares were reported as statistically significant.
  • Agreement among the four observers in classifying tumor response using WHO criteria gave a kappa of 0.544. For 9 of the 31 patients (29%), the observers' summed area measurements led to inconsistent response classifications.
  • At follow-up, observers did not always pick the same scan section to match a given baseline section.
• The authors' conclusion: The authors concluded that, although tumor area captures tumor burden more fully than linear thickness measurements, manual area measurements may not be a robust means of response assessment in mesothelioma patients. They suggested that future studies validate disease volume measurements instead.
• Limitations the authors state:
  • The authors noted that studies with more patients and radiologists would give more complete estimates of interobserver variability.
  • Area measurements are not part of standard clinical workflow, so the observers were less familiar with this task than with linear measurements.
  • Manual area contouring took about 20 minutes per scan, which the authors considered impractical for clinical response assessment.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, CT Scan, confidence interval, Tumor Burden, Mesothelioma.

Related studies

• Observer variability in mesothelioma tumor thickness measurements: defining minimally measurable lesions — S.G. Armato, A.K. Nowak, et al. (2014)
• Lung volume measurements as a surrogate marker for patient response in malignant pleural mesothelioma — Z.E. Labby, S.G. Armato, et al. (2013)
• Assessment of therapy responses and prediction of survival in malignant pleural mesothelioma through computer-aided volumetric measurement on computed tomography scans — F. Liu, B. Zhao, et al. (2010)
• Influence of inter-observer delineation variability on radiomics stability in different tumor sites — M. Pavic, M. Bogowicz, et al. (2018)
• Correlation of patient survival with clinical tumor measurements in malignant pleural mesothelioma — F. Li, M. Ahmad, et al. (2019)
• Disease volumes as a marker for patient response in malignant pleural mesothelioma — Z.E. Labby, A.K. Nowak, et al. (2013)

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