North American Multicenter Volumetric CT Study for Clinical Staging of Malignant Pleural Mesothelioma: Feasibility and Logistics of Setting Up a Quantitative Imaging Study

Our plain-English summary of North American Multicenter Volumetric CT Study for Clinical Staging of Malignant Pleural Mesothelioma: Feasibility and Logistics of Setting Up a Quantitative Imaging Study, by R.R. Gill, D.P. Naidich, A. Mitchell, et al (Journal of Thoracic Oncology, 2016).

The study

• Authors: R.R. Gill, D.P. Naidich, A. Mitchell, M. Ginsberg, J. Erasmus, S.G. Armato, C. Straus, S. Katz, D. Patios, W.G. Richards, V.W. Rusch, Malignant Mesothelioma Volumetric CT Study Group
• Journal: Journal of Thoracic Oncology
• Published: 2016;11(8):1335-1344
• Cited by: 46 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Clinical tumor (T), node, and metastasis staging is based on a qualitative assessment of features defining T descriptors and has been found to be suboptimal for predicting the prognosis of patients with malignant pleural mesothelioma (MPM). Previous work suggests that volumetric computed tomography (VolCT) is prognostic and, if found practical and reproducible, could improve clinical MPM classification.

Methods: Six North American institutions electronically submitted clinical, pathologic, and imaging data on patients with stages I to IV MPM to an established multicenter database and biostatistical center. Two reference radiologists blinded to clinical data independently reviewed the scans; calculated clinical T, node, and metastasis stage by standard criteria; performed semiautomated tumor volume calculations using commercially available software; and submitted the findings to the biostatistical center. Study end points included the feasibility of a multi-institutional VolCT network, concordance of independent VolCT assessments, and association of VolCT with pathological T classification.

Results: Of 164 submitted cases, 129 were evaluated by both reference radiologists. Discordant clinical staging of most cases confirmed the inadequacy of current criteria. The overall correlation between VolCT estimates was good (Spearman correlation 0.822), but some were significantly discordant. Root cause analysis of the most discordant estimates identified four common sources of variability. Despite these limitations, median tumor volume estimates were similar within subgroups of cases representing each pathological T descriptor and increased monotonically for each reference radiologist with increasing pathological T status.

Conclusions: The good correlation between VolCT estimates obtained for most cases reviewed by two independent radiologists and qualitative association of VolCT with pathological T status combine to encourage further study. The identified sources of user error will inform design of a follow-up prospective trial to more formally assess interobserver variability of VolCT and its potential contribution to clinical MPM staging.

Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

In plain English

This multicenter pilot study tested whether tumor volume could be measured consistently on CT scans (volumetric CT, or VolCT) in malignant pleural mesothelioma, using scans of past cases. Six North American institutions sent scans of patients operated on between 2005 and 2013. Of 164 cases submitted, 130 were measured by two reference radiologists; after one extreme outlier was excluded, 129 paired cases remained. Both worked independently, blinded to clinical data, with the same software. The study did not examine asbestos exposure. Their standard clinical T staging agreed poorly. Both overestimated the number of early-stage tumors and underestimated late-stage tumors versus pathology. Their volume estimates correlated well overall (Spearman correlation 0.822), but some cases differed widely. Discrepancies in the 35 cases differing by more than 60 cc were traced to four kinds of error, such as data entry and software use. Median volumes rose with higher pathological T category for each radiologist. The authors concluded that VolCT may contribute to clinical staging and warrants a more formal prospective study. They noted that using only two reference radiologists precluded formal assessment of variability between observers.

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: Multi-institutional feasibility (pilot) study, described by the authors as prospective, using CT scans of retrospective cases drawn from an existing international database
• Who was studied: Patients with pathologically proven malignant pleural mesothelioma, clinical stage I-IV, considered candidates for surgery, who had surgery between January 1, 2005 and December 31, 2013 at six North American institutions (MD Anderson, Memorial Sloan-Kettering, New York University, University of Chicago, University of Pennsylvania, University of Toronto). 164 cases were registered. 8 were used for training and 2 had poor-quality scans, leaving 154 eligible. Of these, 130 were analyzed by both reference radiologists. One extreme outlier was then excluded, leaving 129 paired cases.
• Exposure: No asbestos exposure was studied. What was examined was preoperative CT scans, measured for tumor volume by two reference radiologists with semiautomated software (Vitrea Enterprise suite 6.0), and compared with standard clinical T staging and pathological T classification.
• Main results:
  • Across the 129 paired cases, tumor volume estimates by the two reference radiologists correlated well overall (Spearman correlation 0.822), although variability was large for several cases.
  • Reference radiologist A tended to assign larger volumes than reference radiologist B. The mean difference (B minus A) was -47.9 cc with a standard deviation of 178.2 cc, p = 0.0027.
  • Median tumor volume increased steadily with increasing pathological T status for each reference radiologist (radiologist A: p = 0.0034; radiologist B: p = 0.0001).
  • Clinical T categorization by standard criteria agreed poorly between the two reference radiologists. The Results text says radiologist B assigned 80% of cases to T3 and radiologist A 28%. However, the article's Table 1 shows 84 of 129 (65%) for B and 27 of 129 (21%) for A, and the Discussion gives 80% and 20%.
  • Compared with pathological stage, both reference radiologists overestimated the number of early-stage tumors and underestimated late-stage tumors. Staging by the submitting sites' radiologists put 63 patients (49%) at Stage III and 18 (14%) at Stage IV. Pathological staging found 54 cases (42%) at Stage III and 58 (45%) at Stage IV.
  • The 35 discordant cases with a volume difference larger than 60 cc were re-reviewed. The text attributes 8 to data entry errors, 6 to perception errors, 8 to limited distinction between tumor and adjacent tissues, and 12 to user error with the software's sculpting tools.
• The authors' conclusion: The authors concluded that a network for multicenter evaluation of VolCT was successfully set up. In their view, the study supported the feasibility of a more formal prospective study and suggested that VolCT may contribute to quantitative clinical staging of malignant pleural mesothelioma.
• Limitations the authors state:
  • As a pilot, the analysis was limited to two reference radiologists. This prevented formal assessment of variability between observers.
  • Because scans came from an existing retrospective database, broad scan-quality criteria led to varied scan parameters.

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: Staging, Pleural Mesothelioma, Metastasis, Prognosis.

Related studies

• A Multicenter Study of Volumetric Computed Tomography for Staging Malignant Pleural Mesothelioma — V.W. Rusch, R. Gill, et al. (2016)
• Quantitative Perfusion Scintigraphy or Anatomic Segment Method in lung cancer resection — T. Holvoet, J.P. van Meerbeeck, et al. (2011)
• Radiologic Considerations and Standardization of Malignant Pleural Mesothelioma Imaging Within Clinical Trials: Consensus Statement from the NCI Thoracic Malignancy Steering Committee - International Association for the Study of Lung Cancer - Mesothelioma Applied Research Foundation Clinical Trials Planning Meeting — R.R. Gill, A.S. Tsao, et al. (2019)
• Malignant pleural mesothelioma: overview of the North American and European experience — J. Kukreja, M.T. Jaklitsch, et al. (2004)
• 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)
• Extra-pleural pneumonectomy versus no extra-pleural pneumonectomy for patients with malignant pleural mesothelioma: clinical outcomes of the Mesothelioma and Radical Surgery (MARS) randomised feasibility study — T. Treasure, L. Lang-Lazdunski, et al. (2011)

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