A Multicenter Study of Volumetric Computed Tomography for Staging Malignant Pleural Mesothelioma

Our plain-English summary of A Multicenter Study of Volumetric Computed Tomography for Staging Malignant Pleural Mesothelioma, by V.W. Rusch, R. Gill, A. Mitchell, et al (The Annals of Thoracic Surgery, 2016).

The study

• Authors: V.W. Rusch, R. Gill, A. Mitchell, D. Naidich, D.C. Rice, H.I. Pass, H.L. Kindler, M. De Perrot, J. Friedberg, Malignant Mesothelioma Volumetric CT Study Group
• Journal: The Annals of Thoracic Surgery
• Published: 2016;102(4):1059-66
• Cited by: 61 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Standard imaging modalities are inaccurate in staging malignant pleural mesothelioma (MPM). Single-institution studies suggest that volumetric computed tomography (CT) is more accurate but labor intensive. We established a multicenter network to test interobserver variability, accuracy (relative to pathologic stage), and the prognostic significance of semiautomated volumetric CT.

Methods: Six institutions electronically submitted to an established multicenter database clinical and pathologic data for patients with MPM who had operations. Institutional radiologists reviewed preoperative CT scans for quality and then submitted by electronic network (AG Mednet, www.agmednet.com) to the biostatistical center. Two reference radiologists blinded to clinical data performed semiautomated tumor volume calculations using Vitrea Enterprise 6.0 software (Vital Images, Minnetonka, MN) and then submitted readings to the biostatistical center. Study end points included feasibility of the network, interobserver variability for volumetric CT, correlation of tumor volume to pTN stages, and overall survival (OS).

Results: Of 164 patients, the CT scans for 129 were analyzable and read by reference radiologists. Most tumors were less than 500 cm(3). A small bias was observed between readers because one provided consistently larger measurements than the other (mean difference, 47.9; p = .0027), but for 80%, the absolute difference was 200 cm(3) or less. Spearman correlation between readers was 0.822. Volume correlated with pTN stages and OS, best defined by three groups with average volumes of 91.2, 245.3, and 511.3 cm(3) associated with median OS of 37, 18, and 8 months, respectively.

Conclusions: For the first time, a multicenter network was established and initial correlations of tumor volume with pTN stages and OS are shown. A larger multicenter international study is planned to confirm the results and refine correlations.

Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

In plain English

This feasibility study, run across 6 North American institutions, tested whether CT scans could be used to measure the volume of malignant pleural mesothelioma tumors, and whether that volume matched surgical/pathologic stage and survival. It used past records of patients with pathologically proven disease who had operations between 2005 and 2013. Of 164 registered patients, scans for 129 were measured by two reference radiologists using semiautomated software. The study did not examine asbestos exposure. Considerable upstaging occurred at surgery: most patients had stage III (42%) or IV (45%) disease. The two readers' volume measurements correlated well (Spearman 0.822), though one reader measured consistently larger. In 80% of cases the two readers differed by 200 cm3 or less. Volume rose with pathologic T stage, though T1 cases were too few for a reliable estimate. Three volume groups (average 91.2, 245.3 and 511.3 cm3) had median overall survival of 37, 18 and 8 months. The authors treated the survival analyses as exploratory and, given the small numbers, called this reasonable evidence of a trend. They concluded that a multicenter network was feasible and planned a larger international study to confirm the results.

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: Multicenter feasibility study using retrospective clinical and imaging data, with blinded volume readings by two reference radiologists
• Who was studied: Patients with pathologically proven malignant pleural mesothelioma who had a preoperative chest CT and surgical exploration, operated on between January 1, 2005, and December 31, 2013, at 6 North American institutions. 164 were registered: 8 scans were used as training cases and 2 were excluded for CT quality. 129 patients formed the basis of the report.
• Exposure: No asbestos exposure was studied. The study examined tumor volume measured by semiautomated volumetric CT using Vitrea Enterprise suite 6.0 software.
• Main results:
  • At surgery, most of the 129 patients had pathologic stage III (42%) or IV (45%) disease. By clinical stage, most had been stage II (29%) or III (49%).
  • The two reference radiologists often differed on clinical T stage from standard CT reading: one assigned T3 or T4 to 80% of patients, the other to 28%.
  • Most tumors measured less than 500 cm3: 84 by both readers and 103 by at least 1 reader.
  • In 80% of cases, the two readers' volumes differed by 200 cm3 or less. In more than 40% of cases they differed by less than 60 cm3.
  • The two readers agreed about 67% of the time when tumors were sorted into four volume categories.
  • Overall correlation between the two readers was good (Spearman correlation 0.822).
  • There was a small measurement bias: one reader measured consistently larger than the other (mean difference 47.9, p equal to .0027 by paired t test).
  • Tumor volume correlated with surgical/pathologic T stage, with median volumes ranging from 23.8 cm3 for pT1 to 387.9 cm3 for pT4. There were too few T1 cases to give reliable estimates for that group, but otherwise the data suggested that volume increases with pathologic T category.
  • Tumor volume also correlated with pN stage. Only N0, N2 and NX had enough patients for reliable estimates, and N2 tumors measured larger than N0 tumors.
  • Tumor volume correlated with overall survival. Three groups with average volumes of 91.2, 245.3 and 511.3 cm3 had median overall survival of 37, 18 and 8 months, respectively.
  • In pairwise log-rank comparisons, the lowest-volume quartile differed from the next quartile (p 0.0018). The middle quartiles were similar (p 0.7350) and were combined. The middle group compared with the highest quartile gave p 0.0639. Given the small number of patients, the authors described this as reasonable evidence of a trend.
  • The most common histologic subtype was epithelioid, at 105 of 129 patients (81%).
• The authors' conclusion: The authors concluded that, to their knowledge, this was the first study to show that a multicenter network for evaluating volumetric CT in the clinical staging of malignant pleural mesothelioma was feasible. They concluded that it showed initial correlations of tumor volume with pathologic stage and overall survival, and that a larger international study was planned to confirm the results.
• Limitations the authors state:
  • The study was not designed to assess volumetric CT in prognostic models that include other known important variables.
  • Relationships between volume and the other secondary end points, such as survival, were exploratory only.
  • The log-rank p value alone would not be enough to support statements about differences between survival groups.
  • Too few patients had non-epithelioid histology to test the link between volume and histologic subtype.
  • There were too few T1 cases to give reliable volume estimates for that group.
  • CT quality varied: 57% of scans had 5-mm slices. The authors said stricter criteria for CT quality, a third reference radiologist and more training were needed to reduce variation.

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, CT Scan, Overall Survival.

Related studies

• North American Multicenter Volumetric CT Study for Clinical Staging of Malignant Pleural Mesothelioma: Feasibility and Logistics of Setting Up a Quantitative Imaging Study — R.R. Gill, D.P. Naidich, et al. (2016)
• 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)
• Positron Emission Tomography/Computed Tomography for the Pleural Staging of Malignant Pleural Mesothelioma: How Accurate Is It? — V. Pinelli, E. Roca, et al. (2015)
• Use of computed tomography and positron emission tomography/computed tomography for staging of local extent in patients with malignant pleural mesothelioma — T. Frauenfelder, P. Kestenholz, et al. (2015)
• Clinical implications of 18F-fluorodeoxyglucose positron emission tomography/computed tomography at delayed phase for diagnosis and prognosis of malignant pleural mesothelioma — Y. Abe, K. Tamura, et al. (2012)
• Trimodality Treatment of Malignant Pleural Mesothelioma: An Institutional Review — M. Kapeles, M.F. Gensheimer, et al. (2018)

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