Early Contrast Enhancement: A novel magnetic resonance imaging biomarker of pleural malignancy

Our plain-English summary of Early Contrast Enhancement: A novel magnetic resonance imaging biomarker of pleural malignancy, by S. Tsim, C.A. Humphreys, G.W. Cowell, et al (Lung Cancer, 2018).

The study

• Authors: S. Tsim, C.A. Humphreys, G.W. Cowell, D.B. Stobo, C. Noble, R. Woodward, C.A. Kelly, L. Alexander, J.E. Foster, C. Dick, K.G. Blyth
• Journal: Lung Cancer
• Published: 2018;118:48-56
• Cited by: 28 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Introduction: Pleural Malignancy (PM) is often occult on subjective radiological assessment. We sought to define a novel, semi-objective Magnetic Resonance Imaging (MRI) biomarker of PM, targeted to increased tumour microvessel density (MVD) and applicable to minimal pleural thickening.

Materials And Methods: 60 consecutive patients with suspected PM underwent contrast-enhanced 3-T MRI then pleural biopsy. In 58/60, parietal pleura signal intensity (SI) was measured in multiple regions of interest (ROI) at multiple time-points, generating ROI SI/time curves and Mean SI gradient (MSIG: SI increment/time). The diagnostic performance of Early Contrast Enhancement (ECE; which was defined as a SI peak in at least one ROI at or before 4.5 min) was compared with subjective MRI and Computed Tomography (CT) morphology results. MSIG was correlated against tumour MVD (based on Factor VIII immunostain) in 31 patients with Mesothelioma.

Results: 71% (41/58) patients had PM. Pleural thickening was <10 mm in 49/58 (84%). ECE sensitivity was 83% (95% CI 61-94%), specificity 83% (95% CI 68-91%), positive predictive value 68% (95% CI 47-84%), negative predictive value 92% (78-97%). ECE performance was similar or superior to subjective CT and MRI. MSIG correlated with MVD (r = 0.4258, p = .02).

Discussion: ECE is a semi-objective, perfusion-based biomarker of PM, measurable in minimal pleural thickening. Further studies are warranted.

Copyright © 2018 Elsevier B.V. All rights reserved.

In plain English

This prospective cohort study in Glasgow, UK, tested whether a new MRI measure, Early Contrast Enhancement (ECE), could tell pleural malignancy from benign pleural disease. Of consecutive patients with suspected pleural malignancy having contrast-enhanced MRI before biopsy in 2013 to 2016, 58 completed the protocol. Of these, 67% had asbestos exposure. Final diagnosis was pleural malignancy in 36 of 58, including 31 with malignant pleural mesothelioma. Another 22 had benign disease, half benign asbestos pleural effusion. Most had pleural thickening under 10 mm. A patient was ECE-positive if MRI signal peaked at or before 4.5 minutes after contrast in at least one measured pleural region. ECE had sensitivity 83% (95% CI 61 to 94%) and specificity 83% (68 to 91%); CT appearance had 56% (37 to 72%) and 77% (60 to 89%). After adjustment for multiple comparisons, differences between methods were not statistically significant. In mesothelioma patients, an MRI signal measure correlated with tumour blood-vessel density. The authors concluded that ECE appeared sensitive, specific and reproducible, meriting a larger multi-centre study. Their main stated limitation was small sample size.

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: Prospective cohort study of diagnostic imaging, combining patients from an MRI pilot study and the DIAPHRAGM study's MRI sub-study
• Who was studied: Consecutive patients with suspected pleural malignancy needing pleural biopsy, seen at the Glasgow Pleural Disease Unit, UK, from January 2013 to October 2016. 60 had contrast-enhanced MRI and 58 completed the protocol. Median age was 76 and 51/58 (88%) were male.
• Exposure: The test studied was contrast-enhanced 3-Tesla MRI using gadobutrol contrast, compared with CT and MRI appearance. Asbestos exposure was recorded for 39/58 (67%) patients; no fiber types or jobs were given.
• Main results:
  • Of 58 patients, 36 (62%) had a final diagnosis of pleural malignancy. Of these 36, 31 (86%) had malignant pleural mesothelioma and 5 had secondary pleural cancer.
  • 22/58 (38%) had benign pleural disease. Half of these (n = 11) had benign asbestos pleural effusion (BAPE).
  • At MRI, 49/58 (84%) patients had pleural thickening under 10 mm. Median thickness was 5 mm (4 to 7 mm).
  • ECE was counted as present, and the patient classified as malignant, if at least one region-of-interest signal curve peaked at or before 4.5 minutes.
  • ECE sensitivity was 83% (95% CI 61 to 94%) and specificity was 83% (95% CI 68 to 91%).
  • In Table 2, CT appearance (morphology) had sensitivity 56% (95% CI 37 to 72%) and specificity 77% (95% CI 60 to 89%).
  • ECE had sensitivity 83% and negative predictive value 92%. CT appearance had 56% and 67%, and MRI appearance had 68% and 78%.
  • After adjustment for multiple comparisons, the differences in diagnostic performance were not statistically significant.
  • ECE correctly classified 12/12 pleural malignancy cases with nodular disease and 21/24 (87.5%) with non-nodular, effusion-dominant disease. All three false negatives had mesothelioma.
  • Agreement between two readers (kappa) was 0.784 for ECE, 0.65 for CT appearance and 0.593 for MRI appearance.
  • The mean signal intensity gradient (MSIG) was 0.58 (0.27 to 0.88) AU/s in patients with pleural malignancy. In patients with benign disease it was 0.2 (0.06 to 0.29) AU/s, p less than .0001.
  • In mesothelioma patients, MSIG correlated positively with tumour microvessel density (r = 0.4258, p = .02). In mesothelioma patients without nodular disease, the correlation was r = 0.6594, p = .003, n = 18.
  • In mesothelioma patients, higher microvessel density was linked to shorter median survival: 10 months versus 20 months, HR 2.723 (95% CI 1.093 to 6.784), p = .03.
• The authors' conclusion: The authors concluded that in this preliminary study ECE appeared to be a sensitive, specific and reproducible marker of pleural malignancy, with a high negative predictive value, meriting a large multi-centre study.
• Limitations the authors state:
  • The sample size was relatively small, giving wide confidence intervals around some measures.
  • The regions where signal was measured were chosen by the user, which is a potential source of inconsistency.
  • Perfusion CT was not performed for comparison with ECE.
  • ECE was defined from patients with bulky nodular tumour. A different definition might work better for lower-volume tumour or other cancer types.
  • ECE analysis is slower than assessing the scan's appearance.

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: Biomarker, Pleural Thickening, Pleural Biopsy, Parietal Pleura, Mesothelioma.

Related studies

• Asbestos-related pleural disease: value of dedicated magnetic resonance imaging techniques — M.A. Weber, M. Bock, et al. (2004)
• Magnetic resonance imaging of the thorax in the evaluation of asbestosis — S.I. Bekkelund, U. Aasebø, et al. (1998)
• 18F-Fluorodeoxyglucose PET/CT and dynamic contrast-enhanced MRI as imaging biomarkers in malignant pleural mesothelioma — D.O. Hall, C.E. Hooper, et al. (2018)
• New applications of magnetic resonance imaging for thoracic oncology — Y. Ohno (2014)
• Applications of Magnetic Resonance Imaging of the Thorax in Pleural Diseases: A State-of-the-Art Review — F.M. Pessôa, A.S. de Melo, et al. (2016)
• The use of magnetic resonance imaging in malignant mesothelioma — J. Entwisle (2004)

Browse more research in Lung Cancer, or return to medical research.