Lung volume measurements as a surrogate marker for patient response in malignant pleural mesothelioma

Our plain-English summary of Lung volume measurements as a surrogate marker for patient response in malignant pleural mesothelioma, by Z.E. Labby, S.G. Armato, J.J. Dignam, et al (Journal of Thoracic Oncology, 2013).

The study

• Authors: Z.E. Labby, S.G. Armato, J.J. Dignam, C. Straus, H.L. Kindler, A.K. Nowak
• Journal: Journal of Thoracic Oncology
• Published: 2013;8(4):478-86
• Cited by: 20 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Introduction: The purpose of this study was to investigate the continuous changes in three distinct response assessment methods during treatment as a marker of response for patients with mesothelioma. Linear tumor thickness measurements, disease volume measurements, and lung volume measurements (a physiological correlate of disease volumes) were investigated in this study.

Methods: Serial computed tomography scans were obtained during the course of clinically standard chemotherapy for 61 patients. For each of the 216 computed tomography scans, the aerated lung volumes were segmented using a fully automated method, and the pleural disease volume was segmented using a semiautomated method. Modified Response Evaluation Criteria in Solid Tumors linear-thickness measurements were acquired clinically. Diseased (ipsilateral) lung volumes were normalized by the respective contralateral lung volumes to account for the differences in inspiration between scans for each patient. Relative changes in each metric from baseline were tracked over the course of follow-up imaging. Survival modeling was performed using Cox proportional hazards models with time-varying covariates.

Results: Median survival from pretreatment baseline imaging was 12.7 months. A negative correlation was observed between measurements of lung volume and disease volume, and a positive correlation was observed between linear-thickness measurements and disease volume. As continuous numerical parameters, all three response assessment methods were significant imaging biomarkers of patient prognosis in independent survival models.

Conclusions: Analysis of trajectories of linear-thickness measurements, disease volume measurements, and lung volume measurements during chemotherapy for patients with mesothelioma indicates that increasing linear thickness, increasing disease volume, and decreasing lung volume are all significantly and independently associated with poor patient prognosis.

In plain English

This study re-analyzed chest CT scans from 61 patients with malignant pleural mesothelioma on one side of the chest. They were treated with chemotherapy in Australia and enrolled from late 2003 to 2010; 55 had known asbestos exposure. Across 216 scans, the authors compared three measures. One was hand-measured tumor thickness. Another was pleural disease volume, which could include fluid as well as tumor. The third was affected-side air-filled lung volume divided by healthy-side lung volume, to allow for breathing differences. Median survival from the first scan was 12.7 months (95% CI 10.2 to 15.3). Changes in disease volume and adjusted lung volume moved in opposite directions (Spearman correlation −0.687). The measures were modeled as continuous growth rates. Faster growth in thickness (hazard ratio 1.53) and disease volume (1.32) was linked to poorer survival. Faster growth in adjusted lung volume was linked to better survival (0.76). In separate models adjusted for histology, breathlessness and performance status, these were 1.47 (95% CI 1.18 to 1.84), 1.33 (1.13 to 1.58) and 0.76 (0.64 to 0.91). No model was significantly better. The authors called adjusted lung volume change a useful response measure but noted the small group.

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: Retrospective analysis of imaging and clinical data collected in an earlier prospective study, comparing three CT-based tumor response measures in survival models
• Who was studied: 61 adults with malignant pleural mesothelioma (MPM) affecting one side of the chest, with no previous chemotherapy, enrolled late 2003 to 2010 at Sir Charles Gairdner Hospital, Nedlands, Australia; 216 CT scans in total
• Exposure: Not an asbestos exposure study. Patients received chemotherapy: cisplatin and gemcitabine at first, later cisplatin and pemetrexed; Table 1 also lists carboplatin and pemetrexed. Table 1 lists 55 of the 61 patients with known asbestos exposure, but exposure was not analyzed.
• Main results:
  • The lung volume measure was the affected-side (ipsilateral) aerated lung volume divided by the healthy-side (contralateral) lung volume on each scan, to control for differences in inspiration
  • Median survival from pretreatment baseline imaging was 12.7 months (95% CI 10.2 to 15.3 months). Of the 61 patients, 58 died during follow-up.
  • Relative changes from baseline in normalized affected-side lung volume and in disease volume were negatively correlated (Spearman −0.687; Pearson −0.494)
  • Patients whose normalized affected-side lung volume increased during therapy (n=36) and those whose normalized lung volume decreased (n=25) differed significantly in survival
  • In single-factor survival models, the measures were treated as continuous time-varying specific growth rates. Increases in linear thickness (HR 1.53, p less than 0.0001) and in disease volume (HR 1.32, p = 0.0003) were associated with poor prognosis. Decreases in normalized lung volume were also associated with poor prognosis (HR 0.76, p = 0.003).
  • In separate models that added disease histology, dyspnea and ECOG performance status, all three measures remained significantly associated with survival. The adjusted hazard ratios were 1.47 for linear thickness (95% CI 1.18 to 1.84), 1.33 for disease volume (95% CI 1.13 to 1.58) and 0.76 for normalized lung volume (95% CI 0.64 to 0.91), from Table 2.
  • The three survival models did not differ significantly in predictive performance (C-tau 0.692 for thickness, 0.680 for disease volume and 0.670 for lung volume)
  • Tumor thickness changes fit the spherical model assumed by RECIST poorly (R2 = 0.35)
  • Automated lung area measurements agreed closely with a radiologist's manual tracings on 132 sections
• The authors' conclusion: The authors concluded that changes in normalized lung volume form a useful response assessment measure. All three measures were significantly associated with survival, and no model was significantly better than the others.
• Limitations the authors state:
  • Relatively small number of patients
  • The models need validation in independent patient groups
  • Prognostic performance of about 0.65 is far from perfect
  • Results may not apply to patients receiving biologically different treatments
  • Lung volume assessment requires disease on one side only, which excludes some patients
  • Disease volume measurement does not separate tumor from pleural fluid

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Mesothelioma, Chemotherapy, Modified RECIST (mRECIST), Median Survival, Biomarker, Prognosis.

Related studies

• Disease volumes as a marker for patient response in malignant pleural mesothelioma — Z.E. Labby, A.K. Nowak, et al. (2013)
• Soluble mesothelin, megakaryocyte potentiating factor, and osteopontin as markers of patient response and outcome in mesothelioma — K. Hollevoet, K. Nackaerts, et al. (2011)
• Optimization of response classification criteria for patients with malignant pleural mesothelioma — Z.E. Labby, S.G. Armato, et al. (2012)
• Volume-based parameter of 18)F-FDG PET/CT in malignant pleural mesothelioma: prediction of therapeutic response and prognostic implications — H.Y. Lee, S.H. Hyun, et al. (2010)
• Thymidylate synthase and folyl-polyglutamate synthase are not clinically useful markers of response to pemetrexed in patients with malignant pleural mesothelioma — D.E. Lustgarten, C. Deshpande, et al. (2013)
• Variability of tumor area measurements for response assessment in malignant pleural mesothelioma — Z.E. Labby, C. Straus, et al. (2013)

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