The current standard for medical image-based tumor response assessment for patients with malignant pleural mesothelioma is the modified Response Evaluation Criteria In Solid Tumors (RECIST) measurement technique with changes classified according to the standard RECIST response classification criteria. While the modified RECIST measurement technique was developed specifically for the unique morphology and growth patterns of mesothelioma, the standard RECIST classification criteria are used across a wide range of diseases and are certainly not specific to any one disease. As a coherent progression, this work extends the definition of radiologic response for patients with malignant pleural mesothelioma from one to three dimensions, both in the context of a discrete classification system and as a continuous prognostic model. Furthermore, temporal and spatial measurements are combined in an investigation of dynamic imaging for patients with mesothelioma.
This work begins by quantifying the association between standard tumor response classification from thoracic computed tomography (CT) scans and patient survival in a study focused on the standard linear thickness measurement technique. The association between tumor response and patient survival was improved by identifying new response classification criteria specifically for a database of treated mesothelioma patients. In place of summed linear thickness measurements, summed measurements of disease area from a limited number of CT sections were investigated as a more complete and potentially less variable metric for tumor response assessment. However, the inter-observer variability in such measurements, even in a constrained follow-up contouring task, was too broad for reliable use as a response assessment technique in patients with mesothelioma. Next, full volumetric segmentations of pleural disease volume were investigated as a response assessment measurement technique. A comprehensive model to predict patient survival was built using time-changing measurements of disease volume in conjunction with other clinical covariates, where it was shown that increasing pleural disease volumes are significantly associated with poor patient prognosis in both univariate and multivariate prognostic models. Automatically segmented lung volumes were also investigated as an alternate response assessment measurement technique. Because of the anatomy associated with mesothelioma, when the disease volume increases, it is reasonable to believe that the aerated lung volume will decrease correspondingly. Lung volume segmentation is a completely automated process and is a computationally simpler task than pleural disease volume segmentation. As expected, decreases in lung volume were shown to be significantly associated with poor patient prognosis, and the performance of the prognostic model using lung volume measurements was statistically nearly identical to the model using disease volume measurements. Both models were compared with a model using summed linear thickness measurements, and the performance of the linear measurement model was on average better than the performance of either the disease volume or lung volume models (though not significantly so). This work provides the first evidence that trajectories of three distinct response assessment measurement techniques are significantly associated with mesothelioma patient survival in univariate and multivariate models. Finally, this work reports the results of a pilot study on dynamic contrast-enhanced (DCE) CT for patients with mesothelioma. A DCE-CT imaging protocol was developed to dovetail with a clinically indicated standard chest CT scan, and software tools were developed to analyze DCE-CT parameters from volumetric regions of interest in a spatially co-registered reference frame. DCE-CT parameter values are reported for individual scans and changes in DCE-CT parameters are calculated for two cohorts of patients, one undergoing treatment and the other on observation. Only 13 patients have received both DCE-CT scans; the initial pilot study will continue until a final accrual goal of 20 patients with two DCE-CT scans each. This dissertation investigated a variety of new response assessment strategies for patients with malignant pleural mesothelioma. These techniques will hopefully impact the tools clinicians use to assess patient response in both phase II clinical trials and routine patient care.
|Advisor:||Armato, Samuel G., III|
|Commitee:||Dignam, James J., Giger, Maryellen L., Kindler, Hedy L., Straus, Christopher|
|School:||The University of Chicago|
|School Location:||United States -- Illinois|
|Source:||DAI-B 73/11(E), Dissertation Abstracts International|
|Keywords:||Health and environmental sciences, Mesothelioma, Prognosis, Response assessment, Survival analysis|
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