1. Biomarker-Integrated Neoadjuvant Dasatinib Trial in Resectable Malignant Pleural Mesothelioma 
Anne S. Tsao, MD, Heather Lin, Brett W. Carter, MD, J. Jack Lee, PhD, David Rice, MD, Ara Vaporcyan, MD, Steven Swisher, MD, Reza Mehran, MD, John Heymach, MD, PhD, Monique Nilsson, PhD, Youhong Fan, Maria Nunez, Lixia Diao, Jing Wang, PhD, Junya Fujimoto, PhD, Ignacio I. Wistuba, MD, Waun Ki Hong, MD 
Journal of Thoracic Oncology 
Volume 13, Issue 2, Pages (February 2018)
DOI: /j.jtho
Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions

2. Figure 1
Downregulation of p-SrcTyr419 by neoadjuvant dasatinib therapy correlates with a metabolic response on positron emission tomography/computed tomography scans. (A) Positron emission tomography/computed tomography imaging of two patients before and after neoadjuvant dasatinib therapy. Images were obtained at baseline and after 4 weeks of dasatinib therapy. Cytologic examination–proven nonmalignant pleural effusions developed in both patients. The green arrows indicate areas where tumor shrinkage was seen. (B) The corresponding microphotographs of patient 1 (epithelioid malignant pleural mesothelioma [i–iv]) and patient 2 (biphasic malignant pleural mesothelioma [v–viii]), with hematoxylin and eosin staining (i, iii, v, and vii) and phosphorylated (p)-SrcTyr419 immunohistochemistry (IHC) expression (positive staining is seen as brown staining) before (ii and vi) and after (iv and viii) neoadjuvant dasatinib therapy. The pretreatment photos (ii and vi) show strong membrane p-SrcTyr419 expression at baseline, whereas after neoadjuvant dasatinib, the tumor p-SrcTyr419 IHC expression markedly diminishes (iv and viii), reflecting positive modulation of IHC p-SrcTyr419 by dasatinib therapy. Both patients with a decrease in standardized uptake value levels had significant downregulation of p-SrcTyr419 after neoadjuvant dasatinib treatment.
Journal of Thoracic Oncology  , DOI: ( /j.jtho )
Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions

3. Figure 2
(A) Box plot distributions of averaged baseline p-SrcTyr419 immunohistochemistry (IHC) scores compared with week 4 scores after dasatinib therapy, which demonstrate a decrease in averaged p-SrcTyr419 levels. (B) Baseline phosphorylated (p)-SrcTyr419 IHC scores correlated with the radiographic response by standardized uptake value (SUV) levels after dasatinib therapy, showing that higher baseline p-SrcTyr419 IHC levels associate with a SUV radiographic response. (C) The delta change of p-SrcTyr419 IHC expression from baseline to week 4, with the difference between the two time points calculated as the averaged IHC score at week 4 p-SrcTyr419 minus the p-SrcTyr419 IHC score at baseline and the change in p-SrcTyr419 correlated with radiographic response by SUV levels. Patients with a decrease in p-SrcTyr419 were more likely to have a decrease in SUV levels, whereas those with an increase in p-SrcTyr419 IHC levels were more likely to have an increase in SUV levels.
Journal of Thoracic Oncology  , DOI: ( /j.jtho )
Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions

4. Figure 3
Increased p-SrcTyr419 levels after 4 weeks of neoadjuvant dasatinib therapy correlated with shorter progression-free survival (PFS). This figure illustrates the Kaplan-Meier curves for PFS when clinical outcomes were correlated to the change in immunohistochemistry (IHC) scores between the pretreatment and posttreatment tumor specimens. Two methods of analyzing the IHC data are shown. (A) PFS results when pretreatment and posttreatment IHC scores are assessed using the single highest or maximum individual phosphorylated (p)-SrcTyr419 IHC score from the multiple biopsy specimens at each time point. Patients who had an increase in single maximum individual IHC score had a worse PFS than patients who had a decrease (p = 0.002). (B) PFS results when all IHC scores for p-SrcTyr419 from each time point were averaged and this averaged score at baseline was compared with the posttreatment averaged score. Patients who had an increase in averaged p-SrcTyr419 IHC scores from baseline had a worse PFS than those who had a decrease (p = 0.03). Abbreviations: E, event; N, number.
Journal of Thoracic Oncology  , DOI: ( /j.jtho )
Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions

5. Figure 4
Platelet-derived growth factor receptor (PDGFR) pathway biomarkers and clinical outcomes. PDGFR biomarkers by response at baseline (A) and after neoadjuvant dasatinib (B). (C) and (D) PDGFR biomarkers by improved or worse progression-free survival (PFS). An increase in nuclear PDGFRβ after neoadjuvant dasatinib therapy was associated with improved PFS (p = 0.006). (E) illustrates that in all surgically resected patients, high p-PDGFRβ expression in the stroma correlated with a worse PFS outcome (HR = 3.26, p = 0.05).
Journal of Thoracic Oncology  , DOI: ( /j.jtho )
Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions