Heart Dose Is an Independent Dosimetric Predictor of Overall Survival in Locally Advanced Non–Small Cell Lung Cancer Christina K. Speirs, MD, PhD, Todd.

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Heart Dose Is an Independent Dosimetric Predictor of Overall Survival in Locally Advanced Non–Small Cell Lung Cancer Christina K. Speirs, MD, PhD, Todd A. DeWees, PhD, Sana Rehman, MD, Alerson Molotievschi, MD, MBA, Maria A. Velez, MD, Daniel Mullen, DDS, Sandra Fergus, BA, Marco Trovo, MD, Jeffrey D. Bradley, MD, Cliff G. Robinson, MD Journal of Thoracic Oncology Volume 12, Issue 2, Pages 293-301 (February 2017) DOI: 10.1016/j.jtho.2016.09.134 Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

Figure 1 (A) Kaplan-Meier curve for overall survival (OS) in patients with locally advanced NSCLC. The number at risk is shown below the graph at each time interval (in months). The 1-year OS was 61%, and the 2-year OS was 38%. (B) Kaplan-Meier curves for OS in patients with locally advanced NSCLC dichotomized by a heart V50 value less than 25% (blue) versus a heart V50 value of at least 25% (red) (p < 0.0001). The number at risk is shown below the graph at each time interval (in months). The 1-year OS was 70.2% (V50 < 25%) versus 46.8% (V50 ≥ 25%), and the 2-year OS was 45.9% (V50 < 25%) versus 26.7% (V50 ≥ 25%). heart V50 < 25%, less than 25% of the heart receiving at least 50 Gy; heart V50 ≥ 25%, at least 25% of the heart receiving at least 50 Gy. Journal of Thoracic Oncology 2017 12, 293-301DOI: (10.1016/j.jtho.2016.09.134) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

Figure 2 Univariate analysis for overall survival (by forest plot representation). x Axis shows the hazard ratio. Only a subgroup of variables with statistically significant p values (p < 0.05) is shown (see Supplementary Table 3 for additional variables and associated p values). Heart dosimetry variables are listed in red; lung dosimetry is listed in blue. RT, radiation therapy; CCI, Charlson comorbidity index; LLL, left lower lobe; LN, lymph node; PTV, planning target volume; cc, cubic centimeters/milliliters; V5, volume of the organ receiving at least 5 Gy. Journal of Thoracic Oncology 2017 12, 293-301DOI: (10.1016/j.jtho.2016.09.134) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

Figure 3 Multivariate analysis for overall survival (OS) (by forest plot representation) for all patients analyzed (N = 251) (A) and patients receiving concurrent chemoradiotherapy (n = 200); (B) the hazard ratio (HR), 95% CI (confidence interval), and p values are indicated for each variable. The x Axis shows HR. Red squares (planning parameter) or black (clinical parameter) squares indicate worsened OS with the variable, whereas the blue square indicates improved OS with the variable. Heart V50, volume of the heart receiving at least 50 Gy. Lung V5, proportion of the lung structure (excluding the target volume) receiving at least 5 Gy; LN, lymph node; MLD, mean lung dose; LLL, left lower lobe. Journal of Thoracic Oncology 2017 12, 293-301DOI: (10.1016/j.jtho.2016.09.134) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

Figure 4 Three-dimensional conformal radiation therapy (3D-CRT) (n = 249) versus intensity-modulated radiation therapy (IMRT) (n = 163) for posttreatment toxicities (based on the Common Terminology Criteria for Adverse Events [CTCAE], version 4). Fisher’s exact test was performed; the two-tailed p values are indicated (*p < 0.008, **p < 0.0001). The percentage of all 3D-CRT versus IMRT toxicity events for CTCAE grade 0 (yellow), grade 1 (orange), grade 2 (blue), grade 3 (red), grade 4 (purple), and grade 5 (black) toxicities are indicated. Journal of Thoracic Oncology 2017 12, 293-301DOI: (10.1016/j.jtho.2016.09.134) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions