Association Between Radiation Heart Dose and Overall Survival in Lung Stereotactic Body Radiation Therapy

Abstract

<h3>Purpose/Objective(s)</h3> To determine if heart radiation dose and location affects overall survival (OS) in patients treated with Stereotactic Body Radiation Therapy (SBRT) to the lung. <h3>Materials/Methods</h3> Patients treated with SBRT to the lung at a single institution were identified. Pertinent information regarding patient characteristics, treatment delivered, and patient outcomes were obtained from a prospectively maintained cancer registry and the medical record. Radiation treatment information was obtained from the treatment planning system. Radiation dose in each voxel was extracted from the treatment planning system, mapped on anatomical organs, and converted to 2 Gy equivalent dose using linear quadratic model. The V% dosimetric variable, a percentage of volume receiving the dose ‘D' or greater, was used in the statistical analysis. Multivariate Cox regression analysis with Akaike Information Criterion (AIC) was used to determine which patient specific variables were predictive for OS. All predictive variables were further used in the Cox model with an addition of dosimetric variables for the heart. We examined V%_D variables for the whole heart, heart digitally subdivided into four segments (right-superior, left-superior, right-inferior, left-inferior), and heart digitally subdivided into 64 segments. <h3>Results</h3> 197 patients treated for lung lesions with SBRT were selected for this study. 135 patients were treated for primary lung cancer (117 stage I, 18 stage II) and 42 patients were treated for lung metastasis from other primary sites. There were 79 patients with lung adenocarcinoma, 38 with lung squamous cell carcinoma (SCC), and 62 patients with other histologies. Dose prescriptions were 50 Gy in 5 fractions (35%) and 48 Gy in 4 fractions (65%). The reference patient was 72.2 years old, with stage I, primary lung adenocarcinoma. Mean OS was 76.8 months and mean follow up was 40 months (2 – 230). Patient age (HR = 1.08/year, <i>P</i> < 0.01), histology (HR = 2.8 for SCC, <i>P</i> < 0.01) and stage (HR = 3.5 for stage II primary lung cancer, <i>P</i> < 0.01) were predictive for OS. Patients with right lung disease had longer OS than patients with left lung disease (HR = 0.6, <i>P</i> = 0.03). Whole heart DVH analysis did not reveal statistically significant predictors for OS. A DVH analysis of the heart divided into four segments suggested that low doses in the inferior segments of the heart decreased OS (V%_2 Gy, HR = 1.007/1%, <i>P</i> = 0.02). Maximum dose in the right-inferior portion of the heart was also predictive for OS (HR = 1.02/Gy, <i>P</i> = 0.02). A more detailed analysis of 3D dose distributions in the heart, using a digital subdivision of the heart into 64 segments, confirmed that low doses to the inferior part of the heart decreased OS (<i>P</i> = 0.01). <h3>Conclusion</h3> Low doses to the inferior portion of the heart may be associated with reduced OS in patients treated with SBRT to the lung. Age, histology and stage were associated with OS.