Radiation therapy (RT)-induced cardiopulmonary injury, usually manifest as shortness of breath, is a major source of morbidity, and limits the delivery of RT for thoracic tumors. The physiologic determinants of RT-induced cardiopulmonary injury are not fully understood. In prior funding periods, we defined the relationship between changes in regional lung perfusion and changes in pulmonary function tests and symptoms. However, we also demonstrated that current methods to predict such RT-induced injury are suboptimal. In separate clinical studies, we have shown that RT causes reductions in regional myocardial perfusion that are correlated with abnormalities in heart wall motion and ejection fraction. The present proposal aims to simultaneously study RT-induced changes in lung and heart function and quantify their impact on global cardiopulmonary function. Animal and human data suggest that RT-induced heart and lung injury act together to cause cardiopulmonary dysfunction. Further, new conformal RT methods (e.g., intensity modulated RT, radiosurgery), often expose large portions of the lung and heart to diverse RT doses and fraction sizes. The impact of dose and fraction size on the pathogenesis of clinically significant lung and heart injury is not fully known. The current proposal builds on our prior work in the context of evolving clinical practice. We will simultaneously study RT-induced heart and lung injury in patients receiving modern conformal RT for lung cancer. We will prospectively determine the time, dose, and fraction-size dependence of RT-induced changes in regional lung perfusion (Aim 1), and regional heart perfusion/function (Aim 2). Heart and lung perfusion/function will be assessed with nuclear medicine and magnetic resonance imaging. We will quantify the relationship between RT-induced changes in regional lung perfusion, regional heart perfusion/function, and associated changes in global cardiopulmonary function (e.g. exercise testing) (Aim 3). This project is first to comprehensively evaluate both the lung-based and heart-based dosimetric and physiologic determinants of RT-induced cardiopulmonary injury. This information will lead to algorithms that accurately predict the risk of cardiopulmonary injury, facilitate the design of "safer" 3D dose distributions, and thus improve patient care.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
Project #
Application #
Study Section
Radiation Therapeutics and Biology Study Section (RTB)
Program Officer
Vikram, Bhadrasain
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of North Carolina Chapel Hill
Schools of Medicine
Chapel Hill
United States
Zip Code
Kelsey, Chris R; Jackson, Isabel L; Langdon, Scott et al. (2013) Analysis of single nucleotide polymorphisms and radiation sensitivity of the lung assessed with an objective radiologic endpoin. Clin Lung Cancer 14:267-74
Palma, David A; Senan, Suresh; Tsujino, Kayoko et al. (2013) Predicting radiation pneumonitis after chemoradiation therapy for lung cancer: an international individual patient data meta-analysis. Int J Radiat Oncol Biol Phys 85:444-50
Yirmibesoglu, Eda; Higginson, Daniel S; Fayda, Merdan et al. (2012) Challenges scoring radiation pneumonitis in patients irradiated for lung cancer. Lung Cancer 76:350-3
Zhang, Junan; Ma, Jinli; Zhou, Sumin et al. (2010) Radiation-induced reductions in regional lung perfusion: 0.1-12 year data from a prospective clinical study. Int J Radiat Oncol Biol Phys 76:425-32
Ma, Jinli; Zhang, Junan; Zhou, Sumin et al. (2010) Regional lung density changes after radiation therapy for tumors in and around thorax. Int J Radiat Oncol Biol Phys 76:116-22
Yin, Lingshu; Shcherbinin, Sergey; Celler, Anna et al. (2010) Incorporating quantitative single photon emission computed tomography into radiation therapy treatment planning for lung cancer: impact of attenuation and scatter correction on the single photon emission computed tomography-weighted mean dose and function Int J Radiat Oncol Biol Phys 78:587-94
Ma, Jinli; Zhang, Junan; Zhou, Sumin et al. (2009) Association between RT-induced changes in lung tissue density and global lung function. Int J Radiat Oncol Biol Phys 74:781-9
Gayou, Olivier; Das, Shiva K; Zhou, Su-Min et al. (2008) A genetic algorithm for variable selection in logistic regression analysis of radiotherapy treatment outcomes. Med Phys 35:5426-33
Chen, Shifeng; Zhou, Sumin; Yin, Fang-Fang et al. (2008) Using patient data similarities to predict radiation pneumonitis via a self-organizing map. Phys Med Biol 53:203-16
Das, Shiva K; Chen, Shifeng; Deasy, Joseph O et al. (2008) Combining multiple models to generate consensus: application to radiation-induced pneumonitis prediction. Med Phys 35:5098-109

Showing the most recent 10 out of 17 publications