High Doses to the Heart Are Associated with Reduced Overall Survival in Stage III Non-Small Cell Lung Cancer Patients Undergoing Radiation Therapy

Abstract

To determine if radiation induced cardiac toxicity influences overall survival (OS) in stage III non-small cell lung cancer (NSCLC) patients undergoing radiation therapy (RT). A single institution database of 134 stage III NSCLC patients, treated with conventionally fractionated radiation therapy, was retrospectively analyzed in this study. The heart structure was contoured for each patient within a treatment planning system. Dose Volume Histogram (DVH) indices were computed from the cumulative whole heart DVH and were used together with patient specific characteristics in Multivariate Cox Regression model. A family of models, each using a single DVH index and prescription dose, patient age, mean lung dose, lungV20, tumor site, tumor laterality and disease stage were examined to find dosimetric indices which were most predictive for OS. Akaike Information Criterion was used in each model to find significant predictors for the OS. Subsequently, each heart was digitally subdivided into four parts along sup-inf and left-right axes. The same analysis was repeated using cumulative DVHs in each sub-part separately. 60% of patients presented with stage IIIA and 40% with stage IIIB cancer. Doses prescribed were 61.9±6.8Gy in 2Gy fractions, and 77% of patients also received chemotherapy. The mean time to the last follow-up was 1.5 years, with a range of 0.13 to 6.8 years. The mean age was 70.5 years with a range of 42 to 91 years. High doses to the heart were found to be significant predictors for OS, specifically: V%_55Gy (p=0.01) and V%_60Gy (p=0.04), where V%_D is the percentage of the volume which received dose D, or greater. The hazard ratio (HR) associated with heart irradiation was approximately 1.05 per 1% of whole heart volume irradiated to the dose 55Gy, or greater. Three patient characteristics were also found to be predictive for OS in all models: cancer stage (IIIA/IIIB, HR=1.7, p=0.02), chemotherapy (HR=0.34, p<0.01) and age before RT (HR=1.03/year, p=0.02). The analysis of digitally subdivided heart structures showed that V%_55Gy (p=0.01) and V%_60Gy (p=0.02) in the right-superior portion of the heart were significant predictors for the OS, while doses to the remaining three segments of the heart were not predictive. High doses to the heart reduce overall survival in stage III NSCLC patients treated with radiation therapy. High doses to the right-superior portion of the heart appear to be primarily responsible for the decrease in OS.