TITLE:
Using Novel Statistical Techniques to Accurately Determine the Predictive Dose Range in a Study of Overall Survival after Definitive Radiotherapy for Stage III Non-Small Cell Lung Cancer in Association with Heart Dose
AUTHORS:
Joshua R. Niska, Jiuyun Hu, Jing Li, Michael G. Herman, Cameron S. Thorpe, Steven E. Schild, Mirek Fatyga
KEYWORDS:
Lung Cancer, Cardiac Toxicity, Lung Radiation Therapy, Non-Small Cell Lung Cancer, Radiation Toxicity
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.12 No.9,
September
29,
2021
ABSTRACT: Purpose: Recent studies of radiotherapy (RT) for stage III non-small-cell lung cancer (NSCLC) have
associated high dose to the heart with cardiac toxicity and decreased overall survival (OS). We used advanced
statistical techniques to account for correlations between dosimetric
variables and more accurately
determine the range of heart doses which are associated with reduced OS in
patients receiving RT for stage III NSCLC. Methods: From 2006 to 2013,
119 patients with stage III NSCLC received definitive RT at our institution. OS data was obtained from
institutional tumor registry. We used multivariate Cox model to determine patient
specific covariates predictive for reduced overall survival. We examined age,
prescription dose, mean lung dose, lung V20, RT technique, stage, chemotherapy,
tumor laterality, tumor volume, and tumor site as candidate covariates. We subsequently used novel
statistical techniques within multivariate Cox model to systematically search the whole heart dose-volume
histogram (DVH) for dose
parameters associated with OS. Results: Patients were followed until death or 2.5 to 81.2 months (median
30.4 months) in those alive at last follow up. On multivariate analysis of
whole heart DVH, the dose of 51 Gy was identified as a
threshold dose above which the dose volume relationship becomes predictive for
OS. We identified V55Gy (percentage of the whole heart volume receiving at least 55 Gy) as the best single
DVH index which can be used to set treatment optimization constraints (Hazard Ratio = 1.044
per 1% increase in heart volume exposed to at least 55 Gy, P = 0.03). Additional characteristics correlated with OS
on multivariate analysis were age, stage (IIIA/IIIB), and administration of
chemotherapy. Conclusion: Doses above 51 Gy, applied to small volumes of the heart, are associated with worse OS in stage III NSCLC
patients treated with definitive RT. Higher stage, older age and lack of
chemotherapy were also associated with reduced OS.