Radiotherapy-related lymphopenia affects overall survival in patients with lung cancer

Abstract

Introduction: Lymphopenia following radiotherapy has an adverse effect on patient's outcome. However, the relationship between radiotherapy dose delivery and lymphopenia is not fully understood. This work is utilizing image-based data mining to identify anatomical regions where the received dose is correlated with severe lymphopenia. Methods: 901 lung cancer patients were analyzed. A Cox model was used to assess prognostic factors of overall survival (OS). Two matched groups were defined-patients with and without lymphopenia?G3-based on tumor volume, baseline lymphocytes, and delivered dose. Then, data mining was used to identify regions where dose correlates significantly with lymphopenia?G3. For this, dose matrices were aligned using registration of the computed tomography (CT) images to one reference patient. Mean dose distributions were obtained for the two groups and organs of significance were detected. Dosimetric parameters from the identified organs that had the highest correlation with lymphocytes at nadir were selected. Multivariable analysis was conducted for lymphopenia?G3 on the full lung cohort and the model was tested on 305 esophageal cancer patients. Results: Adjusted Cox regression showed that lymphopenia?G3 was an independent factor of OS. The anatomical regions identified were heart, lung, and thoracic vertebrae. Dosimetric parameters for lymphopenia included vertebrae V20, mean lung dose and, mean heart dose which was further validated in the esophageal cancer cohort. Conclusions: We have shown severe lymphopenia during radiotherapy is a significant poor prognostic factor for OS in lung cancer patients and could be mitigated by minimizing vertebrae V20, mean lung and heart dose to limit irradiation of stem cells and blood pool. Keywords: Image-based data mining; chemoradiotherapy; esophageal cancer; lung cancer; lymphopenia; radiotherapy.