Purpose: To investigate the dosimetric feasibility of lymphocyte-sparing radiotherapy in locally advanced lung cancer. We hypothesized that dose to lymphocyte-related organs at risk (LOAR) can be reduced while maintaining target coverage and adherence to standard OAR constraints.
Methods: Fifteen consecutive patients with stage III non-small cell lung cancer were selected from a previous prospective clinical trial. LOARs included thoracic active bone marrow (ABM), heart and lungs. Thoracic ABM was defined as subvolume of thoracic vertebrae with a standardized uptake value greater than the mean on the coregistered FDG-PET image. Each patient had two volumetric modulated arc therapy plans: baseline and LOAR-sparing. Baseline plans used conventional dose-volume constraints for the planning target volume (PTV) and standard OARs, while LOAR-sparing plans used the same constraints and the following additional constraints for the LOARs: thoracic ABM V20Gy ≤45%, heart V5Gy ≤48%, and lung V5Gy ≤51% (defined based on published data demonstrating an association with radiation-induced lymphopenia). We compared dose-volume metrics of the PTV, standard OARs, LOARs, and effective dose to circulating immune cells (EDIC) (previously associated with lymphopenia) between the baseline and LOAR-sparing plans using the Wilcoxon signed-rank test.
Results: Compared with the baseline plans, LOAR-sparing plans had a mean absolute reduction of 6.2% (range, -2.8%─21.7%) in the ABM V20Gy (p=0.012), 14.4% (-1.4%─42.5%) in the heart V5Gy (p=0.002), 12.4% (0.5%─32.8%) in the lung V5Gy (p<0.001), and 0.7 Gy (0.0─2.3 Gy) in EDIC (p<0.001), along with reductions in the conventional heart and lung constraints. LOAR-sparing plans had greater dose heterogeneity in the PTV and higher maximum dose to the spinal cord, which were clinically acceptable.
Conclusion: In this first investigation on the feasibility of lymphocyte-sparing radiotherapy, we demonstrated that dose to LOARs can be reduced while maintaining target coverage and adherence to standard OARs, providing evidence to support further investigations.