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.
Treatment Planning, Lung, Radiation Effects
TH- External Beam- Photons: treatment planning/virtual clinical studies