Risk Factors for Radiation Induced Lymphopenia in Patients With Breast Cancer: Does Radiotherapy Technique Matter?

PURPOSE/OBJECTIVE(S) Lymphopenia is a known risk factor for poor outcome in cancer patients. This study aimed to validate radiation induced lymphopenia and study the potential risk factors in patients with breast cancer receiving adjuvant radiotherapy (RT). MATERIALS/METHODS This is a retrospective study of consecutive patients who received adjuvant radiotherapy. Eligible patients must have invasive breast cancer with peripheral lymphocyte counts (PLC) prior to and at the end of RT. Patient characteristics, tumor and treatment factors were collected for risk assessment. Data were presented as mean and 95% confidence interval (95% CI) unless otherwise specified. The primary endpoints were lymphopenia post-RT and nadir-PLC/pre-PLC < 0.8. The effects of potential risk factors were estimated using univariate and multivariable analyses. Matched analysis was used to evaluate the influence of volumetric modulated arc therapy (VMAT)technique. RESULTS Between 2015 and 2020, 735 patients met study criteria. The mean PLC was 1.58*109/L (95% CI: 1.54-1.62*109/L) before and 0.99*109/L (95% CI: 0.96-1.01*109/L) after RT (P < 0.001). At the end of RT, 60.5% (445/735, 95% CI: 60.4-60.6%) patients had lymphopenia, rendering 30.7%, 23.4%, 6.1% and 0.3% for grade 1, 2, 3, and 4, respectively. The reduction of PLC was most remarkable of all different kinds of the peripheral blood cells. Univariate and multivariable analyses showed radiotherapy technique with VMAT, mean lung dose and chemotherapy were significant risk factors (P < 0.05) for lymphopenia post-RT. RT technique was the only significant risk factor (P < 0.05) for nadir-PLC/pre-PLC < 0.8. Patients treated with VMAT technique had significantly greater reduction of PLC along with greater V5s of the lungs, even after matching mean lung dose and radiated treatment volume. CONCLUSION Lymphopenia is common in patients with breast cancer after adjuvant RT. RT technique is the only significant factor for both lymphopenia and nadir-PLC/pre-PLC < 0.8, suggesting the significance of RT optimization to minimize lymphopenia to improve treatment outcome.