Dosimetric correlation of integral dose-dependent lymphopenia in bone marrow after pelvic radiotherapy in locally advanced prostate cancer

We investigated dosimetrically lymphopenia concerning radiotherapy (RT) in patients receiving pelvic RT due to locally advanced prostate cancer (LAPCA). A total of 195 patients with lymph node–positive LAPCA were retrospectively evaluated and included in this single-center study. The relationship among absolute lymphocyte count (ALC), treatment modality, clinical stage, RT dose, and existence of pre-RT and post-RT lymphopenia (Grade≥2) was evaluated. Dependent McNemar analyses revealed significant relationship in pre-RT and post-RT (p<0.001). Of those with Grade<2, 108 (56.5%) developed Grade≥2 post-RT lymphopenia (p<0.001). V20-whole pelvic bone marrow (WPBM) (p=0.036), V30-WPBM (p=0.025), and V50-WPBM (p=0.008) values were significantly higher in Grade≥2 lymphopenia group. Also, V5-lumbo-sacral BM (LSBM) (p=0.013), V10-LSBM (p=0.041), V20-LSBM (p=0.015), and V30-LSBM (p=0.007) values were significant in Grade≥2 lymphopenia group. However, V30-lower-pelvis BM (LPBM) (p=0.024) and V50-LPBM (p<0.001) values were significant in Grade≥2 lymphopenia group. ROC analysis showed a significant effect on the development of Grade≥2 lymphopenia post-RT. Pre-RT baseline ALC values were associated with the development of Grade≥2 lymphopenia at a cut-off value of ≤1805 (p<0.001). Additionally, cut-off values of ≥76.1% for V20-WPBM (p=0.036), ≥47.3% for V30-WPBM (p=0.021), ≥7.3% for V50-WPBM (p=0.008), ≥68.5% for V30-WPBM (p=0.007), ≥41.2% for V30-LPBM (p=0.023), and ≥4.3% for V50-LPBM (p=0.001) were associated with development of Grade≥2 lymphopenia. Among all dosimetric parameters, V50-LPBM emerged as the strongest predictor of Grade ≥2 lymphopenia after RT. In clinical evaluations, no significant difference was seen in OS or PFS between Grades ≥2 and <2 groups (OS: p=0.194; PFS: p=0.489). This study demonstrated the clinical importance of pre-RT hematologic status and BM dosimetry, demonstrating that low pre-RT ALC and V50-LPBM values were the most significant predictors of Grade ≥2 lymphopenia after PNRT. These findings highlight importance of considering BM as an organ at risk and considering appropriate BM-sparing strategies in PNRT planning.