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

Purpose: We investigated dosimetrically lymphopenia concerning radiotherapy (RT) in patients receiving pelvic RT due to locally advanced prostate cancer (LAPCA). Materials and Methods: 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). Results: 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). Conclusions: 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.