Bone Marrow Suppression during Postoperative Radiation for Bladder Cancer and Comparative Benefit of Proton Therapy-Phase 2 Trial Secondary Analysis

Abstract

Purpose: For patients with high-risk bladder cancer (pT3þ or Nþ), local regional failure remains a challenge after chemotherapy and cystectomy. An ongoing prospective phase 2 trial (NCT01954173) is examining the role of postoperative photon radiation therapy for high-risk patients using volumetric modulated arc therapy. Proton beam therapy (PBT) may be beneficial in this setting to reduce hematologic toxicity. We evaluated for dosimetric relationships with pelvic bone marrow (PBM) and changes in hematologic counts before and after pelvic radiation therapy and explored the potential of PBT treatment plans to achieve reductions in PBM dose. Materials and Methods: All enrolled patients were retrospectively analyzed after pelvic radiation per protocol with 50.4 to 55.8 Gy in 28 to 31 fractions. Comparative PBT plans were generated using pencil-beam scanning and a 3-beam multifield optimization technique. Changes in hematologic nadirs were assessed using paired t test. Correlation of mean nadirs and relative PBM dose levels were assessed using the Pearson correlation coefficient (CC). Results: Eighteen patients with a median age of 70 were analyzed. Mean cell count values after radiation therapy decreased compared with preradiation therapy values for white blood cells (WBCs), absolute neutrophil count (ANC), absolute lymphocyte count (all P,.001), and platelets (P ¼.03). Increased mean PBM dose was associated with lower nadirs in WBC (Pearson CC -0.593, P ¼.02), ANC (Pearson CC -0.597, P ¼.02), and hemoglobin (Pearson CC -0.506, P ¼.046), whereas the PBM V30 to V40 correlated with lower WBC (Pearson CC -0.512 to -0.618, P,.05), and V20 to V30 correlated with lower ANC (Pearson CC -0.569 to -0.598, P,.04). Comparative proton therapy plans decreased the mean PBM dose from 26.5 Gy to 16.1 Gy (P,.001) and had significant reductions in the volume of PBM receiving doses from 5 to 40 Gy (P,.001). Conclusion: Increased PBM mean dose and V20 to V40 were associated with lower hematologic nadirs. PBT plans reduced PBM dose and may be a valuable strategy to reduce the risk of hematologic toxicity in these patients.