Tumor Burden and Intraosseous Metabolic Activity as Predictors of Bone Marrow Failure during Radioisotope Therapy in Metastasized Prostate Cancer Patients

Abstract

Rationale. Radium-223-Dichloride (Ra-223) is an alpha-emitter, used to treat bone metastases. Patients with high metastatic burden and/or with increased trabecular bone uptake could present a higher incidence of hematologic toxicity. We hypothesized that these two factors are predictors of bone marrow failure. Material and Methods. A computer algorithm discriminated between trabecular bone (BVol) and tumor metastases (MVol) within pretherapeutic whole-body skeletal SPECT/CT (N=47). The program calculated the metastatic invasion percent (INV%) as the MVol/(MVol+BVol) ratio and extracted the BVol mean counts. BVol counts were correlated to % drop of hemoglobin (Hb), leukocytes (WBC), and platelets (PLT) after 3/6 Ra-223 cycles. Patient-specific and computational-derived parameters were tested as predictors of hematologic toxicity with MANOVA. Results. BVol counts correlated with drop of Hb (R = 0,65, p<0.01) and PLT (R = 0,45, p<0.01). Appendicular BVol counts showed a better correlation (p<0.05, p<0.01, and p<0.001 for Hb, WBC, and PLT, resp.). INV% directly correlated with BVol counts (R = 0.68, p<0.001). At MANOVA, grade III/IV toxicity was predicted by INV% (p<0.01), by long-bone invasion (p<0.005), and by BVol counts (p<0.05). Conclusions. In patients with significant bone tumor burden, degree of bone invasion and trabecular bone uptake are predictors of subsequent bone marrow failure.