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 (B_Vol) and tumor metastases (M_Vol) within pretherapeutic whole-body skeletal SPECT/CT (N = 47). The program calculated the metastatic invasion percent (INV%) as the M_Vol/(M_Vol + B_Vol) ratio and extracted the B_Vol mean counts. B_Vol 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: B_Vol counts correlated with drop of Hb (R = 0,65, p < 0.01) and PLT (R = 0,45, p < 0.01). Appendicular B_Vol 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 B_Vol 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 B_Vol 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.