Pilot study of targeted skeletal radiation therapy for bone-only metastatic breast cancer

Purpose: Bone-targeted radiation therapy is an attractive strategy for addressing bone disease with minimal systemic toxicity. This pilot study was designed to determine the safety and efficacy of ¹⁶⁶Holmium (Ho)-DOTMP for irradiating malignant cells and adjacent marrow in women with bone-only metastatic breast cancer. Patients and Methods: Subjects included 6 women aged ≤ 65 years with breast cancer and bone-only metastases at M. D. Anderson Cancer Center. The activity of 166Ho-DOTMP was calculated to deliver a therapeutic absorbed dose of 22 Gy (n = 3) or 28 Gy (n = 3) to the marrow. Treatment was followed by autologous stem cell transplantation to circumvent the anticipated myelosuppresion. Median follow-up time was 40 months. Results: All subjects showed prompt hematologic recovery. No patient experienced grade 3/4 acute toxicity aside from myelosuppression. Two patients developed hemorrhagic cystitis 2 years after therapy. One patient developed myelodysplastic syndrome but was found to have had pre-existing trisomy 8. Two patients remained progression free without evidence of disease for more than 6 years. Five women experienced disease relapse (4 at extraosseous sites) and died of progressive disease. Median time to progression was 10.4 months. Conclusion: The approach of bone-targeted radiation therapy with ¹⁶⁶Ho-DOTMP had an acceptable toxicity profile, and sustained complete response was obtained in 2 of 6 patients. We are conducting a phase II study to evaluate the efficacy of targeted skeletal radiation therapy for treating bone-only metastases.