Predicting bone marrow suppression from urinal 8-hydroxy-2'-deoxyguanosine level during the treatment with radium-223 in patients with cancer bone metastasis.

Background: Cancer bone metastasis (BM) from castration-resistant prostate cancer (CRPC) is the terminal stage of cancer, and it demonstrates a decreasing quality of life (QOL) due to skeletal-related events such as pain and bone fracture. Radium-223 dichloride administration is frequently selected as an internal radionuclide target therapy. This radioactive molecule has a potency of accumulation in bone minerals and emits alpha particles by decaying radium-223. These physical properties cause cellular damage to bone metastatic CRPC cells. However, some poor outcomes of patients are occasionally observed, such as bone marrow suppression. Therefore, in order to understand the status of deep BM, it is necessary to discover biomarkers that effectively reflect bone metabolism. In this study, we investigated whether urinal 8-hydroxy-2'-deoxyguanosine (8-OHdG), a one of oxidative stress marker, could be a predictive biomarker to identify whether radium-223 administration causes bone marrow suppression in patients.

Methods: The urine and blood serum from four cancer patients with BM were collected and stored at -80 ℃ deep freezer until analysis. Following radiotherapeutic guidelines, three to six radium-223 internal radiotherapy doses were prescribed based on the patient, and it was terminated due to decreased therapeutic reserve.

Results: The patients who were administered six radium-223 doses demonstrated upregulation of urinal 8-OHdG, serum C-terminal telopeptide of type I collagen (1CTP), and type I collagen cross-linked N-telopeptide (NTX) concentrations. Conversely, serum bone alkaline phosphatase (BAP) was downregulated. The patients who were administered less than five radium-223 doses exhibited urinal 8-OHdG downregulation and similar serum 1CTP, NTX, and BAP levels compared to before administration. In the patient who had bone marrow suppression, a negative correlation between time after first administration of radium-223 and urinal 8-OHdG was observed.

Conclusions: These results suggest that a urinal 8-OHdG concentration has a potency of biomarker for bone marrow suppression under the administration of radium-223 in the patient with BM from CRPC.