Serum carboxyterminal telopeptide (ICTP) as a prognostic marker in bone metastases (BM) treated with bisphosphonates

Abstract

10107 Background: Biochemical markers of bone turnover, such as N- and C-terminal cross-linking telopeptide of type I collagen have been evaluated as prognostic matkers in patients with BM. In one of such study, we found that ICTP was not affected by bisphosphonate (BP) therapy (Costa, et al., JCO 2002; 20:850–856). In this prospective study we analyzed whether the baseline level of ICTP was predictive of skeletal related events (SREs) as defined by: pathologic fractures (PF), radiation to treat BM (RT) or spinal cord compression (SCC); time to progression (TTP) and overall survival (OS) in patients with BM from solid tumors under BP therapy. Methods: We studied 116 BM patients, median age: 64 years; 67% females; 61% breast cancer; 19% prostate cancer; and 20% other tumor types. The x-ray pattern of BM was lytic in 54% patients, blastic in 23%, and mixed in 21%. At the time of study entry, all patients had serum ICTP levels measured with RIA reagents from Orion Diagnostica (reference range: 2.5–4.0 μg/L). A serum ICTP cutoff of 6.2 μg/L was established using the mean + 2D. The occurrence of SREs was recorded during the study and an objective evaluation of BM status was performed every 4–6 months. During the time period on study, patients received treatment with IV zoledronate (57%), IV pamidronate (28%), or more than one BP. The proportional hazards model was used to investigate the correlation of ICTP baseline level with time to first SRE (TTSRE), TTP, and OS; and Poisson regression with the skeletal morbidity rate (SMR): number of SREs/person/year. Results: The median follow-up was 21 months. 81.9% patients had ICTP level above 6.2 μg/L and the mean value of ICTP was 15.1 (SD 11.9) μg/L. During the time period on study, 38% had PF, 57% had RT, and 9.5% had SCC. Median TTSRE was 20 months and the SMR was 0.84. Median TTP was 12 months and median OS time was 29 months. ICTP levels above 6.2 μg/L were associated with increased mortality risk (hazard ratio (HR) 2.86, 95%CI 1.37–6.00, p=0.005) and increased SMR (incidence rate ratio 1.88, 95%CI 0.98–3.60, p=0.057), but not with TTP (HR 1.18, 95%CI 0.67–2.07, p=0,57) or TTSRE (HR 1.59, 95%CI 0.82–3.08, p=0.17). Conclusions: Elevated serum ICTP levels is associated with decreased survival and increased incidence of SREs in BM patients on BP therapy. No significant financial relationships to disclose.