title: RANKL: A promising circulating marker for bone metastasis response.
abstract: Bone metastases are a frequent event in patients with solid tumors. Although great advances have been made in the treatment of these patients, the identification of novel, accurate indicators of bone response would greatly facilitate the clinical management of the disease. The receptor activator of nuclear factor-κB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) signaling pathway is significantly involved in bone metastasis formation. The main aim of the present study was to evaluate the role of circulating RANK, RANKL and OPG levels in predicting bone response. Marker accuracy was also compared with that of the conventional tumor marker N-terminal telopeptide of type I collagen (NTX). A prospective study was performed on 49 patients with bone metastases from breast, lung and prostate cancer, who were undergoing treatment with zoledronic acid. Patients were monitored for 1 year with blood tests, clinical evaluation and instrumental exams according to the response evaluation criteria of the University of Texas M. D. Anderson Cancer Center (Houston, TX, USA) and the Positron Emission Tomography Response Criteria in Solid Tumors. Circulating RANK/RANKL/OPG transcripts and NTX levels were evaluated by reverse transcription-quantitative polymerase chain reaction and immune enzymatic assay, respectively. The baseline RANKL levels differed significantly between responders and non-responders, whereas no differences in NTX levels were observed between the two groups. Receiver operating characteristic curve evaluation for all markers revealed that RANKL was the most accurate marker, with an area under the curve of 0.74 (95% confidence interval, 0.54-0.93). In addition, RANKL, which is the target of the novel monoclonal antibody denosumab, was the most accurate predictor of bone response in the present series of patients with bone metastases. Thus, the use of RANKL as a marker could potentially improve clinical practice, as current bone response evaluation is still somewhat problematic.
authors.affiliation: Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, I-47014 Meldola, Italy.
authors.forename: Toni
authors.initials: T
authors.lastname: Ibrahim
authors.affiliation: Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, I-47014 Meldola, Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: Ricci
authors.affiliation: Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, I-47014 Meldola, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Scarpi
authors.affiliation: Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, I-47014 Meldola, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Bongiovanni
authors.affiliation: Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, I-47014 Meldola, Italy.
authors.forename: Rossana
authors.initials: R
authors.lastname: Ricci
authors.affiliation: Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, I-47014 Meldola, Italy.
authors.forename: Nada
authors.initials: N
authors.lastname: Riva
authors.affiliation: Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, I-47014 Meldola, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Liverani
authors.affiliation: Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, I-47014 Meldola, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: De Vita
authors.affiliation: Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, I-47014 Meldola, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: La Manna
authors.affiliation: Radiology Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, I-47014 Meldola, Italy.
authors.forename: Devil
authors.initials: D
authors.lastname: Oboldi
authors.affiliation: Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, I-47014 Meldola, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Serra
authors.affiliation: Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, I-47014 Meldola, Italy.
authors.forename: Flavia
authors.initials: F
authors.lastname: Foca
authors.affiliation: Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, I-47014 Meldola, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Cecconetto
authors.affiliation: Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, I-47014 Meldola, Italy.
authors.forename: Dino
authors.initials: D
authors.lastname: Amadori
authors.affiliation: Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, I-47014 Meldola, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Mercatali
keywords: NTX; OPG; RANK; RANKL; bone metastases