Clinical and Genetic Factors Related to Cancer-Induced Bone Pain and Bone Pain Relief

1. Emanuela Scarpi^a,

+ Author Affiliations

1. ^aBiostatistics and Clinical Trials Unit, ^bBiosciences Laboratory, ^cDepartment of Medical Oncology, and ^dPalliative Care Clinic, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS, Meldola, Italy; ^eDepartment of Anesthesiology and Intensive Care Medicine and ^fCancer Clinic, St. Olavs University Hospital, Trondheim, Norway; ^gEuropean Palliative Care Research Centre, Department of Cancer Research and Molecular Medicine, ^hDepartment of Circulation and Medical Imaging, and ⁱDepartment of Laboratory Medicine, Children’s and Women’s Health and European Palliative Care Research Centre, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway

1. Correspondence: Marco Maltoni, M.D., Palliative Care Clinic, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS, Via P. Maroncelli 40, 47014 Meldola (FC), Italy. Telephone: 39 0543 733332; E-Mail: ma.maltoni@ausl.fo.it malto.ma@tin.it

Abstract

Objective. The study objective was to evaluate whether there are clinical or genetic differences between patients with cancer-induced bone pain (CIBP) and patients with non-CIBP, and, in the CIBP group, in those with good versus poor opioid response.

Materials and Methods. A total of 2,294 adult patients with cancer who were receiving opioids for moderate or severe pain were included in the European Pharmacogenetic Opioid Study. Pain intensity and pain relief were measured using the Brief Pain Inventory. Linkage disequilibrium of 112 single nucleotide polymorphisms was evaluated in 25 candidate genes, and 43 haplotypes were assessed. Correlations among demographical factors, disease-related factors, genetic factors, CIBP, and pain relief were analyzed by logistic regression models corrected for multiple testing. Patients with bone metastases and bone/soft tissue pain were defined as having prevalent bone pain (CIBP population). This population was compared with patients who had other types of cancer pain (non-CIBP).

Results. A total of 577 patients (26.2%) had CIBP, and 1,624 patients (73.8%) had non-CIBP. Patients with CIBP had more breakthrough cancer pain episodes (64.2% vs. 56.4%, p = .001), had significantly higher pain interference in “walking ability in the past 24 hours” (p < .0001), used more adjuvant drugs (84.1% vs. 78.3%, p = .003), and had a higher, albeit nonsignificant, median overall survival (3.8 vs. 2.9 months, p = .716) than patients with non-CIBP. None of the examined haplotypes exceeded p values corrected for multiple testing for the investigated outcomes.

Conclusion. Patients with CIBP who were taking opioids had a clinical profile slightly different from that of the non-CIBP group. However, no specific genetic pattern emerged for CIBP versus non-CIBP and for responsive versus nonresponsive patients with CIBP.