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Title: Cancer-induced bone pain (CIBP) : clinical characterisation and biomarker development
Author: Scott, Angela C.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2010
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Background: Cancer-induced bone pain (CIBP) is a major clinical problem and a considerable therapeutic challenge. Radiotherapy (XRT) is the gold standard treatment for CIBP, but only half of patients achieve adequate analgesia. Patients have increased morbidity, anxiety and depression and reduced performance and quality of life. Despite these issues, CIBP is a neglected area of clinical research. Animal models have increased current knowledge of the pathophysiology, but clinical research is needed to translate these findings from bench to bedside. Also lacking is a standardised, comprehensive tool to assess CIBP and clinical biomarkers to predict analgesic response to treatment. Aims: 1) To summarise current understanding of the pathophysiology, epidemiology, clinical features, assessment and management of malignant bone disease and CIBP. 2) To characterise CIBP using quantitative sensory testing as a measure of altered sensory processing. 3) To establish systematically the sensory, cognitive, affective and functional components of CIBP to develop a comprehensive assessment tool. 4) To explore whether clinical biomarkers can be developed to aid prediction of response to treatment for CIBP, in particular XRT. Results: Assessment of CIBP, characterising the multi-dimensional components, was clinically practical and acceptable to patients. Using objective measures of function, patients with CIBP were a frailer, less active population compared with healthy adults. Prior to treatment, pain was severe with relationships seen between CIBP and sensation, mood, fear avoidance, catastrophizing and function. Patients who dropped out prior to follow up were significantly less active, with higher levels of depression and fear avoidance behaviour. Sixty-nine percent of evaluable patients who completed two assessments (48% of all patients on an intention-to-treat basis), achieved an analgesic response to XRT for CIBP, as defined as an improvement of ≥ 30% in the Brief Pain Inventory worst pain score two months after treatment. All dimensions of pain, fear avoidance and catastrophizing improved significantly in responders, but not non-responders. Anxiety, depression and emotional distress fell by a greater degree in responders. No objective functional differences were seen after XRT. Clear evidence of altered sensory processing was seen at the site of CIBP with abnormalities in both mechanical and thermal parameters. XRT resulted in alterations in response to evoked stimuli in responders with a greater number of patients in whom sensation normalised after XRT compared with non-responders. Patients with a combination of altered sensation to thermal, pin prick and wind up stimuli showed the largest reduction in worst pain after XRT. Abnormal cool sensation at the site of CIBP was an independent predictor of analgesic response to treatment. Conclusion: Strong associations exist between CIBP, sensation, cognition, mood and function. Multi-dimensional assessment should be performed to improve quality of life. Translational research to provide targeted individualised treatment should be high on the research agenda. Future work should focus on thermal sensory processing as a potential clinical biomarker of response to palliative XRT for CIBP.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available