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Title: The involvement of the central nervous system in chemotherapy-induced peripheral neuropathy, and the symptom burden and health-related quality of life in patients with multiple myeloma
Author: Cachia, Elaine
ISNI:       0000 0004 2737 8441
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2013
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Background: Modern treatments extend life expectancy in patients with multiple myeloma (MM) and a high incidence of chemotherapy-induced peripheral neuropathy (CIPN) has evolved. The impact of disease and treatment on health-related quality of life (HRQoL) in MM is poorly characterised. This work aimed to investigate (i) the neuroanatomical functional correlates of pain processing in CIPN and (ii) HRQoL and symptom burden in advanced, intensively-treated myeloma. Methods: First study: twelve neurophysiologically assessed patients with CIPN and 12 healthy volunteers underwent fMRI to determine the brain's haemodynamic response to noxious heat stimuli applied to the extremities. Second study: detailed HRQoL and neuropathy assessments, serum IL-6 and TNF-α levels were measured in 32 patients with MM (median age = 61 yrs, duration of disease = 5.5 yrs) who had previously undergone 3 lines of treatment. Results: First study: Neurophysiological testing in MM patients confirmed peripheral neuropathy in the feet. Significant hypo-activation of the right superior frontal gyrus and hyper-activation in the precuneus were present in response to foot stimulation in the CIPN-myeloma compared to healthy control groups. Significant positive correlation existed between neuropathy score and frontal opercula activation, during foot stimulation in CIPN-myeloma patients. Second study: Thirty-two MM patients (duration of disease = 5.5 yrs) were recruited. Physical functioning was significantly compromised (p < 0.001) and associated with progressive work disability and concerns regarding loss of independence. Fatigue and pain were the predominant symptoms, impacting negatively on physical functioning (p < 0.001). Half of the patients reported neuropathic pain. This sub-group scored lower measures of physical, role and social functioning on EORTC QLQ-C30 and future perspectives from the EORTC MY20 assessments compared to patients without neuropathy. Average pain and pain interference from the BPI-SF were positively correlated (p < 0.05 and p < 0.005, respectively) with serum IL-6 levels. Conclusion: Patients with MM suffer from a high peripheral neuropathy symptomatology burden, leading to a worsening functioning and increased pain. FMRI data indicates that heat-pain stimuli evoke differential activation of distinct cortical regions, suggesting different central pain processing mechanisms in CIPN-myeloma patients. Despite disease control and supportive care, intensively-treated myeloma survivors have significantly compromised HRQoL related to symptom burden.
Supervisor: Wilkinson, Iain ; Ahmedzai, Sam Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available