Quantifying functional imaging modalities and their application in the assessment of treatment response and prognosis in bone metastases

Abstract

Bone metastases are common in malignancy and cause morbidity. However, assessing treatment response of bone metastases with morphological changes is insensitive, variable and lacks specificity. This thesis reports initial recruitment data from three prospective trials, examining the potential role of functional imaging methods as early biomarkers of response and prognosis. Breast and prostate cancer patients with bone metastases had 18F-Fluoride Positron Emission Tomography (PET) and Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI) before treatment and again at 8-12 weeks following treatment commencement. Clinical response outcomes were appraised up to 24 weeks. For both imaging methods, there were significant differences in the parameters between breast and prostate metastases reflecting different bone metastasis pathophysiology of these tumours, and significant intra-patient inter-lesion heterogeneity was evident. 18F-Fluoride per-lesion analysis (62 lesions) identified: an increase in SUVmax (p=0.048predicted for treatment response, a lower SUVmean/max/peak/entropy/Ki and higher SUVenergy before treatment were significantly associated with OS benefit (all p<0.05) and higher %ΔSUVmean/max/peak/entropy/Ki, and lower %ΔSUVenergy at 8 weeks were significantly associated with an OS benefit (all p<0.05). DW-MRI per-lesion analysis (92 lesions) identified a higher %ΔADC predicted for treatment response (p=0.029) and a lower baseline ADC is prognostic of OS (p<0.05). Per-patient analyses (18F-Fluoride PET n=12; DW-MRI n=20) yielded less predictive and prognostic value, and have demonstrated the significant impact of VOI definition methods on the 18F-Fluoride quantification. Whole-body methods have been developed for DW-MRI and 18F-Fluoride PET to enable quantification of the heterogeneous skeletal metastatic burden; whole-body parameters were not more predictive or prognostic than per-patient analyses. DW-MRI and 18F-Fluoride PET have shown potential as early imaging biomarkers of treatment response and prognosis for bone metastases in breast and prostate cancer, and significant methodological factors have been considered, aiming to achieve practical clinical utility of these techniques.

Date of Award	2017
Original language	English
Awarding Institution	King's College London
Supervisor	Gary Cook (Supervisor)