A feasibility study evaluating the functional diffusion map as a predictive imaging biomarker for detection of treatment response in a patient with metastatic prostate cancer to the bone

Kuei C Lee, Deborah A. Bradley, Maha Hussain, Charles Meyer, Thomas L Chenevert, Jon A Jacobson, Timothy D Johnson, Craig J Galban, Alnawaz Rehemtulla, Kenneth J Pienta and Brian D Ross

Year 1998, Volume , Issue

Abstract

Prostate cancer is the most commonly diagnosed cancer in American men. Among those men, a subset will inevitably present with metastatic disease to the bone, which is the predominant site of metastasis. Though advances in therapeutic strategies have decreased the overall mortality rate of this disease, metastatic prostate cancer is still deemed incurable. A well recognized limitation in evaluating new treatments for metastatic prostate cancer is the inability to use imaging modalities including CT, MRI, skeletal scintigraphy and plain radiography to objectively and quantitatively assess response to therapy. In fact, current clinical response criteria consider bone metastases to be "unmeasureable". We recently reported the application of the functional diffusion map (fDM), a relatively new imaging biomarker purported for treatment response assessment, to be useful for measuring treatment response of prostate cancer bone metastases in mice. In this study, we evaluated the feasibility of clinically translating the fDM approach for quantification of the spatiotemporal effects of treatment of bone tumor response in a patient treated for metastatic prostate cancer with bone metastases. In this study, a patient beginning androgen deprivation therapy was scanned using CT, bone scan and MRI (proton-density, T2-weighted and diffusion) prior to treatment. Follow up MRI scans were performed 2 weeks and 8 weeks post treatment initiation to monitor changes in tumor diffusion values. Three lesions were identified for fDM analysis of which, all three demonstrated a quantifiable, early increase in tumor diffusion values at 2 weeks and increased further at 8 weeks post-treatment-initiation. Moreover, this finding correlated with a decrease in the patient’s PSA levels suggestive of patient response. CT, bone scans and anatomical MRI images obtained at 8-9 weeks post treatment were not useful for assessing treatment effectiveness. This study reveals the feasibility of obtaining fDM measurements in osseous lesions over time and shows that detected changes were consistent with therapeutic response. While further patient accrual is ongoing, validation of the fDM imaging biomarker, if successful, would provide a major advance for the development of clinical trials with a quantifiable therapeutic endpoint to assess response in patients with metastatic cancer.

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