BACKGROUND The majority (~ 90%) of patients with metastatic prostate cancer will have multiple bony metastases. Despite being the most common area of metastases in prostate cancer, reliably evaluating the burden of bony metastases at baseline and monitoring response to different therapeutic interventions is challenging and not standardised. Isotope Bone Scan (IBS) is the most widely utilised imaging modality in staging and initial management decisions in prostate cancer. Presently, the standard interpretation of IBS relies on subjective assessment of the number and geographical distribution of metastases. Automated Bone Scan Index (aBSI) is a quantitative analysis of IBS reflecting the extension of tumour burden in bone as present of the total skeleton weight calculated from IBS. This method allows a standardised approach to comparing distribution of bony metastatic disease. Figure 1. Schematic of aBSI methodology OBJECTIVE The objective of this study was to evaluate aBSI as an Imaging Biomarker in Metastatic Castration Sensitive Prostate Cancer (mCSPC) in a novel clinical trial with Radium-223 (Ra-223) and External Beam Radiotherapy (EBRT). METHODS We present preliminary data from a Phase II trial exploring the use of Ra-223 in combination with prostate and pelvic EBRT post-docetaxel in mCSPC (>3 bone metastases, no lymph node or visceral disease T4N0/1M1b). Fifteen of 28 patients enrolled in the trialhad baseline and treatment follow-up IBS available for aBSI analysis. The EXINI aBSI software programmed was used to retrospectively analyse the IBS and generate the aBSI value. Alkaline phosphatase (ALP) values and Prostate Specific Antigen (PSA) were collected. RESULTS Fifteen patients had baseline and follow-up bone scans (pre and post Ra-223) available in DICOM format for aBSI analysis. All 15 patients had a reduction or stability in the aBSI reading. There was a median reduction of 71.5% in the aBSI with a number of patients having almost complete resolution of quantifiable disease on IBS as evidenced in Figure 2. All patients had a reduction in ALP from Cycle 1 to Cycle 6 with treatment, median reduction from Cycle 1 90 (65-236) to Cycle 6 59 (37-165). Over a median follow up period of 25.9 months the median overall survival and progression free survival have not yet been reached. Two-thirds of the patients in this study have prolonged reductions in aBSI in excess of 2 years post-commencement of LHRHa. Figure 2. An illustrative example of aBSI change over the course of treatment on IBS (baseline and follow-up scans) in comparison with MRI scans. CONCLUSION This is the first quantitative evaluation of changes in bone metastatic burden in mCSPC patients treated with Ra-223 and EBRT. aBSI allows quantitative measurement of response to bone targeted therapies The aBSI as a response imaging biomarker to the treatment was correlated with ALP response and with overall survival. It is more standardised, readily available and more economically sustainable than other modalities as a post therapeutic monitoring tool in bony metastatic setting. Further comparison with whole body MRI in this study will allow comparison of response and prognostic information. We present the first documented use of aBSI in mCSPC. This tool may improve analysis of response to bone metastases in the metastatic setting. It may reduce risk of reporter bias and can be used to systematically follow up patients with multiple therapeutic interventions in this patient cohort. Sequential whole body MRI’s are available for comparison and will be evaluated on completion of this novel clinical trial. The use of aBSI in conjunction with ALP and PSA may help prognosticate response in mCSPC.
|Number of pages||1|
|Journal||Journal of Medical Imaging and Radiation Sciences|
|Publication status||Published - 01 Dec 2019|
|Event||11TH INTERNATIONAL SYMPOSIUM ON TARGETED ALPHA THERAPY - CANADA, OTTAWA, Canada|
Duration: 01 Apr 2019 → 04 Apr 2019