Phase I/II trials of (186)Re-HEDP in metastatic castration-resistant prostate cancer: post-hoc analysis of the impact of administered activity and dosimetry on survival

To investigate the role of patient-specific dosimetry as a predictive marker of survival and as a potential tool for individualised molecular radiotherapy treatment planning of bone metastases from castration-resistant prostate cancer, and to assess whether higher administered levels of activity are associated with a survival benefit.

Clinical data from 57 patients who received 2.5-5.1 GBq of (186)Re-HEDP as part of NIH-funded phase I/II clinical trials were analysed. Whole-body and SPECT-based absorbed doses to the whole body and bone lesions were calculated for 22 patients receiving 5 GBq. The patient mean absorbed dose was defined as the mean of all bone lesion-absorbed doses in any given patient. Kaplan-Meier curves, log-rank tests, Cox's proportional hazards model and Pearson's correlation coefficients were used for overall survival (OS) and correlation analyses.

A statistically significantly longer OS was associated with administered activities above 3.5 GBq in the 57 patients (20.1 vs 7.1 months, hazard ratio: 0.39, 95 % CI: 0.10-0.58, P = 0.002). A total of 379 bone lesions were identified in 22 patients. The mean of the patient mean absorbed dose was 19 (±6) Gy and the mean of the whole-body absorbed dose was 0.33 (±0.11) Gy for the 22 patients. The patient mean absorbed dose (r = 0.65, P = 0.001) and the whole-body absorbed dose (r = 0.63, P = 0.002) showed a positive correlation with disease volume. Significant differences in OS were observed for the univariate group analyses according to disease volume as measured from SPECT imaging of (186)Re-HEDP (P = 0.03) and patient mean absorbed dose (P = 0.01), whilst only the disease volume remained significant in a multivariable analysis (P = 0.004).

This study demonstrated that higher administered activities led to prolonged survival and that for a fixed administered activity, the whole-body and patient mean absorbed doses correlated with the extent of disease, which, in turn, correlated with survival. This study shows the importance of patient stratification to establish absorbed dose-response correlations and indicates the potential to individualise treatment of bone metastases with radiopharmaceuticals according to patient-specific imaging and dosimetry.

European journal of nuclear medicine and molecular imaging. 2016 Oct 21 [Epub ahead of print]

Ana M Denis-Bacelar, Sarah J Chittenden, David P Dearnaley, Antigoni Divoli, Joe M O'Sullivan, V Ralph McCready, Bernadette Johnson, Yong Du, Glenn D Flux

Joint Department of Physics, The Institute of Cancer Research and The Royal Marsden Hospital NHS Foundation Trust, London, UK. ., Joint Department of Physics, The Institute of Cancer Research and The Royal Marsden Hospital NHS Foundation Trust, London, UK., Division of Radiotherapy and Imaging, The Institute of Cancer Research and The Royal Marsden Hospital NHS Foundation Trust, London, UK., Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, UK., Department of Nuclear Medicine, Brighton and Sussex University Hospitals NHS Trust, Brighton, UK., Department of Nuclear Medicine and PET/CT, The Royal Marsden Hospital NHS Foundation Trust, London, UK.

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