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

• Published in: European journal of nuclear medicine and molecular imaging 2017-04, Vol.44 (4), p.620-629
• Main Authors: Denis-Bacelar, Ana M, Chittenden, Sarah J, Dearnaley, David P, Divoli, Antigoni, O'Sullivan, Joe M, McCready, VRalph, Johnson, Bernadette, Du, Yong, Flux, Glenn D
• Format: Article
• Language: English
• ISSN: 1619-7070; 1619-7089
• DOI: 10.1007/s00259-016-3543-x

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 super(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 ( plus or minus 6) Gy and the mean of the whole-body absorbed dose was 0.33 ( plus or minus 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 super(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.