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dc.contributor.authorDenis-Bacelar, AMen_US
dc.contributor.authorChittenden, SJen_US
dc.contributor.authorDearnaley, DPen_US
dc.contributor.authorDivoli, Aen_US
dc.contributor.authorO'Sullivan, JMen_US
dc.contributor.authorMcCready, VRen_US
dc.contributor.authorJohnson, Ben_US
dc.contributor.authorDu, Yen_US
dc.contributor.authorFlux, GDen_US
dc.coverage.spatialGermanyen_US
dc.date.accessioned2016-11-14T16:54:59Z
dc.date.issued2017-04en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/27770145en_US
dc.identifier10.1007/s00259-016-3543-xen_US
dc.identifier.citationEur J Nucl Med Mol Imaging, 2017, 44 (4), pp. 620 - 629en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/206
dc.identifier.eissn1619-7089en_US
dc.identifier.doi10.1007/s00259-016-3543-xen_US
dc.description.abstractPURPOSE: 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. METHODS: Clinical data from 57 patients who received 2.5-5.1 GBq of 186Re-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. RESULTS: 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 186Re-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). CONCLUSION: 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.en_US
dc.format.extent620 - 629en_US
dc.languageengen_US
dc.language.isoengen_US
dc.subjectBone metastasesen_US
dc.subjectDosimetryen_US
dc.subjectMolecular radiotherapyen_US
dc.subjectProstate canceren_US
dc.subjectRadiopharmaceuticalen_US
dc.subjectSurvivalen_US
dc.subjectBone Neoplasmsen_US
dc.subjectClinical Trials, Phase I as Topicen_US
dc.subjectClinical Trials, Phase II as Topicen_US
dc.subjectEtidronic Aciden_US
dc.subjectHumansen_US
dc.subjectMaleen_US
dc.subjectOrganometallic Compoundsen_US
dc.subjectProstatic Neoplasms, Castration-Resistanten_US
dc.subjectRadiation Dosageen_US
dc.subjectRadiopharmaceuticalsen_US
dc.subjectRadiotherapy Dosageen_US
dc.subjectRadiotherapy Planning, Computer-Assisteden_US
dc.subjectSurvival Analysisen_US
dc.subjectTomography, Emission-Computed, Single-Photonen_US
dc.titlePhase I/II trials of 186Re-HEDP in metastatic castration-resistant prostate cancer: post-hoc analysis of the impact of administered activity and dosimetry on survival.en_US
dc.typeJournal Article
dcterms.dateAccepted2016-09-30en_US
rioxxterms.versionofrecord10.1007/s00259-016-3543-xen_US
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0en_US
rioxxterms.licenseref.startdate2017-04en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfEur J Nucl Med Mol Imagingen_US
pubs.issue4en_US
pubs.notesNo embargoen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Clinical Academic Radiotherapy (Dearnaley)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Radioisotope Physics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Radioisotope Physics/Radioisotope Physics (hon.)
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublisheden_US
pubs.volume44en_US
pubs.embargo.termsNo embargoen_US
icr.researchteamClinical Academic Radiotherapy (Dearnaley)en_US
icr.researchteamRadioisotope Physicsen_US
dc.contributor.icrauthorDearnaley, Daviden_US
dc.contributor.icrauthorFlux, Glennen_US
dc.contributor.icrauthorDenis-Bacelar, Anaen_US
dc.contributor.icrauthorMarsden,en_US


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