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dc.contributor.authorDenis-Bacelar, AM
dc.contributor.authorChittenden, SJ
dc.contributor.authorDearnaley, DP
dc.contributor.authorDivoli, A
dc.contributor.authorO'Sullivan, JM
dc.contributor.authorMcCready, VR
dc.contributor.authorJohnson, B
dc.contributor.authorDu, Y
dc.contributor.authorFlux, GD
dc.date.accessioned2016-11-14T16:54:59Z
dc.date.issued2017-04
dc.identifier.citationEuropean journal of nuclear medicine and molecular imaging, 2017, 44 (4), pp. 620 - 629
dc.identifier.issn1619-7070
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/206
dc.identifier.eissn1619-7089
dc.identifier.doi10.1007/s00259-016-3543-x
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 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.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 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).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.
dc.formatPrint-Electronic
dc.format.extent620 - 629
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectHumans
dc.subjectBone Neoplasms
dc.subjectOrganometallic Compounds
dc.subjectEtidronic Acid
dc.subjectRadiopharmaceuticals
dc.subjectTomography, Emission-Computed, Single-Photon
dc.subjectRadiotherapy Dosage
dc.subjectRadiotherapy Planning, Computer-Assisted
dc.subjectSurvival Analysis
dc.subjectRadiation Dosage
dc.subjectMale
dc.subjectClinical Trials, Phase I as Topic
dc.subjectClinical Trials, Phase II as Topic
dc.subjectProstatic Neoplasms, Castration-Resistant
dc.titlePhase I/II trials of <sup>186</sup>Re-HEDP in metastatic castration-resistant prostate cancer: post-hoc analysis of the impact of administered activity and dosimetry on survival.
dc.typeJournal Article
dcterms.dateAccepted2016-09-30
rioxxterms.versionofrecord10.1007/s00259-016-3543-x
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2017-04
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfEuropean journal of nuclear medicine and molecular imaging
pubs.issue4
pubs.notesNo embargo
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/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Clinical Academic Radiotherapy (Dearnaley)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
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.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/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Clinical Academic Radiotherapy (Dearnaley)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
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-statusPublished
pubs.volume44
pubs.embargo.termsNo embargo
icr.researchteamClinical Academic Radiotherapy (Dearnaley)en_US
icr.researchteamRadioisotope Physicsen_US
dc.contributor.icrauthorDenis-Bacelar, Anaen
dc.contributor.icrauthorDearnaley, Daviden
dc.contributor.icrauthorFlux, Glennen
dc.contributor.icrauthorMarsden,en


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