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dc.contributor.authorLorente, D
dc.contributor.authorOlmos, D
dc.contributor.authorMateo, J
dc.contributor.authorDolling, D
dc.contributor.authorBianchini, D
dc.contributor.authorSeed, G
dc.contributor.authorFlohr, P
dc.contributor.authorCrespo, M
dc.contributor.authorFigueiredo, I
dc.contributor.authorMiranda, S
dc.contributor.authorScher, HI
dc.contributor.authorTerstappen, LWMM
dc.contributor.authorde Bono, JS
dc.date.accessioned2019-04-24T08:46:33Z
dc.date.issued2018-07
dc.identifier.citationAnnals of oncology : official journal of the European Society for Medical Oncology, 2018, 29 (7), pp. 1554 - 1560
dc.identifier.issn0923-7534
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3202
dc.identifier.eissn1569-8041
dc.identifier.doi10.1093/annonc/mdy172
dc.description.abstractBackground:The development of treatment response and surrogate biomarkers for advanced prostate cancer care is an unmet clinical need. Patients with baseline circulating tumour cell (BLCTCs) counts <5/7.5 mL represent a good prognosis subgroup but are non-evaluable for response assessment (decrease in CTCs). The aim of the study is to determine the value of any increase in CTCs (CTC progression) as an indicator of progression in prostate cancer patients with low pre-treatment CTCs (<5). Patients and methods:We carried out a post hoc analysis of patients with BLCTCs < 5 treated in the COU-AA-301 (abiraterone or placebo + prednisone) and IMMC-38 (chemotherapy) trials. The association of CTC progression (increase in CTCs at 4, 8 or 12 weeks) with overall survival (OS) was evaluated in multi-variable Cox regression models. Performance of survival models with and without CTC progression was evaluated by calculating ROC curve area under the curves (AUCs) and weighted c-indices. Results:Overall, 511 patients with CTCs < 5 (421 in COU-AA-301 and 90 in IMMC-38) were selected; 212 (41.7%) had CTC progression at 4, 8 or 12 weeks after treatment initiation. CTC progression was associated with significantly worse OS [27.1 versus 15.1 m; hazard ratio (HR) 3.4 (95% confidence interval [CI] 2.5-4.5; P < 0.001)], independent of baseline CTCs and established clinical variables. Adding CTC progression to the OS model significantly improved ROC AUC (0.77 versus 0.66; P < 0.001). Models including CTC progression had superior ROC AUC (0.77 versus 0.69; P < 0.001) and weighted c-index [0.750 versus 0.705; delta c-index: 0.045 (95% CI 0.019-0.071)] values than those including CTC conversion (increase to CTCs ≥ 5). In COU-AA-301, the impact of CTC progression was independent of treatment arm. Conclusions:Increasing CTCs during the first 12 weeks of treatment are independently associated with worse OS from advanced prostate cancer in patients with baseline CTCs < 5 treated with abiraterone or chemotherapy and improve models with established prognostic variables. These findings must be prospectively validated.
dc.formatPrint
dc.format.extent1554 - 1560
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectHumans
dc.subjectNeoplasm Metastasis
dc.subjectDisease Progression
dc.subjectAndrostenes
dc.subjectPrednisone
dc.subjectAntineoplastic Combined Chemotherapy Protocols
dc.subjectPrognosis
dc.subjectSurvival Rate
dc.subjectFollow-Up Studies
dc.subjectProspective Studies
dc.subjectMale
dc.subjectNeoplastic Cells, Circulating
dc.subjectProstatic Neoplasms, Castration-Resistant
dc.subjectBiomarkers, Tumor
dc.titleCirculating tumour cell increase as a biomarker of disease progression in metastatic castration-resistant prostate cancer patients with low baseline CTC counts.
dc.typeJournal Article
rioxxterms.versionofrecord10.1093/annonc/mdy172
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2018-07
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfAnnals of oncology : official journal of the European Society for Medical Oncology
pubs.issue7
pubs.notesNot known
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/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Cancer Biomarkers
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Cancer Biomarkers
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group
pubs.organisational-group/ICR/Students
pubs.organisational-group/ICR/Students/PhD and MPhil
pubs.organisational-group/ICR/Students/PhD and MPhil/16/17 Starting Cohort
pubs.organisational-group/ICR/Students/PhD and MPhil/18/19 Starting Cohort
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/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Cancer Biomarkers
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Cancer Biomarkers
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group
pubs.organisational-group/ICR/Students
pubs.organisational-group/ICR/Students/PhD and MPhil
pubs.organisational-group/ICR/Students/PhD and MPhil/16/17 Starting Cohort
pubs.organisational-group/ICR/Students/PhD and MPhil/18/19 Starting Cohort
pubs.publication-statusPublished
pubs.volume29
pubs.embargo.termsNot known
icr.researchteamCancer Biomarkersen_US
icr.researchteamProstate Cancer Targeted Therapy Groupen_US
dc.contributor.icrauthorSeed, Georgeen
dc.contributor.icrauthorDe Bono, Johannen
dc.contributor.icrauthorMiranda, Susanaen
dc.contributor.icrauthorCrespo, Mateusen


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