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Verfasst von:Gafita, Andrei [VerfasserIn]   i
 Calais, Jeremie [VerfasserIn]   i
 Grogan, Tristan R [VerfasserIn]   i
 Hadaschik, Boris [VerfasserIn]   i
 Wang, Hui [VerfasserIn]   i
 Weber, Manuel [VerfasserIn]   i
 Sandhu, Shahneen [VerfasserIn]   i
 Kratochwil, Clemens [VerfasserIn]   i
 Esfandiari, Rouzbeh [VerfasserIn]   i
 Tauber, Robert [VerfasserIn]   i
 Zeldin, Anna [VerfasserIn]   i
 Rathke, Hendrik [VerfasserIn]   i
 Armstrong, Wesley R [VerfasserIn]   i
 Robertson, Andrew [VerfasserIn]   i
 Thin, Pan [VerfasserIn]   i
 D'Alessandria, Calogero [VerfasserIn]   i
 Rettig, Matthew B [VerfasserIn]   i
 Delpassand, Ebrahim S [VerfasserIn]   i
 Haberkorn, Uwe [VerfasserIn]   i
 Elashoff, David [VerfasserIn]   i
 Herrmann, Ken [VerfasserIn]   i
 Czernin, Johannes [VerfasserIn]   i
 Hofman, Michael S [VerfasserIn]   i
 Fendler, Wolfgang P [VerfasserIn]   i
 Eiber, Matthias [VerfasserIn]   i
Titel:Nomograms to predict outcomes after 177Lu-PSMA therapy in men with metastatic castration-resistant prostate cancer
Titelzusatz:an international, multicentre, retrospective study
Verf.angabe:Andrei Gafita, Jeremie Calais, Tristan R Grogan, Boris Hadaschik, Hui Wang, Manuel Weber, Shahneen Sandhu, Clemens Kratochwil, Rouzbeh Esfandiari, Robert Tauber, Anna Zeldin, Hendrik Rathke, Wesley R Armstrong, Andrew Robertson, Pan Thin, Calogero D'Alessandria, Matthew B Rettig, Ebrahim S Delpassand, Uwe Haberkorn, David Elashoff, Ken Herrmann, Johannes Czernin, Michael S Hofman, Wolfgang P Fendler, Matthias Eiber
E-Jahr:2021
Jahr:July 8, 2021
Umfang:11 S.
Teil:volume:22
 year:2021
 number:8
 month:08
 pages:1115-1125
 extent:11
Fussnoten:Im Text ist "177" hochgestellt ; Gesehen am 18.10.2021
Titel Quelle:Enthalten in: The lancet <London> / Oncology
Ort Quelle:London : The Lancet Publ. Group, 2000
Jahr Quelle:2021
Band/Heft Quelle:22(2021), 8 vom: Aug., Seite 1115-1125
ISSN Quelle:1474-5488
Abstract:Background - Lutetium-177 (177Lu) prostate-specific membrane antigen (177Lu-PSMA) is a novel targeted treatment for patients with metastatic castration-resistant prostate cancer (mCRPC). Predictors of outcomes after 177Lu-PSMA to enhance its clinical implementation are yet to be identified. We aimed to develop nomograms to predict outcomes after 177Lu-PSMA in patients with mCRPC. - Methods - In this multicentre, retrospective study, we screened patients with mCRPC who had received 177Lu-PSMA between Dec 10, 2014, and July 19, 2019, as part of the previous phase 2 trials (NCT03042312, ACTRN12615000912583) or compassionate access programmes at six hospitals and academic centres in Germany, the USA, and Australia. Eligible patients had received intravenous 6·0-8·5 GBq 177Lu-PSMA once every 6-8 weeks, for a maximum of four to six cycles, and had available baseline [68Ga]Ga-PSMA-11 PET/CT scan, clinical data, and survival outcomes. Putative predictors included 18 pretherapeutic clinicopathological and [68Ga]Ga-PSMA-11 PET/CT variables. Data were collected locally and centralised. Primary outcomes for the nomograms were overall survival and prostate-specific antigen (PSA)-progression-free survival. Nomograms for each outcome were computed from Cox regression models with LASSO penalty for variable selection. Model performance was measured by examining discrimination (Harrell's C-index), calibration (calibration plots), and utility (patient stratification into low-risk vs high-risk groups). Models were validated internally using bootstrapping and externally by calculating their performance on a validation cohort. - Findings - Between April 23, 2019, and Jan 13, 2020, 414 patients were screened; 270 (65%) of whom were eligible and were divided into development (n=196) and validation (n=74) cohorts. The median duration of follow-up was 21·5 months (IQR 13·3-30·7). Predictors included in the nomograms were time since initial diagnosis of prostate cancer, chemotherapy status, baseline haemoglobin concentration, and [68Ga]Ga-PSMA-11 PET/CT parameters (molecular imaging TNM classification and tumour burden). The C-index of the overall survival model was 0·71 (95% CI 0·69-0·73). Similar C-indices were achieved at internal validation (0·71 [0·69-0·73]) and external validation (0·72 [0·68-0·76]). The C-index of the PSA-progression-free survival model was 0·70 (95% CI 0·68-0·72). Similar C-indices were achieved at internal validation (0·70 [0·68-0·72]) and external validation (0·71 [0·68-0·74]). Both models were adequately calibrated and their predictions correlated with the observed outcome. Compared with high-risk patients, low-risk patients had significantly longer overall survival in the validation cohort (24·9 months [95% CI 16·8-27·3] vs 7·4 months [4·0-10·8]; p<0·0001) and PSA-progression-free survival (6·6 months [6·0-7·1] vs 2·5 months [1·2-3·8]; p=0·022). - Interpretation - These externally validated nomograms that are predictive of outcomes after 177Lu-PSMA in patients with mCRPC might help in clinical trial design and individual clinical decision making, particularly at institutions where 177Lu-PSMA is introduced as a novel therapeutic option. - Funding - Prostate Cancer Foundation.
DOI:doi:10.1016/S1470-2045(21)00274-6
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext ; Verlag: https://doi.org/10.1016/S1470-2045(21)00274-6
 Volltext: https://www.sciencedirect.com/science/article/pii/S1470204521002746
 DOI: https://doi.org/10.1016/S1470-2045(21)00274-6
Datenträger:Online-Ressource
Sprache:eng
K10plus-PPN:177433447X
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