Clinical validity of circulating tumour cells in patients with metastatic breast cancer: a pooled analysis of individual patient data

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• 作者：Franç ; ois-Clé ; ment Bidard ; MD^a ; ^b ; Dieter J Peeters ; MD^c ; ^d ; Prof Tanja Fehm ; MD^e ; Franco Nolé ; MD^f ; Rafael Gisbert-Criado ; MD^g ; Prof Dimitrios Mavroudis ; MD^h ; Salvatore Grisanti ; MDⁱ ; Daniele Generali ; MD^j ; Jose A Garcia-Saenz ; MD^k ; Prof Justin Stebbing ; MD^l ; Prof Carlos Caldas ; MD^m ; ⁿ ; ^o ; Paola Gazzaniga ; MD^p ; Luis Manso ; MD^q ; Rita Zamarchi ; MD^r ; Angela Fernandez de Lascoiti ; MD^s ; Leticia De Mattos-Arruda ; MD^t ; Michail Ignatiadis ; MD^u ; Ronald Lebofsky ; PhD^a ; Prof Steven J van Laere ; PhD^c ; ^d ; ^v ; Franziska Meier-Stiegen ; PhD^e ; Maria-Teresa Sandri ; MD^w ; Jose Vidal-Martinez ; MD^g ; Eleni Politaki ; MSc^h ; Francesca Consoli ; MDⁱ ; Alberto Bottini ; MD^j ; Prof Eduardo Diaz-Rubio ; MD^k ; Jonathan Krell ; MD^l ; Sarah-Jane Dawson ; MD^m ; Cristina Raimondi ; MD^p ; Annemie Rutten ; MD^c ; Prof Wolfgang Janni ; MD^x ; Elisabetta Munzone ; MD^f ; Vicente Carañ ; ana ; MD^y ; Sofia Agelaki ; MD^h ; Camillo Almici ; MDⁱ ; Luc Dirix ; MD^c ; ^d ; Prof Erich-Franz Solomayer ; MD^z ; Laura Zorzino ; MSc^w ; Helene Johannes ; MSc^aa ; Prof Jorge S Reis-Filho ; MD^b ; Prof Klaus Pantel ; MD^ab ; ^&dagger ; ; Prof Jean-Yves Pierga ; MD^a ; ^ac ; ^&dagger ; ; ^{jean-yves.pierga@curie.fr" class="auth_mail} ; Stefan Michiels ; PhD^ad ; ^&dagger ;
• 刊名：Lancet Oncology
• 出版年：April, 2014
• 年：2014
• 卷：15
• 期：4
• 页码：406-414
• 全文大小：377 K

文摘

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Summary

Background

We aimed to assess the clinical validity of circulating tumour cell (CTC) quantification for prognostication of patients with metastatic breast cancer by undertaking a pooled analysis of individual patient data.

Methods

We contacted 51 European centres and asked them to provide reported and unreported anonymised data for individual patients with metastatic breast cancer who participated in studies between January, 2003, and July, 2012. Eligible studies had participants starting a new line of therapy, data for progression-free survival or overall survival, or both, and CTC quantification by the CellSearch method at baseline (before start of new treatment). We used Cox regression models, stratified by study, to establish the association between CTC count and progression-free survival and overall survival. We used the landmark method to assess the prognostic value of CTC and serum marker changes during treatment. We assessed the added value of CTCs or serum markers to prognostic clinicopathological models in a resampling procedure using likelihood ratio (LR) 蠂² statistics.

Findings

17 centres provided data for 1944 eligible patients from 20 studies. 911 patients (46路9%) had a CTC count of 5 per 7路5 mL or higher at baseline, which was associated with decreased progression-free survival (hazard ratio [HR] 1路92, 95% CI 1路73-2路14, p<0路0001) and overall survival (HR 2路78, 95% CI 2路42-3路19, p<0路0001) compared with patients with a CTC count of less than 5 per 7路5 mL at baseline. Increased CTC counts 3-5 weeks after start of treatment, adjusted for CTC count at baseline, were associated with shortened progression-free survival (HR 1路85, 95% CI 1路48-2路32, p<0路0001) and overall survival (HR 2路26, 95% CI 1路68-3路03) as were increased CTC counts after 6-8 weeks (progression-free survival HR 2路20, 95% CI 1路66-2路90, p<0路0001; overall survival HR 2路91, 95% CI 2路01-4路23, p<0路0001). Survival prediction was significantly improved by addition of baseline CTC count to the clinicopathological models (progression-free survival LR 38路4, 95% CI 21路9-60路3, p<0路0001; overall survival LR 64路9, 95% CI 41路3-93路4, p<0路0001). This model was further improved by addition of CTC change at 3-5 weeks (progression-free survival LR 8路2, 95% CI 0路78-20路4, p=0路004; overall survival LR 11路5, 95% CI 2路6-25路1, p=0路0007) and at 6-8 weeks (progression-free survival LR 15路3, 95% CI 5路2-28路3; overall survival LR 14路6, 95% CI 4路0-30路6; both p<0路0001). Carcinoembryonic antigen and cancer antigen 15-3 concentrations at baseline and during therapy did not add significant information to the best baseline model.

Interpretation

These data confirm the independent prognostic effect of CTC count on progression-free survival and overall survival. CTC count also improves the prognostication of metastatic breast cancer when added to full clinicopathological predictive models, whereas serum tumour markers do not.

Funding

Janssen Diagnostics, the Nuovo-Soldati foundation for cancer research.