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Dynamic changes of phenotypically different circulating tumor cells sub-populations in patients with recurrent/refractory small cell lung cancer treated with pazopanib

The aim of the study was to investigate the effect of 2(nd)-line pazopanib on the different CTCs subpopulations in SCLC patients and evaluate the clinical relevance of their changes. Different CTCs subpopulations were evaluated before pazopanib initiation (n = 56 patients), after one-cycle (n = 35)...

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Autores principales: Messaritakis, Ippokratis, Politaki, Eleni, Koinis, Fillipos, Stoltidis, Dimitris, Apostolaki, Stella, Plataki, Maria, Dermitzaki, Eleftheria-Kleio, Georgoulias, Vassilis, Kotsakis, Athanasios
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5797076/
https://www.ncbi.nlm.nih.gov/pubmed/29396560
http://dx.doi.org/10.1038/s41598-018-20502-1
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author Messaritakis, Ippokratis
Politaki, Eleni
Koinis, Fillipos
Stoltidis, Dimitris
Apostolaki, Stella
Plataki, Maria
Dermitzaki, Eleftheria-Kleio
Georgoulias, Vassilis
Kotsakis, Athanasios
author_facet Messaritakis, Ippokratis
Politaki, Eleni
Koinis, Fillipos
Stoltidis, Dimitris
Apostolaki, Stella
Plataki, Maria
Dermitzaki, Eleftheria-Kleio
Georgoulias, Vassilis
Kotsakis, Athanasios
author_sort Messaritakis, Ippokratis
collection PubMed
description The aim of the study was to investigate the effect of 2(nd)-line pazopanib on the different CTCs subpopulations in SCLC patients and evaluate the clinical relevance of their changes. Different CTCs subpopulations were evaluated before pazopanib initiation (n = 56 patients), after one-cycle (n = 35) and on disease progression (n = 45) by CellSearch and double immunofluorescence using anti-CKs and anti-Ki67, anti-M30 or anti-Vimentin antibodies. Before treatment, CTCs were detected in 50% of patients by CellSearch whereas 53.4%, 15.5% and 74.1% patients had CK(+)/Ki67(+), CK(+)/M30(+) and CK(+)/Vim(+) CTCs, respectively. One pazopanib cycle significantly decreased the number of CTCs as detected by CellSearch (p = 0.043) as well as the number of CK(+)/Ki67(+) (p < 0.001), CK(+)/M30(+) (p = 0(.)015) and CK(+)/Vim(+) (p < 0(.)001) cells. On disease progression, both the incidence and CTC numbers were significantly increased (CellSearch, p = 0.027; CK(+)/Ki67(+), p < 0.001; CK(+/)M30(+), p = 0.001 and CK(+)/Vim(+), p < 0(.)001)(.) In multivariate analysis, the detection of CK(+)/Vim(+) CTCs after one treatment cycle (HR: 7.9, 95% CI: 2.9–21.8; p < 0.001) and CTCs number on disease progression, as assessed by CellSearch, (HR: 2.0, 95% CI: 1.0–6.0; p = 0.005) were emerged as independent factors associated with decreased OS. In conclusion, pazopanib can eliminate different CTC subpopulations in patients with relapsed SCLC. The analysis of CTCs could be used as a dynamic biomarker of treatment efficacy.
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spelling pubmed-57970762018-02-12 Dynamic changes of phenotypically different circulating tumor cells sub-populations in patients with recurrent/refractory small cell lung cancer treated with pazopanib Messaritakis, Ippokratis Politaki, Eleni Koinis, Fillipos Stoltidis, Dimitris Apostolaki, Stella Plataki, Maria Dermitzaki, Eleftheria-Kleio Georgoulias, Vassilis Kotsakis, Athanasios Sci Rep Article The aim of the study was to investigate the effect of 2(nd)-line pazopanib on the different CTCs subpopulations in SCLC patients and evaluate the clinical relevance of their changes. Different CTCs subpopulations were evaluated before pazopanib initiation (n = 56 patients), after one-cycle (n = 35) and on disease progression (n = 45) by CellSearch and double immunofluorescence using anti-CKs and anti-Ki67, anti-M30 or anti-Vimentin antibodies. Before treatment, CTCs were detected in 50% of patients by CellSearch whereas 53.4%, 15.5% and 74.1% patients had CK(+)/Ki67(+), CK(+)/M30(+) and CK(+)/Vim(+) CTCs, respectively. One pazopanib cycle significantly decreased the number of CTCs as detected by CellSearch (p = 0.043) as well as the number of CK(+)/Ki67(+) (p < 0.001), CK(+)/M30(+) (p = 0(.)015) and CK(+)/Vim(+) (p < 0(.)001) cells. On disease progression, both the incidence and CTC numbers were significantly increased (CellSearch, p = 0.027; CK(+)/Ki67(+), p < 0.001; CK(+/)M30(+), p = 0.001 and CK(+)/Vim(+), p < 0(.)001)(.) In multivariate analysis, the detection of CK(+)/Vim(+) CTCs after one treatment cycle (HR: 7.9, 95% CI: 2.9–21.8; p < 0.001) and CTCs number on disease progression, as assessed by CellSearch, (HR: 2.0, 95% CI: 1.0–6.0; p = 0.005) were emerged as independent factors associated with decreased OS. In conclusion, pazopanib can eliminate different CTC subpopulations in patients with relapsed SCLC. The analysis of CTCs could be used as a dynamic biomarker of treatment efficacy. Nature Publishing Group UK 2018-02-02 /pmc/articles/PMC5797076/ /pubmed/29396560 http://dx.doi.org/10.1038/s41598-018-20502-1 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Messaritakis, Ippokratis
Politaki, Eleni
Koinis, Fillipos
Stoltidis, Dimitris
Apostolaki, Stella
Plataki, Maria
Dermitzaki, Eleftheria-Kleio
Georgoulias, Vassilis
Kotsakis, Athanasios
Dynamic changes of phenotypically different circulating tumor cells sub-populations in patients with recurrent/refractory small cell lung cancer treated with pazopanib
title Dynamic changes of phenotypically different circulating tumor cells sub-populations in patients with recurrent/refractory small cell lung cancer treated with pazopanib
title_full Dynamic changes of phenotypically different circulating tumor cells sub-populations in patients with recurrent/refractory small cell lung cancer treated with pazopanib
title_fullStr Dynamic changes of phenotypically different circulating tumor cells sub-populations in patients with recurrent/refractory small cell lung cancer treated with pazopanib
title_full_unstemmed Dynamic changes of phenotypically different circulating tumor cells sub-populations in patients with recurrent/refractory small cell lung cancer treated with pazopanib
title_short Dynamic changes of phenotypically different circulating tumor cells sub-populations in patients with recurrent/refractory small cell lung cancer treated with pazopanib
title_sort dynamic changes of phenotypically different circulating tumor cells sub-populations in patients with recurrent/refractory small cell lung cancer treated with pazopanib
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5797076/
https://www.ncbi.nlm.nih.gov/pubmed/29396560
http://dx.doi.org/10.1038/s41598-018-20502-1
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