Dynamic changes of live/apoptotic circulating tumour cells as predictive marker of response to Sunitinib in metastatic renal cancer

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Background:

Recently, we developed an apoptotic assay for expanding the monitoring capabilities of the circulating tumour cells (CTC) test during therapy. An automated platform for computing CTCs was integrated with a mAb (M30) targeting a neoepitope disclosed by caspase cleavage at cytokeratin 18 in early apoptosis; we showed that live CTCs were associated with progression, consistent with enhanced cell migration and invasion. The test was first applied here to mRCC.

Methods:

Live/apoptotic CTCs changes were measured in mRCC patients receiving first-line Sunitinib and compared with circulating endothelial cell (CEC) levels.

Results:

The presence of EpCAM-positive, live CTCs predicts progression in individual mRCC patient, being associated with distant metastasis under first-line Sunitinib. Synchronous detection of CTCs and CEC levels discloses for the first time an association between their dynamic changes and outcome: a rapid increase of the CEC number as early as the first cycle of therapy is associated with CTC decrease in non-progressed patients, whereas a delayed response of CECs is related to higher CTC values in the progressed group indicating treatment failure.

Conclusion:

We demonstrated that a delayed response to antiangiogenic treatment indicated by persistent detection of CECs correlates with persistent live CTCs and more aggressive disease.

Related collections

Most cited references 31

Record: found
Abstract: found
Article: not found

Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases.

W Jeffrey Allard, Jeri Matera, M. Craig Miller … (2004)

The purpose of this study was to determine the accuracy, precision, and linearity of the CellSearch system and evaluate the number of circulating tumor cells (CTCs) per 7.5 mL of blood in healthy subjects, patients with nonmalignant diseases, and patients with a variety of metastatic carcinomas. The CellSearch system was used to enumerate CTCs in 7.5 mL of blood. Blood samples spiked with cells from tumor cell lines were used to establish analytical accuracy, reproducibility, and linearity. Prevalence of CTCs was determined in blood from 199 patients with nonmalignant diseases, 964 patients with metastatic carcinomas, and 145 healthy donors. Enumeration of spiked tumor cells was linear over the range of 5 to 1,142 cells, with an average recovery of >/=85% at each spike level. Only 1 of the 344 (0.3%) healthy and nonmalignant disease subjects had >/=2 CTCs per 7.5 mL of blood. In 2,183 blood samples from 964 metastatic carcinoma patients, CTCs ranged from 0 to 23,618 CTCs per 7.5 mL (mean, 60 +/- 693 CTCs per 7.5 mL), and 36% (781 of 2,183) of the specimens had >/=2 CTCs. Detection of >/=2 CTCs occurred at the following rates: 57% (107 of 188) of prostate cancers, 37% (489 of 1,316) of breast cancers, 37% (20 of 53) of ovarian cancers, 30% (99 of 333) of colorectal cancers, 20% (34 of 168) of lung cancers, and 26% (32 of 125) of other cancers. The CellSearch system can be standardized across multiple laboratories and may be used to determine the clinical utility of CTCs. CTCs are extremely rare in healthy subjects and patients with nonmalignant diseases but present in various metastatic carcinomas with a wide range of frequencies.

0 comments Cited 853 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

REporting recommendations for tumour MARKer prognostic studies (REMARK)

L M McShane, D Altman, W Sauerbrei … (2005)

Despite years of research and hundreds of reports on tumour markers in oncology, the number of markers that have emerged as clinically useful is pitifully small. Often initially reported studies of a marker show great promise, but subsequent studies on the same or related markers yield inconsistent conclusions or stand in direct contradiction to the promising results. It is imperative that we attempt to understand the reasons that multiple studies of the same marker lead to differing conclusions. A variety of methodological problems have been cited to explain these discrepancies. Unfortunately, many tumour marker studies have not been reported in a rigorous fashion, and published articles often lack sufficient information to allow adequate assessment of the quality of the study or the generalisability of the study results. The development of guidelines for the reporting of tumour marker studies was a major recommendation of the US National Cancer Institute and the European Organisation for Research and Treatment of Cancer (NCI-EORTC) First International Meeting on Cancer Diagnostics in 2000. Similar to the successful CONSORT initiative for randomised trials and the STARD statement for diagnostic studies, we suggest guidelines to provide relevant information about the study design, preplanned hypotheses, patient and specimen characteristics, assay methods, and statistical analysis methods. In addition, the guidelines suggest helpful presentations of data and important elements to include in discussions. The goal of these guidelines is to encourage transparent and complete reporting so that the relevant information will be available to others to help them to judge the usefulness of the data and understand the context in which the conclusions apply.

0 comments Cited 588 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis.

John M L Ebos, Christina R Lee, William Cruz-Munoz … (2009)

Herein we report that the VEGFR/PDGFR kinase inhibitor sunitinib/SU11248 can accelerate metastatic tumor growth and decrease overall survival in mice receiving short-term therapy in various metastasis assays, including after intravenous injection of tumor cells or after removal of primary orthotopically grown tumors. Acceleration of metastasis was also observed in mice receiving sunitinib prior to intravenous implantation of tumor cells, suggesting possible "metastatic conditioning" in multiple organs. Similar findings with additional VEGF receptor tyrosine kinase inhibitors implicate a class-specific effect for such agents. Importantly, these observations of metastatic acceleration were in contrast to the demonstrable antitumor benefits obtained when the same human breast cancer cells, as well as mouse or human melanoma cells, were grown orthotopically as primary tumors and subjected to identical sunitinib treatments.

0 comments Cited 502 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): Br J Cancer

Journal ID (iso-abbrev): Br. J. Cancer

Title: British Journal of Cancer

Publisher: Nature Publishing Group

ISSN (Print): 0007-0920

ISSN (Electronic): 1532-1827

Publication date (Print): 09 October 2012

Publication date (Electronic): 06 September 2012

Volume: 107

Issue: 8

Pages: 1286-1294

Affiliations

[1 ]Department of Surgery, Oncology and Gastroenterology, Oncology Section, University of Padova , Padova, Italy

[2 ]Department of Medical Diagnostic Sciences & Special Therapies, Surgical Pathology & Cytopathology Unit, University of Padova , Padova, Italy

[3 ]IRCCS-CROB, Rionero in Vulture (PZ), Italy

[4 ]IOV-IRCCS , via Gattamelata, 64, 35128 Padova, Italy

[5 ]Metabolic Unit, ISIB-CNR , Padova, Italy

[6 ]U.O.C Oncology – Ospedale ‘Santa Maria della Misericordia' , Rovigo, Italy

[7 ]Department of Medical Oncology, University of Verona , Verona, Italy

[8 ]Department of Medical Oncology, Fox Chase Cancer Center , Philadelphia, PA, USA

Author notes

[* ]E-mail: rita.zamarchi@ 123456unipd.it

Article

Publisher Item ID: bjc2012388

DOI: 10.1038/bjc.2012.388

PMC ID: 3494437

PubMed ID: 22955853

SO-VID: a0100c8e-0666-4c4d-94e2-2dc43ad8480b

License:

From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/

History

Date received : 11 June 2012

Date revision received : 31 July 2012

Date accepted : 03 August 2012

Comments

Comment on this article

scite_

Smart Citations

Citing PublicationsSupportingMentioningContrasting

View Citations

See how this article has been cited at scite.ai

scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.

Cited by 20

See all cited by

Most referenced authors 1,143

See all reference authors

Dynamic changes of live/apoptotic circulating tumour cells as predictive marker of response to Sunitinib in metastatic renal cancer

Read this article at

Abstract

Background:

Methods:

Results:

Conclusion:

Related collections

Journal of Circulating Biomarkers

Most cited references 31

Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases.

REporting recommendations for tumour MARKer prognostic studies (REMARK)

Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis.

Author and article information

Journal

Affiliations

Author notes

Article

History

Categories

Comments

Comment on this article

Similar content 872

Cited by 20

Most referenced authors 1,143