Dataset Information

Interpretation of changes in circulating tumor cell counts.

ABSTRACT: The presence of circulating tumor cells (CTCs) in the blood of cancer patients may guide the use of therapy. We investigated how to evaluate a reduction in the number of CTCs after administration of therapy. CTCs were enumerated with the CellSearch system in 111 metastatic breast and 185 metastatic prostate cancer patients before start of a new line of chemotherapy and after initiation of therapy. Different means to express changes in CTC counts were evaluated with respect to overall survival (OS). A static CTC cutoff is the best method to determine whether a therapy is effective. This is exemplified by the highest Cox hazard ratio of 2.1 for OS; three methods to express relative differences performed worse. A lookup table is provided from which the significance of a change in CTCs can be derived. The aim of therapy should be the elimination of all CTCs. A period of 10 to 12 weeks of therapy is needed to reach the treatment effect on CTCs.

SUBMITTER: Coumans FA

PROVIDER: S-EPMC3542841 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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Interpretation of changes in circulating tumor cell counts.

Coumans Frank Aw FA Ligthart Sjoerd T ST Terstappen Leon Wmm LW

Translational oncology 20121201 6

The presence of circulating tumor cells (CTCs) in the blood of cancer patients may guide the use of therapy. We investigated how to evaluate a reduction in the number of CTCs after administration of therapy. CTCs were enumerated with the CellSearch system in 111 metastatic breast and 185 metastatic prostate cancer patients before start of a new line of chemotherapy and after initiation of therapy. Different means to express changes in CTC counts were evaluated with respect to overall survival (O ...[more]

PMID: 23323160

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Project description:Population time series analysis is an integral part of conservation biology in the current context of global changes. To quantify changes in population size, wildlife counts only provide estimates because of various sources of error. When unaccounted for, such errors can obscure important ecological patterns and reduce confidence in the derived trend. In the case of highly gregarious species, which are common in the animal kingdom, the estimation of group size is an important potential bias, which is characterized by high variance among observers. In this context, it is crucial to quantify the impact of observer changes, inherent to population monitoring, on i) the minimum length of population time series required to detect significant trends and ii) the accuracy (bias and precision) of the trend estimate.We acquired group size estimation error data by an experimental protocol where 24 experienced observers conducted counting simulation tests on group sizes. We used this empirical data to simulate observations over 25 years of a declining population distributed over 100 sites. Five scenarios of changes in observer identity over time and sites were tested for each of three simulated trends (true population size evolving according to deterministic models parameterized with declines of 1.1%, 3.9% or 7.4% per year that justify respectively a "declining," "vulnerable" or "endangered" population under IUCN criteria).We found that under realistic field conditions observers detected the accurate value of the population trend in only 1.3% of the cases. Our results also show that trend estimates are similar if many observers are spatially distributed among the different sites, or if one single observer counts all sites. However, successive changes in observer identity over time lead to a clear decrease in the ability to reliably estimate a given population trend, and an increase in the number of years of monitoring required to adequately detect the trend.Minimizing temporal changes of observers improve the quality of count data and help taking appropriate management decisions and setting conservation priorities. The same occurs when increasing the number of observers spread over 100 sites. If the population surveyed is composed of few sites, then it is preferable to perform the survey by one observer. In this context, it is important to reconsider how we use estimated population trend values and potentially to scale our decisions according to the direction and duration of estimated trends, instead of setting too precise threshold values before action.

Project description:Enumerating circulating tumor cells (CTCs) has been demonstrably useful in cancer treatment. Although there are several approaches that have proved effective in isolating CTC-like cells, the crucial identification of CTCs continues to rely on the manual interpretation of immunofluorescence images of all cells that have been isolated. This procedure is time consuming and more importantly, CTC identification relies on subjective criteria that may differ between examiners. In this study, we describe the design, testing, and verification of a microfluidic platform that provides accurate and automated CTC enumeration using a common objective criterion. Methods: The platform consists of a multi-functional microfluidic chip and a unique image processing algorithm. The microfluidic chip integrates blood filtering, cell isolation, and single cell positioning to ensure minimal cell loss, efficient cell isolation, and fixed arraying of single cells to facilitate downstream image processing. By taking advantage of the microfluidic chip design to reduce calculation loads and eliminate measurement errors, our specially designed algorithm has the capability of rapidly interpreting hundreds of images to provide accurate CTC counts. Results: Following intensive optimization of the microfluidic chip, the image processing algorithm, and their collaboration, we verified the complete platform by enumerating CTCs from six clinical blood samples of patients with breast cancer. Compared to tube-based CTC isolation and manual CTC identification, our platform had better accuracy and reduced the time needed from sample loading to result review by 50%. Conclusion: This automated CTC enumeration platform demonstrates not only a sound strategy in integrating a specially designed multi-functional microfluidic chip with a unique image processing algorithm for robust, accurate, and "hands-free" CTC enumeration, but may also lead to its use as a novel in vitro diagnostic device used in clinics and laboratories as readily as a routine blood test.

Dataset Information

Interpretation of changes in circulating tumor cell counts.

Publications

Interpretation of changes in circulating tumor cell counts.

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