Detection of cancer before distant metastasis

BMC Cancer

Frank AW Coumans¹  Sabine Siesling²  Leon WMM Terstappen¹ 

[1] Medical Cell BioPhysics group, MIRA Institute, University of Twente, Room CR4437, Hallenweg 23, 7522 NH, Enschede, The Netherlands

[2] Department of HTSR, MIRA institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, the Netherlands

关键词: Circulating tumor cells;    Tumor size;    Modeling;    Diagnostic imaging;    Metastasis;   

Others  :  1079707
DOI  :  10.1186/1471-2407-13-283

 received in 2013-03-14, accepted in 2013-05-21,  发布年份 2013

【 摘 要 】

Background

To establish a distant metastasis (DM) cells must disseminate from the primary tumor and overcome a series of obstacles, the metastatic cascade. In this study we develop a mathematical model for this cascade to estimate the tumor size and the circulating tumor cell (CTC) load before the first metastasis has formed from a primary breast cancer tumor.

Methods

The metastatic cascade is described in discrete steps: 1. local tumor growth; 2. dissemination into circulation; 3. survival in circulation; 4. extravasation into tissue; and 5. growth into a metastasis. The model was built using data and relationships described in the literature to predict the relationship between tumor size and probability of distant metastasis for 38715 patients with surgically removed T_XN_XM₀ primary breast cancer from the Netherlands Cancer Registry. The model was calibrated using primary tumor size, probability of distant metastasis and time to distant metastasis for 1489 patients with stage T_1BN_XM₀ (25% of total patients with T_1BN_XM₀). Validation of the model was done with data for all patients.

Results

From the time to distant metastasis of these 38715 breast cancer patients, we determined a tumor doubling time of 1.7 ± 0.9 months. Fitting the data for 25% of T_1B patients estimates a metastatic efficiency of 1 metastasis formed per 60 million disseminated tumor cells. Validation of the model to data of patients in all T-stages shows good agreement between model and epidemiological data. To reduce the 5-year risk of distant metastasis for T_XN_XM₀ from 9.2% to 1.0%, the primary tumor needs to be detected and removed before it reaches a diameter of 2.7 ± 1.6 mm. At this size, the model predicts that there will be 9 ± 6 CTC/L blood.

Conclusions

To reduce the rate of distant metastasis in surgically treated T_XN_XM₀ breast cancer to 1%, imaging technology will need to be able to detect lesions of 2.7 mm in diameter or smaller. Before CTC detection can be applied in the early disease setting, sensitivity will need to be improved by at least 15-fold and combined with technology that minimizes false positives.

【 授权许可】

   
2013 Coumans et al.; licensee BioMed Central Ltd.

【 图 表 】

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