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12.1 TUMOR GROWTH AND CELL KINETICS

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Tumors grow because the homeostatic mechanisms that maintain the appropriate number of cells in normal tissues are defective, leading to an imbalance between cell proliferation and cell death and to expansion of the cell population. The use of autoradiography with tritiated thymidine in the 1950s and 1960s, and the subsequent application of flow cytometry, have allowed a detailed analysis of tumor growth in terms of the kinetics of proliferation of the constituent cells. The proliferative rate of tumor cells varies widely between tumors; slowly proliferating or nonproliferating cells are common, and there is often a high rate of cell death. Several normal tissues, including bone marrow and intestine, contain cells with high rates of proliferation, and damage to these cells is often dose-limiting for chemotherapy. The rate of cell proliferation in tumors may be an important factor in determining prognosis and response to therapy.

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12.1.1 Growth of Human Tumors

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Because tumors are generally treated rather than observed, most of the data on growth rates of untreated human cancers are from studies that were undertaken prior to the development of more effective therapies. Accurate measurements could be made only on tumors from selected sites, and most studies have examined lung metastases using serial chest radiographs. There have been only a few reported measurements of the growth of untreated primary tumors (which generally were removed by operation or irradiated). Because there is a limited observation period between the time of tumor detection and either death of the host or initiation of therapy, such measurements represent only a small fraction of the history of the tumor's growth (see Fig. 12–1). Despite these limitations, Steel (1977) was able to review measurements of the rate of growth of more than 600 human tumors, and a few general conclusions may be stated:

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FIGURE 12–1

A) Growth rate of a human breast cancer using linear axes. B) Growth of the same tumor using a logarithmic scale for tumor volume. C) Hypothetical growth curve indicating initial latency and later slowing of tumor growth.

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  1. There is wide variation in growth rate, even among tumors of the same histological type and site of origin.

  2. Childhood tumors and adult tumors that are known to be responsive to chemotherapy (eg, lymphoma, cancer of the testis) tend to grow more rapidly than less-responsive tumors.

  3. Lung metastases tend to grow more rapidly than the primary tumor in the same patient.

  4. Over the period of observation, the time for the tumor volume to double was often constant, implying exponential growth. Doubling times for lung metastases of common tumors in humans were in the range of 2 to 3 months; Table 12–1 summarizes the doubling times for various types of cancer.

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TABLE 12–1Volume doubling time (TD) ...

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