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ALERT - Adverse Late Effects of Cancer Treatment pp 205–226Cite as

Radiotherapy-Induced Carcinogenesis and Leukemogenesis: Mechanisms and Quantitative Modeling

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Part of the book series: Medical Radiology ((Med Radiol Radiat Oncol))

Abstract

Biologically-based modeling of spontaneous and radiation-induced carcinogenesis has a history spanning several decades. Such models are important conceptual and quantitative tools, particularly useful whenever cancer risks must be estimated under exposure situations for which no data yet exist, e.g., for novel and prospective radiotherapy protocols. Direct extrapolation from existing data is often not possible due to complex differences between the data sets, but quantitative models can accommodate such extrapolation. Many carcinogenesis models can be characterized as short-term, in that they focus on those processes occurring during and shortly after irradiation. The main advantage of this class of models is that they provide a detailed initial dose response for short-term endpoints which are used as surrogates for carcinogenesis. The main disadvantage is that the possibly substantial modulations of the magnitude and shape of this initial dose response during the lengthy period between irradiation and manifestation of typical solid tumors are not considered. In contrast with the short-term models, another class of biologically-motivated models can be characterized as long-term, in the sense that they track carcinogenesis mechanisms throughout the entire human life span. The main advantages of long-term models are: (1) modulation of the radiation dose response during the long latency period between exposure and diagnosis of cancer is included; and (2) extensive data on spontaneous cancers can be used to help determine the adjustable parameters needed to estimate cancer risks. The main disadvantage is that the early radiation response is typically treated in a less-mechanistic manner than in the short-term models. Here we review some short- and long-term model examples and the carcinogenesis mechanisms which they incorporate. We also discuss an example of unification of both model classes, focusing on application of such formalisms for quantifying radiotherapy-induced second cancer risks.

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  1. Center for Radiological Research, Columbia University Medical Center, New York, NY, USA

    David J. Brenner & Igor Shuryak

  2. Departments of Mathematics and Physics, University of California, Berkeley, CA, USA

    Rainer K. Sachs

Authors
  1. David J. Brenner
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  2. Igor Shuryak
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  3. Rainer K. Sachs
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Correspondence to David J. Brenner .

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Editors and Affiliations

  1. Dept. Radiation Oncology, University of Rochester Medical Center James P. Wilmot Cancer Ctr., Rochester, New York, USA

    Philip Rubin

  2. Department of Radiation Oncology, University of Rochester Medical Center James P. Wilmot Cancer Ctr., Rochester, New York, USA

    Louis S. Constine

  3. Department of Radiation Oncology, University of North Carolina, Chapel Hill, North Carolina, USA

    Lawrence B. Marks

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© 2014 Springer-Verlag Berlin Heidelberg

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Brenner, D.J., Shuryak, I., Sachs, R.K. (2014). Radiotherapy-Induced Carcinogenesis and Leukemogenesis: Mechanisms and Quantitative Modeling. In: Rubin, P., Constine, L., Marks, L. (eds) ALERT - Adverse Late Effects of Cancer Treatment. Medical Radiology(). Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-72314-1_14

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  • DOI: https://doi.org/10.1007/978-3-540-72314-1_14

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  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-72313-4

  • Online ISBN: 978-3-540-72314-1

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