The Radiation Spectrum of Normal Tissue Toxicity and Tolerance — Multiorgan Domino Effect

Conceptually, normal tissue tolerance is often viewed and defined in terms of a single specific normal tissue/organ site with the clinical illusion that during radiation treatment the adverse effects are localized and limited to those normal tissues within the radiation field. However, with the technological advances of highly computerized treatment delivery and dynamic multileaf collimation, the widespread use of intensity modulated radiation therapy (IMRT) allows for administering higher doses to defined tumor volume contours but in the process delivers more radiation to all the surrounding normal tissues in the axial segments being treated (Fig. 13.1) [1, 2]. Thus, there is an increasing need to recognize the spectrum of normal tissues and organs which are exposed but often obscured in color wash isodose curves. Although each critical structure has radiation tolerance limits well defined, it is important to have a more holistic view of the radiation effects in the large variety of normal tissues adjacent to the tumor, recognizing that all modalities leave the persistence of the memory of an untoward perturbation of their cellular, genetic, and molecular elements (Fig. 13.2) [3]. Open image in new window Fig. 13.1a,b. Percent relative isodose distributions for the 3DCRT plan (a) and IMRT-2 plan (b). The dose distributions show that the IMRT-2 plan is more conformal than the 3DCRT plan at the cost of slightly losing target coverage. Unlike the UTCP plan values, the UTCPQALY values, which incorporate clinically realistic quality of life data, suggest that the UTCPQALY formalism provides better differentiation between plans. (Reprinted with permission from [2]) Open image in new window Fig. 13.2. Animal models for radiation counter-measures research. The overall goal of research is to go from underlying molecular mechanism to human application. This requires many model systems. (Adapted and reprinted with permission from [3]