1 Adriana Dalea DOS 523 Treatment Planning March 30, 2014 Normal Tissue Complication Probability NTCP Improving

the treatment outcomes in radiation therapy is the ultimate goal for the team involved in the process. The purpose of creating a treatment plan when delivering radiation to a patient is to cover the tumor with the prescribed dose and spare the normal tissues in the vicinity as much as possible. Tumor control probability (TCP) and normal tissue complication probability (NTCP) are two factors that are used in order to optimize the treatment plans. The radiobiological effects on the cells are the base of the discussion. They have to be taken into account and plan accordingly. I will focus on the NTCP factor and briefly describe it in this paper.

doi:10.1371/journal.pcbi.1003295.g001 Figure 1. Cell cycle, response to environmental factors and radiation as implemented in the model Normal tissue complication probability can be described as a certain percentage on the population can experience unfavorable reactions to the tumor adjacent normal tissues at a particular dose. For every organ that is radiosensitive, the normal tissue complication probability depends of the dose and the irradiated volume.1 Tumor control probability (TCP) and normal

2 tissue control probability (NTCP) are interrelated and increase with increasing the dose.2 There is a therapeutic window between TCP and NTCP, this is the consideration taken when creating a plan. Figure 2 clearly demonstrates the two curves on the graph, and the therapeutic range in between.

Figure 2. Dependence of TCP and NTCP on dose. The probability of tumor control without normal issue complications receives its maximum in the so-called therapeutic window. | dkfz.de There were many models proposed for computing NCTP of nonuniformly irradiated organs.3 Due to the fact that the current knowledge of the biologic response data for a large range of tissues is unreliable and poorly documented, these models are simplistic and subject to criticism and debate. Most models are grouped in three categories: DVH-reduction models, tissue architecture models and multimetric models.4(Marks). The DVH-reduction models are based on estimated complication probability under uniform dose distribution, but their applications are generally for the nonuniform dose distribution. The Lyman-Kutcher-Burman (LKB) model is one that uses the tissue tolerance described as a power law to define the risks associated with partial organ volume uniform irradiation.

3 The tissue architecture models include the serial and parallel complication endpoints. In the parallel complications the partial volumes of an organ function independently, small portions of tissues can be damages without any clinical effect. Only if a critical volume is affected, there will be complications observed. In contrast, the serial complications occur if only a small portion of the tissue volume is involved. In the multimetric models, the risk of complication is estimated using a single point on the DVH based on statistically significant dose/volume cutout points from completed studies. These single volume threshold guidelines are manipulated by the planner or the optimizing software, depending of the applicable situation. With the continuously improvement in radiation oncology, research and clinical studies, NTCP models will develop accuracy and will continue to remain tool in obtaining the most successful treatment plans.

4 References 1. Kukolowicz P. Clinical aspects of normal tissue complication probability. Reports of Practical Oncology and Radiotherapy. 2004; 9:261-7. http://www.rpor.eu/?m=3&a=8&IDman=479 Accessed March 30, 2014. 2. Peschke P. Simulation of growth and radiation response of tumors. German Cancer Research Center dkfz Web site. https://www.dkfz.de/en/medphys/appl_med_rad_physics/Biological_models.html March 25, 2007. Accessed March 30, 2014. 3. Khan FM, Gerbi BJ. Treatment Planning in Radiation Oncology. 3rd ed. Philadelphia, PA: Lippincott, Williams, and Wilkins; 2012. 4. Marks LB, Yorke ED, Jackson A, et al. Use of normal tissue complication probability models in the clinic. International Journal of Radiation Oncology * Biology * Physics. 2010; 76(3): S10-S19. http://www.redjournal.org/article/S0360-3016(09)03288X/fulltext#sec12 March 1, 2010. Accessed March 30, 2014.