Use of normal tissue complication probability models in the clinic

Abstract

The Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) review summarizes the currently available three-dimensional dose/volume/outcome data to update and refine the normal tissue dose/volume tolerance guidelines provided by the classic Emami et al. paper published in 1991. A "clinician's view" on using the QUANTEC information in a responsible manner is presented along with a description of the most commonly used normal tissue complication probability (NTCP) models. A summary of organ-specific dose/volume/outcome data, based on the QUANTEC reviews, is included.

Figure 1

A 3D dose distribution is reduced to a 2D DVH by discarding all spatial, anatomic and physiologic data. The 2D graph is then further reduced to a single value of merit, such as the mean dose, the percent of the organ receiving ≥20 Gy (V20), or a model-based NTCP (Normal tissue complication probability).

Figure 2

As the (idealized) irradiated organ fraction decreases, the tolerance dose (D) increases, more so for larger values of n, or smaller values of a (=1/n). V_Reference represents the reference volume (usually the full organ volume), and V_Irradiated represents the volume irradiated.

Figure 3. The volume-effect parameter

The effect of changing the ‘n’ parameter (= 1/a) in the Lyman model with the generalized equivalent uniform dose equation to compute NTCP is shown. Starting with a (real) rectal DVH computed for an IMRT prostate patient plan (upper left), the DVH is first transformed into a single number by the generalized equivalent uniform dose equation that weights dose values exponentially. The lower figure shows the cumulative contribution of each part of the DVH to the overall gEUD for all bins below the given dose value. As one can see, if a is set to 1 (rightmost curve), gEUD would equal the mean dose (e.g., for parallel organs), and many voxels with doses as low as 20-30 Gy contribute significantly to the gEUD, and therefore may increase the final NTCP value (although contributions are proportional to dose, so higher dose still does contribute more for the same volume). As ‘n’ decreases, the value of gEUD is a determined mainly by the highest dose voxels (e.g., for series organs). Typical clinical values for late rectal bleeding are ~n = 0.1. Unfortunately, investigators sometimes report a (especially when discussing the gEUD) and other-times use n, where n=1/a.