1. A Tumour Control Probability based approach to the development of Plan Acceptance Criteria for Planning Target Volume in Intensity Modulated Radiation Therapy for Non-Small Cell Lung Cancer Colin Kelly, Pierre Thirion, Csaba Petnahazi, J Armstrong. Clinical Trials Unit St Luke’s Hospital Ireland

2. Background It has been long recognised that the probability of tumour control is dependent on the Prescribed Dose (PD) and the homogeneity of dose within the Planning Target Volume (PTV). 3-Dimensional Conformal Radiation Therapy (3DCRT) has traditionally used the recommendations of ICRU 50 for dose prescription within the PTV. Intensity Modulated Radiation Therapy (IMRT) can produce supra conformal dose distributions with significant advantages over 3DCRT in terms of organ at risk (OAR) sparing. The consequence of this is that IMRT can less easily fulfill the dose constraints of ICRU 50.

3. Purpose The purpose of this study was threefold as follows: To evaluate the use of a TCP model for the expression of dose distributions inside the PTV To use the model to compare Uniform, Homogenous (ICRU 50), and inhomogenous (non ICRU 50) PTV irradiations To develop TCP based Plan Acceptance Criteria for IMRT schemes for the treatment of NSCLC

4. Model Overview PTV Cuboid of volume 100cc divided into 1000 Voxels of dimension 0.1cc Random No.Generator Randomly assigns dose values to each voxel between pre-defined max and min values DVH Generates DVH from voxel data TCP Calculates unique Control prob. from DVH data

5. TCP Calculation Based on the model of Nahum and Tait α,β are the classic radiosensitivity parameters of the LQ model with α expressed as a Gaussian function of K events. ρ j is the density of clonogenic cells (assumed constant across the PTV) V t is the PTV volume N is the total no. of fractions and d j is the dose per fraction per voxel

6. Three theoretical regimes for dose escalation in NSCLC were assessed i.e. 72/24, 81/27 and 90/30. Three types of dose distribution were analysed as follows -Uniform : all voxels receive the PD. -Homogenous (ICRU 50) : all voxels receive a dose of between 95 and 107% of the PD. -Inhomogenous : voxels could receive a dose of between 90-107% of the PD (i.e. non ICRU 50). Input Parameters Model parameters are taken from the literature with α/β=10, α mean = 0.38+/-0.088 Gy -1, K=10 4, ρ = 10 7 cc -1

7. Results I Normal distribution curves illustrating the range of TCP values obtained for 1,000 unique calculations for each irradiation type. PD=72Gy N=24

8. Results II PD= 81 N=27 Normal distribution curves illustrating the range of TCP values obtained for 1,000 unique calculations for each irradiation type.

9. Results III Normal distribution curves illustrating the range of TCP values obtained for 1,000 unique calculations for each irradiation type. PD=90 N=30

10. Summary of Results The spread of TCP values observed for uniform irradiation is associated with the distribution of α values entered into the model. The spread of TCP values is inversely proportional to the PD due to the incresing numbers of voxels receiving a lethal dose. For a significant number of cases inhomogenous irradiation can Result in TCP at least equivalent to homogenous irradiation. This phenomenon increases with PD.

11. Conclusions The difficulty in obtaining IMRT solutions for NSCLC which comply with ICRU 50 is significant. Use of a TCP model suggests that equivalent tumour control can be achieved despite a relaxation of the dose volume constraints of ICRU 50. Although there is some uncertainty regarding r/biol parameters, TCP based physical accetance criteria takes into account tumour radiosensitivity, dose fractionation, and cellular biology. A TCP based approach offers the potential for a more clinically relevant definition of optimum dose distribution within the PTV.