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

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.

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

Model Overview

0

20

40

60

80

100

120

80 85 90 95 100 105 110 115 120

PTVCuboid of volume 100cc divided into 1000Voxels of dimension 0.1cc

Random No.GeneratorRandomly assigns dose values to each voxel between pre-defined max and min values

DVHGenerates DVHfrom voxel data

TCPCalculates uniqueControl prob. from DVHdata

TCP Calculation

Based on the model of Nahum and Tait

n

j

K

i

eV jdjdiNtje

KTCP

1 1

)2(1

α,β are the classic radiosensitivity parameters of the LQ model withα expressed as a Gaussian function of K events. ρj is the density of clonogenic cells (assumed constant across the PTV)Vt is the PTV volumeN is the total no. of fractions and dj is the dose per fraction per voxel

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 withα/β=10, αmean= 0.38+/-0.088 Gy-1, K=104, ρ = 107 cc-1

Results I

Normal distribution curves illustrating the range of TCP valuesobtained for 1,000 unique calculations for each irradiation type.

85 90 95 100

TCP (%)

Uniform

Homog

Inhomog

PD=72GyN=24

Results II

85 90 95 100

TCP (%)

Uniform

Homog

Inhomog

PD= 81N=27

Normal distribution curves illustrating the range of TCP valuesobtained for 1,000 unique calculations for each irradiation type.

Results III

85 90 95 100

TCP (%)

Uniform

Homog

Inhomog

Normal distribution curves illustrating the range of TCP valuesobtained for 1,000 unique calculations for each irradiation type.

PD=90N=30

Summary of Results

The spread of TCP values observed for uniform irradiationis associated with the distribution of α values entered into the model.

The spread of TCP values is inversely proportional to the PD dueto 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. Thisphenomenon increases with PD.

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 controlcan 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 moreclinically relevant definition of optimum dose distribution within the PTV.