IMRT optimization including random and systematic geometric errors based on the expectation of TCP and NTCP.

The purpose of this work was the development of a probabilistic planning method with biological cost functions that does not require the definition of margins. Geometrical uncertainties were integrated in tumor control probability (TCP) and normal tissue complication probability (NTCP) objective functions for inverse planning. For efficiency reasons random errors were included by blurring the dose distribution and systematic errors by shifting structures with respect to the dose. Treatment plans were made for 19 prostate patients following four inverse strategies: Conformal with homogeneous dose to the planning target volume (PTV), a simultaneous integrated boost using a second PTV, optimization using TCP and NTCP functions together with a PTV, and probabilistic TCP and NTCP optimization for the clinical target volume without PTV. The resulting plans were evaluated by independent Monte Carlo simulation of many possible treatment histories including geometrical uncertainties. The results showed that the probabilistic optimization technique reduced the rectal wall volume receiving high dose, while at the same time increasing the dose to the clinical target volume. Without sacrificing the expected local control rate, the expected rectum toxicity could be reduced by 50% relative to the boost technique. The improvement over the conformal technique was larger yet. The margin based biological technique led to toxicity in between the boost and probabilistic techniques, but its control rates were very variable and relatively low. During evaluations, the sensitivity of the local control probability to variations in biological parameters appeared similar for all four strategies. The sensitivity to variations of the geometrical error distributions was strongest for the probabilistic technique. It is concluded that probabilistic optimization based on tumor control probability and normal tissue complication probability is feasible. It results in robust prostate treatment plans with an improved balance between local control and rectum toxicity, compared to conventional techniques.

Impact of geometrical uncertainties on 3D CRT and IMRT dose distributions for lung cancer treatment.

PURPOSE: To quantify the effect of set-up errors and respiratory motion on dose distributions for non-small cell lung cancer (NSCLC) treatment. METHODS AND MATERIALS: Irradiations of 5 NSCLC patients were planned with 3 techniques, two (conformal radiation therapy (CRT) and intensity modulated radiation therapy (IMRT1)) with a homogeneous dose in the planning target volume (PTV) and a third (IMRT2) with dose heterogeneity. Set-up errors were simulated for gross target volume (GTV) and organs at risk (OARs). For the GTV, the respiration was also simulated with a periodical motion around a varying average. Two configurations were studied for the breathing motion, to describe the situations of free-breathing (FB) and respiration-correlated (RC) CT scans, each with 2 amplitudes (5 and 10 mm), thus resulting in 4 scenarios (FB_5, FB_10, RC_5 and RC_10). Five thousand treatment courses were simulated, producing probability distributions for the dosimetric parameters. RESULTS: For CRT and IMRT1, RC_5, RC_10 and FB_5 were associated with a small degradation of the GTV coverage. IMRT2 with FB_10 showed the largest deterioration of the GTV dosimetric indices, reaching 7% for Dmin at the 95% probability level. Removing the systematic error due to the periodic breathing motion was advantageous for a 10 mm respiration amplitude. The estimated probability of radiation pneumonitis and acute complication for the esophagus showed limited sensitivity to geometrical uncertainties. Dmax in the spinal cord and the parameters predicting the risk of late esophageal toxicity were associated to a probability up to 50% of violating the dose tolerances. CONCLUSIONS: Simulating the effect of geometrical uncertainties on the individual patient plan should become part of the standard pre-treatment verification procedure.

The sensitivity of dose distributions for organ motion and set-up uncertainties in prostate IMRT.

BACKGROUND AND PURPOSE: To determine the effect of organ motion and set-up uncertainties on IMRT dose distributions for prostate. METHODS: For five patients, IMRT techniques were designed to irradiate the CTV (prostate plus seminal vesicles). Technique I delivered 78 Gy to PTV1 (CTV+10 mm margin). Technique II delivered 68 Gy to PTV1, and a 10 Gy boost to PTV2 (CTV+an anisotropic margin of 0 to 5 mm). Technique III delivered 68 Gy to PTV1 and simultaneously 78 Gy to PTV2. Uncertainties were simulated using population statistics of organ motion and set-up accuracy. The average TCP (TCPpop) of the CTV and average NTCP (NTCPpop) of the rectal wall were calculated. RESULTS: The planning TCP was a good predictor for TCPpop for Techniques I and II. Technique III was sensitive for geometrical uncertainties, reducing TCPpop by 0.8 to 2.4% compared to planning. NTCPpop was reduced for Technique III by a factor 2.6 compared to Technique I. For all plans, the planning NTCP was strongly correlated with NTCPpop. CONCLUSIONS: Dose distributions created with Techniques I and II are insensitive for geometrical uncertainties, while Technique III resulted in a reduction of TCPpop. This reduction can be compensated by a small dose escalation, while still resulting in an NTCPpop of the rectal wall that is lower or comparable to Technique I.

The effects of target size and tissue density on the minimum margin required for random errors.

The minimum margins required to compensate for random geometric uncertainties in the delivery of radiotherapy treatment were determined for a spherical Clinical Target Volume, using an analytic model for the cumulative dose. Margins were calculated such that the minimum dose in the target would be no less than 95% of the prescribed dose for 90% of the patients. The dose distribution model incorporated two Gaussians, and could accurately represent realistic dose profiles for various target sizes in lung and water. It was found that variations in target size and tissue density lead to significant changes in the minimum margin required for random errors. The random error margin increased with tissue density, and decreased with target size. The required margins were similar for dose distributions of spherical and cylindrical symmetry. Significant dose outside the spherical high dose region, as could result from multiple incident beams, lead to an increased margin for the larger targets. We could confirm that the previously proposed margin of 0.7 times the standard deviation of the random errors is safe for standard deviations up to 5 mm, except for very small targets in dense material.

Biologic and physical fractionation effects of random geometric errors.

PURPOSE: We are developing a system to model the effect of random and systematic geometric errors on radiotherapy delivery. The purpose of this study was to investigate biologic and physical fractionation effects of random geometric errors and respiration motion and compare the resulting dose distributions with Gaussian blurring of the planned dose. MATERIALS AND METHODS: A hypothetical dose distribution with Gaussian penumbra was used. Random errors drawn from a normal distribution, optionally combined with simulated respiration motion (in the cranio-caudal direction), were used to displace the dose distribution for N simulated fractions. To simulate biologic effects of fractionation, the physical dose was converted to a biologically effective dose using the linear-quadratic model (including repopulation), then summed and converted back to physical dose for comparison. Differences between dose distributions were quantified in terms of the distance between selected isodose levels. RESULTS: A limited number of fractions led to an uncertainty in the position of isodose levels in the total dose with as standard deviation (SD) the SD of the random error divided by radical N. Due to biologic fractionation effects, the total dose distribution became slightly wider: 0.4 mm for alpha/beta = 1 Gy and a random error SD of 3 mm. The widening increased with random error and reduced with increasing alpha/beta but does not depend on the number of fractions or on repopulation. Respiration motion caused an asymmetric deviation in the shape of the total dose distribution, but no additional dose widening was seen from the biologic effect of fractionation. With a random error SD of 3 mm and respiration amplitude, A, of 1 cm or less (SD < 0.36 cm), the asymmetry was negligible. For larger respiration amplitudes (combined with the same random error), the shift of the 95% isodose level was about 0.25*A caudally, and 0.45*A cranially. CONCLUSIONS: Gaussian blurring with a combined SD of organ motion, setup error, and respiration motion is a valid approximation for the effect of purely random errors in fractionated radiotherapy. For respiration motion in excess of 1 cm in amplitude, isodose lines shift in a distinctly asymmetric fashion and asymmetric margins need to be used.