Correlation between pneumonitis risk in radiation oncology and lung density measured with X-ray computed tomography

Abstract

Background: The risk of toxicity with radiation oncology for lung cancer limits the maximal radiation dose that can be delivered to thoracic tumors. This study aims at investigating the correlation between normal tissue complication probability (NTCP) and physical lung density by analyzing the computed tomography (CT) scan imaging used for radiotherapy dose planning.Methods: Data from CT of lung cancer patients (n=10), treated with three dimensional radiotherapy, were selected for this study. The dose was calculated using analytical anisotropic algorithm (AAA). Dose volume histograms (DVH) for healthy lung (lung excluding targets) were calculated. The NTCP for lung radiation induced pneumonitis was computed using initial radiobiological parameters from Lyman-Kutcher and Burman (LKB) model and readjusted parameters for AAA, with α/β=3. The correlation coefficient "rho" was calculated using Spearman's rank test. The bootstrap method was used to estimate the 95% confidence interval (95% CI). Wilcoxon paired test was used to calculate P values.Results: Bootstrapping simulation revealed significant difference between NTCP computed with the initial radiobiological parameters and that computed with the parameters readjusted for AAA (P=0.03). The results of simulations based on 1,000 replications showed no correlation for NTCP with density, with "rho" <0.3.Conclusions: For a given set of patients, we assessed the correlation between NTCP and lung density using bootstrap analysis. The lack of correlation could result either from a very accurate dose calculation, by AAA, whatever the lung density yielding a NTCP result only dependant of the dose and not any more of the density; or to the very limited range of natural variation of relative electronic density (0.15 to 0.20) observed in this small series of patients. Another important parameter is the bootstrap simulation with 1,000 random samplings may have underestimated the correlation, since the initial data (n=10) showed a weak correlation.Keywords: Normal tissue complication probability (NTCP); radiotherapy; bootstrap; physical density of lung and statistical concepts, to estimate the tumor control probability (TCP) as well as the normal tissue complication probability (NTCP) (2-9). Most theoretical models, that have been developed to estimate the benefits/risks balance, are based on physical dose distribution and the biological effect in normal tissue. However, the accuracy of the estimated TCP/NTCP depends on the accuracy of the assessment of the delivered dose as well as uncertainties related to the clinical data and dose calculation methods. The purpose of this paper is to evaluate and quantify the correlation between NTCP estimates and physical lung density. The NTCP was computed using dosimetric data derived from the patients' dose volume histograms (DVH) with Lyman model. Methods Clinical cases and dose calculationData from computed tomography (CT-scans) in ten lung cancer patients, treated with 3-dimensional radiotherapy, were selected for this study. The clini...

Impact of dose calculation models on radiotherapy outcomes and quality adjusted life years for lung cancer treatment: do we need to measure radiotherapy outcomes to tune the radiobiological parameters of a normal tissue complication probability model?

“…A better calibration should produce a better correlation coefficient from Q c and Q m and so on. Providing to have a sufficient number of patients to ensure that we can capture the variation within the patient population, the body of data could be extended even more by a bootstrap simulation method (22).…”