NTCP Models Research Articles

SU-FF-T-204: Evaluation of 3-D Cluster Formation in Inhomogeneous Dose Distributions

Purpose: One shortcoming of using dose volume histogram (DVH) to evaluate a radiotherapytreatment plan is that the spatial distribution of the high dose voxels is not accounted. Cluster models, on the other hand, address not only the volumes but also their spatial location. This study is to evaluate cluster formation in clinical volume or organ at risk (OAR) receiving an inhomogeneous dose distribution. Method and Materials: In this study, upper five‐centimeter esophagus in patients with squamous cell carcinoma of the head and neck was used as the OAR. The patients were treated using IMRT. An in‐house program has been developed to analyze the Pinnacle dose grid, and to perform cluster searching. We studied one‐ and two‐connectivity of cluster formation. Results: The characteristics of cluster formation are very different under different fractional density. The size of the largest cluster shows a distribution with a peak and also some extent of spread. The cluster size can vary in a large range and cannot be accurately predicted. Therefore, the clinical outcome of the same DVH could be potentially different. The relationship between the mean size of the largest cluster (MSLC) and fractional density is non‐linear. Above a specific fractional density there is a dramatic increase in the MSLC, which possibly also represents an increase of the chance of percolation. At a certain high fractional density, MSLC increases linearly with fractional density, and additional voxels just increase the size of the existing largest cluster instead of forming new independent short clusters. Comparing one‐connectivity with two‐connectivity, two‐connectivity presents a steeper slope in the exponential increase area on the MSLC v.s. fractional density curve. Conclusion:Our investigation on the superior section of esophagus disclosed some interesting charasteristics. In the future, it may also be possible to incorporate these new NTCP models in the dose optimization algorithm.

SU‐FF‐T‐71: An Interactive Software Tool for Modifying Outcome Models and Predicting Patient Specific Outcomes in Treatment Planning

Purpose: For patient‐specific radiotherapy outcomes predictions (i.e., NTCP predictions), the choice of model and its parameters is of utmost importance. Our goal is to develop a software tool which will let clinicians conveniently select the model, understand the effects of the model parameter values, and thereafter predict plan specific outcomes. Method: This module has been developed within CERR (Computational Environment for Radiotherapy Research), an open source Matlab‐based software system. Two commonly used NTCP analytical models implemented are the Lyman‐Kutcher‐Burman (LKB) and the Critical volume (CV). The parameters of LKB model include: the exponent for calculating EUD, D50, and the slope parameter m; whereas the parameters of the CV model include the mean relative damaged volume, critical fraction of FSUs, and interpatient variability. Our interactive outcomes estimation module lets the user change the model and parameters and observe the change in predicted outcome simultaneously. We have also implemented a new model to predict radiation lung injury, which is a logistic regression model with two predictors — mean dose to lung (MDL) and the GTV location (GTV‐superior‐inferior position). We developed an interactive nomogram to let users look at the variation in outcome with respect to MDL and GTV‐SI position. Results: The interactive outcomes‐prediction module within CERR was tested on sample plans. The user is presented with slider bars to change the parameter values, or the user can input their own values, and the estimated outcome is simultaneously updated. The interface is simple, user‐friendly, and easily extensible to include other outcomes models. Conclusion: This outcomes prediction module, along with other graphical visualization and analysis capabilities within CERR, may aid clinicians in understanding and using NTCP models for radiation treatment planning.This research was partially supported by NIH grant R01CA85181 as well as a grant from TomoTherapy, Inc.

Normal tissue complication probability modelling of tissue fibrosis following breast radiotherapy

Cosmetic late effects of radiotherapy such as tissue fibrosis are increasingly regarded as being of importance. It is generally considered that the complication probability of a radiotherapy plan is dependent on the dose uniformity, and can be reduced by using better compensation to remove dose hotspots. This work aimed to model the effects of improved dose homogeneity on complication probability. The Lyman and relative seriality NTCP models were fitted to clinical fibrosis data for the breast collated from the literature. Breast outlines were obtained from a commercially available Rando phantom using the Osiris system. Multislice breast treatment plans were produced using a variety of compensation methods. Dose–volume histograms (DVHs) obtained for each treatment plan were reduced to simple numerical parameters using the equivalent uniform dose and effective volume DVH reduction methods. These parameters were input into the models to obtain complication probability predictions. The fitted model parameters were consistent with a parallel tissue architecture. Conventional clinical plans generally showed reducing complication probabilities with increasing compensation sophistication. Extremely homogenous plans representing idealized IMRT treatments showed increased complication probabilities compared to conventional planning methods, as a result of increased dose to areas receiving sub-prescription doses using conventional techniques.

2240: Investigation of EUD- and Dose-Volume Based NTCP Models for Rectal Bleeding, Augmented by Principal Component Analysis of DVH Patterns

We applied different NTCP models to rectal wall DVHs and follow-up data of 319 patients in order to identify the dosimetric factors most predictive for a higher risk of late rectal bleeding. PCA was used to investigate variability of DVH patterns in the patient population and its relationship to toxicity.

490 Evaluation of the probability density of the Lyman's and Kallman's relative seriality parameters NTCP models of two endpoints concerning the rectum and the bladder

490 Evaluation of the probability density of the Lyman's and Kallman's relative seriality parameters NTCP models of two endpoints concerning the rectum and the bladder

Data on dose–volume effects in the rat spinal cord do not support existing NTCP models

To evaluate several existing dose-volume effect models for their ability to describe the occurrence of white matter necrosis in rat spinal cord after irradiation with small proton beams. A large number of dose-volume effect models has been fitted to data on the occurrence of white matter necrosis after irradiation with small proton beams. The fitting was done with the maximum likelihood method. For each model, the goodness of fit was calculated. An empirical tolerance dose-volume (eTDV) model was designed to describe data obtained after uniform irradiation. The eTDV model, the critical element model, and critical volume model with inclusion of the repair-by-migration principle described by Shirato, were able to describe the data obtained after irradiation with uniform dose distributions of varying sizes. However, none of the models under investigation was able to describe all the data. Extension of the developed empirical model with a repair mechanism with a limited range resulted in a good description of the tolerance doses. In the rat spinal cord, a nonlocal repair mechanism, acting from nonirradiated to irradiated tissue, plays an important role in the (prevention of the) occurrence of white matter necrosis after irradiation. Models that take into account this effect need to be developed.

Analytical approach to estimate normal tissue complication probability using best fit of normal tissue tolerance doses into the NTCP equation of the linear quadratic model.

Aims and objectives of this study are to get the best fit of the normal tissue tolerance doses to the NTCP model of the linear quadratic model. To compute the NTCP, the modified form of the Poisson cell kill model of NTCP, based on linear-quadratic model, is used. The model has been applied to compute the parameters of the NTCP model using clinical tolerance doses of various normal tissues / organs extracted from published reports of various authors. The normal tissue tolerance doses are calculated for partial volumes of the organs using the values of above-said parameters for published data on normal tissue tolerance doses. In this article, a graphical representation of the computed NTCP for bladder, brain, heart and rectum is presented. A fairly good correspondence is found between the curves of 2 sets of data for brain, heart and rectum. Hence the model may, therefore, be used to interpolate clinical data to provide an estimate of NTCP for these organs for any altered fractionated treatment schedule.

112 oral Is NTCP modelling really useful for the prediction of radiation induced pneumonitis? Dose-response parameters from breast radiotherapy

112 oral Is NTCP modelling really useful for the prediction of radiation induced pneumonitis? Dose-response parameters from breast radiotherapy

116 oral Impact of uncertainties on rectal NTCP modelling: fitting clinical data with the Lyman model

116 oral Impact of uncertainties on rectal NTCP modelling: fitting clinical data with the Lyman model

NTCP modeling for acute esophagitis in patients treated with conformal radiation therapy for non-small cell lung cancer (NSCLC)

NTCP modeling for acute esophagitis in patients treated with conformal radiation therapy for non-small cell lung cancer (NSCLC)

Biological integration of parallel architecture NTCP model for radiation-induced liver disease

Materials/Methods: From 1993 to 2001 a total of 151 patients (89 with hepatocellular carcinoma and 62 with gastric cancer) underwent 3DCRT to part of liver were included in this study. The isocenter dose ranged from 33.0 to 66.0Gy (mean: 48.0Gy). Dose distribution and the corresponding volumetric data were obtained from the computerized planning system. A complication (RILD) was defined as grade 3 or higher RTOG liver toxicity within 4 months after completing 3DCRT. Patient-related and dosimetric factors were tested for their correlation with RILD in univariate and multivariate analyses. A maximal likelihood analysis was used to yield the best estimates for the parallel NTCP model parameters of the whole group and the subgroups. Patients were divided by statistically significant non-dosimetric factors, which were integrated into the modeling process for better describing the occurrence of RILD. Goodness of fit analysis was used to estimate the deviance of NTCP model parameters of subgroups from the whole group.

NTCP modeling for acute esophagitis in patients treated with conformal radiation therapy for non-small cell lung cancer (NSCLC)

Acute esophagitis is a common side effect of thoracic irradiation. Several dosimetric cutoffs, based on the irradiated surface, volume or length of the esophagus, have been observed to correlate with the occurrence of esophageal toxicity. However, in practice, these single threshold descriptors often don’t provide useful information for discrimination among rival treatment plans or for optimization of IMRT. Thus, there is interest in exploring the use of standard NTCP models (such as the Lyman-Kutcher-Burman model, LKB) for characterization of esophageal toxicities.

Lung V20 measurements: in regard to Seppenwoolde et al. (int j radiat oncol biol phys 2003;55:724?735), AND Tsujino et al. (int j radiat oncol biol phys 2003;56:1208?1209)

We have read with great interest the articles by Seppenwoolde et al. ( 1 Seppenwoolde Y. Lebesque J.V. de Jaeger K. et al. Comparing different NTCP models that predict the incidence of radiation pneumonitis. Normal tissue complication probability. Int J Radiat Oncol Biol Phys. 2003; 55: 724-735 Abstract Full Text Full Text PDF PubMed Scopus (360) Google Scholar ), and Tsujino et al. ( 2 Tsujino K. Hirota S. Endo M. et al. Predictive value of dose-volume histogram parameters for predicting radiation pneumonitis after concurrent chemoradiation for lung cancer. Int J Radiat Oncol Biol Phys. 2003; 55: 110-115 Abstract Full Text Full Text PDF PubMed Scopus (285) Google Scholar ) on radiation pneumonitis and their recent letters to the editor ( 3 Seppenwoolde Y. De Jaeger K. Lebesque J.V. In regard to Tsujino et al.: Predictive value of dose-volume histogram parameters for predicting radiation pneumonitis after concurrent chemoradiation for lung cancer. IJROBP. 2003; 55 (Int J Radiat Oncol Biol Phys 2003;56:1208–1209): 110-111 Google Scholar ). The letter to the editor and the response are well written, and we are happy to see that some of the limitations of this comparison were described. However, we have concerns that were not addressed by either group. 1.Definitions of V20 vary from study to study. 2.Chemotherapy was used in 42% of Dr. Graham's non–small-cell lung cancer cohort, yet they are included in the analysis of 382 radiotherapy-alone patients.

Late rectal bleeding: fitting clinical data with different NTCP models

T. Rancati, G. Gagliardi, G.M. Cattaneo, C. Cozzarini, G. Fellin, G. Girelli, G. Sanguineti, V. Vavassori, R. Valdagni, C. Fiorino University of Milan, Milan, Italy, Medical Physics and Radiotherapy, H. S. Raffaele, Milan, Italy, Hospital Physics, Karolinska Hospital, Stockholm, Sweden, Radiotherapy, Ospedale S. Chiara, Trento, Italy, Radiotherapy, Azienda Ospedaliera ASL 9, Ivrea, Italy, Radiotherapy, UTMB, Galveston, TX, Medical Physics and Radiotherapy, Ospedale di Circolo, Varese, Italy, Radiotherapy, Clinica Pio X, Milan, Italy

164 oral Analysis of clinical complication data on late rectal bleeding: fitting to different NTCP models

164 oral Analysis of clinical complication data on late rectal bleeding: fitting to different NTCP models

16 The role of NTCP models in the Optimisation Of IMRT

16 The role of NTCP models in the Optimisation Of IMRT

535 Verification of Fluence Map (FM) in dynamic radiotherapy techniques

Curative radiotherapy for prostate cancer may lead to anorectal side effects, including rectal bleeding, fecal incontinence, increased stool frequency and rectal pain. The main objective of this study was to develop multivariable NTCP models for these side effects.The study sample was composed of 262 patients with localized or locally advanced prostate cancer (stage T1–3). Anorectal toxicity was prospectively assessed using a standardized follow-up program. Different anatomical subregions within and around the anorectum were delineated. A LASSO logistic regression analysis was used to analyze dose volume effects on toxicity.In the univariable analysis, rectal bleeding, increase in stool frequency and fecal incontinence were significantly associated with a large number of dosimetric parameters. The collinearity between these predictors was high (VIF > 5). In the multivariable model, rectal bleeding was associated with the anorectum (V70) and anticoagulant use, fecal incontinence was associated with the external sphincter (V15) and the iliococcygeal muscle (V55). Finally, increase in stool frequency was associated with the iliococcygeal muscle (V45) and the levator ani (V40). No significant associations were found for rectal pain.Different anorectal side effects are associated with different anatomical substructures within and around the anorectum. The dosimetric variables associated with these side effects can be used to optimize radiotherapy treatment planning aiming at prevention of specific side effects and to estimate the benefit of new radiation technologies.

29 disc Dose-volume effects in the rat spinal cord: mathematical NTCP models put to the test

29 disc Dose-volume effects in the rat spinal cord: mathematical NTCP models put to the test

30 disc NTCP modelling of radiation damage to the parotid glands of the rat assessed from stimulated flow measurements

30 disc NTCP modelling of radiation damage to the parotid glands of the rat assessed from stimulated flow measurements

Derivation of the expressions for γ50 and D50 for different individual TCP and NTCP models

This paper presents a complete set of formulae for the position (D50) and the normalized slope (γ50) of the dose–response relationship based on the most commonly used radiobiological models for tumours as well as for normal tissues. The functional subunit response models (critical element and critical volume) are used in the derivation of the formulae for the normal tissue. Binomial statistics are used to describe the tumour control probability, the functional subunit response as well as the normal tissue complication probability. The formulae are derived for the single hit and linear quadratic models of cell kill in terms of the number of fractions and dose per fraction. It is shown that the functional subunit models predict very steep, almost step-like, normal tissue individual dose–response relationships. Furthermore, the formulae for the normalized gradient depend on the cellular parameters α and β when written in terms of number of fractions, but not when written in terms of dose per fraction.