Optimal Dose Distribution Research Articles

TH‐AB‐304‐09: A Patient‐Specific Heterogeneous Radiobiological Model for Glioblastoma Multiforme

Purpose:Gliomas tumors proliferate and invade healthy brain tissue rapidly, yielding short life expectancies. Radiation therapy is commonly used, but gliomas are known to be radio‐resistant, and almost always recur following treatment. Current radiotherapy protocols are based on the classic linear‐quadratic radiobiological model, assuming a homogeneous (one‐component) tumor. Gliomas are very heterogeneous, consisting of normoxic, hypoxic, and necrotic tissues, each responding differently to radiation. An enhanced linear‐quadratic model which takes into account the different responses of the heterogeneous tumor regions to radiation can guide treatment planning to optimize dose distributions to maximize the therapeutic effect.Methods:We used a set of differential equations to model the growth of glioma tumors. Our model expands on the one‐component model developed by (Rockne,2010) by including normoxic, hypoxic, and necrotic components and radiosensitivity values for each component. Proliferation and diffusion parameters are extracted by contouring the tumor on two sets of pre‐treatment MRIs and modeling it as a volume equivalent sphere.Results:We compared two examples of glioma tumors presented in (Rockne,2010) with our three component model and find better predictive capabilities for post‐RT tumor volumes using the three component model. In both cases, the one‐component model over predicts the effects of radiation on the tumor core, while the three‐component model more accurately fits the data by accounting for radioresistance of the hypoxic core. Additionally, we applied the model to a UCSF patient with a recurring tumor and use the model to predict time to fatal tumor burden.Conclusion:The three‐component model accurately matches tumor growth dynamics derived from MRIs for two example cases presented in literature, and one case from UCSF. Spatial information about hypoxic, necrotic, and normoxic cell densities are derived from the model providing information needed to more intelligently prescribe dose distributions tailored to a specific patient's tumor.[Rockne,et.al.,PhysMedBio,2010]

New radiation therapy techniques for head and neck tumors: Progress and prospects

During the last twenty years, major advances have been made in treating head and neck cancer using radiation therapy with three axis of technical optimization, namely, a better definition of target volumes, an optimization of dose distribution to the tumor, and a decrease of dose to healthy organs. These new radiation therapy techniques can improve the patient’s quality of life without decreasing local control and survival.

Available evidence on re-irradiation with stereotactic ablative radiotherapy following high-dose previous thoracic radiotherapy for lung malignancies.

Patients affected with intra-thoracic recurrences of primary or secondary lung malignancies after a first course of definitive radiotherapy have limited therapeutic options, and they are often treated with a palliative intent. Re-irradiation with stereotactic ablative radiotherapy (SABR) represents an appealing approach, due to the optimized dose distribution that allows for high-dose delivery with better sparing of organs at risk. This strategy has the goal of long-term control and even cure. Aim of this review is to report and discuss published data on re-irradiation with SABR in terms of efficacy and toxicity. Results indicate that thoracic re-irradiation may offer satisfactory disease control, however the data on outcome and toxicity are derived from low quality retrospective studies, and results should be cautiously interpreted. As SABR may be associated with serious toxicity, attention should be paid for an accurate patients' selection.

Ion therapy of prostate cancer: daily rectal dose reduction by application of spacer gel.

BackgroundIon beam therapy represents a promising approach to treat prostate cancer, mainly due to its high conformity and radiobiological effectiveness. However, the presence of prostate motion, patient positioning and range uncertainties may deteriorate target dose and increase exposure of organs at risk. Spacer gel injected between prostate and rectum may increase the safety of prostate cancer (PC) radiation therapy by separating the rectum from the target dose field. The dosimetric impact of the application of spacer gel for scanned carbon ion therapy of PC has been analyzed at Heidelberg Ion-Beam Therapy Center (HIT).Materials and methodsThe robustness of ion therapy treatment plans was investigated by comparison of two data sets of patients treated with and without spacer gel. A research treatment planning system for ion therapy was used for treatment plan optimization and calculation of daily dose distributions on 2 to 9 Computed Tomography (CT) studies available for each of the 19 patients. Planning and daily dose distributions were analyzed with respect to target coverage, maximal dose to the rectum (excluding 1 ml of the greatest dose; Dmax-1 ml) and the rectal volume receiving dose greater than 90% of prescribed target dose (V90Rectum), respectively.ResultsThe application of spacer gel did substantially diminish rectum dose. Dmax-1 ml on the treatment planning CT was on average reduced from 100.0 ± 1.0% to 90.2 ± 4.8%, when spacer gel was applied. The robustness analysis performed with daily CT studies demonstrated for all analyzed patient cases that application of spacer gel results in a decrease of the daily V90Rectum index, which calculated over all patient cases and CT studies was 10.2 ± 10.4 [ml] and 1.1 ± 2.1 [ml] for patients without and with spacer gel, respectively.ConclusionsThe dosimetric benefit of increasing the distance between prostate and rectum using spacer gel for PC treatment with carbon ion beams has been quantified. Application of spacer gel substantially reduced rectal exposure to high treatment dose and, therefore, can reduce the hazard of rectal toxicity in ion beam therapy of PC. The results of this study enable modifications of the PC ion therapy protocol such as dose escalation or hypofractionation.Electronic supplementary materialThe online version of this article (doi:10.1186/s13014-015-0348-1) contains supplementary material, which is available to authorized users.

Multiple anatomy optimization of accumulated dose.

To investigate the potential advantages of multiple anatomy optimization (MAO) for lung cancer radiation therapy compared to the internal target volume (ITV) approach. MAO aims to optimize a single fluence to be delivered under free-breathing conditions such that the accumulated dose meets the plan objectives, where accumulated dose is defined as the sum of deformably mapped doses computed on each phase of a single four dimensional computed tomography (4DCT) dataset. Phantom and patient simulation studies were carried out to investigate potential advantages of MAO compared to ITV planning. Through simulated delivery of the ITV- and MAO-plans, target dose variations were also investigated. By optimizing the accumulated dose, MAO shows the potential to ensure dose to the moving target meets plan objectives while simultaneously reducing dose to organs at risk (OARs) compared with ITV planning. While consistently superior to the ITV approach, MAO resulted in equivalent OAR dosimetry at planning objective dose levels to within 2% volume in 14/30 plans and to within 3% volume in 19/30 plans for each lung V20, esophagus V25, and heart V30. Despite large variations in per-fraction respiratory phase weights in simulated deliveries at high dose rates (e.g., treating 4/10 phases during single fraction beams) the cumulative clinical target volume (CTV) dose after 30 fractions and per-fraction dose were constant independent of planning technique. In one case considered, however, per-phase CTV dose varied from 74% to 117% of prescription implying the level of ITV-dose heterogeneity may not be appropriate with conventional, free-breathing delivery. MAO incorporates 4DCT information in an optimized dose distribution and can achieve a superior plan in terms of accumulated dose to the moving target and OAR sparing compared to ITV-plans. An appropriate level of dose heterogeneity in MAO plans must be further investigated.

Arrêt de la commercialisation des fils d’iridium 192 en France : proposition du groupe de curiethérapie de la Société française de radiothérapie oncologique

In 2014, the production of iridium 192 wires in France ended. Thus brachytherapy departments had to move to high-dose rate and pulsed-dose rate afterloading techniques. Most of them had already made this migration for some indications, based on the habits and investments. The brachytherapy group organised meetings and opened discussions to share the clinical knowledge and answer to the questions raised by this migration. This made it possible to resolve and describe quite all the clinical and technical cases of brachytherapy. The development of high technology included the use of 3D dosimetry and optimisation of dose distribution and fractionation. The teaching policy of new technologies contributes to the improvement of treatment quality. Last but not least, a better reimbursement of brachytherapy is necessary and currently negotiated.

Dosimetric Evaluation of Treatment Planing System on High-Dose-Rate (HDR) Brachytherapy Using Monte Carlo Method and Radiochomic Film

The increasing use of 3D brachytherapy in countries of South America has promoted numerous discussions about how to evaluate the ability of treatment planning system (TPS) to accurately calculate doses in target and organs at risk. Based on patient's CT, MRI images and implant geometry given by the applier, the TPS is used for (i) methods for dose calculation around sources, (ii) methods for source location, (iii) 3D visualization of target volume, organs at risk dose distribution, (iv) optimization of dose distribution to the target volume, (v) evaluation of dose distribution using dose - volume histograms and (vi) combination of brachytherapy and external beam distributions.

Recent advances in radiation oncology.

Stereotactic radiotherapy (SRT) for extracranial tumors has been referred to as stereotactic body radiation therapy (SBRT) or stereotactic ablative radiotherapy (SABR) and has been used recently to treat primary lung cancer and liver cancer [1]. The advantage of SBRT, with a smaller irradiated volume enabled by more precise set-up, is hypofractionated radiotherapy leading to a shorter treatment course of a week. Its clinical significance in both inoperable and operable T1N0M0 primary lung cancer has been reported throughout the world. Its advances in physics and technology are marvelous. However, its biological basis is still controversial, especially regarding whether the linearquadratic (L-Q) model can be applied for this single highdose radiotherapy. In this issue, Dr. Song, who is one of the world’s leading radiation biologists, has written a critical review article. In this paper, he looks at the importance of vascular damage caused by the effect of a single high dose on tumor cell death. A new biological model taking vascular damage into consideration may therefore be required for SBRT. On the other hand, the advances in intensity-modulated radiotherapy (IMRT) throughout the world are remarkable. This is a new technique for achieving optimal dose distributions using a multi-leaf collimator and computer technology. In Japan, more than 130 institutions make clinical use of IMRT. The cancers treated by IMRT include prostate cancer, head and neck cancer, brain tumor and all other localized tumors. Clinical evidence demonstrating a decrease in toxicities and improvement in local control and survival has been emerging. Dr. Nakamura, who is one of the world’s leading radiation oncologists, has written a critical review article from the clinical point of view. The topics are brain, head and neck, breast, lung, prostate, uterus, and spinal metastases. He was able to find several reports demonstrating decreases in toxicity, although he could not find evidence of improvements in local control and survival. The significance of IMRT on clinical outcome should be continuously evaluated.

WE-G-16A-01: Evolution of Radiation Treatment Planning

WE-G-16A-01: Evolution of Radiation Treatment Planning

TU‐F‐BRF‐08: Intensity Modulation Expanded to Spatio‐Temporal Space; IMRT Combined with Optimal Fractionation Schedule

Purpose:Past efforts to improve the therapeutic ratio have focused on a spatial approach where highly conformal radiation dose is given to tumors while minimizing dose to normal tissues, e.g., IMRT, VMAT, and IGRT. However, the fractionation schedule, i.e., a temporal approach to radiotherapy, has been largely overlooked so far in maximizing the therapeutic ratio. We establish a rigorous mathematical spatio‐temporal approach to systematically investigate the feasibility and potential benefits of simultaneously optimizing radiation dose distribution in space and time.Methods:Stochastic control formalism is constructed to maximize the average tumor BED by choosing an optimal radiation dose distribution for an optimal number of fractions subject to normal tissue BED constraints. Three separate simulations are run on two groups of phantom cases; 5 cases with prostate cancer and 5 cases with head‐and‐neck cancer. (1) Conventional IMRT with 70Gy/35fx for head‐and‐neck, and 81Gy/45fx for prostate, (2) IMRT is done independently from the fractionation schedule optimization (S‐model), (3) integrated spatio‐temporal approach (I‐model) where radiation intensities are simultaneously optimized for the first time ever in space and time. Final tumor BEDs from the three trials are compared in prostate and head‐and‐neck cases.Results:Numerical simulations show that final tumor BED from I‐model is 20–90% larger than conventional IMRT, and 20‐50% larger than S‐model for head‐and‐neck cancer with α/β=10 and Tdouble=2–50 days. Final tumor BED from I‐model is also 90–140% larger than conventional IMRT, and 20–30% larger than S‐model for prostate cancer with α/β=2 and Tdouble=5–80 days.Conclusion:Our spatio‐temporal optimization of radiotherapy allows an expansion of search space for the optimal treatment plans to include the temporal distribution of radiation dose in addition to the spatial distribution. Such spatio‐temporal approach shows great potential to improve the therapeutic ratio, particularly with fast growing, aggressive tumors with short doubling time and/or low α/β.

SU‐E‐T‐21: A Novel Sampling Algorithm to Reduce Intensity‐Modulated Radiation Therapy (IMRT) Optimization Time

Purpose:The IMRT optimization problem requires substantial computer time to find optimal dose distributions because of the large number of variables and constraints. Voxel sampling reduces the number of constraints and accelerates the optimization process, but usually deteriorates the quality of the dose distributions to the organs. We propose a novel sampling algorithm that accelerates the IMRT optimization process without significantly deteriorating the quality of the dose distribution.Methods:We included all boundary voxels, as well as a sampled fraction of interior voxels of organs in the optimization. We selected a fraction of interior voxels using a clustering algorithm, that creates clusters of voxels that have similar influence matrix signatures. A few voxels are selected from each cluster based on the pre‐set sampling rate.Results:We ran sampling and no‐sampling IMRT plans for de‐identified head and neck treatment plans. Testing with the different sampling rates, we found that including 10% of inner voxels produced the good dose distributions. For this optimal sampling rate, the algorithm accelerated IMRT optimization by a factor of 2–3 times with a negligible loss of accuracy that was, on average, 0.3% for common dosimetric planning criteria.Conclusion:We demonstrated that a sampling could be developed that reduces optimization time by more than a factor of 2, without significantly degrading the dose quality.

SU‐E‐T‐420: Impact of Different Prescription Isodose Lines On Plan Quality for Brain Metastases Using Multiplan System

Purpose:With the sequential optimization algorithm in MultiPlan system, clinical objectives (homogeneity, PTV coverage, conformity, normal tissue protection) can be optimized in sequence. However, the prescription isodose line (RxIDL) varies widely among institutions, which can influence the optimized dose distribution. The aim of this study is to investigate the impact of different prescription isodose lines on plan quality for the treatment of brain metastases using CyberKnife Multiplan system.Methods:Ten patients with multiple metastases were selected for this study. Four plans were generated for each patient such that 100% of the target volume receives the prescribed dose of 18 Gy, which was 50%, 60%, 70%, and 80% prescription Isodose line, separately. The prescription isodose was calculated as the ratio of the prescription dose and the maximum dose in target volume. The dosimetric parameters, including PTV coverage, conformity index (CI), gradient index (GI) and the volume covered by 12 Gy (V12Gy) were analyzed. The plan Monitor Units (MU) and treatment time were also compared.Results:All plans can provide the same target coverage (100%) and similar conformity index (1.26, 1.30, 1.32, and 1.29 on average for 80%, 70%, 60%, and 50% RxIDL plans, separately); there was no difference in critical structure dose. The 50% RxIDL plans have much lower GI (4.21±1.79 for 50% and 5.56±2.92 for 80% RxIDL plans) and V12Gy (13.36±10.31cc for 50% and 15.87±11.85cc for 80% RxIDL plans). The variation in estimated treatment delivery time was insignificant.Conclusion:The dose falloff is much faster for the lower RxIDL plans in terms of GI and V12Gy. For 50% RxIDL plans, the average V12Gy decreases by 16% compared to 80% RxIDL plans, which indicates that the normal tissue can be better protected by decreasing the prescription Isodose line.

WE‐E‐BRE‐04: Dual Focal Spot Dose Painting for Precision Preclinical Radiobiological Investigations

Purpose:Recent progress in small animal radiotherapy systems has provided the foundation for delivering the heterogeneous, millimeter scale dose distributions demanded by preclinical radiobiology investigations. Despite advances in preclinical dose planning, delivery of highly heterogeneous dose distributions is constrained by the fixed collimation systems and large x‐ray focal spot common in small animal radiotherapy systems. This work proposes a dual focal spot dose optimization and delivery method with a large x‐ray focal spot used to deliver homogeneous dose regions and a small focal spot to paint spatially heterogeneous dose regions.Methods:Two‐dimensional dose kernels were measured for a 1 mm circular collimator with radiochromic film at 10 mm depth in a solid water phantom for the small and large x‐ray focal spots on a recently developed small animal microirradiator. These kernels were used in an optimization framework which segmented a desired dose distribution into low‐ and high‐spatial frequency regions for delivery by the large and small focal spot, respectively. For each region, the method determined an optimal set of stage positions and beam‐on times. The method was demonstrated by optimizing a bullseye pattern consisting of 0.75 mm radius circular target and 0.5 and 1.0 mm wide rings alternating between 0 and 2 Gy.Results:Compared to a large focal spot technique, the dual focal spot technique improved the optimized dose distribution: 69.2% of the optimized dose was within 0.5 Gy of the intended dose for the large focal spot, compared to 80.6% for the dual focal spot method. The dual focal spot design required 14.0 minutes of optimization, and will require 178.3 minutes for automated delivery.Conclusion:The dual focal spot optimization and delivery framework is a novel option for delivering conformal and heterogeneous dose distributions at the preclinical level and provides a new experimental option for unique radiobiological investigations.Funding Support: this work is supported by funding the National Sciences and Engineering Research Council of Canada, and a Mitacs‐accelerate fellowship.Conflict of Interest: Dr. Lindsay and Dr. Jaffray are listed as inventors of the small animal microirradiator described herein. This system has been licensed for commercial development.

Implementation of a dose gradient method into optimization of dose distribution in prostate cancer 3D-CRT plans

AimThe aim of this work is to present a method of beam weight and wedge angle optimization for patients with prostate cancer. Background3D-CRT is usually realized with forward planning based on a trial and error method. Several authors have published a few methods of beam weight optimization applicable to the 3D-CRT. Still, none on these methods is in common use. Materials and methodsOptimization is based on the assumption that the best plan is achieved if dose gradient at ICRU point is equal to zero. Our optimization algorithm requires beam quality index, depth of maximum dose, profiles of wedged fields and maximum dose to femoral heads. The method was tested for 10 patients with prostate cancer, treated with the 3-field technique. Optimized plans were compared with plans prepared by 12 experienced planners. Dose standard deviation in target volume, and minimum and maximum doses were analyzed. ResultsThe quality of plans obtained with the proposed optimization algorithms was comparable to that prepared by experienced planners. Mean difference in target dose standard deviation was 0.1% in favor of the plans prepared by planners for optimization of beam weights and wedge angles. Introducing a correction factor for patient body outline for dose gradient at ICRU point improved dose distribution homogeneity. On average, a 0.1% lower standard deviation was achieved with the optimization algorithm. No significant difference in mean dose–volume histogram for the rectum was observed. ConclusionsOptimization shortens very much time planning. The average planning time was 5min and less than a minute for forward and computer optimization, respectively.

A GEANT4 web‐based application to support Intra‐Operative Electron Radiotherapy using the European grid infrastructure

SummaryRadiotherapy techniques deliver ionizing radiations (X‐rays, photons, electrons, protons, etc.) inside cancerous tissues to kill the abnormal cells. Radiotherapy‐related activities such as the optimization of the therapeutic radiation dose to patients, workers' radioprotection, linear accelerator commissioning, quality assurance processes and technical innovations of linear accelerators are strongly based on the ability to predict the dose distribution. Monte Carlo based simulations are so far the most accurate tool for the calculation of dosimetric parameters, with the drawback of requiring extensive computing resources to achieve statistically meaningful results in a reasonable time frame. In the last years, advanced cancer treatment clinical and research communities have used e‐Infrastructures to support their activities. The present paper reports on the development of a computing facility for helping clinical researchers in using modern R&E networking and distributed computing and storage resources for a new radiotherapy technique: the Intra‐Operative Electron Radiotherapy. The web application developed addresses some technical and clinical needs as the design of linear accelerators' collimation systems and the optimization of the patient therapeutic dose distribution. Copyright © 2014 John Wiley & Sons, Ltd.

Radiation treatment dose optimisation using Poisson tumour control probability parameters

This study examines the Poisson tumour control probability (TCP) γ37 and D37 parameters of a uniformly irradiated numerical tumour model using changes in tumour burden as a surrogate for treatment response information. An optimum dose Di for a tumour sub-volume element Vi is described that maximizes TCP as a function of fixed tumour integral dose ξ. TCP was calculated for spatially-varying clonogen density for a total 108 cells and radiosensitivity α with mean radiosensitivity in the range 0.4 – 1.0 Gy−1. A bivariate normal distribution is used to describe the radiosensitivity α and the linear term of the linear-quadratic (LQ) cell kill governed the changes in the regional tumour burden within sub-volumes Vi. The optimum dose distribution, Di, for Vi is obtained as a function of fixed tumour integral dose ξ. For a uniform dose delivery and for TCP = 37%, γ37 and D37 are described by the effective radiosensitivity αeff and the effective clonogen number N0,eff, respectively. αeff is equivalent to differential dose changes in the number of clonogenic cells (tumour burden). The γ37 values were found to be inversely correlated with variance of the probability density function of the α distribution. For the biologically optimum dose distribution, γ37 was found to converge to the theoretical maximum limit and D37 was found to reduce relative to that obtained for the uniform dose case. The TCP parameters γ37 and D37 could thus be useful in optimising individual radiation treatment doses even when tumour heterogeneity is taken into account.

Treatment Planning Methods in High Dose Rate Interstitial Brachytherapy of Carcinoma Cervix: A Dosimetric and Radiobiological Analysis

Treatment planning is a trial and error process that determines optimal dwell times, dose distribution, and loading pattern for high dose rate brachytherapy. Planning systems offer a number of dose calculation methods to either normalize or optimize the radiation dose. Each method has its own characteristics for achieving therapeutic dose to mitigate cancer growth without harming contiguous normal tissues. Our aim is to propose the best suited method for planning interstitial brachytherapy. 40 cervical cancer patients were randomly selected and 5 planning methods were iterated. Graphical optimization was compared with implant geometry and dose point normalization/optimization techniques using dosimetrical and radiobiological plan quality indices retrospectively. Mean tumor control probability was similar in all the methods with no statistical significance. Mean normal tissue complication probability for bladder and rectum is 0.3252 and 0.3126 (P = 0.0001), respectively, in graphical optimized plans compared to other methods. There was no significant correlation found between Conformity Index and tumor control probability when the plans were ranked according to Pearson product moment method (r = −0.120). Graphical optimization can result in maximum sparing of normal tissues.

Technical Advancement of Radiation Therapy

Technical Advancement of Radiation Therapy

Dose to organs at risk in the upper abdomen in patients treated with extended fields by helical tomotherapy: a dosimetric and clinical preliminary study

BackgroundThe aim of this work was to determine the technical feasibility and safety of extended-field radiotherapy (EF), performed by Helical TomoTherapy, in patients with positive pelvic and/or para-aortic nodes. Dosimetric data were collected and acute and sub-acute toxicities of the upper abdominal organs at risk (OAR) were evaluated.MethodsTwenty-nine patients suitable for EF irradiation for local disease and/or nodal disease in the pelvic or para-aortic area were treated. The prescription dose was 50.4/54 Gy (1.7-1.8 Gy/fraction) for prophylactic lymph nodes (N-) and 60–70.5 Gy (2–2.35 Gy/fraction) for clinically evident gross disease (N+). Modulation factor (MF), pitch and field width (FW) were chosen to optimize dose distribution and treatment duration. Dose values of PTVs and OAR were analysed. The length of the treatment field, the N + and N- volumes, and treatment duration were reported. To evaluate the safety of treatment, haematological, hepatic, renal and pancreatic functions were assessed before, during and after treatment. The median follow-up time was 17.6 months (range: 6–22 months).ResultsThe treatment was well tolerated and all patients but one completed treatment without interruption. Four of the 29 patients experienced G3 haematological acute toxicity (13.8%), but no patient experienced sub-acute grade G3 toxicity. Ten patients experienced G1 and three G2 acute gastrointestinal toxicity (nausea). No sub-acute gastrointestinal or renal toxicity was observed. Only one (3.7%) patient had a persistent slight increase of pancreatic enzymes and two (7.4%) patients a slight increase of hepatic enzymes six months after radiotherapy (G1 toxicity).ConclusionsWith our treatment design and dose regimen, we found that EF treatment by TomoTherapy could be safely and effectively delivered with minimal acute and sub-acute toxicities in the upper abdomen area.

Microscopic disease extensions as a risk factor for loco-regional recurrence of NSCLC after SBRT

PurposeStereotactic body radiotherapy (SBRT) is a highly conformal technique that allows a more accurate irradiation of lung tumors. However, a highly conformal dose distribution may underdose undetected microscopic disease extensions (MDE) near the tumor leading to loco-regional failure in tumor control. The purpose of the current work is to assess the risk of loco-regional failure in SBRT by analyzing pre-treatment scans. Methods and materialsA model to predict the risk of occurrence of MDE from pretreatment images was developed based on pathology samples of 47 lung cancer patients. This model was used to assess the outcome of 238 SBRT treatments. ResultsPatients with high risk of MDE presence showed significantly lower 2-year loco-regional control (82.0% vs. 91.8%) and shorter time to loco-regional failure (8.4months vs. 20.7months) than low risk patients. The minimum dose delivered in the volume surrounding the GTV affected the model predictive power. The model remained predictive for patients who received less than 31Gy in that volume. For patients who received larger doses, the MDE risk classification was not significant. ConclusionsThe results show that MDEs are, at least partially, responsible of loco-regional failure in highly conformal radiotherapy. This information could be used to optimize dose distributions.