Brachytherapy For Treatment Of Cancer Research Articles

GSOR3 Presentation Time: 9:10 AM: Adding Free Needles and Optimization to Tandem and Ovoids in High Dose Rate Brachytherapy Treatment for Cervical Cancer: How Much Do They Matter?

<h3>Purpose</h3> With increased MRI utilization, targets for cervical cancer are more customized. This in turn makes hybrid applicators more essential, creating treatment plans which deviate significantly from classical pear-shaped dose distributions. This study analyzes the dosimetric impact of integrating free needles into tandem and ovoid (T&O) HDR-brachytherapy treatment for locally advanced cervical cancer. <h3>Materials and Methods</h3> 29 patients with cervical cancers (FIGO stage IB-IIIC2) were treated with 125 fractions. HR_CTV and OARs (bladder, rectum, sigmoid) were contoured by one physician. All delivered plans were optimized using a previously described ‘two-step' optimization procedure, with the goal of maximizing D90(HR-CTV), minimizing dose to OARs, while maintaining the pear aspect of the Prescription Dose iso-surface. These plans were then compared to two additional plans, created using only T&O, re-optimized to either match the original plans for coverage (D90 to HR-CTV) or for OAR sparing (D2cc). Dosimetric information was extracted from TPS and distributions evaluated using histograms and statistical t-test. <h3>Results</h3> The CTV_HR volume for this series was 53.58±23.46 cm3. The dose coverage of the target for the clinical plans was excellent, at 99.14±6.62 %PD. There was a negative correlation between D90 and HR-CTV, in that larger volume of HR-CTV in HDR brachytherapy cervical cancer cases tends to have an outcome of lower dose coverage (shown in figure 1). When clinical plans, using T&O and free needles, were compared with T&O only plans optimized to match D90, the mean D2cc calculated from plans without needles was higher than those from original plans by an average of 29%, 22%, 27% for bladder, rectum and sigmoid, respectively. A t-test between the two populations, with a p-values < 0.00006 shows that they are significantly different. The highest difference of D2cc between original plans and re-optimized plans were 261%, 294%, and 193% for bladder, rectum, and sigmoid, respectively. When clinical plans were compared to re-optimized T&O only, matching OAR toxicity, the D90(HR-CTV) coverage of the plans without needles, was as expected, lower by an average of 21% for the entire series. The T-test between the two populations had a p-value < 2.2e-16. The maximum percentage difference of the dose coverage was 128% compared between re-optimized T&O only and original plans with matched toxicity. <h3>Conclusions</h3> Free handed needles are an easy to implement, inexpensive add-on to a classical T&O, in order to create a ‘hybrid' applicator. Based on this series of patients and the dosimetric data from their clinical plans, we believe that integrating free-handed needles and optimization methods into traditional T&O cervical cancer brachytherapy treatment is highly beneficial for controlling organs-at-risk toxicity while achieving optimal coverage for HR-CTV and preserving an overall ‘pear'-shape-like aspect of the overall dose distribution. Our findings suggest that the use of additional needles should be considered for cases with a larger or asymmetric volume of HR-CTV. This study, is to our knowledge, the first to quantify the dosimetric benefits of free-needles augmented T&O when compared to classical T&O. We recommend in addition to adding free needles the two step optimization method to best take advantage of the degrees of freedom one has by using hybrid applicators.

Continuous liquid interface production of 3D printed drug-loaded spacers to improve prostate cancer brachytherapy treatment

Brachytherapy, which is the placement of radioactive seeds directly into tissue such as the prostate, is an important curative treatment for prostate cancer. By delivering a high dose of radiation from within the prostate gland, brachytherapy is an effective method of killing prostate cancer cells while limiting radiation dose to normal tissue. The main shortcomings of this treatment are: less efficacy against high grade tumor cells, acute urinary retention, and sub-acute urinary frequency and urgency. One strategy to improve brachytherapy is to incorporate therapeutics into brachytherapy. Drugs, such as docetaxel, can improve therapeutic efficacy, and dexamethasone is known to decrease urinary side effects. However, both therapeutics have high systemic side effects. To overcome this challenge, we hypothesized that we can incorporate therapeutics into the inert polymer spacers that are used to correctly space brachytherapy seeds during brachytherapy to enable local drug delivery. To accomplish this, we engineered 3D printed drug-loaded brachytherapy spacers using continuous liquid interface production (CLIP) with different surface patterns to control drug release. These devices have the same physical size as existing spacers, allowing them to easily replace commercial spacers. We examined these drug-loaded spacers using docetaxel and dexamethasone as model drugs in a murine model of prostate cancer. We found that drug-loaded spacers led to higher therapeutic efficacy for brachytherapy, and there was no discernable systemic toxicity from the drug-loaded spacers. Statement of significanceThere has been high interest in the application of 3D printing to engineer novel medical devices. However, such efforts have been limited by the lack of technologies that can fabricate devices suitable for real world medical applications. In this study, we demonstrate a unique application for 3D printing to enhance brachytherapy for cancer treatment. We engineered drug-loaded brachytherapy spacers that can be fabricated using Continuous Liquid Interface Production (CLIP) 3D printing, allowing tunable printing of drug-loaded devices, and implanted intraoperatively with brachytherapy seeds. In combined chemotherapy and brachytherapy we are able to achieve greater therapeutic efficacy through local drug delivery and without systemic toxicities. We believe our work will facilitate further investigation in medical applications of 3D printing.

Increasing Brachytherapy Mentorship and Representation Through #NextGenBrachy

Despite the critical role of brachytherapy in cancer treatment, recent trends show a decline in utilization. Additionally, women providers have been shown to be underrepresented. A resident survey identified high interest in on-the-job training. To address these challenges, a national mentorship program was developed with the aim of improving representation and on-the-job mentorship, with the long-term goal of increasing brachytherapy utilization.

Study the Calibration of the High Dose Rate Brachytherapy Radioactive Source 60Co

Aim of this work is to calibrate the high dose rate (HDR) brachytherapy source 60Co. The radioactive source calibration is a very important part of the quality assurance program for dosimetry of brachytherapy source. The goal of this project is the calibration of HDR Brachytherapy source in radiation therapy is the measurement of the air kerma rate which required actual dose to deliver. The source calibration is an essential part of the quality assurance program for dosimetry of brachytherapy source. This research will help the patient who is involving brachytherapy treatment. HDR brachytherapy source 60Co is inserted directly or in close to the tumor. Most commonly using method for calibration of HDR brachytherapy source 60CO is well type ionization chamber. Calibration of the radioactive source 60Co brachytherapy source is very important for the treatment of cancer patient. We have got the variation between RAKR from TPS and measured Air Kerma Rate of 60Co brachytherapy source are 3.2% and 3.04% and which give very good agreement with the Air Kerma Rate (RAKR) is 5% (from BEBIG protocol, Germany). So, our results were satisfied for brachytherapy treatment. From these results, it must be concluded that, 60Co brachytherapy source is suitable for brachytherapy cancer treatment. It is very difficult to calculate treatment deliver dose without calibrating AKR of HDR brachytherapy source. It is very important to verify the calculated Air Kerma Rate by TPS Air Kerma Rate.

Automatic tandem and ring reconstruction using MRI for cervical cancer brachytherapy.

The MRI-guided cervical cancer brachytherapy provides unparalleled soft-tissue contrast for target and normal tissue contouring, but eliminates the ability to use conventional metallic fiducials for radiation source path reconstruction as required for treatment planning. Instead, the source path is reconstructed by manually aligning a library model to the signal void produced by the applicator, which takes time intraoperatively and precludes fully automated treatment planning. The purpose of this study is to present and validate an algorithm to automatically reconstruct tandem and ring applicators using MRI for cervical cancer brachytherapy treatment planning. Applicators were reconstructed using T2-weighted MR images acquired at 1.5T from 33 brachytherapy fractions including 10 patients using a model-to-image registration algorithm. The algorithm involves (a) image filtering and maximum intensity projection to highlight the applicator, (b) ring center identification using the circular Hough transform, and (c) three-dimensional surface model registration, optimized by maximizing the image intensity gradient normal to the model surface. Two independent observers manually reconstructed all applicators, enabling the calculation of interobserver variability and establishing a ground truth. Algorithm variability was calculated by comparing algorithm results to each individual observer, and algorithm accuracy was calculated by comparing algorithm results to the ground truth. The algorithm variability and accuracy were compared to the interobserver variability using paired t-tests. Mean±SD interobserver variability was 0.83±0.31mm and 0.78±0.29mm for the ring and tandem, respectively. The algorithm had mean±SD variability and accuracy of 0.72±0.32mm (P=0.02) and 0.60±0.24mm (P=0.0005) for the ring, and 0.70±0.29mm (P=0.11) and 0.58±0.24mm (P=0.004) for the tandem, respectively. The algorithm variability and accuracy were within the interobserver variability measured in this study. The algorithm accuracy and mean execution time of 10.0s are sufficient for clinical tandem and ring reconstruction, and are a step toward fully automated tandem and ring brachytherapy treatment planning.

EP-2262: Novel application of Gold-Nanoparticles in prostate LDR brachytherapy cancer treatment

EP-2262: Novel application of Gold-Nanoparticles in prostate LDR brachytherapy cancer treatment

Current status of brachytherapy in cancer treatment - short overview.

Cancer incidence and mortality depend on a number of factors, including age, socio-economic status and geographical location, and its prevalence is growing around the world. Most of cancer treatments include external beam radiotherapy or brachytherapy. Brachytherapy, a type of radiotherapy with energy from radionuclides inserted directly into the tumor, is increasingly used in cancer treatment. For cervical and skin cancers, it has become a standard therapy for more than 100 years as well as an important part of the treatment guidelines for other malignancies, including head and neck, skin, breast, and prostate cancers. Compared to external beam radiotherapy, brachytherapy has the potential to deliver an ablative radiation dose over a short period of time directly to the altered tissue area with the advantage of a rapid fall-off in dose, and consequently, sparing of adjacent organs. As a result, the patient is able to complete the treatment earlier, and the risks of occurrence of another cancer are lower than in conventional radiotherapy treatment. Brachytherapy has increased its use as a radical or palliative treatment, and become more advanced with the spread of pulsed-dose-rate and high-dose-rate afterloading machines; the use of new 3D/4D planning systems has additionally improved the quality of the treatment. The aim of the present study was to present short summaries of current studies on brachytherapy for the most frequently diagnosed tumors. Data presented in this manuscript should help especially young physicians or physicists to explore and introduce brachytherapy in cancer treatments.

A 3D computer-assisted treatment planning system for breast cancer brachytherapy treatment.

Purpose Brachytherapy is an option for treatment of breast cancer in some cases. This modality requires patient-specific dosimetry based on CT simulator scans. A 3D computer-assisted breast brachytherapy treatment planning system called Vision was developed and tested.Methods The brachytherapy treatment planning system used volume estimation and dose analysis with advanced 3D visualization. The patient treatment volume reconstruction was designed to ensure high-volume accuracy requirement of radioactive seed implantation procedure for this treatment. The system enables interactive placement of radioactive seeds embedded in original patient CT images with 3D display.Results The system achieved 99.73 % accuracy in volume estimation measured against the true volume and is statistically significantly more accurate than current existing commercial software at the p=0.05 level.Conclusion A virtual 3D environment was developed to perform volume measurements, seed placements, and dose distribution planning and analysis based on 2D contours on patient CT images. This system was demonstrated to be feasible and accurate in a clinical setting.

Commissioning of a grid-based Boltzmann solver for cervical cancer brachytherapy treatment planning with shielded colpostats

We sought to commission a gynecologic shielded colpostat analytic model provided from a treatment planning system (TPS) library. We have reported retrospectively the dosimetric impact of this applicator model in a cohort of patients. A commercial TPS with a grid-based Boltzmann solver (GBBS) was commissioned for (192)Ir high-dose-rate (HDR) brachytherapy for cervical cancer with stainless steel-shielded colpostats. Verification of the colpostat analytic model was verified using a radiograph and vendor schematics. MCNPX v2.6 Monte Carlo simulations were performed to compare dose distributions around the applicator in water with the TPS GBBS dose predictions. Retrospectively, the dosimetric impact was assessed over 24 cervical cancer patients' HDR plans. Applicator (TPS ID #AL13122005) shield dimensions were within 0.4mm of the independent shield dimensions verification. GBBS profiles in planes bisecting the cap around the applicator agreed with Monte Carlo simulations within 2% at most locations; differing screw representations resulted in differences of up to 9%. For the retrospective study, the GBBS doses differed from TG-43 as follows (meanvalue ±standard deviation [min, max]): International Commission on Radiation units [ICRU]rectum (-8.4±2.5% [-14.1, -4.1%]), ICRUbladder (-7.2±3.6% [-15.7, -2.1%]), D2cc-rectum (-6.2±2.6% [-11.9, -0.8%]), D2cc-sigmoid (-5.6±2.6% [-9.3, -2.0%]), and D2cc-bladder (-3.4±1.9% [-7.2, -1.1%]). As brachytherapy TPSs implement advanced model-based dose calculations, the analytic applicator models stored in TPSs should be independently validated before clinical use. For this cohort, clinically meaningful differences (>5%) from TG-43 were observed. Accurate dosimetric modeling of shielded applicators may help to refine organ toxicity studies.

SU‐E‐T‐695: Dose Calculation of a Breast Cancer Brachytherapy Treatment Using Monte Carlo Simulation

Purpose: To develop a dose calculation package based on Monte Carlo simulation for SAVI breast cancer brachytherapy treatment using patientˈs CT data. Methods: A realistic model of the patient was created using anonymized patient data including images, structures and plans from the treatment planning system. Images were then voxelized and each voxel assigned a density and material value base on its calibrated Hounsfield units. Materials included were fat, muscle, lung, air, bone, and Nitinol. This data was then imported into the penEasy Monte Carlo code. Each source position from the plan was then run individually and the dose was totaled after weighting each source by its dwell time from the original plan. Energies used were those of the VariSource IR‐192. Results: The resulting dose was compared to the dose from the original plan and plotted side by side. Dose differences were considered that occurred outside the air cavity, particularly in the evaluated planning target volume (PTVeval), which is calculated as 1 cm outside the cavity subtracting the cavity itself, the skin and the chest wall. Dose from the Monte simulation looked similar in shape and intensity to the original plan. Conclusions: We have developed a Monte Carlo simulation package to calculate dose distributions for SAVI based breast cancer brachytherapy using patientˈs CT and plan parameters extracted directly from a commercial planning system.

Interactive simulation of surgical needle insertion and steering

We present algorithms for simulating and visualizing the insertion and steering of needles through deformable tissues for surgical training and planning. Needle insertion is an essential component of many clinical procedures such as biopsies, injections, neurosurgery, and brachytherapy cancer treatment. The success of these procedures depends on accurate guidance of the needle tip to a clinical target while avoiding vital tissues. Needle insertion deforms body tissues, making accurate placement difficult. Our interactive needle insertion simulator models the coupling between a steerable needle and deformable tissue. We introduce (1) a novel algorithm for local remeshing that quickly enforces the conformity of a tetrahedral mesh to a curvilinear needle path, enabling accurate computation of contact forces, (2) an efficient method for coupling a 3D finite element simulation with a 1D inextensible rod with stick-slip friction, and (3) optimizations that reduce the computation time for physically based simulations. We can realistically and interactively simulate needle insertion into a prostate mesh of 13,375 tetrahedra and 2,763 vertices at a 25 Hz frame rate on an 8-core 3.0 GHz Intel Xeon PC. The simulation models prostate brachytherapy with needles of varying stiffness, steering needles around obstacles, and supports motion planning for robotic needle insertion. We evaluate the accuracy of the simulation by comparing against real-world experiments in which flexible, steerable needles were inserted into gel tissue phantoms.

Comparison of dose calculation algorithms for colorectal cancer brachytherapy treatment with a shielded applicator

Colorectal cancer patients are treated at our hospital with 192Ir high dose rate (HDR) brachytherapy using an applicator that allows the introduction of a lead or tungsten shielding rod to reduce the dose to healthy tissue. The clinical dose planning calculations are, however, currently performed without taking the shielding into account. To study the dose distributions in shielded cases, three techniques were employed. The first technique was to adapt a shielding algorithm which is part of the Nucletron PLATO HDR treatment planning system. The isodose pattern exhibited unexpected features but was found to be a reasonable approximation. The second technique employed a ray tracing algorithm that assigns a constant dose ratio with/without shielding behind the shielding along a radial line originating from the source. The dose calculation results were similar to the results from the first technique but with improved accuracy. The third and most accurate technique used a dose-matrix-superposition algorithm, based on Monte Carlo calculations. The results from the latter technique showed quantitatively that the dose to healthy tissue is reduced significantly in the presence of shielding. However, it was also found that the dose to the tumor may be affected by the presence of shielding; for about a quarter of the patients treated the volume covered by the 100% isodose lines was reduced by more than 5%, leading to potential tumor cold spots. Use of any of the three shielding algorithms results in improved dose estimates to healthy tissue and the tumor.

A mathematical approach for evaluating the influence of dose heterogeneity on TCP for prostate cancer brachytherapy treatment

The low-dose-rate brachytherapy technique has proven suitable for the management of prostate cancer. However, published data generally report the clinical outcome and the minimum peripheral dose (mPD) to the target volume and not the actual dose distribution in patients. To this end, modern guidelines recommend the use of specific dose and volume indices describing dose distribution throughout the target. The introduction of a method, based on the standard linear quadratic model and Poisson statistics, entitled the F-factor allows the TCP from different DVHs to be calculated, by using the TCP from a uniform dose distribution as the reference. The F-factor sensitivity against radiobiological parameters and influence of the DVH were evaluated. We applied the F-formula on the post-plan DVHs of 58 patients treated with 125I permanent seed implant brachytherapy for localized prostate cancer. F shows a strong correlation with dosimetric parameters already reported as significant predictors of the biochemical outcome.

Validation of a dose deposited by low-energy photons using GATE/GEANT4

The GATE Monte Carlo simulation platform based on the Geant4 toolkit has now become a diffused tool for simulating PET and SPECT imaging devices. In this paper, we explore its relevance for dosimetry of low-energy 125I photon brachytherapy sources used to treat prostate cancers. To that end, three 125-iodine sources widely used in prostate cancer brachytherapy treatment have been modelled. GATE simulations reproducing dosimetric reference observables such as radial dose function g(r), anisotropy function F(r, θ) and dose-rate constant (Λ) were performed in liquid water. The calculations were splitted on the EGEE grid infrastructure to reduce the computing time of the simulations. The results were compared to other relevant Monte Carlo results and to measurements published and fixed as recommended values by the AAPM Task Group 43. GATE results agree with consensus values published by AAPM Task Group 43 with an accuracy better than 2%, demonstrating that GATE is a relevant tool for the study of the dose induced by low-energy photons.

A fibre optic dosimeter customised for brachytherapy

In-vivo dosimetry for brachytherapy cancer treatment requires a small dosimeter with a real time readout capability that can be inserted into the patient to determine the dose to critical organs. Fibre optic scintillation dosimeters, consisting of a plastic scintillator coupled to an optical fibre, are a promising dosimeter for this application. We have implemented specific design features to optimise the performance of the dosimeter for specific in-vivo dosimetry during brachytherapy. Two sizes of the BrachyFOD™scintillation dosimeter have been developed, with external diameters of approximately 2 and 1 mm. We have determined their important dosimetric characteristics (depth dose relation, angular dependence, energy dependence). We have shown that the background signal created by Čerenkov and fibre fluorescence does not significantly affect the performance in most clinical geometries. The dosimeter design enables readout at less than 0.5 s intervals. The clinical demands of real time in-vivo brachytherapy dosimetry can uniquely be satisfied by the BrachyFOD™.

Discrete Event Simulation of Remote Afterloading Brachytherapy Cancer Treatment

The Nuclear Regulatory Commission (NRC) is investigating the use of discrete event simulation (DES) modeling techniques to assess risk in the performance of medical treatments that use radioactive byproducts. Pursuant to this interest, Micro Analysis and Design, Inc. developed a DES model to determine the feasibility and utility of simulation for assessing the effects of human, hardware, and software errors in these types of medical processes. Recent research by the NRC resulted in a comprehensive task and error analysis of Remote Afterloading Brachytherapy cancer treatment. The results of this analysis formed the basis for the DES model. The model demonstrates how a DES can be used to evaluate the effects of changes in procedures for delivering the medical treatment and responding to hardware and software failures could reduce risk to patients.

American Brachytherapy Society (ABS) consensus guidelines for brachytherapy of esophageal cancer

There is wide variation in the indications, treatment regimens, and dosimetry for brachytherapy in the treatment of cancer of the esophagus. No guidelines for optimal therapy currently exist. Utilizing published reports and clinical experience, representatives of the Clinical Research Committee of the American Brachytherapy Society (ABS) formulated guidelines for brachytherapy in esophageal cancer. Recommendations were made for brachytherapy in the definitive and palliative treatment of esophageal cancer. (A) Definitive treatment: Good candidates for brachytherapy include patients with unifocal thoracic adeno- or squamous cancers < or = 10 cm in length, with no evidence of intra-abdominal or metastatic disease. Contraindications include tracheal or bronchial involvement, cervical esophagus location, or stenosis that cannot be bypassed. The esophageal brachytherapy applicator should have an external diameter of 6-10 mm. If 5FU-based chemotherapy and 45-50-Gy external beam are used, recommended brachytherapy is either: (i) HDR 10 Gy in two weekly fractions of 5 Gy each; or (ii) LDR 20 Gy in a single course at 0.4-1 Gy/hr. All doses are specified 1 cm from the midsource or mid-dwell position. Brachytherapy should follow external beam radiation therapy and should not be given concurrently with chemotherapy. (B) Palliative treatment: Patients with adeno- or squamous cancers of the thoracic esophagus with distant metastases or unresectable local disease progression/recurrence after definitive radiation treatment should be considered for brachytherapy with palliative intent. After limited dose (30 Gy) EBRT, the recommended brachytherapy is either: (i) HDR 10-14 Gy in one or two fractions; or (ii) LDR 20-25 Gy in a single course at 0.4-1 Gy/hr. The need for external beam radiation in newly diagnosed patients with a life expectancy of less than 3 months is controversial. In these cases, HDR of 15-20 Gy in two to four fractions or LDR of 25-40 Gy at 0.4-1 Gy/hr may be of benefit. ABS guidelines for esophageal brachytherapy now exist and will be updated by the ABS in the future, as clinical data using more uniform treatment techniques becomes available.

218High dose rate brachytherapy in primary treatment of cancer of the uterine cervix

218High dose rate brachytherapy in primary treatment of cancer of the uterine cervix

A microdosimetric-kinetic model of cell death from exposure to ionizing radiation of any LET, with experimental and clinical applications.

A model of mammalian cell death and survival following exposure to ionizing radiation that combines a kinetic description of repair and injury processes with a microdosimetric description of radiation energy deposition is presented. With reduction of one of the defining kinetic equations from quadratic to linear form, relations are obtained that describe the results of commonly performed variations of the cell survival experiment. These include single-dose survival of linear-quadratic form, survival after split-dose treatment and after post-irradiation change ill culture conditions and survival after exposure to continuously administered irradiation at low constant dose-rate. The effect of the inhomogeneous deposition of radiation energy inherent in exposure to radiation of significantly non-zero LET is included in these relations which apply to radiation of any LET. The values of the kinetic rate and time constants for repair and the processes that lead to cell death postulated in the model, which compose the alpha and beta parameters of the linear-quadratic survival relation, are estimated from cell survival experiments and DNA double-strand break measurements from the literature. A relation for estimating the daily fractional dose equivalent to continuous irradiation as employed in low dose-rate brachytherapy cancer treatment is presented.

543 The role of intra luminal brachytherapy in treatment of cancer of the oesophagus

A prospective, non-randomized study was performed in 201 patients with inoperable cancer of the oesophagus. 101 were treated with palliative reason with Intra Luminal Brachytherapy (ILB), (n = 56), or combined External Beam RadioTherapy (EBRT) and ILB, (n = 45). 100 patients were treated with Radical Radiotherapy: group 1) 50 Gy EBRT + 2 × 7.5 Gy ILB, (n = 54), group 2) 60 Gy EBRT + 2 × 6 Gy ILB, (n = 46). Results ILB as single modality treatment results in good, life long improvement of dysphagia. Median survival is 3.4 months and 1-year overall survival 5%. EBRT + ILB has equal effects, with median and 1-year overall survival of 4.7 months and 13% respectively. Treatment related complications were rare. In the radical group 50 Gy + 2 × 7.5 leads to a median, 1- and 2-year survival of 9.3 months, 40% and 13% respectively. For 60 Gy + 2 × 6 this was 11.8 months, 43% and 31%. Complications were mild. Conclusions Intraluminal Brachytherapy is save and effective in palliation for carcinoma of the oesophagus. Results with intraluminal brachytherapy alone are comparable with combination of EBRT + ILB. In Radical Radiotherapy increasing EBRT dose from 50 to 60 Gy + ILB 2 × 6 Gy increases local control as well as overall survival.