Evaluation of the clinical impact of the differences between planned and delivered dose in prostate cancer radiotherapy based on CT-on-rails IGRT and patient-reported outcome scores.

PURPOSE: To estimate the clinical impact of differences between delivered and planned dose using dose metrics and normal tissue complication probability (NTCP) modeling. METHODS: Forty-six consecutive patients with prostate adenocarcinoma between 2010 and 2015 treated with intensity-modulated radiation therapy (IMRT) and who had undergone computed tomography on rails imaging were included. Delivered doses to bladder and rectum were estimated using a contour-based deformable image registration method. The bladder and rectum NTCP were calculated using dose-response parameters applied to planned and delivered dose distributions. Seven urinary and gastrointestinal symptoms were prospectively collected using the validated prostate cancer symptom indices patient reported outcome (PRO) at pre-treatment, weekly treatment, and post-treatment follow-up visits. Correlations between planned and delivered doses against PRO were evaluated in this study. RESULTS: Planned mean doses to bladder and rectum were 44.9 ± 13.6 Gy and 42.8 ± 7.3 Gy, while delivered doses were 46.1 ± 13.4 Gy and 41.3 ± 8.7 Gy, respectively. D10cc for rectum was 64.1 ± 7.6 Gy for planned and 60.1 ± 9.3 Gy for delivered doses. NTCP values of treatment plan were 22.3% ± 8.4% and 12.6% ± 5.9%, while those for delivered doses were 23.2% ± 8.4% and 9.9% ± 8.3% for bladder and rectum, respectively. Seven of 25 patients with follow-up data showed urinary complications (28%) and three had rectal complications (12%). Correlations of NTCP values of planned and delivered doses with PRO follow-up data were random for bladder and moderate for rectum (0.68 and 0.67, respectively). CONCLUSION: Sensitivity of bladder to clinical variations of dose accumulation indicates that an automated solution based on a DIR that considers inter-fractional organ deformation could recommend intervention. This is intended to achieve additional rectum sparing in cases that indicate higher than expected dose accumulation early during patient treatment in order to prevent acute severity of bowel symptoms.

Stereotactic body radiotherapy optimization to reduce the risk of carotid blowout syndrome using normal tissue complication probability objectives.

PURPOSE: To determine the possibility of further improving clinical stereotactic body radiotherapy (SBRT) plans using normal tissue complication probability (NTCP) objectives in order to minimize the risk for carotid blowout syndrome (CBOS). METHODS: 10 patients with inoperable locally recurrent head and neck cancer, who underwent SBRT using CyberKnife were analyzed. For each patient, three treatment plans were examined: (1) cone-based without delineation of the ipsilateral internal carotid (clinical plan used to treat the patients); (2) cone-based with the carotid retrospectively delineated and spared; and (3) Iris-based with carotid sparing. The dose-volume histograms of the target and primary organs at risk were calculated. The three sets of plans were compared based on dosimetric and TCP/NTCP (tumor control and normal tissue complication probabilities) metrics. For the NTCP values of carotid, the relative seriality model was used with the following parameters: D50 = 40 Gy, γ = 0.75, and s = 1.0. RESULTS: Across the 10 patient plans, the average TCP did not significantly change when the plans were re-optimized to spare the carotid. The estimated risk of CBOS was significantly decreased in the re-optimized plans, by 14.9% ± 7.4% for the cone-based plans and 17.7% ± 7.1% for the iris-based plans (p = 0.002 for both). The iris-based plans had significant (p = 0.02) reduced CBOS risk and delivery time (20.1% ± 7.4% time reduction, p = 0.002) compared to the cone-based plans. CONCLUSION: A significant improvement in the quality of the clinical plans could be achieved through the delineation of the internal carotids and the use of more modern treatment delivery modalities. In this way, for the same target coverage, a significant reduction in the risk of CBOS could be achieved. The range of risk reduction varied depending on the proximity of carotid artery to the target.

Evaluation of a commercial DIR platform for contour propagation in prostate cancer patients treated with IMRT/VMAT.

PURPOSE: To assess the performance and limitations of contour propagation with three commercial deformable image registration (DIR) algorithms using fractional scans of CT-on-rails (CTOR) and Cone Beam CT (CBCT) in image guided prostate therapy patients treated with IMRT/VMAT. METHODS: Twenty prostate cancer patients treated with IMRT/VMAT were selected for analysis. A total of 453 fractions across those patients were analyzed. Image data were imported into MIM (MIM Software, Inc., Cleveland, OH) and three DIR algorithms (DIR Profile, normalized intensity-based (NIB) and shadowed NIB DIR algorithms) were applied to deformably register each fraction with the planning CT. Manually drawn contours of bladder and rectum were utilized for comparison against the DIR propagated contours in each fraction. Four metrics were utilized in the evaluation of contour similarity, the Hausdorff Distance (HD), Mean Distance to Agreement (MDA), Dice Similarity Coefficient (DSC), and Jaccard indices. A subfactor analysis was performed per modality (CTOR vs. CBCT) and time (fraction). Point estimates and 95% confidence intervals were assessed via a Linear Mixed Effect model for the contour similarity metrics. RESULTS: No statistically significant differences were observed between the DIR Profile and NIB algorithms. However, statistically significant differences were observed between the shadowed NIB and NIB algorithms for some of the DIR evaluation metrics. The Hausdorff Distance calculation showed the NIB propagated contours vs. shadowed NIB propagated contours against the manual contours were 14.82 mm vs. 8.34 mm for bladder and 15.87 mm vs. 11 mm for rectum, respectively. Similarly, the Mean Distance to Agreement calculation comparing the NIB propagated contours vs. shadowed NIB propagated contours against the manual contours were 2.43 mm vs. 0.98 mm for bladder and 2.57 mm vs. 1.00 mm for rectum, respectively. The Dice Similarity Coefficients comparing the NIB propagated contours and shadowed NIB propagated contours against the manual contours were 0.844 against 0.936 for bladder and 0.772 against 0.907 for rectum, respectively. The Jaccard indices comparing the NIB propagated contours and shadowed NIB propagated contours against the manual contours were 0.749 against 0.884 for bladder and 0.637 against 0.831 for rectum, respectively. The shadowed NIB DIR, which showed the closest agreement with the manual contours performed significantly better than the DIR Profile in all the comparisons. The OAR with the greatest agreement varied substantially across patients and image guided radiation therapy (IGRT) modality. Intra-patient variability of contour metric evaluation was insignificant across all the DIR algorithms. Statistical significance at α = 0.05 was observed for manual vs. deformably propagated contours for bladder for all the metrics except Hausdorff Distance (P = 0.01 for MDA, P = 0.02 for DSC, P = 0.01 for Jaccard), whereas the corresponding values for rectum were: P = 0.03 for HD, P = 0.01 for MDA, P < 0.01 for DSC, P < 0.01 for Jaccard. The performance of the different metrics varied slightly across the fractions of each patient, which indicates that weekly contour propagation models provide a reasonable approximation of the daily contour propagation models. CONCLUSION: The high variance of Hausdorff Distance across all automated methods for bladder indicates widely variable agreement across fractions for all patients. Lower variance across all modalities, methods, and metrics were observed for rectum. The shadowed NIB propagated contours were substantially more similar to the manual contours than the DIR Profile or NIB contours for both the CTOR and CBCT imaging modalities. The relationship of each algorithm to similarity with manual contours is consistent across all observed metrics and organs. Screening of image guidance for substantial differences in bladder and rectal filling compared with the planning CT reference could aid in identifying fractions for which automated DIR would prove insufficient.

Incorporating biological modeling into patient-specific plan verification.

PURPOSE: Dose-volume histogram (DVH) measurements have been integrated into commercially available quality assurance systems to provide a metric for evaluating accuracy of delivery in addition to gamma analysis. We hypothesize that tumor control probability and normal tissue complication probability calculations can provide additional insight beyond conventional dose delivery verification methods. METHODS: A commercial quality assurance system was used to generate DVHs of treatment plan using the planning CT images and patient-specific QA measurements on a phantom. Biological modeling was performed on the DVHs produced by both the treatment planning system and the quality assurance system. RESULTS: The complication-free tumor control probability, P+ , has been calculated for previously treated intensity modulated radiotherapy (IMRT) patients with diseases in the following sites: brain (-3.9% ± 5.8%), head-neck (+4.8% ± 8.5%), lung (+7.8% ± 1.3%), pelvis (+7.1% ± 12.1%), and prostate (+0.5% ± 3.6%). CONCLUSION: Dose measurements on a phantom can be used for pretreatment estimation of tumor control and normal tissue complication probabilities. Results in this study show how biological modeling can be used to provide additional insight about accuracy of delivery during pretreatment verification.

A quantitative measure for radiation treatment plan quality.

PURPOSE: To develop and validate an intensity modulated radiation therapy (IMRT) treatment plan quantitative score using QUANTEC dose/volume parameters to assess plan quality. METHODS: 132 IMRT and volumetric modulated Arc therapy (VMAT) patient plans of various treatment sites were evaluated. The optimized plan's dose volume histogram (DVH) was exported to Velocity for evaluation. The proposed scoring was based on calculating the shortest distance from the QUANTEC objective to the DVH line of each organ. Each plan was normalized against the ideal plan where the organs at risk (OARs) received no dose and hence the distance between the QUANTEC objective and the DVH line was maximized. These normalized scores enabled the comparison of the quality of plans across treatment sites and dosimetrists. The scores were plotted and statistically analyzed to serve as a basis for future research. RESULTS: The score for each treatment site was evaluated and the average percentage scores±SD were found to be 43.5 ± 21.0, 33.3 ± 31.7, 42.6 ± 23.3, 40.2 ± 24.4, 33.5 ± 23.5 for the sites of abdomen, brain, chest, head/neck, and pelvis respectively. Differences in scores between the treatment sites were largely attributed to OAR segmentation and proximity of the OAR to the planning target volume (PTV). Small score differences between dosimetrists were attributed to the number of plans they have completed. CONCLUSION: This approach allows comparison of patient treatments which will help improve patient care and treatment outcomes. A larger sample of treatment plans is being evaluated to investigate the effect of dosimetrist's experience on plan quality.

Investigation of error detection capabilities of phantom, EPID and MLC log file based IMRT QA methods.

A patient specific quality assurance (QA) should detect errors that originate anywhere in the treatment planning process. However, the increasing complexity of treatment plans has increased the need for improvements in the accuracy of the patient specific pretreatment verification process. This has led to the utilization of higher resolution QA methods such as the electronic portal imaging device (EPID) as well as MLC log files and it is important to know the types of errors that can be detected with these methods. In this study, we will compare the ability of three QA methods (Delta4 ®, MU-EPID, Dynalog QA) to detect specific errors. Multileaf collimator (MLC) errors, gantry angle, and dose errors were introduced into five volumetric modulated arc therapy (VMAT) plans for a total of 30 plans containing errors. The original plans (without errors) were measured five times with each method to set a threshold for detectability using two standard deviations from the mean and receiver operating characteristic (ROC) derived limits. Gamma passing percentages as well as percentage error of planning target volume (PTV) were used for passing determination. When applying the standard 95% pass rate at 3%/3 mm gamma analysis errors were detected at a rate of 47, 70, and 27% for the Delta4 , MU-EPID and Dynalog QA respectively. When using thresholds set at 2 standard deviations from our base line measurements errors were detected at a rate of 60, 30, and 47% for the Delta4 , MU-EPID and Dynalog QA respectively. When using ROC derived thresholds errors were detected at a rate of 60, 27, and 47% for the Delta4 , MU-EPID and Dynalog QA respectively. When using dose to the PTV and the Dynalog method 11 of the 15 small MLC errors were detected while none were caught using gamma analysis. A combination of the EPID and Dynalog QA methods (scaling Dynalog doses using EPID images) matches the detection capabilities of the Delta4 by adding additional comparison metrics. These additional metrics are vital in relating the QA measurement to the dose received by the patient which is ultimately what is being confirmed.

Dosimetric and radiobiological comparison for quality assurance of IMRT and VMAT plans.

INTRODUCTION: The gamma analysis used for quality assurance of a complex radiotherapy plan examines the dosimetric equivalence between planned and measured dose distributions within some tolerance. This study explores whether the dosimetric difference is correlated with any radiobiological difference between delivered and planned dose. METHODS: VMAT or IMRT plans optimized for 14 cancer patients were calculated and delivered to a QA device. Measured dose was compared against planned dose using 2-D gamma analysis. Dose volume histograms (for various patient structures) obtained by interpolating measured data were compared against the planned ones using a 3-D gamma analysis. Dose volume histograms were used in the Poisson model to calculate tumor control probability for the treatment targets and in the Sigmoid dose-response model to calculate normal tissue complication probability for the organs at risk. RESULTS: Differences in measured and planned dosimetric data for the patient plans passing at ≥94.9% rate at 3%/3 mm criteria are not statistically significant. Average ± standard deviation tumor control probabilities based on measured and planned data are 65.8±4.0% and 67.8±4.1% for head and neck, and 71.9±2.7% and 73.3±3.1% for lung plans, respectively. The differences in tumor control probabilities obtained from measured and planned dose are statistically insignificant. However, the differences in normal tissue complication probabilities for larynx, lungs-GTV, heart, and cord are statistically significant for the patient plans meeting ≥94.9% passing criterion at 3%/3 mm. CONCLUSION: A ≥90% gamma passing criterion at 3%/3 mm cannot assure the radiobiological equivalence between planned and delivered dose. These results agree with the published literature demonstrating the inadequacy of the criterion for dosimetric QA and suggest for a tighter tolerance.

Anatomy-based, patient-specific VMAT QA using EPID or MLC log files.

In this project, we investigated the use of an electronic portal imaging device (EPID), together with the treatment planning system (TPS) and MLC log files, to determine the delivered doses to the patient and evaluate the agreement between the treatment plan and the delivered dose distribution. The QA analysis results are presented for 15 VMAT patients using the EPID measurements, the ScandiDos Delta4 dosimeter, and the beam fluence calculated from the multileaf collimator (MLC) log file. EPID fluence images were acquired in continuous acquisition mode for each of the patients and they were processed through an in-house MATLAB program to create an opening density matrix (ODM), which was used as the input fluence for the dose calculation in the TPS (Pinnacle3). The EPID used in this study was the aSi1000 Varian on a Novalis TX linac equipped with high-definition MLC. The actual MLC positions and gantry angles were retrieved from the MLC log files and the data were used to calculate the delivered dose distributions in Pinnacle. The resulting dose distributions were then compared against the corresponding planned dose distributions using the 3D gamma index with 3 mm/3% passing criteria. The ScandiDos Delta4 phantom was also used to measure a 2D dose distribution for all the 15 patients and a 2D gamma was calculated for each patient using the Delta4 software. The average 3D gamma using the EPID images was 96.1% ± 2.2%. The average 3D gamma using the log files was 98.7% ± 0.5%. The average 2D gamma from the Delta4 was 98.1% ± 2.1%. Our results indicate that the use of the EPID, combined with MLC log files and a TPS, is a viable method for QA of VMAT plans.

Stereotactic body radiation therapy patient specific quality assurance using a two-dimensional array at extended source to surface distance.

METHODS: Five patients with 38 fields have been analyzed in this study. The plans were optimized for the following clinical sites: one liver, one lung, one brain, one prostate and one spine. The detector array used for the measurements was the PTW Seven29 array. All the plans were optimized and calculated using Eclipse v8.9. The center of the array was setup at 215 cm from the source and all the fields were measured and analyzed one by one. All the 30 measurements were performed on a NovalisTX linear accelerator equipped with a high definition multileaf collimator. The evaluation was based mainly on gamma index passing rates using 2 mm distance to agreement (DTA) and 2% dose difference. RESULTS: The accuracy of the Eclipse Treatment Planning System (TPS) at extended Source to Surface Distances (SSDs) using an ionization chamber was measured to be within 1.0%. All the field measurements were performed and analyzed 35 individually. The percent of the points that had a gamma index of less than 1 using 3%/3 mm was >99% for all the measurements. In order to better evaluate our process and distinguish smaller differences a new set of results was obtained by applying gamma index tolerances of 2%/2mm. In this case, the gamma index passing rates ranged from 90.8 to 100% (95.5%±3%). The profile comparison showed that the detector array measurements followed closely the calculated 40 profiles, even for fields optimized with multiple peaks and valleys. CONCLUSION: The choice of the IMRT QA device has an important role in the results of the patient specific QA of the delivered dose to the patient in the case of small targets as in the treatment of spinal targets. In this study, we demonstrated that an extended SSD measurement can improve the sampling resolution of a two-dimensional (2D) detector array, in our case the PTW 45 Seven29 array. This method was shown to be accurate and efficient for measuring highly modulated small fields for pre-treatment patient specific QA.

Comparing conformal, arc radiotherapy and helical tomotherapy in craniospinal irradiation planning.

Currently, radiotherapy treatment plan acceptance is based primarily on dosimetric performance measures. However, use of radiobiological analysis to assess benefit in terms of tumor control and harm in terms of injury to normal tissues can be advantageous. For pediatric craniospinal axis irradiation (CSI) patients, in particular, knowing the technique that will optimize the probabilities of benefit versus injury can lead to better long-term outcomes. Twenty-four CSI pediatric patients (median age 10) were retrospectively planned with three techniques: three-dimensional conformal radiation therapy (3D CRT), volumetric-modulated arc therapy (VMAT), and helical tomotherapy (HT). VMAT plans consisted of one superior and one inferior full arc, and tomotherapy plans were created using a 5.02cm field width and helical pitch of 0.287. Each plan was normalized to 95% of target volume (whole brain and spinal cord) receiving prescription dose 23.4Gy in 13 fractions. Using an in-house MATLAB code and DVH data from each plan, the three techniques were evaluated based on biologically effective uniform dose (D=), the complication-free tumor control probability (P+), and the width of the therapeutically beneficial range. Overall, 3D CRT and VMAT plans had similar values of D= (24.1 and 24.2 Gy), while HT had a D= slightly lower (23.6 Gy). The average values of the P+ index were 64.6, 67.4, and 56.6% for 3D CRT, VMAT, and HT plans, respectively, with the VMAT plans having a statistically significant increase in P+. Optimal values of D= were 28.4, 33.0, and 31.9 Gy for 3D CRT, VMAT, and HT plans, respectively. Although P+ values that correspond to the initial dose prescription were lower for HT, after optimizing the D= prescription level, the optimal P+ became 94.1, 99.5, and 99.6% for 3D CRT, VMAT, and HT, respectively, with the VMAT and HT plans having statistically significant increases in P+. If the optimal dose level is prescribed using a radiobiological evaluation method, as opposed to a purely dosimetric one, the two IMRT techniques, VMAT and HT, will yield largest overall benefit to CSI patients by maximizing tumor control and limiting normal tissue injury. Using VMAT or HT may provide these pediatric patients with better long-term outcomes after radiotherapy.

NTCP Modeling and Dose-Volume Correlations of Significant Hematocrit Drop 3 Months After Prostate Radiation Therapy.

Purpose: Our purpose was to determine and model the dose-response relations of different parts of the pelvis regarding the endpoint of hematocrit level drop after pelvic radiation therapy (RT). Methods and Materials: Two hundred and twenty-one patients treated with RT for prostate adenocarcinoma between 2014 and 2016 were included. All patients had complete blood counts collected at baseline and 3 months post-RT. The net difference of hematocrit level post-RT versus baseline was calculated, and the level of the 15th percentiles defined the thresholds of response in each case. The doses to 8 different pelvic structures were derived and fitted to the hematocrit levels using the relative seriality normal tissue complication probability model and the biologically equivalent uniform dose (D=). Results: Pelvic structures that correlated with significant decreases in hematocrit were the os coxae bilaterally superior to the acetabulum (OCUB), the total os coxae bilaterally, and the bone volume of the whole pelvis. The structure showing the highest correlation was OCUB with a maximum area under the curve (AUC) of 0.74. For V20 Gy < 30% the odds ratio was 9.8 with 95% CI of 2.9 to 32.9. For mean dose (Dmean) to OCUB, an AUC of 0.73 was observed where the dose threshold was 23 Gy and the odds ratio was 2.7 and 95% CI 1.3 to 5.6. The values for the D50, γ, and s parameters of the relative seriality model were 26.9 Gy (25.9-27.9), 1.3 (1.2-2.2), and 0.12 (0.10-0.83), respectively. The AUC of D= was 0.73 and patients with D= to OCUB ≥ 27 Gy had 8.2 times higher rate of significant hematocrit drop versus <27 Gy. Conclusions: These findings confirm the association of radiation-induced damage to pelvic bone marrow with a drop in hematocrit. A threshold of V20 Gy < 30%, Dmean < 23 Gy, or D= < 27 Gy to OCUB may significantly reduce the risk for this endpoint.

Dose-response modeling and treatment plan assessment with a python software toolkit.

This software assistant aims at calculating the dose-response relations of tumors and normal tissues, or clinically assessing already determined values by other researchers. It can also indicate the optimal dose prescription by optimizing the expected treatment outcome. The software is developed solely in python programming language, and it employs PSFL license for its Graphical User Interface (GUI), NUMPY, MATPLOTLIB, and SCIPY libraries. It comprises of two components. The first is the Dose-response relations derivation component, which takes as input the dose volume histograms (DVHs) of patients and their recorded responses regarding a given clinical endpoint to determine the parameters of different tumor control probability (TCP) or normal tissue complication probability (NTCP) models. The second is the Treatment Plan Assessment component, which uses the DVHs of a plan and the dose-response parameters values of the involved tumors and organs at risk (OARs) to calculate their expected responses. Additionally, the overall probabilities of benefit (PB), injury (PI) and complication-free tumor control (P+) are calculated. The software calculates rapidly the corresponding generalized equivalent uniform doses (gEUD) and biologically effective uniform doses (D‾‾) for the Lyman-Kutcher-Burman (LKB), parallel volume (PV) and relative seriality (RS) models respectively, determining the model parameters. In the Dose-Response Relations Derivation component, the software plots the dose-response curves of the irradiated organ with the relevant confidence internals along with the data of the patients with and without toxicity. It also calculates the odds ratio (OR) and the area under the curve (AUC) of different dose metrics or model parameter values against the individual patient outcomes to determine their discrimination capacity. It also performs a goodness-of-fit evaluation of any model parameter set. The user has the option of viewing plots like Scatter, 3D surfaces, and Bootstrap plots. In the Treatment Plan Assessment part, the software calculates the TCP and NTCP values of the involved tumors and OARs, respectively. Furthermore, it plots the dose-response curves of the TCPs, NTCPs, PB, PI, and P+ for a range of prescription doses for different treatment plans. The presented software is ideal for efficiently conducting studies of radiobiological modeling. Furthermore, it is ideal for performing treatment plan assessment, comparison, and optimization studies.

Hypofractionated Stereotactic Radiation Therapy Dosimetric Tolerances for the Inferior Aspect of the Brachial Plexus: A Systematic Review.

We sought to systematically review and summarize dosimetric factors associated with radiation-induced brachial plexopathy (RIBP) after stereotactic body radiation therapy (SBRT) or hypofractionated image guided radiation therapy (HIGRT). From published studies identified from searches of PubMed and Embase databases, data quantifying risks of RIBP after 1- to 10-fraction SBRT/HIGRT were extracted and summarized. Published studies have reported <10% risks of RIBP with maximum doses (Dmax) to the inferior aspect of the brachial plexus of 32 Gy in 5 fractions and 25 Gy in 3 fractions. For 10-fraction HIGRT, risks of RIBP appear to be low with Dmax < 40 to 50 Gy. For a given dose value, greater risks are anticipated with point volume-based metrics (ie, D0.03-0.035cc: minimum dose to hottest 0.03-0.035 cc) versus Dmax. With SBRT/HIGRT, there were insufficient published data to predict risks of RIBP relative to brachial plexus dose-volume exposure. Minimizing maximum doses and possibly volume exposure of the brachial plexus can reduce risks of RIBP after SBRT/HIGRT. Further study is needed to better understand the effect of volume exposure on the brachial plexus and whether there are location-specific susceptibilities along or within the brachial plexus structure.

Comparison Between EPI DWI and PROPELLER DWI in Brain MR Imaging.

OBJECTIVE: EPI DWI is a routinely used sequence in brain imaging but it has limitations when it comes to SNR and artifact reduction. PROPELLER DWI has the benefit of improving image quality compared to EPI DWI. The aim of this study is to compare the EPI DWI sequence in brain MR imaging with the PROPELLER DWI sequence. The objective is to identify which sequence is more beneficial in brain imaging by evaluating image quality and the depiction of pathologies. MATERIALS AND METHODS: A total of 101 patients (55 females and 46 males, mean age 56 years) underwent brain MRI examination on a 1.5 T scanner. EPI DWI and PROPELLER DWI sequences were acquired in every exam and were reviewed by 2 radiologists. The images were evaluated by performing a quantitative analysis based on Relative Contrast and a qualitative analysis (overall image quality, conspicuousness of lesions, artifact reduction, etc.). RESULTS: In both the qualitative and quantitative analysis PROPELLER DWI achieved better results than EPI DWI. PROPELLER DWI showed statistical significance in the overall image quality (P < 0.001), the elimination of susceptibility (P < 0.001) and flow pulsation artifacts (P < 0.001), as well as in the contrast between CSF with white (P < 0.001) and grey matter (P < 0.001). Also, PROPELLER DWI presented better delineation of pathologies like ischemic strokes, metastasis, tumors and vasogenic edemas than conventional EPI DWI. CONCLUSION: PROPELLER DWI was the preferred sequence during the image evaluation. Compared to EPI DWI, PROPELLER DWI managed to reduce susceptibility and flow pulsation whilst achieving higher image quality and lesion delineation and earlier depiction of ischemic strokes than the conventional EPI DWI. PROPELLER DWI may be incorporated in brain MR imaging replacing EPI DWI.

Radiation-induced inferior brachial plexopathy after stereotactic body radiotherapy: Pooled analyses of risks.

INTRODUCTION: Radiation-induced brachial plexopathy (RIBP), resulting in symptomatic motor or sensory deficits of the upper extremity, is a risk after exposure of the brachial plexus to therapeutic doses of radiation. We sought to model dosimetric factors associated with risks of RIBP after stereotactic body radiotherapy (SBRT). METHODS: From a prior systematic review, 4 studies were identified that included individual patient data amenable to normal tissue complication probability (NTCP) modelling after SBRT for apical lung tumors. Two probit NTCP models were derived: one from 4 studies (including 221 patients with 229 targets and 18 events); and another from 3 studies (including 185 patients with 192 targets and 11 events) that similarly contoured the brachial plexus. RESULTS: NTCP models suggest ≈10% risks associated with brachial plexus maximum dose (Dmax) of ∼32-34 Gy in 3 fractions and ∼40-43 Gy in 5 fractions. RIBP risks increase with increasing brachial plexus Dmax. Compared to previously published data from conventionally-fractionated or moderately-hypofractionated radiotherapy for breast, lung and head and neck cancers (which tend to utilize radiation fields that circumferentially irradiate the brachial plexus), SBRT (characterized by steep dose gradients outside of the target volume) exhibits a much less steep dose-response with brachial plexus Dmax > 90-100 Gy in 2-Gy equivalents. CONCLUSIONS: A dose-response for risk of RIBP after SBRT is observed relative to brachial plexus Dmax. Comparisons to data from less conformal radiotherapy suggests potential dose-volume dependences of RIBP risks, though published data were not amenable to NTCP modelling of dose-volume measures associated with RIBP after SBRT.

NTCP modelling of xerostomia after radiotherapy for oropharyngeal cancer using the PRO-CTCAE and CTCAE scoring systems at different time-points post-RT.

PURPOSE: This study aims at determining the parameter values of three normal tissue complication probability (NTCP) models for the contralateral parotid gland, contralateral submandibular gland (SMG) and contralateral salivary glands regarding the endpoint of xerostomia 6-24 months after radiotherapy for oropharynx cancer. METHODS: The treatment and outcome data of 231 patients with favorable risk, HPV-associated oropharyngeal squamous cell carcinoma are analyzed. 60 Gy intensity modulated radiotherapy was delivered to all the patients. The presence and severity of xerostomia was recorded (pre- and post- radiotherapy) by the PRO-CTCAE and the CTCAE scoring systems. In both scoring systems, patients with a change in symptom severity (from baseline) of ≥ 2 were considered responders. RESULTS: Xerostomia was observed in 61.3 %, 39.2 %, 28.6 % and 27.0 % of the patients based on the PRO-CTCAE scoring system at 6-, 12-, 18- and 24-months post-RT, respectively. The AUCs of the contralateral salivary glands ranged between 0.58-0.64 in the LKB model with the gEUD ranging between 20.3 Gy and 24.7 Gy. CONCLUSIONS: Based on the PRO-CTCAE scores, mean dose < 22 Gy, V50 < 10 % for the contralateral salivary glands and mean dose < 18 Gy, V45 < 10 % for the contralateral parotid were found to significantly reduce by a factor of 2-3 the risk for radiation induced xerostomia that is observed at 6-24 months post-RT, respectively. Also, gEUD < 22 Gy to the contralateral salivary glands and < 18 Gy to the contralateral parotid was found to significantly reduce the risk for radiation induced xerostomia that is observed at 6-24 months post-RT by 2.0-2.3 times.

The radiobiological P(+) index for pretreatment plan assessment with emphasis on four-dimensional radiotherapy modalities.

PURPOSE: Radiation treatment modalities will continue to emerge that promise better clinical outcomes albeit technologically challenging to implement. An important question facing the radiotherapy community then is the need to justify the added technological effort for the clinical return. Mobile tumor radiotherapy is a typical example, where 4D tumor tracking radiotherapy (4DTRT) has been proposed over the simpler conventional modality for better results. The modality choice per patient can depend on a wide variety of factors. In this work, we studied the complication-free tumor control probability (P(+)) index, which combines the physical complexity of the treatment plan with the radiobiological characteristics of the clinical case at hand and therefore found to be useful in evaluating different treatment techniques and estimating the expected clinical effectiveness of different radiation modalities. METHODS: 4DCT volumes of 18 previously treated lung cancer patients with tumor motion and size ranging from 2 mm to 15 mm and from 4 cc to 462 cc, respectively, were used. For each patient, 4D treatment plans were generated to extract the 4D dose distributions, which were subsequently used with clinically derived radiobiological parameters to compute the P(+) index per modality. RESULTS: The authors observed, on average, a statistically significant increase in P(+) of 3.4% ± 3.8% (p < 0.003) in favor of 4DTRT. There was high variability among the patients with a <0.5% up to 13.4% improvement in P(+). CONCLUSIONS: The observed variability in the improvement of the clinical effectiveness suggests that the relative benefit of tracking should be evaluated on a per patient basis. Most importantly, this variability could be effectively captured in the computed P(+). The index can thus be useful to discriminate and hence point out the need for a complex modality like 4DTRT over another. Besides tumor mobility, a wide range of other factors, e.g., size, location, fractionation, etc., can affect the relative benefits. Application of the P(+) objective is a simple and effective way to combine these factors in the evaluation of a treatment plan.

Investigating the dosimetric and tumor control consequences of prostate seed loss and migration.

PURPOSE: Low dose-rate brachytherapy is commonly used to treat prostate cancer. However, once implanted, the seeds are vulnerable to loss and movement. The goal of this work is to investigate the dosimetric and radiobiological effects of the types of seed loss and migration commonly seen in prostate brachytherapy. METHODS: Five patients were used in this study. For each patient three treatment plans were created using Iodine-125, Palladium-103, and Cesium-131 seeds. The three seeds that were closest to the urethra were identified and modeled as the seeds lost through the urethra. The three seeds closest to the exterior of prostatic capsule were identified and modeled as those lost from the prostate periphery. The seed locations and organ contours were exported from Prowess and used by in-house software to perform the dosimetric and radiobiological evaluation. Seed loss was simulated by simultaneously removing 1, 2, or 3 seeds near the urethra 0, 2, or 4 days after the implant or removing seeds near the exterior of the prostate 14, 21, or 28 days after the implant. RESULTS: Loss of one, two or three seeds through the urethra results in a D(90) reduction of 2%, 5%, and 7% loss, respectively. Due to delayed loss of peripheral seeds, the dosimetric effects are less severe than for loss through the urethra. However, while the dose reduction is modest for multiple lost seeds, the reduction in tumor control probability was minimal. CONCLUSIONS: The goal of this work was to investigate the dosimetric and radiobiological effects of the types of seed loss and migration commonly seen in prostate brachytherapy. The results presented show that loss of multiple seeds can cause a substantial reduction of D(90) coverage. However, for the patients in this study the dose reduction was not seen to reduce tumor control probability.

Performance of independent dose calculation in helical tomotherapy: implementation of the MCSIM code.

Currently, a software-based second check dose calculation for helical tomotherapy (HT) is not available. The goal of this study is to evaluate the dose calculation accuracy of the in-house software using EGS4/MCSIM Monte Carlo environment against the treatment planning system calculations. In-house software was used to convert HT treatment plan information into a non-helical format. The MCSIM dose calculation code was evaluated by comparing point dose calculations and dose profiles against those from the HT treatment plan. Fifteen patients, representing five treatment sites, were used in this comparison. Point dose calculations between the HT treatment planning system and the EGS4/MCSIM Monte Carlo environment had percent difference values below 5 % for the majority of this study. Vertical and horizontal planar profiles also had percent difference values below 5 % for the majority of this study. Down sampling was seen to improve speed without much loss of accuracy. EGS4/MCSIM Monte Carlo environment showed good agreement with point dose measurements, compared to the HT treatment plans. Vertical and horizontal profiles also showed good agreement. Significant time saving may be obtained by down-sampling beam projections. The dose calculation accuracy of the in-house software using the MCSIM code against the treatment planning system calculations was evaluated. By comparing point doses and dose profiles, the EGS4/MCSIM Monte Carlo environment was seen to provide an accurate independent dose calculation.

Stereotactic Body Radiation Therapy for Apical Lung Tumors: Dosimetric Analysis of the Brachial Plexus and Preliminary Clinical Outcomes.

PURPOSE: Dosimetric constraints of the brachial plexus have not yet been well-established for patients undergoing stereotactic body radiation therapy (SBRT). This study evaluated long-term experience with the treatment of early-stage apical lung tumors with SBRT and reports on dosimetric correlates of outcome. METHODS AND MATERIALS: Between 2009 and 2018, a total of 78 consecutive patients with 81 apical lung tumors underwent SBRT for T1-3N0 non-small cell lung cancer. Apical tumors were those with tumor epicenter superior to the aortic arch. The brachial plexus (BP) was anatomically contoured according to the Radiation Therapy Oncology Group atlas. Patient medical records were reviewed retrospectively to determine incidence of brachial plexus injury (BPI) and a normal tissue complication probability model was applied to the dosimetric data. RESULTS: Five patients (6.4%) reported neuropathic symptoms consistent with BPI and occurred a median 11.9 months after treatment (range, 5.2-28.1 months). Most common dose and fractionation in those developing BPI were 50 Gy in 5 fractions (4 patients). Symptoms consisted of pain in 2 patients (40.0%), numbness in the hand or axilla in 4 patients (80.0%), and ipsilateral hand weakness in 1 patient (20.0%). In the overall cohort the median BP Dmax (EQD23 Gy) was 5.13 Gy (range, 0.18-217.2 Gy) and in patients with BPI the median BP Dmax (EQD23 Gy) was 32.14 Gy (range, 13.4-99.9 Gy). The normal tissue complication probability model gave good fit with an area under the curve of 0.75 (odds ratio, 7.3; 95% confidence interval, 0.8-68.3) for BP Dmax (EQD23 Gy) threshold of 20 Gy. CONCLUSIONS: Significant variation exists in the dose delivered to the brachial plexus for patients treated by SBRT for apical lung tumors. The incidence of neuropathic symptoms in the post-SBRT setting was appreciable and prospective clinical correlation with dosimetric information should be used to develop evidence-based dose constraints.