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.

The use of the normal tissue non-complication probability (NTCP0) methodology as a new alternative of assessing side-effects in brachytherapy treatments.

Background: The NTCP methodology evaluating side-effects (S-Es) was initially used in radiotherapy (RT), and later was extended to brachytherapy (BT). The NTCP0 methodology has been recently introduced in RT. Given the advantages, this methodology could replace NTCP. Materials and methods: Revisions of studies related to use of NTCP in the evaluations of S-Es in BT. Development of the first versions of two Matlab applications of the NTCP0 methodology. These applications have three options. Two of them employ the well-known aspects of a phenomenological model, or the probabilistic relationship between NTCP0 and total NTCP (TNTCP) that is the sum(NTCP(x i )) i: i th complication i:1..nc: Number of complications; where NTCP0 = 100% - TNTCP; and the third option assumes a NTCP(xi) discrete probabilistic distribution generated by the binomial distribution, where one of its parameters is automatically obtained from a databased of the Disease locations Vs. Late complications. Results: The NTCP0cal and NTCP0calDr Matlab applications have been developed, and respectively used for fractional continuous low dose-rate BT. Conclusions: NTCP0 is defined as the ratio of the number of patients without acute/late complications and total of them, and also can be obtained using our Matlab applications. NTCP0 works do not disregard the last 10-15 years of NTCP research; but NTCP0 was not considered during these years. A generic example was used for showing the variations of the late complications and NTCP0 for a BT treatment of a constant number of fractions and six different dose per fraction values.

Cleaning the dose falloff in lung SBRT plan.

PURPOSE: To investigate a planning technique that can possibly reduce low-to-intermediate dose spillage (measured by R50%, D2cm values) in lung SBRT plans. MATERIALS AND METHODS: Dose falloff outside the target was studied retrospectively in 102 SBRT VMAT plans of lung tumor. Plans having R50% and/or D2cm higher than recommended tolerances in RTOG protocols 0813 and 0915 were replanned with new optimization constraints using novel shell structures and novel constraints. Violations in the RTOG R50% value can be rectified with a dose constraint to a novel shell structure ("OptiForR50"). The construction of structure OptiForR50% and the novel optimization criteria translate the RTOG goals for R50% into direct inputs for the optimizer. Violations in the D2cm can be rectified using constraints on a 0.5 cm thick shell structure with inner surface 2cm from the PTV surface. Wilcoxon signed-rank test was used to compare differences in dose conformity, volume of hot spots, R50%, D2cm of the target in addition to the OAR doses. A two-sided P-value of 0.05 was used to assess statistical significance. RESULTS: Among 102 lung SBRT plans with PTV sizes ranging from 5 to 179 cc, 32 plans with violations in R50% or D2cm were reoptimized. The mean reduction in R50% (4.68 vs 3.89) and D2cm (56.49 vs 52.51) was statistically significant both having P < 0.01. Target conformity index, volume of 105% isodose contour outside PTV, normal lung V20, and mean dose to heart and aorta were significantly lowered with P < 0.05. CONCLUSION: The novel planning methodology using multiple shells including the novel OptiForR50 shell with precisely calculated dimensions and optimizer constraints lead to significantly lower values of R50% and D2cm and lower dose spillage in lung SBRT plans. All plans were successfully brought into the zone of no RTOG violations.

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.

Definitive single fraction stereotactic ablative radiotherapy for inoperable early-stage breast cancer: A case report.

We review a case of inoperable early stage breast cancer treated definitively with the use of stereotactic ablative radiotherapy (SABR). A 57-year-old female with a history of decompensated cirrhosis with early stage breast cancer was treated with 25 Gy in one fraction. At her 7-month follow up visit, there was a complete resolution of disease on imaging. This case represents a novel approach for the treatment of breast cancer with SABR when surgery is contraindicated.

Radiosurgery for mesial temporal lobe epilepsy following ROSE trial guidelines - A planning comparison between Gamma Knife, Eclipse, and Brainlab.

PURPOSE: This study aims to compare stereotactic radiosurgery (SRS) planning of epilepsy that complies with Radiosurgery or Open Surgery for Epilepsy (ROSE) guidelines in GammaKnife, non-coplanar conformal (NCC) plan in Eclipse, dynamic conformal arc (DCA) plan in Brainlab, and a volumetric modulated arc therapy (VMAT) plan in Eclipse. METHODS: Twenty plans targeting Mesial temporal lobe epilepsy (MTLE) was generated using GammaKnife, Eclipse with 20 NCC beams, Brainlab with 5 DCA, and Eclipse VMAT with 4 arcs observing ROSE trial guidelines. Multivariate analysis of variance and Wilcoxon signed-rank test were used to compare dosimetric data of the plans and perform pairwise comparison, respectively. RESULTS: The plans obeyed the recommended prescription isodose volume (PIV) within 5.5-7.5 cc and maximum doses to brainstem, optic apparatus (OA) of 10 and 8 Gy, respectively, for a prescription dose of 24 Gy. The volumes of the target were in the range 4.0-7.4 cc. Mean PIV, maximum dose to brainstem, OA were 6.5 cc, 10 Gy, 7.9 Gy in GammaKnife; 7.2 cc, 6.1 Gy, 4.5 Gy in Eclipse NCC; 7.2 cc, 6.4 Gy, 5.7 Gy in Brainlab DCA; and 5.2 cc, 8.4 Gy, 6.1 Gy in Eclipse VMAT plans, respectively. Multivariate analysis of variance showed significant differences among the 4 SRS planning techniques (P-values < 0.01). CONCLUSIONS: Among the 4 SRS planning methods, VMAT with least PIV and acceptable maximum doses to brainstem and OA showed highest compliance with ROSE trial. Having the most conformal dose distribution and least dose inhomogeneity, VMAT scored higher than GK, Eclipse NCC, and Brainlab DCA plans.

Robust optimization in lung treatment plans accounting for geometric uncertainty.

Robust optimization generates scenario-based plans by a minimax optimization method to find optimal scenario for the trade-off between target coverage robustness and organ-at-risk (OAR) sparing. In this study, 20 lung cancer patients with tumors located at various anatomical regions within the lungs were selected and robust optimization photon treatment plans including intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) plans were generated. The plan robustness was analyzed using perturbed doses with setup error boundary of ±3 mm in anterior/posterior (AP), ±3 mm in left/right (LR), and ±5 mm in inferior/superior (IS) directions from isocenter. Perturbed doses for D99 , D98 , and D95 were computed from six shifted isocenter plans to evaluate plan robustness. Dosimetric study was performed to compare the internal target volume-based robust optimization plans (ITV-IMRT and ITV-VMAT) and conventional PTV margin-based plans (PTV-IMRT and PTV-VMAT). The dosimetric comparison parameters were: ITV target mean dose (Dmean ), R95 (D95 /Dprescription ), Paddick's conformity index (CI), homogeneity index (HI), monitor unit (MU), and OAR doses including lung (Dmean , V20 Gy and V15 Gy ), chest wall, heart, esophagus, and maximum cord doses. A comparison of optimization results showed the robust optimization plan had better ITV dose coverage, better CI, worse HI, and lower OAR doses than conventional PTV margin-based plans. Plan robustness evaluation showed that the perturbed doses of D99 , D98 , and D95 were all satisfied at least 99% of the ITV to received 95% of prescription doses. It was also observed that PTV margin-based plans had higher MU than robust optimization plans. The results also showed robust optimization can generate plans that offer increased OAR sparing, especially for normal lungs and OARs near or abutting the target. Weak correlation was found between normal lung dose and target size, and no other correlation was observed in this study.

Therapeutic benefits in grid irradiation on Tomotherapy for bulky, radiation-resistant tumors.

INTRODUCTION: Spatially fractionated radiation therapy (SFRT or grid therapy) has proven to be effective in management of bulky tumors. The aim of this project is to study the therapeutic ratio (TR) of helical Tomotherapy (HT)-based grid therapy using linear-quadratic cell survival model. MATERIAL AND METHODS: HT-based grid (or HT-GRID) plan was generated using a patient-specific virtual grid pattern of high-dose cylindrical regions using MLCs. TR was defined as the ratio of normal tissue surviving fraction (SF) under HT-GRID irradiation to an open debulking field of an equivalent dose that result in the same tumor cell SF. TR was estimated from DVH data on ten HT-GRID patient plans with deep seated, bulky tumor. Dependence of the TR values on radiosensitivity of the tumor cells and prescription dose was analyzed. RESULTS: The mean ± standard deviation (SD) of TR was 4.0 ± 0.7 (range: 3.1-5.5) for the 10 patients with single fraction maximum dose of 20 Gy to GTV assuming a tumor cell SF at 2 Gy (SF2t) value of 0·5. In addition, the mean ± SD of TR values for SF2t values of 0.3 and 0.7 were found to be 1 ± 0.1 and 18.0 ± 5.1, respectively. Reducing the prescription dose to 15 and 10 Gy lowered the respective TR values to 2.0 ± 0.2 and 1.2 ± 0.04 for a SF2t value of 0.5. CONCLUSION: HT-GRID therapy demonstrates a significant therapeutic advantage over uniform dose from an open field irradiation for the same tumor cell kill. TR increases with the radioresistance of the tumor cells and with prescription dose.

Dosimetric validation of Monaco treatment planning system on an Elekta VersaHD linear accelerator.

The purpose of this study is to perform dosimetric validation of Monaco treatment planning system version 5.1. The Elekta VersaHD linear accelerator with high dose rate flattening filter-free photon modes and electron energies was used in this study. The dosimetric output of the new Agility head combined with the FFF photon modes warranted this investigation into the dosimetric accuracy prior to clinical usage. A model of the VersaHD linac was created in Monaco TPS by Elekta using commissioned beam data including percent depth dose curves, beam profiles, and output factors. A variety of 3D conformal fields were created in Monaco TPS on a combined Plastic water/Styrofoam phantom and validated against measurements with a calibrated ion chamber. Some of the parameters varied including source to surface distance, field size, wedges, gantry angle, and depth for all photon and electron energies. In addition, a series of step and shoot IMRT, VMAT test plans, and patient plans on various anatomical sites were verified against measurements on a Delta4 diode array. The agreement in point dose measurements was within 2% for all photon and electron energies in the homogeneous phantom and within 3% for photon energies in the heterogeneous phantom. The mean ± SD gamma passing rates of IMRT test fields yielded 93.8 ± 4.7% based on 2% dose difference and 2 mm distance-to-agreement criteria. Eight previously treated IMRT patient plans were replanned in Monaco TPS and five measurements on each yielded an average gamma passing rate of 95% with 6.7% confidence limit based on 3%, 3 mm gamma criteria. This investigation on dosimetric validation ensures accuracy of modeling VersaHD linac in Monaco TPS thereby improving patient safety.

Helical tomotherapy to LINAC plan conversion utilizing RayStation Fallback planning.

RaySearch RayStation Fallback (FB) planning module can generate an equivalent backup radiotherapy treatment plan facilitating treatment on other linear accelerators. FB plans were generated from the RayStation FB module by simulating the original plan target and organ at risk (OAR) dose distribution and delivered in various backup linear accelerators. In this study, helical tomotherapy (HT) backup plans used in Varian TrueBeam linear accelerator were generated with the RayStation FB module. About 30 patients, 10 with lung cancer, 10 with head and neck (HN) cancer, and 10 with prostate cancer, who were treated with HT, were included in this study. Intensity-modulated radiotherapy Fallback plans (FB-IMRT) were generated for all patients, and three-dimensional conformal radiotherapy Fallback plans (FB-3D) were only generated for lung cancer patients. Dosimetric comparison study evaluated FB plans based on dose coverage to 95% of the PTV volume (R95), PTV mean dose (Dmean), Paddick's conformity index (CI), and dose homogeneity index (HI). The evaluation results showed that all IMRT plans were statistically comparable between HT and FB-IMRT plans except that PTV HI was worse in prostate, and PTV R95 and HI were worse in HN multitarget plans for FB-IMRT plans. For 3D lung cancer plans, only the PTV R95 was statistically comparable between HT and FB-3D plans, PTV Dmean was higher, and CI and HI were worse compared to HT plans. The FB plans using a TrueBeam linear accelerator generally offer better OAR sparing compared to HT plans for all the patients. In this study, all cases of FB-IMRT plans and 9/10 cases of FB-3D plans were clinically acceptable without further modification and optimization once the FB plans were generated. However, the statistical differences between HT and FB-IMRT/3D plans might not be of any clinically significant. One FB-3D plan failed to simulate the original plan without further optimization.

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.

Effect of electron contamination on in vivo dosimetry for lung block shielding during TBI.

Our institution performs in vivo verification measurement for each of our total body irradiation (TBI) patients with optically stimulated luminescent dosimeters (OSLD). The lung block verification measurements were commonly higher than expected. The aim of this work is to understand this discrepancy and improve the accuracy of these lung block verification measurements. Initially, the thickness of the lung block was increased to provide adequate lung sparing. Further tests revealed the increase was due to electron contamination dose emanating from the lung block. The thickness of the bolus material covering the OSLD behind the lung block was increased to offset the electron contamination. In addition, the distance from the lung block to the dosimeter was evaluated for its effect on the OSLD reading and found to be clinically insignificant over the range of variability in our clinic. The results show that the improved TBI treatment technique provides for better accuracy of measured dose in vivo and consistency of patient setup.

Commissioning an Elekta Versa HD linear accelerator.

The purpose of this study is to report the dosimetric aspects of commissioning performed on an Elekta Versa HD linear accelerator (linac) with high-dose-rate flattening filter-free (FFF) photon modes and electron modes. Acceptance and commissioning was performed on the Elekta Versa HD linac with five photon energies (6 MV, 10 MV, 18 MV, 6 MV FFF, 10 MV FFF), four electron energies (6 MeV, 9MeV, 12 MeV, 15 MeV) and 160-leaf (5 mm wide) multileaf collimators (MLCs). Mechanical and dosimetric data were measured and evaluated. The measurements include percent depth doses (PDDs), in-plane and cross-plane profiles, head scatter factor (Sc), relative photon output factors (Scp), universal wedge transmission factor, MLC transmission factors, and electron cone factors. Gantry, collimator, and couch isocentricity measurements were within 1 mm, 0.7 mm, and 0.7 mm diameter, respectively. The PDDs of 6 MV FFF and 10 MV FFF beams show deeper dmax and steeper falloff with depth than the corresponding flattened beams. While flatness values of 6 MV FFF and 10 MV FFF normalized profiles were expectedly higher than the corresponding flattened beams, the symmetry values were almost identical. The cross-plane penumbra values were higher than the in-plane penumbra values for all the energies. The MLC transmission values were 0.5%, 0.6%, and 0.6% for 6 MV, 10 MV, and 18 MV photon beams, respectively. The electron PDDs, profiles, and cone factors agree well with the literature. The outcome of radiation treatment is directly related to the accuracy in the dose modeled in the treatment planning system, which is based on the commissioned data. Commissioning data provided us a valuable insight into the dosimetric characteristics of the beam. This set of commissioning data can provide comparison data to others performing Versa HD commissioning, thereby improving patient safety.

Pinnacle3 modeling and end-to-end dosimetric testing of a Versa HD linear accelerator with the Agility head and flattening filter-free modes.

The Elekta Versa HD incorporates a variety of upgrades to the line of Elekta linear accelerators, primarily including the Agility head and flattening filter-free (FFF) photon beam delivery. The completely distinct dosimetric output of the head from its predecessors, combined with the FFF beams, requires a new investigation of modeling in treatment planning systems. A model was created in Pinnacle3 v9.8 with the commissioned beam data. A phantom consisting of several plastic water and Styrofoam slabs was scanned and imported into Pinnacle3, where beams of different field sizes, source-to-surface distances (SSDs), wedges, and gantry angles were devised. Beams included all of the available photon energies (6, 10, 18, 6FFF, and 10 FFF MV), as well as the four electron energies commissioned for clinical use (6, 9, 12, and 15 MeV). The plans were verified at calculation points by measurement with a calibrated ionization chamber. Homogeneous and hetero-geneous point-dose measurements agreed within 2% relative to maximum dose for all photon and electron beams. AP photon open field measurements along the central axis at 100 cm SSD passed within 1%. In addition, IMRT testing was also performed with three standard plans (step and shoot IMRT, as well as a small- and large-field VMAT plan). The IMRT plans were delivered on the Delta4 IMRT QA phantom, for which a gamma passing rate was > 99.5% for all plans with a 3% dose deviation, 3 mm distance-to-agreement, and 10% dose threshold. The IMRT QA results for the first 23 patients yielded gamma passing rates of 97.4% ± 2.3%. Such testing ensures confidence in the ability of Pinnacle3 to model photon and electron beams with the Agility head.

Evaluation of Dosimetry Check software for IMRT patient-specific quality assurance.

The purpose of this study is to evaluate the use of the Dosimetry Check system for patient-specific IMRT QA. Typical QA methods measure the dose in an array dosimeter surrounded by homogenous medium for which the treatment plan has been recomputed. With the Dosimetry Check system, fluence measurements acquired on a portal dosimeter is applied to the patient's CT scans. Instead of making dose comparisons in a plane, Dosimetry Check system produces isodose lines and dose-volume histograms based on the planning CT images. By exporting the dose distribution from the treatment planning system into the Dosimetry Check system, one is able to make a direct comparison between the calculated dose and the planned dose. The versatility of the software is evaluated with respect to the two IMRT techniques - step and shoot and volumetric arc therapy. The system analyzed measurements made using EPID, PTW seven29, and IBA MatriXX, and an intercomparison study was performed. Plans from patients previously treated at our institution with treated anatomical site on brain, head & neck, liver, lung, and prostate were analyzed using Dosimetry Check system for any anatomical site dependence. We have recommendations and possible precautions that may be necessary to ensure proper QA with the Dosimetry Check system.

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.

The use of the normal tissue non-complication probability (NTCP0) in the safety evaluations as a new alternative of assessing the side-effects of the radiation oncology treatments.

PURPOSE: To encourage the use of the NTCP0 for evaluating safety as a new alternative of assessing the S-Es of the radiation oncology treatments; and the use of the 'NTCP0cal' methodology that calculates/estimates NTCP0. METHOD: Revisions of studies related to use of the NTCP in the evaluations of S-Es. Development of the first version of the Matlab application of our methodology, which provides three options, two of them employ the well-known aspects of a phenomenological model, or the relationship with the TNTCP; where NTCP0 = 100%-TNTCP; and the third option determines NTCP0 from an assumed NTCP discrete probabilistic distribution from the binomial distribution, where one of its parameters is automatically defined from a databased of the Disease locations Vs. Late complications. RESULT: As result of revisions of some QUANTEC studies, we can say that: (1) The majority of current NTCP models are DVH-based; (2) The risk of toxicity is the way of evaluating the S-Es of the radiation oncology treatments; and (3) The NTCP are used mainly for evaluations of individual or principal complications or Endpoints of the radiation treatments. The 'NTCP0cal' Matlab application developed in this study has three calculation options. Two of the options provide additional graphical information about the distributions. CONCLUSIONS: The NTCP0 is a new radiobiological concept, its introduction let to correct some current P + and UTCP formulations, and will allow evaluating S-Es in whatever activity involving ionizing radiation, like radiation treatments; and its phenomenological model function of dose prescribed (D = n*d) will allow calculating values of NTCP0 for a range of dose per fraction (d) in a treatment with a determined number of fractions (n), or for range of n for a constant d. The DVH is irrelevant for this model. For whatever radiation treatment given to a population of similar patients under similar circumstances, the NTCP0 is calculated as ratio of the number of patients without acute/late complications and total of them. When this number is unknown, then NTCP0 can be obtained using the 'NTCP0cal' application.

Cleaning the dose falloff with low modulation in SBRT lung plans.

Purpose.This dosimetric study is intended to lower the modulation factor in lung SBRT plans generated in the Eclipse TPS that could replace highly modulated plans that are prone to the interplay effect.Materials and methods.Twenty clinical lung SBRT plans with high modulation factors (≥4) were replanned in Varian Eclipse TPS version 15.5 utilizing 2 mm craniocaudal and 1 mm axial block margins followed by light optimization in order to reduce modulation. A unique plan optimization methodology, which utilizes a novel shell structure (OptiForR50) for R50%optimization in addition to five consecutive concentric 5 mm shells, was utilized to control dose falloff according to RTOG 0813 and 0915 recommendations. The prescription varied from 34-54 Gy in 1-4 fractions, and the dose objectives were PTV D95%= Rx, PTV Dmax< 140% of Rx, and minimizing the modulation factor. Plan evaluation metrics included modulation factor, CIRTOG, homogeneity index (HI), R50%, D2cm, V105%, and lung V8-12.8Gy(Timmerman Constraint). A random-intercept linear mixed effects model was used with a p ≤ 0.05 threshold to test for statistical significance.Results.The retrospectively generated plans had significantly lower modulation factors (3.65 ± 0.35 versus 4.59 ± 0.54; p < 0.001), lower CIRTOG(0.97 ± 0.02 versus 1.02 ± 0.06; p = 0.001), higher HI (1.35 ± 0.06 versus 1.14 ± 0.04; p < 0.001), lower R50%(4.09 ± 0.45 versus 4.56 ± 0.56; p < 0.001), and lower lungs V8-12.8Gy(Timmerman) (4.61% ± 3.18% versus 4.92% ± 3.37%; p < 0.001). The high dose spillage V105%was borderline significantly lower (0.44% ± 0.49% versus 1.10% ± 1.64%; p = 0.051). The D2cmwas not statistically different (46.06% ± 4.01% versus 46.19% ± 2.80%; p = 0.835).Conclusion.Lung SBRT plans with significantly lower modulation factors can be generated that meet the RTOG constraints, using our planning strategy.

Development and multi-institutional validation of a convolutional neural network to detect vertebral body mis-alignments in 2D x-ray setup images.

BACKGROUND: Misalignment to the incorrect vertebral body remains a rare but serious patient safety risk in image-guided radiotherapy (IGRT). PURPOSE: Our group has proposed that an automated image-review algorithm be inserted into the IGRT process as an interlock to detect off-by-one vertebral body errors. This study presents the development and multi-institutional validation of a convolutional neural network (CNN)-based approach for such an algorithm using patient image data from a planar stereoscopic x-ray IGRT system. METHODS: X-rays and digitally reconstructed radiographs (DRRs) were collected from 429 spine radiotherapy patients (1592 treatment fractions) treated at six institutions using a stereoscopic x-ray image guidance system. Clinically-applied, physician approved, alignments were used for true-negative, "no-error" cases. "Off-by-one vertebral body" errors were simulated by translating DRRs along the spinal column using a semi-automated method. A leave-one-institution-out approach was used to estimate model accuracy on data from unseen institutions as follows: All of the images from five of the institutions were used to train a CNN model from scratch using a fixed network architecture and hyper-parameters. The size of this training set ranged from 5700 to 9372 images, depending on exactly which five institutions were contributing data. The training set was randomized and split using a 75/25 split into the final training/ validation sets. X-ray/ DRR image pairs and the associated binary labels of "no-error" or "shift" were used as the model input. Model accuracy was evaluated using images from the sixth institution, which were left out of the training phase entirely. This test set ranged from 180 to 3852 images, again depending on which institution had been left out of the training phase. The trained model was used to classify the images from the test set as either "no-error" or "shifted", and the model predictions were compared to the ground truth labels to assess the model accuracy. This process was repeated until each institution's images had been used as the testing dataset. RESULTS: When the six models were used to classify unseen image pairs from the institution left out during training, the resulting receiver operating characteristic area under the curve values ranged from 0.976 to 0.998. With the specificity fixed at 99%, the corresponding sensitivities ranged from 61.9% to 99.2% (mean: 77.6%). With the specificity fixed at 95%, sensitivities ranged from 85.5% to 99.8% (mean: 92.9%). CONCLUSION: This study demonstrated the CNN-based vertebral body misalignment model is robust when applied to previously unseen test data from an outside institution, indicating that this proposed additional safeguard against misalignment is feasible.

A phantom-based study and clinical implementation of brainlab's treatment planning system for radiosurgical treatments of arteriovenous malformations.

PURPOSE: Development of a simple, phantom-based methodology allowing for pilot applications for the Elements TPS cranio-vascular module and clinical implementation prior to AVM treatments. METHODS: A customized phantom was developed to be visible in MRI and CT images. High resolution digital subtraction angiograms (DSAs) and CT images of the phantom were acquired and imported into the Brainlab Elements treatment planning system. A clinical treatment plan with 5 arcs was generated in cranial vascular planning module and delivered to the phantom using a Varian TrueBeam STx Linac equipped with HD-MLCs and Brainlab ExacTrac imaging system for non-coplanar setup verification. The delivered dose was verified using a calibrated ionization chamber placed in the phantom. Upon verification of the TPS workflow, three patients with AVM who have been treated to date at our center using the Brainlab's cranial vascular module for AVM are presented here for retrospective review. RESULTS: The difference between the planed and measured dose by the ionization chamber was found to be less than 1%. Following a successful dose verification study, a clinical workflow was created. Currently, three AVM patients have been treated successfully. Clinical aspects of imaging and treatment planning consideration are presented in retrospective setting. CONCLUSIONS: Dose verification of the Brainlab Elements cranial vascular planning module for intracranial SRS treatments of AVM on Varian TrueBeam was successfully implemented using a custom-made phantom with <1% discrepancy. The Brainlab Elements' cranial vascular module was successfully implemented in clinical workflow to treat patients with AVM. This manuscript provides a guideline for clinical implementation of frameless Linac-based AVM treatment using the Brainlab Elements TPS.