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.

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) 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.

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.

An Analysis of Risk Factors for Radiation Necrosis Following Cranial Radiation.

Introduction Radiation necrosis in the brain is a frequent complication of brain radiation therapy (RT) and is characterized by various neurological symptoms including cognitive dysfunction, headaches, weakness, apraxia, aphasia, and numbness. These symptoms may be progressive and treatment-resistant. Currently, risk factors for radiation necrosis are not well characterized. The goal of this study is to identify risk factors for cerebral radiation necrosis in order to improve clinicians' ability to appropriately weigh the risks and benefits of brain RT. Methods A retrospective chart review was performed on patients who were diagnosed with brain tumors and received RT (3D conformal therapy, volumetric modulated arc therapy, stereotactic radiosurgery, or stereotactic radiotherapy) at the University of Arkansas for Medical Sciences from July 1, 2017, to July 1, 2019. Data regarding demographics, characteristics of cancer, chemotherapy status and class, comorbidities, and additional medications of patients were collected via EPIC. Total RT dose, fraction size, volume of brain receiving 12 Gy (V12), and retreatment of locally recurrent tumors were recorded from Eclipse. The diagnosis of radiation necrosis was based on MRI reports that were examined for a time period of 24 months following the completion of radiation treatment and confirmed, when possible, by biopsy. Cases that did not have an MRI available at least two months after the completion of RT were excluded. Statistical association analyses were used to identify candidate risk factors to radiation necrosis. These candidate risk factors were further used to assess their associations to demographics and other characteristics of cancer and treatments. Finally, adjusted and unadjusted logistic regression models were used to predict radiation necrosis using a single risk factor or multiple risk factors. ROC curves were used to evaluate the performance of prediction or discrimination of the logistic regression models. Results A total of 139 patients were studied. The mean ± standard deviation (SD) for age was 60.4 ± 13.6 years, female:male ratio was 71:68, and White:African American:other race ratio was 112:24:3. A total of 43 (30.9%) patients were diagnosed with radiation necrosis. Radiation adjuvant to surgery, concurrent systemic therapy status, total dose, and V12 were found to be significantly associated with radiation necrosis and considered candidate risk factors of radiation necrosis in the study. Predictive models showed adjusted odds ratios ([aORs] 95% confidence intervals or CIs) of 3.70 (1.01-13.56) and 8.19 (1.78-37.78) with radiation adjuvant to surgery and concurrent systemic therapy, respectively. For every one unit (log-transformed) increase of total dose and V12, the aORs (95% CI's) were 27.35 (3.74-200.16) and 1.63 (1.15-2.32), respectively. Conclusion Our study suggested a positive correlation of concurrent systemic therapy status and post-surgical adjuvant RT with the incidence of radiation necrosis. It further demonstrated that greater total RT dose and V12 were related to the risk of developing radiation necrosis following brain RT. Given the findings of this study, the aforementioned factors should be considered when weighing the risk of radiation necrosis with the benefits of treatment.

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.

A dosimetric comparative analysis of Brainlab elements and Eclipse RapidArc for spine SBRT treatment planning.

Purpose. This is a dosimetric study comparing stereotactic body radiotherapy (SBRT) plans of spine tumors using Brainlab Elements Spine planning module against Eclipse RapidArc plans. Dose conformity, dose gradient, dose fall-off, and patient-specific quality assurance (QA) metrics were evaluated. Methods:Twenty patients were immobilized in supine position using half Vac-Lok. A prescription dose of 16 Gy in a single fraction was planned for Varian TrueBeam. Conformal arc plans were generated with Pencil beam (PB), MonteCarlo (MC) in Elements, and RapidArc with Acuros XB algorithm in Eclipse using identical treatment geometry.Results. Eclipse, Elements PB, and Elements MC generated dosimetrically conformal plans having Inverse Paddick Conformity Index (IPCI) <1.3. All plans satisfied the dose constraints to target and OARs. Elements PB had a sharper gradient than Elements MC with average GI of 3.67(95% CI: 3.52-3.82) and 4.06 (95% CI: 3.93-4.20) respectively. Eclipse plans were more homogeneous with mean HI = 1.22 (95% CI: 1.20-1.23) that is lower than others. Average maximum clinical target volume (CTV) doses were higher in Elements MC with 22.31 Gy (95% CI: 21.87-22.74), while PB plans have 21.15 Gy (95% CI: 20.36-21.96), respectively. Elements MC and PB plans had lower average dose to 0.35 c.c. of spinal cord (D0.35cc) of 7.60 Gy (95% CI: 7.18-8.02) and 8.42 Gy (95% CI: 7.83-9.01). All plans had >95% points passing the gamma QA criteria at 3%/2 mm.Conclusion. All treatment plans achieved clinically acceptable target coverage >95% and meet spinal cord dose limits. Smart optimization in Brainlab Elements spine module produced dosimetrically superior plans by better spinal cord sparing.

Output factor measurements with multiple detectors in CyberKnife® Robotic Radiosurgery System.

AIM: The aim of this study was to measure and compare the output factor (OF) of a CyberKnife Robotic Radiosurgery System with eight different small field detectors and validate with Technical Report Series (TRS) report 483. BACKGROUND: Accurate dosimetry of CyberKnife system is limited due to the challenges in small field dosimetry. OF is a vital dosimetric parameter used in the photon beam modeling and any error would affect the dose calculation accuracy. MATERIALS AND METHODS: In this study, the OF was measured with eight different small-field detectors for the 12 IRIS collimators at 800 mm SAD setup at 15 mm depth. The detectors used were PTW 31016 PinPoint 3D, IBA PFD shielded diode, IBA EFD unshielded diode, IBA SFD unshielded diode (stereotactic), PTW 60008 shielded diode, PTW 60012 unshielded diode, PTW 60018 unshielded diode (stereotactic), and PTW 60019 CVD diamond detector. OF was obtained after correcting for field output correction factors from IAEA TRS No. 483. RESULTS: The field OFs in CyberKnife are derived from the measured data by applying the correction factors from Table 23 in TRS 483 for the eight small field detectors. These field OFs matched within 2% of peer-reviewed published values. The range and standard deviation showed a decreasing trend with collimator diameter. CONCLUSION: The field OF obtained after applying the appropriate correction factor from TRS 483 matched well with the peer-reviewed published OFs. The inter-detector variation showed a decreasing trend with increasing collimator field size. This study gives physicists confidence in measuring field OFs while using small field detectors mentioned in this work.

Simultaneous exposure to chronic irradiation and simulated microgravity differentially alters immune cell phenotype in mouse thymus and spleen.

Deep-space missions may alter immune cell phenotype in the primary (e.g., thymus) and secondary (e.g., spleen) lymphoid organs contributing to the progression of a variety of diseases. In deep space missions, astronauts will be exposed to chronic low doses of HZE radiation while being in microgravity. Ground-based models of long-term uninterrupted exposures to HZE radiation are not yet available. To obtain insight in the effects of concurrent exposure to microgravity and chronic irradiation (CIR), mice received a cumulative dose of chronic 0.5 Gy gamma rays over one month ± simulated microgravity (SMG). To obtain insight in a dose rate effect, additional mice were exposed to single acute irradiation (AIR) at 0.5 Gy gamma rays. We measured proportions of immune cells relative to total number of live cells in the thymus and spleen, stress level markers in plasma, and change in body weight, food consumption, and water intake. CIR affected thymic CD3+/CD335+ natural killer T (NK-T) cells, CD25+ regulatory T (Treg) cells, CD27+/CD335- natural killer (NK1) cells and CD11c+/CD11b- dendritic cells (DCs) differently in mice subjected to SMG than in mice with normal loading. No such effects of CIR on SMG as compared to normal loading were observed in cell types from the spleen. Differences between CIR and AIR groups (both under normal loading) were found in thymic Treg and DCs. Food consumption, water intake, and body weight were less after coexposure than singular or no exposure. Compared to sham, all treatment groups exhibited elevated plasma levels of the stress marker catecholamines. These data suggest that microgravity and chronic irradiation may interact with each other to alter immune cell phenotypes in an organ-specific manner and appropriate strategies are required to reduce the health risk of crewmembers.

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.

Evidence for Early Stage Anti-Tumor Immunity Elicited by Spatially Fractionated Radiotherapy-Immunotherapy Combinations.

The combination of radiotherapy and immunotherapy may generate synergistic anti-tumor host immune responses and promote abscopal effects. Spatial fractionation of a radiation dose has been found to promote unique physiological responses of tumors, which might promote synergy with immunotherapy. To determine whether spatial fractionation may augment immune activity, whole-tumor or spatial fractionation grid radiation treatment (GRID) alone or in combination with antibodies against immune checkpoints PD1 and CTLA-4 were tested in an immunocompetent mouse model using a triple negative breast tumor (4T1). Tumor growth delay, immunohistochemistry and flow cytometry were used to characterize the effects of each treatment type. Whole-beam radiation with immune checkpoint inhibition significantly restrained tumor growth in the irradiated tumor, but not abscopal tumors, compared to either of these treatments alone. In mice that received spatially fractionated irradiation, evidence of abscopal immune responses were observed in contralateral tumors with markedly enhanced infiltration of both antigen-presenting cells and activated T cells, which were preceded by increased systemic IFNγ production and led to eventual tumor growth delay. These studies suggest that systemic immune activation may be triggered by employing GRID to a primary tumor lesion, promoting anti-tumor immune responses outside the treatment field. Interestingly, PD-L1 was found to be upregulated in abscopal tumors from GRID-treated mice. Combined radio-immunotherapy therapy is becoming a validated and novel approach in the treatment of cancer. With the potential increased benefit of GRID to augment both local and metastatic disease responses, further exploration of GRID treatment as a part of current standards of care is warranted.

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.

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.

Dose Calculation Comparisons between Three Modern Treatment Planning Systems.

PURPOSE: Monaco treatment planning system (TPS) version 5.1 uses a Monte-Carlo (MC)-based dose calculation engine. The aim of this study is to verify and compare the Monaco-based dose calculations with both Pinnacle3 collapsed cone convolution superposition (CCCS) and Eclipse anisotropic analytical algorithm (AAA) calculations. MATERIALS AND METHODS: For this study, 18 previously treated lung and head-and-neck (HN) cancer patients were chosen to compare the dose calculations between Pinnacle, Monaco, and Eclipse. Plans were chosen from those that had been treated using the Elekta VersaHD or a Novalis Tx linac. All of the treated volumetric-modulated arc therapy plans used 6 MV or 10 MV photon beams. The original plans calculated with CCCS or AAA along with the recalculated ones using MC from the three TPS were exported into Velocity software for intercomparison. RESULTS: To compare the dose calculations, Planning target volume (PTV) heterogeneity indexes and conformity indexes were calculated from the dose volume histograms (DVH) of all plans. While mean lung dose (MLD), lung V5 and V20 values were recorded for lung plans, the computed dose to parotids, brainstem, and mandible were documented for HN plans. In plan evaluation, percent differences of the above dosimetric values in Monaco computation were compared against each of the other TPS computations. CONCLUSION: It could be concluded through this research that there can be differences in the calculation of dose across different TPSs. Although relatively small, these differences could become apparent when compared using DVH. These differences most likely arise from the different dose calculation algorithms used in each TPS. Monaco employs the MC allowing it to have much more detailed calculations that result in it being seen as the most accurate and the gold standard.

Correlation between Biological Effective Dose and Radiation-induced Liver Disease from Hypofractionated Radiotherapy.

BACKGROUND: The prevention of radiation-induced liver disease (RILD) is very significant in ensuring a safe radiation treatment and high quality of life. AIMS AND OBJECTIVES: The purpose of this study is to investigate the correlation of physical and biological effective dose (BED) metrics with liver toxicity from hypo-fractionated liver radiotherapy. MATERIALS AND METHODS: 41 hypo-fractionated patients in 2 groups were evaluated for classic radiation-induced liver disease (RILD) and chronic RILD, respectively. Patients were graded for effective toxicity (post-treatment minus pre-treatment) using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Physical dose (PD) distributions were converted to BED. The V10Gy, V15Gy, V20Gy, V25Gy and V30Gy physical dose-volume metrics were used in the analysis together with their respective BED-converted metrics of V16.7Gy3, V30Gy3, V46.7Gy3, V66.7Gy3 and V90Gy3. All levels were normalized to their respective patient normal liver volumes (NLV) and evaluated for correlation to RILD. Results were measured quantitatively using R2 regression analysis. RESULTS: The classic RILD group had median follow-up time of 1.9 months and the average PD-NLV normalized V10Gy, V15Gy, V20Gy, V25Gy and V30Gy metrics per grade were plotted against RILD yielding R2 correlations of 0.84, 0.72, 0.73, 0.65 and 0.70, respectively while the BED-volume metrics of V16.7Gy3, V30Gy3, V46.7Gy3, V66.7Gy3 and V90Gy3 resulted in correlation values of 0.84, 0.74, 0.66, 0.78 and 0.74, respectively. BED compared to PD showed a statistically significant (p=.03) increase in R2 for the classic RILD group. Chronic RILD group had median follow-up time of 12.3 months and the average PD-NLV normalized V10Gy, V15Gy, V20Gy, V25Gy and V30Gy metrics per grade were plotted against RILD grade yielding R2 correlations of 0.48, 0.92, 0.88, 0.90 and 0.99 while the BED-volume metrics of V16.7Gy3, V30Gy3, V46.7Gy3, V66.7Gy3 and V90Gy3 resulted in correlation values of 0.43, 0.94, 0.99, 0.21 and 0.00, respectively. CONCLUSION: The strong correlations of the V10Gy and V15Gy PD-volume metrics as well as the V16.7Gy3 (BED of V10Gy) to both classic and chronic RILD imply the appropriateness of the current 15Gy evaluation level for liver toxicity with hypo-fractionated treatments.

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.

Physical and Radiobiological Evaluation of Accelerated Intensity Modulated Radiotherapy for Locally Advanced Head and Neck Cancer and Comparison with Short-Term Clinical Outcomes.

Objective: The present study aims to evaluate the accelerated intensity modulated radiotherapy (IMRT) of head and neck (HandN) treatments using physical indices and radiobiological models with its clinical correlation using histogram analysis in radiation therapy (HART). The radiobiological evaluation in terms of tumor control probability (TCP) and normal tissue complication probability (NTCP) indices were compared with acute toxicity. Materials and Methods: A total of twenty patients with stage III and IV of HandN cases treated with accelerated IMRT using 6MV photons were chosen for the study. Using HART software, physical indices of the IMRT plans have been defined by universal plan indices (UPI's) which summarize the various recognized plan indices. The overall quality factor (QF) of a plan was determined by a linear combination of all indices in UPI set. The clinical outcomes in terms of the acute toxicity like dysphagia and xerostomia were compared with NTCP values of the OAR calculated from HART software. Results: The mean QF and the mean Poisson TCP index was found to be 0.993±0.02 and 0.86 ±0.02 respectively. The mean JT Lyman NTCP index for bilateral parotid, constrictors, and larynx were found to be 0.23±0.14, 0.30±0.17 and 0.22±0.15 respectively. The acute toxicities in terms of severity of xerostomia and dysphagia have shown a moderate correlation with NTCP values of bilateral parotids, constrictors, and larynx, respectively. Conclusion: The mean QF based on UPI was found to be close to unity, which correlates with being a better IMRT plan. The present study suggested the existence of a moderate correlation between the calculated NTCP values and their respective severities of the organ at risk (OAR's). Accelerated IMRT with chemotherapy is a clinically feasible option in the treatment of locally advanced head and neck squamous cell carcinoma (HNSCC) with encouraging initial tumor response and acceptable acute toxicities.

Clinical Evaluation of a Two-dimensional Liquid-Filled Ion chamber Detector Array for Verification of High Modulation Small Fields in Radiotherapy.

INTRODUCTION: Clinical evaluation of a two-dimensional (2D) liquid-filled ion chamber detector array used in the verification of highly modulated small beams of stereotactic body radiation therapy (SBRT) has been conducted. MATERIALS AND METHODS: Measurements with the Octavius 1000 SRS (PTW, Freiburg, Germany) detector with 977 liquid-filled ion chambers were compared against EDR2 film and PTW Octavius Seven29. The performance of detector array has been evaluated on ten SBRT patient plans. Dose profiles of individual and composite fields' calculated using Pinnacle3 treatment planning system were compared against measurements with Octavius 1000 SRS detector array, EDR2 film, and Octavius Seven29 detector. Gamma index and profile comparison were used in the evaluation and assessment of the detector's performance. RESULTS: The Gamma index measurements show agreement between Pinnacle3 computations and Octavius 1000 SRS array, PTW Octavius Seven29, and EDR2 film for >90% of the points using 2%, 2 mm tolerance criteria. Profiles obtained with the Octavius 1000 SRS were in agreement with the EDR2 film profiles, demonstrating the detector's superior sampling rate. CONCLUSIONS: The Octavius 1000 SRS is a dosimetrically accurate device to perform quality assurance checks in SBRT treatments. The broad range of measurements performed in this study quantified the dosimetric accuracy of Octavius 1000 SRS detector in the clinical setup of the small fields in radiotherapy.

A dosimetric comparison between volumetric-modulated arc therapy and dynamic conformal arc therapy in SBRT.

PURPOSE: The purpose of this study was to investigate the dosimetric equivalency of dynamic conformal arc therapy (DCAT) against volumetric modulated arc therapy (VMAT) plans in stereotactic body radiation therapy (SBRT) of lung and liver lesions and to examine if efficiency can be increased. METHODS: Nineteen patients previously treated for lung and liver cancer lesions with SBRT were included. Organs at risk (OAR) and targets were contoured by a single radiation oncologist. All plans were optimized by the same dosimetrist using ELEKTA Monaco treatment planning system version 5.0 for 6MV flattening filter free (FFF) photon beam in a VersaHD (ELEKTA, Crawley, UK). A VMAT and DCAT plan was optimized using the same objectives using coplanar arcs of 225o arc span. RESULTS: All plans have achieved the target and OAR planning objectives. The target dose conformity was comparable (mean VMAT PTVr=1.3 and DCAT PTVr=1.4), and the low dose spillage were similar (mean VMAT R50=4.5 and DCAT R50=4.6). However, monitor units (MU) for DCAT plans were lower by 2.5 times on average than VMAT plans. It was observed that in 75% of cases where OARs overlapped with the PTV, maximum doses to OAR were higher in VMAT than DCAT plans, but the difference was not significant. Patient specific quality assurance (QA) plans were measured using the Scandidos Delta4 phantom and gamma analysis performed using 2mm distance to agreement (DTA) and 2% dose difference yielded more than 95% passing rates on both VMAT and DCAT plans. CONCLUSIONS: DCAT delivery for lung and liver SBRT is a dosimetrically equivalent and an efficient alternative to VMAT plans.