Purpose: In breast radiotherapy with intensity modulation, it is a well established practice to extend the dose fluence outside the limit of the body contour to account for small changes in size and ...position of the target and the rest of the tissues due to respiration or to possible oedema. A simple approach is not applicable with RapidArc volumetric modulated arc therapy not being based on a fixed field fluence delivery. In this study, a viable technical strategy to account for this need is presented.Methods: RapidArc (RA) plans for six breast cancer patients (three right and three left cases), were optimized (PRO version III) on the original CT data set (O) and on an alternative CT (E) generated with an artificial expansion (and assignment of soft-tissue equivalent HU) of 10 mm of the body in the breast region and of the PTV contours toward the external direction. Final dose calculations for the two set of plans were performed on the same original CT data set O, normalizing the dose prescription (50 Gy) to the target mean. In this way, two treatment plans on the same CT set O for each patient were obtained: the no action plan (OO) and the alternative plan based on an expanded optimization (EO). Fixing MU, these two plans were then recomputed on the expanded CT data set and on an intermediate one (with expansion = 5 mm), to mimic, possible changes in size due to edema during treatment or residual displacements due to breathing not properly controlled. Aim of the study was to quantify the robustness of this planning strategy on dose distributions when either the OO or the EO strategies were adopted. For all the combinations, a DVH analysis of all involved structures is reported.Results: I. The two optimization approaches gave comparable dose distributions on the original CT data set. II. When plans were evaluated on the expanded CTs (mimicking the presence of edema), the EO approach showed improved target coverage if compared to OO: on CT_10 mm, D
V = 98% % = 92.5 ± 0.9 and 68.5 ± 3.1, respectively, for EO and OO. Minor changes were registered in organs at risk sparing for both EO and OO. III. From dose distributions and DVHs, EO approach allowed to irradiate at near to prescription levels also the expanded fraction of the target: this would account also for residual intrafraction movements.Conclusions: The proposed plan strategy could represent a robust approach to account for moderate changes in target or body volume during the course of breast radiotherapy and to account for residual intrafractional respiratory motion in volumetric modulated arc therapy. The strategy, logistically simple to implement requiring only modifications to the standard planning workflow was routinely implemented at author’s institute for treatment of breast patients with RapidArc.
To evaluate the performance of a model-based optimisation process for volumetric modulated arc therapy applied to prostate cancer in a multicentric cooperative group. The RapidPlan (RP) ...knowledge-based engine was tested for the planning of Volumetric modulated arc therapy with RapidArc on prostate cancer patients. The study was conducted in the frame of the German RapidPlan Consortium (GRC).
43 patients from one institute of the GRC were used to build and train a RP model. This was further shared with all members of the GRC plus an external site from a different country to increase the heterogeneity of the patient's sampling. An in silico multicentric validation of the model was performed at planning level by comparing RP against reference plans optimized according to institutional procedures. A total of 60 patients from 7 institutes were used.
On average, the automated RP based plans resulted fully consistent with the manually optimised set with a modest tendency to improvement in the medium-to-high dose region. A per-site stratification allowed to identify different patterns of performance of the model with some organs at risk resulting better spared with the manual or with the automated approach but in all cases the RP data fulfilled the clinical acceptability requirements. Discrepancies in the performance were due to different contouring protocols or to different emphasis put in the optimization of the manual cases.
The multicentric validation demonstrated that it was possible to satisfactorily optimize with the knowledge based model patients from all participating centres. In the presence of possibly significant differences in the contouring protocols, the automated plans, though acceptable and fulfilling the benchmark goals, might benefit from further fine tuning of the constraints. The study demonstrates that, at least for the case of prostate cancer patients, it is possibile to share models among different clinical institutes in a cooperative framework.
To appraise the ability of a radiomics based analysis to predict local response and overall survival for patients with hepatocellular carcinoma.
A set of 138 consecutive patients (112 males and 26 ...females, median age 66 years) presented with Barcelona Clinic Liver Cancer (BCLC) stage A to C were retrospectively studied. For a subset of these patients (106) complete information about treatment outcome, namely local control, was available. Radiomic features were computed for the clinical target volume. A total of 35 features were extracted and analyzed. Univariate analysis was used to identify clinical and radiomics significant features. Multivariate models by Cox-regression hazards model were built for local control and survival outcome. Models were evaluated by area under the curve (AUC) of receiver operating characteristic (ROC) curve. For the LC analysis, two models selecting two groups of uncorrelated features were analyzes while one single model was built for the OS analysis.
The univariate analysis lead to the identification of 15 significant radiomics features but the analysis of cross correlation showed several cross related covariates. The un-correlated variables were used to build two separate models; both resulted into a single significant radiomic covariate: model-1: energy p < 0.05, AUC of ROC 0.6659, C.I.: 0.5585-0.7732; model-2: GLNU p < 0.05, AUC 0.6396, C.I.:0.5266-0.7526. The univariate analysis for covariates significant with respect to local control resulted in 9 clinical and 13 radiomics features with multiple and complex cross-correlations. After elastic net regularization, the most significant covariates were compacity and BCLC stage, with only compacity significant to Cox model fitting (Cox model likelihood ratio test p < 0.0001, compacity p < 0.00001; AUC of the model is 0.8014 (C.I. = 0.7232-0.8797)).
A robust radiomic signature, made by one single feature was finally identified. A validation phases, based on independent set of patients is scheduled to be performed to confirm the results.
To appraise the ability of a radiomics signature to predict clinical outcome after stereotactic body radiation therapy (SBRT) for pancreas carcinoma.
A cohort of 100 patients was included in this ...retrospective, single institution analysis. Radiomics texture features were extracted from computed tomography (CT) images obtained for the clinical target volume. The cohort of patients was randomly divided into two separate groups for the training (60 patients) and validation (40 patients). Cox regression models were built to predict overall survival and local control. The significant predictors at univariate analysis were included in a multivariate model. The quality of the models was appraised by means of area under the curve and concordance index.
A clinical-radiomic signature associated with Overall Survival (OS) was found significant in both training and validation sets (p = 0.01 and 0.05 and concordance index 0.73 and 0.75 respectively). Similarly, a signature was found for Local Control (LC) with p = 0.007 and 0.004 and concordance index 0.69 and 0.75. In the low risk group, the median OS and LC in the validation group were 14.4 and 28.6 months while in the high-risk group were 9.0 and 17.5 months respectively.
A CT based radiomic signature was identified which correlate with OS and LC after SBRT and allowed to identify low and high-risk groups of patients.
Purpose:
Small field measurements are challenging, due to the physical characteristics coming from the lack of charged particle equilibrium, the partial occlusion of the finite radiation source, and ...to the detector response. These characteristics can be modeled in the dose calculations in the treatment planning systems. Aim of the present work is to evaluate the MU calculation accuracy for small fields, defined by jaw or MLC, for anisotropic analytical algorithm (AAA) and Acuros XB algorithms, relative to output measurements on the beam central axis.
Methods:
Single point output factor measurement was acquired with a PTW microDiamond detector for 6 MV, 6 and 10 MV unflattened beams generated by a Varian TrueBeam STx equipped with high definition-MLC. Fields defined by jaw or MLC apertures were set; jaw-defined: 0.6 × 0.6, 0.8 × 0.8, 1 × 1, 2 × 2, 3 × 3, 4 × 4, 5 × 5, and 10 × 10 cm2; MLC-defined: 0.5 × 0.5 cm2 to the maximum field defined by the jaw, with 0.5 cm stepping, and jaws set to: 2 × 2, 3 × 3, 4 × 4, 5 × 5, and 10 × 10 cm2. MU calculation was obtained with 1 mm grid in a virtual water phantom for the same fields, for AAA and Acuros algorithms implemented in the Varian eclipse treatment planning system (version 13.6). Configuration parameters as the effective spot size (ESS) and the dosimetric leaf gap (DLG) were varied to find the best parameter setting. Differences between calculated and measured doses were analyzed.
Results:
Agreement better than 0.5% was found for field sizes equal to or larger than 2 × 2 cm2 for both algorithms. A dose overestimation was present for smaller jaw-defined fields, with the best agreement, averaged over all the energies, of 1.6% and 4.6% for a 1 × 1 cm2 field calculated by AAA and Acuros, respectively, for a configuration with ESS = 1 mm for both X and Y directions for AAA, and ESS = 1.5 and 0 mm for X and Y directions for Acuros. Conversely, a calculated dose underestimation was found for small MLC-defined fields, with the best agreement averaged over all the energies, of −3.9% and 0.2% for a 1 × 1 cm2 field calculated by AAA and Acuros, respectively, for a configuration with ESS = 0 mm for both directions and both algorithms.
Conclusions:
For optimal setting applied in the algorithm configuration phase, the agreement of Acuros calculations with measurements could achieve the 3% for MLC-defined fields as small as 0.5 × 0.5 cm2. Similar agreement was found for AAA for fields as small as 1 × 1 cm2.
This study evaluates the volumetric modulated arc therapy (VMAT) dosimetric comparison between Halcyon ring gantry and TrueBeam c-arm linear accelerators for craniospinal irradiation (CSI) of the ...neuro-axis. 25 patients, who received treatment for medulloblastoma and primitive neuro-ectodermal tumors between 2018 and 2021, were planned for VMAT in True Beam (TB), and Halcyon (HAL) linear accelerators using 6 MV unflattened (FFF) photon beams (HALFFF and TBFFF). Dose-volume statistics for the target and organs at risk (OARs) and the total number of monitoring units (MUs) in the treatment plans were compared which included dose received by 95% PTV volume (V95%), volume receiving ≥ 107% dose, homogeneity index (HI), conformity index (PI), MU and dose spillage (D10%, D30%, D50%, D70%, D90%). In all 26 OARs were considered of which five were serial and the remaining were parallel structures. For the former, the dose received by 0.2 cm
, volume = D0.2 cm
) were evaluated and for the latter mean dose were evaluated. Both arms were statistically compared with paired sample t-test with a significant value of ≤ 0.05. 11 patients received treatment with the Halcyon and the rest 14 in the TrueBeam C-arm linear accelerator. Patients in the low- and intermediate-risk category (n = 13) received 23.4 Gy in 13 fractions. The remaining patients were in the high-risk category and received 35 Gy in 21 fractions or 36 Gy in 20 fractions. For HALFFF and TBFFF, PTVV95% were 97.5 ± 0.8% and 97.4 ± 0.9% respectively (p = 0.371) while the V107% were 0.6 ± 0.4% and 0.5 ± 0.5 respectively (p = 0.504). However, the number of monitoring units showed statistical significance (p < 0.001) with values of 1331.9 ± 243.4 MU and 1089 ± 206.7 MU respectively for the HAL and TB plans. The differences in spillage dose were also statistically significant, favouring HAL plans at D30% (p = 0.002), D50% (p < 0.001), D70% (p = 0.039), and D90% (p = 0.01) level except for D10% (p = 0.090). Conformity index also showed statistical significance with PI_HAL = 0.9 ± 0.02 and PI_TB = 0.89 ± 0.03 (p = 0.029). For 10 of the 21 parallel structures, the mean dose differences were statistically significant in favouring of HAL plans. Halcyon based VMAT CSI plans are dosimetrically superior in terms of organ dose, especially for the large organs, and offer lower spillage doses than the TrueBeam plans. Plans generated by both linear accelerators are suitable for the patients' treatments.
The aim of this study was to evaluate long-term efficacy and survival prognostic factors of stereotactic body radiation therapy (SBRT) for un-resectable liver metastases in patients enrolled in a ...prospective phase II trial.
5-year local control (LC), overall survival (OS), progression free survival (PFS) and toxicity rates were analyzed in patients with un-resectable liver metastases enrolled in a Phase II Trial on liver SBRT, with a prescription dose of 75Gy in 3 consecutive fractions.
A total of 61 patients with 76 lesions were enrolled, with a median follow-up time of 6.1 years. One, three and 5 year LC rates were 94 ± 3.1%, 78.0 ± 5.9% and 78.0 ± 5.9%, without reaching the median LC time. Median OS was 27.6 months and the survival rates were 85.2 ± 4.5%, 31.1 ± 5.9% and 18.0 ± 4.9% at 1, 3 and 5-year after SBRT, respectively. Univariate analysis showed that favorable primary site (colorectal, breast and gynecological) of metastases (p = 0.001) improved survival. Toxicity was moderate. One patient experienced G3 late chest wall pain, which resolved within 1 year from SBRT. No cases of Radiation Induced Liver Disease (RILD) were detected.
Long-term results of this Phase II study suggest the efficacy and safety of SBRT for un-resectable liver metastases after 5-year of follow up. Selection of cases with positive prognostic factors may improve long-term survival of these oligo-metastastic patients and may confirm the role of SBRT as an effective alternative local therapy for liver metastases.
To evaluate the performance of a broad scope model-based optimisation process for volumetric modulated arc therapy applied to esophageal cancer.
A set of 70 previously treated patients in two ...different institutions, were selected to train a model for the prediction of dose-volume constraints. The model was built with a broad-scope purpose, aiming to be effective for different dose prescriptions and tumour localisations. It was validated on three groups of patients from the same institution and from another clinic not providing patients for the training phase. Comparison of the automated plans was done against reference cases given by the clinically accepted plans.
Quantitative improvements (statistically significant for the majority of the analysed dose-volume parameters) were observed between the benchmark and the test plans. Of 624 dose-volume objectives assessed for plan evaluation, in 21 cases (3.3 %) the reference plans failed to respect the constraints while the model-based plans succeeded. Only in 3 cases (<0.5 %) the reference plans passed the criteria while the model-based failed. In 5.3 % of the cases both groups of plans failed and in the remaining cases both passed the tests.
Plans were optimised using a broad scope knowledge-based model to determine the dose-volume constraints. The results showed dosimetric improvements when compared to the benchmark data. Particularly the plans optimised for patients from the third centre, not participating to the training, resulted in superior quality. The data suggests that the new engine is reliable and could encourage its application to clinical practice.
To evaluate the performance of a model-based optimisation process for volumetric modulated arc therapy, VMAT, applied to whole breast irradiation.
A set of 150 VMAT dose plans with simultaneous ...integrated boost were selected to train a model for the prediction of dose-volume constraints. The dosimetric validation was done on different groups of patients from three institutes for single (50 cases) and bilateral breast (20 cases).
Quantitative improvements were observed between the model-based and the reference plans, particularly for heart dose. Of 460 analysed dose-volume objectives, 13% of the clinical plans failed to meet the constraints while the respective model-based plans succeeded. Only in 5 cases did the reference plans pass while the respective model-based failed the criteria. For the bilateral breast analysis, the model-based plans resulted in superior or equivalent dose distributions to the reference plans in 96% of the cases.
Plans optimised using a knowledge-based model to determine the dose-volume constraints showed dosimetric improvements when compared to earlier approved clinical plans. The model was applicable to patients from different centres for both single and bilateral breast irradiation. The data suggests that the dose-volume constraint optimisation can be effectively automated with the new engine and could encourage its application to clinical practice.
Purpose:
To ascertain whether a new delivery system (the Halcyon system) equipped with dual-layer stacked multileaf collimator operating in a mode, which allows independent, fully interdigitating ...motion of both layers and 6 flattening filter free energy, could generate plans of high clinical quality compared to a well-established delivery system with single layer multileaf collimator.
Methods:
Twenty patients in each of the 3 groups (advanced head and neck, breast, and high-risk prostate) were selected for an in silico planning study. For each patient, reference plans were developed for volumetric modulated arc therapy technique with 6 MV photon beams from a TrueBeam linear accelerator and compared against the corresponding plans for the Halcyon system. Plan comparison was performed in terms of dose volume histogram quantitative analysis.
Results:
Concerning the planning target volumes, with identical dose calculation and optimization algorithms and with identical planning techniques, no clinically relevant difference in coverage (D98%), hot spot (D2%), or homogeneity was observed. Similarly, for all the organs at risk, the dosimetric findings showed that (1) all planning constraints were met by the 2 delivery systems and (2) although statistical significant differences were reported for most of the parameters but none of these were judged of potential clinical relevance.
Conclusion:
The data presented confirmed that the new delivery system can generate treatment plans for volumetric modulated arc therapy with the same dosimetric quality of what is achievable with other systems routinely used in the clinics without significantly changing the current practice. Additional studies which customize the optimization parameters for each delivery device would complement the spectrum of investigations.
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