Marco Fusella

Optimized Volumetric Modulated Arc Therapy Versus 3D-CRT for Early Stage Mediastinal Hodgkin Lymphoma Without Axillary Involvement: A Comparison of Second Cancers and Heart Disease Risk

PURPOSE The purpose of this study was to evaluate the risks of second cancers and cardiovascular diseases associated with an optimized volumetric modulated arc therapy (VMAT) planning solution in a selected cohort of stage I/II Hodgkin lymphoma (HL) patients treated with either involved-node or involved-site radiation therapy in comparison with 3-dimensional conformal radiation therapy (3D-CRT). METHODS AND MATERIALS Thirty-eight patients (13 males and 25 females) were included. Disease extent was mediastinum alone (n=8, 21.1%); mediastinum plus unilateral neck (n=19, 50%); mediastinum plus bilateral neck (n=11, 29.9%). Prescription dose was 30 Gy in 2-Gy fractions. Only 5 patients had mediastinal bulky disease at diagnosis (13.1%). Anteroposterior 3D-CRT was compared with a multiarc optimized VMAT solution. Lung, breast, and thyroid cancer risks were estimated by calculating a lifetime attributable risk (LAR), with a LAR ratio (LAR(VMAT)-to-LAR(3D-CRT)) as a comparative measure. Cardiac toxicity risks were estimated by calculating absolute excess risk (AER). RESULTS The LAR ratio favored 3D-CRT for lung cancer induction risk in mediastinal alone (P=.004) and mediastinal plus unilateral neck (P=.02) presentations. LAR ratio for breast cancer was lower for VMAT in mediastinal plus bilateral neck presentations (P=.02), without differences for other sites. For thyroid cancer, no significant differences were observed, regardless of anatomical presentation. A significantly lower AER of cardiac (P=.038) and valvular diseases (P<.0001) was observed for VMAT regardless of disease extent. CONCLUSIONS In a cohort of patients with favorable characteristics in terms of disease extent at diagnosis (large prevalence of nonbulky presentations without axillary involvement), optimized VMAT reduced heart disease risk with comparable risks of thyroid and breast cancer, with an increase in lung cancer induction probability. The results are however strongly influenced by the different anatomical presentations, supporting an individualized approach.

Comparison of Gafchromic EBT2 and EBT3 for patient‐specific quality assurance: Cranial stereotactic radiosurgery using volumetric modulated arc therapy with multiple noncoplanar arcs

PURPOSE Patient-specific quality assurance in volumetric modulated arc therapy (VMAT) brain stereotactic radiosurgery raises specific issues on dosimetric procedures, mainly represented by the small radiation fields associated with the lack of lateral electronic equilibrium, the need of small detectors and the high dose delivered (up to 30 Gy). GafchromicTM EBT2 and EBT3 films may be considered the dosimeter of choice, and the authors here provide some additional data about uniformity correction for this new generation of radiochromic films. METHODS A new analysis method using blue channel for marker dye correction was proposed for uniformity correction both for EBT2 and EBT3 films. Symmetry, flatness, and field-width of a reference field were analyzed to provide an evaluation in a high-spatial resolution of the film uniformity for EBT3. Absolute doses were compared with thermoluminescent dosimeters (TLD) as baseline. VMAT plans with multiple noncoplanar arcs were generated with a treatment planning system on a selected pool of eleven patients with cranial lesions and then recalculated on a water-equivalent plastic phantom by Monte Carlo algorithm for patient-specific QA. 2D quantitative dose comparison parameters were calculated, for the computed and measured dose distributions, and tested for statistically significant differences. RESULTS Sensitometric curves showed a different behavior above dose of 5 Gy for EBT2 and EBT3 films; with the use of inhouse marker-dye correction method, the authors obtained values of 2.5% for flatness, 1.5% of symmetry, and a field width of 4.8 cm for a 5×5 cm2 reference field. Compared with TLD and selecting a 5% dose tolerance, the percentage of points with ICRU index below 1 was 100% for EBT2 and 83% for EBT3. Patients analysis revealed statistically significant differences (p<0.05) between EBT2 and EBT3 in the percentage of points with gamma values<1 (p=0.009 and p=0.016); the percent difference as well as the mean difference between calculated and measured isodoses (20% and 80%) were found not to be significant (p=0.074, p=0.185, and p=0.57). CONCLUSIONS Excellent performances in terms of dose homogeneity were obtained using a new blue channel method for marker-dye correction on both EBT2 and EBT3 GafchromicTM films. In comparison with TLD, the passing rates for the EBT2 film were higher than for EBT3; a good agreement with estimated data by Monte Carlo algorithm was found for both films, with some statistically significant differences again in favor of EBT2. These results suggest that the use of GafchromicTM EBT2 and EBT3 films is appropriate for dose verification measurements in VMAT stereotactic radiosurgery; taking into account the uncertainty associated with Gafchromic film dosimetry, the use of adequate action levels is strongly advised, in particular, for EBT3.

Changes in breast cancer risk associated with different volumes, doses, and techniques in female Hodgkin lymphoma patients treated with supra-diaphragmatic radiation therapy

PURPOSE The contribution of thoracic radiation in increasing secondary breast cancer (BC) risk in female Hodgkin lymphoma patients is well known, and recent changes in radiation therapy volumes, doses and techniques are supposed to minimize it. In this study, we compared different radiation therapy solutions in terms of secondary BC induction risk with the aim of selecting which could be considered the most protective. METHODS AND MATERIALS In 10 female patients under 30 years old we estimated breast cancer risk for different combined treatment solutions (involved field vs involved nodal radiation therapy [IFRT vs INRT], 30 Gy vs 20 Gy, 3-dimensional conformal radiation therapy vs volumetric modulated arc therapy [3DCRT vs VMAT]). The organ equivalent dose (OED) method was used for dose calculation, as OED is directly related to the excess risk. Estimated OED mean values for all options in all patients were then analyzed and compared. RESULTS INRT was significantly associated with a lower OED, regardless of total dose and technique (0.43 vs 1.15, P < .0001). The relative OED reduction from IFRT to INRT was approximately 60%. The dose of 20 Gy resulted in a significant reduction of OED, approximately 25% (0.68 vs 0.9, P < .01). VMAT did not show significantly higher OED when compared with 3DCRT (0.84 vs 0.74, P = .15). The combination of INRT and 20 Gy lead to a decrease in OED of approximately 70% if compared with IFRT 30 Gy. CONCLUSIONS The INRT approach substantially reduces OED, independent of dose and technique; the dose reduction from 30 Gy to 20 Gy also has a significant impact, and as expected INRT-20 Gy resulted to be the solution at lowest risk. No differences were observed when comparing different techniques (3DCRT vs VMAT). The combination of these innovative approaches might lead to a substantial reduction in secondary breast cancer risk in this patient population.

Performance of commercially available deformable image registration platforms for contour propagation using patient‐based computational phantoms: A multi‐institutional study

PURPOSE To investigate the performance of various algorithms for deformable image registration (DIR) to propagate regions of interest (ROIs) using multiple commercial platforms. METHODS AND MATERIALS Thirteen institutions participated in the study with six commercial platforms: RayStation (RaySearch Laboratories, Stockholm, Sweden), MIM (Cleveland, OH, USA), VelocityAI and Smart Adapt (Varian Medical Systems, Palo Alto, CA, USA), Mirada XD (Mirada Medical Ltd, Oxford, UK), and ABAS (Elekta AB, Stockholm, Sweden). The DIR algorithms were tested on synthetic images generated with the ImSimQA package (Oncology Systems Limited, Shrewsbury, UK) by applying two specific Deformation Vector Fields (DVF) to real patient data-sets. Head-and-neck (HN), thorax, and pelvis sites were included. The accuracy of the algorithms was assessed by comparing the DIR-mapped ROIs from each center with those of reference, using the Dice Similarity Coefficient (DSC) and Mean Distance to Conformity (MDC) metrics. Statistical inference on validation results was carried out in order to identify the prognostic factors of DIR performances. RESULTS DVF intensity, anatomic site and participating center were significant prognostic factors of DIR performances. Sub-voxel accuracy was obtained in the HN by all algorithms. Large errors, with MDC ranging up to 6 mm, were observed in low-contrast regions that underwent significant deformation, such as in the pelvis, or large DVF with strong contrast, such as the clinical tumor volume (CTV) in the lung. Under these conditions, the hybrid DIR algorithms performed significantly better than the free-form intensity based algorithms and resulted robust against intercenter variability. CONCLUSIONS The performances of the systems proved to be site specific, depending on the DVF type and the platforms and the procedures used at the various centers. The pelvis was the most challenging site for most of the algorithms, which failed to achieve sub-voxel accuracy. Improved reproducibility was observed among the centers using the same hybrid registration algorithm.

Interobserver variability in clinical target volume delineation for primary mediastinal B-cell lymphoma

PURPOSE The purpose of this study was to evaluate interobserver variability among radiation oncologists with experience in the field of lymphoma radiation therapy in the delineation of clinical target volume (CTV) in a challenging case of primary mediastinal B-cell lymphoma. METHODS AND MATERIALS Ten experienced radiation oncologists were invited to a 1-day contouring session. The case of a 56-year-old man with primary mediastinal B-cell lymphoma with complete metabolic response after chemotherapy was chosen as the sample for the study. A brief presentation of his clinical history was given, together with guidelines for contouring. The 10 CTVs obtained were then compared in terms of variation in total volume and in craniocaudal, laterolateral, and anteroposterior diameters. The CTV with the best Dice similarity coefficient (DSC) between the union of all 10 CTVs and the individual CTV was considered the reference CTV, and the DSC and the Hausdorff distance (HD) for each volume compared with the reference CTV were then calculated. RESULTS A significant variability was found in total volume (mean, 498.3 cm(3); range, 181.8-1003 cm(3)) and craniocaudal (median, 144.7 mm; range, 80.6-159 mm), laterolateral (median, 133.5 mm; range, 83.7-149.5 mm), and anteroposterior diameters (median, 136.2 mm; range, 84-150.5 mm). Analysis of the DSC and the HD showed a mean DSC of 0.53 (range, 0.31-0.74) and a mean HD of 6.4 cm (range, 1.8-14.8 cm). CONCLUSIONS Results of this study strongly indicate the need to develop and share appropriate contouring guidelines among experts and suggest the promotion of specific educational activities to improve radiation therapy quality in both clinical trials and routine clinical practice.

Reducing inter- and intra-planner variability in radiotherapy plan output with a commercial knowledge-based planning solution

PURPOSE This study measured to which extent RapidPlan can drive a reduction of the human-caused variability in prostate cancer treatment planning. METHODS Seventy clinical prostate plans were used to train a RapidPlan model. Seven planners, with different levels of planning experience, were asked to plan a VMAT treatment for fifteen prostate cancer patients with and without RapidPlan assistance. The plans were compared on the basis of target coverage, conformance and OAR sparing. Inter-planner and intra-planner variability were assessed on the basis of the Plan Quality Metric formalism. Differences in mean values and InterQuartile Ranges between patients and operators were assessed. RESULTS RapidPlan-assisted plans matched manual planning in terms of target coverage, homogeneity, conformance and bladder sparing but outperformed it for rectum and femoral heads sparing. 8 out of 15 patients showed a statistically significant increase in overall quality. Inter-planner variability is reduced in RapidPlan-assisted planning for rectum and femoral heads while bladder variability was constant. The inter-planner variability of the overall plan quality, IQR of PQM%, was approximately halved for all patients. RapidPlan assistance induced a larger increase in plan quality for less experienced planners. At the same time, a reduction in intra-planner variability is measured with a significant overall reduction. CONCLUSIONS The assistance of RapidPlan during the optimization of treatments for prostate cancer induces a significant increase of plan quality and a contextual reduction of plan variability. RapidPlan is proven to be a valuable tool to leverage the planning skills of less experienced planners ensuring a better homogeneity of treatment plan quality.

Efficiently train and validate a RapidPlan model through APQM scoring

PURPOSE The aim of this study was to propose and validate an intuitive method for training and to validate knowledge-based planning (KBP) systems based on a patient-specific plan quality scoring. METHODS A sample of 80 clinical plans of prostate cancer patients were ranked on the basis of the Adjusted Plan Quality Metric (APQM%). This quality metric was computed normalizing the Plan Quality Metric (PQM%) score to the best possible OAR sparing estimated by the Feasibility DVH (FDVH) algorithm. Two different plan libraries were created, purging all the plans below the first quartile or below the median the APQM% distribution. These libraries were used to populate and train two RapidPlan models: respectively, the APMQ25% and the APMQ50% models. No further refinements or actions were undertaken on these two models. Their performances were benchmarked against another two RapidPlan models. An Uncleaned model, which was populated and trained with the initial sample of 80 plans, and a Cleaned model, obtained through the standard iterative cleaning and refinement process suggested by the vendor and in literature. The outcomes of a planning test based on 20 patients within the training library (closed loop) and 20 patients outside of the training library (open-loop) were compared through various DVH metrics and the PQM% score. RESULTS The selection through APQM% thresholding roughly preserves the geometric variety of the Cleaned model; only the APMQ50% model showed a modest broadness reduction. The models generated through APQM% thresholding showed target coverage and OARs sparing equal or superior to the Uncleaned and Cleaned models both for the closed- and the open-loop tests. No significant differences were found between the four models. PQM% analysis ranked the overall plan quality as: 86.5 ± 6.5% APQM50% , 83.1 ± 5.9% APQM25% , 80.39 ± 10.6% Cleaned and 79.4 ± 8.5% Uncleaned in the closed-loop test; 84.9 ± 7.6% APQM50% , 82.6 ± 7.9% APQM25% , 80.39 ± 10.6% Cleaned and 79.4 ± 8.5% Uncleaned in the open-loop test. CONCLUSIONS Forward feeding a RapidPlan model through a thresholding selection based on APQM% is proven to produce equal or better results than a model based on a manually and iteratively refined population. A tighter APQM% threshold turns approximately into a higher average quality of plans generated with RapidPlan. A trade-off must be found between the mean quality of the KBP library and its numerosity. The proposed KBP feeding method helps the KBP user, because it makes the model refinement more intuitive and less time consuming.

Evaluation of dose recalculation vs dose deformation in a commercial platform for deformable image registration with a computational phantom

Deformable image registration (DIR) is an important tool for mapping both dose and contours of a new set of planning images when recurrent, that is, adaptive radiotherapy, or further treatment, that is, re-treatment, is required. The aim of this study was to evaluate the need for plan recalculation in deformed anatomies and to develop a reliable workflow for validating the DIR algorithm to be applied to dose warping such as dose accumulation (DA) for adaptive radiation therapy, and dose summation (DS) in the case of re-treatment. A set of 3 computational phantoms was developed to validate the application of B-Spline-based registrations for dose mapping among the various computed tomography image data sets. Two different versions were defined for each phantom to simulate clinical needs: adaptive radiotherapy and re-treatment; a DIR was performed to obtain a displacement vector field (DVF) for dose applications. Comparison of calculated and deformed doses was carried out by means of known markers inside the virtual phantoms. The differences were evaluated using a 3% dose index as acceptance criteria. A paired Wilcoxon signed-rank test was carried out to test the statistical significance of differences within the markers. Significant differences were only observed for the deformed dose in the DA test; no significant differences were observed for recalculated dose values in the DA and DS tests. The dose index is in accordance with these results. The warping dose process obtained by registering various sets of images was validated; a recalculation approach seems to be more accurate for DA purposes and image-guided adaptive radiation therapy (IGART) applications.

TU-H-CAMPUS-JeP1-04: Deformable Image Registration Performances in Pelvis Patients: Impact of CBCT Image Quality

PURPOSE To investigate the accuracy and robustness, against image noise and artifacts (typical of CBCT images), of a commercial algorithm for deformable image registration (DIR), to propagate regions of interest (ROIs) in computational phantoms based on real prostate patient images. METHODS The Anaconda DIR algorithm, implemented in RayStation was tested. Two specific Deformation Vector Fields (DVFs) were applied to the reference data set (CTref) using the ImSimQA software, obtaining two deformed CTs. For each dataset twenty-four different level of noise and/or capping artifacts were applied to simulate CBCT images. DIR was performed between CTref and each deformed CTs and CBCTs. In order to investigate the relationship between image quality parameters and the DIR results (expressed by a logit transform of the Dice Index) a bilinear regression was defined. RESULTS More than 550 DIR-mapped ROIs were analyzed. The Statistical analysis states that deformation strenght and artifacts were significant prognostic factors of DIR performances, while noise appeared to have a minor role in DIR process as implemented in RayStation as expected by the image similarity metric built in the registration algorithm. Capping artifacts reveals a determinant role for the accuracy of DIR results. Two optimal values for capping artifacts were found to obtain acceptable DIR results (DICE> 075/ 0.85). Various clinical CBCT acquisition protocol were reported to evaluate the significance of the study. CONCLUSION This work illustrates the impact of image quality on DIR performance. Clinical issues like Adaptive Radiation Therapy (ART) and Dose Accumulation need accurate and robust DIR software. The RayStation DIR algorithm resulted robust against noise, but sensitive to image artifacts. This result highlights the need of robustness quality assurance against image noise and artifacts in the commissioning of a DIR commercial system and underlines the importance to adopt optimized protocols for CBCT image acquisitions in ART clinical implementation.

WE‐AB‐BRA‐08: Results of a Multi‐Institutional Study for the Evaluation of Deformable Image Registration Algorithms for Structure Delineation Via Computational Phantoms

Purpose: To investigate the accuracy of various algorithms for deformable image registration (DIR), to propagate regions of interest (ROIs) in computational phantoms based on patient images using different commercial systems. This work is part of an Italian multi-institutional study to test on common datasets the accuracy, reproducibility and safety of DIR applications in Adaptive Radiotherapy. Methods: Eleven institutions with three available commercial solutions provided data to assess the agreement of DIR-propagated ROIs with automatically drown ROIs considered as ground-truth for the comparison. The DIR algorithms were tested on real patient data from three different anatomical districts: head and neck, thorax and pelvis. For every dataset two specific Deformation Vector Fields (DVFs) provided by ImSimQA software were applied to the reference data set. Three different commercial software were used in this study: RayStation, Velocity and Mirada. The DIR-mapped ROIs were then compared with the reference ROIs using the Jaccard Conformity Index (JCI). Results: More than 600 DIR-mapped ROIs were analyzed. Putting together all JCI data of all institutions for the first DVF, the mean JCI was 0.87 ± 0.7 (1 SD) while for the second DVF JCI was 0.8 ± 0.13 (1 SD). Several considerations on different structures are available from collected data: the standard deviation among different institutions on specific structure raise as the larger is the applied DVF. The higher value is 10% for bladder. Conclusion: Although the complexity of deformation of human body is very difficult to model, this work illustrates some clinical scenarios with well-known DVFs provided by specific software. CI parameter gives the inter-user variability and may put in evidence the need of improving the working protocol in order to reduce the inter-institution JCI variability.