Incorporating plan complexity into the statistical process control of volumetric modulated arc therapy pre-treatment verifications.

BACKGROUND: Statistical process control (SPC) is a powerful statistical tool for process monitoring that has been highly recommended in healthcare applications, including radiation therapy quality assurance (QA). The AAPM TG-218 report described the clinical implementation of SPC for Volumetric Modulated Arc Therapy (VMAT) pre-treatment verifications, pointing out the need to adjust tolerance limits based on plan complexity. However, the quantification of plan complexity and its integration into SPC remains an unresolved challenge. PURPOSE: The primary aim of this study is to investigate the incorporation of plan complexity into the SPC framework for VMAT pre-treatment verifications. The study explores and evaluates various strategies for this incorporation, discussing their merits and limitations, and provides recommendations for clinical application. METHODS: A retrospective analysis was conducted on 309 VMAT plans from diverse anatomical sites using the PTW OCTAVIUS 4D device for QA measurements. Gamma Passing Rates (GPR) were obtained, and lower control limits were computed using both the conventional Shewhart method and three heuristic methods (scaled weighted variance, weighted standard deviations, and skewness correction) to accommodate non-normal data distributions. The 'Identify-Eliminate-Recalculate' method was employed for robust analysis. Eight complexity metrics were analyzed and two distinct strategies for incorporating plan complexity into SPC were assessed. The first strategy focused on establishing control limits for different treatment sites, while the second was based on the determination of control limits as a function of individual plan complexity. The study extensively examines the correlation between control limits and plan complexity and assesses the impact of complexity metrics on the control process. RESULTS: The control limits established using SPC were strongly influenced by the complexity of treatment plans. In the first strategy, a clear correlation was found between control limits and average plan complexity for each site. The second approach derived control limits based on individual plan complexity metrics, enabling tailored tolerance limits. In both strategies, tolerance limits inversely correlated with plan complexity, resulting in all highly complex plans being classified as in control. In contrast, when plans were collectively analyzed without considering complexity, all the out-of-control plans were highly complex. CONCLUSIONS: Incorporating plan complexity into SPC for VMAT verifications requires meticulous and comprehensive analysis. To ensure overall process control, we advocate for stringent control and minimization of plan complexity during treatment planning, especially when control limits are adjusted based on plan complexity.

Impact of inter-observer variability on first axillary level dosimetry in breast cancer radiotherapy: An AIRO multi-institutional study.

This study quantified the incidental dose to the first axillary level (L1) in locoregional treatment plan for breast cancer. Eighteen radiotherapy centres contoured L1-L4 on three different patients (P1,2,3), created the L2-L4 planning target volume (single centre planning target volume, SC-PTV) and elaborated a locoregional treatment plan. The L2-L4 gold standard clinical target volume (CTV) along with the gold standard L1 contour (GS-L1) were created by an expert consensus. The SC-PTV was then replaced by the GS-PTV and the incidental dose to GS-L1 was measured. Dosimetric data were analysed with Kruskal-Wallis test. Plans were intensity modulated radiotherapy (IMRT)-based. P3 with 90° arm setup had statistically significant higher L1 dose across the board than P1 and P2, with the mean dose (Dmean) reaching clinical significance. Dmean of P1 and P2 was consistent with the literature (77.4% and 74.7%, respectively). The incidental dose depended mostly on L1 proportion included in the breast fields, underlining the importance of the setup, even in case of IMRT.

Patient specific quality assurance in SBRT: a systematic review of measurement-based methods.

This topical review focuses on Patient-Specific Quality Assurance (PSQA) approaches to stereotactic body radiation therapy (SBRT). SBRT requires stricter accuracy than standard radiation therapy due to the high dose per fraction and the limited number of fractions. The review considered various PSQA methods reported in 36 articles between 01/2010 and 07/2022 for SBRT treatment. In particular comparison among devices and devices designed for SBRT, sensitivity and resolution, verification methodology, gamma analysis were specifically considered. The review identified a list of essential data needed to reproduce the results in other clinics, highlighted the partial miss of data reported in scientific papers, and formulated recommendations for successful implementation of a PSQA protocol.

Immunogenicity after two and three doses of mRNA vaccine in patients with cancer treated with exclusive radiotherapy.

BACKGROUND AND PURPOSE: Data on immunoresponse after SARS-CoV-2 vaccines for patients treated with exclusive radiotherapy (RT) are scarce. Since RT may affect the immune system, we conducted the MORA trial (Antibody response and cell-mediated immunity of MOderna mRNA-1273 vaccine in patients treated with RAdiotherapy). MATERIALS AND METHODS: Data regarding humoral and cellular immune response of patients treated with RT were prospectively collected after the second and third dose of mRNA vaccines. RESULTS: Ninety-two patients were enrolled. With a median of 147 days after the second dose, the median SARS-CoV-2 IgG titer was 300 BAU/mL: six patients were seronegative (Spike IgG titer ≤ 40 BAU/mL), whereas 24, 46 and 16 were poor responders (Spike IgG titer:41-200 BAU/mL), responders (Spike IgG titer:201-800 BAU/mL) and ultraresponders (Spike IgG titer > 800 BAU/mL), respectively. Among seronegative patients, two patients were negative also for cell mediated response, as tested with IFN-γ release Assay (IGRA) test. With a median of 85 days after the third dose, the median SARS-CoV-2 IgG titer was 1632 BAU/mL in 81 patients: only two patients were seronegative, whereas 16 and 63 patients were responders and ultraresponders, respectively. Among the 2 persistently seronegative patients, IGRA test was negative in one who had previously received anti-CD20 therapy. Documented paucisymptomatic (n = 3) or asymptomatic (n = 4) infection occurred after the third dose, during the Omicron wave. CONCLUSION: In patients treated with exclusive RT, even during the Omicron breakthrough, robust humoral response and clinical protection from severe SARS-CoV-2 disease were achievable with three doses of mRNA vaccine.

Universal evaluation of MLC models in treatment planning systems based on a common set of dynamic tests.

PURPOSE: To demonstrate the feasibility of characterising MLCs and MLC models implemented in TPSs using a common set of dynamic beams. MATERIALS AND METHODS: A set of tests containing synchronous (SG) and asynchronous sweeping gaps (aSG) was distributed among twenty-five participating centres. Doses were measured with a Farmer-type ion chamber and computed in TPSs, which provided a dosimetric characterisation of the leaf tip, tongue-and-groove, and MLC transmission of each MLC, as well as an assessment of the MLC model in each TPS. Five MLC types and four TPSs were evaluated, covering the most frequent combinations used in radiotherapy departments. RESULTS: Measured differences within each MLC type were minimal, while large differences were found between MLC models implemented in clinical TPSs. This resulted in some concerning discrepancies, especially for the HD120 and Agility MLCs, for which differences between measured and calculated doses for some MLC-TPS combinations exceeded 10%. These large differences were particularly evident for small gap sizes (5 and 10 mm), as well as for larger gaps in the presence of tongue-and-groove effects. A much better agreement was found for the Millennium120 and Halcyon MLCs, differences being within ± 5% and ± 2.5%, respectively. CONCLUSIONS: The feasibility of using a common set of tests to assess MLC models in TPSs was demonstrated. Measurements within MLC types were very similar, but TPS dose calculations showed large variations. Standardisation of the MLC configuration in TPSs is necessary. The proposed procedure can be readily applied in radiotherapy departments and can be a valuable tool in IMRT and credentialing audits.

The role of EPID in vivo dosimetry in the risk management of stereotactic lung treatments.

BACKGROUND AND OBJECTIVE: In this work we report our experience with the use of in vivo dosimetry (IVD) in the risk management of stereotactic lung treatments. METHODS: A commercial software based on the electronic portal imaging device (EPID) signal was used to reconstruct the actual planning target volume (PTV) dose of stereotactic lung treatments. The study was designed in two phases: i) in the observational phase, the IVD results of 41 consecutive patients were reviewed and out-of-tolerance cases were studied for root cause analysis; ii) in the active phase, the IVD results of 52 patients were analyzed and corrective actions were taken when needed. Moreover, proactive preventions were further introduced to reduce the risk of future failures. The error occurrence rate was analyzed to evaluate the effectiveness of proactive actions. RESULTS: A total of 330 fractions were analyzed. In the first phase, 13 errors were identified. In the active phase, 12 errors were detected, 5 of which needed corrective actions; in 4 patients the actions taken corrected the error. Several preventions and barriers were introduced to reduce the risk of future failures: the planning checklist was updated, the procedure for vacuum pillows was improved, and use of the respiratory compression belt was optimized. A decrease in the failure rate was observed, showing the effectiveness of procedural adjustment. CONCLUSION: The use of IVD allowed the quality of lung stereotactic body radiation therapy (SBRT) treatments to be improved. Patient-specific and procedural corrective actions were successfully taken as part of risk management, leading to an overall improvement in the dosimetric accuracy.

Applications of artificial intelligence in stereotactic body radiation therapy.

This topical review focuses on the applications of artificial intelligence (AI) tools to stereotactic body radiation therapy (SBRT). The high dose per fraction and the limited number of fractions in SBRT require stricter accuracy than standard radiation therapy. The intent of this review is to describe the development and evaluate the possible benefit of AI tools integration into the radiation oncology workflow for SBRT automation. The selected papers were subdivided into four sections, representative of the whole radiotherapy process: 'AI in SBRT target and organs at risk contouring', 'AI in SBRT planning', 'AI during the SBRT delivery', and 'AI for outcome prediction after SBRT'. Each section summarises the challenges, as well as limits and needs for improvement to achieve better integration of AI tools in the clinical workflow.

The influence of basic plan parameters on calculated small field output factors - A multicenter study.

PURPOSE: The influence of basic plan parameters such as slice thickness, grid resolution, algorithm type and field size on calculated small field output factors (OFs) was evaluated in a multicentric study. METHODS AND MATERIALS: Three computational homogeneous water phantoms with slice thicknesses (ST) 1, 2 and 3 mm were shared among twenty-one centers to calculate OFs for 1x1, 2x2 and 3x3 cm2 field sizes (FSs) (normalized to 10x10 cm2 FS), with their own treatment planning system (TPS) and the energy clinically used for stereotactic body radiation therapy delivery. OFs were calculated for each combination of grid resolution (GR) (1, 2 and 3 mm) and ST and finally compared with the OFs measured for the TPS commissioning. A multivariate analysis was performed to test the effect of basic plan parameters on calculated OFs. RESULTS: A total of 509 data points were collected. Calculated OFs are slightly higher than measured ones. The multivariate analysis showed that Center, GR, algorithm type, and FS are predictive variables of the difference between calculated and measured OFs (p < 0.001). As FS decreases, the spread in the difference between calculated and measured OFs became larger when increasing the GR. Monte Carlo and Analytical Anisotropic Algorithms, presented a dependence on GR (p < 0.01), while Collapsed Cone Convolution and Acuros did not. The effect of the ST was found to be negligible. CONCLUSIONS: Modern TPSs slightly overestimate the calculated small field OFs compared with measured ones. Grid resolution, algorithm, center number and field size influence the calculation of small field OFs.

Artificial intelligence applications in medical imaging: A review of the medical physics research in Italy.

PURPOSE: To perform a systematic review on the research on the application of artificial intelligence (AI) to imaging published in Italy and identify its fields of application, methods and results. MATERIALS AND METHODS: A Pubmed search was conducted using terms Artificial Intelligence, Machine Learning, Deep learning, imaging, and Italy as affiliation, excluding reviews and papers outside time interval 2015-2020. In a second phase, participants of the working group AI4MP on Artificial Intelligence of the Italian Association of Physics in Medicine (AIFM) searched for papers on AI in imaging. RESULTS: The Pubmed search produced 794 results. 168 studies were selected, of which 122 were from Pubmed search and 46 from the working group. The most used imaging modality was MRI (44%) followed by CT(12%) ad radiography/mammography (11%). The most common clinical indication were neurological diseases (29%) and diagnosis of cancer (25%). Classification was the most common task for AI (57%) followed by segmentation (16%). 65% of studies used machine learning and 35% used deep learning. We observed a rapid increase of research in Italy on artificial intelligence in the last 5 years, peaking at 155% from 2018 to 2019. CONCLUSIONS: We are witnessing an unprecedented interest in AI applied to imaging in Italy, in a diversity of fields and imaging techniques. Further initiatives are needed to build common frameworks and databases, collaborations among different types of institutions, and guidelines for research on AI.

Geometric contour variation in clinical target volume of axillary lymph nodes in breast cancer radiotherapy: an AIRO multi-institutional study.

OBJECTIVES: To determine interobserver variability in axillary nodal contouring in breast cancer (BC) radiotherapy (RT) by comparing the clinical target volume of participating single centres (SC-CTV) with a gold-standard CTV (GS-CTV). METHODS: The GS-CTV of three patients (P1, P2, P3) with increasing complexity was created in DICOM format from the median contour of axillary CTVs drawn by BC experts, validated using the simultaneous truth and performance-level estimation and peer-reviewed. GS-CTVs were compared with the correspondent SC-CTVs drawn by radiation oncologists, using validated metrics and a total score (TS) integrating all of them. RESULTS: Eighteen RT centres participated in the study. Comparative analyses revealed that, on average, the SC-CTVs were smaller than GS-CTV for P1 and P2 (by -29.25% and -27.83%, respectively) and larger for P3 (by +12.53%). The mean Jaccard index was greater for P1 and P2 compared to P3, but the overlap extent value was around 0.50 or less. Regarding nodal levels, L4 showed the highest concordance with the GS. In the intra-patient comparison, L2 and L3 achieved lower TS than L4. Nodal levels showed discrepancy with GS, which was not statistically significant for P1, and negligible for P2, while P3 had the worst agreement. DICE similarity coefficient did not exceed the minimum threshold for agreement of 0.70 in all the measurements. CONCLUSIONS: Substantial differences were observed between SC- and GS-CTV, especially for P3 with altered arm setup. L2 and L3 were the most critical levels. The study highlighted these key points to address. ADVANCES IN KNOWLEDGE: The present study compares, by means of validated geometric indexes, manual segmentations of axillary lymph nodes in breast cancer from different observers and different institutions made on radiotherapy planning CT images. Assessing such variability is of paramount importance, as geometric uncertainties might lead to incorrect dosimetry and compromise oncological outcome.

Lean Thinking to manage a national working group on physics aspects of Stereotactic Body Radiation Therapy.

PURPOSE: To report how the adoption of a Lean Thinking mindset in the management of a national working group (WG) on the physics of stereotactic body radiation therapy (SBRT) contributed to achieve SBRT standardization objectives. METHODS: Vision for the WG has been established as fragmentation reduction and process harmonization enhancement in SBRT for Italian centers. Two main research themes of the technical aspects of SBRT emerged as areas with major standardization improvement needs, small field dosimetry and SBRT planning comparisons, to be investigated through multi-institutional studies. The management of the WG leveraged on the Lean concept of fostering self-organization in a non-hierarchical environment. Four progressive involvement levels were defined for each study. No specific "scientific" pre-experience was required to propose and coordinate a project, just requiring a voluntary commitment. People engagement was measured in terms of number of published articles. The standardization goals have been conducted through a simplified "5S" (Sort, Set in Order, Shine, Standardize, and Sustain) methodology, first considering a phase of awareness (the first three "S"), then identifying and implementing standardization actions (the last two "S"). RESULTS: Since the beginning, 157 medical physicists joined the AIFM/SBRT-WG. Twenty-four papers/reviews/letters have been published in the period 2014-2019 on major radiation oncology journals, authored by >100 physicists (>50% working in small hospitals). Six over 12 first authors worked in peripheral/small hospitals, with no prior publication as first author. These studies contributed to the awareness and standardization phases for both small-field dosimetry and planning. In particular, errors in small-field measurements in 8% of centers were detected thanks to a generalized output factor curve in function of the effective field size created by averaging data available from different Linacs. Furthermore, planner's experience in SBRT was correlated with dosimetric parameters in the awareness phase; while sharing median dose volume histograms (DVHs) reduced variability among centers while keeping the same level of plan complexity. Finally, all the dosimetric parameters statistically significant to the planner experience during the awareness phase, were no longer significantly different in the standardization phase. CONCLUSIONS: The experience of our SBRT-WG has shown how a Lean Thinking mindset could foster the SBRT procedure standardization and spread the physics of SBRT knowledge, enhancing personal growth. Our expectation is to inspire other scientific societies that have to deal with fragmented contexts or pursue processes harmonization through Lean principles.

The influence of small field output factors simulated uncertainties on the calculated dose in VMAT plans for brain metastases: a multicentre study.

OBJECTIVES: This multicentric study was carried out to investigate the impact of small field output factors (OFs) inaccuracies on the calculated dose in volumetric arctherapy (VMAT) radiosurgery brain plans. METHODS: Nine centres, realised the same five VMAT plans with common planning rules and their specific clinical equipment Linac/treatment planning system commissioned with their OFs measured values (OFbaseline). In order to simulate OFs errors, two new OFs sets were generated for each centre by changing only the OFs values of the smallest field sizes (from 3.2 × 3.2 cm2 to 1 × 1 cm2) with well-defined amounts (positive and negative). Consequently, two virtual machines for each centre were recommissioned using the new OFs and the percentage dose differences ΔD (%) between the baseline plans and the same plans recalculated using the incremented (OFup) and decremented (OFdown) values were evaluated. The ΔD (%) were analysed in terms of planning target volume (PTV) coverage and organs at risk (OARs) sparing at selected dose/volume points. RESULTS: The plans recalculated with OFdown sets resulted in higher variation of doses than baseline within 1.6 and 3.4% to PTVs and OARs respectively; while the plans with OFup sets resulted in lower variation within 1.3% to both PTVs and OARs. Our analysis highlights that OFs variations affect calculated dose depending on the algorithm and on the delivery mode (field jaw/MLC-defined). The Monte Carlo (MC) algorithm resulted significantly more sensitive to OFs variations than all of the other algorithms. CONCLUSION: The aim of our study was to evaluate how small fields OFs inaccuracies can affect the dose calculation in VMAT brain radiosurgery treatments plans. It was observed that simulated OFs errors, return dosimetric calculation accuracies within the 3% between concurrent plans analysed in terms of percentage dose differences at selected dose/volume points of the PTV coverage and OARs sparing. ADVANCES IN KNOWLEDGE: First multicentre study involving different Planning/Linacs about undetectable errors in commissioning output factor for small fields.

Clinical implementation of 3D in vivo dosimetry for abdominal and pelvic stereotactic treatments.

PURPOSE: To analyze results from three years of in vivo transit EPID dosimetry of abdominal and pelvic stereotactic radiotherapy and to establish tolerance levels for routine clinical use. MATERIAL: 80 stereotactic VMAT treatments (152 fractions) targeting the abdomen or pelvis were analyzed. In vivo 3D doses were reconstructed with an EPID commercial algorithm. Gamma Agreement Index (GAI) and DVH differences in Planning Target Volume (PTV) and Clinical Target Volume (CTV) were evaluated. Initial tolerance level was set to GAI > 85% in PTV. Fractions Over Tolerance Level (OTL) were deemed to be due to set-up errors, incorrect use of immobilization devices, 4D errors, transit EPID algorithm errors and unknown/unidentified errors. Statistical Process Control (SPC) was applied to determine local tolerance levels. RESULTS: Average GAI were (82.7 ± 20.9) % in PTV and (72.9 ± 29.7) % in CTV. 37.8% of fractions resulted OTL and were classified as: set-up errors (3.3%), incorrect use of immobilization devices (2.1%), 4D errors (2.1%), EPID transit algorithm errors (17.1%). OTL causes for the remaining 13.2% of fractions were not identified. The differences between PTV and CTV measured in vivo and calculated mean dose (average difference ± standard deviation) were (-3.3% ± 3.2%) and (-2.3% ± 3.0%). When tolerance levels based on SPC to PTV mean dose differences were applied, the percentage of OTL decreased to 7% and no EPID algorithm error occurred. One error was not identified. CONCLUSIONS: The application of local tolerance levels to EPID in vivo dosimetry proved to be useful for detecting extra-lung SBRT treatment errors.

Estimating dose delivery accuracy in stereotactic body radiation therapy: A review of in-vivo measurement methods.

Stereotactic body radiation therapy (SBRT) has been recognized as a standard treatment option for many anatomical sites. Sophisticated radiation therapy techniques have been developed for carrying out these treatments and new quality assurance (QA) programs are therefore required to guarantee high geometrical and dosimetric accuracy. This paper focuses on recent advances on in-vivo measurements methods (IVM) for SBRT treatment. More specifically, all of the online QA methods for estimating the effective dose delivered to patients were compared. Determining the optimal IVM for performing SBRT treatments would reduce the risk of errors that could jeopardize treatment outcome. A total of 89 papers were included. The papers were subdivided into the following topics: point dosimeters (PD), transmission detectors (TD), log file analysis (LFA), electronic portal imaging device dosimetry (EPID), dose accumulation methods (DAM). The detectability capability of the main IVM detectors/devices were evaluated. All of the systems have some limitations: PD has no spatial data, EPID has limited sensitivity towards set-up errors and intra-fraction motion in some anatomical sites, TD is insensitive towards patient related errors, LFA is not an independent measure, DAMs are not always based on measures. In order to minimize errors in SBRT dose delivery, we recommend using synergic combinations of two or more of the systems described in our review: on-line tumor position and patient information should be combined with MLC position and linac output detection accuracy. In this way the effects of SBRT dose delivery errors will be reduced.

Dosimetric Multicenter Planning Comparison Studies for Stereotactic Body Radiation Therapy: Methodology and Future Perspectives.

In this review a summary of the published literature pertaining to the stereotactic body radiation therapy multiplanning comparison, data sharing strategies, and implementation of benchmark planning cases to improve the skills and knowledge of the participating centers was investigated. A total of 30 full-text articles were included. The studies were subdivided in 3 categories: multiplanning studies on dosimetric variability, planning harmonization before clinical trials, and technical and methodologic studies. The methodology used in the studies were critically analyzed to find common and original elements with the pros and cons. Multicenter planning studies have played a key role in improving treatment plan harmonization, treatment plan compliance, and even clinical practices. This review has highlighted that some fundamental steps should be taken to transform a simple treatment planning comparison study into a potential credentialing method for stereotactic body radiation therapy accreditation. In particular, prescription and general requirements should always be well defined; data analysis should be performed with independent dose volume histogram or dose calculations; quality score indices should be constructed; feedback and correction strategies should be provided; and a simple web-based collaboration platform should be used. The results reported clearly showed that a crowd-based replanning approach is a viable method for achieving harmonization and standardization of treatment planning among centers using different technologies.

Multi-site evaluation of the Razor stereotactic diode for CyberKnife small field relative dosimetry.

PURPOSE: The aims of this study were: (i) to validate in a multi-site context the suitability of the IBA Razor silicon diode detector for CyberKnife relative dosimetry. (ii) to fit the multi-center experimental data into a function relating the field output factors to the effective field size (EFS). METHODS AND MATERIALS: Ratio of detector readings in clinical and reference field (OFdet) and beam profiles were acquired on five CyberKnife units for fixed collimator diameters (range 5-60 mm), using both Razor and PTW 60017 diodes. Measured OFdet were corrected using published MonteCarlo correction factors to get field output factors ΩQclin,Qmsrfclin,fmsr. Profiles were analyzed in terms of penumbra and EFS. ΩQclin,Qmsrfclin,fmsr obtained in four centers were fitted as a function of EFS, while the data of the 5th center were used to validate the fitting curve. RESULTS: Differences between Razor and PTW60017 ΩQclin,Qmsrfclin,fmsr were within 1.5% over all centers down to 7.5 mm aperture and within 3.5% for the 5 mm diameter. The fit showed a coefficient of determination R2 = 0.997. The mean deviation of measured points from the predictive curve was within 0.5%. Data of the 5th center showed a mean deviation of 0.4% from the curve, with maximum differences within 2.5% for the 7.5 mm aperture. CONCLUSIONS: The results confirmed the suitability of Razor detector for CyberKnife dosimetry by comparison to the PTW 60017 diode which has been well characterized and is in widespread use. The proposed mathematical relation between ΩQclin,Qmsrfclin,fmsr and EFS is a robust predictive model applicable to different CyberKnife systems and detectors.