Radiotherapy Quality Assurance Research Articles

Optimizing the Region for Evaluation of Global Gamma Analysis for Nasopharyngeal Cancer (NPC) Pretreatment IMRT QA by COMPASS: A Retrospective Study.

BackgroundThe global gamma passing rate is the most commonly used metric for patient-specific pretreatment quality assurance in radiation therapy. However, the optimal region for evaluation and specific action limits (ALs) need to be explored. Therefore, this study was carried out to explore the optimal region for evaluation of the global gamma passing rate and define ALs by using the COMPASS software.MethodsA total of 93 intensity-modulated radiation therapy (IMRT) plans for nasopharyngeal cancer (NPC) patients, including 61 original plans and 32 multileaf collimator (MLC) error-introduced test plans, were selected for retrospective analysis. Firstly, the dose distribution was divided into six isodose regions (“≥10%”, “≥20%”, “≥30%”, “≥40%”, “≥50%”, and “≥60%”) based on the prescribed dose and one clinically oriented region for evaluation (“whole”) to perform the three-dimensional (3D) global gamma reanalysis. Meanwhile, the percentage gamma passing rate (%GP), mean gamma index (μGI) based on 3%/2 mm criteria, and percentage dose error (%DE) of the dose–volume histogram (DVH) metrics were recorded by COMPASS application. Secondly, the Pearson’s correlation coefficient was used to analyze the correlation between %GP and %DE and between μGI and %DE in different regions. Additionally, receiver operating characteristic (ROC) methodology was applied to quantify the fraction of patient-specific plans evaluated as “fail” and “pass”. In order to improve the correlation between gamma analysis result and clinical criteria, ROC analysis was carried out in accordance with hybridization analysis criteria (%DE ≤3%, %GP ≥90% and %DE ≤3%, μGI ≤0.6). ROC was performed for two purposes: 1) to analyze the sensitivity and specificity of %GP and μGI in different regions for evaluation and 2) to define the ALs of %GP and μGI in the optimal region for evaluation. Finally, the plans introduced with MLC errors were prepared for validation. Moreover, we also compared the positive rate of ALs of both %GP and μGI in detecting MLC error-introduced plans in different regions.Results1) In our study, a number of DVH-based metrics were found to be correlated with the evaluation parameters. The corresponding number was 4, 2, 1, 1, 1, 1, and 3 in γwhole, γ10%, γ20%, γ30%, γ40%, γ50%, and γ60%, respectively, and 5, 3, 0, 1, 1, 4, and 2 in μGIwhole, μGI10%, μGI20%, μGI30%, μGI40%, μGI50%, and μGI60%, respectively. The results by COMPASS have revealed that the %DE of specific structures has a slightly higher correlation with both %GP and μGI of the “whole” region compared with that of any other region. However, it is a moderate correlation (0.5 ≤ |r| < 0.8). 2) The areas under the curves (AUCs) of γwhole, μGIwhole, μGI40%, μGI50%, and μGI60% were >0.7 based on 3%/2 mm criteria. According to the Youden coefficient, we defined the ALs of γwhole ≥92%, μGIwhole ≤0.36, μGI40% ≤0.43, and μGI60% ≤0.40 based on 3%/2 mm criteria. 3) In the validation, for original plans, the accuracy of ALγwhole, ALγ10%, ALμGIwhole, ALμGI40%, ALμGI50%, and ALμGI60% was 23%, 9.8%, 90%, 80.3%, 9.8%, and 88.5%, respectively. For test plans with systematic MLC errors smaller than 0.8 mm, the positive rates of ALγwhole, ALγ10%, ALμGIwhole, ALμGI40%, ALμGI50%, and ALμGI60% were 25%, 58%, 92%, 92%, 42%, and 100%, respectively. For the plans with systematic MLC errors higher than 0.8 mm, the positive rates of all AL%GP and ALμGI were 100%. From the COMPASS validation results, the accuracy of γwhole, μGIwhole, μGI40%, and μGI60% was higher than that of the conventional γ10% and commonly used μGI50%.ConclusionsCompared with the traditional evaluation region (i.e., the criteria with a threshold of 10% or a threshold of 50%, it was the same with the isodose regions of “≥10%”, “≥50%” based on the prescribed dose in our study), the “whole” region is more meaningful to the clinic by COMPASS. The accuracy of μGIwhole is higher than that of the conventional γ10% and the commonly used μGI50%.

ATNEC: A multicenter, randomized trial investigating whether axillary treatment can be avoided in patients with T1-3N1M0 breast cancer with no residual cancer in the lymph glands after neoadjuvant chemotherapy.

TPS615 Background: Neoadjuvant chemotherapy (NACT) results in eradication of cancer in the axillary nodes in 40-70% of patients. This raises questions about the benefit of further axillary treatment in patients with no evidence of residual nodal disease (ypN0) post NACT. Methods: Design: ATNEC is a phase 3, randomized (1:1), multi-center UK trial, with embedded economic evaluation. Patients with proven axillary node metastases on needle biopsy receive NACT followed by sentinel node biopsy (SNB). If the sentinel nodes have converted to benign (ypN0), ATNEC randomly assigns patients to axillary treatment (nodal radiotherapy [ART] or axillary nodal clearance [ALND]) vs no further axillary treatment. Stratification: Institution, type of surgery (breast conserving surgery vs mastectomy), receptor status (triple negative vs HER2 positive vs ER positive and/or PR positive and HER2 negative).Inclusion criteria: Age ≥ 18; Male or female; T1-3N1M0 breast cancer at diagnosis (pre-NACT); FNA or core biopsy confirmed axillary nodal metastases at presentation; ER and HER2 status evaluated on primary tumor; Received standard NACT as per local guidelines; Imaging of the axilla to assess response to NACT;Dual tracer SNB post-NACT and at least 3 nodes removed (sentinel nodes and marked node): If a single tracer is used, the patient is eligible if the involved node is marked pre-NACT and at least 3 nodes removed (including the marked node), If axillary node sampling is performed following failed localization of sentinel nodes, patient is eligible if at least 3 nodes removed (including the marked node), If node is not marked, or marked node is not removed, patient is eligible if the histology report shows evidence of down-staging with complete pathological response in at least one node and at least 3 nodes removed; No evidence of nodal metastases post NACT (ypN0). Exclusion criteria: Bilateral invasive breast cancer; SNB prior to NACT; Previous ipsilateral axillary nodal surgery; Previous cancer within last 5 years or concomitant malignancy. Aims: To assess whether omitting further axillary treatment (ALND &amp; ART) for patients with early-stage breast cancer and axillary nodal metastases on needle biopsy - who after NACT have no residual nodal disease on SNB (ypN0) - is non-inferior to axillary treatment in terms of disease-free survival, and reduces lymphoedema at 5 years. Statistical methods: All analyses will be carried out on an intention-to-treat basis to preserve randomization, avoid bias from exclusions and preserve statistical power. Radiotherapy Quality Assurance: Study has in-built radiotherapy QA program that will be coordinated by National Radiotherapy Trials QA (RTTQA) group. Target accrual: 1,900 Status: Recruiting. As of 11-Feb-2022, 39 sites open, 87 patients enrolled, 31 randomized. Clinical trial information: NCT04109079.

MO-0219 Quality assurance of preoperative radiotherapy in the CRITICS-II gastric cancer trial

MO-0219 Quality assurance of preoperative radiotherapy in the CRITICS-II gastric cancer trial

OC-0108 Impact of the Radiation Therapy Quality Assurance in the phase II/III CONCORDE trial.

OC-0108 Impact of the Radiation Therapy Quality Assurance in the phase II/III CONCORDE trial.

OC-0609 Radiotherapy quality assurance of the PEACE-1 trial: Initial results of individual case reviews

OC-0609 Radiotherapy quality assurance of the PEACE-1 trial: Initial results of individual case reviews

PO-1071 Radiotherapy Quality Assurance; is volume review all that matters?

PO-1071 Radiotherapy Quality Assurance; is volume review all that matters?

Oligorecurrent nodal prostate cancer: Radiotherapy quality assurance of the randomized PEACE V-STORM phase II trial

PurposeAim of this study is to report the results of the radiotherapy quality assurance program of the PEACE V-STORM randomized phase II trial for pelvic nodal oligorecurrent prostate cancer (PCa). Material and methodsA benchmark case (BC) consisting of a postoperative case with 2 nodal recurrences was used for both stereotactic body radiotherapy (SBRT, 30 Gy/3 fx) and whole pelvic radiotherapy (WPRT, 45 Gy/25 fx + SIB boost to 65 Gy). ResultsBC of 24 centers were analyzed. The overall grading for delineation variation of the 1st BC was rated as ‘UV’ (Unacceptable Variation) or ‘AV’ (Acceptable Variation) for 1 and 7 centers for SBRT (33%), and 3 and 8 centers for WPRT (46%), respectively. An inadequate upper limit of the WPRT CTV (n = 2), a missing delineation of the prostate bed (n = 1), and a missing nodal target volume (n = 1 for SBRT and WPRT) constituted the observed ‘UV’. With the 2nd BC (n = 11), the overall delineation review showed 2 and 8 ‘AV’ for SBRT and WPRT, respectively, with no ‘UV’. For the plan review of the 2nd BC, all treatment plans were per protocol for WPRT. SBRT plans showed variability in dose normalization (Median D90% = 30.1 Gy, range 22.9–33.2 Gy and 30.6 Gy, range 26.8–34.2 Gy for nodes 1 and 2 respectively). ConclusionsUp to 46% of protocol deviations were observed in delineation of WPRT for nodal oligorecurrent PCa, while dosimetric results of SBRT showed the greatest disparities between centers. Repeated BC resulted in an improved adherence to the protocol, translating in an overall acceptable contouring and planning compliance rate among participating centers.

A preclinical radiotherapy dosimetry audit using a realistic 3D printed murine phantom

Preclinical radiation research lacks standardized dosimetry procedures that provide traceability to a primary standard. Consequently, ensuring accuracy and reproducibility between studies is challenging. Using 3D printed murine phantoms we undertook a dosimetry audit of Xstrahl Small Animal Radiation Research Platforms (SARRPs) installed at 7 UK centres. The geometrically realistic phantom accommodated alanine pellets and Gafchromic EBT3 film for simultaneous measurement of the dose delivered and the dose distribution within a 2D plane, respectively. Two irradiation scenarios were developed: (1) a 10 × 10 mm2 static field targeting the pelvis, and (2) a 5 × 5 mm2 90° arc targeting the brain. For static fields, the absolute difference between the planned dose and alanine measurement across all centres was 4.1 ± 4.3% (mean ± standard deviation), with an overall range of − 2.3 to 10.5%. For arc fields, the difference was − 1.2% ± 6.1%, with a range of − 13.1 to 7.7%. EBT3 dose measurements were greater than alanine by 2.0 ± 2.5% and 3.5 ± 6.0% (mean ± standard deviation) for the static and arc fields, respectively. 2D dose distributions showed discrepancies to the planned dose at the field edges. The audit demonstrates that further work on preclinical radiotherapy quality assurance processes is merited.

Impact of a Centralized Database System on Radiation Therapy Quality Assurance Management at a Large Health Care Network: 5 Years’ Experience

PurposeThis study reports the impact of using a centralized database system for major equipment quality assurance (QA) at a large institution. Methods and MaterialsA centralized database system has been implemented for radiation therapy machine QA in our institution at 6 campuses with 11 computed tomographies and 22 linear accelerators (LINACs). The database system was customized to manage monthly and annual computed tomography and LINAC QA. This includes providing the same set of QA procedures across the enterprise, digitally storing all measurement records, and generating trend analyses. Compared with conventional methods (ie, paper forms), the effectiveness of the database system was quantified by changes in the compliance of QA tests and perceptions of staff to the efficiency of data retrieval and analyses. An anonymized questionnaire was provided to physicists enterprise-wide to assess workflow changes. ResultsWith the implementation of the database system, the compliance of QA test completion improved from 80% to >99% for the entire institution. This resonates with the 56% of physicists who found the database system helpful in guiding them through QA, and 25% of physicists found the contrary, and 19% reported no difference (n = 16). Meanwhile, 40% of physicists reported longer times needed to record data using the database system compared with conventional methods, and another 40% suggested otherwise. In addition, 87% and 80% found the database more efficient to analyze and retrieve previous data, respectively. This was also reflected by the shorter time taken to generate year-end QA statistics using the software (5 vs 30 min per LINAC). Overall, 94% of physicists preferred the centralized database system over conventional methods and endorsed continued use of the system. ConclusionsA centralized database system is useful and can improve the effectiveness and efficiency of QA management in a large institution. With consistent data collection and proper data storage using a database, high-quality data can be obtained for failure modes and effects analyses as per TG 100.

Gantry QA Using Three-dimensional Diode Array Detector on O-ring Linear Accelerator

It is necessary to perform gantry quality assurance (QA) in high precision radiotherapy. However, the O-ring type linear accelerator (Halcyon) does not have a light field and laser as a reference of isocenter point. The aim of this study is to investigate the usefulness of a three-dimensional diode array detector for gantry angle QA, and an O-ring type linear accelerator. The gantry angle and rotational center were verified using the ArcCHECK 3D diode array on the general linear accelerator (TrueBeam) as a reference and Halcyon. The gantry angles were measured at 0, 90, 180, and 270°. The accuracy of the gantry rotational center was evaluated using rotational irradiation in the clockwise and counterclockwise directions between 181° and 179°. The QA system with ArcCHECK was able to apply on the TrueBeam and Halcyon. As a result of the accuracy of the gantry angle, the maximum error of value calculated from ArcCHECK was 0.1° compared with the nominal gantry angle of Halcyon. As a result of the accuracy of the gantry rotation isocenter of Halcyon, the distance between the isocenter and the gantry rotation center was 0.45 mm and 0.41 mm in the clockwise and counterclockwise directions, respectively. The QA system with ArcCHECK was useful for the gantry angle and the rotation center accuracy on the Halcyon.

Implementing and evaluating a high-resolution diode array for patient-specific quality assurance of robotic brain stereotactic radiosurgery/radiotherapy.

The purpose of the study was to introduce and evaluate a high‐resolution diode array for patient‐specific quality assurance (PSQA) of CyberKnife brain stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT). Thirty‐three intracranial plans were retrospectively delivered on the SRS MapCHECK using fixed cone, Iris, and multileaf collimator (MLC). The plans were selected to cover a range of sites from large tumor bed, single/multiple small brain metastases (METs) to trigeminal neuralgia. Fiducial tracking using the four fiducials embedded around the detector plane was used as image guidance. Results were analyzed before and after registration based on absolute dose gamma criterion of 1 mm distance‐to‐agreement and 0.5%–3% dose‐difference. Overall, the gamma passing rates (1 mm and 3% criterion) before registration for all the patients were above 90% for all three treatment modalities (96.8 ± 3.5%, the lowest passing rate of 90.4%), and were improved after registration (99.3 ± 1.5%). When tighter criteria (1 mm and 2%) were applied, the gamma passing rates after registration for all the cases dropped to 97.3 ± 3.2%. For trigeminal neuralgia cases, we applied 1 mm and 0.5% criterion and the passing rates dropped from 100 ± 0.0% to 98.5 ± 2.0%. The mean delivery time was 33.4 ± 11.7 min, 24.0 ± 4.9 min, and 17.1 ± 2.6 min for the fixed cone, Iris, and MLC, respectively. With superior gamma passing rates and reasonable quality assurance (QA) time, we believe the SRS MapCHECK could be a good option for routine PSQA for CyberKnife SRS/SRT.

Abstract OT1-04-01: ATNEC: A multi-centre, randomised trial investigating whether axillary treatment can be avoided in T1-3N1M0 breast cancer patients with no residual cancer in the lymph glands after neoadjuvant chemotherapy (clinicaltrials.gov: nct04109079)

Abstract Background: For patients who are node positive to start at presentation and are found to have a complete nodal tumour response (ypN0) post neoadjuvant chemotherapy (NACT), we do not yet know whether local axillary therapy can be modified based on the response to NACT. ATNEC randomised trial specifically address axillary management following NACT in patients with proven axillary node metastases. Methods: Design: ATNEC is a phase III, randomised (1:1), multi-centre trial, with embedded economic evaluation. Patients with proven axillary node metastases on needle biopsy receive NACT followed by sentinel node biopsy (SNB). If the sentinel nodes have converted to benign (ypN0), ATNEC randomly assigns patients to axillary treatment (nodal radiotherapy or axillary nodal clearance) vs. no axillary treatment (without further surgery). Aims: To assess whether, omitting further axillary treatment (ALND and ART) for patients with early stage breast cancer and axillary nodal metastases on needle biopsy - who after NACT have no residual nodal disease on SNB - is non-inferior to axillary treatment in terms of disease free survival, and reduces the risk of lymphoedema at 5 years. Stratification: Institution, type of surgery (breast conserving surgery [BCS] vs mastectomy), receptor status (triple negative vs HER2 positive vs ER status positive and/or PR status positive and HER2 negative). Inclusion criteria:. • Age ≥ 18. • Male or female. • T1-3N1M0 breast cancer at diagnosis (pre-NACT). • FNA or core biopsy confirmed axillary nodal metastases at presentation. • ER and HER2 status evaluated on primary tumour. • Received standard NACT as per local guidelines. • Imaging assessment of the axilla at completion of NACT. • Dual tracer SNB after NACT and at least 3 nodes removed (sentinel nodes and marked node). o If a single tracer is used, the patient is eligible if the involved node is marked before NACT and at least 3 nodes removed (including the marked node). o If axillary node sampling is performed following failed localisation of sentinel nodes, patient is eligible if at least 3 nodes removed (including the marked node). o If node is not marked, or marked node is not removed, patient is eligible if the histology report shows evidence of down-staging with complete pathological response in at least one node and at least 3 nodes removed. • No evidence of nodal metastases post NACT (ypN0). Exclusion criteria:. • Bilateral invasive breast cancer. • SNB prior to NACT. • Previous ipsilateral axillary nodal surgery. • Previous cancer within last 5 years or concomitant malignancy. Radiotherapy Quality Assurance: ATNEC has in-built radiotherapy QA programme that is coordinated by National Radiotherapy Trials QA (RTTQA) group. Target accrual: 1900 Number of sites: 100 Trial Status: Recruiting. Trial is open to new sites. Disclaimer: This study is funded by the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme (Reference - HTA NIHR128311). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. Citation Format: Amit Goyal, Sophie Cramp, Andrea Marshall, Duncan Wheatley, Natalie Hammonds, Shama Puri, Tara Homer, Luke Vale, Roeum Butt, Romaana Mir, Janice Rose, Helen Teresa Edwards, Samreen Ahmed, Abeer Shaaban, Beatrix Elsberger, Julie Bruce, Sophie Gasson, Valerie Speirs, Jacqui Shaw, Helen Higgins, Janet Dunn. ATNEC: A multi-centre, randomised trial investigating whether axillary treatment can be avoided in T1-3N1M0 breast cancer patients with no residual cancer in the lymph glands after neoadjuvant chemotherapy (clinicaltrials.gov: nct04109079) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT1-04-01.

Spectral fiber dosimetry with beryllium oxide for quality assurance in hadron radiation therapy

Using the radioluminescence light of solid state probes coupled to long and flexible fibers for dosimetry in radiotherapy offers many advantages in terms of probe size, robustness and cost efficiency. However, especially in hadron fields, radioluminophores exhibit quenching effects dependent on the linear energy transfer. This work describes the discovery of a spectral shift in the radioluminescence light of beryllium oxide in dependence on the residual range at therapeutic proton energies. A spectrally resolving measurement setup has been developed and tested in scanned proton fields. It is shown that such a system can not only quantitatively reconstruct the dose, but might also give information on the residual proton range at the point of measurement.

Development and evaluation of a thallium (I) bromide dosimeter for intracavitary radiotherapy quality assurance

In intracavitary radiotherapy, incorrect source locations can result in excessive doses to normal tissues. Therefore, it is essential to accurately evaluate the source location. In this study, we investigated a digital line dosimeter based on thallium (I) bromide (TlBr) to improve the existing analogue verification method. Therefore, a polycrystalline TlBr unit cell dosimeter was manufactured, and the measurement performance of iridium-192 (Ir-192) sources was evaluated. We found that the dosimeter's reproducibility satisfied the evaluation criteria of 1.5% with a relative standard deviation of 1.44%. Moreover, the linearity showed excellent results (linear coefficient, R 2 = 0.9999). The distance dependence showed a difference of 0.03 cm at 50% intensity when compared to the inverse square value, whereas the angular dependence showed a large difference when compared to a diode. As the angle increased, the intensity gradually decreased, resulting in a difference of up to 41.9%. These results demonstrate the excellent performance of the TlBr dosimeter. However, because of the significant influence of angular dependence, a measurement distance that minimises this error should be applied when manufacturing line dosimeters in the future.

Tissue-equivalent dosimeters based on copper doped lithium tetraborate single crystals for radiotherapy

Advancements in radiotherapy techniques demand the development of stringent quality assurance (QA) protocols and new dosimeters for achieving better accuracy in the measurement of the delivered dose. The objective of the present study is to assess performance of in-house developed tissue equivalent lithium tetraborate (Li2B4O7) single crystal based thermoluminescent dosimeters (TLDs) for medical dosimetry in radiotherapy. For this, single crystals of copper doped lithium tetraborate, abbreviated as LTB:Cu, were grown using the Czochralski crystal pulling technique and transparent TLDs of the dimensions 3×3x0.6 mm3 in chip form were fabricated in our laboratory. Complete dosimetric characterization of TLDs was done to assess its suitability as a dosimeter for radiotherapy dosimetry. The LTB:Cu TLDs were studied for dosimetric properties such as linearity of response with delivered dose, fading, energy dependence, angular dependence and dose rate dependence. The central-axis depth dose parameters such as percentage depth dose (PDD) and output factors were measured using the developed LTB:Cu TLDs for the clinically relevant depths and field sizes and were compared with the response of commercially established TLD-100 and reference values measured by ionisationchamber.Performance of LTB:Cu TLDs has been assessed for their reliable use in dose verification of treatment planning system (TPS) and QA in radiotherapy. The TLDs were used in the clinical set up for measuring the doses to target and critical organs in the in-house developed thorax phantom and the results were compared with the TPS calculated doses. The doses were delivered using three-dimensional conformal radiotherapy (3D-CRT) and volumetric modulated arc therapy (VMAT) techniques. The planned and measured doses agreed within the acceptable limits of 3%. These studies have shown the great potential for the applicability of the developed TLDs in the radiotherapy dosimetry applications.

Understanding machine learning classifier decisions in automated radiotherapy quality assurance

The complexity of generating radiotherapy treatments demands a rigorous quality assurance (QA) process to ensure patient safety and to avoid clinically significant errors. Machine learning classifiers have been explored to augment the scope and efficiency of the traditional radiotherapy treatment planning QA process. However, one important gap in relying on classifiers for QA of radiotherapy treatment plans is the lack of understanding behind a specific classifier prediction. We develop explanation methods to understand the decisions of two automated QA classifiers: (1) a region of interest (ROI) segmentation/labeling classifier, and (2) a treatment plan acceptance classifier. For each classifier, a local interpretable model-agnostic explanation (LIME) framework and a novel adaption of team-based Shapley values framework are constructed. We test these methods in datasets for two radiotherapy treatment sites (prostate and breast), and demonstrate the importance of evaluating QA classifiers using interpretable machine learning approaches. We additionally develop a notion of explanation consistency to assess classifier performance. Our explanation method allows for easy visualization and human expert assessment of classifier decisions in radiotherapy QA. Notably, we find that our team-based Shapley approach is more consistent than LIME. The ability to explain and validate automated decision-making is critical in medical treatments. This analysis allows us to conclude that both QA classifiers are moderately trustworthy and can be used to confirm expert decisions, though the current QA classifiers should not be viewed as a replacement for the human QA process.

Clinical Trials in High-Risk Medulloblastoma: Evolution of the SIOP-Europe HR-MB Trial.

Simple SummaryPatients with medulloblastoma receive treatment according to a risk stratification, which is a combination of clinical and biological factors. To date there have been a limited number of trials for high-risk disease in children older than 3 years, with a wide range of treatment philosophies that usually involve higher doses of radiotherapy delivered either conventionally or in hyper-fractionated/accelerated regimens. Similarly, both standard and high-dose chemotherapies were assessed. However, to date, trials in high-risk medulloblastoma have commonly been institutional or national, based on modest cohort sizes, and have not evaluated the relative performance of different strategies in a randomised fashion. We describe the concepts and design of the SIOP-E high-risk medulloblastoma clinical trial (SIOP-HR-MB), the first international, biomarker-driven, randomised clinical trial for high-risk medulloblastoma. SIOP-HR-MB is programmed to recruit >800 patients in 16 countries across Europe; its primary objectives are to assess the relative efficacies of the alternative established regimens.Medulloblastoma patients receive adapted therapies stratified according to their risk-profile. Favourable, standard, and high disease-risk groups are each defined by the status of clinical and pathological risk factors, alongside an evolving repertoire of diagnostic and prognostic biomarkers. Medulloblastoma clinical trials in Europe are coordinated by the International Society for Paediatric Oncology (SIOP-Europe) brain tumour group. Favourable and standard-risk patients are eligible for the SIOP-PNET5-MB clinical trial protocol. In contrast, therapies for high-risk disease worldwide have, to date, encompassed a range of different treatment philosophies, with no clear consensus on approach. Higher radiotherapy doses are typically deployed, delivered either conventionally or in hyper-fractionated/accelerated regimens. Similarly, both standard and high-dose chemotherapies were assessed. However, trials to date in high-risk medulloblastoma have commonly been institutional or national, based on modest cohort sizes, and have not evaluated the relative performance of different strategies in a randomised fashion. We describe the concepts and design of the SIOP-E high-risk medulloblastoma clinical trial (SIOP-HR-MB), the first international biomarker-driven, randomised, clinical trial for high-risk medulloblastoma. SIOP-HR-MB is programmed to recruit >800 patients in 16 countries across Europe; its primary objectives are to assess the relative efficacies of the alternative established regimens. The HR-MB patient population is molecularly and clinically defined, and upfront assessments incorporate a standardised central review of molecular pathology, radiology, and radiotherapy quality assurance. Secondary objectives include the assessment of (i) novel therapies within an upfront ‘window’ and (ii) therapy-associated neuropsychology, toxicity, and late effects, alongside (iii) the collection of materials for comprehensive integrated studies of biological determinants within the SIOP-HR-MB cohort.

Adherence to Contouring and Treatment Planning Requirements Within a Multicentric Trial: Results of the Quality Assurance of the SAKK 09/10 trial

To evaluate the results of the radiation therapy (RT) quality assurance (QA) program of the phase 3 randomized SAKK 09/10 trial in patients with biochemically recurrent prostate cancer after prostatectomy. Within the Schweizerische Arbeitsgemeinschaft für Klinische Krebsforschung (SAKK) 09/10 trial testing 64-Gy versus 70-Gy salvage RT, a central collection of treatment plans was performed and thoroughly reviewed by a dedicated medical physicist and radiation oncologist. Adherence to the treatment protocol and specifically to the European Organization for the Research and Treatment of Cancer (EORTC) guidelines for target volume definition (classified as deviation observed yes vs no) and its potential correlation with acute and late toxicity (Common Terminology Criteria for Adverse Events version 4.0) and freedom from biochemical progression (FFBP) were investigated. The treatment plans for 344 patients treated between February 2011 and April 2014 depicted important deviations from the EORTC guidelines and the recommendations per trial protocol. For example, in up to half of the cases, the delineated structures deviated from the protocol (eg, prostate bed in 48.8%, rectal wall [RW] in 41%). In addition, variations in clinical target volume (CTV) and planning target volume (PTV) occurred frequently (eg, CTV and PTV deviations in up to 42.4% and 25.9%, respectively). The detected deviations showed a significant association with a lower risk of grade ≥2 gastrointestinal acute toxicity when the CTV did not overlap the RW versus when the CTV overlapped the RW (odds ratio [OR], 0.43; 95% confidence interval [CI], 0.22-0.85; P=.014), and a higher rate of grade ≥2 late genitourinary (GU) toxicity when the CTV overlapped the RW (OR, 2.58; 95% CI, 1.17-5.72; P=.019). A marginally significant lower risk of grade ≥2 late GU toxicity was observed when the prostate bed did not overlap versus did overlap the RW (OR, 0.51; 95% CI, 0.25-1.03; P=.06). In addition, a marginally significant decrease in FFBP was observed in patients with PTV not including surgical clips as potential markers of the limits of the prostate bed (hazard ratio, 1.44; 95% CI, 0.96-2.17; P=.07). Despite a thorough QA program, the central review of a phase 3 trial showed limited adherence to treatment protocol recommendations, which was associated with a higher risk of toxicity by means of acute or late gastrointestinal or GU toxicity and showed a trend toward worse FFBP. Data from this QA review might help to refine future QA programs and prostate bed delineation guidelines.

Error Detectability of Isodose Volumes as ROIs in Prostate Intensity-modulated RT QA

To evaluate the quality of error detectability with a three-dimensional verification system using isodose volumes as regions of interest (ROIs) in quality assurance (QA) of intensity-modulated radiation therapy. Treatment plans with four types of intentional errors were created from the data of 20 patients with localized prostate cancer. These plans underwent QA using the three-dimensional verification system. The datasets of another 30 cases without inserted errors were assessed as controls. The ROIs used in the evaluations were those used in our conventional method (planning target volume, rectum, and bladder). The isodose volume method (5%, 50% and 95% isodose volume) and the error detection rates (measurement above the tolerance values, as set from the other 30 cases) were assessed and compared. There was significantly higher multileaf collimator systematic closed error detectability with the isodose volume method compared to the conventional method (A-side 0.2 mm: p=0.005, A-side 0.35 mm: p=0.002, B-side 0.2 mm: p=0.001 and B-side 0.35 mm: p=0.010). There were no error types for which the error detection rate of the isodose volume method was lower than that of the conventional method. The isodose volume method was able to evaluate the irradiated ROIs that could be delineated, and improved error detectability. This method has the potential to provide a wider margin of safety in intensity-modulated radiation therapy.

End-to-End Quality Assurance of Stereotactic Radiation Therapy Using an Anthropomorphic Head Phantom

In the clinic, routine quality assurance tests ensure the proper functioning of each individual aspect of a radiation therapy treatment delivery. However, these tests may not guarantee an accurate treatment delivery. In this work, we present the design and application of a head phantom (using 3D printing technology) developed for end-to-end quality assurance of a stereotactic radiation therapy treatment for brain metastases, coupled with inserts for ion chamber, and film and gel dosimeters. The head phantom was subjected to the entire clinical workflow, with each stage of the process being performed by the appropriate clinical personnel to ensure that this quality assurance test mimics the clinical scenario.