An international survey on the clinical use of rigid and deformable image registration in radiotherapy.

OBJECTIVES: Rigid image registration (RIR) and deformable image registration (DIR) are widely used in radiotherapy. This project aims to capture current international approaches to image registration. METHODS: A survey was designed to identify variations in use, resources, implementation, and decision-making criteria for clinical image registration. This was distributed to radiotherapy centers internationally in 2018. RESULTS: There were 57 responses internationally, from the Americas (46%), Australia/New Zealand (32%), Europe (12%), and Asia (10%). Rigid image registration and DIR were used clinically for computed tomography (CT)-CT registration (96% and 51%, respectively), followed by CT-PET (81% and 47%), CT-CBCT (84% and 19%), CT-MR (93% and 19%), MR-MR (49% and 5%), and CT-US (9% and 0%). Respondent centers performed DIR using dedicated software (75%) and treatment planning systems (29%), with 84% having some form of DIR software. Centers have clinically implemented DIR for atlas-based segmentation (47%), multi-modality treatment planning (65%), and dose deformation (63%). The clinical use of DIR for multi-modality treatment planning and accounting for retreatments was considered to have the highest benefit-to-risk ratio (69% and 67%, respectively). CONCLUSIONS: This survey data provides useful insights on where, when, and how image registration has been implemented in radiotherapy centers around the world. DIR is mainly in clinical use for CT-CT (51%) and CT-PET (47%) for the head and neck (43-57% over all use cases) region. The highest benefit-risk ratio for clinical use of DIR was for multi-modality treatment planning and accounting for retreatments, which also had higher clinical use than for adaptive radiotherapy and atlas-based segmentation.

Applicability and usage of dose mapping/accumulation in radiotherapy.

Dose mapping/accumulation (DMA) is a topic in radiotherapy (RT) for years, but has not yet found its widespread way into clinical RT routine. During the ESTRO Physics workshop 2021 on "commissioning and quality assurance of deformable image registration (DIR) for current and future RT applications", we built a working group on DMA from which we present the results of our discussions in this article. Our aim in this manuscript is to shed light on the current situation of DMA in RT and to highlight the issues that hinder consciously integrating it into clinical RT routine. As a first outcome of our discussions, we present a scheme where representative RT use cases are positioned, considering expected anatomical variations and the impact of dose mapping uncertainties on patient safety, which we have named the DMA landscape (DMAL). This tool is useful for future reference when DMA applications get closer to clinical day-to-day use. Secondly, we discussed current challenges, lightly touching on first-order effects (related to the impact of DIR uncertainties in dose mapping), and focusing in detail on second-order effects often dismissed in the current literature (as resampling and interpolation, quality assurance considerations, and radiobiological issues). Finally, we developed recommendations, and guidelines for vendors and users. Our main point include: Strive for context-driven DIR (by considering their impact on clinical decisions/judgements) rather than perfect DIR; be conscious of the limitations of the implemented DIR algorithm; and consider when dose mapping (with properly quantified uncertainties) is a better alternative than no mapping.

MIRSIG position paper: the use of image registration and fusion algorithms in radiotherapy.

The report of the American Association of Physicists in Medicine (AAPM) Task Group No. 132 published in 2017 reviewed rigid image registration and deformable image registration (DIR) approaches and solutions to provide recommendations for quality assurance and quality control of clinical image registration and fusion techniques in radiotherapy. However, that report did not include the use of DIR for advanced applications such as dose warping or warping of other matrices of interest. Considering that DIR warping tools are now readily available, discussions were hosted by the Medical Image Registration Special Interest Group (MIRSIG) of the Australasian College of Physical Scientists & Engineers in Medicine in 2018 to form a consensus on best practice guidelines. This position statement authored by MIRSIG endorses the recommendations of the report of AAPM task group 132 and expands on the best practice advice from the 'Deforming to Best Practice' MIRSIG publication to provide guidelines on the use of DIR for advanced applications.

A study into the relationship between the measured penumbra and effective source size in the modeling of the Pinnacle RTPS.

The effect of detector size in the broadening of the penumbra on the model in the Pinnacle RTPS is investigated. A second order polynomial was devised to correlate the source size parameter with the RTPS-calculated penumbra. The optimal source size parameter was calculated for penumbra measurements based on the diamond detector and a standard ionization chamber (IC). This work was done for Jaw fields, MLC fields with a leaf end radius of 8 cm, and MLC fields with a leaf end radius of 12 cm. The optimum source size of the 8 cm MLC fields matched the jaw fields, and an average (based on field sizes studied) of 1.1 mm for the diamond detector data and 2.4 mm for the ionization chamber was established. The effect of this overestimation of the source size parameter based on detector-induced penumbra broadening was considered for a clinical IMRT prostate plan by using two models (diamond and IC). There were differences in the DVH of the PTV and of OARs but these effects were of negligible clinical significance. Dose difference distributions showed dose difference areas to be in penumbra regions of the segments, with larger dose differences where penumbras intersected and/or there was a significant weighting on the segment. Gamma analysis was also performed between the two plans, and was found to increase the amount of fail rates significantly for both 2%/2 mm and 3%/3 mm criteria. This decreases the sensitivity of IMRT QA in the detection of systematic errors.

Use of deformable image registration techniques to estimate dose to organs at risk following prostate external beam radiation therapy and high-dose-rate brachytherapy.

PURPOSE: The purpose of this investigation was to examine differences in estimates of accumulated rectal dose when using deformable image registration (DIR) compared with rigid image registration (RIR) methods, and parameter addition methods for combined transrectal ultrasound (TRUS)-based high-dose-rate brachytherapy (HDR-BT) and external beam radiation therapy (EBRT) treatments of prostate cancer. MATERIAL AND METHODS: In this retrospective study, data from 10 patients who had previously received HDR-BT in one 15 Gy fraction, followed by 46 Gy EBRT in twenty-three fractions were used. To estimate total combined dose to the rectum, dose accumulation using both DIR and RIR methods were compared with parameter addition methods, which assume the same region of rectal anatomy receives the maximum dose from both treatment modalities. For both rigid and deformable image registration techniques, the quality of image registration was evaluated through metrics, including mean distance to agreement and dice similarity coefficient of prostate contours. Total D1cc and D2cc for the rectum was calculated and compared using each method. RESULTS: The parameter addition methods predicted the highest accumulated dose to the rectum. On average, the predicted D2cc dose was higher than that calculated by the DIR method by 6.59 Gy EQD2 (range, -3.03 to 13.68 Gy EQD2) for partial parameter addition (PPA), and 4.88 Gy EQD2 (range, -3.41 to 11.97 Gy EQD2) for the full parameter addition (FPA) methods. Similarly, RIR predicted higher average doses compared with DIR, with a difference of 3.46 Gy EQD2 (range, -5.50 to 7.90 Gy EQD2). The results showed a significant difference between DIR and parameter addition methods for dose estimation. CONCLUSIONS: This retrospective study demonstrates significant differences in accumulated rectal dose prediction using different image registration methods. Each method has limitations in its application, and when used with real-time HDR-BT dose planning, awareness of these limitations is essential.

The RABBIT risk-based approach to clinical implementation of new technology: SRS as a case study.

Radiation oncology technology continues to evolve rapidly, resulting in advanced versions frequently being brought to market. Before a new product is used standard tests are carried out to reduce the risks associated with failure of the equipment to comply with well-established technical specifications. It is much harder to identify and reduce the risks associated with how the new technology is used clinically, such as those related to poor communication and high workload. To ensure that new technology and techniques are used safely and appropriately the implementation project should be managed by a multidisciplinary team (MDT) made up of representatives from all the relevant professions. The MDT's role is to agree on the project scope, identify and rank all risks and benefits, and direct resources towards mitigating the highest risks. Before clinical release there should be consensus from the MDT that the benefits of the new technology outweigh the residual risks. The introduction of initiatives to optimise current practice may involve major changes which can be met with barriers such as limited support from management, insufficient time for MDT meetings, and staff fearful of being shown to have poor practices. To help overcome these challenges our team at St George Hospital Cancer Care Centre has developed a Risk and Benefit Balance Impact Template (RABBIT), which guides an MDT through the rapid implementation and safe use of new technology and techniques with an easy to follow Microsoft Word document. The implementation of stereotactic radiosurgery is used as a case study to illustrate the RABBIT methodology. The RABBIT is a user-friendly method for a busy radiotherapy clinic to transition to a risk-based MDT approach for the implementation of new technologies and techniques. When staff from all disciplines feel empowered to raise concerns about risks the workplace become inherently safer for patients and staff alike.

Deforming to Best Practice: Key considerations for deformable image registration in radiotherapy.

Image registration is a process that underlies many new techniques in radiation oncology - from multimodal imaging and contour propagation in treatment planning to dose accumulation throughout treatment. Deformable image registration (DIR) is a subset of image registration subject to high levels of complexity in process and validation. A need for local guidance to assist in high-quality utilisation and best practice was identified within the Australian community, leading to collaborative activity and workshops. This report communicates the current limitations and best practice advice from early adopters to help guide those implementing DIR in the clinic at this early stage. They are based on the state of image registration applications in radiotherapy in Australia and New Zealand (ANZ), and consensus discussions made at the 'Deforming to Best Practice' workshops in 2018. The current status of clinical application use cases is presented, including multimodal imaging, automatic segmentation, adaptive radiotherapy, retreatment, dose accumulation and response assessment, along with uptake, accuracy and limitations. Key areas of concern and preliminary suggestions for commissioning, quality assurance, education and training, and the use of automation are also reported. Many questions remain, and the radiotherapy community will benefit from continued research in this area. However, DIR is available to clinics and this report is intended to aid departments using or about to use DIR tools now.

Use of the AAPM Safety Profile Assessment Tool to Evaluate the Change in Safety Culture After Implementing the RABBIT Prospective Risk Management System.

PURPOSE: Hospitals traditionally focus on reactive risk management such as incident reporting, but prospective risk management systems such as failure modes and effects analysis are also important tools to reduce risks and improve the safety culture. In 2015, the St George Cancer Care Centre (STGCCC) developed a multidisciplinary risk-based system for the safe and effective implementation of new technologies and techniques, using risk and benefit balance impact templates (RABBIT) developed in-house. The purpose of this study was to determine whether risk management and the safety culture in radiation oncology were perceived to have improved since the introduction of the RABBIT system. METHODS AND MATERIALS: In 2017, radiation oncologists, radiation therapists, and medical physicists were asked to rate the department before and after the introduction of the RABBIT using questions from the American Association of Physicists in Medicine Safety Profile Assessment (SPA) tool. Answers relating to the implementation of new technology/techniques are presented. RESULTS: STGCCC staff confirmed that the RABBIT system has improved the implementation of new technology/techniques, with an average SPA question score improvement from 3.9 to 4.4 (of 5.0). This compares favorably with the SPA world average of 3.5 (October 2017). The improvement is attributed to risks being formally identified and managed and adequate staff training being mandatory and systematic. There were also perceived improvements in teamwork, probably because the introduction of structured multidisciplinary teams resulted in each group having a better understanding of the workflows and priorities of the other groups. CONCLUSIONS: This study shows that prospective risk management at STGCCC has improved the perceived quality of the implementation of new technology/techniques. The RABBIT is a simple and effective method for achieving this improvement in safety culture. The American Association of Physicists in Medicine SPA is a valuable tool for assessing the success of quality initiatives and identifying opportunities for further improvement.

The cytokinesis-block micronucleus assay as a biological dosimeter for targeted alpha therapy.

Ionizing radiation causes structural chromosomal aberrations, a proportion of which give rise to chromosome fragments without spindle attachment organelles. When a cell divides, some of these fragments are excluded from the main daughter nuclei and form small nuclei within the cytoplasm. The cytokinesis-block micronucleus assay allows these micronuclei (MN) to be counted, providing an in situ biological dosimeter. In this study, we evaluated the micronucleus frequency in peripheral blood lymphocytes after in vitro incubation with the alpha conjugates (213)BiI(3) and (213)Bi-9.2.27 (AIC). Lymphocytes were inoculated in vitro AIC for 3 h. Further, we report the first MN measurements in melanoma patients after targeted alpha therapy (TAT) with (213)Bi-9.2.27. Patients were injected with 260-360 MBq of AIC, and blood samples taken at 3 h, 2 weeks and 4 weeks post-treatment. Absorbed dose (MIRD) and effective total body dose (PED) were calculated. The MN frequency in lymphocytes was similar for equal in vitro incubation activities of (213)BiI(3) and (213)Bi-9.2.27 (P=0.5), indicating that there is no selective targeting of lymphocytes by the alpha conjugates. After inoculation with 10-1200 kBq mL-1 of AIC, there was a substantial activity-related increase in MN. The number of MN in the blood of treated patients peaked at 3 h post-TAT, slowly returning to baseline levels by 4 weeks. The mean photon equivalent dose (PED) is 0.43 Gy (SD 0.15) and the mean MIRD calculated absorbed dose is 0.11 Gy (SD 0.03), giving an RBE=4+/-0.4 for this study.

A risk-based approach to development of ultrasound-based high-dose-rate prostate brachytherapy quality management.

PURPOSE: The purpose of this study was to apply a risk-based approach to the development of a quality management (QM) program for ultrasound-based high-dose-rate (HDR) prostate brachytherapy (pBT) treatment planning and delivery. METHODS AND MATERIALS: A QM program was developed by a multidisciplinary team, using both an in-house risk-and-benefit balance impact template (RABBIT) tool and a failure modes and effect analysis (FMEA). FMEA scores were determined by three physicists, one radiation therapist and two radiation oncologists who were familiar with the protocol. The QM program produced by both risk-based techniques was then compared and consolidated. RESULTS: The RABBIT tool identified 26 potential risks during the treatment planning and delivery process. During the FMEA, a total of 35 potential failure modes were identified from the seven major processes in ultrasound-based HDR pBT. For the 35 potential failure modes, risk priority number scores ranged from 14 to 267. The highest ranked failure mode was identified to be mislabeling/connection of the transfer tubes/catheters. From the risks analyses, a comprehensive QM program was developed. CONCLUSION: Both the RABBIT tool and process mapping and FMEA were shown to be valuable tools in developing a QM program for ultrasound-based HDR pBT treatments. A considerable number of the potential failure modes identified in both tools were related to human or procedural errors, highlighting the importance of checklists and protocols in delivering a safe and effective ultrasound-based HDR pBT treatment.

Dose accumulation of multiple high dose rate prostate brachytherapy treatments in two commercially available image registration systems.

PURPOSE: The purpose of this study was to assess whether deformable image registration (DIR) is required for dose accumulation of multiple high dose rate prostate brachytherapy (HDRPBT) plans treated with the same catheter pattern on two different CT datasets. METHOD: DIR was applied to 20 HDRPBT patients' planning CT images who received two treatment fractions on sequential days, on two different CT datasets, with the same implant. Quality of DIR in Velocity and MIM image registration systems was assessed by calculating the Dice Similarity Coefficient (DSC) and mean distance to agreement (MDA) for the prostate, urethra and rectum contours. Accumulated doses from each system were then calculated using the same DIR technique and dose volume histogram (DVH) parameters compared to manual addition with no DIR. RESULTS: The average DSC was found to be 0.83 (Velocity) and 0.84 (MIM), 0.80 (Velocity) and 0.80 (MIM), 0.80 (Velocity) and 0.81 (MIM), for the prostate, rectum and urethra contours, respectively. The average difference in calculated DVH parameters between the two systems using dose accumulation was less than 1%, and there was no statistically significant difference found between deformably accumulated doses in the two systems versus manual DVH addition with no DIR. CONCLUSION: Contour propagation using DIR in velocity and MIM was shown to be at least equivalent to inter-observer contouring variability on CT. The results also indicate that dose accumulation through manual addition of DVH parameters may be sufficient for HDRPBT treatments treated with the same catheter pattern on two different CT datasets.