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BACKGROUND: Auto-segmentation of organs-at-risk (OARs) in the head and neck (HN) on computed tomography (CT) images is a time-consuming component of the radiation therapy pipeline that suffers from inter-observer variability. Deep learning (DL) has shown state-of-the-art results in CT auto-segmentation, with larger and more diverse datasets showing better segmentation performance. Institutional CT auto-segmentation datasets have been small historically (n < 50) due to the time required for manual curation of images and anatomical labels. Recently, large public CT auto-segmentation datasets (n > 1000 aggregated) have become available through online repositories such as The Cancer Imaging Archive. Transfer learning is a technique applied when training samples are scarce, but a large dataset from a closely related domain is available. PURPOSE: The purpose of this study was to investigate whether a large public dataset could be used in place of an institutional dataset (n > 500), or to augment performance via transfer learning, when building HN OAR auto-segmentation models for institutional use. METHODS: Auto-segmentation models were trained on a large public dataset (public models) and a smaller institutional dataset (institutional models). The public models were fine-tuned on the institutional dataset using transfer learning (transfer models). We assessed both public model generalizability and transfer model performance by comparison with institutional models. Additionally, the effect of institutional dataset size on both transfer and institutional models was investigated. All DL models used a high-resolution, two-stage architecture based on the popular 3D U-Net. Model performance was evaluated using five geometric measures: the dice similarity coefficient (DSC), surface DSC, 95th percentile Hausdorff distance, mean surface distance (MSD), and added path length. RESULTS: For a small subset of OARs (left/right optic nerve, spinal cord, left submandibular), the public m

PURPOSE: This study aimed to analyse correlations between planning factors including plan geometry and plan complexity with robustness to patient setup errors. METHODS: Multiple-target brain stereotactic radiosurgery (SRS) plans were obtained through the Trans-Tasman Radiation Oncology Group (TROG) international treatment planning challenge (2018). The challenge dataset consisted of five intra-cranial targets with a 20 Gy prescription. Setup error was simulated using an in-house tool. Dose to targets was assessed via dose covering 99 % (D99 %) of gross tumour volume (GTV) and 98 % of planning target volume (PTV). Dose to organs at risk was assessed using volume of normal brain receiving 12 Gy and maximum dose covering 0.03 cc of brainstem. Plan complexity was assessed via edge metric, modulation complexity score, mean multi-leaf collimator (MLC) gap, mean MLC speed and plan modulation. RESULTS: Even for small (0.5 mm/°) errors, GTV D99 % was reduced by up to 20 %. The strongest correlation was found between lower complexity plans (larger mean MLC gap and lower edge metric) and higher robustness to setup error. Lower complexity plans had 1 %-20 % fewer targets/scenarios with GTV D99 % falling below the specified tolerance threshold. These complexity metrics correlated with 100 % isodose volume sphericity and dose conformity, though similar conformity was achievable with a range of complexities. CONCLUSIONS: A higher level of importance should be directed towards plan complexity when considering plan robustness. It is recommended when planning multi-target SRS, larger MLC gaps and lower MLC aperture irregularity be considered during plan optimisation due to higher robustness should patient positioning errors occur.

The Brain Imaging Data Structure (BIDS) is a community-driven standard for the organization of data and metadata from a growing range of neuroscience modalities. This paper is meant as a history of how the standard has developed and grown over time. We outline the principles behind the project, the mechanisms by which it has been extended, and some of the challenges being addressed as it evolves. We also discuss the lessons learned through the project, with the aim of enabling researchers in other domains to learn from the success of BIDS.

The Brain Imaging Data Structure (BIDS) is a community-driven standard for the organization of data and metadata from a growing range of neuroscience modalities. This paper is meant as a history of how the standard has developed and grown over time. We outline the principles behind the project, and the mechanisms by which it has been extended. We also discuss the lessons learned through the project, with the aim of enabling researchers in other domains to learn from the success of BIDS.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.In a randomized phase II clinical trial, the Trans Tasman Radiation Oncology Group compared single- versus multifraction stereotactic ablative body radiotherapy (SABR) in 90 patients with 133 oligometastases to the lung. The study found no differences in safety, efficacy, systemic immunogenicity, or survival between arms, with single-fraction SABR picked as the winner on the basis of cost-effectiveness. In this article, we report the final updated survival outcome analysis. The protocol mandated no concurrent or post-therapy systemic therapy until progression. Modified disease-free survival (mDFS) was defined as any progression not addressable by local therapy, or death. At a median follow-up of 5.4 years, the 3- and 5-year estimates for overall survival (OS) were 70% (95% CI, 59 to 78) and 51% (95% CI, 39 to 61). There were no significant differences between the multi- and single-fraction arms for OS (hazard ratio [HR], 1.1 [95% CI, 0.6 to 2.0]; P = .81). The 3- and 5-year estimates for disease-free survival were 24% (95% CI, 16 to 33) and 20% (95% CI, 13 to 29), with no differences between arms (HR, 1.0 [95% CI, 0.6 to 1.6]; P = .92). The 3- and 5-year estimates for mDFS were 39% (95% CI, 29 to 49) and 34% (95% CI, 24 to 44), with no differences between arms (HR, 1.0 [95% CI, 0.6 to 1.8]; P = .90). In this patient population, where patients receive SABR in lieu of systemic therapy, one-in-three patients are alive without disease in the long term. There were no differences in outcomes by fractionation schedule.

Pulmonary functional imaging has demonstrated potential to improve thoracic radiotherapy. The purpose of this study was twofold: 1) to quantify ventilation/perfusion relationships in lung cancer patients using a new functional imaging approach, gallium-68 (68Ga)-positron emission tomography/computed tomography (PET/CT); and 2) to compare ventilation/perfusion matching with diffusing capacity of the lung for carbon monoxide (DLCO). Voxel-wise correlations between ventilation and perfusion varied widely among 19 patients (range: 0.26-0.88). 68Ga-PET/CT-measured percent gas exchanging lung volume was moderately correlated with DLCO (≤0.59). Our findings suggested that 68Ga-PET/CT ventilation/perfusion imaging provided complementary information and a reasonable surrogate for gas exchange in lung cancer patients.

BACKGROUND: Biology-guided radiotherapy (BgRT) delivers dose to tumours triggered from positron emission tomography (PET) detection. Prostate specific membrane antigen (PSMA) PET uptake is abundant in the dominant intraprostatic lesion (DIL). This study investigates the feasibility of BgRT to PSMA-avid subvolume in the prostate region. METHODS: Patients enrolled in the prospective randomized trial ProPSMA at our institution were included (ID: ANZCTR12617000005358). Gross tumour volumes (GTVs) were delineated on the PET component of a PET/CT scan from a standardized uptake value (SUV) threshold technique. Suitability for BgRT requires a strong signal-to-background ratio with a surrounding tissue free of significant PSMA uptake. The signal-to-background ratio was quantified from the calculation of the normalized SUV (nSUV), defined as the ratio between SUVmax within the GTV and SUVmean inside a 3D margin expansion of the GTV. The PSMA distribution surrounding the tumour was quantified as a function of the distance from the GTV. RESULTS: In this cohort of 84 patients, 83 primary tumours were included. Prostate volume ranged from 19 cm3 to 148 cm3 (median = 52 cm3; IQR = 39 cm3 - 63 cm3). SUVmax inside the prostate was between 2 and 125 (median = 19; IQR = 11 - 30). More than 50% of GTVs generated with threshold between 25%SUVmax (median volume = 10.0 cm3; IQR = 4.5 cm3 - 20.0 cm3) and 50%SUVmax (median volume = 1.9 cm3; IQR = 1.1 cm3 - 3.8 cm3) were suitable for BgRT by using nSUV ≥ 3 and a margin expansion of 5 mm. CONCLUSIONS: It is feasible to identify GTVs suitable for BgRT in the prostate. These GTVs are characterized by a strong signal-to-background ratio and a surrounding tissue free of PSMA uptake.

BACKGROUND: Biology-guided radiotherapy (BgRT) uses real-time functional imaging to guide radiation therapy treatment. Positron emission tomography (PET) tracers targeting prostate-specific membrane antigen (PSMA) are superior for prostate cancer detection than conventional imaging. This study aims at describing nodal and distant metastasis distribution from prostate cancer and at determining the proportion of metastatic lesions suitable for BgRT. METHODS: A single-institution patient subset from the ProPSMA trial (ID ACTRN12617000005358) was analysed. Gross tumour volumes (GTV) were delineated on the CT component of a PSMA PET/CT scan. To determine the suitability of BgRT tracking zones, the normalized SUV (nSUV) was calculated as the ratio of SUVmax inside the GTV to the SUVmean of adjacent three-dimensional shells of thickness 5 mm/10 mm/20 mm as a measure of signal to background contrast. Targets were suitable for BgRT if (1) nSUV was larger than an nSUV threshold and (2) non-tumour tissue inside adjacent shell was free of PET-avid uptake. RESULTS: Of this cohort of 84 patients, 24 had at least one pelvic node or metastatic site disease, 1 to 13 lesions per patient, with a total of 98 lesions (60 pelvic nodes/38 extra-pelvic nodal diseases and haematogenous metastases). Target volumes ranged from 0.08 to 9.6 cm3 while SUVmax ranged from 2.1 to 55.0. nSUV ranged from 1.9 to 15.7/2.4 to 25.7/2.5 to 34.5 for the 5 mm/10 mm/20 mm shell expansion. Furthermore, 74%/68%/34% of the lesions had nSUV ≥ 3 and were free of PSMA PET uptake inside the GTV outer shell margin expansion of 5 mm/10 mm/20 mm. Adjacent avid organs were another lesion, bladder, bowel, ureter, prostate, and liver. CONCLUSIONS: The majority of PSMA PET/CT-defined radiotherapy targets would be suitable for BgRT by using a 10-mm tracking zone in prostate cancer. A subset of lesions had adjacent non-tumour uptake, mainly due to the proximity of ureter or bladder, and may require exclusion from emission t

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.

Delivering radiotherapy to patients in an upright position can allow for increased patient comfort, reduction in normal tissue irradiation, or reduction of machine size and complexity. This paper gives an overview of the requirements for the delivery of contemporary arc and modulated radiation therapy to upright patients. We explore i) patient positioning and immobilization, ii) simulation imaging, iii) treatment planning and iv) online setup and image guidance. Treatment chairs have been designed to reproducibly position seated patients for treatment and can be augmented by several existing immobilisation systems or promising emerging technologies such as soft robotics. There are few solutions for acquiring CT images for upright patients, however, cone beam computed tomography (CBCT) scans of upright patients can be produced using the imaging capabilities of standard Linacs combined with an additional patient rotation device. While these images will require corrections to make them appropriate for treatment planning, several methods indicate the viability of this approach. Treatment planning is largely unchanged apart from translating gantry rotation to patient rotation, allowing for a fixed beam with a patient rotating relative to it. Rotation can be provided by a turntable during treatment delivery. Imaging the patient with the same machinery as used in treatment could be advantageous for online plan adaption. While the current focus is using clinical linacs in existing facilities, developments in this area could also extend to lower-cost and mobile linacs and heavy ion therapy.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is established as the preferred method of mediastinal lymph node (LN) staging in non-small cell lung cancer (NSCLC). Selective (targeted) LN sampling is most commonly performed however studies in early stage NSCLC and locally advanced NSCLC confirm systematic EBUS-TBNA evaluation improves accuracy of mediastinal staging. This study aims to establish the rate of detection of positron emission tomography (PET)-occult LN metastases following systematic LN staging by EBUS-TBNA, and to determine the utility of systematic mediastinal staging for accurate delineation of radiation treatment fields in patients with locally advanced NSCLC. METHODS: Consecutive patients undergoing EBUS-TBNA for diagnosis/staging of locally advanced NSCLC will be enrolled in this international multi-centre single arm study. Systematic mediastinal LN evaluation will be performed, with all LN exceeding 6 mm to be sampled by TBNA. Where feasible, endoscopic ultrasound staging (EUS-B) may also be performed. Results of minimally invasive staging will be compared to FDG-PET. The primary end-point is proportion of patients in whom systematic LN staging identified PET-occult NSCLC metastases. Secondary outcome measures include (i) rate of nodal upstaging, (ii) false positive rate of PET for mediastinal LN assessment, (iii) analysis of clinicoradiologic risk factors for presence of PET-occult LN metastases, (iv) impact of systematic LN staging in patients with discrepant findings on PET and EBUS-TBNA on target coverage and dose to organs at risk (OAR) in patients undergoing radiotherapy. DISCUSSION: With specificity of PET of 90%, guidelines recommend tissue confirmation of positive mediastinal LN to ensure potentially early stage patients are not erroneously denied potentially curative resection. However, while confirmation of pathologic LN is routinely sought, the exact extent of mediastinal LN involvement in NSCL

Knowledge-based planning (KBP) can increase plan quality, consistency and efficiency. In this study, we assess the success of a using a publicly available KBP model compared with developing an in-house model for prostate cancer radiotherapy using a single, commercially available treatment planning system based on the ability of the model to achieve the centre's planning goals. Two radiation oncology centres each created a prostate cancer KBP model using the Eclipse RapidPlan software. These two models and a third publicly-available, shared model were tested at three centres in a retrospective planning study. The publicly-available model achieved lower rectum doses than the other two models. However, the planning-target-volume (PTV) doses did not meet the local planning goals and the model could not be adjusted to correct this. As a result, the plans most likely to satisfy local planning goals and requirements were created using an in-house model. For centres without an existing in-house model, a model created by another centre with similar planning goals was found to be preferred. Variations in local planning practices including contouring, treatment technique and planning goals can influence the relative performance of KBP. The value of publicly available KBP models could be enhanced through standardisation of planning goals and contouring guidelines, providing information related to the planning goals used to create the model and increased flexibility to allow local adaptation of the KBP model.

PURPOSE: Stereotactic ablative radiation therapy (SABR) delivered in a single fraction (SF) can be considered to have higher uncertainty given that the error probability is concentrated in a single session. This study aims to report the variation in technology and technique used and its effect on intrafraction motion based on a 10 years of experience in SF SABR. METHODS AND MATERIALS: Records of patients receiving SF SABR delivered at our instruction between 2010 and 2019 were included. Treatment parameters were extracted from the patient management database by using an in-house script. Treatment time was defined as the time difference between the first image acquisition to the last beam off of a single session. The intrafraction variation was measured from the 3-dimensional couch displacement measured after the first cone beam computed tomography (CBCT) acquired during a treatment. RESULTS: The number of SF SABR increased continuously from 2010 to 2019 and were mainly lung treatments. Treatment time was minimized by using volumetric modulated arc therapy, flattening filter-free dose rate, and coplanar field (24 ± 9 min). Treatment time increased as the number of CBCTs per session increased. The most common scenario involved both 2 and 3 CBCTs per session. On the average, a CBCT acquisition added 6 minutes to the treatment time. All treatments considered, the average intrafraction variation was 1.7 ± 1.6 mm. CONCLUSIONS: SF SABR usage increased with time in our institution. The intrafraction motion was acceptable and therefore a single fraction is an efficacious treatment option when considering SABR.

BACKGROUND: Delivered organs at risk (OARs) dose may vary from planned dose due to interfraction and intrafraction motion during kidney SABR treatment. Cases of bowel stricture requiring surgery post SABR treatment were reported in our institution. This study aims to provide strategies to reduce dose deposited to OARs during SABR treatment and mitigate risk of gastrointestinal toxicity. METHODS: Small bowel (SB), large bowel (LB) and stomach (STO) were delineated on the last cone beam CT (CBCT) acquired before any dose had been delivered (PRE CBCT) and on the first CBCT acquired after any dose had been delivered (MID CBCT). OAR interfraction and intrafraction motion were estimated from the shortest distance between OAR and the internal target volume (ITV). Adaptive radiation therapy (ART) was used if dose limits were exceeded by projecting the planned dose on the anatomy of the day. RESULTS: In 36 patients, OARs were segmented on 76 PRE CBCTs and 30 MID CBCTs. Interfraction motion was larger than intrafraction motion in STO (p-value = 0.04) but was similar in SB (p-value = 0.8) and LB (p-value = 0.2). LB was inside the planned 100% isodose in all PRE CBCTs and MID CBCTs in the three patients that suffered from bowel stricture. SB D0.03cc was exceeded in 8 fractions (4 patients). LB D1.5cc was exceeded in 4 fractions (2 patients). Doses to OARs were lowered and limits were all met with ART on the anatomy of the day. CONCLUSIONS: Interfraction motion was responsible for OARs overdosage. Dose limits were respected by using ART with the anatomy of the day.

Artificial intelligence and radiomics have the potential to revolutionise cancer prognostication and personalised treatment. Manual outlining of the tumour volume for extraction of radiomics features (RF) is a subjective process. This study investigates robustness of RF to inter-observer variation (IOV) in contouring in lung cancer. We utilised two public imaging datasets: 'NSCLC-Radiomics' and 'NSCLC-Radiomics-Interobserver1' ('Interobserver'). For 'NSCLC-Radiomics', we created an additional set of manual contours for 92 patients, and for 'Interobserver', there were five manual and five semi-automated contours available for 20 patients. Dice coefficients (DC) were calculated for contours. 1113 RF were extracted including shape, first order and texture features. Intraclass correlation coefficient (ICC) was computed to assess robustness of RF to IOV. Cox regression analysis for overall survival (OS) was performed with a previously published radiomics signature. The median DC ranged from 0.81 ('NSCLC-Radiomics') to 0.85 ('Interobserver'-semi-automated). The median ICC for the 'NSCLC-Radiomics', 'Interobserver' (manual) and 'Interobserver' (semi-automated) were 0.90, 0.88 and 0.93 respectively. The ICC varied by feature type and was lower for first order and gray level co-occurrence matrix (GLCM) features. Shape features had a lower median ICC in the 'NSCLC-Radiomics' dataset compared to the 'Interobserver' dataset. Survival analysis showed similar separation of curves for three of four RF apart from 'original_shape_Compactness2', a feature with low ICC (0.61). The majority of RF are robust to IOV, with first order, GLCM and shape features being the least robust. Semi-automated contouring improves feature stability. Decreased robustness of a feature is significant as it may impact upon the features' prognostic capability.

Double mitral and aortic mechanical valves present an access challenge when planning a ventricular tachycardia (VT) ablation. In this case report, we describe a patient who was considered for stereotactic ablative radiotherapy but was unable to proceed due to unfavorable anatomy making them at high risk of fistula formation. The patient went on to have an endocardial VT ablation via mini-thoracotomy and transapical access without complication. This case highlights the need for careful consideration when planning treatment for patients with double mechanical valves.

PURPOSE: This study aimed to develop a physical geometric phantom for the deformable image registration (DIR) credentialing of radiotherapy centers for a clinical trial and tested the feasibility of the proposed phantom at multiple domestic and international institutions. METHODS AND MATERIALS: The phantom reproduced tumor shrinkage, rectum shape change, and body shrinkage using several physical phantoms with custom inserts. We tested the feasibility of the proposed phantom using 5 DIR patterns at 17 domestic and 2 international institutions (21 datasets). Eight institutions used the MIM software (MIM Software Inc, Cleveland, OH); seven used Velocity (Varian Medical Systems, Palo Alto, CA), and six used RayStation (RaySearch Laboratories, Stockholm, Sweden). The DIR accuracy was evaluated using the Dice similarity coefficient (DSC) and Hausdorff distance (HD). RESULTS: The mean and one standard deviation (SD) values (range) of DSC were 0.909 ± 0.088 (0.434-0.984) and 0.909 ± 0.048 (0.726-0.972) for tumor and rectum proxies, respectively. The mean and one SD values (range) of the HD value were 5.02 ± 3.32 (1.53-20.35) and 5.79 ± 3.47 (1.22-21.48) (mm) for the tumor and rectum proxies, respectively. In three patterns evaluating the DIR accuracy within the entire phantom, 61.9% of the data had more than a DSC of 0.8 in both tumor and rectum proxies. In two patterns evaluating the DIR accuracy by focusing on tumor and rectum proxies, all data had more than a DSC of 0.8 in both tumor and rectum proxies. CONCLUSIONS: The wide range of DIR performance highlights the importance of optimizing the DIR process. Thus, the proposed method has considerable potential as an evaluation tool for DIR credentialing and quality assurance.

BACKGROUND: Muscle wasting (Sarcopenia) is associated with poor outcomes in cancer patients. Early identification of sarcopenia can facilitate nutritional and exercise intervention. Cross-sectional skeletal muscle (SM) area at the third lumbar vertebra (L3) slice of a computed tomography (CT) image is increasingly used to assess body composition and calculate SM index (SMI), a validated surrogate marker for sarcopenia in cancer. Manual segmentation of SM requires multiple steps, which limits use in routine clinical practice. This project aims to develop an automatic method to segment L3 muscle in CT scans. METHODS: Attenuation correction CTs from full body PET-CT scans from patients enrolled in two prospective trials were used. The training set consisted of 66 non-small cell lung cancer (NSCLC) patients who underwent curative intent radiotherapy. An additional 42 NSCLC patients prescribed curative intent chemo-radiotherapy from a second trial were used for testing. Each patient had multiple CT scans taken at different time points prior to and post- treatment (147 CTs in the training and validation set and 116 CTs in the independent testing set). Skeletal muscle at L3 vertebra was manually segmented by two observers, according to the Alberta protocol to serve as ground truth labels. This included 40 images segmented by both observers to measure inter-observer variation. An ensemble of 2.5D fully convolutional neural networks (U-Nets) was used to perform the segmentation. The final layer of U-Net produced the binary classification of the pixels into muscle and non-muscle area. The model performance was calculated using Dice score and absolute percentage error (APE) in skeletal muscle area between manual and automated contours. RESULTS: We trained five 2.5D U-Nets using 5-fold cross validation and used them to predict the contours in the testing set. The model achieved a mean Dice score of 0.92 and an APE of 3.1% on the independent testing set. This was similar to inte

PURPOSE: To investigate multiple deep learning methods for automated segmentation (auto-segmentation) of the parotid glands, submandibular glands, and level II and level III lymph nodes on magnetic resonance imaging (MRI). Outlining radiosensitive organs on images used to assist radiation therapy (radiotherapy) of patients with head and neck cancer (HNC) is a time-consuming task, in which variability between observers may directly impact on patient treatment outcomes. Auto-segmentation on computed tomography imaging has been shown to result in significant time reductions and more consistent outlines of the organs at risk. METHODS: Three convolutional neural network (CNN)-based auto-segmentation architectures were developed using manual segmentations and T2-weighted MRI images provided from the American Association of Physicists in Medicine (AAPM) radiotherapy MRI auto-contouring (RT-MAC) challenge dataset (n = 31). Auto-segmentation performance was evaluated with segmentation similarity and surface distance metrics on the RT-MAC dataset with institutional manual segmentations (n = 10). The generalizability of the auto-segmentation methods was assessed on an institutional MRI dataset (n = 10). RESULTS: Auto-segmentation performance on the RT-MAC images with institutional segmentations was higher than previously reported MRI methods for the parotid glands (Dice: 0.860 ± 0.067, mean surface distance [MSD]: 1.33 ± 0.40 mm) and the first report of MRI performance for submandibular glands (Dice: 0.830 ± 0.032, MSD: 1.16 ± 0.47 mm). We demonstrate that high-resolution auto-segmentations with improved geometric accuracy can be generated for the parotid and submandibular glands by cascading a localizer CNN and a cropped high-resolution CNN. Improved MSDs were observed between automatic and manual segmentations of the submandibular glands when a low-resolution auto-segmentation was used as prior knowledge in the second-stage CNN. Reduced auto-segmentation performance was obse

BACKGROUND AND PURPOSE: Stereotactic radiotherapy combines image guidance and high precision delivery with small fields to deliver high doses per fraction in short treatment courses. In preparation for extension of these treatment techniques to paediatric patients we characterised and compared doses out-of-field in a paediatric anthropomorphic phantom for small flattened and flattening filter free (FFF) photon beams. METHOD AND MATERIALS: Dose measurements were taken in several organs and structures outside the primary field in an anthropomorphic phantom of a 5 year old child (CIRS) using thermoluminescence dosimetry (LiF:Mg,Cu,P). Out-of-field doses from a medical linear accelerator were assessed for 6 MV flattened and FFF beams of field sizes between 2 × 2 and 10 × 10 cm2. RESULTS: FFF beams resulted in reduced out-of-field doses for all field sizes when compared to flattened beams. Doses for FFF and flattened beams converged for all field sizes at larger distances (>40 cm) from the central axis as leakage becomes the primary source of out-of-field dose. Rotating the collimator to place the MLC bank in the longitudinal axis of the patient was shown to reduce the peripheral doses measured by up to 50% in Varian linear accelerators. CONCLUSION: Minimising out-of-field doses by using FFF beams and aligning the couch and collimator to provide tertiary shielding demonstrated advantages of small field, FFF treatments in a paediatric setting.

BACKGROUND AND PURPOSE: The purpose of this work is to present the clinical experience from the first-in-human trial of real-time tumor targeting via MLC tracking for stereotactic ablative body radiotherapy (SABR) of lung lesions. METHODS AND MATERIALS: Seventeen patients with stage 1 non-small cell lung cancer (NSCLC) or lung metastases were included in a study of electromagnetic transponder-guided MLC tracking for SABR (NCT02514512). Patients had electromagnetic transponders inserted near the tumor. An MLC tracking SABR plan was generated with planning target volume (PTV) expanded 5 mm from the end-exhale gross tumor volume (GTV). A clinically approved comparator plan was generated with PTV expanded 5 mm from a 4DCT-derived internal target volume (ITV). Treatment was delivered using a standard linear accelerator to continuously adapt the MLC based on transponder motion. Treated volumes and reconstructed delivered dose were compared between MLC tracking and comparator ITV-based treatment. RESULTS: All seventeen patients were successfully treated with MLC tracking (70 successful fractions). MLC tracking treatment delivery time averaged 8 minutes. The time from the start of CBCT to the end of treatment averaged 22 minutes. The MLC tracking PTV for 16/17 patients was smaller than the ITV-based PTV (range -1.6% to 44% reduction, or -0.6 to 18 cc). Reductions in mean lung dose (27 cGy) and V20Gy (50 cc) were statistically significant (p < 0.02). Reconstruction of treatment doses confirmed a statistically significant improvement in delivered GTV D98% (p < 0.05) from planned dose compared with the ITV-based plans. CONCLUSION: The first treatments with lung MLC tracking have been successfully performed in seventeen SABR patients. MLC tracking for lung SABR is feasible, efficient and delivers high-precision target dose and lower normal tissue dose.

Machine learning technology has a growing impact on radiation oncology with an increasing presence in research and industry. The prevalence of diverse data including 3D imaging and the 3D radiation dose delivery presents potential for future automation and scope for treatment improvements for cancer patients. Harnessing this potential requires standardization of tools and data, and focused collaboration between fields of expertise. The rapid advancement of radiation oncology treatment technologies presents opportunities for machine learning integration with investments targeted towards data quality, data extraction, software, and engagement with clinical expertise. In this review, we provide an overview of machine learning concepts before reviewing advances in applying machine learning to radiation oncology and integrating these techniques into the radiation oncology workflows. Several key areas are outlined in the radiation oncology workflow where machine learning has been applied and where it can have a significant impact in terms of efficiency, consistency in treatment and overall treatment outcomes. This review highlights that machine learning has key early applications in radiation oncology due to the repetitive nature of many tasks that also currently have human review. Standardized data management of routinely collected imaging and radiation dose data are also highlighted as enabling engagement in research utilizing machine learning and the ability integrate these technologies into clinical workflow to benefit patients. Physicists need to be part of the conversation to facilitate this technical integration.

PURPOSE: Functional lung mapping from Ga68-ventilation/perfusion (V/Q) PET/CT, which has been shown to correlate with pulmonary function tests (PFTs), may be beneficial in a number of clinical applications where sparing regions of high lung function is of interest. Regions of clumping in the proximal airways in patients with airways disease can result in areas of focal intense activity and artefact in ventilation imaging. These artefacts may even shine through to subsequent perfusion images and create a challenge for quantitative analysis of PET imaging. We aimed to develop an automated algorithm that interprets the uptake histogram of PET images to calculate a peak uptake value more representative of the global lung volume. METHODS: Sixty-six patients recruited from a prospective clinical trial underwent both V/Q PET/CT imaging and PFT analysis before treatment. PET images were normalised using an iterative histogram analysis technique to account for tracer hotspots prior to the threshold-based delineation of varying values. Pearson's correlation between fractional lung function and PFT score was calculated for ventilation, perfusion, and matched imaging volumes at varying threshold values. RESULTS: For all functional imaging thresholds, only FEV1/FVC PFT yielded reasonable correlations to image-based functional volume. For ventilation, a range of 10-30% of adapted peak uptake value provided a reasonable threshold to define a volume that correlated with FEV1/FVC (r = 0.54-0.61). For perfusion imaging, a similar correlation was observed (r = 0.51-0.56) in the range of 20-60% adapted peak threshold. Matched volumes were closely linked to ventilation with a threshold range of 15-35% yielding a similar correlation (r = 0.55-0.58). CONCLUSIONS: Histogram normalisation may be implemented to determine the presence of tracer clumping hotspots in Ga-68 V/Q PET imaging allowing for automated delineation of functional lung and standardisation of functional volume reporting.

BACKGROUND: Stereotactic ablative body radiotherapy (SABR) of primary kidney cancers is confounded by motion. There is a risk of interplay effect if the dose is delivered using volumetric modulated arc therapy (VMAT) and flattening filter-free (FFF) dose rates due to target and linac motion. This study aims to provide an efficient way to generate plans with minimal aperture complexity. METHODS: In this retrospective study, 62 patients who received kidney SABR were reviewed. For each patient, two plans were created using internal target volume based motion management, on the average intensity projection of a four-dimensional CT. In the first plan, optimization was performed using a knowledge-based planning model based on delivered clinical plans in our institution. In the second plan, the optimization was repeated, with a maximum monitor unit (MU) objective applied in the optimization. Dose-volume, conformity, and complexity metric (with the field edge metric and the modulation complexity score) were compared between the two plans. Results are shown in terms of median (first quartile - third quartile). RESULTS: Similar dosimetry was obtained with and without the utilization of an objective on the MU. However, complexity was reduced by using the objective on the MUs (modulation complexity score = 0.55 (0.50-0.61) / 0.33 (0.29-0.36), P-value < 10-10 , with/without the MU objective). Reduction of complexity was driven by a larger aperture area (area aperture variability = 0.68 (0.64-0.73) / 0.42 (0.37-0.45), P-value < 10-10 , with/without the MU objective). Using the objective on the MUs resulted in a more spherical dose distribution (sphericity 50% isodose = 0.73 (0.69-0.75) / 0.64 (0.60-0.68), P-value < 10-8 , with/without the MU objective) reducing dose to organs at risk given respiratory motion. CONCLUSIONS: Aperture complexity is reduced in kidney SABR by using an objective on the MU delivery with VMAT and FFF dose rate.

INTRODUCTION: Quality assurance (QA) of treatment plans in clinical trials improves protocol compliance and patient outcomes. Retrospective use of knowledge-based-planning (KBP) in clinical trials has demonstrated improved treatment plan quality and consistency. We report the results of prospective use of KBP for real-time QA of treatment plan quality in the TROG 15.03 FASTRACK II trial, which evaluates efficacy of stereotactic ablative body radiotherapy (SABR) for kidney cancer. METHODS: A KBP model was generated based on single institution data. For each patient in the KBP phase (open to the last 31 patients in the trial), the treating centre submitted treatment plans 7 days prior to treatment. A treatment plan was created by using the KBP model, which was compared with the submitted plan for each organ-at-risk (OAR) dose constraint. A report comparing each plan for each OAR constraint was provided to the submitting centre within 24 h of receiving the plan. The centre could then modify the plan based on the KBP report, or continue with the existing plan. RESULTS: Real-time feedback using KBP was provided in 24/31 cases. Consistent plan quality was in general achieved between KBP and the submitted plan. KBP review resulted in replan and improvement of OAR dosimetry in two patients. All centres indicated that the feedback was a useful QA check of their treatment plan. CONCLUSION: KBP for real-time treatment plan review was feasible for 24/31 cases, and demonstrated ability to improve treatment plan quality in two cases. Challenges include integration of KBP feedback into clinical timelines, interpretation of KBP results with respect to clinical trade-offs, and determination of appropriate plan quality improvement criteria.

BACKGROUND: Fiducial markers are used as surrogates for tumor location during radiation therapy treatment. Developments in lung fiducial marker and implantation technology have provided a means to insert markers endobronchially for tracking of lung tumors. This study quantifies the surrogacy uncertainty (SU) when using endobronchially implanted markers as a surrogate for lung tumor position. METHODS: We evaluated SU for 17 patients treated in a prospective electromagnetic-guided MLC tracking trial. Tumor and markers were segmented on all phases of treatment planning 4DCTs and all frames of pretreatment kilovoltage fluoroscopy acquired from lateral and frontal views. The difference in tumor and marker position relative to end-exhale position was calculated as the SU for both imaging methods and the distributions of uncertainties analyzed. RESULTS: The mean (range) tumor motion amplitude in the 4DCT scan was 5.9 mm (1.7-11.7 mm) in the superior-inferior (SI) direction, 2.2 mm (0.9-5.5 mm) in the left-right (LR) direction, and 3.9 mm (1.2-12.9 mm) in the anterior-posterior (AP) direction. Population-based analysis indicated symmetric SU centered close to 0 mm, with maximum 5th/95th percentile values over all axes of -2.0 mm/2.1 mm with 4DCT, and -2.3/1.3 mm for fluoroscopy. There was poor correlation between the SU measured with 4DCT and that measured with fluoroscopy on a per-patient basis. We observed increasing SU with increasing surrogate motion. Based on fluoroscopy analysis, the mean (95% CI) SU was 5% (2%-8%) of the motion magnitude in the SI direction, 16% (6%-26%) of the motion magnitude in the LR direction, and 33% (23%-42%) of the motion magnitude in the AP direction. There was no dependence of SU on marker distance from the tumor. CONCLUSION: We have quantified SU due to use of implanted markers as surrogates for lung tumor motion. Population 95th percentile range are up to 2.3 mm, indicating the approximate contribution of SU to total geometric uncertainty

INTRODUCTION: Low muscle mass and low muscle attenuation (radiodensity), reflecting increased muscle adiposity, are prevalent muscle abnormalities in people with lung cancer receiving curative intent chemoradiation therapy (CRT) or radiation therapy (RT). Currently, there is a limited understanding of the magnitude, determinants and clinical significance of these muscle abnormalities in the lung cancer CRT/RT population. The primary objective of this study is to identify the predictors of muscle abnormalities (low muscle mass and muscle attenuation) and their depletion over time in people with lung cancer receiving CRT/RT. Secondary objectives are to assess the magnitude of change in these parameters and their association with health-related quality of life, treatment completion, toxicities and survival. METHODS AND ANALYSIS: Patients diagnosed with lung cancer and planned for treatment with CRT/RT are invited to participate in this prospective observational study, with a target of 120 participants. The impact and predictors of muscle abnormalities (assessed via CT at the third lumbar vertebra) prior to and 2 months post CRT/RT on the severity of treatment toxicities, treatment completion and survival will be assessed by examining the following variables: demographic and clinical factors, weight loss, malnutrition, muscle strength, physical performance, energy and protein intake, physical activity and sedentary time, risk of sarcopenia (Strength, Assistance in walking, Rise from a chair, Climb stairs, Falls history (SARC-F) score alone and with calf-circumference) and systemic inflammation. A sample of purposively selected participants with muscle abnormalities will be invited to take part in semistructured interviews to understand their ability to cope with treatment and explore preference for treatment strategies focused on nutrition and exercise. ETHICS AND DISSEMINATION: The PREDICT study received ethics approval from the Human Research Ethics Committee at Peter

PURPOSE: Fewer attendances for radiation therapy results in increased efficiency and less foot traffic within a radiation therapy department. We investigated outcomes after single-fraction (SF) stereotactic body radiation therapy (SBRT) in patients with oligometastatic disease. METHODS AND MATERIALS: Between February 2010 and June 2019, patients who received SF SBRT to 1 to 5 sites of oligometastatic disease were included in this retrospective study. The primary objective was to describe patterns of first failure after SBRT. Secondary objectives included overall survival (OS), progression-free survival (PFS), high-grade treatment-related toxicity (Common Terminology Criteria for Adverse Events grade ≥3), and freedom from systemic therapy (FFST). RESULTS: In total, 371 patients with 494 extracranial oligometastases received SF SBRT ranging from 16 Gy to 28 Gy. The most common primary malignancies were prostate (n = 107), lung (n = 63), kidney (n = 52), gastrointestinal (n = 51), and breast cancers (n = 42). The median follow-up was 3.1 years. The 1-, 3-, and 5-year OS was 93%, 69%, and 55%, respectively; PFS was 48%, 19%, and 14%, respectively; and FFST was 70%, 43%, and 35%, respectively. Twelve patients (3%) developed grade 3 to 4 treatment-related toxicity, with no grade 5 toxicity. As the first site of failure, the cumulative incidence of local failure (irrespective of other failures) at 1, 3 and 5 years was 4%, 8%, and 8%, respectively; locoregional relapse at the primary was 10%, 18%, and 18%, respectively; and distant failure was 45%, 66%, and 70%, respectively. CONCLUSIONS: SF SBRT is safe and effective, and a significant proportion of patients remain FFST for several years after therapy. This approach could be considered in resource-constrained or bundled-payment environments. Locoregional failure of the primary site is the second most common pattern of failure, suggesting a role for optimization of primary control during metastasis-directed therapy.

Radiomics is a promising technique for discovering image based biomarkers of therapy response in cancer. Reproducibility of radiomics features is a known issue that is addressed by the image biomarker standardisation initiative (IBSI), but it remains challenging to interpret previously published radiomics signatures. This study investigates the reproducibility of radiomics features calculated with two widely used radiomics software packages (IBEX, MaZda) in comparison to an IBSI compliant software package (PyRadiomics). Intensity histogram, shape and textural features were extracted from 334 diffusion weighted magnetic resonance images of 59 head and neck cancer (HNC) patients from the PREDICT-HN observational radiotherapy study. Based on name and linear correlation, PyRadiomics shares 83 features with IBEX and 49 features with MaZda, a sub-set of well correlated features are considered reproducible (IBEX: 15 features, MaZda: 18 features). We explore the impact of including non-reproducible radiomics features in a HNC radiotherapy response model. It is possible to classify equivalent patient groups using radiomic features from either software, but only when restricting the model to reliable features using a correlation threshold method. This is relevant for clinical biomarker validation trials as it provides a framework to assess the reproducibility of reported radiomic signatures from existing trials.

BACKGROUND: Stereotactic Ablative Body Radiotherapy (SABR) is a non-invasive treatment which allows delivery of an ablative radiation dose with high accuracy and precision. SABR is an established treatment for both primary and secondary liver malignancies, and technological advances have improved its efficacy and safety. Respiratory motion management to reduce tumour motion and image guidance to achieve targeting accuracy are crucial elements of liver SABR. This phase II multi-institutional TROG 17.03 study, Liver Ablative Radiotherapy using Kilovoltage intrafraction monitoring (LARK), aims to investigate and assess the dosimetric impact of the KIM real-time image guidance technology. KIM utilises standard linear accelerator equipment and therefore has the potential to be a widely available real-time image guidance technology for liver SABR. METHODS: Forty-six patients with either hepatocellular carcinoma or oligometastatic disease to the liver suitable for and treated with SABR using Kilovoltage Intrafraction Monitoring (KIM) guidance will be included in the study. The dosimetric impact will be assessed by quantifying accumulated patient dose distribution with or without the KIM intervention. The patient treatment outcomes of local control, toxicity and quality of life will be measured. DISCUSSION: Liver SABR is a highly effective treatment, but precise dose delivery is challenging due to organ motion. Currently, there is a lack of widely available options for performing real-time tumour localisation to assist with accurate delivery of liver SABR. This study will provide an assessment of the impact of KIM as a potential solution for real-time image guidance in liver SABR. TRIAL REGISTRATION: This trial was registered on December 7th 2016 on ClinicalTrials.gov under the trial-ID NCT02984566 .

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BACKGROUND: Stereotactic Ablative Body Radiotherapy (SABR) is a non-invasive treatment which allows delivery of an ablative radiation dose with high accuracy and precision. SABR is an established treatment for both primary and secondary liver malignancies, and technological advances have improved its efficacy and safety. Respiratory motion management to reduce tumour motion and image guidance to achieve targeting accuracy are crucial elements of liver SABR. This phase II multi-institutional TROG 17.03 study, Liver Ablative Radiotherapy using Kilovoltage intrafraction monitoring (LARK), aims to investigate and assess the dosimetric impact of the KIM real-time image guidance technology. KIM utilises standard linear accelerator equipment and therefore has the potential to be a widely available real-time image guidance technology for liver SABR. METHODS: Forty-six patients with either hepatocellular carcinoma or oligometastatic disease to the liver suitable for and treated with SABR using Kilovoltage Intrafraction Monitoring (KIM) guidance will be included in the study. The dosimetric impact will be assessed by quantifying accumulated patient dose distribution with or without the KIM intervention. The patient treatment outcomes of local control, toxicity and quality of life will be measured. DISCUSSION: Liver SABR is a highly effective treatment, but precise dose delivery is challenging due to organ motion. Currently, there is a lack of widely available options for performing real-time tumour localisation to assist with accurate delivery of liver SABR. This study will provide an assessment of the impact of KIM as a potential solution for real-time image guidance in liver SABR. TRIAL REGISTRATION: This trial was registered on December 7th 2016 on ClinicalTrials.gov under the trial-ID NCT02984566 .

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Stereotactic ablative body radiotherapy (SABR) is demonstrating good local control for patients with inoperable primary renal cell carcinoma. In a previous pilot study we identified magnetic resonance imaging (MRI) early response biomarkers that correlate with later morphological changes in computed tomography (CT) images. These early functional changes in diffusion and perfusion following radiotherapy were observed on MRI and have the potential to identify non-responders who may benefit from adjuvant or salvage therapies. Here we detail the imaging protocol for an MRI sub-study of the Focal Ablative STereotactic Radiosurgery for Cancers of the Kidney (FASTRACK II) trial. A preliminary patient case demonstrates the high quality of the imaging data, with discussion of the improvements made from the pilot protocol for improved motion management and correction. We aim to validate the previously identified early response MRI biomarkers with this rich prospective multi-centre dataset.

Since the early days of megavoltage Radiation Therapy (RT), the potential of delivering treatment to a sub group of patients in an upright position has been recognized. Compared to lying horizontally, treating patients in an upright position offers potential benefits in terms of patient comfort especially for patients experiencing dyspnoea and saliva accumulation when lying down. Dosimetric benefits can also be gained from changes in the volume and location of lungs and heart in an upright position, which are potentially advantageous for clinical situations including Hodgkin's disease, lung and breast malignancies. Since the 1950's, upright stabilization mechanisms have ranged from standalone chair based apparatus to couch-top attachments with increasingly customizable solutions. The introduction of Computed-Tomography (CT) based three-dimensional (3D) dosimetry in the 1980's−90's necessitated image acquisition in a horizontal position (supine or prone), significantly reducing options for alternative patient positioning and upright techniques. Despite this, upright techniques have still been utilized where clinically indicated for palliative and novel approaches often involving non-standard treatment scenarios. More recently, a small number of centers have reported on specialized equipment capable of acquiring planning data with the patient in a vertical position. The possibility of acquiring planning quality Cone Beam CT (CBCT) on linear accelerators has recently reinvigorated the potential to deliver highly accurate and targeted treatments to patients in an upright position. This paper reflects on the historical applications of upright RT and explores new possibilities for this technology in modern RT departments.

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.

BACKGROUND: In the curative-intent treatment of locally advanced lung cancer, significant morbidity and mortality can result from thoracic radiation therapy. Symptomatic radiation pneumonitis occurs in one in three patients and can lead to radiation-induced fibrosis. Local failure occurs in one in three patients due to the lungs being a dose-limiting organ, conventionally restricting tumour doses to around 60 Gy. Functional lung imaging using positron emission tomography (PET)/CT provides a geographic map of regional lung function and preclinical studies suggest this enables personalised lung radiotherapy. This map of lung function can be integrated into Volumetric Modulated Arc Therapy (VMAT) radiotherapy planning systems, enabling conformal avoidance of highly functioning regions of lung, thereby facilitating increased doses to tumour while reducing normal tissue doses. METHODS AND ANALYSIS: This prospective interventional study will investigate the use of ventilation and perfusion PET/CT to identify highly functioning lung volumes and avoidance of these using VMAT planning. This single-arm trial will be conducted across two large public teaching hospitals in Australia. Twenty patients with stage III non-small cell lung cancer will be recruited. All patients enrolled will receive dose-escalated (69 Gy) functional avoidance radiation therapy. The primary endpoint is feasibility with this achieved if ≥15 out of 20 patients meet pre-defined feasibility criteria. Patients will be followed for 12 months post-treatment with serial imaging, biomarkers, toxicity assessment and quality of life assessment. DISCUSSION: Using advanced techniques such as VMAT functionally adapted radiation therapy may enable safe moderate dose escalation with an aim of improving local control and concurrently decreasing treatment related toxicity. If this technique is proven feasible, it will inform the design of a prospective randomised trial to assess the clinical benefits of functional lung

Four-dimensional computerized tomography (4DCT) is required for stereotactic ablative body radiotherapy (SABR) of mobile targets to account for tumor motion during treatment planning and delivery. In this study, we report on the impact of an image review quality assurance process performed prior to treatment planning by medical physicists for 4DCT scans used for SABR treatment. Reviews were performed of 211 4DCT scans (193 patients) over a 3-yr period (October 2014 to October 2017). Treatment sites included lung (n = 168), kidney/adrenal/adrenal gland (n = 12), rib (n = 4), mediastinum (n = 10), liver (n = 2), T-spine (n = 1), and other abdominal sites (n = 14). It was found that in 23% (n = 49) of cases patient management was altered due to the review process. The most frequent intervention involved patient-specific contouring advice (n = 35 cases, 17%) including adjustment of internal target volume (ITV) margins. In 13 cases (6%) a rescan was requested due to extensive motion artifact rendering the scan inadequate for SABR treatment planning. 4DCT review by medical physicists was found to be an effective method to improve plan quality for SABR.

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.

PURPOSE: The aim of this study was to provide a comprehensive assessment of patient intrafraction motion in linac-based frameless stereotactic radiosurgery (SRS) and radiotherapy (SRT). METHODS: A retrospective review was performed on 101 intracranial SRS/SRT patients immobilized with the Klarity stereotactic thermoplastic mask (compatible with the Brainlab frameless stereotactic system) and aligned on a 6 Degree of Freedom (DoF) couch with the Brainlab ExacTrac image guidance system. Both pretreatment and intrafraction correction data are provided as observed by the ExacTrac system. The effects of couch angle and treatment duration on positioning outcomes are also explored. RESULTS: Initial setup data for patients is shown to vary by up to ±4.18 mm, ±2.97°, but when corrected with a single x-ray image set with ExacTrac, patient positions are corrected to within ±2.11 mm, ±2.27°. Intrafraction patient motion is shown to be uniformly random and independent of both time and couch angle. Patient motion was also limited to within approximately 3 mm, 3° by the thermoplastic mask. CONCLUSIONS: Our results indicate that since patient intrafraction motion is unrelated to couch rotation and treatment duration, intrafraction patient monitoring in 6 DoF is required to minimize intracranial SRS/SRT margins.

Peripheral lung lesions treated with a single fraction of stereotactic ablative body radiotherapy (SABR) utilizing volumetric modulated arc therapy (VMAT) delivery and flattening filter-free (FFF) beams represent a potentially high-risk scenario for clinically significant dose blurring effects due to interplay between the respiratory motion of the lesion and dynamic multi-leaf collimators (MLCs). The aim of this study was to determine an efficient means of developing low-modulation VMAT plans in the Eclipse treatment planning system (v15.5, Varian Medical Systems, Palo Alto, USA) in order to minimize this risk, while maintaining dosimetric quality. The study involved 19 patients where an internal target volume (ITV) was contoured to encompass the entire range of tumor motion, and a planning target volume (PTV) created using a 5-mm isotropic expansion of this contour. Each patient had seven plan variations created, with each rescaled to achieve the clinical planning goal for PTV coverage. All plan variations used the same field arrangement, and consisted of one dynamic conformal arc therapy (DCAT) plan, and six VMAT plans with varying degrees of modulation restriction, achieved through utilizing different combinations of the aperture shape controller (ASC) in the calculation parameters, and monitor unit (MU) objective during optimization. The dosimetric quality was assessed based on RTOG conformity indices (CI100/CI50), as well as adherence to dose-volume metrics used clinically at our institution. Plan complexity was assessed based on the modulation factor (MU/cGy) and the field edge metric. While VMAT plans with the least modulation restriction achieved the best dosimetry, it was found that there was no clinically significant trade-off in terms of dose to organs at risk and conformity by reducing complexity. Furthermore, it was found that utilizing the ASC and MU objective could reduce plan complexity to near-DCAT levels with improved dosimetry, which may be suffic

PURPOSE: This study focused on determining risks from stereotactic radiotherapy using flattening filter-free (FFF) beams for patients with cardiac implantable electronic device (CIEDs). Two strategies were employed: a) a retrospective analysis of patients with CIEDs who underwent stereotactic radiosurgery (SRS)/SBRT at the Peter MacCallum Cancer Centre between 2014 and 2018 and b) an experimental study on the impact of FFF beams on CIEDs. METHODS: A retrospective review was performed. Subsequently, a phantom study was performed using 30 fully functional explanted CIEDs from two different manufacturers. Irradiation was carried out in a slab phantom with 6-MV and 10-MV FFF beams. First, a repetition-rate test (RRT) with a range of beam pulse frequencies was conducted. Then, multifraction SBRT (48 Gy/4 Fx) and single-fraction SBRT (28 Gy/1 Fx) treatment plans were used for lung tumors delivered to the phantom. RESULTS: Between 2014 and 2018, 13 cases were treated with an FFF beam (6 MV, 1400 MU/min or 10 MV, 2400 MU/min), and 15 cases were treated with a flattening filter (FF) beam (6 MV, 600 MU/min). All the devices were positioned outside the treatment field at a distance of more than 5 cm, except for one case, and no failures were reported due to SBRT/SRS. In the phantom rep-rate tests, inappropriate sensing occurred, starting at a rep-rate of 1200 MU/min. Cardiac implantable electronic device anomalies during and after delivering VMAT-SBRT with a 10-MV FFF beam were observed. CONCLUSIONS: The study showed that caution should be paid to managing CIED patients when they undergo SBRT using FFF beams, as it is recommended by AAPM TG-203. Correspondingly, it was found that for FFF beams although there is small risk from dose-rate effects, delivering high dose of radiation with beam energy greater than 6 MV and high-dose rate to CIEDs positioned in close vicinity of the PTV may present issues.

PURPOSE: Kilovoltage intrafraction monitoring (KIM) is a novel software platform implemented on standard radiation therapy systems and enabling real-time image guided radiation therapy (IGRT). In a multi-institutional prospective trial, we investigated whether real-time IGRT improved the accuracy of the dose patients with prostate cancer received during radiation therapy. METHODS AND MATERIALS: Forty-eight patients with prostate cancer were treated with KIM-guided SABR with 36.25 Gy in 5 fractions. During KIM-guided treatment, the prostate motion was corrected for by either beam gating with couch shifts or multileaf collimator tracking. A dose reconstruction method was used to evaluate the dose delivered to the target and organs at risk with and without real-time IGRT. Primary outcome was the effect of real-time IGRT on dose distributions. Secondary outcomes included patient-reported outcomes and toxicity. RESULTS: Motion correction occurred in ≥1 treatment for 88% of patients (42 of 48) and 51% of treatments (121 of 235). With real-time IGRT, no treatments had prostate clinical target volume (CTV) D98% dose 5% less than planned. Without real-time IGRT, 13 treatments (5.5%) had prostate CTV D98% doses 5% less than planned. The prostate CTV D98% dose with real-time IGRT was closer to the plan by an average of 1.0% (range, -2.8% to 20.3%). Patient outcomes showed no change in the 12-month patient-reported outcomes compared with baseline and no grade ≥3 genitourinary or gastrointestinal toxicities. CONCLUSIONS: Real-time IGRT is clinically effective for prostate cancer SABR.

Radiation dose is the therapeutic agent in radiotherapy where the objective is to maximise radiation dose to a target while minimising the dose to surrounding healthy tissues. Dose in this context is typically associated with the quantity “absorbed dose” as energy deposited per unit mass and measured in J/kg of tissue. However, even if high doses are delivered (no stochastic distribution considered) and photon or electron radiation is considered (no neutrons or heavy charged particles), there will be differences in the actual dose delivered to different tissue types as the stopping power for the electrons that deliver the vast majority of dose varies with elemental composition. Historically, radiation beam calibration and dose calculations were performed in water as a readily available, easily standardised material that closely matches the radiation properties of many human tissues. However, many superior dose calculation algorithms that have recently become available due to improved computer power (Monte Carlo Calculations, Acuros) calculate dose as deposited in the medium. The present paper examines arguments for both and proposes that based on the current scientific and political developments specification of dose as dose to medium would be the more robust and future proof choice.

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