The impact of rectal spacers in MR-guided adaptive radiotherapy.

Background and purpose: The use of stereotactic ablative radiotherapy (SABR) for prostate cancer has increased significantly. However, SABR can elevate the risk of moderate gastrointestinal (GI) side effects. Rectal spacers mitigate this risk by reducing the rectal dose. This study evaluates the impact of rectal spacers in MR-guided adaptive radiotherapy (MRgART) for prostate SABR. Materials and methods: A retrospective analysis was conducted on twenty patients with localised prostate cancer treated on the Unity MR-Linac at a single centre. Half of the cohort (n = 10) had rectal spacers placed before treatment. The adapt-to-shape strategy was used for online MRgART, and non-adapted plans were later generated offline for comparison. Dosimetric assessments were made between spacer and no-spacer cohorts, and between online adapted and non-adapted plans. Clinician-reported outcomes for genitourinary (GU) and GI toxicity were assessed at 3-, 6-, and 12-months post-treatment using Common Terminology Criteria for Adverse Events v.5.0. Results: No grade 2 or higher toxicity was observed in either cohort. Overall, the dosimetric analysis showed comparable results between the cohorts for target volumes, with D95% of 36.3 Gy in the spacer cohort and 36.0 Gy in the no-spacer cohort (p = 0.08). The spacer cohort demonstrated significant benefits in all rectal dose objectives (p < 0.0001) and in some bladder objectives (V40, p = 0.03; V36, p = 0.03). Failure rates for achieving planning objectives were similar between spacer and no-spacer groups for online adapted plans, with most rates ranging from 0 % to 4 % in both groups. Conclusion: The findings from this cohort suggest that MRgART is safe and effective for prostate SABR, with comparable toxicity rates in both spacer and no-spacer cohorts. While rectal spacers offer dosimetric advantages, the adaptive nature of MRgART can mitigate some dosimetric disparities, potentially reducing the need for invasive spacer placement. However, further studies with larger patient populations are needed to confirm these results.

Dosimetric impact of variable air cavity within PTV for rectum cancer.

PURPOSE: The aim of this study is to determine the impact of rectal air volume changes on treatment plan quality, and subsequently inform daily cone-beam computed tomography (CBCT) evaluation constraints, in terms of acceptable rectal air volume during treatment. METHODS: Twelve rectal cancer patients who exhibited rectal air within the PTV on their planning CT were selected. A study was conducted to evaluate the deterioration in plan quality due to expanding air volume. For each case, the air cavity volume was isotropically expanded in three dimensions using predefined margins of 3, 5, 7, and 10 mm, while deforming bladder and rectum contours. A constraint was applied to the bony anatomy to restrict the deformation. Treatment plans were then generated for all twelve patients by recalculating the reference plan with the expanded air cavity volume. RESULTS: As the air cavity expanded, the maximum relative change in D98% coverage, compared to the reference plan, decreased by 10.8% ± 3.5%, while the D2% increased by 3.5% ± 0.9%. The positioning of the air cavity notably influenced the D98% variability with the 3 mm expansion. D98% coverage falls below 95% when the air cavity volume exceeds 17 cm3. On average, D2% coverage increased by 0.5% with each expansion. At the largest expansion, extensive coverage of 102% and 105% isodoses was observed compared to the reference plan. CONCLUSION: Air cavity volumes above 17 cm3 can potentially degrade the high-dose PTV coverage while increasing the regions covered by the 102% and 105% isodoses. Clinical CBCT guidelines were deduced, recommending a maximum threshold of 3.2 cm in diameter in any direction.

Tools and recommendations for commissioning and quality assurance of deformable image registration in radiotherapy.

Multiple tools are available for commissioning and quality assurance of deformable image registration (DIR), each with their own advantages and disadvantages in the context of radiotherapy. The selection of appropriate tools should depend on the DIR application with its corresponding available input, desired output, and time requirement. Discussions were hosted by the ESTRO Physics Workshop 2021 on Commissioning and Quality Assurance for DIR in Radiotherapy. A consensus was reached on what requirements are needed for commissioning and quality assurance for different applications, and what combination of tools is associated with this. For commissioning, we recommend the target registration error of manually annotated anatomical landmarks or the distance-to-agreement of manually delineated contours to evaluate alignment. These should be supplemented by the distance to discordance and/or biomechanical criteria to evaluate consistency and plausibility. Digital phantoms can be useful to evaluate DIR for dose accumulation but are currently only available for a limited range of anatomies, image modalities and types of deformations. For quality assurance of DIR for contour propagation, we recommend at least a visual inspection of the registered image and contour. For quality assurance of DIR for warping quantitative information such as dose, Hounsfield units or positron emission tomography-data, we recommend visual inspection of the registered image together with image similarity to evaluate alignment, supplemented by an inspection of the Jacobian determinant or bending energy to evaluate plausibility, and by the dose (gradient) to evaluate relevance. We acknowledge that some of these metrics are still missing in currently available commercial solutions.

Adapting outside the box: Simulation-free MR-guided stereotactic ablative radiotherapy for prostate cancer.

BACKGROUND AND PURPOSE: Magnetic resonance (MR)-guided radiotherapy (MRgRT) enhances treatment precision and adaptive capabilities, potentially supporting a simulation-free (sim-free) workflow. This work reports the first clinical implementation of a sim-free workflow using the MR-Linac for prostate cancer patients treated with stereotactic ablative radiotherapy (SABR). MATERIALS AND METHODS: Fifteen patients who had undergone a prostate-specific membrane antigen positron emission tomography/CT (PSMA-PET/CT) scan as part of diagnostic workup were included in this work. Two reference plans were generated per patient: one using PSMA-PET/CT (sim-free plan) and the other using standard simulation CT (simCT plan). Dosimetric evaluations included comparisons between simCT, sim-free, and first fraction plans. Timing measurements were conducted to assess durations for both simCT and sim-free pre-treatment workflows. RESULTS: All 15 patients underwent successful treatment using a sim-free workflow. Dosimetric differences between simCT, sim-free, and first fraction plans were minor and within acceptable clinical limits, with no major violations of standardised criteria. The sim-free workflow took on average 130 min, while the simCT workflow took 103 min. CONCLUSION: This work demonstrates the feasibility and benefits of sim-free MR-guided adaptive radiotherapy for prostate SABR, representing the first reported clinical experience in an ablative setting. By eliminating traditional simulation scans, this approach reduces patient burden by minimising hospital visits and enhances treatment accessibility.

Does a peer review group consensus process for MR-Linac patients affect clinical care? Evaluation of impact and feasibility.

Background and purpose: Peer review is an important component of quality assurance in radiotherapy. To our knowledge, there are no studies reporting on the feasibility and outcomes of the peer review process for magnetic resonance (MR) guided radiotherapy (MRgRT) on the MR linear accelerator (MR-Linac) despite the planning complexity involved and its evolving clinical indications. This study aimed to quantify the rate of change in treatment plans post-peer review and the time and resources required. Materials and methods: Fifty-five cases presented at weekly MR-Linac peer review meetings across two centres from 8 June to 21 September 2023 were prospectively collected. Cases were analysed to determine the rate and extent of plan changes based on the Peer Review Audit Tool for radiation oncology (PRAT) developed by the Royal Australian and New Zealand College of Radiologists (RANZCR). Results: Peer review resulted in changes to 36.4 % of treatment plans (n = 20), with 3.6 % (n = 2) having major changes requiring deferment of treatment. The most frequent changes were to organs at risk (OAR) volumes involving both delineation and increased OAR sparing (16.4 %, n = 9), total dose and fractionation (10.9 %, n = 6) and target volume dose coverage (5.5 %, n = 3). Patients with SBRT plans (39.1 % cf 22.2 %), oligometastatic/oligoprogressive sites (38.1 % cf 30.7 %) and reirradiation cases (41.2 % cf 34.2 %) had higher rates of change. Cases took a mean of 7 min (range 2-15 minutes) to discuss. Conclusion: The high rates of plan changes support the value of peer review in MRgRT. We recommend, where possible that all MRgRT cases, particularly those involving SBRT plans, oligometastatic/oligoprogressive sites, and/or reirradiation, be subject to peer review.

Open-source hardware and software for the measurement, characterization, reporting, and correction of geometric distortion in MRI.

BACKGROUND: Geometric distortion is a serious problem in MRI, particularly in MRI guided therapy. A lack of affordable and adaptable tools in this area limits research progress and harmonized quality assurance. PURPOSE: To develop and test a suite of open-source hardware and software tools for the measurement, characterization, reporting, and correction of geometric distortion in MRI. METHODS: An open-source python library was developed, comprising modules for parametric phantom design, data processing, spherical harmonics, distortion correction, and interactive reporting. The code was used to design and manufacture a distortion phantom consisting of 618 oil filled markers covering a sphere of radius 150 mm. This phantom was imaged on a CT scanner and a novel split-bore 1.0 T MRI magnet. The CT images provide distortion-free dataset. These data were used to test all modules of the open-source software. RESULTS: All markers were successfully extracted from all images. The distorted MRI markers were mapped to undistorted CT data using an iterative search approach. Spherical harmonics reconstructed the fitted gradient data to 1.0 ± 0.6% of the input data. High resolution data were reconstructed via spherical harmonics and used to generate an interactive report. Finally, distortion correction on an independent data set reduced distortion inside the DSV from 5.5 ± 3.1 to 1.6 ± 0.8 mm. CONCLUSION: Open-source hardware and software for the measurement, characterization, reporting, and correction of geometric distortion in MRI have been developed. The utility of these tools has been demonstrated via their application on a novel 1.0 T split bore magnet.

Technical note: Cryostat transmission characterization for MR linac - temporal stability, clinical impact and change implementation.

BACKGROUND: In the Unity MR linac (Elekta AB, Stockholm, Sweden), the radiation beam traverses the cryostat and the coil support structure. The resulting beam attenuation must be considered for output calibration and its variation with gantry angle must be characterized in the treatment planning system (TPS). PURPOSE: The aim of this work was to investigate the impact of a change of the cryostat transmission characterization (CTC) curve, due to the helium level modification, on clinical treatment plan dosimetry and to report on the experience with the CTC curve update. METHODS: Twenty stereotactic body radiotherapy (SBRT) treatment plans: 10 prostate and 10 oligo-metastatic cancer plans, prepared with a beam model incorporating the CTC curve acquired at installation time, were re-calculated using the model implementing CTC curve post helium top-up. To account for the CTC change as well as to align our system to the recent reference conditions recommendations, the new model was commissioned with the emphasis on the specifics associated with the treatment plan adaptation and the existence of the offline and online TPS components. RESULTS: Average CTV mean dose reduction by 0.45% in prostate cases and average GTV mean dose reduction by 0.22% in oligo-metastatic cases was observed. Updated model validation showcased good agreement between measurements and TPS calculations. CONCLUSIONS: The agreement between CTC measurements demonstrates its temporal constancy and robustness of the measurement method employed. A helium fill level change was shown to affect the CTC and led to a small but systematic dose calculation inaccuracy. Finally, model validation and end-to-end testing results presented, underscore the minimal impact of transitioning to the new beam model and new reference conditions.

Evaluating the relationship between contouring variability and modelled treatment outcome for prostate bed radiotherapy.

Objectives.Contouring similarity metrics are often used in studies of inter-observer variation and automatic segmentation but do not provide an assessment of clinical impact. This study focused on post-prostatectomy radiotherapy and aimed to (1) identify if there is a relationship between variations in commonly used contouring similarity metrics and resulting dosimetry and (2) identify the variation in clinical target volume (CTV) contouring that significantly impacts dosimetry.Approach.The study retrospectively analysed CT scans of 10 patients from the TROG 08.03 RAVES trial. The CTV, rectum, and bladder were contoured independently by three experienced observers. Using these contours reference simultaneous truth and performance level estimation (STAPLE) volumes were established. Additional CTVs were generated using an atlas algorithm based on a single benchmark case with 42 manual contours. Volumetric-modulated arc therapy (VMAT) treatment plans were generated for the observer, atlas, and reference volumes. The dosimetry was evaluated using radiobiological metrics. Correlations between contouring similarity and dosimetry metrics were calculated using Spearman coefficient (Γ). To access impact of variations in planning target volume (PTV) margin, the STAPLE PTV was uniformly contracted and expanded, with plans created for each PTV volume. STAPLE dose-volume histograms (DVHs) were exported for plans generated based on the contracted/expanded volumes, and dose-volume metrics assessed.Mainresults. The study found no strong correlations between the considered similarity metrics and modelled outcomes. Moderate correlations (0.5 <Γ< 0.7) were observed for Dice similarity coefficient, Jaccard, and mean distance to agreement metrics and rectum toxicities. The observations of this study indicate a tendency for variations in CTV contraction/expansion below 5 mm to result in minor dosimetric impacts.Significance. Contouring similarity metrics must be used with caution when interpreting them as indicators of treatment plan variation. For post-prostatectomy VMAT patients, this work showed variations in contours with an expansion/contraction of less than 5 mm did not lead to notable dosimetric differences, this should be explored in a larger dataset to assess generalisability.

Magnetic resonance guided adaptive post prostatectomy radiotherapy: Accumulated dose comparison of different workflows.

PURPOSE: The aim of this study was to assess the use of magnetic resonance guided adaptive radiotherapy (MRgART) in the post-prostatectomy setting; comparing dose accumulation for our initial seven patients treated with fully adaptive workflow on the Unity MR-Linac (MRL) and with non-adaptive plans generated offline. Additionally, we analyzed toxicity in patients receiving treatment. METHODS: Seven patients were treated with MRgART. The prescription was 70-72 Gy in 35-36 fractions. Patients were treated with an adapt to shape (ATS) technique. For each clinically delivered plan, a non-adaptive plan based upon the reference plan was generated and compared to the associated clinically delivered plan. A total of 468 plans were analyzed. Concordance Index of target and Organs at Risk (OARs) for each fraction with reference contours was analyzed. Acute toxicity was then assessed at six-months following completion of treatment with Common Terminology for Adverse Events (CTCAE) Toxicity Criteria. RESULTS: A total of 246 fractions were clinically delivered to seven patients; 234 fractions were delivered via MRgART and 12 fractions delivered via a traditional linear accelerator due to machine issues. Pre-treatment reference plans met CTV and OAR criteria. PTV coverage satisfaction was higher in the clinically delivered adaptive plans than non-adaptive comparison plans; 42.93% versus 7.27% respectively. Six-month CTCAE genitourinary and gastrointestinal toxicity was absent in most patients, and mild-to-moderate in a minority of patients (Grade 1 GU toxicity in one patient and Grade 2 GI toxicity in one patient). CONCLUSIONS: Daily MRgART treatment consistently met planning criteria. Target volume variability in prostate bed treatment can be mitigated by using MRgART and deliver satisfactory coverage of CTV whilst minimizing dose to adjacent OARs and reducing toxicity.

Selenium speciation studies in cancer patients to evaluate the responses of biomarkers of selenium status to different selenium compounds.

This work presents the first systematic comparison of selenium (Se) speciation in plasma from cancer patients treated orally with three Se compounds (sodium selenite, SS; L-selenomethionine, SeMet; or Se-methylselenocysteine, MSC) at 400 µg/day for 28 days. The primary goal was to investigate how these chemical forms of Se affect the plasma Se distribution, aiming to identify the most effective Se compound for optimal selenoprotein expression. This was achieved using methodology based on HPLC-ICP-MS after sample preparation/fractionation approaches. Measurements of total Se in plasma samples collected before and after 4 weeks of treatment showed that median total Se levels increased significantly from 89.6 to 126.4 µg kg-1 Se (p < 0.001), particularly when SeMet was administered (190.4 µg kg-1 Se). Speciation studies showed that the most critical differences between treated and baseline samples were seen for selenoprotein P (SELENOP) and selenoalbumin after administration with MSC (p = 5.8 × 10-4) and SeMet (p = 6.8 × 10-5), respectively. Notably, selenosugar-1 was detected in all low-molecular-weight plasma fractions following treatment, particularly with MSC. Two different chromatographic approaches and spiking experiments demonstrated that about 45% of that increase in SELENOP levels (to ~ 8.8 mg L-1) with SeMet is likely due to the non-specific incorporation of SeMet into the SELENOP affinity fraction. To the authors' knowledge, this has not been reported to date. Therefore, SELENOP is probably part of both the regulated (55%) and non-regulated (45%) Se pools after SeMet administration, whereas SS and MSC mainly contribute to the regulated one.

Management of rectal cancer in the era of total neoadjuvant therapy and watch and wait: A multidisciplinary team discussion at the Australasian Gastro-Intestinal Trials Group (AGITG) Annual Scientific Meeting 2022.

Rectal cancer is a common malignancy. The management of rectal cancer has recently evolved and has undergone a paradigm shift with the advent of treatment approaches such as total neoadjuvant therapy and the watch-and-wait approach. However, despite the recently available evidence, there is no consensus on the optimal management approach in the setting of locally advanced rectal cancer. To address some of the controversies, a joint multidisciplinary panel discussion was conducted at the Australasian Gastro-Intestinal Trials Group (AGITG) Annual Scientific Meeting in November 2022. Members from different subspecialties formed two panels and discussed three clinical cases in a debate format. Each case represented some of the complex issues faced by clinicians in this setting. The discussion is now presented in this manuscript, which depicts the different available management approaches and reiterates the importance of a multidisciplinary approach.

Glycerol contributes to tuberculosis susceptibility in male mice with type 2 diabetes.

Diabetes mellitus increases risk for tuberculosis disease and adverse outcomes. Most people with both conditions have type 2 diabetes, but it is unknown if type 1 and type 2 diabetes have identical effects on tuberculosis susceptibility. Here we show that male mice receiving a high-fat diet and streptozotocin to model type 2 diabetes, have higher mortality, more lung pathology, and higher bacterial burden following Mycobacterium tuberculosis infection compared to mice treated with streptozotocin or high-fat diet alone. Type 2 diabetes model mice have elevated plasma glycerol, which is a preferred carbon source for M. tuberculosis. Infection studies with glycerol kinase mutant M. tuberculosis reveal that glycerol utilization contributes to the susceptibility of the type 2 diabetes mice. Hyperglycemia impairs protective immunity against M. tuberculosis in both forms of diabetes, but our data show that elevated glycerol contributes to an additional adverse effect uniquely relevant to type 2 diabetes.

Optimising the MR-Linac as a standard treatment modality.

The magnetic resonance linear accelerator (MR-Linac) offers a new treatment paradigm, providing improved visualisation of targets and organs at risk while allowing for daily adaptation of treatment plans in real time. Online MR-guided adaptive treatment has reduced treatment uncertainties; however, the additional treatment time and resource requirements may be a concern. We present our experience of integrating an MR-Linac into a busy department and provide recommendations for improved clinical and resource efficiency. Furthermore, we discuss potential future technological innovations that can further optimise clinical productivity in a busy department.

Towards simulation-free MR-linac treatment: utilizing male pelvis PSMA-PET/CT and population-based electron density assignments.

Objective. This study aimed to investigate the dosimetric impact of using population-based relative electron density (RED) overrides in lieu of simulation computerized tomography (CT) in a magnetic resonance linear accelerator (MRL) workflow for male pelvis patients. Additionally, the feasibility of using prostate specific membrane antigen positron emission tomography/CT (PSMA-PET/CT) scans to assess patients' eligibility for this proposed workflow was examined.Approach. In this study, 74 male pelvis patients treated on an Elekta Unity 1.5 T MRL were retrospectively selected. The patients' individual RED values for 8 organs of interest were extracted from their simulation-CT images to establish population-based RED values. These values were used to generate individual (IndD) and population-based (PopD) RED dose plans, representing current and proposed MRL workflows, respectively. Lastly, this study compared RED values obtained from CT and PET-CT scanners in a phantom and a subset of patients.Results. Population-based RED values were mostly within two standard deviations of ICRU Report 46 values. PopD plans were comparable to IndD plans, with the average %difference magnitudes of 0.5%, 0.6%, and 0.6% for mean dose (all organs), D0.1cm3(non-target organs) and D95%/D98% (target organs), respectively. Both phantom and patient PET-CT derived RED values had high agreement with corresponding CT-derived values, with correlation coefficients ≥ 0.9.Significance. Population-based RED values were considered suitable in a simulation-free MRL treatment workflow. Utilizing these RED values resulted in similar dosimetric uncertainties as per the current workflow. Initial findings also suggested that PET-CT scans may be used to assess prospective patients' eligibility for the proposed workflow. Future investigations will evaluate the clinical feasibility of implementing this workflow for prospective patients in the clinical setting. This is aimed to reduce patient burden during radiotherapy and increase department efficiencies.

Clinical target volume delineation quality assurance for MRI-guided prostate radiotherapy using deep learning with uncertainty estimation.

BACKGROUND AND PURPOSE: Previous studies on automatic delineation quality assurance (QA) have mostly focused on CT-based planning. As MRI-guided radiotherapy is increasingly utilized in prostate cancer treatment, there is a need for more research on MRI-specific automatic QA. This work proposes a clinical target volume (CTV) delineation QA framework based on deep learning (DL) for MRI-guided prostate radiotherapy. MATERIALS AND METHODS: The proposed workflow utilized a 3D dropblock ResUnet++ (DB-ResUnet++) to generate multiple segmentation predictions via Monte Carlo dropout which were used to compute an average delineation and area of uncertainty. A logistic regression (LR) classifier was employed to classify the manual delineation as pass or discrepancy based on the spatial association between the manual delineation and the network's outputs. This approach was evaluated on a multicentre MRI-only prostate radiotherapy dataset and compared with our previously published QA framework based on AN-AG Unet. RESULTS: The proposed framework achieved an area under the receiver operating curve (AUROC) of 0.92, a true positive rate (TPR) of 0.92 and a false positive rate of 0.09 with an average processing time per delineation of 1.3 min. Compared with our previous work using AN-AG Unet, this method generated fewer false positive detections at the same TPR with a much faster processing speed. CONCLUSION: To the best of our knowledge, this is the first study to propose an automatic delineation QA tool using DL with uncertainty estimation for MRI-guided prostate radiotherapy, which can potentially be used for reviewing prostate CTV delineation in multicentre clinical trials.

Changes in serial multiparametric MRI and FDG-PET/CT functional imaging during radiation therapy can predict treatment response in patients with head and neck cancer.

OBJECTIVES: To test if tumour changes measured using combination of diffusion-weighted imaging (DWI) MRI and FDG-PET/CT performed serially during radiotherapy (RT) in mucosal head and neck carcinoma can predict treatment response. METHODS: Fifty-five patients from two prospective imaging biomarker studies were analysed. FDG-PET/CT was performed at baseline, during RT (week 3), and post RT (3 months). DWI was performed at baseline, during RT (weeks 2, 3, 5, 6), and post RT (1 and 3 months). The ADCmean from DWI and FDG-PET parameters SUVmax, SUVmean, metabolic tumour volume (MTV), and total lesion glycolysis (TLG) were measured. Absolute and relative change (%∆) in DWI and PET parameters were correlated to 1-year local recurrence. Patients were categorised into favourable, mixed, and unfavourable imaging response using optimal cut-off (OC) values of DWI and FDG-PET parameters and correlated to local control. RESULTS: The 1-year local, regional, and distant recurrence rates were 18.2% (10/55), 7.3% (4/55), and 12.7% (7/55), respectively. ∆Week 3 ADCmean (AUC 0.825, p = 0.003; OC ∆ > 24.4%) and ∆MTV (AUC 0.833, p = 0.001; OC ∆ > 50.4%) were the best predictors of local recurrence. Week 3 was the optimal time point for assessing DWI imaging response. Using a combination of ∆ADCmean and ∆MTV improved the strength of correlation to local recurrence (p ≤ 0.001). In patients who underwent both week 3 MRI and FDG-PET/CT, significant differences in local recurrence rates were seen between patients with favourable (0%), mixed (17%), and unfavourable (78%) combined imaging response. CONCLUSIONS: Changes in mid-treatment DWI and FDG-PET/CT imaging can predict treatment response and could be utilised in the design of future adaptive clinical trials. CLINICAL RELEVANCE STATEMENT: Our study shows the complementary information provided by two functional imaging modalities for mid-treatment response prediction in patients with head and neck cancer. KEY POINTS: •FDG-PET/CT and DWI MRI changes in tumour during radiotherapy in head and neck cancer can predict treatment response. •Combination of FDG-PET/CT and DWI parameters improved correlation to clinical outcome. •Week 3 was the optimal time point for DWI MRI imaging response assessment.

Mid-treatment 18F-FDG PET imaging changes in parotid gland correlates to radiation-induced xerostomia.

BACKGROUND: The aim of this study was to measure functional changes in parotid glands using mid-treatment FDG-PET/CT and correlate early imaging changes to subsequent xerostomia in mucosal head and neck squamous cell carcinoma patients undergoing radiotherapy. MATERIALS AND METHODS: 56 patients from two prospective imaging biomarker studies underwent FDG-PET/CT at baseline and during radiotherapy (week 3). Both parotid glands were volumetrically delineated at each time point. PET parameter SUVmedian were calculated for ipsilateral and contralateral parotid glands. Absolute and relative change (Δ) in SUVmedian were correlated to moderate-severe xerostomia (CTCAE grade ≥ 2) at 6 months. Four predictive models were subsequently created using multivariate logistic regression using clinical and radiotherapy planning parameters. Model performance was calculated using ROC analysis and compared using Akaike information criterion (AIC) RESULTS: 29 patients (51.8%) developed grade ≥ 2 xerostomia. Compared to baseline, there was an increase in SUVmedian at week 3 in ipsilateral (8.4%) and contralateral (5.5%) parotid glands. Increase in ipsilateral parotid Δ SUVmedian (p = 0.04) and contralateral mean parotid dose (p = 0.04) were correlated to xerostomia. The reference 'clinical' model correlated to xerostomia (AUC 0.667, AIC 70.9). Addition of ipsilateral parotid Δ SUVmedian to the clinical model resulted in the highest correlation to xerostomia (AUC 0.777, AIC 65.4). CONCLUSION: Our study shows functional changes occurring in the parotid gland early during radiotherapy. We demonstrate that integration of baseline and mid-treatment FDG-PET/CT changes in the parotid gland with clinical factors has the potential to improve xerostomia risk prediction which could be utilised for personalised head and neck radiotherapy.

Impact of tumour region of interest delineation method for mid-treatment FDG-PET response prediction in head and neck squamous cell carcinoma undergoing radiotherapy.

Background: The aim of this study was to evaluate the impact of tumour region of interest (ROI) delineation method on mid-treatment 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) response prediction in mucosal head and neck squamous cell carcinoma during radiotherapy. Methods: A total of 52 patients undergoing definitive radiotherapy with or without systemic therapy from two prospective imaging biomarker studies were analysed. FDG-PET was performed at baseline and during radiotherapy (week 3). Primary tumour was delineated using a fixed SUV 2.5 threshold (MTV2.5), relative threshold (MTV40%) and a gradient based segmentation method (PET Edge). PET parameters SUVmax, SUVmean, metabolic tumour volume (MTV) and total lesion glycolysis (TLG) were calculated using different ROI methods. Absolute and relative change (∆) in PET parameters were correlated to 2-year locoregional recurrence. Strength of correlation was tested using receiver operator characteristic analysis using area under the curve (AUC). Response was categorized using optimal cut-off (OC) values. Correlation and agreement between different ROI methods was determined using Bland-Altman analysis. Results: A significant difference in SUVmean, MTV and TLG values were noted between ROI delineation methods. When measuring relative change at week 3, a greater agreement was seen between PET Edge and MTV2.5 methods with average difference in ∆SUVmax, ∆SUVmean, ∆MTV and ∆TLG of 0.0%, 3.6%, 10.3% and 13.6% respectively. A total of 12 patients (22.2%) experienced locoregional recurrence. ∆MTV using PET Edge was the best predictor of locoregional recurrence (AUC =0.761, 95% CI: 0.573-0.948, P=0.001; OC ∆>50%). The corresponding 2-year locoregional recurrence rate was 7% vs. 35%, P=0.001. Conclusions: Our findings suggest that it is preferable to use gradient based method to assess volumetric tumour response during radiotherapy and offers advantage in predicting treatment outcomes compared with threshold-based methods. This finding requires further validation and can assist in future response-adaptive clinical trials.

MR-Linac guided adaptive stereotactic ablative body radiotherapy for recurrent cardiac sarcoma with mitral valve bioprosthesis - a case report.

We present the first case in the literature of a 78-year-old woman with recurrent cardiac sarcoma adjacent to a bioprosthetic mitral valve treated with magnetic resonance linear accelerator (MR-Linac) guided adaptive stereotactic ablative body radiotherapy (SABR). The patient was treated using a 1.5 T Unity MR-Linac system (Elekta AB, Stockholm, Sweden). The mean gross tumour volume (GTV) size was 17.9 cm3 (range 16.6-18.9 cm3 ) based on daily contours and the mean dose received by the GTV was 41.4 Gy (range 40.9-41.6 Gy) in five fractions. All fractions were completed as planned and the patient tolerated the treatment well with no acute toxicity reported. Follow-up appointments at 2 and 5 months after the last treatment showed stable disease and good symptomatic relief. Results of transthoracic echocardiogram after radiotherapy showed that the mitral valve prosthesis was normally seated with regular functionality. This study provides evidence that MR-Linac guided adaptive SABR is a safe and viable option for the treatment of recurrent cardiac sarcoma with mitral valve bioprosthesis.

ACPSEM position paper: the safety of magnetic resonance imaging linear accelerators.

Magnetic Resonance Imaging linear-accelerator (MRI-linac) equipment has recently been introduced to multiple centres in Australia and New Zealand. MRI equipment creates hazards for staff, patients and others in the MR environment; these hazards must be well understood, and risks managed by a system of environmental controls, written procedures and a trained workforce. While MRI-linac hazards are similar to the diagnostic paradigm, the equipment, workforce and environment are sufficiently different that additional safety guidance is warranted. In 2019 the Australasian College of Physical Scientists and Engineers in Medicine (ACPSEM) formed the Magnetic Resonance Imaging Linear-Accelerator Working Group (MRILWG) to support the safe clinical introduction and optimal use of MR-guided radiation therapy treatment units. This Position Paper is intended to provide safety guidance and education for Medical Physicists and others planning for and working with MRI-linac technology. This document summarises MRI-linac hazards and describes particular effects which arise from the combination of strong magnetic fields with an external radiation treatment beam. This document also provides guidance on safety governance and training, and recommends a system of hazard management tailored to the MRI-linac environment, ancillary equipment, and workforce.