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Background: Establishing a new head and neck cancer (HNC) treatment center requires multidisciplinary team management and expertise. To our knowledge, there are no clear recommendations or guidelines in the literature for the commencement of HNC radiation therapy (RT) at a new cancer center. We propose a novel framework outlining the necessary components required to set-up a new radiation therapy HNC treatment., Methods: We reviewed the infrastructure and methodology in the commencement of HNC radiation therapy in our cancer care center and invited several external, experienced metropolitan head and neck radiation oncologists to develop a novel consensus guideline that may be used by new RT centers to treat HNC. Recommendations were presented to our internal and external staff specialists using a survey questionnaire with ratings utilized to determine consensus using pre-defined thresholds as per the American Society of Clinical Oncology Guidelines Methodology Manual., Conclusion: This consensus recommendation aims to improve RT utilization whilst advocating for optimal patient outcomes by presenting a framework for new radiation therapy centers ready to step up and manage the treatment of head and neck cancer patients. We propose these evidence-based consensus guidelines endorsed by external HNC radiation oncologists., (© 2023 John Wiley & Sons Australia, Ltd.)

Objectives: Diffusion-weighted MRI (DWI) may provide biologically relevant target volumes for dose-escalated radiotherapy in locally advanced rectal cancer (LARC). This planning study assessed the dosimetric feasibility of delivering hypofractionated boost treatment to intra-tumoural regions of restricted diffusion prior to conventional long-course radiotherapy., Methods: Ten patients previously treated with curative-intent standard long-course radiotherapy (50 Gy/25#) were re-planned. Boost target volumes ( BTVs ) were delineated semi-automatically using 40th centile intra-tumoural apparent diffusion coefficient value with expansions (anteroposterior 11 mm, transverse 7 mm, craniocaudal 13 mm). Biased-dosed combined plans consisted of a single-fraction volumetric modulated arc therapy flattening-filter-free (VMAT-FFF) boost (phase 1) of 5, 7, or 10 Gy before long-course VMAT (phase 2). Phase 1 plans were assessed with reference to stereotactic conformality and deliverability measures. Combined plans were evaluated with reference to standard long-course therapy dose constraints., Results: Phase 1 BTV dose targets at 5/7/10 Gy were met in all instances. Conformality constraints were met with only 1 minor violation at 5 and 7 Gy. All phase 1 and combined phase 1 + 2 plans passed patient-specific quality assurance. Combined phase 1 + 2 plans generally met organ-at-risk dose constraints. Exceptions included high-dose spillage to bladder and large bowel, predominantly in cases where previously administered, clinically acceptable non-boosted plans also could not meet constraints., Conclusions: Targeted upfront LARC radiotherapy dose escalation to DWI-defined is feasible with appropriate patient selection and preparation., Advances in Knowledge: This is the first study to evaluate the feasibility of DWI-targeted upfront radiotherapy boost in LARC. This work will inform an upcoming clinical feasibility study., Competing Interests: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Institute of Radiology.)

Magnetic resonance imaging (MRI) is being integrated into routine radiation therapy (RT) planning workflows. To reap the benefits of this imaging modality, patient positioning, image acquisition parameters and a quality assurance programme must be considered for accurate use. This paper will report on the implementation of a retrofit MRI Simulator for RT planning, demonstrating an economical, resource efficient solution to improve the accuracy of MRI in this setting., (© 2023 The Authors. Journal of Medical Radiation Sciences published by John Wiley & Sons Australia, Ltd on behalf of Australian Society of Medical Imaging and Radiation Therapy and New Zealand Institute of Medical Radiation Technology.)

Objective: The optimal method for delineation of dominant intraprostatic lesions (DIL) for targeted radiotherapy dose escalation is unclear. This study evaluated interobserver and intermodality variability of delineations on biparametric MRI (bpMRI), consisting of T 2 weighted ( T 2 W) and diffusion-weighted (DWI) sequences, and 68 Ga-PSMA-PET/CT; and compared manually delineated GTV contours with semi-automated segmentations based on quantitative thresholding of intraprostatic apparent diffusion coefficient (ADC) and standardised uptake values (SUV)., Methods: 16 patients who had bpMRI and PSMA-PET scanning performed prior to any treatment were eligible for inclusion. Four observers (two radiation oncologists, two radiologists) manually delineated the DIL on: (1) bpMRI (GTV MRI ), (2) PSMA-PET (GTV PSMA ) and (3) co-registered bpMRI/PSMA-PET (GTV Fused ) in separate sittings. Interobserver, intermodality and semi-automated comparisons were evaluated against consensus Simultaneous Truth and Performance Level Estimation (STAPLE) volumes, created from the relevant manual delineations of all observers with equal weighting. Comparisons included the Dice Similarity Coefficient (DSC), mean distance to agreement (MDA) and other metrics., Results: Interobserver agreement was significantly higher ( p < 0.05) for GTV PSMA (DSC: 0.822, MDA: 1.12 mm) and GTV Fused (DSC: 0.787, MDA: 1.34 mm) than for GTV MRI (DSC: 0.705, MDA 2.44 mm). Intermodality agreement between GTV MRI and GTV PSMA was low (DSC: 0.440, MDA: 4.64 mm). Agreement between semi-automated volumes and consensus GTV was low for MRI (DSC: 0.370, MDA: 8.16 mm) and significantly higher for PSMA-PET (0.571, MDA: 4.45 mm, p < 0.05)., Conclusion: 68 Ga-PSMA-PET appears to improve interobserver consistency of DIL localisation vs bpMRI and may be more viable for simple quantitative delineation approaches; however, more sophisticated approaches to semi-automatic delineation factoring for patient- and disease-related heterogeneity are likely required., Advances in Knowledge: This is the first study to evaluate the interobserver variability of prostate GTV delineations with co-registered bpMRI and 68 Ga-PSMA-PET.

Objectives: To evaluate interobserver agreement for T 2 weighted ( T 2 W) and diffusion-weighted MRI (DW-MRI) contours of locally advanced rectal cancer (LARC); and to evaluate manual and semi-automated delineations of restricted diffusion tumour subvolumes., Methods: 20 cases of LARC were reviewed by 2 radiation oncologists and 2 radiologists. Contours of gross tumour volume (GTV) on T 2 W, DW-MRI and co-registered T 2 W/DW-MRI were independently delineated and compared using Dice Similarity Coefficient (DSC), mean distance to agreement (MDA) and other metrics of interobserver agreement. Restricted diffusion subvolumes within GTVs were manually delineated and compared to semi-automatically generated contours corresponding to intratumoral apparent diffusion coefficient (ADC) centile values., Results: Observers were able to delineate subvolumes of restricted diffusion with moderate agreement (DSC 0.666, MDA 1.92 mm). Semi-automated segmentation based on the 40th centile intratumoral ADC value demonstrated moderate average agreement with consensus delineations (DSC 0.581, MDA 2.44 mm), with errors noted in image registration and luminal variation between acquisitions. A small validation set of four cases with optimised planning MRI demonstrated improvement (DSC 0.669, MDA 1.91 mm)., Conclusion: Contours based on co-registered T 2 W and DW-MRI could be used for delineation of biologically relevant tumour subvolumes. Semi-automated delineation based on patient-specific intratumoral ADC thresholds may standardise subvolume delineation if registration between acquisitions is sufficiently accurate., Advances in Knowledge: This is the first study to evaluate the feasibility of semi-automated diffusion-based subvolume delineation in LARC. This approach could be applied to dose escalation or 'dose painting' protocols to improve delineation reproducibility.

Objective: A cohort of high dose-rate (HDR) monotherapy patients was analyzed to (i) establish the frequency of non-malignant urethral stricture; (ii) explore the relation between stricture formation with the dose distribution along the length of the urethra, and MRI radiomics features of the prostate gland., Methods: A retrospective review of treatment records of patients who received 19 Gy single fraction of HDR brachytherapy (BT) was carried out. A matched pair analysis used one control for each stricture case matched with pre-treatment International Prostate Symptom Score (IPSS) score, number of needles used and clinical target volume volume for each stricture case identified.For all data sets, pre-treatment T 2 weighted MRI images were used to define regions of interests along the urethra and within the whole prostate gland. MRI textural radiomics features-energy, contrast and homogeneity were selected. Wilcoxon signed-rank test was performed to investigate significant differences in dosimetric parameters and MRI radiomics feature values between cases and controls., Results: From Nov 2010 to July 2017, there were 178 patients treated with HDR BT delivering 19 Gy in a single dose. With a median follow-up of 28.2 months, a total of 5/178 (3%) strictures were identified.10 patients were included in the matched pair analysis. The urethral dosimetric parameters investigated were not statistically different between cases and controls ( p > 0.05). With regards to MRI radiomics feature analysis, significant differences were found in contrast and homogeneity between cases and controls ( p < 0.05). However, this did not apply to the energy feature ( p = 0.28)., Conclusion: In this matched pair analysis, no association between post-treatment stricture and urethral dosimetry was identified. Our study generated a preliminary clinical hypothesis suggesting that the MRI radiomics features of homogeneity and contrast of the prostate gland can potentially identify patients who develop strictures after HDR BT. Although the sample size is small, this warrants further validation in a larger patient cohort., Advances in Knowledge: Urethral stricture has been reported as a specific late effect with prostate HDR brachytherapy. Our study reported a relatively low stricture rate of 3% and no association between post-treatment stricture and urethral dosimetry was identified. MRI radiomics features can potentially identify patients who are more prone to develop strictures.

We sought to compare the effects of the thiazolidinedione ciglitazone with the endogenous fatty acid PPARgamma agonists 9- and 13-hydroxyoctadecadienoic acid (9- and 13-HODE), in U937 monocytic cells. Ciglitazone and 9-HODE inhibited cell proliferation and all three agonists increased cellular content of C18:0 fatty acids. Ciglitazone and 13-HODE resulted in an increased percentage of cells in S phase and ciglitazone reduced the percentage of cells in G2/M phase of cell cycle, whilst 9-HODE increased the percentage of cells in G0/1 and reduced the fraction in S and G2/M phases. 9-HODE selectively induced apoptosis in U937 cells, and increased PPARgamma2 gene expression. Induction of apoptosis by 9-HODE was not abrogated by the presence of the PPARgamma antagonist GW9662. Synthetic (TZD) and endogenous fatty acid ligands for PPARgamma, ciglitazone and 9- and 13-HODE, possess differential, ligand specific actions in monocytic cells to regulate cell cycle progression, apoptosis and PPARgamma2 gene expression.