Sir Peter MacCallum Department of Oncology - Research Publications

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    The interlace deposition method of bone equivalent material extrusion 3D printing for imaging in radiotherapy
    Tino, R ; Yeo, A ; Brandt, M ; Leary, M ; Kron, T (ELSEVIER SCI LTD, 2021-01-06)
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    Report dose-to-medium in clinical trials where available; a consensus from the Global Harmonisation Group to maximize consistency
    Kry, SF ; Lye, J ; Clark, CH ; Andratschke, N ; Dimitriadis, A ; Followill, D ; Howell, R ; Hussein, M ; Ishikawa, M ; Kito, S ; Kron, T ; Lee, J ; Michalski, J ; Monti, AF ; Reynaert, N ; Taylor, P ; Venables, K ; Xiao, Y ; Lehmann, J (ELSEVIER IRELAND LTD, 2021-04-03)
    PURPOSE: To promote consistency in clinical trials by recommending a uniform framework as it relates to radiation transport and dose calculation in water versus in medium. METHODS: The Global Quality Assurance of Radiation Therapy Clinical Trials Harmonisation Group (GHG; www.rtqaharmonization.org) compared the differences between dose to water in water (Dw,w), dose to water in medium (Dw,m), and dose to medium in medium (Dm,m). This was done based on a review of historical frameworks, existing literature and standards, clinical issues in the context of clinical trials, and the trajectory of radiation dose calculations. Based on these factors, recommendations were developed. RESULTS: No framework was found to be ideal or perfect given the history, complexity, and current status of radiation therapy. Nevertheless, based on the evidence available, the GHG established a recommendation preferring dose to medium in medium (Dm,m). CONCLUSIONS: Dose to medium in medium (Dm,m) is the preferred dose calculation and reporting framework. If an institution's planning system can only calculate dose to water in water (Dw,w), this is acceptable.
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    Feasibility of biology-guided radiotherapy using PSMA-PET to boost to dominant intraprostatic tumour
    Gaudreault, M ; Chang, D ; Hardcastle, N ; Jackson, P ; Kron, T ; Hofman, MS ; Siva, S (ELSEVIER IRELAND LTD, 2022-07-01)
    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.
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    Utility of Biology-Guided Radiotherapy to De Novo Metastases Diagnosed During Staging of High-Risk Biopsy-Proven Prostate Cancer
    Gaudreault, M ; Chang, D ; Hardcastle, N ; Jackson, P ; Kron, T ; Hanna, GG ; Hofman, MS ; Siva, S (FRONTIERS MEDIA SA, 2022-04-12)
    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 tracking during BgRT.
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    Multi-jet fusion for additive manufacturing of radiotherapy immobilization devices: Effects of color, thickness, and orientation on surface dose and tensile strength
    Asfia, A ; Deepak, B ; Novak, JI ; Rolfe, B ; Kron, T (WILEY, 2022-02-25)
    Immobilization devices are used to obtain reproducible patient setup during radiotherapy treatment, improving accuracy, and reducing damage to surrounding healthy tissue. Additive manufacturing is emerging as a viable method for manufacturing and personalizing such devices. The goal of this study was to investigate the dosimetric and mechanical properties of a recent additive technology called multi-jet fusion (MJF) for radiotherapy applications, including the ability for this process to produce full color parts. Skin dose testing included 50 samples with dimensions 100 mm × 100 mm with five different thicknesses (1 mm, 2 mm, 3 mm, 4 mm, and 5 mm) and grouped into colored (cyan, magenta, yellow, and black (CMYK) additives) and non-colored (white) samples. Results using a 6 MV beam found that surface dose readings were predominantly independent of the colored additives. However, for an 18 MV beam, the additives affected the surface dose, with black recording significantly lower surface dose readings compare to other colors. The accompanying tensile testing of 175 samples designed to ASTM D638 type I standards found that the black agent resulted in the lowest ultimate tensile strength (UTS) for each thickness of 1-5 mm. It was also found that the print orientation had influence on the skin dose and mechanical properties of the samples. When all data were combined and analyzed using a multiple-criteria decision-making technique, magenta was found to offer the best balance between high UTS and low surface dose across different thicknesses and orientations, making it an optimal choice for immobilization devices. This is the first study to consider the use of color MJF for radiotherapy immobilization devices, and suggests that color additives can affect both dosimetry and mechanical performance. This is important as industrial additive technologies like MJF become increasingly adopted in the health and medical sectors.
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    A system for real-time monitoring of breath-hold via assessment of internal anatomy in tangential breast radiotherapy
    Vasina, EN ; Greer, P ; Thwaites, D ; Kron, T ; Lehmann, J (WILEY, 2021-11-18)
    The deep inspiration breath-hold (DIBH) technique assists in sparing the heart, lungs, and liver during breast radiotherapy (RT). The quality of DIBH is currently assessed via surrogates which correlate to varying degrees with the patient's internal anatomy. Since modern linacs are equipped with an electronic portal imaging device (EPID), images of the irradiated anatomy streamed from EPIDs and analyzed in real time could significantly improve assessment of the quality of DIBH. A system has been developed to quantify the quality of DIBH during tangential breast RT by analyzing the "beam's eye view" images of the treatment fields. The system measures the lung depth (LD) and the distance from the breast surface to the posterior tangential radiation field edge (skin distance, SD) at three user-defined locations. LD and SD measured in real time in EPID images of two RT phantoms showing different geometrical characteristics of their chest wall regions (computed tomography dose index [CTDI] and "END-TO-END" stereotactic body radiation therapy [E2E SBRT]) were compared with ground truth displacements provided by a precision motion platform. Performance of the new system was evaluated via static and dynamic (sine wave motion) measurements of LD and SD, covering clinical situations with stable and unstable breath-hold. The accuracy and precision of the system were calculated as the mean and standard deviation of the differences between the ground truth and measured values. The accuracy of the static measurements of LD and SD for the CTDI phantom was 0.31 (1.09) mm [mean (standard deviation)] and -0.10 (0.14) mm, respectively. The accuracy of the static measurements for E2E SBRT phantom was 0.01 (0.18) mm and 0.05 (0.08) mm. The accuracy of the dynamic LD and SD measurements for the CTDI phantom was -0.50 (1.18) mm and 0.01 (0.12) mm, respectively. The accuracy of the dynamic measurements for E2E SBRT phantom was -0.03 (0.19) mm and 0.01 (0.11) mm.
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    Please Place Your Seat in the Full Upright Position: A Technical Framework for Landing Upright Radiation Therapy in the 21(st) Century
    Hegarty, S ; Hardcastle, N ; Korte, J ; Kron, T ; Everitt, S ; Rahim, S ; Hegi-Johnson, F ; Franich, R (FRONTIERS MEDIA SA, 2022-03-03)
    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.
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    Importance of quality in radiation oncology
    Foroudi, F ; Kron, T (WILEY, 2017-10-01)
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    Stereotactic ablative body radiotherapy for inoperable primary kidney cancer: a prospective clinical trial
    Siva, S ; Pham, D ; Kron, T ; Bressel, M ; Lam, J ; Tan, TH ; Chesson, B ; Shaw, M ; Chander, S ; Gill, S ; Brook, NR ; Lawrentschuk, N ; Murphy, DG ; Foroudi, F (WILEY, 2017-11-01)
    OBJECTIVE: To assess the feasibility and safety of stereotactic ablative body radiotherapy (SABR) for renal cell carcinoma (RCC) in patients unsuitable for surgery. Secondary objectives were to assess oncological and functional outcomes. MATERIALS AND METHODS: This was a prospective interventional clinical trial with institutional ethics board approval. Inoperable patients were enrolled, after multidisciplinary consensus, for intervention with informed consent. Tumour response was defined using Response Evaluation Criteria In Solid Tumors v1.1. Toxicities were recorded using Common Terminology Criteria for Adverse Events v4.0. Time-to-event outcomes were described using the Kaplan-Meier method, and associations of baseline variables with tumour shrinkage was assessed using linear regression. Patients received either single fraction of 26 Gy or three fractions of 14 Gy, dependent on tumour size. RESULTS: Of 37 patients (median age 78 years), 62% had T1b, 35% had T1a and 3% had T2a disease. One patient presented with bilateral primaries. Histology was confirmed in 92%. In total, 33 patients and 34 kidneys received all prescribed SABR fractions (89% feasibility). The median follow-up was 24 months. Treatment-related grade 1-2 toxicities occurred in 26 patients (78%) and grade 3 toxicity in one patient (3%). No grade 4-5 toxicities were recorded and six patients (18%) reported no toxicity. Freedom from local progression, distant progression and overall survival rates at 2 years were 100%, 89% and 92%, respectively. The mean baseline glomerular filtration rate was 55 mL/min, which decreased to 44 mL/min at 1 and 2 years (P < 0.001). Neutrophil:lymphocyte ratio correlated to % change in tumour size at 1 year, r2 = 0.45 (P < 0.001). CONCLUSION: The study results show that SABR for primary RCC was feasible and well tolerated. We observed encouraging cancer control, functional preservation and early survival outcomes in an inoperable cohort. Baseline neutrophil:lymphocyte ratio may be predictive of immune-mediated response and warrants further investigation.
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    Cone-beam computed tomography for lung cancer - validation with CT and monitoring tumour response during chemo-radiation therapy
    Michienzi, A ; Kron, T ; Callahan, J ; Plumridge, N ; Ball, D ; Everitt, S (WILEY, 2017-04-01)
    INTRODUCTION: Cone-beam computed tomography (CBCT) is a valuable image-guidance tool in radiation therapy (RT). This study was initiated to assess the accuracy of CBCT for quantifying non-small cell lung cancer (NSCLC) tumour volumes compared to the anatomical 'gold standard', CT. Tumour regression or progression on CBCT was also analysed. METHODS: Patients with Stage I-III NSCLC, prescribed 60 Gy in 30 fractions RT with concurrent platinum-based chemotherapy, routine CBCT and enrolled in a prospective study of serial PET/CT (baseline, weeks two and four) were eligible. Time-matched CBCT and CT gross tumour volumes (GTVs) were manually delineated by a single observer on MIM software, and were analysed descriptively and using Pearson's correlation coefficient (r) and linear regression (R2 ). RESULTS: Of 94 CT/CBCT pairs, 30 patients were eligible for inclusion. The mean (± SD) CT GTV vs CBCT GTV on the four time-matched pairs were 95 (±182) vs 98.8 (±160.3), 73.6 (±132.4) vs 70.7 (±96.6), 54.7 (±92.9) vs 61.0 (±98.8) and 61.3 (±53.3) vs 62.1 (±47.9) respectively. Pearson's correlation coefficient (r) was 0.98 (95% CI 0.97-0.99, ρ < 0.001). The mean (±SD) CT/CBCT Dice's similarity coefficient was 0.66 (±0.16). Of 289 CBCT scans, tumours in 27 (90%) patients regressed by a mean (±SD) rate of 1.5% (±0.75) per fraction. The mean (±SD) GTV regression was 43.1% (±23.1) from the first to final CBCT. CONCLUSION: Primary lung tumour volumes observed on CBCT and time-matched CT are highly correlated (although not identical), thereby validating observations of GTV regression on CBCT in NSCLC.