Nicholas Hardcastle

Peter MacCallum Cancer Centre

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Co-Authors

Tomas Kron

University of Melbourne

110

Shankar Siva

Peter MacCallum Cancer Centre

107

David Ball

University of Melbourne

Michael S. Hofman

Peter MacCallum Cancer Centre

Paul Keall

University of Sydney

Mathias Bressel

Peter MacCallum Cancer Centre

Jeremy Booth

University of Sydney

Mathieu Gaudreault

University of Melbourne

Wolfgang A. Tomé

Albert Einstein College of Medicine

Thomas Eade

Royal North Shore Hospital

Cooperative Institutions

Peter MacCallum Cancer Centre

190

University of Melbourne

147

University of Sydney

108

University of Wollongong

Royal North Shore Hospital

Monash University

The Royal Melbourne Hospital

UNSW Sydney

University of Wisconsin–Madison

University of Queensland

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Personalising treatment plan quality review with knowledge-based planning in the TROG 15.03 trial for stereotactic ablative body radiotherapy in primary kidney cancer

Radiation Oncology (2021)

Nicholas Hardcastle Olivia Cook Xenia Ray Alisha Moore Kevin L. Moore

Abstract 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.

Ablative case

10.1186/s13014-021-01820-7

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Citations (11)

Deep Learning Renal Segmentation for Fully Automated Radiation Dose Estimation in Unsealed Source Therapy

Frontiers in Oncology (2018)

Price Jackson Nicholas Hardcastle Noel Dawe Tomas Kron Michael S. Hofman

Convolutional neural networks (CNNs) have been shown to be powerful tools to assist with object detection and-like a human observer-may be trained based on a relatively small cohort of reference subjects. Rapid, accurate organ recognition in medical imaging permits a variety of new quantitative diagnostic techniques. In the case of therapy with targeted radionuclides, it may permit comprehensive radiation dose analysis in a manner that would often be prohibitively time-consuming using conventional methods.An automated image segmentation tool was developed based on three-dimensional CNNs to detect right and left kidney contours on non-contrast CT images. Model was trained based on 89 manually contoured cases and tested on a cohort of patients receiving therapy with 177Lu-prostate-specific membrane antigen-617 for metastatic prostate cancer. Automatically generated contours were compared with those drawn by an expert and assessed for similarity based on dice score, mean distance-to-agreement, and total segmented volume. Further, the contours were applied to voxel dose maps computed from post-treatment quantitative SPECT imaging to estimate renal radiation dose from therapy.Neural network segmentation was able to identify right and left kidneys in all patients with a high degree of accuracy. The system was integrated into the hospital image database, returning contours for a selected study in approximately 90 s. Mean dice score was 0.91 and 0.86 for right and left kidneys, respectively. Poor performance was observed in three patients with cystic kidneys of which only few were included in the training data. No significant difference in mean radiation absorbed dose was observed between the manual and automated algorithms.Automated contouring using CNNs shows promise in providing quantitative assessment of functional SPECT and possibly PET images; in this case demonstrating comparable accuracy for radiation dose interpretation in unsealed source therapy relative to a human observer.

10.3389/fonc.2018.00215

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Monte carlo study of MOSFET packaging, optimised for improved energy response: single MOSFET filtration

Radiation Protection Dosimetry (2010)

Mohd Amir Radhi Othman Dean Cutajar Nicholas Hardcastle Susanna Guatelli Anatoly Rosenfeld

Monte Carlo simulations of the energy response of a conventionally packaged single metal-oxide field effect transistors (MOSFET) detector were performed with the goal of improving MOSFET energy dependence for personal accident or military dosimetry. The MOSFET detector packaging was optimised. Two different ‘drop-in’ design packages for a single MOSFET detector were modelled and optimised using the GEANT4 Monte Carlo toolkit. Absorbed photon dose simulations of the MOSFET dosemeter placed in free-air response, corresponding to the absorbed doses at depths of 0.07 mm (Dw(0.07)) and 10 mm (Dw(10)) in a water equivalent phantom of size 30 × 30 × 30 cm3 for photon energies of 0.015–2 MeV were performed. Energy dependence was reduced to within ±60 % for photon energies 0.06–2 MeV for both Dw(0.07) and Dw(10). Variations in the response for photon energies of 15–60 keV were 200 and 330 % for Dw(0.07) and Dw(10), respectively. The obtained energy dependence was reduced compared with that for conventionally packaged MOSFET detectors, which usually exhibit a 500–700 % over-response when used in free-air geometry.

Photon energy

10.1093/rpd/ncq144

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MO-FG-BRA-06: Electromagnetic Beacon Insertion in Lung Cancer Patients and Resultant Surrogacy Errors for Dynamic MLC Tumour Tracking

Medical Physics (2016)

Nicholas Hardcastle Jeremy Booth Vincent Caillet Ricky O’Brien Carol Haddad

Purpose: To assess endo-bronchial electromagnetic beacon insertion and to quantify the geometric accuracy of using beacons as a surrogate for tumour motion in real-time multileaf collimator (MLC) tracking of lung tumours. Methods: The LIGHT SABR trial is a world-first clinical trial in which the MLC leaves move with lung tumours in real time on a standard linear accelerator. Tracking is performed based on implanted electromagnetic beacons (CalypsoTM, Varian Medical Systems, USA) as a surrogate for tumour motion. Five patients have been treated and have each had three beacons implanted endo-bronchially under fluoroscopic guidance. The centre of mass (C.O.M) has been used to adapt the MLC in real-time. The geometric error in using the beacon C.O.M as a surrogate for tumour motion was measured by measuring the tumour and beacon C.O.M in all phases of the respiratory cycle of a 4DCT. The surrogacy error was defined as the difference in beacon and tumour C.O.M relative to the reference phase (maximum exhale). Results: All five patients have had three beacons successfully implanted with no migration between simulation and end of treatment. Beacon placement relative to tumour C.O.M varied from 14 to 74 mm and in one patient spanned two lobes. Surrogacy error was measured in each patient on the simulation 4DCT and ranged from 0 to 3 mm. Surrogacy error as measured on 4DCT was subject to artefacts in mid-ventilation phases. Surrogacy error was a function of breathing phase and was typically larger at maximum inhale. Conclusion: Beacon placement and thus surrogacy error is a major component of geometric uncertainty in MLC tracking of lung tumours. Surrogacy error must be measured on each patient and incorporated into margin calculation. Reduction of surrogacy error is limited by airway anatomy, however should be taken into consideration when performing beacon insertion and planning. This research is funded by Varian Medical Systems via a collaborative research agreement.

Beacon

Multileaf collimator

Tracking (education)

10.1118/1.4957299

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NeoAdjuvant Pembrolizumab and STEreotactic Radiotherapy Prior to Nephrectomy for Renal Cell Carcinoma (NAPSTER): A Phase Ii Randomised Clinical Trial

SSRN Electronic Journal (2022)

Muhammad Ali Simon N. Wood David B. Pryor Daniel Moon Mathias Bressel

Background: Surgery remains the standard of care for localised renal cell carcinoma (RCC). Nevertheless, nearly 50% of patients with high-risk disease experience relapse after surgery, with distant sites being common. Considering improved outcomes in terms of disease-free survival with adjuvant immunotherapy with pembrolizumab, we hypothesise that neoadjuvant SABR with or without the addition of pembrolizumab before nephrectomy will lead to improved disease outcomes by evoking better immune response in the presence of an extensive reserve of tumor-associated antigens.Methods and analysis: This prospective, open-label, phase II, randomised, non-comparative, clinical trial will investigate the use of neoadjuvant stereotactic ablative body radiotherapy (SABR) with or without pembrolizumab prior to nephrectomy. The trial will be conducted at two centres in Australia that are well established for delivering SABR to primary RCC patients. Twenty-six patients with biopsy-proven clear cell RCC will be recruited over two years. Patients will be randomised to either SABR or SABR/pembrolizumab. Patients in both arms will undergo surgery at 9 weeks after completion of experimental treatment. The primary objectives are to describe major pathological response and changes in tumour-responsive T-cells in each arm. Patients will be followed for sixty days post-surgery.Outcomes and significance: We hypothesize that SABR alone or SABR plus pembrolizumab will induce significant tumor-specific immune response and major pathological response. In that case, either one or both arms could justifiably be used as a neoadjuvant treatment approach in future randomized trials in the high-risk patient population.

10.2139/ssrn.4234591

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Citations (0)

DETERMINATION OF FUNCTIONAL PERFUSED LUNG SUBVOLUMES FROM DUAL-ENERGY CT AND PET IMAGING FOR FUNCTIONAL LUNG AVOIDANCE RADIOTHERAPY

Physica Medica (2022)

Mathieu Gaudreault James Korte Nicholas Bucknell Beverley Woon Mr Tony Mulcahy

Dual energy

Functional Imaging

10.1016/s1120-1797(22)02141-x

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A stereotactic ablative body radiotherapy (SABR) program founded on clinical trials: A report of the first 100 patients treated in an Australian academic institution

Shankar Siva Farshad Foroudi Marcus Sarmiento Mark Shaw Sarat Chander

Poster: 2014 CSM / R-0132 / A stereotactic ablative body radiotherapy (SABR) program founded on clinical trials: A report of the first 100 patients treated in an Australian academic institution by: Siva, F. Foroudi, M. Sarmiento, M. Shaw, S. Chander, L. Te Marvelde, N. Hardcastle, A. Lim, D. Pham, S. Gill, C. Brent, T. Kron, D. Ball; EAST MELBOURNE/AU

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The challenge of planning vertebral body SBRT: Optimizing target volume coverage

Medical dosimetry (2020)

Nicholas Hardcastle Fiona Bignell Benjamin E. Nelms Shankar Siva Andrew Kneebone

10.1016/j.meddos.2020.02.005

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Citations (11)

A multi-institution evaluation of deformable image registration algorithms for automatic organ delineation in adaptive head and neck radiotherapy

Radiation Oncology (2012)

Nicholas Hardcastle Wolfgang A. Tomé Donald M. Cannon Charlotte L. Brouwer P.W.H. Wittendorp

Adaptive Radiotherapy aims to identify anatomical deviations during a radiotherapy course and modify the treatment plan to maintain treatment objectives. This requires regions of interest (ROIs) to be defined using the most recent imaging data. This study investigates the clinical utility of using deformable image registration (DIR) to automatically propagate ROIs. Target (GTV) and organ-at-risk (OAR) ROIs were non-rigidly propagated from a planning CT scan to a per-treatment CT scan for 22 patients. Propagated ROIs were quantitatively compared with expert physician-drawn ROIs on the per-treatment scan using Dice scores and mean slicewise Hausdorff distances, and center of mass distances for GTVs. The propagated ROIs were qualitatively examined by experts and scored based on their clinical utility. Good agreement between the DIR-propagated ROIs and expert-drawn ROIs was observed based on the metrics used. 94% of all ROIs generated using DIR were scored as being clinically useful, requiring minimal or no edits. However, 27% (12/44) of the GTVs required major edits. DIR was successfully used on 22 patients to propagate target and OAR structures for ART with good anatomical agreement for OARs. It is recommended that propagated target structures be thoroughly reviewed by the treating physician.

Image registration

10.1186/1748-717x-7-90

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Citations (82)

In vivoreal-time rectal wall dosimetry for prostate radiotherapy

Physics in Medicine and Biology (2010)

Nicholas Hardcastle Dean Cutajar Peter Metcalfe Michael Lerch Vladimir L. Perevertaylo

Rectal balloons are used in external beam prostate radiotherapy to provide reproducible anatomy and rectal dose reductions. This is an investigation into the combination of a MOSFET radiation detector with a rectal balloon for real-time in vivo rectal wall dosimetry. The MOSFET used in the study is a radiation detector that provides a water equivalent depth of measurement of 70 µm. Two MOSFETs were combined in a face-to-face orientation. The reproducibility, sensitivity and angular dependence were measured for the dual MOSFET in a 6 MV photon beam. The dual MOSFET was combined with a rectal balloon and irradiated with hypothetical prostate treatments in a phantom. The anterior rectal wall dose was measured in real time and compared with the planning system calculated dose. The dual MOSFET showed angular dependence within ±2.5% in the azimuth and +2.5%/−4% in the polar axes. When compared with an ion chamber measurement in a phantom, the dual MOSFET agreed within 2.5% for a range of radiation path lengths and incident angles. The dual MOSFET had reproducible sensitivity for fraction sizes of 2–10 Gy. For the hypothetical prostate treatments the measured anterior rectal wall dose was 2.6 and 3.2% lower than the calculated dose for 3DCRT and IMRT plans. This was expected due to limitations of the dose calculation method used at the balloon cavity interface. A dual MOSFET combined with a commercial rectal balloon was shown to provide reproducible measurements of the anterior rectal wall dose in real time. The measured anterior rectal wall dose agreed with the expected dose from the treatment plan for 3DCRT and IMRT plans. The dual MOSFET could be read out in real time during the irradiation, providing the capability for real-time dose monitoring of the rectal wall dose during treatment.

10.1088/0031-9155/55/13/019

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Citations (59)