Publications by authors named "Annette Haworth"

76 Publications

Biologically Targeted Radiation Therapy: Incorporating Patient-Specific Hypoxia Data Derived from Quantitative Magnetic Resonance Imaging.

Cancers (Basel) 2021 Sep 29;13(19). Epub 2021 Sep 29.

School of Physics, Mathematics and Computing, University of Western Australia, Perth, WA 6009, Australia.

Purpose: Hypoxia has been linked to radioresistance. Strategies to safely dose escalate dominant intraprostatic lesions have shown promising results, but further dose escalation to overcome the effects of hypoxia require a novel approach to constrain the dose in normal tissue.to safe levels. In this study, we demonstrate a biologically targeted radiotherapy (BiRT) approach that can utilise multiparametric magnetic resonance imaging (mpMRI) to target hypoxia for favourable treatment outcomes.

Methods: mpMRI-derived tumour biology maps, developed via a radiogenomics study, were used to generate individualised, hypoxia-targeting prostate IMRT plans using an ultra- hypofractionation schedule. The spatial distribution of mpMRI textural features associated with hypoxia-related genetic profiles was used as a surrogate of tumour hypoxia. The effectiveness of the proposed approach was assessed by quantifying the potential benefit of a general focal boost approach on tumour control probability, and also by comparing the dose to organs at risk (OARs) with hypoxia-guided focal dose escalation (DE) plans generated for five patients.

Results: Applying an appropriately guided focal boost can greatly mitigate the impact of hypoxia. Statistically significant reductions in rectal and bladder dose were observed for hypoxia-targeting, biologically optimised plans compared to isoeffective focal DE plans.

Conclusion: Results of this study suggest the use of mpMRI for voxel-level targeting of hypoxia, along with biological optimisation, can provide a mechanism for guiding focal DE that is considerably more efficient than application of a general, dose-based optimisation, focal boost.
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http://dx.doi.org/10.3390/cancers13194897DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8507789PMC
September 2021

Automatic radiotherapy delineation quality assurance on prostate MRI with deep learning in a multicentre clinical trial.

Phys Med Biol 2021 Sep 28;66(19). Epub 2021 Sep 28.

Ingham Institute for Applied Medical Research, Sydney, New South Wales, Australia.

Volume delineation quality assurance (QA) is particularly important in clinical trial settings where consistent protocol implementation is required, as outcomes will affect future as well current patients. Currently, where feasible, this is conducted manually, which is time consuming and resource intensive. Although previous studies mostly focused on automating delineation QA on CT, magnetic resonance imaging (MRI) is being increasingly used in radiotherapy treatment. In this work, we propose to perform automatic delineation QA on prostate MRI for both the clinical target volume (CTV) and organs-at-risk (OARs) by using delineations generated by 3D Unet variants as benchmarks for QA. These networks were trained on a small gold standard atlas set and applied on a multicentre radiotherapy clinical trial dataset to generate benchmark delineations. Then, a QA stage was designed to recommend 'pass', 'minor correction' and 'major correction' for each manual delineation in the trial set by thresholding its Dice similarity coefficient to the network generated delineation. Among all 3D Unet variants explored, the Unet with anatomical gates in an AtlasNet architecture performed the best in delineation QA, achieving an area under the receiver operating characteristics curve of 0.97, 0.92, 0.89 and 0.97 for identifying unacceptable (major correction) delineations with a sensitivity of 0.93, 0.73, 0.74 and 0.90 at a specificity of 0.93, 0.86, 0.86 and 0.95 for bladder, prostate CTV, rectum and gel spacer respectively. To the best of our knowledge, this is the first study to propose automated delineation QA for a multicentre radiotherapy clinical trial with treatment planning MRI. The methods proposed in this work can potentially improve the accuracy and consistency of CTV and OAR delineation in radiotherapy treatment planning.
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http://dx.doi.org/10.1088/1361-6560/ac25d5DOI Listing
September 2021

Artificial intelligence in medical imaging and radiation oncology: Opportunities and challenges.

J Med Imaging Radiat Oncol 2021 Aug;65(5):481-485

Institute of Medical Physics, School of Physics, University of Sydney, Sydney, New South Wales, Australia.

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http://dx.doi.org/10.1111/1754-9485.13275DOI Listing
August 2021

A review of medical image data augmentation techniques for deep learning applications.

J Med Imaging Radiat Oncol 2021 Aug 19;65(5):545-563. Epub 2021 Jun 19.

Institute of Medical Physics, University of Sydney, Sydney, New South Wales, Australia.

Research in artificial intelligence for radiology and radiotherapy has recently become increasingly reliant on the use of deep learning-based algorithms. While the performance of the models which these algorithms produce can significantly outperform more traditional machine learning methods, they do rely on larger datasets being available for training. To address this issue, data augmentation has become a popular method for increasing the size of a training dataset, particularly in fields where large datasets aren't typically available, which is often the case when working with medical images. Data augmentation aims to generate additional data which is used to train the model and has been shown to improve performance when validated on a separate unseen dataset. This approach has become commonplace so to help understand the types of data augmentation techniques used in state-of-the-art deep learning models, we conducted a systematic review of the literature where data augmentation was utilised on medical images (limited to CT and MRI) to train a deep learning model. Articles were categorised into basic, deformable, deep learning or other data augmentation techniques. As artificial intelligence models trained using augmented data make their way into the clinic, this review aims to give an insight to these techniques and confidence in the validity of the models produced.
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http://dx.doi.org/10.1111/1754-9485.13261DOI Listing
August 2021

Artificial intelligence and imaging biomarkers for prostate radiation therapy during and after treatment.

J Med Imaging Radiat Oncol 2021 May 31. Epub 2021 May 31.

Institute of Medical Physics, School of Physics, Faculty of Science, The University of Sydney, Sydney, New South Wales, Australia.

Magnetic resonance imaging (MRI) is increasingly used in the management of prostate cancer (PCa). Quantitative MRI (qMRI) parameters, derived from multi-parametric MRI, provide indirect measures of tumour characteristics such as cellularity, angiogenesis and hypoxia. Using Artificial Intelligence (AI), relevant information and patterns can be efficiently identified in these complex data to develop quantitative imaging biomarkers (QIBs) of tumour function and biology. Such QIBs have already demonstrated potential in the diagnosis and staging of PCa. In this review, we explore the role of these QIBs in monitoring treatment response during and after PCa radiotherapy (RT). Recurrence of PCa after RT is not uncommon, and early detection prior to development of metastases provides an opportunity for salvage treatments with curative intent. However, the current method of monitoring treatment response using prostate-specific antigen levels lacks specificity. QIBs, derived from qMRI and developed using AI techniques, can be used to monitor biological changes post-RT providing the potential for accurate and early diagnosis of recurrent disease.
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http://dx.doi.org/10.1111/1754-9485.13242DOI Listing
May 2021

Use of deformable image registration techniques to estimate dose to organs at risk following prostate external beam radiation therapy and high-dose-rate brachytherapy.

J Contemp Brachytherapy 2021 Feb 18;13(1):72-79. Epub 2021 Feb 18.

School of Physics, University of Sydney, Sydney, Australia.

Purpose: The purpose of this investigation was to examine differences in estimates of accumulated rectal dose when using deformable image registration (DIR) compared with rigid image registration (RIR) methods, and parameter addition methods for combined transrectal ultrasound (TRUS)-based high-dose-rate brachytherapy (HDR-BT) and external beam radiation therapy (EBRT) treatments of prostate cancer.

Material And Methods: In this retrospective study, data from 10 patients who had previously received HDR-BT in one 15 Gy fraction, followed by 46 Gy EBRT in twenty-three fractions were used. To estimate total combined dose to the rectum, dose accumulation using both DIR and RIR methods were compared with parameter addition methods, which assume the same region of rectal anatomy receives the maximum dose from both treatment modalities. For both rigid and deformable image registration techniques, the quality of image registration was evaluated through metrics, including mean distance to agreement and dice similarity coefficient of prostate contours. Total D and D for the rectum was calculated and compared using each method.

Results: The parameter addition methods predicted the highest accumulated dose to the rectum. On average, the predicted D dose was higher than that calculated by the DIR method by 6.59 Gy EQD (range, -3.03 to 13.68 Gy EQD) for partial parameter addition (PPA), and 4.88 Gy EQD (range, -3.41 to 11.97 Gy EQD) for the full parameter addition (FPA) methods. Similarly, RIR predicted higher average doses compared with DIR, with a difference of 3.46 Gy EQD (range, -5.50 to 7.90 Gy EQD). The results showed a significant difference between DIR and parameter addition methods for dose estimation.

Conclusions: This retrospective study demonstrates significant differences in accumulated rectal dose prediction using different image registration methods. Each method has limitations in its application, and when used with real-time HDR-BT dose planning, awareness of these limitations is essential.
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http://dx.doi.org/10.5114/jcb.2021.103589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117714PMC
February 2021

MRI radiomics in the prediction of therapeutic response to neoadjuvant therapy for locoregionally advanced rectal cancer: a systematic review.

Expert Rev Anticancer Ther 2021 04 11;21(4):425-449. Epub 2021 Jan 11.

School of Physics, University of Sydney, Camperdown, NSW, Australia.

: The standard of care for locoregionally advanced rectal cancer is neoadjuvant therapy (NA CRT) prior to surgery, of which 10-30% experience a complete pathologic response (pCR). There has been interest in using imaging features, also known as radiomics features, to predict pCR and potentially avoid surgery. This systematic review aims to describe the spectrum of MRI studies examining high-performing radiomic features that predict NA CRT response.: This article reviews the use of pre-therapy MRI in predicting NA CRT response for patients with locoregionally advanced rectal cancer (T3/T4 and/or N1+). The primary outcome was to identify MRI radiomic studies; secondary outcomes included the power and the frequency of use of radiomic features.: Advanced models incorporating multiple radiomics categories appear to be the most promising. However, there is a need for standardization across studies with regards to; the definition of NA CRT response, imaging protocols, and radiomics features incorporated. Further studies are needed to validate current radiomics models and to fully ascertain the value of MRI radiomics in the response prediction for locoregionally advanced rectal cancer.
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http://dx.doi.org/10.1080/14737140.2021.1860762DOI Listing
April 2021

Adjuvant radiotherapy versus early salvage radiotherapy following radical prostatectomy (TROG 08.03/ANZUP RAVES): a randomised, controlled, phase 3, non-inferiority trial.

Lancet Oncol 2020 10;21(10):1331-1340

Auckland Hospital, Auckland, New Zealand.

Background: Adjuvant radiotherapy has been shown to halve the risk of biochemical progression for patients with high-risk disease after radical prostatectomy. Early salvage radiotherapy could result in similar biochemical control with lower treatment toxicity. We aimed to compare biochemical progression between patients given adjuvant radiotherapy and those given salvage radiotherapy.

Methods: We did a phase 3, randomised, controlled, non-inferiority trial across 32 oncology centres in Australia and New Zealand. Eligible patients were aged at least 18 years and had undergone a radical prostatectomy for adenocarcinoma of the prostate with pathological staging showing high-risk features defined as positive surgical margins, extraprostatic extension, or seminal vesicle invasion; had an Eastern Cooperative Oncology Group performance status of 0-1, and had a postoperative prostate-specific antigen (PSA) concentration of 0·10 ng/mL or less. Patients were randomly assigned (1:1) using a minimisation technique via an internet-based, independently generated allocation to either adjuvant radiotherapy within 6 months of radical prostatectomy or early salvage radiotherapy triggered by a PSA of 0·20 ng/mL or more. Allocation sequence was concealed from investigators and patients, but treatment assignment for individual randomisations was not masked. Patients were stratified by radiotherapy centre, preoperative PSA, Gleason score, surgical margin status, and seminal vesicle invasion status. Radiotherapy in both groups was 64 Gy in 32 fractions to the prostate bed without androgen deprivation therapy with real-time review of plan quality on all cases before treatment. The primary endpoint was freedom from biochemical progression. Salvage radiotherapy would be deemed non-inferior to adjuvant radiotherapy if freedom from biochemical progression at 5 years was within 10% of that for adjuvant radiotherapy with a hazard ratio (HR) for salvage radiotherapy versus adjuvant radiotherapy of 1·48. The primary analysis was done on an intention-to-treat basis. This study is registered with ClinicalTrials.gov, NCT00860652.

Findings: Between March 27, 2009, and Dec 31, 2015, 333 patients were randomly assigned (166 to adjuvant radiotherapy; 167 to salvage radiotherapy). Median follow-up was 6·1 years (IQR 4·3-7·5). An independent data monitoring committee recommended premature closure of enrolment because of unexpectedly low event rates. 84 (50%) patients in the salvage radiotherapy group had radiotherapy triggered by a PSA of 0·20 ng/mL or more. 5-year freedom from biochemical progression was 86% (95% CI 81-92) in the adjuvant radiotherapy group versus 87% (82-93) in the salvage radiotherapy group (stratified HR 1·12, 95% CI 0·65-1·90; p=0·15). The grade 2 or worse genitourinary toxicity rate was lower in the salvage radiotherapy group (90 [54%] of 167) than in the adjuvant radiotherapy group (116 [70%] of 166). The grade 2 or worse gastrointestinal toxicity rate was similar between the salvage radiotherapy group (16 [10%]) and the adjuvant radiotherapy group (24 [14%]).

Interpretation: Salvage radiotherapy did not meet trial specified criteria for non-inferiority. However, these data support the use of salvage radiotherapy as it results in similar biochemical control to adjuvant radiotherapy, spares around half of men from pelvic radiation, and is associated with significantly lower genitourinary toxicity.

Funding: New Zealand Health Research Council, Australian National Health Medical Research Council, Cancer Council Victoria, Cancer Council NSW, Auckland Hospital Charitable Trust, Trans-Tasman Radiation Oncology Group Seed Funding, Cancer Research Trust New Zealand, Royal Australian and New Zealand College of Radiologists, Cancer Institute NSW, Prostate Cancer Foundation Australia, and Cancer Australia.
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http://dx.doi.org/10.1016/S1470-2045(20)30456-3DOI Listing
October 2020

Increased Dose to Organs in Urinary Tract Associates With Measures of Genitourinary Toxicity in Pooled Voxel-Based Analysis of 3 Randomized Phase III Trials.

Front Oncol 2020 22;10:1174. Epub 2020 Jul 22.

Department of Radiation Oncology, Sir Charles Gairdner Hospital, Nedlands, WA, Australia.

Dose information from organ sub-regions has been shown to be more predictive of genitourinary toxicity than whole organ dose volume histogram information. This study aimed to identify anatomically-localized regions where 3D dose is associated with genitourinary toxicities in healthy tissues throughout the pelvic anatomy. Dose distributions for up to 656 patients of the Trans-Tasman Radiation Oncology Group 03.04 RADAR trial were deformably registered onto a single exemplar CT dataset. Voxel- based multiple comparison permutation dose difference testing, Cox regression modeling and LASSO feature selection were used to identify regions where 3D dose-increase was associated with late grade ≥ 2 genitourinary dysuria, incontinence and frequency, and late grade ≥ 1 haematuria. This was externally validated by registering dose distributions from the RT01 (up to = 388) and CHHiP (up to = 247) trials onto the same exemplar and repeating the voxel-based tests on each of these data sets. All three datasets were then combined, and the tests repeated. Voxel-based Cox regression and multiple comparison permutation dose difference testing revealed regions where increased dose was correlated with genitourinary toxicity. Increased dose in the vicinity of the membranous and spongy urethra was associated with dysuria for all datasets. Haematuria was similarly correlated with increased dose at the membranous and spongy urethra, for the RADAR, CHHiP, and combined datasets. Some evidence was found for the association between incontinence and increased dose at the internal and external urethral sphincter for RADAR and the internal sphincter alone for the combined dataset. Incontinence was also strongly correlated with dose from posterior oblique beams. Patients with fields extending inferiorly and posteriorly to the CTV, adjacent to the membranous and spongy urethra, were found to experience increased frequency. Anatomically-localized dose-toxicity relationships were determined for late genitourinary symptoms in the urethra and urinary sphincters. Low-intermediate doses to the extraprostatic urethra were associated with risk of late dysuria and haematuria, while dose to the urinary sphincters was associated with incontinence.
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http://dx.doi.org/10.3389/fonc.2020.01174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7387667PMC
July 2020

Relationships between rectal and perirectal doses and rectal bleeding or tenesmus in pooled voxel-based analysis of 3 randomised phase III trials.

Radiother Oncol 2020 09 31;150:281-292. Epub 2020 Jul 31.

Department of Physics, University of Western Australia, Crawley, Australia; Department of Radiation Oncology, Sir Charles Gairdner Hospital, Nedlands, Australia; 5D Clinics, Claremont, Australia.

Background And Purpose: This study aimed to identify anatomically-localised regions where planned radiotherapy dose is associated with gastrointestinal toxicities in healthy tissues throughout the pelvic anatomy.

Materials And Methods: Planned dose distributions for up to 657 patients of the Trans Tasman Radiation Oncology Group 03.04 RADAR trial were deformably registered onto a single exemplar computed tomography dataset. Voxel-based multiple comparison permutation dose difference testing, Cox regression modelling and LASSO feature selection were used to identify regions where dose-increase was associated with grade ≥2 rectal bleeding (RB) or tenesmus, according to the LENT/SOMA scale. This was externally validated by registering dose distributions from the RT01 (n = 388) and CHHiP (n = 241) trials onto the same exemplar and repeating the tests on each of these data sets, and on all three datasets combined.

Results: Voxel-based Cox regression and permutation dose difference testing revealed regions where increased dose was correlated with gastrointestinal toxicity. Grade ≥2 RB was associated with posteriorly extended lateral beams that manifested high doses (>55 Gy) in a small rectal volume adjacent to the clinical target volume. A correlation was found between grade ≥2 tenesmus and increased low-intermediate dose (∼25 Gy) at the posterior beam region, including the posterior rectum and perirectal fat space (PRFS).

Conclusions: The serial response of the rectum with respect to RB has been demonstrated in patients with posteriorly extended lateral beams. Similarly, the parallel response of the PRFS with respect to tenesmus has been demonstrated in patients treated with the posterior beam.
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http://dx.doi.org/10.1016/j.radonc.2020.07.048DOI Listing
September 2020

Deforming to Best Practice: Key considerations for deformable image registration in radiotherapy.

J Med Radiat Sci 2020 Dec 2;67(4):318-332. Epub 2020 Aug 2.

Sydney West Radiation Oncology Network, Blacktown and Westmead, NSW, Australia.

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.
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http://dx.doi.org/10.1002/jmrs.417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754021PMC
December 2020

Reduced Dose Posterior to Prostate Correlates With Increased PSA Progression in Voxel-Based Analysis of 3 Randomized Phase 3 Trials.

Int J Radiat Oncol Biol Phys 2020 12 30;108(5):1304-1318. Epub 2020 Jul 30.

Department of Physics, University of Western Australia, Perth, Western Australia, Australia; Department of Radiation Oncology, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia; 5D Clinics, Claremont, Perth, Western Australia, Australia.

Purpose: Reducing margins during treatment planning to decrease dose to healthy organs surrounding the prostate can risk inadequate treatment of subclinical disease. This study aimed to investigate whether lack of dose to subclinical disease is associated with increased disease progression by using high-quality prostate radiation therapy clinical trial data to identify anatomically localized regions where dose variation is associated with prostate-specific antigen progression (PSAP).

Methods And Materials: Planned dose distributions for 683 patients of the Trans-Tasman Radiation Oncology Group 03.04 Randomized Androgen Deprivation and Radiotherapy (RADAR) trial were deformably registered onto a single exemplar computed tomography data set. These were divided into high-risk and intermediate-risk subgroups for analysis. Three independent voxel-based statistical tests, using permutation testing, Cox regression modeling, and least absolute shrinkage selection operator feature selection, were applied to identify regions where dose variation was associated with PSAP. Results from the intermediate-risk RADAR subgroup were externally validated by registering dose distributions from the RT01 (n = 388) and Conventional or Hypofractionated High Dose Intensity Modulated Radiotherapy for Prostate Cancer Trial (CHHiP) (n = 253) trials onto the same exemplar and repeating the tests on each of these data sets.

Results: Voxel-based Cox regression revealed regions where reduced dose was correlated with increased prostate-specific androgen progression. Reduced dose in regions associated with coverage at the posterior prostate, in the immediate periphery of the posterior prostate, and in regions corresponding to the posterior oblique beams or posterior lateral beam boundary, was associated with increased PSAP for RADAR and RT01 patients, but not for CHHiP patients. Reduced dose to the seminal vesicle region was also associated with increased PSAP for RADAR intermediate-risk patients.

Conclusions: Ensuring adequate dose coverage at the posterior prostate and immediately surrounding posterior region (including the seminal vesicles), where aggressive cancer spread may be occurring, may improve tumor control. It is recommended that particular care be taken when defining margins at the prostate posterior, acknowledging the trade-off between quality of life due to rectal dose and the preferences of clinicians and patients.
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http://dx.doi.org/10.1016/j.ijrobp.2020.07.030DOI Listing
December 2020

Stereotactic ablative body radiation therapy (SABR) in NSW.

Phys Eng Sci Med 2020 Jun 7;43(2):641-650. Epub 2020 Apr 7.

School of Physics, University of Sydney, Sydney, Australia.

A survey was conducted to establish the current utilisation of stereotactic ablative radiation therapy (SABR) services in NSW. The objective of the survey was to generate baseline data to inform requirements for a networked approach to the implementation of new radiation therapy techniques and technologies. All radiation therapy services in NSW were contacted by email with a request to complete a SABR service survey. Questions were designed to identify equipment used, treatment techniques in place, clinical sites treated with a SABR technique and plans to expand the current services offered. Each professional group was asked to identify areas of service delivery they would most like to improve. Sixteen responses were received representing 24 of 27 (89%) of NSW radiation therapy centres. The results indicate that most centres now treat with SABR, however the number of centres and the treatment sites are still increasing. VMAT treatments and 3D imaging are now commonplace. Liver was the most commonly reported treatment site where confidence in service delivery needed improvement. Data from the survey will be useful in formulating future collaborative and educational activities aimed at improving safety and efficacy in SABR service delivery to all patients in NSW and potentially the rest of the country.
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http://dx.doi.org/10.1007/s13246-020-00866-3DOI Listing
June 2020

Progress towards Patient-Specific, Spatially-Continuous Radiobiological Dose Prescription and Planning in Prostate Cancer IMRT: An Overview.

Cancers (Basel) 2020 Apr 1;12(4). Epub 2020 Apr 1.

Department of Physics, University of Western Australia, Crawley, WA 6009, Australia.

Advances in imaging have enabled the identification of prostate cancer foci with an initial application to focal dose escalation, with subvolumes created with image intensity thresholds. Through quantitative imaging techniques, correlations between image parameters and tumour characteristics have been identified. Mathematical functions are typically used to relate image parameters to prescription dose to improve the clinical relevance of the resulting dose distribution. However, these relationships have remained speculative or invalidated. In contrast, the use of radiobiological models during treatment planning optimisation, termed biological optimisation, has the advantage of directly considering the biological effect of the resulting dose distribution. This has led to an increased interest in the accurate derivation of radiobiological parameters from quantitative imaging to inform the models. This article reviews the progress in treatment planning using image-informed tumour biology, from focal dose escalation to the current trend of individualised biological treatment planning using image-derived radiobiological parameters, with the focus on prostate intensity-modulated radiotherapy (IMRT).
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http://dx.doi.org/10.3390/cancers12040854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226478PMC
April 2020

Radiation Dose Escalation or Longer Androgen Suppression to Prevent Distant Progression in Men With Locally Advanced Prostate Cancer: 10-Year Data From the TROG 03.04 RADAR Trial.

Int J Radiat Oncol Biol Phys 2020 03;106(4):693-702

School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia; Hunter Medical Research Institute, Newcastle, New South Wales, Australia.

Purpose: To clarify the relative effects of duration of androgen suppression (AS) and radiation dose escalation (RDE) on distant progression (DP) in men with locally advanced prostate cancer.

Methods And Materials: Participants with locally advanced prostate cancer in the TROG 03.04 RADAR trial were randomized to 6 or 18 months AS ± 18 months zoledronic acid (Z). The trial incorporated a RDE program by stratification at randomization and dosing options were 66, 70, or 74 Gy external beam radiation therapy (EBRT), or 46 Gy EBRT plus high-dose-rate brachytherapy boost (HDRB). The primary endpoint for this study was distant progression (DP). Secondary endpoints included local progression, bone progression, prostate cancer-specific mortality and all-cause mortality. Effect estimates for AS duration and RDE were derived using Fine and Gray competing risk models adjusting for use of Z, age, tumor stage, Gleason grade group, prostate-specific antigen, and treatment center. Cumulative incidence at 10 years was estimated for each RDE group.

Results: A total of 1051 out of 1071 randomized subjects were eligible for inclusion in this analysis. Compared with 6 months AS, 18 months AS significantly reduced DP independently of radiation dose (subhazard ratio 0.70; 95% confidence interval [CI], 0.56-0.87; P = .002). No statistically significant interaction between effect of AS duration and RT dose was observed (Wald test P = .76). In subgroup analyses, DP was significantly reduced by the longer duration of AS in the 70 Gy and HDRB groups but not in the 66 Gy and 74 Gy. Compared with 70 Gy, HDRB significantly reduced DP (subhazard ratio 0.68 [95% CI, 0.57-0.80]; P < .0001) independently of AS duration. At 10 years, adjusted cumulative incidences were 26.1% (95% CI, 18.9%-33.2%), 26.7% (22.9%-30.6%), 24.9% (20.0%-29.8%) and 19.7% (15.5%-23.8%) for DPs in the respective radiation dose groups.

Conclusions: Compared with 6 months AS, 18 months AS reduced DP independently of radiation dose. Men treated with HDRB gained a significant benefit from a longer duration of AS. Evidence of improved oncologic outcomes for HDRB compared with dose-escalated EBRT needs to be confirmed in a randomized trial.
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http://dx.doi.org/10.1016/j.ijrobp.2019.11.415DOI Listing
March 2020

Low-dose-rate iodine-125 seed air kerma strength measurement intercomparison.

Brachytherapy 2020 Jan - Feb;19(1):119-125. Epub 2019 Nov 19.

School of Physics, University of Sydney, Camperdown, New South Wales, Australia.

Purpose: The purpose of this study was to investigate the rate of compliance of air kerma strength (AKS) measurements of iodine-125 (I-125) seeds with international recommendations by departments in Australia and determine the potential impact of noncompliance.

Methods And Materials: To achieve this aim, we present an intercomparison of AKS measurements for a single I-125 seed performed by 11 radiotherapy departments in Australia. Measurements were performed at two sites, with each participating department traveling to one of the two host sites and measuring the AKS using their own equipment and local protocols. Each of the AKS measurements was compared with each other and the manufacturer-certified AKS.

Results: Nine of the 11 participating departments measured AKS fell within ±3% of the manufacturer's calibration certificate value, whereas all participating departments measured AKS within ±5% of the manufacturer's calibration certificate value. The total spread of the measured AKS among the 11 departments was 7.7%. Only two of the 11 participating departments complied with international recommendations and had their well chamber calibrated within the last 2 years. In addition, 2 of the 11 departments used a well chamber calibrated that was calibrated with a different seed model used during the intercomparison, whereas 4 of the 11 departments calibrated their well chamber "in-house" using a factory-calibrated seed provided by the seed manufacturer.

Conclusions: A significant variation in the methods used and frequency of calibration of well chambers were observed among the participating departments. The results of this study support the international recommendations on frequency and methodology of well chamber calibration. Failure to follow these recommendations significantly increases the uncertainty in AKS measurement of I-125 seeds.
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http://dx.doi.org/10.1016/j.brachy.2019.10.001DOI Listing
September 2020

Association analysis between quantitative MRI features and hypoxia-related genetic profiles in prostate cancer: a pilot study.

Br J Radiol 2019 Dec 30;92(1104):20190373. Epub 2019 Jul 30.

The University of Sydney, Sydney, New South Wales, Australia.

Objective: To investigate the association between multiparametric MRI (mpMRI) imaging features and hypoxia-related genetic profiles in prostate cancer.

Methods: mpMRI was acquired from six patients prior to radical prostatectomy. Sequences included weighted (TW) imaging, diffusion-weighted imaging, dynamic contrast enhanced MRI and blood oxygen-level dependent imaging. Imaging data were co-registered with histology using three-dimensional deformable registration methods. Texture features were extracted from W images and parametric maps from functional MRI. Full transcriptome genetic profiles were obtained using next generation sequencing from the prostate specimens. Pearson correlation coefficients were calculated between mpMRI data and hypoxia-related gene expression levels. Results were validated using glucose transporter one immunohistochemistry (IHC).

Results: Correlation analysis identified 34 candidate imaging features (six from the mpMRI data and 28 from W texture features). The IHC validation showed that 16 out of the 28 W texture features achieved weak but significant correlations ( < 0.05).

Conclusions: Weak associations between mpMRI features and hypoxia gene expressions were found. This indicates the potential use of MRI in assessing hypoxia status in prostate cancer. Further validation is required due to the low correlation levels.

Advances In Knowledge: This is a pilot study using radiogenomics approaches to address hypoxia within the prostate, which provides an opportunity for hypoxia-guided selective treatment techniques.
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http://dx.doi.org/10.1259/bjr.20190373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6913351PMC
December 2019

Automatic stratification of prostate tumour aggressiveness using multiparametric MRI: a horizontal comparison of texture features.

Acta Oncol 2019 Aug 17;58(8):1118-1126. Epub 2019 Apr 17.

a The Sir Peter MacCallum Department of Oncology , The University of Melbourne , Melbourne , Australia.

Previous studies have identified apparent diffusion coefficient (ADC) from diffusion-weighted imaging (DWI) can stratify prostate cancer into high- and low-grade disease (HG and LG, respectively). In this study, we consider the improvement of incorporating texture features (TFs) from T2-weighted (T2w) multiparametric magnetic resonance imaging (mpMRI) relative to mpMRI alone to predict HG and LG disease. mpMRI was acquired from 30 patients prior to radical prostatectomy. Sequences included T2w imaging, DWI and dynamic contrast enhanced (DCE) MRI. mpMRI data were co-registered with 'ground truth' histology. Tumours were delineated on the histology with Gleason scores (GSs) and classed as HG if GS ≥ 4 + 3, or LG if GS ≤ 3 + 4. Texture features based on three statistical families, namely the grey-level co-occurrence matrix (GLCM), grey-level run length matrix (GLRLM) and the grey-level size zone matrix (GLSZM), were computed from . Logistic regression models were trained using different feature subsets to classify each lesion as either HG or LG. To avoid overfitting, fivefold cross validation was applied on feature selection, model training and performance evaluation. Performance of all models generated was evaluated using the area under the curve (AUC) method. Consistent with previous studies, ADC was found to discriminate between HG and LG with an AUC of 0.76. Of the three statistical TF families, GLCM (plus select mpMRI features including ADC) scored the highest AUC (0.84) with GLRLM plus mpMRI similarly performing well (AUC  =  0.82). When all TFs were considered in combination, an AUC of 0.91 (95% confidence interval 0.87-0.95) was achieved. Incorporating T2w TFs significantly improved model performance for classifying prostate tumour aggressiveness. This result, however, requires further validation in a larger patient cohort.
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http://dx.doi.org/10.1080/0284186X.2019.1598576DOI Listing
August 2019

Contour variation is a primary source of error when delivering post prostatectomy radiotherapy: Results of the Trans-Tasman Radiation Oncology Group 08.03 Radiotherapy Adjuvant Versus Early Salvage (RAVES) benchmarking exercise.

J Med Imaging Radiat Oncol 2019 Jun 5;63(3):390-398. Epub 2019 Apr 5.

University of Sydney, Sydney, New South Wales, Australia.

Introduction: Variation in target volume delineation from clinical trial protocols has been shown to contribute to poorer patient outcomes. A clinical trial quality assurance framework can support compliance with trial protocol. Results of the TROG 08.03 RAVES benchmarking exercise considering variation from protocol, inter-observer variability and impact on dosimetry are reported in this paper.

Methods: Clinicians were required to contour and plan a benchmarking case according to trial protocol. Geometric pjmirometers including volume, Hausdorff Distance, Mean Distance to Agreement and DICE similarity coefficient were analysed for targets and organs at risk. Submitted volumes were compared to a STAPLE and consensus 'reference' volume for each structure. Dosimetric analysis was performed using dose volume histogram data.

Results: Benchmarking exercise submissions were received from 96 clinicians. In total 205 protocol variations were identified. The most common variation was inadequate contouring of the CTV in 84/205 (41%). The CTV volume ranged from 65.3 to 193.1 cm with a median of 113.2 cm . The most common dosimetric protocol variation related to rectal dosimetry. The mean submitted rectal volume receiving 40 Gy and 60 Gy, respectively, was 56.14% ± 5.55% and 30.25% ± 6.15%. When corrected to the protocol defined length the mean rectal volume receiving 40 Gy was 60.8% ± 7.92%, while the volume receiving 60 Gy was 33.86% ± 8.21%.

Conclusion: Variations from protocol were found in the RAVES benchmarking exercise, most notably in CTV and rectum delineation. Inter-observer variability was evident. Incorrect delineation of the rectum impacted on dosimetric compliance with protocol.
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http://dx.doi.org/10.1111/1754-9485.12884DOI Listing
June 2019

Multiparametric MRI and radiomics in prostate cancer: a review.

Australas Phys Eng Sci Med 2019 Mar 14;42(1):3-25. Epub 2019 Feb 14.

University of Sydney, Sydney, Australia.

Multiparametric MRI (mpMRI) is an imaging modality that combines anatomical MR imaging with one or more functional MRI sequences. It has become a versatile tool for detecting and characterising prostate cancer (PCa). The traditional role of mpMRI was confined to PCa staging, but due to the advanced imaging techniques, its role has expanded to various stages in clinical practises including tumour detection, disease monitor during active surveillance and sequential imaging for patient follow-up. Meanwhile, with the growing speed of data generation and the increasing volume of imaging data, it is highly demanded to apply computerised methods to process mpMRI data and extract useful information. Hence quantitative analysis for imaging data using radiomics has become an emerging paradigm. The application of radiomics approaches in prostate cancer has not only enabled automatic localisation of the disease but also provided a non-invasive solution to assess tumour biology (e.g. aggressiveness and the presence of hypoxia). This article reviews mpMRI and its expanding role in PCa detection, staging and patient management. Following that, an overview of prostate radiomics will be provided, with a special focus on its current applications as well as its future directions.
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http://dx.doi.org/10.1007/s13246-019-00730-zDOI Listing
March 2019

Voxel-wise correlation of positron emission tomography/computed tomography with multiparametric magnetic resonance imaging and histology of the prostate using a sophisticated registration framework.

BJU Int 2019 06 28;123(6):1020-1030. Epub 2019 Jan 28.

School of Physics, The University of Sydney, Sydney, New South Wales, Australia.

Objectives: To develop a registration framework for correlating positron emission tomography/computed tomography (PET/CT) images with multiparametric magnetic resonance imaging (mpMRI) and histology of the prostate, thereby enabling voxel-wise analysis of imaging parameters.

Patients And Methods: In this prospective proof-of-concept study, nine patients scheduled for radical prostatectomy underwent mpMRI and PET/CT imaging before surgery. One had PET imaging using F-fluoromethylcholine, five using Ga-labelled prostate-specific membrane antigen (PSMA)-HBED-CC (PMSA-11), and three using a trial Ga-labelled THP-PSMA tracer. PET/CT data were co-registered with mpMRI via the CT scan and an in vivo three-dimensional T2-weighted (T2w) MRI, and then co-registered with ground truth histology data using ex vivo MRI of the prostate specimen. Maximum and mean standardised uptake values (SUV and SUV ) were extracted from PET data using tumour annotations from histology, and Kolmogorov-Smirnov tests were used to compare between tumour- and benign-voxel values. Correlation analysis was performed between mpMRI and PET SUV tumour voxel values using Pearson's correlation coefficient and R statistics.

Results: PET/CT data from all nine patients were successfully registered with mpMRI and histology data. SUV and SUV ranged from 2.21 to 12.11 and 1.08 to 4.21, respectively. All patients showed the PET SUV values in benign and tumour voxels were from statistically different distributions. Correlation analysis showed no consistent trend between the T2w or apparent diffusion coefficient values and PET SUV. However, parameters from dynamic contrast-enhanced (DCE) MRI including the maximum enhancement, volume transfer constant (K ), and the initial area under the contrast agent concentration curve for the first 60 s after injection (iAUGC60), showed consistent positive correlations with PET SUV. Furthermore, R2* values from blood oxygen level-dependent (BOLD) MRI showed consistent negative correlations with PET SUV-voxel values.

Conclusion: We have developed a novel framework for registering and correlating PET/CT data at a voxel-level with mpMRI and histology. Despite registration uncertainties, perfusion and oxygenation parameters from DCE MRI and BOLD imaging showed correlations with PET SUV. Further analysis will be performed on a larger patient cohort to quantify these proof-of-concept findings. Improved understanding of the correlation between mpMRI and PET will provide supportive information for focal therapy planning of the prostate.
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http://dx.doi.org/10.1111/bju.14648DOI Listing
June 2019

Women and men in the Australasian College of Physical Scientists and Engineers in Medicine: workforce survey.

Australas Phys Eng Sci Med 2019 Mar 2;42(1):33-41. Epub 2018 Nov 2.

Chris O'Brien Lifehouse, Camperdown, NSW, Australia.

A survey was designed to determine aspirations, motivations and workplace experiences of both female and male members of the Australasian College of Physical Scientists and Engineers in Medicine (ACPSEM). The survey collected both quantitate and qualitative data, including open ended questions. This paper reports the survey's qualitative results. The research was approved by Ethics at University of South Australia and endorsed by ACPSEM. All 205 women (30% of total membership) and 440 men were invited to complete the survey online. The data for the qualitative analysis were responses to open-ended questions within the survey. 102 women and 150 men completed surveys were received, with 66 surveys analysed, before data saturation was reached. The survey revealed a number of themes that reflect concerns and opportunities identifying the direction for improving work-life balance and gender equity within the medical physics profession in Australasia. Issues around managing challenging workloads and professional development were amplified for women with children and child-rearing responsibilities, directly contributing to a reduction in work capacity and a reorientation of work-life priorities. The survey provides direction for strategies to improve work-life balance and enable equitable engagement in the profession. The first is to identify and develop role models that actively model successful work-life balance and flexibility in gender roles and in professional conduct. The second is to improve the management skills of current and emerging administrators, advocating for improved work conditions for medical physics professionals at an organisation level. Finally, efforts need to be made to establish flexible professional development and career progression opportunities amongst those that are unable to commit to large workloads, which is common for those with child-rearing responsibilities. The realisation of these strategic goals will reduce the identified barriers to full female participation in the workforce, and shift gender-based subcultures within the workplace.
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http://dx.doi.org/10.1007/s13246-018-0706-zDOI Listing
March 2019

Voxel-wise prostate cell density prediction using multiparametric magnetic resonance imaging and machine learning.

Acta Oncol 2018 Nov 26;57(11):1540-1546. Epub 2018 Apr 26.

a The Sir Peter MacCallum Department of Oncology , The University of Melbourne , Melbourne , Australia.

Background: There are currently no methods to estimate cell density in the prostate. This study aimed to develop predictive models to estimate prostate cell density from multiparametric magnetic resonance imaging (mpMRI) data at a voxel level using machine learning techniques.

Material And Methods: In vivo mpMRI data were collected from 30 patients before radical prostatectomy. Sequences included T2-weighted imaging, diffusion-weighted imaging and dynamic contrast-enhanced imaging. Ground truth cell density maps were computed from histology and co-registered with mpMRI. Feature extraction and selection were performed on mpMRI data. Final models were fitted using three regression algorithms including multivariate adaptive regression spline (MARS), polynomial regression (PR) and generalised additive model (GAM). Model parameters were optimised using leave-one-out cross-validation on the training data and model performance was evaluated on test data using root mean square error (RMSE) measurements.

Results: Predictive models to estimate voxel-wise prostate cell density were successfully trained and tested using the three algorithms. The best model (GAM) achieved a RMSE of 1.06 (± 0.06) × 10 cells/mm and a relative deviation of 13.3 ± 0.8%.

Conclusion: Prostate cell density can be quantitatively estimated non-invasively from mpMRI data using high-quality co-registered data at a voxel level. These cell density predictions could be used for tissue classification, treatment response evaluation and personalised radiotherapy.
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http://dx.doi.org/10.1080/0284186X.2018.1468084DOI Listing
November 2018

Association between measures of treatment quality and disease progression in prostate cancer radiotherapy: An exploratory analysis from the TROG 03.04 RADAR trial.

J Med Imaging Radiat Oncol 2018 Apr 8;62(2):248-255. Epub 2017 Dec 8.

School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia.

Introduction: Quality assurance methods are incorporated into multicentre radiotherapy clinical trials for ensuring consistent application of trial protocol and quantifying treatment uncertainties. The study's purpose was to determine whether post-treatment disease progression is associated with measures of the quality of radiotherapy treatment.

Methods: The TROG 03.04 RADAR trial tested the impact of androgen deprivation on prostate cancer patients receiving dose-escalated external beam radiation therapy. The trial incorporated a plan-review process and Level III dosimetric intercomparison at each centre, from which variables suggestive of treatment quality were collected. Kaplan-Meier statistics and Fine and Gray competing risk modelling were employed to test for associations between quality-related variables and the participant outcome local composite progression.

Results: Increased 'dose-difference' at the prostatic apex and at the anterior rectal wall, between planned and measured dose, was associated with reduced progression. Participants whose treatment plans included clinical target volume (CTV) to planning target volume (PTV) margins exceeding protocol requirements also experienced reduced progression. Other quality-related variables, including total accrual from participating centres, measures of target coverage and other variations from protocol, were not significantly associated with progression.

Conclusions: This analysis has revealed the association of several treatment quality factors with disease progression. Increased dose and dose margin coverage in the prostate region can reduce disease progression. Extensive and rigorous monitoring has helped to maximise treatment quality, reducing the incidence of quality-indicator outliers, and thus reduce the chance of observing significant associations with progression rates.
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http://dx.doi.org/10.1111/1754-9485.12695DOI Listing
April 2018

Association between treatment planning and delivery factors and disease progression in prostate cancer radiotherapy: Results from the TROG 03.04 RADAR trial.

Radiother Oncol 2018 Feb 6;126(2):249-256. Epub 2017 Nov 6.

School of Medicine and Public Health, University of Newcastle, Australia.

Background And Purpose: To evaluate the impact of treatment planning and delivery factors on treatment outcome as measured by post-treatment disease progression.

Materials And Methods: Accruing 813 external beam radiotherapy participants during 2003-2007, the RADAR trial collected a comprehensive range of clinical treatment factor data for each participant. Both the Fine and Gray competing risks modelling and the Kaplan-Meier (KM) analysis were undertaken to determine the impact of these factors on local-composite progression (LCP), with 709 participants available for analysis.

Results: Participants with treatments involving 7 or more beams experienced significantly higher incidence of LCP, with a sub-hazard ratio (relative to 3-beam participants) of 3.056 (CI: 1.446-6.458, p < 0.0034). Participants treated with a more rigorous dose calculation algorithm also displayed significantly higher incidence of LCP, with a sub-hazard ratio of 1.686 (CI: 1.334-2.132, p < 0.0001). The KM analysis resulted in the same groups showing a higher incidence of LCP, with log-rank test results of p = 0.0005 and p = 0.0008 respectively.

Conclusions: The RADAR dataset has enabled a successful secondary analysis in which the impact of technical modifications has been assessed, challenging several established hypotheses. Increasingly precise treatments should be complemented with increasing accuracy to avoid potential geometric miss.
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http://dx.doi.org/10.1016/j.radonc.2017.10.021DOI Listing
February 2018

A virtual dosimetry audit - Towards transferability of gamma index analysis between clinical trial QA groups.

Radiother Oncol 2017 12;125(3):398-404

Department of Medical Physics, Royal Surrey County Hospital NHS Foundation Trust, Guildford, UK; Metrology for Medical Physics Centre, National Physical Laboratory, Teddington, UK; Radiotherapy Trials QA (RTTQA), UK.

Purpose: Quality assurance (QA) for clinical trials is important. Lack of compliance can affect trial outcome. Clinical trial QA groups have different methods of dose distribution verification and analysis, all with the ultimate aim of ensuring trial compliance. The aim of this study was to gain a better understanding of different processes to inform future dosimetry audit reciprocity.

Materials: Six clinical trial QA groups participated. Intensity modulated treatment plans were generated for three different cases. A range of 17 virtual 'measurements' were generated by introducing a variety of simulated perturbations (such as MLC position deviations, dose differences, gantry rotation errors, Gaussian noise) to three different treatment plan cases. Participants were blinded to the 'measured' data details. Each group analysed the datasets using their own gamma index (γ) technique and using standardised parameters for passing criteria, lower dose threshold, γ normalisation and global γ.

Results: For the same virtual 'measured' datasets, different results were observed using local techniques. For the standardised γ, differences in the percentage of points passing with γ < 1 were also found, however these differences were less pronounced than for each clinical trial QA group's analysis. These variations may be due to different software implementations of γ.

Conclusions: This virtual dosimetry audit has been an informative step in understanding differences in the verification of measured dose distributions between different clinical trial QA groups. This work lays the foundations for audit reciprocity between groups, particularly with more clinical trials being open to international recruitment.
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http://dx.doi.org/10.1016/j.radonc.2017.10.012DOI Listing
December 2017

An integrated system for clinical treatment verification of HDR prostate brachytherapy combining source tracking with pretreatment imaging.

Brachytherapy 2018 Jan - Feb;17(1):111-121. Epub 2017 Sep 22.

School of Science, RMIT University, Melbourne, VIC, Australia.

Purpose: High-dose-rate (HDR) prostate brachytherapy treatment is usually delivered in one or a few large dose fractions. Poor execution of a planned treatment could have significant clinical impact, as high doses are delivered in seconds, and mistakes in an individual fraction cannot be easily rectified. Given that most potential errors in HDR brachytherapy ultimately lead to a geographical miss, a more direct approach to verification of correct treatment delivery is to directly monitor the position of the source throughout the treatment. In this work, we report on the clinical implementation of our treatment verification system that uniquely combines the 2D source-tracking capability with 2D pretreatment imaging, using a single flat panel detector (FPD).

Methods And Materials: The clinical brachytherapy treatment couch was modified to allow integration of the FPD into the couch. This enabled the patient to be set up in the brachytherapy bunker in a position that closely matched that at treatment planning imaging. An anteroposterior image was acquired of the patient immediately before treatment delivery and was assessed by the Radiation Oncologist online, to reestablish the positions of the catheters relative to the prostate. Assessment of catheter positions was performed in the left-right and superior-inferior directions along the entire catheter length and throughout the treatment volume. Source tracking was then performed during treatment delivery, and the measured position of the source dwells were directly compared to the treatment plan for verification.

Results: The treatment verification system was integrated into the clinical environment without significant change to workflow. Two patient cases are presented in this work to provide clinical examples of this system, which is now in routine use for all patient treatments in our clinic. The catheter positions were visualized relative to the prostate, immediately before treatment delivery. For one of the patient cases presented in this work, they agreed with the treatment plan on average by 1.5 mm and were identifiable as a predominantly inferior shift. The source tracking was performed during treatment delivery, and for the same case, the mean deviation from the planned dwell positions was 1.9 mm (max = 4.9 mm) for 280 positions across all catheters.

Conclusion: We have implemented our noninvasive treatment verification system based on an FPD in the clinical environment. The device is integrated into a patient treatment couch, and the process is now included in the routine clinical treatment procedure with minor impact on workflow. The system which combines both 2D pretreatment imaging and HDR 2D source tracking provides a range of information that can be used for comprehensive treatment verification. The system has the potential to meaningfully improve safety standards by allowing widespread adoption of routine treatment verification in HDR brachytherapy.
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http://dx.doi.org/10.1016/j.brachy.2017.08.004DOI Listing
July 2018

Focal therapy for prostate cancer: the technical challenges.

J Contemp Brachytherapy 2017 Aug 30;9(4):383-389. Epub 2017 Aug 30.

Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Vic.

Focal therapy for prostate cancer has been proposed as an alternative treatment to whole gland therapy, offering the opportunity for tumor dose escalation and/or reduced toxicity. Brachytherapy, either low-dose-rate or high-dose-rate, provides an ideal approach, offering both precision in dose delivery and opportunity for a highly conformal, non-uniform dose distribution. Whilst multiple consensus documents have published clinical guidelines for patient selection, there are insufficient data to provide clear guidelines on target volume delineation, treatment planning margins, treatment planning approaches, and many other technical issues that should be considered before implementing a focal brachytherapy program. Without consensus guidelines, there is the potential for a diversity of practices to develop, leading to challenges in interpreting outcome data from multiple centers. This article provides an overview of the technical considerations for the implementation of a clinical service, and discusses related topics that should be considered in the design of clinical trials to ensure precise and accurate methods are applied for focal brachytherapy treatments.
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http://dx.doi.org/10.5114/jcb.2017.69809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5611463PMC
August 2017

Understanding the Relationship Between Interactive Optimisation and Visual Analytics in the Context of Prostate Brachytherapy.

IEEE Trans Vis Comput Graph 2018 01 29;24(1):319-329. Epub 2017 Aug 29.

The fields of operations research and computer science have long sought to find automatic solver techniques that can find high-quality solutions to difficult real-world optimisation problems. The traditional workflow is to exactly model the problem and then enter this model into a general-purpose "black-box" solver. In practice, however, many problems cannot be solved completely automatically, but require a "human-in-the-loop" to iteratively refine the model and give hints to the solver. In this paper, we explore the parallels between this interactive optimisation workflow and the visual analytics sense-making loop. We assert that interactive optimisation is essentially a visual analytics task and propose a problem-solving loop analogous to the sense-making loop. We explore these ideas through an in-depth analysis of a use-case in prostate brachytherapy, an application where interactive optimisation may be able to provide significant assistance to practitioners in creating prostate cancer treatment plans customised to each patient's tumour characteristics. However, current brachytherapy treatment planning is usually a careful, mostly manual process involving multiple professionals. We developed a prototype interactive optimisation tool for brachytherapy that goes beyond current practice in supporting focal therapy - targeting tumour cells directly rather than simply seeking coverage of the whole prostate gland. We conducted semi-structured interviews, in two stages, with seven radiation oncology professionals in order to establish whether they would prefer to use interactive optimisation for treatment planning and whether such a tool could improve their trust in the novel focal therapy approach and in machine generated solutions to the problem.
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http://dx.doi.org/10.1109/TVCG.2017.2744418DOI Listing
January 2018

A generic TG-186 shielded applicator for commissioning model-based dose calculation algorithms for high-dose-rate Ir brachytherapy.

Med Phys 2017 Nov 19;44(11):5961-5976. Epub 2017 Oct 19.

Département de Radio-Oncologie et Axe oncologie du Centre de recherche du CHU de Québec, CHU de Québec, Québec, Québec, G1R 2J6, Canada.

Purpose: A joint working group was created by the American Association of Physicists in Medicine (AAPM), the European Society for Radiotherapy and Oncology (ESTRO), and the Australasian Brachytherapy Group (ABG) with the charge, among others, to develop a set of well-defined test case plans and perform calculations and comparisons with model-based dose calculation algorithms (MBDCAs). Its main goal is to facilitate a smooth transition from the AAPM Task Group No. 43 (TG-43) dose calculation formalism, widely being used in clinical practice for brachytherapy, to the one proposed by Task Group No. 186 (TG-186) for MBDCAs. To do so, in this work a hypothetical, generic high-dose rate (HDR) Ir shielded applicator has been designed and benchmarked.

Methods: A generic HDR Ir shielded applicator was designed based on three commercially available gynecological applicators as well as a virtual cubic water phantom that can be imported into any DICOM-RT compatible treatment planning system (TPS). The absorbed dose distribution around the applicator with the TG-186 Ir source located at one dwell position at its center was computed using two commercial TPSs incorporating MBDCAs (Oncentra Brachy with Advanced Collapsed-cone Engine, ACE™, and BrachyVision ACUROS™) and state-of-the-art Monte Carlo (MC) codes, including ALGEBRA, BrachyDose, egs_brachy, Geant4, MCNP6, and Penelope2008. TPS-based volumetric dose distributions for the previously reported "source centered in water" and "source displaced" test cases, and the new "source centered in applicator" test case, were analyzed here using the MCNP6 dose distribution as a reference. Volumetric dose comparisons of TPS results against results for the other MC codes were also performed. Distributions of local and global dose difference ratios are reported.

Results: The local dose differences among MC codes are comparable to the statistical uncertainties of the reference datasets for the "source centered in water" and "source displaced" test cases and for the clinically relevant part of the unshielded volume in the "source centered in applicator" case. Larger local differences appear in the shielded volume or at large distances. Considering clinically relevant regions, global dose differences are smaller than the local ones. The most disadvantageous case for the MBDCAs is the one including the shielded applicator. In this case, ACUROS agrees with MC within [-4.2%, +4.2%] for the majority of voxels (95%) while presenting dose differences within [-0.12%, +0.12%] of the dose at a clinically relevant reference point. For ACE, 95% of the total volume presents differences with respect to MC in the range [-1.7%, +0.4%] of the dose at the reference point.

Conclusions: The combination of the generic source and generic shielded applicator, together with the previously developed test cases and reference datasets (available in the Brachytherapy Source Registry), lay a solid foundation in supporting uniform commissioning procedures and direct comparisons among treatment planning systems for HDR Ir brachytherapy.
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http://dx.doi.org/10.1002/mp.12459DOI Listing
November 2017
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