Publications by authors named "Tomas Kron"

202 Publications

CT slice alignment to whole-body reference geometry by convolutional neural network.

Phys Eng Sci Med 2021 Sep 10. Epub 2021 Sep 10.

Department of Physical Sciences, Peter MacCallum Cancer Centre, Melbourne, 3000, Australia.

Volumetric medical imaging lacks a standardised coordinate geometry which links image frame-of-reference to specific anatomical regions. This results in an inability to locate anatomy in medical images without visual assessment and precludes a variety of image analysis tasks which could benefit from a standardised, machine-readable coordinate system. In this work, a proposed geometric system that scales based on patient size is described and applied to a variety of cases in computed tomography imaging. Subsequently, a convolutional neural network is trained to associate axial slice CT image appearance with the standardised coordinate value along the patient superior-inferior axis. The trained neural network showed an accuracy of ± 12 mm in the ability to predict per-slice reference location and was relatively stable across all annotated regions ranging from brain to thighs. A version of the trained model along with scripts to perform network training in other applications are made available. Finally, a selection of potential use applications are illustrated including organ localisation, image registration initialisation, and scan length determination for auditing diagnostic reference levels.
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http://dx.doi.org/10.1007/s13246-021-01056-5DOI Listing
September 2021

Radiomics feature stability of open-source software evaluated on apparent diffusion coefficient maps in head and neck cancer.

Sci Rep 2021 Sep 3;11(1):17633. Epub 2021 Sep 3.

Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, USA.

Radiomics is a promising technique for discovering image based biomarkers of therapy response in cancer. Reproducibility of radiomics features is a known issue that is addressed by the image biomarker standardisation initiative (IBSI), but it remains challenging to interpret previously published radiomics signatures. This study investigates the reproducibility of radiomics features calculated with two widely used radiomics software packages (IBEX, MaZda) in comparison to an IBSI compliant software package (PyRadiomics). Intensity histogram, shape and textural features were extracted from 334 diffusion weighted magnetic resonance images of 59 head and neck cancer (HNC) patients from the PREDICT-HN observational radiotherapy study. Based on name and linear correlation, PyRadiomics shares 83 features with IBEX and 49 features with MaZda, a sub-set of well correlated features are considered reproducible (IBEX: 15 features, MaZda: 18 features). We explore the impact of including non-reproducible radiomics features in a HNC radiotherapy response model. It is possible to classify equivalent patient groups using radiomic features from either software, but only when restricting the model to reliable features using a correlation threshold method. This is relevant for clinical biomarker validation trials as it provides a framework to assess the reproducibility of reported radiomic signatures from existing trials.
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http://dx.doi.org/10.1038/s41598-021-96600-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417253PMC
September 2021

Single-Fraction vs Multifraction Stereotactic Ablative Body Radiotherapy for Pulmonary Oligometastases (SAFRON II): The Trans Tasman Radiation Oncology Group 13.01 Phase 2 Randomized Clinical Trial.

JAMA Oncol 2021 Aug 29. Epub 2021 Aug 29.

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

Importance: Evidence is lacking from randomized clinical trials to guide the optimal approach for stereotactic ablative body radiotherapy (SABR) in patients with pulmonary oligometastases.

Objective: To assess whether single-fraction or multifraction SABR is more effective for the treatment of patients with pulmonary oligometastases.

Design, Setting, And Participants: This multicenter, unblinded, phase 2 randomized clinical trial of 90 patients across 13 centers in Australia and New Zealand enrolled patients with 1 to 3 lung oligometastases less than or equal to 5 cm from any nonhematologic malignant tumors located away from the central airways, Eastern Cooperative Oncology Group performance status 0 or 1, and all primary and extrathoracic disease controlled with local therapy. Enrollment was from January 1, 2015, to December 31, 2018, with a minimum patient follow-up of 2 years.

Interventions: Single fraction of 28 Gy (single-fraction arm) or 4 fractions of 12 Gy (multifraction arm) to each oligometastasis.

Main Outcomes And Measures: The main outcome was grade 3 or higher treatment-related adverse events (AEs) occurring within 1 year of SABR. Secondary outcomes were freedom from local failure, overall survival, disease-free survival, and patient-reported outcomes (MD Anderson Symptom Inventory-Lung Cancer and EuroQol 5-dimension visual analog scale).

Results: Ninety participants were randomized, of whom 87 were treated for 133 pulmonary oligometastases. The mean (SD) age was 66.6 [11.6] years; 58 (64%) were male. Median follow-up was 36.5 months (interquartile range, 24.8-43.9 months). The numbers of grade 3 or higher AEs related to treatment at 1 year were 2 (5%; 80% CI, 1%-13%) in the single-fraction arm and 1 (3%; 80% CI, 0%-10%) in the multifraction arm, with no significant difference observed between arms. One grade 5 AE occurred in the multifraction arm. No significant differences were found between the multifraction arm and single-fraction arm for freedom from local failure (hazard ratio [HR], 0.5; 95% CI, 0.2-1.3; P = .13), overall survival (HR, 1.5; 95% CI, 0.6-3.7; P = .44), or disease-free survival (HR, 1.0; 95% CI, 0.6-1.6; P > .99). There were no significant differences observed in patient-reported outcomes.

Conclusions And Relevance: In this randomized clinical trial, neither arm demonstrated evidence of superior safety, efficacy, or symptom burden; however, single-fraction SABR is more efficient to deliver. Therefore, single-fraction SABR, as assessed by the most acceptable outcome profile from all end points, could be chosen to escalate to future studies.

Trial Registration: ClinicalTrials.gov Identifier: NCT01965223.
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http://dx.doi.org/10.1001/jamaoncol.2021.2939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8404145PMC
August 2021

A retrospective review of the long-term outcomes of online adaptive radiation therapy and conventional radiation therapy for muscle invasive bladder cancer.

Clin Transl Radiat Oncol 2021 Sep 6;30:65-70. Epub 2021 Aug 6.

Department of Radiation Oncology, Olivia Newton-John Cancer Wellness & Research Centre, Austin Hospital, Victoria, Australia.

Background And Purpose: To report long-term outcomes of online image-guided (IG) adaptive radiation therapy (aRT) versus conventional IG radiation therapy (cRT) for bladder preservation in muscle-invasive bladder cancer (MIBC).

Materials And Methods: A retrospective review of patients with histologically proven MIBC who were prescribed radical intent radiation therapy (RT) following trans-urethral resection of bladder tumour (TURBT) was conducted. There were three groups based on their RT treatment modality: conventional RT (cRT), margin 5 mm adaptive RT (aRT5mm) and margin 7 mm adaptive RT (aRT7mm).

Results: 171 patients were included in this study, with median age of 79.4 years (41-90). Approximately half of all patients received concurrent chemotherapy. N = 57 underwent cRT, n = 39 underwent aRT5mm, and n = 75 underwent aRT7mm. Response evaluable patients in all three groups (n = 133) had high rates of complete response (CR, 83%) on first post-RT cystoscopy with no significant differences between the groups. At a median follow-up of 54 months, the 5-year freedom from muscle-invasive failure survival (FFMIFS) in the cRT, aRT5mm, and aRT7mm groups were 75%, 59%, and 98%, respectively. The estimated cancer specific survival (CSS) at 5 years were 60%, 30%, and 59%, respectively. The estimated overall survival (OS) at 5 years were 43%, 26%, and 38%, respectively. The incidence of late grade 3 or 4 toxicity was n = 5 in aRT5mm, n = 2 in cRT group, and n = 1 in aRT7mm.

Conclusion: IG aRT with 7 mm expansion for MIBC provides higher rates of FFMIFS, similar 5-year CSS and OS, as well as toxicity outcomes when compared to cRT. aRT with 5 mm expansion with this RT protocol is not recommended for treatment.
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http://dx.doi.org/10.1016/j.ctro.2021.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358463PMC
September 2021

Reducing the impact on renal function of kidney SABR through management of respiratory motion.

Phys Med 2021 Aug 2;89:72-79. Epub 2021 Aug 2.

Department of Physical Sciences, Peter MacCallum Cancer Centre, Melbourne, Victoria 3000, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Victoria 3000, Australia; Centre for Medical Radiation Physics, University of Wollongong, NSW 2522, Australia.

Purpose: Stereotactic ablative body radiotherapy (SABR) is as a viable treatment option to treat kidney cancer. This study quantifies dose reduction to non-tumour ipsilateral kidney and estimated renal function gain from elimination of respiratory motion.

Methods: We reviewed 62 previously treated kidney SABR patients. The gross tumour volume (GTV) was segmented in each phase of a four-dimensional CT (4DCT). Tumour motion amplitude (TMA) was obtained from the GTV centroid on each phase. Low modulation, motion managed (MM) plans were generated on the exhale phase image. Internal target volume (ITV)-based plans were generated on the 4DCT average intensity projection. To estimate delivered kidney dose, the ITV-based plan was copied ten times to the exhale phase image, with isocentre located at the GTV centroid position in each phase. The dose was calculated and averaged to result in non-motion managed plans. Difference in ipsilateral kidney volume receiving 50% of the prescription dose (V50%) and estimated glomerular filtration rate (GFR) change were compared between ITV and MM plans.

Results: The mean ± st.dev. TMA was 0.79 ± 0.49 cm. Removing respiratory motion reduced ipsilateral kidney V50% (slope of the difference = 12 cc/cm of TMA, Pearson-r = 0.69, p-value <10), and estimated GFR was improved (slope = 4.4 %/cm of TMA, Pearson-r = 0.85, p-value < 10).

Conclusions: We have quantified the improvement in healthy kidney dose when removing respiratory motion from kidney SABR plans, and demonstrated an expected gain in GFR of 4.4 %/cm of motion removed.
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http://dx.doi.org/10.1016/j.ejmp.2021.07.020DOI Listing
August 2021

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

Radiat Oncol 2021 Aug 3;16(1):142. Epub 2021 Aug 3.

Department of Oncology, Sir Peter MacCallum, University of Melbourne, Parkville, Australia.

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.
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http://dx.doi.org/10.1186/s13014-021-01820-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8330099PMC
August 2021

Out-of-field dose in stereotactic radiotherapy for paediatric patients.

Phys Imaging Radiat Oncol 2021 Jul 4;19:1-5. Epub 2021 Jun 4.

RMIT University, School of Science, Melbourne, Australia.

Background And Purpose: Stereotactic radiotherapy combines image guidance and high precision delivery with small fields to deliver high doses per fraction in short treatment courses. In preparation for extension of these treatment techniques to paediatric patients we characterised and compared doses out-of-field in a paediatric anthropomorphic phantom for small flattened and flattening filter free (FFF) photon beams.

Method And Materials: Dose measurements were taken in several organs and structures outside the primary field in an anthropomorphic phantom of a 5 year old child (CIRS) using thermoluminescence dosimetry (LiF:Mg,Cu,P). Out-of-field doses from a medical linear accelerator were assessed for 6 MV flattened and FFF beams of field sizes between 2 × 2 and 10 × 10 cm.

Results: FFF beams resulted in reduced out-of-field doses for all field sizes when compared to flattened beams. Doses for FFF and flattened beams converged for all field sizes at larger distances (>40 cm) from the central axis as leakage becomes the primary source of out-of-field dose. Rotating the collimator to place the MLC bank in the longitudinal axis of the patient was shown to reduce the peripheral doses measured by up to 50% in Varian linear accelerators.

Conclusion: Minimising out-of-field doses by using FFF beams and aligning the couch and collimator to provide tertiary shielding demonstrated advantages of small field, FFF treatments in a paediatric setting.
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http://dx.doi.org/10.1016/j.phro.2021.05.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295843PMC
July 2021

Calculation algorithms and penumbra: Underestimation of dose in organs at risk in dosimetry audits.

Med Phys 2021 Jul 21. Epub 2021 Jul 21.

Physical Sciences, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.

Purpose: The aim of this study is to investigate overdose to organs at risk (OARs) observed in dosimetry audits in Monte Carlo (MC) algorithms and Linear Boltzmann Transport Equation (LBTE) algorithms. The impact of penumbra modeling on OAR dose was assessed with the adjustment of MC modeling parameters and the clinical relevance of the audit cases was explored with a planning study of spine and head and neck (H&N) patient cases.

Methods: Dosimetric audits performed by the Australian Clinical Dosimetry Service (ACDS) of 43 anthropomorphic spine plans and 1318 C-shaped target plans compared the planned dose to doses measured with ion chamber, microdiamond, film, and ion chamber array. An MC EGSnrc model was created to simulate the C-shape target case. The electron cut-off energy E was set at 500, 200, and 10 keV, and differences between 1 and 3 mm voxel were calculated. A planning study with 10 patient stereotactic body radiotherapy (SBRT) spine plans and 10 patient H&N plans was calculated in both Acuros XB (AXB) v15.6.06 and Anisotropic Analytical Algorithm (AAA) v15.6.06. The patient contour was overridden to water as only the penumbral differences between the two different algorithms were under investigation.

Results: The dosimetry audit results show that for the SBRT spine case, plans calculated in AXB are colder than what is measured in the spinal cord by 5%-10%. This was also observed for other audit cases where a C-shape target is wrapped around an OAR where the plans were colder by 3%-10%. Plans calculated with Monaco MC were colder than measurements by approximately 7% with the OAR surround by a C-shape target, but these differences were not noted in the SBRT spine case. Results from the clinical patient plans showed that the AXB was on average 7.4% colder than AAA when comparing the minimum dose in the spinal cord OAR. This average difference between AXB and AAA reduced to 4.5% when using the more clinically relevant metric of maximum dose in the spinal cord. For the H&N plans, AXB was cooler on average than AAA in the spinal cord OAR (1.1%), left parotid (1.7%), and right parotid (2.3%). The EGSnrc investigation also noted similar, but smaller differences. The beam penumbra modeled by E  = 500 keV was steeper than the beam penumbra modeled by E  = 10 keV as the full scatter is not accounted for, which resulted in less dose being calculated in a central OAR region where the penumbra contributes much of the dose. The dose difference when using 2.5 mm voxels of the center of the OAR between 500 and 10 keV was 3%, reducing to 1% between 200 and 10 keV.

Conclusions: Lack of full penumbral modeling due to approximations in the algorithms in MC based or LBTE algorithms are a contributing factor as to why these algorithms under-predict the dose to OAR when the treatment volume is wrapped around the OAR. The penumbra modeling approximations also contribute to AXB plans predicting colder doses than AAA in areas that are in the vicinity of beam penumbra. This effect is magnified in regions where there are many beam penumbras, for example in the spinal cord for spine SBRT cases.
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http://dx.doi.org/10.1002/mp.15123DOI Listing
July 2021

Development of a physical geometric phantom for deformable image registration credentialing of radiotherapy centers for a clinical trial.

J Appl Clin Med Phys 2021 Jul 22;22(7):255-265. Epub 2021 Jun 22.

Department of Radiation Oncology and Image-Applied Therapy, Kyoto University, Kyoto, Japan.

Purpose: This study aimed to develop a physical geometric phantom for the deformable image registration (DIR) credentialing of radiotherapy centers for a clinical trial and tested the feasibility of the proposed phantom at multiple domestic and international institutions.

Methods And Materials: The phantom reproduced tumor shrinkage, rectum shape change, and body shrinkage using several physical phantoms with custom inserts. We tested the feasibility of the proposed phantom using 5 DIR patterns at 17 domestic and 2 international institutions (21 datasets). Eight institutions used the MIM software (MIM Software Inc, Cleveland, OH); seven used Velocity (Varian Medical Systems, Palo Alto, CA), and six used RayStation (RaySearch Laboratories, Stockholm, Sweden). The DIR accuracy was evaluated using the Dice similarity coefficient (DSC) and Hausdorff distance (HD).

Results: The mean and one standard deviation (SD) values (range) of DSC were 0.909 ± 0.088 (0.434-0.984) and 0.909 ± 0.048 (0.726-0.972) for tumor and rectum proxies, respectively. The mean and one SD values (range) of the HD value were 5.02 ± 3.32 (1.53-20.35) and 5.79 ± 3.47 (1.22-21.48) (mm) for the tumor and rectum proxies, respectively. In three patterns evaluating the DIR accuracy within the entire phantom, 61.9% of the data had more than a DSC of 0.8 in both tumor and rectum proxies. In two patterns evaluating the DIR accuracy by focusing on tumor and rectum proxies, all data had more than a DSC of 0.8 in both tumor and rectum proxies.

Conclusions: The wide range of DIR performance highlights the importance of optimizing the DIR process. Thus, the proposed method has considerable potential as an evaluation tool for DIR credentialing and quality assurance.
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http://dx.doi.org/10.1002/acm2.13319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292683PMC
July 2021

Contralateral breast dose with electronic compensators and conventional tangential fields - A clinical dosimetric study.

Z Med Phys 2021 Jun 11. Epub 2021 Jun 11.

Peter MacCallum Cancer Centre, Victoria, Australia.

Dose to the contralateral breast (CLB) from radiotherapy treatment has the potential to induce secondary breast cancer. Electronic tissue compensation (eComp) for breast cancer patients is one of the alternative methods to conventional 3D-conformal radiotherapy that eliminates the use of wedges. Several studies have investigated dose to the CLB using tangential fields involving wedges, intensity-modulated radiation therapy and volumetric modulated arc radiation therapy and various other techniques via treatment planning system calculations, Monte Carlo methods and phantoms. However, there are limited data published in assessing the actual dose received by the CLB from treatment with eComp-based tangential fields. In this study, the CLB dose for patients undergoing tangential field radiotherapy with eComp and enhanced dynamic wedged (standard) tangential fields was measured and compared to assess the CLB dose between the two methods. Measurements were conducted on a randomised trial of 40 patients, 20 of them had undergone standard planning, and the remaining 20 were treated with eComp. The mean surface dose measured with TLDs at 3cm from the medial tangential border for eComp and standard techniques was 10.04±1.37% and 10.14±2.05%, respectively for a prescription dose of 2.65Gy/fraction. The estimated dose at 1cm depth in tissue, measured with the use of perspex domes placed over the TLD at the same location, was 5.12±0.87% and 6.29±2.01% for eComp and standard, respectively. The CLB dose is dependent on the proximity of the medial tangential field edge to the contralateral breast and is patient-specific. The results of this study show that at 1cm depth, eComp technique delivers significantly less dose (p<0.05) to the CLB as compared to standard tangential fields. Furthermore, the surface dose measured for both eComp and standard are comparable indicating that the eComp-based tangential field technique does not contribute any excess dose to CLB when compared to standard tangential fields. The excess relative risk (ERR) for radiation-induced cancers for eComp was found to be 0.08, compared to 0.11 for standard tangential fields.
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http://dx.doi.org/10.1016/j.zemedi.2021.04.003DOI Listing
June 2021

On the reduction of aperture complexity in kidney SABR.

J Appl Clin Med Phys 2021 Apr 23;22(4):71-81. Epub 2021 Mar 23.

Department of Physical Sciences, Peter MacCallum Cancer Centre, Melbourne, Vic., Australia.

Background: Stereotactic ablative body radiotherapy (SABR) of primary kidney cancers is confounded by motion. There is a risk of interplay effect if the dose is delivered using volumetric modulated arc therapy (VMAT) and flattening filter-free (FFF) dose rates due to target and linac motion. This study aims to provide an efficient way to generate plans with minimal aperture complexity.

Methods: In this retrospective study, 62 patients who received kidney SABR were reviewed. For each patient, two plans were created using internal target volume based motion management, on the average intensity projection of a four-dimensional CT. In the first plan, optimization was performed using a knowledge-based planning model based on delivered clinical plans in our institution. In the second plan, the optimization was repeated, with a maximum monitor unit (MU) objective applied in the optimization. Dose-volume, conformity, and complexity metric (with the field edge metric and the modulation complexity score) were compared between the two plans. Results are shown in terms of median (first quartile - third quartile).

Results: Similar dosimetry was obtained with and without the utilization of an objective on the MU. However, complexity was reduced by using the objective on the MUs (modulation complexity score = 0.55 (0.50-0.61) / 0.33 (0.29-0.36), P-value < 10 , with/without the MU objective). Reduction of complexity was driven by a larger aperture area (area aperture variability = 0.68 (0.64-0.73) / 0.42 (0.37-0.45), P-value < 10 , with/without the MU objective). Using the objective on the MUs resulted in a more spherical dose distribution (sphericity 50% isodose = 0.73 (0.69-0.75) / 0.64 (0.60-0.68), P-value < 10 , with/without the MU objective) reducing dose to organs at risk given respiratory motion.

Conclusions: Aperture complexity is reduced in kidney SABR by using an objective on the MU delivery with VMAT and FFF dose rate.
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http://dx.doi.org/10.1002/acm2.13215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035567PMC
April 2021

Report dose-to-medium in clinical trials where available; a consensus from the Global Harmonisation Group to maximize consistency.

Radiother Oncol 2021 06 17;159:106-111. Epub 2021 Mar 17.

Trans Tasman Radiation Oncology Group (TROG), Newcastle, Australia; Radiation Oncology Department, Calvary Mater Newcastle, Australia; School of Mathematical and Physical Sciences, University of Newcastle, Australia; Institute of Medical Physics, University of Sydney, Australia.

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 (D), dose to water in medium (D), and dose to medium in medium (D). 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 (D).

Conclusions: Dose to medium in medium (D) is the preferred dose calculation and reporting framework. If an institution's planning system can only calculate dose to water in water (D), this is acceptable.
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http://dx.doi.org/10.1016/j.radonc.2021.03.006DOI Listing
June 2021

Automated assessment of functional lung imaging with Ga-ventilation/perfusion PET/CT using iterative histogram analysis.

EJNMMI Phys 2021 Mar 7;8(1):23. Epub 2021 Mar 7.

Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, 3010, Australia.

Purpose: Functional lung mapping from Ga-ventilation/perfusion (V/Q) PET/CT, which has been shown to correlate with pulmonary function tests (PFTs), may be beneficial in a number of clinical applications where sparing regions of high lung function is of interest. Regions of clumping in the proximal airways in patients with airways disease can result in areas of focal intense activity and artefact in ventilation imaging. These artefacts may even shine through to subsequent perfusion images and create a challenge for quantitative analysis of PET imaging. We aimed to develop an automated algorithm that interprets the uptake histogram of PET images to calculate a peak uptake value more representative of the global lung volume.

Methods: Sixty-six patients recruited from a prospective clinical trial underwent both V/Q PET/CT imaging and PFT analysis before treatment. PET images were normalised using an iterative histogram analysis technique to account for tracer hotspots prior to the threshold-based delineation of varying values. Pearson's correlation between fractional lung function and PFT score was calculated for ventilation, perfusion, and matched imaging volumes at varying threshold values.

Results: For all functional imaging thresholds, only FEV1/FVC PFT yielded reasonable correlations to image-based functional volume. For ventilation, a range of 10-30% of adapted peak uptake value provided a reasonable threshold to define a volume that correlated with FEV1/FVC (r = 0.54-0.61). For perfusion imaging, a similar correlation was observed (r = 0.51-0.56) in the range of 20-60% adapted peak threshold. Matched volumes were closely linked to ventilation with a threshold range of 15-35% yielding a similar correlation (r = 0.55-0.58).

Conclusions: Histogram normalisation may be implemented to determine the presence of tracer clumping hotspots in Ga-68 V/Q PET imaging allowing for automated delineation of functional lung and standardisation of functional volume reporting.
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http://dx.doi.org/10.1186/s40658-021-00375-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937580PMC
March 2021

PhDs: never boring, never dry.

Authors:
Tomas Kron

Phys Eng Sci Med 2021 Mar 25;44(1). Epub 2021 Jan 25.

Peter MacCallum Cancer Centre, Melbourne, Australia.

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http://dx.doi.org/10.1007/s13246-021-00974-8DOI Listing
March 2021

A review of 3D printed patient specific immobilisation devices in radiotherapy.

Phys Imaging Radiat Oncol 2020 Jan 20;13:30-35. Epub 2020 Mar 20.

ARC Industrial Transformation Training Centre in Additive Bio-manufacturing, Brisbane, Queensland, Australia.

Background And Purpose: Radiotherapy is one of the most effective cancer treatment techniques, however, delivering the optimal radiation dosage is challenging due to movements of the patient during treatment. Immobilisation devices are typically used to minimise motion. This paper reviews published research investigating the use of 3D printing (additive manufacturing) to produce patient-specific immobilisation devices, and compares these to traditional devices.

Materials And Methods: A systematic review was conducted across thirty-eight databases, with results limited to those published between January 2000 and January 2019. A total of eighteen papers suitably detailed the use of 3D printing to manufacture and test immobilisers, and were included in this review. This included ten journal papers, five posters, two conference papers and one thesis.

Results: 61% of relevant studies featured human subjects, 22% focussed on animal subjects, 11% used phantoms, and one study utilised experimental test methods. Advantages of 3D printed immobilisers reported in literature included improved patient experience and comfort over traditional methods, as well as high levels of accuracy between immobiliser and patient, repeatable setup, and similar beam attenuation properties to thermoformed immobilisers. Disadvantages included the slow 3D printing process and the potential for inaccuracies in the digitisation of patient geometry.

Conclusion: It was found that a lack of technical knowledge, combined with disparate studies with small patient samples, required further research in order to validate claims supporting the benefits of 3D printing to improve patient comfort or treatment accuracy.
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http://dx.doi.org/10.1016/j.phro.2020.03.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807671PMC
January 2020

Consistency of small-field dosimetry, on and off axis, in beam-matched linacs used for stereotactic radiosurgery.

J Appl Clin Med Phys 2021 Feb 13;22(2):185-193. Epub 2021 Jan 13.

Centre for Medical Radiation Physics, University of Wollongong, NSW, Australia.

Purpose: Stereotactic radiosurgery (SRS) can be delivered with a standard linear accelerator (linac). At institutions having more than one linac, beam matching is common practice. In the literature, there are indications that machine central axis (CAX) matching for broad fields does not guarantee matching of small fields with side ≤2 cm. There is no indication on how matching for broad fields on axis translates to matching small fields off axis. These are of interest to multitarget single-isocenter (MTSI) SRS planning and the present work addresses that gap in the literature.

Methods: We used 6 MV flattening filter free (FFF) beams from four Elekta VersaHD® linacs equipped with an Agility™ multileaf collimator (MLC). The linacs were strictly matched for broad fields on CAX. We compared output factors (OPFs) and effective field size, measured concurrently using a novel 2D solid-state dosimeter "Duo" with a spatial resolution of 0.2 mm, in square and rectangular static fields with sides from 0.5 to 2 cm, either on axis or away from it by 5 to 15 cm.

Results: Among the four linacs, OPF for fields ≥1 × 1 cm ranged 1.3% on CAX, whereas off axis a maximum range of 1.9% was observed at 15 cm. A larger variability in OPF was noted for the 0.5 × 0.5 cm field, with a range of 5.9% on CAX, which improved to a maximum of 2.3% moving off axis. Two linacs showed greater consistency with a range of 1.4% on CAX and 2.2% at 15 cm off axis. Between linacs, the effective field size varied by <0.04 cm in most cases, both on and off axis. Tighter matching was observed for linacs with a similar focal spot position.

Conclusions: Verification of small-field consistency for matched linacs used for SRS is an important task for dosimetric validation. A significant benefit of concurrent measurement of field size and OPF allowed for a comprehensive assessment using a novel diode array. Our study showed the four linacs, strictly matched for broad fields on CAX, were still matched down to a field size of 1 x 1 cm on and off axis.
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http://dx.doi.org/10.1002/acm2.13160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882112PMC
February 2021

THERMOLUMINESCENCE DOSIMETRY (TLD) IN MEDICINE: FIVE 'W'S AND ONE HOW.

Radiat Prot Dosimetry 2020 Dec;192(2):139-151

Department of Radiation Safety and Security, Paul Scherrer Institute, 5200 Villigen, Switzerland.

Thermoluminescence dosimetry (TLD) has a long history of applications in medicine. However, despite its versatility and sensitivity its use is anecdotally diminishing, at least in part due to the complexity and work intensity of a quality TLD service. The present paper explores the role of TLD in medicine using a common inquiry methodology (5W1H) which systematically asks 'Who, What, When, Where, Why and How' to identify what role TLD could and should play in medical applications.
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http://dx.doi.org/10.1093/rpd/ncaa212DOI Listing
December 2020

APPLICATIONS OF OPTICALLY STIMULATED LUMINESCENCE IN MEDICAL DOSIMETRY.

Radiat Prot Dosimetry 2020 Dec;192(2):122-138

Department of Physical Sciences, Peter MacCallum Cancer Centre, 3000 Melbourne, Australia.

If the first decade of the new millennium saw the establishment of a more solid foundation for the use of the Optically Stimulated Luminescence (OSL) in medical dosimetry, the second decade saw the technique take root and become more widely used in clinical studies. Recent publications report not only characterization and feasibility studies of the OSL technique for various applications in radiotherapy and radiology, but also the practical use of OSL for postal audits, estimation of staff dose, in vivo dosimetry, dose verification and dose mapping studies. This review complements previous review papers and reports on the topic, providing a panorama of the new advances and applications in the last decade. Attention is also dedicated to potential future applications, such as LET dosimetry, 2D/3D dosimetry using OSL, dosimetry in magnetic resonance imaging-guided radiotherapy (MRIgRT) and dosimetry of extremely high dose rates (FLASH therapy).
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http://dx.doi.org/10.1093/rpd/ncaa213DOI Listing
December 2020

Protocol for tumour-focused dose-escalated adaptive radiotherapy for the radical treatment of bladder cancer in a multicentre phase II randomised controlled trial (RAIDER): radiotherapy planning and delivery guidance.

BMJ Open 2020 12 31;10(12):e041005. Epub 2020 Dec 31.

Radiotherapy and Imaging, The Institute of Cancer Research, London, UK.

Introduction: Daily radiotherapy delivered with radiosensitisation offers patients with muscle invasive bladder cancer (MIBC) comparable outcomes to cystectomy with functional organ preservation. Most recurrences following radiotherapy occur within the bladder. Increasing the delivered radiotherapy dose to the tumour may further improve local control. Developments in image-guided radiotherapy have allowed bladder tumour-focused 'plan of the day' radiotherapy delivery. We aim to test within a randomised multicentre phase II trial whether this technique will enable dose escalation with acceptable rates of toxicity.

Methods And Analysis: Patients with T2-T4aN0M0 unifocal MIBC will be randomised (1:1:2) between standard/control whole bladder single plan radiotherapy, standard dose adaptive tumour-focused radiotherapy or dose-escalated adaptive tumour-focused radiotherapy (DART). Adaptive tumour-focused radiotherapy will use a library of three plans (small, medium and large) for treatment. A cone beam CT taken prior to each treatment will be used to visualise the anatomy and inform selection of the most appropriate plan for treatment.Two radiotherapy fractionation schedules (32f and 20f) are permitted. A minimum of 120 participants will be randomised in each fractionation cohort (to ensure 57 evaluable DART patients per cohort).A comprehensive radiotherapy quality assurance programme including pretrial and on-trial components is instituted to ensure standardisation of radiotherapy planning and delivery.The trial has a two-stage non-comparative design. The primary end point of stage I is the proportion of patients meeting predefined normal tissue constraints in the DART group. The primary end point of stage II is late Common Terminology Criteria for Adverse Events grade 3 or worse toxicity aiming to exclude a rate of >20% (80% power and 5% alpha, one sided) in each DART fractionation cohort. Secondary end points include locoregional MIBC control, progression-free survival overall survival and patient-reported outcomes.

Ethics And Dissemination: This clinical trial is approved by the London-Surrey Borders Research Ethics Committee (15/LO/0539). The results when available will be disseminated via peer-reviewed scientific journals, conference presentations and submission to regulatory authorities.

Trial Registration Number: NCT02447549; Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2020-041005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780718PMC
December 2020

Single-arm prospective interventional study assessing feasibility of using gallium-68 ventilation and perfusion PET/CT to avoid functional lung in patients with stage III non-small cell lung cancer.

BMJ Open 2020 12 10;10(12):e042465. Epub 2020 Dec 10.

Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.

Background: In the curative-intent treatment of locally advanced lung cancer, significant morbidity and mortality can result from thoracic radiation therapy. Symptomatic radiation pneumonitis occurs in one in three patients and can lead to radiation-induced fibrosis. Local failure occurs in one in three patients due to the lungs being a dose-limiting organ, conventionally restricting tumour doses to around 60 Gy. Functional lung imaging using positron emission tomography (PET)/CT provides a geographic map of regional lung function and preclinical studies suggest this enables personalised lung radiotherapy. This map of lung function can be integrated into Volumetric Modulated Arc Therapy (VMAT) radiotherapy planning systems, enabling conformal avoidance of highly functioning regions of lung, thereby facilitating increased doses to tumour while reducing normal tissue doses.

Methods And Analysis: This prospective interventional study will investigate the use of ventilation and perfusion PET/CT to identify highly functioning lung volumes and avoidance of these using VMAT planning. This single-arm trial will be conducted across two large public teaching hospitals in Australia. Twenty patients with stage III non-small cell lung cancer will be recruited. All patients enrolled will receive dose-escalated (69 Gy) functional avoidance radiation therapy. The primary endpoint is feasibility with this achieved if ≥15 out of 20 patients meet pre-defined feasibility criteria. Patients will be followed for 12 months post-treatment with serial imaging, biomarkers, toxicity assessment and quality of life assessment.

Discussion: Using advanced techniques such as VMAT functionally adapted radiation therapy may enable safe moderate dose escalation with an aim of improving local control and concurrently decreasing treatment related toxicity. If this technique is proven feasible, it will inform the design of a prospective randomised trial to assess the clinical benefits of functional lung avoidance radiation therapy.

Ethics And Dissemination: This study was approved by the Peter MacCallum Human Research Ethics Committee. All participants will provide written informed consent. Results will be disseminated via publications.

Trials Registration Number: NCT03569072; Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2020-042465DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7733178PMC
December 2020

A retrospective analysis of setup and intrafraction positional variation in stereotactic radiotherapy treatments.

J Appl Clin Med Phys 2020 Dec 3;21(12):109-119. Epub 2020 Nov 3.

Department of Physical Sciences, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

Purpose: The aim of this study was to provide a comprehensive assessment of patient intrafraction motion in linac-based frameless stereotactic radiosurgery (SRS) and radiotherapy (SRT).

Methods: A retrospective review was performed on 101 intracranial SRS/SRT patients immobilized with the Klarity stereotactic thermoplastic mask (compatible with the Brainlab frameless stereotactic system) and aligned on a 6 Degree of Freedom (DoF) couch with the Brainlab ExacTrac image guidance system. Both pretreatment and intrafraction correction data are provided as observed by the ExacTrac system. The effects of couch angle and treatment duration on positioning outcomes are also explored.

Results: Initial setup data for patients is shown to vary by up to ±4.18 mm, ±2.97°, but when corrected with a single x-ray image set with ExacTrac, patient positions are corrected to within ±2.11 mm, ±2.27°. Intrafraction patient motion is shown to be uniformly random and independent of both time and couch angle. Patient motion was also limited to within approximately 3 mm, 3° by the thermoplastic mask.

Conclusions: Our results indicate that since patient intrafraction motion is unrelated to couch rotation and treatment duration, intrafraction patient monitoring in 6 DoF is required to minimize intracranial SRS/SRT margins.
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http://dx.doi.org/10.1002/acm2.13076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769413PMC
December 2020

A systematic review and meta-analysis of the prognostic value of radiomics based models in non-small cell lung cancer treated with curative radiotherapy.

Radiother Oncol 2021 02 21;155:188-203. Epub 2020 Oct 21.

Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Peter MacCallum Cancer Centre, Melbourne, Australia.

Background And Purpose: Radiomics allows extraction of quantifiable features from imaging. This study performs a systematic review and meta-analysis of the performance of radiomics based prognostic models in non-small cell lung cancer (NSCLC).

Materials And Methods: A literature review was performed following PRISMA guidelines. Medline, EMBASE and Cochrane databases were searched for articles investigating radiomics features predictive of overall survival (OS) in NSCLC treated with curative intent radiotherapy. A random-effects meta-analysis of Harrell's Concordance Index (C-index) was performed on the performance of radiomics models.

Results: Of the 2746 articles retrieved, 40 studies of 55 datasets and 6223 patients were eligible for inclusion in the systematic review. There was significant heterogeneity in the methodology for feature selection and model development. Twelve datasets reported the C-index of radiomics based models in predicting OS and were included in the meta-analysis. The C-index random effects estimate was 0.57 (95% CI 0.53-0.62). There was significant heterogeneity (I = 70.3%).

Conclusions: Based on this review, radiomics based models for lung cancer have to date demonstrated modest prognostic capabilities. Future research should consider using standardised radiomics features, robust feature selection and model development, and deep learning techniques, absolving the need for pre-defined features, to improve imaging-based models.
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http://dx.doi.org/10.1016/j.radonc.2020.10.023DOI Listing
February 2021

Safety, Efficacy, and Patterns of Failure After Single-Fraction Stereotactic Body Radiation Therapy (SBRT) for Oligometastases.

Int J Radiat Oncol Biol Phys 2021 03 15;109(3):756-763. Epub 2020 Oct 15.

Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia. Electronic address:

Purpose: Fewer attendances for radiation therapy results in increased efficiency and less foot traffic within a radiation therapy department. We investigated outcomes after single-fraction (SF) stereotactic body radiation therapy (SBRT) in patients with oligometastatic disease.

Methods And Materials: Between February 2010 and June 2019, patients who received SF SBRT to 1 to 5 sites of oligometastatic disease were included in this retrospective study. The primary objective was to describe patterns of first failure after SBRT. Secondary objectives included overall survival (OS), progression-free survival (PFS), high-grade treatment-related toxicity (Common Terminology Criteria for Adverse Events grade ≥3), and freedom from systemic therapy (FFST).

Results: In total, 371 patients with 494 extracranial oligometastases received SF SBRT ranging from 16 Gy to 28 Gy. The most common primary malignancies were prostate (n = 107), lung (n = 63), kidney (n = 52), gastrointestinal (n = 51), and breast cancers (n = 42). The median follow-up was 3.1 years. The 1-, 3-, and 5-year OS was 93%, 69%, and 55%, respectively; PFS was 48%, 19%, and 14%, respectively; and FFST was 70%, 43%, and 35%, respectively. Twelve patients (3%) developed grade 3 to 4 treatment-related toxicity, with no grade 5 toxicity. As the first site of failure, the cumulative incidence of local failure (irrespective of other failures) at 1, 3 and 5 years was 4%, 8%, and 8%, respectively; locoregional relapse at the primary was 10%, 18%, and 18%, respectively; and distant failure was 45%, 66%, and 70%, respectively.

Conclusions: SF SBRT is safe and effective, and a significant proportion of patients remain FFST for several years after therapy. This approach could be considered in resource-constrained or bundled-payment environments. Locoregional failure of the primary site is the second most common pattern of failure, suggesting a role for optimization of primary control during metastasis-directed therapy.
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http://dx.doi.org/10.1016/j.ijrobp.2020.10.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7560377PMC
March 2021

Monitoring DNA Damage and Repair in Peripheral Blood Mononuclear Cells of Lung Cancer Radiotherapy Patients.

Cancers (Basel) 2020 Sep 4;12(9). Epub 2020 Sep 4.

Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia.

Thoracic radiotherapy (RT) is required for the curative management of inoperable lung cancer, however, treatment delivery is limited by normal tissue toxicity. Prior studies suggest that using radiation-induced DNA damage response (DDR) in peripheral blood mononuclear cells (PBMC) has potential to predict RT-associated toxicities. We collected PBMC from 38 patients enrolled on a prospective clinical trial who received definitive fractionated RT for non-small cell lung cancer. DDR was measured by automated counting of nuclear γ-H2AX foci in immunofluorescence images. Analysis of samples collected before, during and after RT demonstrated the induction of DNA damage in PBMC collected shortly after RT commenced, however, this damage repaired later. Radiation dose to the tumour and lung contributed to the in vivo induction of γ-H2AX foci. Aliquots of PBMC collected before treatment were also irradiated ex vivo, and γ-H2AX kinetics were analyzed. A trend for increasing of fraction of irreparable DNA damage in patients with higher toxicity grades was revealed. Slow DNA repair in three patients was associated with a combined dysphagia/cough toxicity and was confirmed by elevated in vivo RT-generated irreparable DNA damage. These results warrant inclusion of an assessment of DDR in PBMC in a panel of predictive biomarkers that would identify patients at a higher risk of toxicity.
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http://dx.doi.org/10.3390/cancers12092517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563254PMC
September 2020

Should ACPSEM develop its own position papers or just adopt those of the AAPM?

Phys Eng Sci Med 2020 Sep;43(3):749-753

School of Engineering, College of Science and Engineering, University of Tasmania, Sandy Bay, TAS, 7005, Australia.

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http://dx.doi.org/10.1007/s13246-020-00900-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373210PMC
September 2020

Total body irradiation in Australia and New Zealand: results of a practice survey.

Phys Eng Sci Med 2020 Sep 1;43(3):825-835. Epub 2020 Jul 1.

The Peter MacCallum Cancer Centre, Grattan St, Melbourne, 3000, Australia.

Total body irradiation (TBI) is an important treatment modality for the preparation of patients for bone marrow transplants. It is technically challenging and the actual delivery may vary from clinic to clinic. Knowledge of the pattern of practice may be helpful for clinics to determine future practice. We carried out an email survey from April to September 2019 sending 48 TBI related questions to all radiotherapy clinics in Australia and New Zealand via the Australasian College of Physical Scientists in Medicine email distribution list. Centres not performing TBI were not expected to complete the survey and centres that had participated in a previous survey, or that were known to perform the treatment, were followed up if no response was received. Of a total of approximately 70 centres, 14 clinics responded to the survey. The vast majority of clinics use conventional lateral and/or anterior-posterior beams at extended SSD for TBI treatment delivery. However, treatment planning, ancillary equipment (used for immobilisation/modulation), beam energy and prescribed lung doses vary considerably-with some clinics delivering the prescription dose to the lungs and some aiming to deliver a lung dose which is lower than the prescription dose. Only one clinic reported using an advanced delivery technique with modulated arcs at extended SSD. Centres either said they had no access to outcome data or did not answer this question. Compared with an earlier survey from 2005, 3 clinics have lowered their linac dose rate and 7 are the same or similar. The TBI practice in Australia and New Zealand remains varied, with considerable differences in treatment planning, beam energy, accepted lung doses and delivered dose rates.
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http://dx.doi.org/10.1007/s13246-020-00878-zDOI Listing
September 2020

Single-fraction stereotactic ablative body radiotherapy for sternal metastases in oligometastatic breast cancer: Technique and single institution experience.

J Med Imaging Radiat Oncol 2020 Aug 25;64(4):580-585. Epub 2020 Jun 25.

Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.

Introduction: Due to size and close proximity to skin, the sternum is a complicated target for stereotactic ablative body radiotherapy (SABR). This is a retrospective case series of single-fraction SABR to sternal metastasis in patients with oligometastatic breast cancer.

Methods: Between June 2014 and June 2018, ten breast cancer patients received 20 Gy in 1 fraction to a solitary sternal metastasis. Eligible patients had Eastern Cooperative Oncology Group performance status of 0-2, oligometastatic disease (defined as 1-5 metastases) and a controlled primary site. Patients were treated with 3-dimensional conformal radiotherapy, each patient case comprising of> 6 coplanar beams and 2-6 non-coplanar beams. Local control, pain response and adverse events were retrospectively reviewed.

Results: The median planned target volumes were 84.75cc (range, 14.4-197.8cc). The median conformity index was 1.29 (range, 1.2-1.49). At a median follow-up of 32 months, nine patients achieved in-field control. Two patients had triple negative disease, one of them developed marginal recurrence, and the other had in-field recurrence. Seven patients had sternal pain prior to SABR, and within 3 months after SABR treatment, the pain improved (n = 3) or resolved (n = 2). Four patients developed acute grade 1 and 2 skin reactions, and two patients had late grade 1 skin reactions. There were no grade 3 or 4 toxicities.

Conclusion: Our case series demonstrates safety of SABR with associated disease control and analgesic benefit in selected patients with oligometastatic breast cancer. The marginal recurrence observed in this cohort suggests wider margins could be beneficial to account for microscopic disease.
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http://dx.doi.org/10.1111/1754-9485.13075DOI Listing
August 2020

Single-fraction magnetic resonance guided stereotactic radiotherapy - A game changer?

Phys Imaging Radiat Oncol 2020 Apr 16;14:95-96. Epub 2020 Jun 16.

Section for Biomedical Physics, Department of Radiation Oncology, University of Tübingen, Germany.

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http://dx.doi.org/10.1016/j.phro.2020.06.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7297147PMC
April 2020

COVID-19 pandemic planning: considerations for radiation oncology medical physics.

Phys Eng Sci Med 2020 06 13;43(2):473-480. Epub 2020 Apr 13.

Canterbury District Health Board, Christchurch, New Zealand.

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http://dx.doi.org/10.1007/s13246-020-00869-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7153354PMC
June 2020
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