Sir Peter MacCallum Department of Oncology - Research Publications
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ItemTreatment Time Optimization in Single Fraction Stereotactic Ablative Radiation Therapy: A 10-Year Institutional Experience(ELSEVIER INC, 2022)PURPOSE: Stereotactic ablative radiation therapy (SABR) delivered in a single fraction (SF) can be considered to have higher uncertainty given that the error probability is concentrated in a single session. This study aims to report the variation in technology and technique used and its effect on intrafraction motion based on a 10 years of experience in SF SABR. METHODS AND MATERIALS: Records of patients receiving SF SABR delivered at our instruction between 2010 and 2019 were included. Treatment parameters were extracted from the patient management database by using an in-house script. Treatment time was defined as the time difference between the first image acquisition to the last beam off of a single session. The intrafraction variation was measured from the 3-dimensional couch displacement measured after the first cone beam computed tomography (CBCT) acquired during a treatment. RESULTS: The number of SF SABR increased continuously from 2010 to 2019 and were mainly lung treatments. Treatment time was minimized by using volumetric modulated arc therapy, flattening filter-free dose rate, and coplanar field (24 ± 9 min). Treatment time increased as the number of CBCTs per session increased. The most common scenario involved both 2 and 3 CBCTs per session. On the average, a CBCT acquisition added 6 minutes to the treatment time. All treatments considered, the average intrafraction variation was 1.7 ± 1.6 mm. CONCLUSIONS: SF SABR usage increased with time in our institution. The intrafraction motion was acceptable and therefore a single fraction is an efficacious treatment option when considering SABR.
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ItemThe impact of inter-observer variation in delineation on robustness of radiomics features in non-small cell lung cancer(NATURE PORTFOLIO, 2022-07-27)Artificial intelligence and radiomics have the potential to revolutionise cancer prognostication and personalised treatment. Manual outlining of the tumour volume for extraction of radiomics features (RF) is a subjective process. This study investigates robustness of RF to inter-observer variation (IOV) in contouring in lung cancer. We utilised two public imaging datasets: 'NSCLC-Radiomics' and 'NSCLC-Radiomics-Interobserver1' ('Interobserver'). For 'NSCLC-Radiomics', we created an additional set of manual contours for 92 patients, and for 'Interobserver', there were five manual and five semi-automated contours available for 20 patients. Dice coefficients (DC) were calculated for contours. 1113 RF were extracted including shape, first order and texture features. Intraclass correlation coefficient (ICC) was computed to assess robustness of RF to IOV. Cox regression analysis for overall survival (OS) was performed with a previously published radiomics signature. The median DC ranged from 0.81 ('NSCLC-Radiomics') to 0.85 ('Interobserver'-semi-automated). The median ICC for the 'NSCLC-Radiomics', 'Interobserver' (manual) and 'Interobserver' (semi-automated) were 0.90, 0.88 and 0.93 respectively. The ICC varied by feature type and was lower for first order and gray level co-occurrence matrix (GLCM) features. Shape features had a lower median ICC in the 'NSCLC-Radiomics' dataset compared to the 'Interobserver' dataset. Survival analysis showed similar separation of curves for three of four RF apart from 'original_shape_Compactness2', a feature with low ICC (0.61). The majority of RF are robust to IOV, with first order, GLCM and shape features being the least robust. Semi-automated contouring improves feature stability. Decreased robustness of a feature is significant as it may impact upon the features' prognostic capability.
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ItemAssessing organ at risk position variation and its impact on delivered dose in kidney SABR(BMC, 2022-06-27)BACKGROUND: Delivered organs at risk (OARs) dose may vary from planned dose due to interfraction and intrafraction motion during kidney SABR treatment. Cases of bowel stricture requiring surgery post SABR treatment were reported in our institution. This study aims to provide strategies to reduce dose deposited to OARs during SABR treatment and mitigate risk of gastrointestinal toxicity. METHODS: Small bowel (SB), large bowel (LB) and stomach (STO) were delineated on the last cone beam CT (CBCT) acquired before any dose had been delivered (PRE CBCT) and on the first CBCT acquired after any dose had been delivered (MID CBCT). OAR interfraction and intrafraction motion were estimated from the shortest distance between OAR and the internal target volume (ITV). Adaptive radiation therapy (ART) was used if dose limits were exceeded by projecting the planned dose on the anatomy of the day. RESULTS: In 36 patients, OARs were segmented on 76 PRE CBCTs and 30 MID CBCTs. Interfraction motion was larger than intrafraction motion in STO (p-value = 0.04) but was similar in SB (p-value = 0.8) and LB (p-value = 0.2). LB was inside the planned 100% isodose in all PRE CBCTs and MID CBCTs in the three patients that suffered from bowel stricture. SB D0.03cc was exceeded in 8 fractions (4 patients). LB D1.5cc was exceeded in 4 fractions (2 patients). Doses to OARs were lowered and limits were all met with ART on the anatomy of the day. CONCLUSIONS: Interfraction motion was responsible for OARs overdosage. Dose limits were respected by using ART with the anatomy of the day.
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ItemFeasibility of biology-guided radiotherapy using PSMA-PET to boost to dominant intraprostatic tumour(ELSEVIER IRELAND LTD, 2022-07)BACKGROUND: Biology-guided radiotherapy (BgRT) delivers dose to tumours triggered from positron emission tomography (PET) detection. Prostate specific membrane antigen (PSMA) PET uptake is abundant in the dominant intraprostatic lesion (DIL). This study investigates the feasibility of BgRT to PSMA-avid subvolume in the prostate region. METHODS: Patients enrolled in the prospective randomized trial ProPSMA at our institution were included (ID: ANZCTR12617000005358). Gross tumour volumes (GTVs) were delineated on the PET component of a PET/CT scan from a standardized uptake value (SUV) threshold technique. Suitability for BgRT requires a strong signal-to-background ratio with a surrounding tissue free of significant PSMA uptake. The signal-to-background ratio was quantified from the calculation of the normalized SUV (nSUV), defined as the ratio between SUVmax within the GTV and SUVmean inside a 3D margin expansion of the GTV. The PSMA distribution surrounding the tumour was quantified as a function of the distance from the GTV. RESULTS: In this cohort of 84 patients, 83 primary tumours were included. Prostate volume ranged from 19 cm3 to 148 cm3 (median = 52 cm3; IQR = 39 cm3 - 63 cm3). SUVmax inside the prostate was between 2 and 125 (median = 19; IQR = 11 - 30). More than 50% of GTVs generated with threshold between 25%SUVmax (median volume = 10.0 cm3; IQR = 4.5 cm3 - 20.0 cm3) and 50%SUVmax (median volume = 1.9 cm3; IQR = 1.1 cm3 - 3.8 cm3) were suitable for BgRT by using nSUV ≥ 3 and a margin expansion of 5 mm. CONCLUSIONS: It is feasible to identify GTVs suitable for BgRT in the prostate. These GTVs are characterized by a strong signal-to-background ratio and a surrounding tissue free of PSMA uptake.
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ItemUtility of Biology-Guided Radiotherapy to De Novo Metastases Diagnosed During Staging of High-Risk Biopsy-Proven Prostate Cancer(FRONTIERS MEDIA SA, 2022-04-12)BACKGROUND: Biology-guided radiotherapy (BgRT) uses real-time functional imaging to guide radiation therapy treatment. Positron emission tomography (PET) tracers targeting prostate-specific membrane antigen (PSMA) are superior for prostate cancer detection than conventional imaging. This study aims at describing nodal and distant metastasis distribution from prostate cancer and at determining the proportion of metastatic lesions suitable for BgRT. METHODS: A single-institution patient subset from the ProPSMA trial (ID ACTRN12617000005358) was analysed. Gross tumour volumes (GTV) were delineated on the CT component of a PSMA PET/CT scan. To determine the suitability of BgRT tracking zones, the normalized SUV (nSUV) was calculated as the ratio of SUVmax inside the GTV to the SUVmean of adjacent three-dimensional shells of thickness 5 mm/10 mm/20 mm as a measure of signal to background contrast. Targets were suitable for BgRT if (1) nSUV was larger than an nSUV threshold and (2) non-tumour tissue inside adjacent shell was free of PET-avid uptake. RESULTS: Of this cohort of 84 patients, 24 had at least one pelvic node or metastatic site disease, 1 to 13 lesions per patient, with a total of 98 lesions (60 pelvic nodes/38 extra-pelvic nodal diseases and haematogenous metastases). Target volumes ranged from 0.08 to 9.6 cm3 while SUVmax ranged from 2.1 to 55.0. nSUV ranged from 1.9 to 15.7/2.4 to 25.7/2.5 to 34.5 for the 5 mm/10 mm/20 mm shell expansion. Furthermore, 74%/68%/34% of the lesions had nSUV ≥ 3 and were free of PSMA PET uptake inside the GTV outer shell margin expansion of 5 mm/10 mm/20 mm. Adjacent avid organs were another lesion, bladder, bowel, ureter, prostate, and liver. CONCLUSIONS: The majority of PSMA PET/CT-defined radiotherapy targets would be suitable for BgRT by using a 10-mm tracking zone in prostate cancer. A subset of lesions had adjacent non-tumour uptake, mainly due to the proximity of ureter or bladder, and may require exclusion from emission tracking during BgRT.
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ItemPersonalising treatment plan quality review with knowledge-based planning in the TROG 15.03 trial for stereotactic ablative body radiotherapy in primary kidney cancer(BMC, 2021-08-03)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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ItemOn the reduction of aperture complexity in kidney SABR(WILEY, 2021-04)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 < 10-10 , 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 < 10-10 , 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 < 10-8 , 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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ItemNo Preview AvailableFASTRACK II magnetic resonance imaging sub-study Diffusion and perfusion biomarkers for renal SABR response(IOP Publishing, 2020-10-16)Abstract Stereotactic ablative body radiotherapy (SABR) is demonstrating good local control for patients with inoperable primary renal cell carcinoma. In a previous pilot study we identified magnetic resonance imaging (MRI) early response biomarkers that correlate with later morphological changes in computed tomography (CT) images. These early functional changes in diffusion and perfusion following radiotherapy were observed on MRI and have the potential to identify non-responders who may benefit from adjuvant or salvage therapies. Here we detail the imaging protocol for an MRI sub-study of the Focal Ablative STereotactic Radiosurgery for Cancers of the Kidney (FASTRACK II) trial. A preliminary patient case demonstrates the high quality of the imaging data, with discussion of the improvements made from the pilot protocol for improved motion management and correction. We aim to validate the previously identified early response MRI biomarkers with this rich prospective multi-centre dataset.
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ItemAutomated assessment of functional lung imaging with 68Ga-ventilation/perfusion PET/CT using iterative histogram analysis(SPRINGER, 2021-03-07)PURPOSE: Functional lung mapping from Ga68-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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ItemSingle-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 PUBLISHING GROUP, 2020)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.