Sir Peter MacCallum Department of Oncology - Research Publications
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ItemImportance of quality in radiation oncology(WILEY, 2017-10)
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ItemStereotactic ablative body radiotherapy for inoperable primary kidney cancer: a prospective clinical trial(WILEY, 2017-11)OBJECTIVE: To assess the feasibility and safety of stereotactic ablative body radiotherapy (SABR) for renal cell carcinoma (RCC) in patients unsuitable for surgery. Secondary objectives were to assess oncological and functional outcomes. MATERIALS AND METHODS: This was a prospective interventional clinical trial with institutional ethics board approval. Inoperable patients were enrolled, after multidisciplinary consensus, for intervention with informed consent. Tumour response was defined using Response Evaluation Criteria In Solid Tumors v1.1. Toxicities were recorded using Common Terminology Criteria for Adverse Events v4.0. Time-to-event outcomes were described using the Kaplan-Meier method, and associations of baseline variables with tumour shrinkage was assessed using linear regression. Patients received either single fraction of 26 Gy or three fractions of 14 Gy, dependent on tumour size. RESULTS: Of 37 patients (median age 78 years), 62% had T1b, 35% had T1a and 3% had T2a disease. One patient presented with bilateral primaries. Histology was confirmed in 92%. In total, 33 patients and 34 kidneys received all prescribed SABR fractions (89% feasibility). The median follow-up was 24 months. Treatment-related grade 1-2 toxicities occurred in 26 patients (78%) and grade 3 toxicity in one patient (3%). No grade 4-5 toxicities were recorded and six patients (18%) reported no toxicity. Freedom from local progression, distant progression and overall survival rates at 2 years were 100%, 89% and 92%, respectively. The mean baseline glomerular filtration rate was 55 mL/min, which decreased to 44 mL/min at 1 and 2 years (P < 0.001). Neutrophil:lymphocyte ratio correlated to % change in tumour size at 1 year, r2 = 0.45 (P < 0.001). CONCLUSION: The study results show that SABR for primary RCC was feasible and well tolerated. We observed encouraging cancer control, functional preservation and early survival outcomes in an inoperable cohort. Baseline neutrophil:lymphocyte ratio may be predictive of immune-mediated response and warrants further investigation.
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ItemCone-beam computed tomography for lung cancer - validation with CT and monitoring tumour response during chemo-radiation therapy(WILEY, 2017-04)INTRODUCTION: Cone-beam computed tomography (CBCT) is a valuable image-guidance tool in radiation therapy (RT). This study was initiated to assess the accuracy of CBCT for quantifying non-small cell lung cancer (NSCLC) tumour volumes compared to the anatomical 'gold standard', CT. Tumour regression or progression on CBCT was also analysed. METHODS: Patients with Stage I-III NSCLC, prescribed 60 Gy in 30 fractions RT with concurrent platinum-based chemotherapy, routine CBCT and enrolled in a prospective study of serial PET/CT (baseline, weeks two and four) were eligible. Time-matched CBCT and CT gross tumour volumes (GTVs) were manually delineated by a single observer on MIM software, and were analysed descriptively and using Pearson's correlation coefficient (r) and linear regression (R2 ). RESULTS: Of 94 CT/CBCT pairs, 30 patients were eligible for inclusion. The mean (± SD) CT GTV vs CBCT GTV on the four time-matched pairs were 95 (±182) vs 98.8 (±160.3), 73.6 (±132.4) vs 70.7 (±96.6), 54.7 (±92.9) vs 61.0 (±98.8) and 61.3 (±53.3) vs 62.1 (±47.9) respectively. Pearson's correlation coefficient (r) was 0.98 (95% CI 0.97-0.99, ρ < 0.001). The mean (±SD) CT/CBCT Dice's similarity coefficient was 0.66 (±0.16). Of 289 CBCT scans, tumours in 27 (90%) patients regressed by a mean (±SD) rate of 1.5% (±0.75) per fraction. The mean (±SD) GTV regression was 43.1% (±23.1) from the first to final CBCT. CONCLUSION: Primary lung tumour volumes observed on CBCT and time-matched CT are highly correlated (although not identical), thereby validating observations of GTV regression on CBCT in NSCLC.
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ItemIntraoperative radiotherapy with image guidance: Mix and match(WILEY, 2018-12)
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ItemDose to medium in head and neck radiotherapy: Clinical implications for target volume metrics(ELSEVIER, 2019-07)BACKGROUND AND PURPOSE: In radiotherapy dose calculation, advanced type-B dose calculation algorithms can calculate dose to medium (Dm ), as opposed to Type-B algorithms which compute dose to varying densities of water (Dw ). We investigate the impact of Dm on calculated dose and target coverage metrics in head and neck cancer patients. METHODS AND MATERIALS: We reviewed 27 successfully treated (disease free at two-years post-(chemo)radiotherapy) human papillomavirus-associated (HPV) oropharyngeal cancer (ONC) patients treated with IMRT. Doses were calculated with Type-B and Linear Boltzman Transport Equation (LBTE) algorithms in a commercial treatment planning system, with the treated multi-leaf collimator patterns and monitor units. Coverage for primary Gross Tumour Volume (GTVp), high dose Planning Target Volume (PTV) (PTV_High), mandible within PTV_High (Mand ∩ PTV) and PTV_High excluding bone (PTV-bone) were compared between the algorithms. RESULTS: Dose to 95% of PTV_High with LBTE was on average 1.1 Gy/1.7% lower than with Type-B (95%CI 1.5-1.9%, p < 0.0001). This magnitude was inversely linearly correlated with the relative volume of the PTV_High containing bone (pearson r = -0.81). Dose to 98% of the GTVp was 0.9 Gy/1.3% lower with LBTE compared with Type-B (95%CI 1.1-1.5%, p < 0.05). Dose to 98% of Mand ∩ PTV was on average 3.4 Gy/5.0% lower with LBTE than with Type-B (95%CI 4.6-5.4%, p < 0.0001). CONCLUSION: In OPC treated with IMRT, Dm results in significant reductions in dose to bone in high dose PTVs. Reported GTVp dose was reduced, but by a lower magnitude. Reduced coverage metrics should be expected for OPC patients treated with IMRT, with dose reductions limited to regions of bone.
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ItemDosimetric end-to-end tests in a national audit of 3D conformal radiotherapy(ELSEVIER, 2018-04)BACKGROUND AND PURPOSE: Independent dosimetry audits improve quality and safety of radiation therapy. This work reports on design and findings of a comprehensive 3D conformal radiotherapy (3D-CRT) Level III audit. MATERIALS AND METHODS: The audit was conducted as onsite audit using an anthropomorphic thorax phantom in an end-to-end test by the Australian Clinical Dosimetry Service (ACDS). Absolute dose point measurements were performed with Farmer-type ionization chambers. The audited treatment plans included open and half blocked fields, wedges and lung inhomogeneities. Audit results were determined as Pass Optimal Level (deviations within 3.3%), Pass Action Level (greater than 3.3% but within 5%) and Out of Tolerance (beyond 5%), as well as Reported Not Scored (RNS). The audit has been performed between July 2012 and January 2018 on 94 occasions, covering approximately 90% of all Australian facilities. RESULTS: The audit pass rate was 87% (53% optimal). Fifty recommendations were given, mainly related to planning system commissioning. Dose overestimation behind low density inhomogeneities by the analytical anisotropic algorithm (AAA) was identified across facilities and found to extend to beam setups which resemble a typical breast cancer treatment beam placement. RNS measurements inside lung showed a variation in the opposite direction: AAA under-dosed a target beyond lung and over-dosed the lung upstream and downstream of the target. Results also highlighted shortcomings of some superposition and convolution algorithms in modelling large angle wedges. CONCLUSIONS: This audit showed that 3D-CRT dosimetry audits remain relevant and can identify fundamental global and local problems that also affect advanced treatments.
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ItemAssessment of leakage dose in vivo in patients undergoing radiotherapy for breast cancer(ELSEVIER, 2018-01)BACKGROUND AND PURPOSE: Accurate quantification of the relatively small radiation doses delivered to untargeted regions during breast irradiation in patients with breast cancer is of increasing clinical interest for the purpose of estimating long-term radiation-related risks. Out-of-field dose calculations from commercial planning systems however may be inaccurate which can impact estimates for long-term risks associated with treatment. This work compares calculated and measured dose out-of-field and explores the application of a correction for leakage radiation. MATERIALS AND METHODS: Dose calculations of a Boltzmann transport equation solver, pencil beam-type, and superposition-type algorithms from a commercial treatment planning system (TPS) were compared with in vivo thermoluminescent dosimetry (TLD) measurements conducted out-of-field on the contralateral chest at points corresponding to the thyroid, axilla and contralateral breast of eleven patients undergoing tangential beam radiotherapy for breast cancer. RESULTS: Overall, the TPS was found to under-estimate doses at points distal to the radiation field edge with a modern linear Boltzmann transport equation solver providing the best estimates. Application of an additive correction for leakage (0.04% of central axis dose) improved correlation between the measured and calculated doses at points greater than 15 cm from the field edge. CONCLUSIONS: Application of a correction for leakage doses within peripheral regions is feasible and could improve accuracy of TPS in estimating out-of-field doses in breast radiotherapy.
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ItemDevelopment of a multicentre automated model to reduce planning variability in radiotherapy of prostate cancer(ELSEVIER, 2019-07)BACKGROUND AND PURPOSE: Inter-institutional studies highlighted correlation between consistent radiotherapy quality and improved overall patient survival. In treatment planning automation has the potential to address differences due to user-experience and training, promoting standardisation. The aim of this study was to evaluate implementation and clinical effect of a multicentre collaboratively-developed automated planning model for Intensity-Modulated Radiation Therapy/Volumetric-Modulated Arc Therapy of prostate. The model was built using a variety of public institutions' clinical plans, incorporating different contouring and dose protocols, aiming at minimising their variation. METHODS AND MATERIALS: A model using 110 clinically approved and treated prostate plans provided by different radiotherapy centres was built with RapidPlan (RP), for use on intact and post-prostatectomy prostate cases. The model was validated, distributed and introduced into clinical practice in all institutions. To investigate its impact a total of 126 patients, originally manually inverse planned (OP), were replanned using RP without additional planner manual intervention. Target and organ-at-risk (OAR) metrics were statistically compared between original and automated plans. RESULTS: For all centres combined and individually, RP provided plans comparable or superior to OP for all dose metrics. Statistically significant reductions with RP were found in bladder (V40Gy) and rectal (V50Gy) low doses (within 2.3% and 3.4% for combined and 4% and 10% individually). No clinically significant changes were seen for the PTV, independently of seminal vesicle inclusion. CONCLUSION: This project showed it is feasible to develop, share and implement RP models created with plans from different institutions treated with a variety of techniques and dose protocols, with the potential of improving treatment planning results and/or efficiency despite the original variability.
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ItemDiffusion weighted and dynamic contrast enhanced MRI as an imaging biomarker for stereotactic ablative body radiotherapy (SABR) of primary renal cell carcinoma(PUBLIC LIBRARY SCIENCE, 2018-08-16)PURPOSE: To explore the utility of diffusion and perfusion changes in primary renal cell carcinoma (RCC) after stereotactic ablative body radiotherapy (SABR) as an early biomarker of treatment response, using diffusion weighted (DWI) and dynamic contrast enhanced (DCE) MRI. METHODS: Patients enrolled in a prospective pilot clinical trial received SABR for primary RCC, and had DWI and DCE MRI scheduled at baseline, 14 days and 70 days after SABR. Tumours <5cm diameter received a single fraction of 26 Gy and larger tumours received three fractions of 14 Gy. Apparent diffusion coefficient (ADC) maps were computed from DWI data and parametric and pharmacokinetic maps were fitted to the DCE data. Tumour volumes were contoured and statistics extracted. Spearman's rank correlation coefficients were computed between MRI parameter changes versus the percentage tumour volume change from CT at 6, 12 and 24 months and the last follow-up relative to baseline CT. RESULTS: Twelve patients were eligible for DWI analysis, and a subset of ten patients for DCE MRI analysis. DCE MRI from the second follow-up MRI scan showed correlations between the change in percentage voxels with washout contrast enhancement behaviour and the change in tumour volume (ρ = 0.84, p = 0.004 at 12 month CT, ρ = 0.81, p = 0.02 at 24 month CT, and ρ = 0.89, p = 0.001 at last follow-up CT). The change in mean initial rate of enhancement and mean Ktrans at the second follow-up MRI scan were positively correlated with percent tumour volume change at the 12 month CT onwards (ρ = 0.65, p = 0.05 and ρ = 0.66, p = 0.04 at 12 month CT respectively). Changes in ADC kurtosis from histogram analysis at the first follow-up MRI scan also showed positive correlations with the percentage tumour volume change (ρ = 0.66, p = 0.02 at 12 month CT, ρ = 0.69, p = 0.02 at last follow-up CT), but these results are possibly confounded by inflammation. CONCLUSION: DWI and DCE MRI parameters show potential as early response biomarkers after SABR for primary RCC. Further prospective validation using larger patient cohorts is warranted.