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Pearse M.,Auckland City Hospital | Fraser-Browne C.,Auckland City Hospital | Davis I.D.,Monash University | Fisher R.,Center for Biostatistics and Clinical Trials | And 12 more authors.
BJU International | Year: 2014

Objectives To test the hypothesis that observation with early salvage radiotherapy (SRT) is not inferior to 'standard' treatment with adjuvant RT (ART) with respect to biochemical failure in patients with pT3 disease and/or positive surgical margins (SMs) after radical prostatectomy (RP). To compare the following secondary endpoints between the two arms: patient-reported outcomes, adverse events, biochemical failure-free survival, overall survival, disease-specific survival, time to distant failure, time to local failure, cost utility analysis, quality adjusted life years and time to androgen deprivation. Patients and Methods The Radiotherapy - Adjuvant Versus Early Salvage (RAVES) trial is a phase III multicentre randomised controlled trial led by the Trans Tasman Radiation Oncology Group (TROG), in collaboration with the Urological Society of Australia and New Zealand (USANZ), and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP). In all, 470 patients are planned to be randomised 1:1 to either ART commenced at ≤4 months of RP (standard of care) or close observation with early SRT triggered by a PSA level of >0.20 ng/mL (experimental arm). Eligible patients have had a RP for adenocarcinoma of the prostate with at least one of the following risk factors: positive SMs ± extraprostatic extension ± seminal vesicle involvement. The postoperative PSA level must be ≤0.10 ng/mL. Rigorous investigator credentialing and a quality assurance programme are designed to promote consistent RT delivery among patients. Results Trial is currently underway, with 258 patients randomised as of 31 October 2013. International collaborations have developed, including a planned meta-analysis to be undertaken with the UK Medical Research Council/National Cancer Institute of Canada Clinical Trials Group RADICALS (Radiotherapy and Androgen Deprivation In Combination with Local Surgery) trial and an innovative psycho-oncology sub-study to investigate a patient decision aid resource. Conclusion On the current evidence available, it remains unclear if ART is equivalent or superior to observation with early SRT. © 2014 The Authors.


Lehman M.,Princess Alexandra Hospital | Sidhom M.,Liverpool and Macarthur Cancer Therapy Centres | Kneebone A.B.,Northern Sydney Cancer Center | Hayden A.J.,Westmead Cancer Care Center | And 4 more authors.
Journal of Medical Imaging and Radiation Oncology | Year: 2014

Australian and New Zealand radiation oncologists with an interest in uro-oncology were invited to undertake a pattern of practice survey dealing with issues encountered in the management of high-risk prostate cancer in the post-prostatectomy setting. Responses from practitioners revealed a lack of consensus regarding the optimal timing of radiation therapy the use of whole pelvic radiation therapy and the use of androgen deprivation therapy. A review of the literature outlining the current body of knowledge and the clinical studies that will inform future practice is presented. © 2013 The Royal Australian and New Zealand College of Radiologists.


Lehman M.,Princess Alexandra Hospital | Hayden A.J.,Westmead Cancer Care Center | Martin J.M.,Calvary Materials Newcastle Hospital | Christie D.,Premion | And 4 more authors.
Journal of Medical Imaging and Radiation Oncology | Year: 2014

Australian and New Zealand radiation oncologists with an interest in uro-oncology were invited to participate in a pattern-of-practice survey dealing with the management of intact high-risk prostate cancer. Responses from 46 practitioners (representing 73% of all potential respondents) revealed that high-dose radiation therapy is the standard of care. However, there is variability in practice with regard to the methods used to achieve dose escalation, the use of whole-pelvic radiation therapy and the optimal duration of androgen deprivation therapy employed. A review of the literature outlining the current body of knowledge and the planned and ongoing studies in intact high-risk prostate cancer is presented. © 2013 The Authors. Journal of Medical Imaging and Radiation Oncology published by Wiley Publishing Asia Pty Ltd on behalf of Royal Australian and New Zealand College of Radiologists.


Sundaresan P.,Royal Prince Alfred Hospital | Turner S.,Westmead Hospital | Kneebone A.,Northern Sydney Cancer Center | Pearse M.,Auckland City Hospital | Butow P.,University of Sydney
Radiotherapy and Oncology | Year: 2011

Randomised controlled trials (RCTs) can be hampered by poor patient accrual and retention. Decision aids (DAs) containing simple, evidence-based information, may assist patients with decision-making regarding trial participation. The current DA was of use for 95% of participants. Further evaluation of the DA in a RCT is currently underway. © 2011 Published by Elsevier Ireland Ltd.


Siva S.,University of Melbourne | Siva S.,Peter MacCallum Cancer Center | Kirby K.,Peter MacCallum Cancer Center | Caine H.,Northern Sydney Cancer Center | And 12 more authors.
Clinical Oncology | Year: 2015

Aim: To compare outcomes of single-fraction and multi-fraction stereotactic ablative body radiotherapy (SABR) for pulmonary metastases. Materials and methods: A retrospective review from two academic institutions of patients with one to three pulmonary metastases staged with 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) scans. For single-fraction SABR, 26Gy was prescribed for peripheral targets and 18Gy for central targets. In the multi-fraction cohort, 48Gy/4 or 50Gy/5 was prescribed for peripheral targets and 50Gy/5 was prescribed for central targets. Three-dimensional conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) plans were delivered using heterogeneity corrections. Conformity indices at an intermediate dose (R50%) and at a high dose (R100%) were used to assess a relationship with the planning target volume (PTV). Overall survival, local and distant progression and toxicity rates were analysed from the date of treatment completion. Results: Between February 2010 and June 2013, 65 patients with 85 pulmonary metastases were reviewed. The median follow-up was 2.1 years. Metastases most commonly originated from colorectal cancer (31%), followed by non-small cell lung cancer (25%). 3D-CRT was used in 52 targets, IMRT in 21 and VMAT in 12. 3D-CRT showed a lower median R50% (. P=0.01), but a higher median R100% than IMRT/VMAT (. P=0.04). The R50% index was inversely correlated to the PTV with all techniques (. P=0.01). Overall survival at 1 and 2 years in all patients was 93% (95% confidence interval 87-100%) and 71% (95% confidence interval 58-86%), respectively. The 2 year freedom from local and distant progression was 93% (95% confidence interval 86-100%) and 38% (95% confidence interval 27-55%), respectively. There were no significant differences between overall survival (. P=0 .14), time to distant progression (. P=0.06) or toxicity rates (. P=0.75) between single- and multi-fraction cohorts. Conclusion: We report comparable local control, overall survival and toxicity rates between single-fraction and multi-fraction SABR treatments in patients with FDG-PET-staged pulmonary oligometastases. We propose a guideline for R50% conformity incorporating 3D-CRT/IMRT/VMAT techniques with heterogeneity corrected planning algorithms. © 2015 The Royal College of Radiologists.


PubMed | Peter MacCallum Cancer Center, Northern Sydney Cancer Center and University of Melbourne
Type: Comparative Study | Journal: Clinical oncology (Royal College of Radiologists (Great Britain)) | Year: 2015

To compare outcomes of single-fraction and multi-fraction stereotactic ablative body radiotherapy (SABR) for pulmonary metastases.A retrospective review from two academic institutions of patients with one to three pulmonary metastases staged with (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) scans. For single-fraction SABR, 26 Gy was prescribed for peripheral targets and 18 Gy for central targets. In the multi-fraction cohort, 48 Gy/4 or 50 Gy/5 was prescribed for peripheral targets and 50 Gy/5 was prescribed for central targets. Three-dimensional conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) plans were delivered using heterogeneity corrections. Conformity indices at an intermediate dose (R50%) and at a high dose (R100%) were used to assess a relationship with the planning target volume (PTV). Overall survival, local and distant progression and toxicity rates were analysed from the date of treatment completion.Between February 2010 and June 2013, 65 patients with 85 pulmonary metastases were reviewed. The median follow-up was 2.1 years. Metastases most commonly originated from colorectal cancer (31%), followed by non-small cell lung cancer (25%). 3D-CRT was used in 52 targets, IMRT in 21 and VMAT in 12. 3D-CRT showed a lower median R50% (P=0.01), but a higher median R100% than IMRT/VMAT (P=0.04). The R50% index was inversely correlated to the PTV with all techniques (P=0.01). Overall survival at 1 and 2 years in all patients was 93% (95% confidence interval 87-100%) and 71% (95% confidence interval 58-86%), respectively. The 2 year freedom from local and distant progression was 93% (95% confidence interval 86-100%) and 38% (95% confidence interval 27-55%), respectively. There were no significant differences between overall survival (P=0 .14), time to distant progression (P=0.06) or toxicity rates (P=0.75) between single- and multi-fraction cohorts.We report comparable local control, overall survival and toxicity rates between single-fraction and multi-fraction SABR treatments in patients with FDG-PET-staged pulmonary oligometastases. We propose a guideline for R50% conformity incorporating 3D-CRT/IMRT/VMAT techniques with heterogeneity corrected planning algorithms.


PubMed | University of Florence, Northern Sydney Cancer Center, University of Maryland Baltimore County and Huazhong University of Science and Technology
Type: Journal Article | Journal: Medical physics | Year: 2017

To develop a quantitative radiomics approach for survival prediction of glioblastoma (GBM) patients treated with chemoradiotherapy (CRT).28 GBM patients who received CRT at our institution were retrospectively studied. 255 radiomic features were extracted from 3 gadolinium-enhanced T1 weighted MRIs for 2 regions of interest (ROIs) (the surgical cavity and its surrounding enhancement rim). The 3 MRIs were at pre-treatment, 1-month and 3-month post-CRT. The imaging features comprehensively quantified the intensity, spatial variation (texture), geometric property and their spatial-temporal changes for the 2 ROIs. 3 demographics features (age, race, gender) and 12 clinical parameters (KPS, extent of resection, whether concurrent temozolomide was adjusted/stopped and radiotherapy related information) were also included. 4 Machine learning models (logistic regression (LR), support vector machine (SVM), decision tree (DT), neural network (NN)) were applied to predict overall survival (OS) and progression-free survival (PFS). The number of cases and percentage of cases predicted correctly were collected and AUC (area under the receiver operating characteristic (ROC) curve) were determined after leave-one-out cross-validation.From univariate analysis, 27 features (1 demographic, 1 clinical and 25 imaging) were statistically significant (p<0.05) for both OS and PFS. Two sets of features (each contained 24 features) were algorithmically selected from all features to predict OS and PFS. High prediction accuracy of OS was achieved by using NN (96%, 27 of 28 cases were correctly predicted, AUC = 0.99), LR (93%, 26 of 28 cases were correctly predicted, AUC = 0.95) and SVM (93%, 26 of 28 cases were correctly predicted, AUC = 0.90). When predicting PFS, NN obtained the highest prediction accuracy (89%, 25 of 28 cases were correctly predicted, AUC = 0.92).Radiomics approach combined with patients demographics and clinical parameters can accurately predict survival in GBM patients treated with CRT.


PubMed | University of New South Wales and Northern Sydney Cancer Center
Type: Clinical Trial | Journal: Medical dosimetry : official journal of the American Association of Medical Dosimetrists | Year: 2014

This study is aimed to test a postprostatectomy volumetric-modulated arc therapy (VMAT) planning class solution. The solution applies to both the progressive resolution optimizer algorithm version 2 (PRO 2) and the algorithm version 3 (PRO 3), addressing the effect of an upgraded algorithm. A total of 10 radical postprostatectomy patients received 68 Gy to 95% of the planning target volume (PTV), which was planned using VMAT. Each case followed a set of planning instructions; including contouring, field setup, and predetermined optimization parameters. Each case was run through both algorithms only once, with no user interaction. Results were averaged and compared against Radiation Therapy Oncology Group (RTOG) 0534 end points. In addition, the clinical target volume (CTV) D100, PTV D99, and PTV mean doses were recorded, along with conformity indices (CIs) (95% and 98%) and the homogeneity index. All cases satisfied PTV D95 of 68 Gy and a maximum dose < 74.8 Gy. The average result for the PTV D99 was 64.1 Gy for PRO 2 and 62.1 Gy for PRO 3. The average PTV mean dose for PRO 2 was 71.4 Gy and 71.5 Gy for PRO 3. The CTV D100 average dose was 67.7 and 68.0 Gy for PRO 2 and PRO 3, respectively. The mean homogeneity index for both algorithms was 0.08. The average 95% CI was 1.17 for PRO 2 and 1.19 for PRO 3. For 98%, the average results were 1.08 and 1.12 for PRO 2 and PRO 3, respectively. All cases for each algorithm met the RTOG organs at risk dose constraints. A successful class solution has been established for prostate bed VMAT radiotherapy regardless of the algorithm used.


Park S.W.,Royal North Shore Hospital | Eade T.,University of Sydney | Eade T.,Northern Sydney Cancer Center | Pang L.,Royal North Shore Hospital | And 4 more authors.
Journal of Laryngology and Otology | Year: 2016

Objective: To investigate the rate of occult neck disease in patients with metastatic squamous cell carcinoma to the parotid gland following parotidectomy and neck dissection. Methods: A consecutive series of patients treated between 2000 and 2014 for metastatic squamous cell carcinoma to the parotid were analysed. Patients were included if they had no clinical or radiological evidence of neck disease. Pathology of parotidectomy and neck dissection specimens was reviewed. Other variables analysed included patient immune status, surgery type, complications, use of positron emission tomography scanning and treatment with radiotherapy. Results: Sixty-five patients had no clinical or radiological evidence of neck disease initially. Forty-six patients (70.8 per cent) underwent neck dissection. Occult neck disease was only found in 8 of the 46 patients (17.3 per cent). Occult neck disease was found more often in those with immunocompromise (5.7 vs 38.5 per cent, p = 0.003). Patients who were immunocompromised had a significantly worse disease-specific survival rate at five years (0 vs 92 per cent, p = 0.0001). Conclusion: Occult neck disease was seen in 17.3 per cent of patients and immunosuppression was a significant predictor for this. © Copyright JLO (1984) Limited 2016Â.


Johnston M.,Northern Sydney Cancer Center | Clifford S.,Northern Sydney Cancer Center | Bromley R.,Northern Sydney Cancer Center | Bromley R.,University of Sydney | And 4 more authors.
Clinical Oncology | Year: 2011

Aims: Volumetric-modulated arc therapy (VMAT) allows rapid delivery of radiotherapy. The aim of this planning study was to evaluate VMAT and dynamic intensity-modulated radiotherapy (IMRT) using a simultaneous integrated boost technique. Patients and methods: Planning computed tomography data from 10 patients with locoregionally advanced oropharynx or nasopharynx carcinoma were selected. The prescription dose was 70, 63 and 56. Gy to the high-dose, intermediate-dose and low-dose planning target volume (PTV), respectively, and planning parameters were according to Radiation Therapy Oncology Group IMRT protocols. VMAT and IMRT plans were calculated, and dose-volume histograms were created for plan evaluation and comparison. Results: Clinically acceptable plans were achieved for both IMRT and VMAT plans, although IMRT plans typically required three times the number of monitor units. The coverage of 95% of the PTV70 was between 96 and 100% of the prescribed dose for IMRT plans and 100% for all VMAT plans. There was a trend of improved dose conformity for IMRT plans. Both IMRT and VMAT achieved acceptable plans in terms of sparing of the spinal cord and brainstem. Contralateral parotid sparing was improved with VMAT, with a mean dose of 25.08. Gy (range 21.35-30.02. Gy) for oropharynx and 31.37. Gy (range 23.47-35.52. Gy) for nasopharynx cases. Conclusion: Simultaneous integrated boost VMAT achieved comparable plans to dynamic IMRT in complex head and neck cases and used two-thirds less monitor units. © 2011 The Royal College of Radiologists.

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