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Blakeney W.G.,Bunbury Regional Hospital | Blakeney W.G.,Sir Charles Gairdner Hospital | Zilko S.R.,Fremantle Hospital | Edmonston S.J.,St John of God Murdoch Hospital | And 2 more authors.
Knee Surgery, Sports Traumatology, Arthroscopy | Year: 2017

Purpose: Avulsion of the proximal hamstring tendons is an uncommon injury. To date, few studies have prospectively evaluated outcomes of surgical repair. The aim of the present study is to review the functional outcomes of surgical repair of proximal hamstring tendon avulsions. Methods: This is a prospective series of 96 consecutive proximal hamstring surgical repairs in 94 patients, with a median age of 50 years and median follow-up of 33 months (range 12–58). Functional outcomes were assessed using the Perth Hamstring Assessment Tool (PHAT)—a validated scoring system for proximal hamstring injuries. Results: Significant improvements in functional outcomes were seen across all patients at 1-year follow-up. There was a mean PHAT score improvement of 34.7 points at the 1-year follow-up (p < 0.001, 95% CI 29.9–39.5). The SF-12 PCS scores showed a significant improvement at 1-year follow-up of 13.8 points (p < 0.001, 95% CI 10.7–16.9). These were maintained at final follow-up. Acute repairs had significantly higher improvement in PHAT score with acute patients improving a mean of 38.6 points (p < 0.001, 95% CI 32.0–44.3) and chronic patients only improving by a mean of 25.3 points (p < 0.001, 95% CI 18.2–33.3) at final follow-up. Conclusion: This study establishes that surgical repair of proximal hamstring tendon ruptures leads to improved patient outcomes, in both acute and chronic repairs. Early surgical repair, however, achieves superior outcomes to late repair. These results suggest that surgeons should be operating on proximal hamstring avulsions, and preferably in the acute stage. Level of evidence: II. © 2017 European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA)


Price T.J.,The Queen Elizabeth Hospital | Price T.J.,University of Adelaide | Zannino D.,University of Sydney | Wilson K.,University of Sydney | And 8 more authors.
Annals of Oncology | Year: 2012

Background: In an ageing population, a greater proportion of geriatric patients will be considered for systemic chemotherapy. Colorectal cancer (CRC) is a common malignancy and will be a major health issue in geriatrics. We used the MAX population to investigate whether age affected the improved outcome found in CRC when bevacizumab is added to capecitabine chemotherapy. Patients and methods: MAX, a three arm study of Capecitabine (C) versus CBevacizumab (CB) versus CBMitomycin C (CBM), found an improvement in progression-free survival (PFS), with addition of B [+/- mitomycin C (MMC)] to C. This analysis assesses the effect of adding B (+/- MMC) to C on PFS, overall survival (OS), response rate (RR), toxicity and dose intensity in geriatric patients (age ≥ 75 years). Results: Ninety-nine patients (21%) were aged 75-86 years. Baseline characteristics were well balanced. Eighty-eight per cent commenced C at the lower optional dose of 2000 mg/m. 2/day; days 1-14, q21 (61% for <75 years) and 88% were Eastern Cooperative Oncology Group 0-1. Co-morbidities were as expected in this population. The addition of B significantly improved PFS in geriatric patients(C 5.8 months versus CB 8.8 months, Hazard ratio (HR) 0.65 and C versus CBM 10.4 months HR 0.38). The interaction test for OS, RR and PFS revealed no impact of age. Dose intensity was maintained >90% in all patients. There were no major differences in toxicity patterns between age cohorts. Conclusions: Addition of B to C significantly improved PFS in this geriatric population, with similar benefits to those aged <75 years. Treatment was well tolerated with no signal of increased toxicity (including thromboembolism) when compared with those aged <75 years. © The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.


Dent R.A.,National University of Singapore | Dent R.A.,Sunnybrook Odette Cancer Center | Lindeman G.J.,Walter and Eliza Hall Institute of Medical Research | Clemons M.,The Ottawa Hospital Cancer Center | And 8 more authors.
Breast Cancer Research | Year: 2013

Introduction: This Phase I study evaluated the safety, tolerability and efficacy of olaparib, a potent oral poly(ADP-ribose) polymerase (PARP) inhibitor, in combination with paclitaxel in patients with metastatic triple-negative breast cancer (mTNBC). Methods: Eligible patients who had received ≤1 prior cytotoxic regimen for mTNBC were treated with olaparib 200 mg bid continuously plus weekly paclitaxel 90 mg/m2 for three weeks per four-week cycle. Dose modifications in a large proportion of patients due to neutropenia resulted in enrollment of a second cohort of patients who, if they experienced grade ≥2 neutropenia in cycle 1, received granulocyte-colony stimulating factor, which was continued prophylactically in subsequent cycles. All patients had measurable disease; tumor responses were evaluated according to RECIST (version 1.0). Results:Nineteen patients (cohort 1, n = 9; cohort 2, n = 10) received treatment; 15 had received prior taxane chemotherapy. The most frequent adverse events were diarrhea (n = 12, 63%), nausea (n = 11, 58%) and neutropenia (n = 11, 58%). Seven neutropenia events were reported in cohort 1 (four grade ≥3) and four in cohort 2 (two grade ≥3, including one event of febrile neutropenia). The median (range) dose intensity of paclitaxel was 57% (26 to 100%) in cohort 1 and 73% (29 to 100%) in cohort 2. Seven patients (37%) had a confirmed partial response; one patient remains on olaparib monotherapy without progression. Conclusions: The combination of olaparib and weekly paclitaxel was complicated by a significant clinical interaction, with higher-than-expected rates of neutropenia despite secondary prophylaxis. Given the encouraging response rate, alternative scheduling and dosing strategies should be considered (funded by AstraZeneca; ClinicalTrials.gov, NCT00707707). © 2013 Dent et al.; licensee BioMed Central Ltd.


Miles D.W.,Mount Vernon Cancer Center | De Haas S.L.,Hoffmann-La Roche | Dirix L.Y.,St Augustinus Hospital | Romieu G.,Center Re Gionale Of Lutte Contre Le Cancer | And 7 more authors.
British Journal of Cancer | Year: 2013

Background: Combining bevacizumab with first-line chemotherapy significantly improves progression-free survival (PFS) in HER2-negative metastatic breast cancer (mBC). However, identification of patients benefitting most from bevacizumab remains elusive. The AVADO trial included an extensive optional exploratory biomarker programme. Methods: Patients with HER2-negative mBC were randomised to receive docetaxel with placebo or bevacizumab. The primary end point was PFS. Plasma samples were analysed using a multiplex ELISA. Blood mRNA expression was assessed using quantitative PCR. Tumour tissue samples were analysed by immunohistochemistry. Single-nucleotide polymorphisms (SNPs) involved in the VEGF pathway were analysed in germline DNA.Results:Samples for biomarker analysis were available from 24-54% of the 736 treated patients (depending on specimen type). The most consistent potential predictive effect was observed with plasma VEGF-A and VEGFR-2; high baseline concentrations were associated with greater treatment effect. Blood mRNA analyses suggested a greater bevacizumab effect in patients with high VEGF 121. No consistent predictive effect was seen for tumour neuropilin or other candidate tumour markers by immunohistochemistry, or for any of the SNPs investigated. Conclusion: Plasma VEGF-A and VEGFR-2 are potential predictive markers for bevacizumab efficacy, supporting findings in gastric and pancreatic cancers. Plasma VEGF-A is being evaluated prospectively in mBC in the MERiDiAN trial. © 2013 Cancer Research UK. All rights reserved.


Pili R.,Johns Hopkins University | Rosenthal M.A.,Royal Melbourne Hospital | Mainwaring P.N.,Materials Health Services | Van Hazel G.,Mount Hospital | And 6 more authors.
Clinical Cancer Research | Year: 2010

Purpose: This randomized phase II study evaluated ASA404 (vadimezan; 5,6-dimethylxanthenone-4-acetic acid) in combination with docetaxel in castration-refractory metastatic prostate cancer (CRMPC). Experimental Design: Seventy-four patients with histopathologically confirmed CRMPC previously untreated with chemotherapy were randomized to receive either ≤10 cycles of docetaxel 75 mg/m2 alone (D; n = 39) or docetaxel plus ASA404 1,200 mg/m2 (A-D; n = 35). Study endpoints included prostate-specific antigen response, tumor response, median time to tumor progression, median survival, and toxicity. Results: The overall pattern of adverse events was similar in the two groups; however, there was a higher incidence of cardiac adverse events and neutropenia in the A-D group. Coadministration of ASA404 with docetaxel did not affect total systemic exposure of either drug. A higher prostate-specific antigen response rate was reported with A-D versus D (59.4% versus 36.8%), together with a larger median percentage reduction in prostate-specific antigen (84.0% versus 61.9%) and a shorter median time to prostate-specific antigen nadir (105 versus 119 d). Tumor response rate was 23.1% with A-D and 9.1% with D. Time to tumor progression and median survival were similar in the groups (time to tumor progression, 8.7 mo for A-D and 8.4 mo for D; survival, 17.0 mo for A-D and 17.2 mo for D). Hazard ratios for time to tumor progression and survival were 0.81 and 0.80, respectively, favoring A-D; 2-year survival was 33.3% with A-D and 22.8% with D. Conclusion: The study met some endpoints (prostate-specific antigen response, tumor response) but not others (i.e., time to tumor progression). The results indicate that the combination of ASA404 with docetaxel has acceptable toxicity, lacks adverse pharmacokinetic interaction, and, overall, has activity in CRMPC. ©2010 AACR.


Chan A.,Mount Hospital | Morey A.,St Vincents Hospital | Brown B.,St Vincents Hospital | Hastrich D.,Mount Hospital | And 2 more authors.
BMC Cancer | Year: 2012

Background: Overall survival of HER2 positive metastatic breast cancer patients has been significantly improved with inclusion of trastuzumab to chemotherapy. Several studies have demonstrated discordant HER2 status in the primary and metastatic tumour. However, rates of discordance vary considerably in published reports.Methods: Information collected prospectively was analysed for all patients seen from 1999 to 2009 with primary breast cancer and who had biopsy of a local or distant recurrence. Patients were included if adequate tissue was available from both paired samples. Recurrent samples included fine needle aspirations, core and excisional biopsies. HER2 status in all paired samples was assessed by in-situ hybridisation by a single pathologist in a national reference laboratory. This was compared with HER2 immunohistochemistry results provided in the course of routine diagnosis at regional laboratories.Results: In total, 157 patients with recurrent (n = 137; 87.3%) or synchronous primary and metastatic (n = 20; 12.7%) breast cancer had biopsy of the metastatic site. The study population comprised of 116 patients with adequate tissue in both primary and metastasis. The concordance between HER2 status of the paired samples by local immunohistochemistry testing and central in-situ hybridization were 78% and 99%, respectively. Only one patient demonstrated HER2 discordance - primary lesion was positive whilst a metastatic site was negative.Conclusions: This single institution study demonstrated a low rate of HER2 discordance between primary and recurrent breast cancer as assessed by in-situ hybridisation. This contrasts to results reported by others, which may be explained by differences in study methodology, definition of recurrent disease samples and generally small numbers of patients assessed. Despite the current findings, the decision to obtain metastatic tissue for evaluation is influenced by other factors. These include disease-free interval, which may raise the possibility of a new malignancy and the accuracy of initial HER2 assessment of the primary tumour. © 2012 Chan et al.; licensee BioMed Central Ltd.


Chan A.,Mount Hospital | Miles D.W.,Mount Vernon Cancer Center | Pivot X.,University Hospital njoz
Annals of Oncology | Year: 2010

Background: Taxanes are an established treatment of metastatic breast cancer (mBC). Biological therapies that can be effectively combined with taxanes may provide an alternative to taxane-chemotherapy doublets, which are not suitable for all patients. Patients and methods: Bevacizumab is a humanised mAb against vascular endothelial growth factor (VEGF) which inhibits angiogenesis. This review summarises outcomes from trials evaluating bevacizumab in the first-line treatment of mBC. Results: Bevacizumab demonstrated considerable efficacy in combination with taxane therapy in the first-line treatment of human epidermal growth factor receptor-2 (HER2)-negative mBC in three phase III trials. Improved response rate and progression-free survival (PFS) were also observed in patients who had received taxanes in the adjuvant setting. Bevacizumab-taxane combinations are effective across a broad range of patient subgroups and have greater efficacy than single-agent taxanes in first-line mBC. Importantly, the tolerability of bevacizumab-taxane combinations compares favourably with that of taxanes in combination with other chemotherapy agents. Conclusions: Bevacizumab-taxane combinations provide an alternative to chemotherapy doublet regimens in first-line mBC, with equivalent efficacy and potentially lower toxicity. Ongoing trials are investigating the efficacy and safety of bevacizumab in various stages of breast cancer and in breast cancer with a range of hormonal or receptor characteristics. © The Author 2010. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.


Chan A.,Mount Hospital | McGregor S.R.,Mount Hospital
Internal Medicine Journal | Year: 2012

Aim: To ascertain the prevalence of HER2/neu-positive early breast cancer (EBC), utilisation of adjuvant trastuzumab and incidence of cardiac toxicity in a community private hospital setting. Methods: Prospective data collected by breast oncologist and surgeons in all women diagnosed with EBC at the Mount Hospital (MH) were reviewed. Women with HER2/neu-positive disease diagnosed between 1 October 2006 and 31 March 2009 were included in this analysis. Results: In total, 1128 women with invasive EBC were seen in the 30-month period. All tumours underwent HER2/neu testing by immunohistochemistry, with 61% being evaluated by in situ hybridisation. Time to definitive HER2/neu result improved over time from median of 17 to 14days. The prevalence of HER2 positivity (by in situ hybridisation) in this cohort was 12%. Uptake of trastuzumab-based treatment was 100% in those patients receiving their treatment at the MH, compared to 52% of the 25 patients treated elsewhere. Ninety-eight per cent of MH patients completed the planned 12months of therapy, with one patient developing recurrent disease and two patients experiencing significant cardiac toxicity. Chemotherapy relative dose intensity was 98% in HER2/neu-positive and negative patients. At a median of 25months follow up, actuarial disease-free and overall survival in the HER2/neu-positive cohort is 99% and 100% respectively. Conclusion: In a community private hospital setting, adjuvant trastuzumab and chemotherapy was delivered optimally, in line with national and international guidelines. Early efficacy and safety results in a non-clinical trial setting underscore the significant benefits achieved with this targeted therapy in HER2/neu-positive EBC. © 2011 The Authors. Internal Medicine Journal © 2011 Royal Australasian College of Physicians.


This feasibility study represents the first report of a new carbon dioxide-based tissue expander designed to allow gradual controlled expansion and to eliminate the need for percutaneous injections. Seven patients underwent implantation with a total of 10 (three bilateral) tissue expanders. After intraoperative filling by the surgeon and wound healing, small doses of carbon dioxide were administered on a daily basis by the patient by means of a hand-held dosage controller leading to gradual, incremental expansion. Rapid expansion during the active dosing phase and flexibility to meet individual patient needs during expansion were demonstrated with all subjects. These patients achieved full expansion in an average of 15 days. All seven patients were able to use the device safely and with ease at home, leading to successful tissue expansion and permanent breast reconstruction. Copyright © 2011 by the American Society of Plastic Surgeons.


PubMed | Mount Hospital
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2016

628 Background: In Australia, there is no consistent management approach for locally advanced breast cancer (LABC). Our aim was to assess the feasibility of a standardized multidisciplinary protocol for the management of LABC. In addition, MRI and PET accuracy in predicting extent of residual disease following 6 cycles of TAC was evaluated.Patients with LABC, (T3/4, N2/3, M0); ECOG 0/1, received preoperative chemotherapy (docetaxel 75mg/m50 patients were included from three institutions in Perth, Western Australia, April 2005 to October 2006. Median age 49 yrs (34-78), pre/postmenopausal 25/25, mean tumor diameter 70mm (25-105), T4d 9 (18%), regional nodal metastases 31 (62%). 46 (92%) completed all planned treatments in accordance with protocol. Chemotherapy commenced within 35 days of diagnosis in 90% of patients. Surgery performed within 42 days of last chemotherapy in 82%, radiotherapy commenced within 42 days of surgery in 50%. Clinical response: CR 20%, PR 52%, SD 16%, PD 12%. Twenty-two SAE occurred in 13 patients with 55% of episodes related to neutropenic sepsis. Pathological CR breast 24%, node negative 34%. Pre- and post-chemotherapy MRI and PET scanning were performed in 42 and 38 pts, respectively. MRI was most accurate in assessing the extent of residual cancer. Correlation of clinical, pathological MRI and PET will be presented.The majority of patients with LABC can complete this standardized management protocol. Adopting such an approach is likely to improve outcomes since patients are more likely to receive optimal multimodality treatments. MRI is the most accurate method for assessing residual disease and could be the most useful method for choosing breast-conserving surgery. [Table: see text].

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