Bentleigh East, Australia
Bentleigh East, Australia

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Patel G.S.,Flinders University | Jain K.,Flinders University | Kumar R.,Flinders University | Strickland A.H.,Monash Cancer Center | And 11 more authors.
Supportive Care in Cancer | Year: 2014

Purpose: Indwelling central venous catheters (CVCs) have been increasingly used to enable delivery of intravenous chemotherapy. We aimed to compare the safety and cost of two commonly used CVCs, peripherally inserted central venous catheter (PICCs) and ports, in the delivery of chemotherapy in patients with non-haematological malignancies. Methods: Seventy patients were randomly assigned to receive either a PICC or a port. The primary endpoint was occurrence of major complications, which required removal of the CVC and secondary endpoints included occurrence of any complications. Results: Port devices were associated with fewer complications compared with PICC lines (hazard ratio of 0.25, CI, 0.09-0.86, P = 0.038). Major complication rate was lower in the port arm compared to the PICC arm (0.047 versus 0.193 major complications/100 catheter days, P = 0.034) with 6 versus 20 % of patients experiencing major complications, respectively. Thrombosis, the most common complication, was significantly higher in the PICC arm compared to the port arm (25 versus 0 %, P = 0.013). Quality of life and cost estimates did not differ significantly between the two arms. Conclusions: Port devices are associated with a lower risk of complications, with no difference in cost, compared to PICC lines in patients with non-haematological malignancies receiving intravenous chemotherapy. © 2013 Springer-Verlag Berlin Heidelberg.


Azad A.A.,Joint Austin Ludwig Oncology Unit | Siow S.-F.,Joint Austin Ludwig Oncology Unit | Tafreshi A.,Joint Austin Ludwig Oncology Unit | Moran J.,Austin Health | And 2 more authors.
Journal of Palliative Medicine | Year: 2014

Background: Do-not-resuscitate (DNR) orders prevent medically futile attempts at resuscitation but are not always instituted in hospitalized patients with advanced cancer. One explanation for this underuse is the perception that DNR orders are inevitably associated with withdrawal of all medical interventions and inpatient death. Objectives: To audit discharge and survival outcomes and changes in clinical management in hospitalized adult oncology patients with a DNR order, allowing an assessment of whether such orders lead to cessation of acute interventions and high rates of in-hospital death. Methods: Retrospective data were collected from 270 oncology inpatients at Austin Health, Melbourne, Australia, between February 1, 2012 and November 30, 2012. Results: Mean and median time to institution of DNR orders after admission were 2.1 and 1.0 days, respectively (interquartile range, 0-2 days). Medical interventions continued in 80% or more of cases after DNR orders were placed included blood draws, intravenous antimicrobials, imaging, blood products, and radiotherapy. Two-thirds of patients survived hospitalization and were discharged alive. Survival at 30 days and 90 days after DNR orders were implemented was 63% and 33%, respectively. Baseline Charlson Comorbidity Index score of 5 or less and Eastern Cooperative Oncology Group performance status of 2 or less were associated with a higher probability of being discharged alive and longer overall survival. Conclusions: Most medical interventions were continued with high frequency in adult oncology inpatients after placement of DNR orders. A majority of patients survived hospitalization and remained alive at 30 days after DNR orders were documented. This study offers some reassurance that DNR orders do not inevitably lead to cessation of appropriate medical treatment. © 2014, Mary Ann Liebert, Inc..


PubMed | Jules Bordet Institute, Karolinska Institutet, Institute of Oncology, University of Houston and 76 more.
Type: Review | Journal: ESMO open | Year: 2016

The European Society for Medical Oncology (ESMO) and the American Society of Clinical Oncology (ASCO) are publishing a new edition of the ESMO/ASCO Global Curriculum (GC) thanks to contribution of 64 ESMO-appointed and 32 ASCO-appointed authors. First published in 2004 and updated in 2010, the GC edition 2016 answers to the need for updated recommendations for the training of physicians in medical oncology by defining the standard to be fulfilled to qualify as medical oncologists. At times of internationalisation of healthcare and increased mobility of patients and physicians, the GC aims to provide state-of-the-art cancer care to all patients wherever they live. Recent progress in the field of cancer research has indeed resulted in diagnostic and therapeutic innovations such as targeted therapies as a standard therapeutic approach or personalised cancer medicine apart from the revival of immunotherapy, requiring specialised training for medical oncology trainees. Thus, several new chapters on technical contents such as molecular pathology, translational research or molecular imaging and on conceptual attitudes towards human principles like genetic counselling or survivorship have been integrated in the GC. The GC edition 2016 consists of 12 sections with 17 subsections, 44 chapters and 35 subchapters, respectively. Besides renewal in its contents, the GC underwent a principal formal change taking into consideration modern didactic principles. It is presented in a template-based format that subcategorises the detailed outcome requirements into learning objectives, awareness, knowledge and skills. Consecutive steps will be those of harmonising and implementing teaching and assessment strategies.


Milat F.,Monash Medical Center | Milat F.,Prince Henrys Institute | Milat F.,Monash University | Goh S.,Monash Medical Center | And 12 more authors.
Bone | Year: 2013

Prostate cancer is a leading cause of cancer death, frequently associated with widespread bone metastases. We report two cases of hypocalcemia following the first dose of denosumab in metastatic hormone refractory prostate cancer, the first case requiring 26. days of intravenous calcium therapy. This is the first report of prolonged hypocalcemia following denosumab in a patient with normal renal function. © 2013 .


Whittle J.R.,Royal Melbourne Hospital | Lickliter J.D.,Monash Cancer Center | Gan H.K.,Austin Hospital | Gan H.K.,Ludwig Institute for Cancer Research | And 7 more authors.
Journal of Clinical Neuroscience | Year: 2015

There are limited treatment options for patients with recurrent glioblastoma (GBM). The EnGeneIC delivery vehicle (EDV) is a novel nanocellular (minicell) compound which packages theoretically effective concentrations of chemotherapeutic drugs that are designed to target tumors via minicell-surface attached bispecific proteins (EnGeneIC, Lane Cove West, NSW, Australia). Epidermal growth factor receptor (EGFR) is overexpressed in 40-50% of patients with GBM and is a promising target for new therapeutics. VEDVDox contains doxorubicin (Dox) within the minicells and targets EGFR through Vectibix (V; Amgen Biologicals, Thousand Oaks, CA, USA). We conducted a first in human Phase I study of VEDVDox in adults with recurrent GBM expressing EGFR on immunohistochemistry, following standard therapy including radiation and temozolomide, to establish a safe maximum tolerated dose and determine a recommended Phase II dose (RPTD). VEDVDox was administered weekly in an 8 week cycle, with dose escalation in successive cohorts of patients using a standard 3 + 3 design. In total, 14 patients were treated at three dose levels, and the RPTD was identified as 5 × 109 VEDVDox. Overall VEDVDox was well tolerated, with no dose limiting toxicity and no withdrawals from the study due to adverse events. The most common adverse events were nausea, fever, and chills or rigors, experienced in seven, five and five patients, respectively. Transient uncomplicated hypophosphatemia was seen in seven patients and was not dose-related. Our results demonstrate that VEDVDox, up to a dose of 5 × 109 VEDVDox weekly, is well tolerated in patients with recurrent GBM. © 2015 Elsevier Ltd. All rights reserved.


Lawrence M.G.,Monash University | Pook D.W.,Monash University | Pook D.W.,Monash Cancer Center | Wang H.,Monash University | And 13 more authors.
Prostate | Year: 2015

BACKGROUND Fresh patient specimens of castrate-resistant prostate cancer (CRPC) are invaluable for studying tumor heterogeneity and responses to current treatments. They can be used for primary patient-derived xenografts (PDXs) or serially transplantable PDXs, but only a small proportion of samples grow successfully. To improve the efficiency and quality of PDXs, we investigated the factors that determine the initial engraftment of patient tissues derived from TURP specimens. METHODS Fresh tissue was collected from castrate patients who required a TURP for urinary symptoms. Tissue was grafted under the renal capsule of immune-compromised mice for up to 14 weeks. The abundance of cancer in ungrafted and grafted specimens was compared using histopathology. Mice were castrated or implanted with testosterone pellets to determine the androgen-responsiveness of CRPC PDXs from TURP tissue. RESULTS Primary PDXs were successfully established from 7 of 10 patients that underwent grafting. Of the 112 grafts generated from these 10 patients, 21% contained cancer at harvest. Grafts were most successful when the original patient specimens contained high amounts of viable cancer, defined as samples with (i) at least 50% cancer cells, (ii) no physical damage, and (iii) detectable Ki67 expression. PDX grafts survived in castrated hosts and proliferated in response to testosterone, confirming that they were castrate resistant but androgen-responsive. CONCLUSIONS Primary PDXs of CRPC can be established from TURP specimens with modest success. The take rate can be increased if the original tissues contain sufficient numbers of actively proliferating cancer cells. Selecting specimens with abundant viable cancer will maximize the rate of engraftment and increase the efficiency of establishing PDXs that can be serially transplanted. © 2015 Wiley Periodicals, Inc.


PubMed | Royal Prince Alfred Hospital, Monash Cancer Center, Royal Melbourne Hospital, Peter MacCallum Cancer Center and 2 more.
Type: Clinical Trial, Phase I | Journal: Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia | Year: 2015

There are limited treatment options for patients with recurrent glioblastoma (GBM). The EnGeneIC delivery vehicle (EDV) is a novel nanocellular (minicell) compound which packages theoretically effective concentrations of chemotherapeutic drugs that are designed to target tumors via minicell-surface attached bispecific proteins (EnGeneIC, Lane Cove West, NSW, Australia). Epidermal growth factor receptor (EGFR) is overexpressed in 40-50% of patients with GBM and is a promising target for new therapeutics. (V)EDVDox contains doxorubicin (Dox) within the minicells and targets EGFR through Vectibix (V; Amgen Biologicals, Thousand Oaks, CA, USA). We conducted a first in human Phase I study of (V)EDVDox in adults with recurrent GBM expressing EGFR on immunohistochemistry, following standard therapy including radiation and temozolomide, to establish a safe maximum tolerated dose and determine a recommended Phase II dose (RPTD). (V)EDVDox was administered weekly in an 8week cycle, with dose escalation in successive cohorts of patients using a standard 3+3 design. In total, 14 patients were treated at three dose levels, and the RPTD was identified as 510(9)(V)EDVDox. Overall (V)EDVDox was well tolerated, with no dose limiting toxicity and no withdrawals from the study due to adverse events. The most common adverse events were nausea, fever, and chills or rigors, experienced in seven, five and five patients, respectively. Transient uncomplicated hypophosphatemia was seen in seven patients and was not dose-related. Our results demonstrate that (V)EDVDox, up to a dose of 510(9)(V)EDVDox weekly, is well tolerated in patients with recurrent GBM.


Ng S.P.,Peter MacCallum Cancer Center | David S.,Peter MacCallum Cancer Center | Alamgeer M.,Monash Cancer Center | Ganju V.,Monash Cancer Center
International Journal of Radiation Oncology Biology Physics | Year: 2015

Purpose To assess the diagnostic performance of pretreatment 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and its impact on radiation therapy treatment decisions in patients with locally advanced breast cancer (LABC). Methods and Materials Patients with LABC with Eastern Cooperative Oncology Group performance status <2 and no contraindication to neoadjuvant chemotherapy, surgery, and adjuvant radiation therapy were enrolled on a prospective trial. All patients had pretreatment conventional imaging (CI) performed, including bilateral breast mammography and ultrasound, bone scan, and CT chest, abdomen, and pelvis scans performed. Informed consent was obtained before enrolment. Pretreatment whole-body 18F-FDG PET/CT scans were performed on all patients, and results were compared with CI findings. Results A total of 154 patients with LABC with no clinical or radiologic evidence of distant metastases on CI were enrolled. Median age was 49 years (range, 26-70 years). Imaging with PET/CT detected distant metastatic disease and/or locoregional disease not visualized on CI in 32 patients (20.8%). Distant metastatic disease was detected in 17 patients (11.0%): 6 had bony metastases, 5 had intrathoracic metastases (pulmonary/mediastinal), 2 had distant nodal metastases, 2 had liver metastases, 1 had pulmonary and bony metastases, and 1 had mediastinal and distant nodal metastases. Of the remaining 139 patients, nodal disease outside conventional radiation therapy fields was detected on PET/CT in 15 patients (10.8%), with involvement of ipsilateral internal mammary nodes in 13 and ipsilateral level 5 cervical nodes in 2. Conclusions Imaging with PET/CT provides superior diagnostic and staging information in patients with LABC compared with CI, which has significant therapeutic implications with respect to radiation therapy management. Imaging with PET/CT should be considered in all patients undergoing primary staging for LABC. © 2015 Elsevier Inc.


PubMed | Monash Cancer Center and Peter MacCallum Cancer Center
Type: Evaluation Studies | Journal: International journal of radiation oncology, biology, physics | Year: 2015

To assess the diagnostic performance of pretreatment (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) and its impact on radiation therapy treatment decisions in patients with locally advanced breast cancer (LABC).Patients with LABC with Eastern Cooperative Oncology Group performance status <2 and no contraindication to neoadjuvant chemotherapy, surgery, and adjuvant radiation therapy were enrolled on a prospective trial. All patients had pretreatment conventional imaging (CI) performed, including bilateral breast mammography and ultrasound, bone scan, and CT chest, abdomen, and pelvis scans performed. Informed consent was obtained before enrolment. Pretreatment whole-body (18)F-FDG PET/CT scans were performed on all patients, and results were compared with CI findings.A total of 154 patients with LABC with no clinical or radiologic evidence of distant metastases on CI were enrolled. Median age was 49 years (range, 26-70 years). Imaging with PET/CT detected distant metastatic disease and/or locoregional disease not visualized on CI in 32 patients (20.8%). Distant metastatic disease was detected in 17 patients (11.0%): 6 had bony metastases, 5 had intrathoracic metastases (pulmonary/mediastinal), 2 had distant nodal metastases, 2 had liver metastases, 1 had pulmonary and bony metastases, and 1 had mediastinal and distant nodal metastases. Of the remaining 139 patients, nodal disease outside conventional radiation therapy fields was detected on PET/CT in 15 patients (10.8%), with involvement of ipsilateral internal mammary nodes in 13 and ipsilateral level 5 cervical nodes in 2.Imaging with PET/CT provides superior diagnostic and staging information in patients with LABC compared with CI, which has significant therapeutic implications with respect to radiation therapy management. Imaging with PET/CT should be considered in all patients undergoing primary staging for LABC.

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