Medical Education - Research Publications
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ItemSurvey of practices around pharmaceutical company funding for continuing professional development among medical oncologists and trainees in Australia(WILEY, 2017-08)BACKGROUND: The completion of continuing professional development (CPD) is mandatory for medical oncologists and trainees (MO&T). Pharmaceutical companies may fund some CPD activities, but there is increasing debate about the potential for conflicts of interest (COI). AIM: To assess current practices around funding to attend CPD activities. METHODS: An electronic survey was distributed to Australian MO&T. The survey asked questions about current practices, institutional policies and perceptions about attending CPD funded by pharmaceutical companies. The design looked at comparing responses between MO&T as well as their understanding of and training around institutional and ethical process. RESULTS: A total of 157 of 653 (24%) responses was received, the majority from MO (76%). Most CPD activities attended by MO&T were self-funded (53%), followed by funding from institutions (19%), pharmaceutical companies (16%) and salary award (16%). Most institutions allowed MO&T to receive CPD funding from professional organisations (104/157, 66%) or pharmaceutical companies (90/157, 57%). A minority of respondents (13/157, 8%) reported that the process to use pharmaceutical funds had been considered by an ethics committee. Although 103/157 (66%) had received pharmaceutical funding for CPD, most (109/157, 69%) reported never receiving training about potential COI. The lack of education was more noticeable among trainees (odds ratio (OR) 8.61, P = 0.02). MO&T acknowledged the potential bias towards a pharmaceutical product (P = 0.05) but believed there was adequate separation between themselves and pharmaceutical companies (P < 0.01). CONCLUSION: Majority of CPD attended by MO&T is self-funded. There is lack of clarity in institutional policies regarding external funding support for CPD activities. Formal education about potential COI is lacking.
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ItemPatterns of practice survey for brachytherapy for cervix cancer in Australia and New Zealand(WILEY, 2017-10)INTRODUCTION: The purpose of this survey was to explore the current patterns of practice for brachytherapy in cervix cancer in Australia and New Zealand. The survey was also intended to explore clinician attitudes towards image-guided adaptive brachytherapy (IGABT) and identify barriers to the implementation of IGABT. METHODS: Electronic surveys were sent to all radiotherapy centres in Australia and New Zealand under collaboration with Australia New Zealand Gynaecology and Oncology Group (ANZGOG), in order to identify patterns of radiotherapy practice. The survey was sent out in December 2013, with a reminder in February 2014. RESULTS: Of the 75 radiotherapy centres in Australia and New Zealand, 23 centres replied (31% response rate). Twenty-two responding departments treat cervix cancer with external beam radiation (EBRT) (22/23; 96%). Fourteen responses were from departments that also use intracavitary brachytherapy (14/22; 64%). The remaining eight departments who do not offer intracavitary brachytherapy referred their patients on to other centres for brachytherapy. Ultrasound was used by 86% for applicator guidance. CT and MRI were used by 79%, and 50% respectively for planning. Optimisation was based on organs at risk (93%) and target volumes (64%). CONCLUSIONS: Brachytherapy remains an integral component of definitive treatment for cervix cancer in Australia and New Zealand. There was increased use of soft tissue imaging modalities with emphasis on verification; high rates of volumetric planning, and adherence to a defined overall treatment period. Brachytherapy was not substituted with other EBRT modalities. Despite this, there remain barriers to implementation of image-guided brachytherapy.
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ItemCervical Cancer: A Global Health Crisis(WILEY, 2017-07-01)
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ItemPerceptions of cancer of unknown primary site: a national survey of Australian medical oncologists(WILEY, 2017-04)BACKGROUND: Despite being the sixth most common cause of cancer death in Australia, cancer of unknown primary (CUP) site remains poorly understood. AIMS: To describe practices relating to the diagnosis, investigation, classification, communication and management of CUP among medical oncologists. METHODS: We invited all members of the Medical Oncology Group of Australia to participate in a national, anonymous online survey about CUP. The survey collected data regarding diagnosis acceptance, diagnostic tests, treatment protocols and communication practices around the diagnosis of CUP. RESULTS: Three hundred and two oncologists were invited and 86 (28%) completed the survey. Eighty (93%) respondents were directly involved in the assessment of patients with CUP. Eighty-five (99%) respondents were prepared to make a diagnosis of CUP if, after appropriate diagnostic tests, the primary location could not be ascertained. Eighty-three percent would assign a primary site to obtain Pharmaceutical Benefits Schedule funding of medical therapy. Sixty-two percent did not have a specific treatment protocol designed for CUP. The majority of oncologists used serum tumour markers and computed tomography scans in the initial work-up, while 43% indicated they would use a positron emission tomography scan in the majority of cases. The majority would arrange mammography in female patients. Thematic analysis of responses to open-ended questions about how CUP is described identified little consistency in the language being used. CONCLUSION: The approach to diagnosis, investigation and management of CUP by medical oncologists in Australia is variable. Many preferred to estimate the primary site and treat accordingly. Pharmaceutical Benefits Schedule restrictions may encourage the practice of 'best guessing'.
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ItemResults of the Australasian (Trans-Tasman Oncology Group) radiotherapy benchmarking exercise in preparation for participation in the PORTEC-3 trial(WILEY-BLACKWELL, 2016-08)INTRODUCTION: Protocol deviations in Randomised Controlled Trials have been found to result in a significant decrease in survival and local control. In some cases, the magnitude of the detrimental effect can be larger than the anticipated benefits of the interventions involved. The implementation of appropriate quality assurance of radiotherapy measures for clinical trials has been found to result in fewer deviations from protocol. This paper reports on a benchmarking study conducted in preparation for the PORTEC-3 trial in Australasia. METHODS: A benchmarking CT dataset was sent to each of the Australasian investigators, it was requested they contour and plan the case according to trial protocol using local treatment planning systems. These data was then sent back to Trans-Tasman Oncology Group for collation and analysis. RESULTS: Thirty three investigators from eighteen institutions across Australia and New Zealand took part in the study. The mean clinical target volume (CTV) volume was 383.4 (228.5-497.8) cm(3) and the mean dose to a reference gold standard CTV was 48.8 (46.4-50.3) Gy. CONCLUSIONS: Although there were some large differences in the contouring of the CTV and its constituent parts, these did not translate into large variations in dosimetry. Where individual investigators had deviations from the trial contouring protocol, feedback was provided. The results of this study will be used to compare with the international study QA for the PORTEC-3 trial.
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ItemThe trajectory of patients who die from metastatic prostate cancer: a population-based study(WILEY, 2019-05)OBJECTIVES: To describe health service use, symptom and survival characteristics in metastatic prostate cancer (mPCa) in order to outline usual care practices and identify future opportunities to improve the quality of care in this patient group. PATIENTS AND METHODS: This population cohort study, conducted in Victoria, Australia, used 10 years (2000-2010) of linked hospital discharge, emergency visit, and death registration data, to track patients from their first inpatient admission with mPCa until death. Descriptive statistics on inpatient health service use, symptoms, procedures, survival, and place of death are presented. RESULTS: In all, 4436 patients survived a median (interquartile range [IQR]) of 4 (1, 12) months from their first multiday admission with mPCa. They had a median (IQR) of 3 (1, 9) admissions, 1 (0, 2) emergency department presentation, and 35 (18, 63) days admitted to hospital. Lower urinary tract symptoms were common (50%), and 21% underwent lower urinary tract procedures, whilst 48% had blood product transfusions. In the last month of life, 3685 (83%) had at least one indicator of aggressive end-of-life care, including 48% with more than one acute hospital admission, and 55% staying ≥14 days. Hospital-based palliative care was accessed by 2657 (60%), occurring a median (IQR) of 30 (11, 74) days before death. In all, 23% died in the community, whilst 77% died in hospital, of whom 55% died in an acute hospital bed. CONCLUSION: Half of all decedents first admitted for a multiday stay with mPCa survived <4 months thereafter. They had a marked symptom burden, underwent multiple procedures and had multiple admissions. In all, 40% of patients did not receive any hospital-based palliative care. Several opportunities exist to improve the timely transition to palliative care services with mPCa. These data form a benchmark against which future improvements to palliative care integration may be measured.
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ItemOutcomes of Australian patients receiving non-funded anti-PD-1 immune checkpoint inhibitors for non-melanoma cancers(WILEY, 2018-08)AIM: To characterize the outcomes of patients with nonmelanoma solid tumors receiving anti-PD-1 immunotherapy not funded by the Australian Pharmaceutical Benefits Scheme. METHODS: Medical records of patients with metastatic nonmelanoma tumor diagnoses treated with anti-PD-1 (self-funded pembrolizumab or nivolumab through an access program) from January 1, 2014, to December 31, 2016, at Peter MacCallum Cancer Centre, were retrospectively reviewed. Events after December 31, 2016, were censored. RESULTS: Of 47 patients identified, 27 (57%) had lung cancer. Twenty-six had compassionate access to nivolumab (24 lung, one renal, one gastroesophageal with possible new lung primary). Median overall survival was 5.7 months. Eleven (23%) achieved a partial response; none had complete response. Twenty (43%) had disease progression on first imaging; 16 (48%) of these continued treatment beyond radiological progression, with three achieving subsequent partial responses. Ten (21%) were not re-staged mostly due to rapid deterioration or death. At 6 and 12 months, nine (20%) and two (4%) remained on treatment, respectively. Five (12%) discontinued treatment due to immune-related toxicities. Of 34 patients who died, 71% received treatment within the last month of life; 38% died in an acute hospital. None of 25 patients with poor Eastern Cooperative Oncology Group performance scores of 2-4 responded. CONCLUSION: The response rates and overall survival of patients with NSCLC, renal carcinoma and triple negative breast cancer of good performance status receiving anti-PD-1 therapy outside of a clinical trial are consistent with clinical trial data. However, patients with poor ECOG performance status are unlikely to respond. Careful patient selection and counseling about the potential outcomes of self-funding treatment in this setting is needed.
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ItemSurvival difference according to mutation status in a prospective cohort study of Australian patients with metastatic non-small-cell lung carcinoma(WILEY, 2018-01)BACKGROUND: Non-small-cell lung cancer (NSCLC) is a heterogeneous disease comprising not only different histological subtypes but also different molecular subtypes. AIM: To describe the frequency of oncogenic drivers in patients with metastatic NSCLC, the proportion of patients tested and survival difference according to mutation status in a single-institution study. METHODS: Metastatic NSCLC patients enrolled in a prospective Thoracic Malignancies Cohort Study between July 2012 and August 2016 were selected. Patients underwent molecular testing for epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) gene rearrangements, Kirsten rat sarcoma (KRAS), B-Raf proto-oncogene (BRAF) mutations and ROS1 gene rearrangements. Survival was calculated using the Kaplan-Meier method for groups of interest, and comparisons were made using the log-rank test. RESULTS: A total of 392 patients were included, 43% of whom were female with median age of 64 years (28-92). Of 296 patients tested, 172 patients (58%) were positive for an oncogenic driver: 81 patients (27%) were EGFR positive, 25 patients (9%) were ALK positive, 57 patients (19%) had KRAS mutation and 9 patients (3%) were ROS1 or BRAF positive. Patients with an actionable mutation (EGFR/ALK) had a survival advantage when compared with patients who were mutation negative (hazard ratio (HR) 0.49; 95% confidence interval (CI) 0.33-0.71; P < 0.01). Survival difference between mutation negative and mutation status unknown was not statistically significant when adjusted for confounding factors in a multivariate analysis (HR 1.29; 95% CI 0.97-1.78, P = 0.08). CONCLUSION: In this prospective cohort, the presence of an actionable mutation was the strongest predictor of overall survival. These results confirm the importance of molecular testing and suggest likely survival benefit of identification and treatment of actionable oncogenes.
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ItemPatients' and clinicians' preferences for adjuvant chemotherapy in endometrial cancer: an ANZGOG substudy of the PORTEC-3 intergroup randomised trial(SPRINGERNATURE, 2016-11-08)BACKGROUND: To determine the minimum survival benefits that patients, and their clinicians, judged sufficient to make adjuvant chemotherapy (ACT) worthwhile, in addition to pelvic radiotherapy, for women with high risk and advanced stage endometrial cancer. METHODS: Eighty-three participants in the PORTEC-3 trial completed a time trade-off questionnaire before and after adjuvant therapy; 44 of their clinicians completed it once only. The questionnaire used four hypothetical scenarios including baseline survival times without ACT of 5 and 8 years, and baseline survival rates at 5 years without ACT of 50 and 65%. RESULTS: Over 50% of patients judged an extra 1 year of survival time or an extra 5% in survival rate sufficient to make ACT worthwhile. Over 50% of clinicians judged an extra 1 year of survival time, or an extra 10% in survival rate, sufficient to make ACT worthwhile. Compared with patients, clinicians required similar survival time benefits (medians both 1 year, P=0.4), but larger survival rate benefits (medians 8.5% vs 5%, P=0.03), and clinicians' preferences varied less (IQR 0.5-1.5 years vs 0.4-2 years, P=0.0007; 5-10% vs 1-13%, P=0.004). Patients' preferences changed over time for the survival rate scenarios depending on whether they had ACT or not (change in median benefit - 3 months vs 2.5 months respectively, P=0.028). There were no strong predictors of patients' or clinicians' preferences. CONCLUSIONS: Patients and clinicians judged moderate survival benefits sufficient to make ACT worthwhile after pelvic radiotherapy for endometrial cancer. These benefits are larger than those judged sufficient by patients with breast or colon cancers, but similar to those judged sufficient by patients with lung or ovarian cancers.
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ItemProgression-free and overall survival in ovarian cancer patients treated with CVac, a mucin 1 dendritic cell therapy in a randomized phase 2 trial(BMC, 2016-06-21)BACKGROUND: CAN-003 was a randomized, open-label, Phase 2 trial evaluating the safety, efficacy and immune outcomes of CVac, a mucin 1 targeted-dendritic cell (DC) treatment as a maintenance therapy to patients with epithelial ovarian cancer (EOC). METHODS: Patients (n = 56) in first (CR1) or second clinical remission (CR2) were randomized (1:1) to standard of care (SOC) observation or CVac maintenance treatment. Ten doses were administered over 56 weeks. Both groups were followed for progression-free survival (PFS) and overall survival (OS). RESULTS: Fifty-six patients were randomized: 27 to SOC and 29 to CVac. Therapy was safe with only seven patients with Grade 3-4 treatment-emergent adverse events. A variable but measurable mucin 1 T cell-specific response was induced in all CVac-treated and some standard of care (SOC) patients. Progression free survival (PFS) was not significantly longer in the treated group compared to SOC group (13 vs. 9 months, p = 0.36, hazard ratio [HR] = 0.73). Analysis by remission status showed in the CR1 subgroup a median PFS of 18 months (SOC) vs. 13 months (CVac); p = 0.69 (HR = 1.18; CI 0.52-2.71). However CR2 patients showed a longer median PFS in the CVac-treated group (median PFS not yet reached, >13 vs. 5 months; p = 0.04, HR = 0.32 CI). OS for CR2 patients at 42 months of follow-up showed a difference of 26 months for SOC vs. > 42 months for CVac-treated (as median OS had not been reached; HR = 0.17 (CI 0.02-1.4) with a p = 0.07). CONCLUSIONS: CVac, a mucin 1-dendritic cell maintenance treatment was safe and well tolerated in ovarian cancer patients. A variable but observed CVac-derived, mucin 1-specific T cell response was measured. Notably, CR2 patients showed an improved PFS and lengthened OS. Further studies in CR2 ovarian cancer patients are warranted (NCT01068509). TRIAL REGISTRATION: NCT01068509. Study Initiation Date (first patient screened): 20 July 2010. Study Completion Date (last patient observation): 20 August 2013, the last patient observation for progression-free survival; 29 April 2015, the last patient was documented regarding overall survival.