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Background: Phase 1 oncology trials provide access to new therapies and may improve cancer outcomes. Phase 1 trials conducted in the Asian-Pacific region are increasing at a faster rate than the global trend. This study aimed to describe the changing landscape of phase 1 oncology trials in Australia in the last decade., Methods: This cross-sectional study reviewed phase 1 oncology trials registered on ClinicalTrials.gov conducted in Australia. Phase 1 trials were included for analysis if they enrolled adults with solid organ malignancies, used at least one systemic agent, and were first registered between January 1, 2012, and December 31, 2022. The number of trials, site locations, sponsor type, and drug class were analyzed using descriptive statistics., Results: Over the 10-year period, ClinicalTrials.gov included 493 phase 1 clinical trials across 71 Australian sites. Most sites were in metropolitan locations; in Melbourne, trials were concentrated within selected sites, while in Sydney, trials were spread across a larger number of sites. The number of phase 1 trials per annum increased from 18 in 2012 to 75 in 2022. Since 2020, emerging biopharmaceutical companies have become the predominant sponsor type, a trend that is also seen globally. While most trial sponsors were North American (42%), there was increasing representation from Asian sponsors over the 10-year period (6% in 2012 to 39% in 2022). Immunomodulatory (45%) and targeted approaches (44%) accounted for most drug classes used alone or in combination., Conclusions: There are an increasing number of phase 1 trials conducted within Australia. Sponsors of phase 1 trials are increasingly from Asian countries and are more likely to be emerging biopharmaceutical companies., (© 2024 John Wiley & Sons Australia, Ltd.)

Background: Diagnosis and management of cancers of unknown primary (CUP) remain challenging. This study examines the referral patterns, management and outcomes of patients referred to Australia's first dedicated CUP clinic., Methods: Retrospective medical record review was conducted for patients seen at the Peter MacCallum Cancer Centre CUP clinic between July 2014 and August 2020. Overall survival (OS) was analysed for patients with a CUP diagnosis where treatment information was available., Results: Of 361 patients referred, fewer than half had completed diagnostic work-up at the time of referral. A diagnosis of CUP was established in 137 (38%), malignancy other than CUP in 177 (49%) and benign pathology in 36 (10%) patients. Genomic testing was successfully completed in 62% of patients with initial provisional CUP and impacted management in 32% by identifying a tissue of origin or actionable genomic alteration. The use of site-specific, targeted therapy or immunotherapy was independently associated with longer OS compared to empirical chemotherapy., Conclusion: Our specialised CUP clinic facilitated diagnostic work-up among patients with suspected malignancy and provided access to genomic testing and clinical trials for patients with a CUP diagnosis, all of which are important to improve outcomes in this patient population., (© 2023. The Author(s).)

Introduction: Epidemiological evidence supports an association between higher levels of physical activity and improved cancer survival. Trial evidence is now needed to demonstrate the effect of exercise in a clinical setting. The E xercise during CH emotherapy for O varian cancer (ECHO) trial is a phase III, randomised controlled trial, designed to determine the effect of exercise on progression-free survival and physical well-being for patients receiving first-line chemotherapy for ovarian cancer., Methods and Analysis: Participants (target sample size: n=500) include women with newly diagnosed primary ovarian cancer, scheduled to receive first-line chemotherapy. Consenting participants are randomly allocated (1:1) to either the exercise intervention (plus usual care) or usual care alone, with stratification for recruitment site, age, stage of disease and chemotherapy delivery (neoadjuvant vs adjuvant). The exercise intervention involves individualised exercise prescription with a weekly target of 150 minutes of moderate-intensity, mixed-mode exercise (equivalent to 450 metabolic equivalent minutes per week), delivered for the duration of first-line chemotherapy through weekly telephone sessions with a trial-trained exercise professional. The primary outcomes are progression-free survival and physical well-being. Secondary outcomes include overall survival, physical function, body composition, quality of life, fatigue, sleep, lymphoedema, anxiety, depression, chemotherapy completion rate, chemotherapy-related adverse events, physical activity levels and healthcare usage., Ethics and Dissemination: Ethics approval for the ECHO trial (2019/ETH08923) was granted by the Sydney Local Health District Ethics Review Committee (Royal Prince Alfred Zone) on 21 November 2014. Subsequent approvals were granted for an additional 11 sites across Queensland, New South Wales, Victoria and the Australian Capital Territory. Findings from the ECHO trial are planned to be disseminated via peer-reviewed publications and international exercise and oncology conferences., Trial Registration Number: Australian New Zealand Clinical Trial Registry (ANZCTRN12614001311640; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=367123&isReview=true)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Australian Genomics is a national collaborative partnership of more than 100 organizations piloting a whole-of-system approach to integrating genomics into healthcare, based on federation principles. In the first five years of operation, Australian Genomics has evaluated the outcomes of genomic testing in more than 5,200 individuals across 19 rare disease and cancer flagship studies. Comprehensive analyses of the health economic, policy, ethical, legal, implementation and workforce implications of incorporating genomics in the Australian context have informed evidence-based change in policy and practice, resulting in national government funding and equity of access for a range of genomic tests. Simultaneously, Australian Genomics has built national skills, infrastructure, policy, and data resources to enable effective data sharing to drive discovery research and support improvements in clinical genomic delivery., Competing Interests: Declaration of interests R.L.W. is the Chair of the Medical Services Advisory Committee; the views in this paper are not representing those of the Commonwealth of Australia. I.E.S. has served on scientific advisory boards for BioMarin, Chiesi, Eisai, Encoded Therapeutics, GlaxoSmithKline, Knopp Biosciences, Nutricia, Rogcon, Takeda Pharmaceuticals, UCB, and Xenon Pharmaceuticals; has received speaker honoraria from GlaxoSmithKline, UCB, BioMarin, Biocodex, Chiesi, Liva Nova, Nutricia, Zuellig Pharma, and Eisai; has received funding for travel from UCB, Biocodex, GlaxoSmithKline, Biomarin, and Eisai; has served as an investigator for Anavex Life Sciences, Cerecin Inc, Cerevel Therapeutics, Eisai, Encoded Therapeutics, EpiMinder Inc, Epygenyx, ES-Therapeutics, GW Pharma, Marinus, Neurocrine BioSciences, Ovid Therapeutics, Takeda Pharmaceuticals, UCB, Ultragenyx, Xenon Pharmaceuticals, Zogenix, and Zynerba; and has consulted for Care Beyond Diagnosis, Epilepsy Consortium, Atheneum Partners, Ovid Therapeutics, UCB, Zynerba Pharmaceuticals, BioMarin, Encoded Therapeutics, and Biohaven Pharmaceuticals; and is a Non-Executive Director of Bellberry Ltd and a Director of the Australian Academy of Health and Medical Sciences and the Australian Council of Learned Academies Limited. She may accrue future revenue on pending patent WO61/010,176 (filed: 2008): Therapeutic Compound; has a patent for SCN1A testing held by Bionomics Inc and licensed to various diagnostic companies; and has a patent molecular diagnostic/theranostic target for benign familial infantile epilepsy (BFIE) (PRRT2) 2,011,904,493 & 2,012,900,190 and PCT/AU2012/001,321 (TECH ID:2012-009)., (Copyright © 2023 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Cancer of unknown primary (CUP) is a syndrome defined by clinical absence of a primary cancer after standardised investigations. Gene expression profiling (GEP) and DNA sequencing have been used to predict primary tissue of origin (TOO) in CUP and find molecularly guided treatments; however, a detailed comparison of the diagnostic yield from these two tests has not been described. Here, we compared the diagnostic utility of RNA and DNA tests in 215 CUP patients (82% received both tests) in a prospective Australian study. Based on retrospective assessment of clinicopathological data, 77% (166/215) of CUPs had insufficient evidence to support TOO diagnosis (clinicopathology unresolved). The remainder had either a latent primary diagnosis (10%) or clinicopathological evidence to support a likely TOO diagnosis (13%) (clinicopathology resolved). We applied a microarray (CUPGuide) or custom NanoString 18-class GEP test to 191 CUPs with an accuracy of 91.5% in known metastatic cancers for high-medium confidence predictions. Classification performance was similar in clinicopathology-resolved CUPs - 80% had high-medium predictions and 94% were concordant with pathology. Notably, only 56% of the clinicopathology-unresolved CUPs had high-medium confidence GEP predictions. Diagnostic DNA features were interrogated in 201 CUP tumours guided by the cancer type specificity of mutations observed across 22 cancer types from the AACR Project GENIE database (77,058 tumours) as well as mutational signatures (e.g. smoking). Among the clinicopathology-unresolved CUPs, mutations and mutational signatures provided additional diagnostic evidence in 31% of cases. GEP classification was useful in only 13% of cases and oncoviral detection in 4%. Among CUPs where genomics informed TOO, lung and biliary cancers were the most frequently identified types, while kidney tumours were another identifiable subset. In conclusion, DNA and RNA profiling supported an unconfirmed TOO diagnosis in one-third of CUPs otherwise unresolved by clinicopathology assessment alone. DNA mutation profiling was the more diagnostically informative assay. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland., (© 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.)

Objective: To better serve women with gynaecological cancers, we need a sound understanding of their health, wellbeing and needs. This study sought to explore these issues in a sample of Australian women before commencing curative radiotherapy., Methods: We undertook a secondary analysis of baseline data from a supportive care trial (n = 311). Descriptive statistics were used to summarise responses to measures of wellbeing, general psychological distress, symptom distress, sexual function and vaginal changes, and supportive care needs. Pre-specified regression models were used to examine sources of variation in wellbeing and sexual function., Results: Women reported lower emotional, functional and physical wellbeing than population norms (all p < 0.001). The prevalence of general psychological distress was 31% (95% CI 26-36%). Distress caused by physical symptoms was typically low. Health system and information needs comprised eight of the top ten moderate-to-high supportive care needs. Most women reported no change in interest for physical contact or sex compared to pre-diagnosis, but some sexually active women (16-24%) reported smaller vaginal size, increased dryness, and more pain on intercourse. General psychological distress was a robust marker of poorer wellbeing and sexual function., Conclusions: Before radiotherapy, a substantial minority of women with gynaecological cancers experience general psychological distress, reduced wellbeing and moderate-to-high health system and information needs. A model of comprehensive care incorporating assessment of unmet needs, general psychological distress, and sexual issues is recommended. Healthcare providers may require training to elicit and respond to a constellation of interrelated issues and access relevant services for women requiring additional support., Competing Interests: Declaration of Competing Interest All authors declare no potential sources of conflict of interest., (Crown Copyright © 2022. Published by Elsevier Inc. All rights reserved.)

Objectives: The primary objective of this study was to describe treatment patterns after poly-ADP ribose polymerase (PARP) inhibitor in patients with epithelial ovarian cancer. Secondary objectives were to evaluate duration of response, time to first subsequent therapy, progression-free survival and overall survival., Methods: This was a retrospective analysis of patients with epithelial ovarian cancer treated with PARP inhibitor therapy at six Australian gynecological oncology centers. Eligible patients were identified via clinics, trial databases and pharmacy dispensing logs between January 2005 and September 2019. Information regarding clinico-pathological characteristics and treatment outcomes were collated from medical records., Results: A total of 85 patients with epithelial ovarian cancer were identified. Of these, 61% had germline BRCA1/2 mutations, 9% had somatic BRCA1/2 mutations, 5% had confirmed homologous recombination deficiency and 25% were BRCA1/2 wildtype mutations. A total of seventy-seven (91%) patients received chemotherapy after PARP inhibitor, with fifty-six (72.7%) of these patients receiving platinum-based chemotherapy. Four patients (5%) had a complete response, 15 (20%) a partial response, 15 (20%) stable disease and 41 (55%) progressive disease. Median duration of response to chemotherapy was 7.0 months (range 0.2-20.4). Median time to first subsequent therapy was 17.6 and 15.1 months in patients who received a PARP inhibitor as maintenance therapy and treatment, respectively. Median progression-free survival of first line treatment after PARP inhibitor was 9.6, 3.5 and 4.6 months for platinum doublet, single agent platinum and non-platinum chemotherapy, respectively. Adjusting for age and FIGO (Federation of Gynecological Oncologists classification) stage progression-free survival did not differ between treatment groups (p=0.14). Median overall survival for the cohort was 69 months, and patients with platinum sensitive ovarian cancer had improved survival compared with those with platinum refractory or resistant disease., Conclusion: Platinum doublet chemotherapy resulted in non-significant improved progression-free survival compared with other regimens, suggesting potential independent mechanisms of resistance between PARP inhibitor and platinum compounds., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

The COVID-19 pandemic has placed an overwhelming burden on healthcare delivery globally. This paper examines how COVID-19 has affected cancer care clinicians' capacity to deliver cancer care in the Australian context. We use the lens of 'holding patients' (drawing from attachment theory, psychology and from Australian Indigenous knowledge) to conceptualise cancer clinicians' processes of care and therapeutic relationships with patients. These notions of 'holding' resonate with the deep responsibility cancer care clinicians feel towards their patients. They enrich ethical language beyond duties to benefit, avoid harm, respect patients' autonomy and provide just treatment. We consider the disruptive effects of COVID-19 on care delivery and on clinicians themselves. We then show how models of clinical ethics and other similar reflective discussion approaches are a relevant support mechanism to assist clinicians to process and make sense of COVID-19's disruptions to their professional ethical role of holding patients during and beyond the pandemic., (© 2021 Royal Australasian College of Physicians.)

Introduction: The Australian Council on Healthcare Standards (ACHS) sponsored an expert-led, consensus-driven, four-stage process, based on a modified Delphi methodology, to determine a set of clinical indicators as quality measures of cancer service provision in Australia. This was done in response to requests from institutional health care providers seeking accreditation, which were additional and complementary to the existing radiation oncology set. The steering group members comprised multidisciplinary key opinion leaders and a consumer representative. Five additional participants constituted the stakeholder group, who deliberated on the final indicator set., Methods and Recommendations: An initial meeting of the steering group scoped the high level nature of the desired set. In stage 2, 65 candidate indicators were identified by a literature review and a search of international metrics. These were ranked by survey, based on ease of data accessibility and collectability and clinical relevance. The top 27 candidates were debated by the stakeholder group and culled to a final set of 16 indicators. A user manual was created with indicators mapped to clinical codes. The indicator set was ratified by the Clinical Oncology Society of Australia and is now available for use by health care organisations participating in the ACHS Clinical Indicator Program. This inaugural cancer clinical indicator set covers high level assessment of various critical processes in cancer service provision in Australia. Regular reviews and updates will ensure usability., Changes in Management as a Result of This Statement: This is the inaugural indicator set for cancer care for use across Australia and internationally under the ACHS Clinical Indicator Program. Multidisciplinary involvement through a modified Delphi process selected indicators representing both generic and specific aspects of care across the cancer journey pathway and will provide a functional tool to compare health care delivery across multiple settings. It is anticipated that this will drive continual improvement in cancer care provision., (© 2021 AMPCo Pty Ltd.)

Objectives: To report clinician-perceived changes to cancer service delivery in response to COVID-19., Design: Multidisciplinary Australasian cancer clinician survey in collaboration with the European Society of Medical Oncology., Setting: Between May and June 2020 clinicians from 70 countries were surveyed; majority from Europe (n=196; 39%) with 1846 COVID-19 cases per million people, Australia (AUS)/New Zealand (NZ) (n=188; 38%) with 267/236 per million and Asia (n=75; 15%) with 121 per million at time of survey distribution., Participants: Medical oncologists (n=372; 74%), radiation oncologists (n=91; 18%) and surgical oncologists (n=38; 8%)., Results: Eighty-nine per cent of clinicians reported altering clinical practices; more commonly among those with versus without patients diagnosed with COVID-19 (n=142; 93% vs n=225; 86%, p=0.03) but regardless of community transmission levels (p=0.26). More European clinicians (n=111; 66.1%) had treated patients diagnosed with COVID-19 compared with Asia (n=20; 27.8%) and AUS/NZ (n=8; 4.8%), p<0.001. Many clinicians (n=307; 71.4%) reported concerns that reduced access to standard treatments during the pandemic would negatively impact patient survival. The reported proportion of consultations using telehealth increased by 7.7-fold, with 25.1% (n=108) of clinicians concerned that patient survival would be worse due to this increase. Clinicians reviewed a median of 10 fewer outpatients/week (including non-face to face) compared with prior to the pandemic, translating to 5010 fewer specialist oncology visits per week among the surveyed group. Mental health was negatively impacted for 52.6% (n=190) of clinicians., Conclusion: Clinicians reported widespread changes to oncology services, in regions of both high and low COVID-19 case numbers. Clinician concerns of potential negative impacts on patient outcomes warrant objective assessment, with system and policy implications for healthcare delivery at large., Competing Interests: Competing interests: Some authors of this manuscript hold leadership positions on the ESMO board., (© Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology.)

Background: Clinical audit may improve practice in cancer service provision. The UK National Lung Cancer Audit (NLCA) collects data for all new cases of thoracic cancers., Aim: To collect similar data for our Victorian patients from six hospitals within the Victorian Comprehensive Cancer Centre and associated Western and Central Melbourne Integrated Cancer Service., Methods: We conducted a retrospective audit of all newly diagnosed patients with lung cancer and mesothelioma in 2013 across the six Victorian Comprehensive Cancer Centre/Western and Central Melbourne Integrated Cancer Service hospitals. The objectives were to adapt the NLCA data set for use in the Australian context, to analyse the findings using descriptive statistics and to determine feasibility of implementing a routine, ongoing audit similar to that in the UK. Individual data items were adapted from the NLCA by an expert steering committee. Data were collated from the Victorian Cancer Registry, Victorian Admitted Episodes Dataset and individual hospital databases. Individual medical records were audited for missing data., Results: Eight hundred and forty-five patients were diagnosed across the sites in 2013. Most were aged 65-80 (55%) and were male (62%). Most had non-small-cell lung cancer (81%) with 9% diagnosed with small cell lung cancer and 2% with mesothelioma. Data completeness varied significantly between fields. For those with higher levels of completeness, headline indicators of clinical care were comparable with NLCA data. The Victorian population seem to lack access to specialist lung cancer nurse services., Conclusion: Lung cancer care at participating hospitals appeared to be comparable with the UK in 2013. In future, prospective data collection should be harmonised across sites and correlated with survival outcomes. One area of concern was a lack of documented access to specialist nursing services., (© 2018 Royal Australasian College of Physicians.)

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., (© 2018 John Wiley & Sons Australia, Ltd.)

Background: Although women with endometrial cancer generally have a favourable prognosis, those with high-risk disease features are at increased risk of recurrence. The PORTEC-3 trial was initiated to investigate the benefit of adjuvant chemotherapy during and after radiotherapy (chemoradiotherapy) versus pelvic radiotherapy alone for women with high-risk endometrial cancer., Methods: PORTEC-3 was an open-label, international, randomised, phase 3 trial involving 103 centres in six clinical trials collaborating in the Gynaecological Cancer Intergroup. Eligible women had high-risk endometrial cancer with FIGO 2009 stage I, endometrioid-type grade 3 with deep myometrial invasion or lymph-vascular space invasion (or both), endometrioid-type stage II or III, or stage I to III with serous or clear cell histology. Women were randomly assigned (1:1) to receive radiotherapy alone (48·6 Gy in 1·8 Gy fractions given on 5 days per week) or radiotherapy and chemotherapy (consisting of two cycles of cisplatin 50 mg/m 2 given during radiotherapy, followed by four cycles of carboplatin AUC5 and paclitaxel 175 mg/m 2 ) using a biased-coin minimisation procedure with stratification for participating centre, lymphadenectomy, stage of cancer, and histological type. The co-primary endpoints were overall survival and failure-free survival. We used the Kaplan-Meier method, log-rank test, and Cox regression analysis for final analysis by intention to treat and adjusted for stratification factors. The study was closed on Dec 20, 2013, after achieving complete accrual; follow-up is ongoing. PORTEC-3 is registered with ISRCTN, number ISRCTN14387080, and ClinicalTrials.gov, number NCT00411138., Results: 686 women were enrolled between Nov 23, 2006, and Dec 20, 2013. 660 eligible patients were included in the final analysis, of whom 330 were assigned to chemoradiotherapy and 330 were assigned to radiotherapy. Median follow-up was 60·2 months (IQR 48·1-73·1). 5-year overall survival was 81·8% (95% CI 77·5-86·2) with chemoradiotherapy versus 76·7% (72·1-81·6) with radiotherapy (adjusted hazard ratio [HR] 0·76, 95% CI 0·54-1·06; p=0·11); 5-year failure-free survival was 75·5% (95% CI 70·3-79·9) versus 68·6% (63·1-73·4; HR 0·71, 95% CI 0·53-0·95; p=0·022). Grade 3 or worse adverse events during treatment occurred in 198 (60%) of 330 who received chemoradiotherapy versus 41 (12%) of 330 patients who received radiotherapy (p<0·0001). Neuropathy (grade 2 or worse) persisted significantly more often after chemoradiotherapy than after radiotherapy (20 [8%] women vs one [1%] at 3 years; p<0·0001). Most deaths were due to endometrial cancer; in four patients (two in each group), the cause of death was uncertain. One death in the radiotherapy group was due to either disease progression or late treatment complications; three deaths (two in the chemoradiotherapy group and one in the radiotherapy group) were due to either intercurrent disease or late treatment-related toxicity., Interpretation: Adjuvant chemotherapy given during and after radiotherapy for high-risk endometrial cancer did not improve 5-year overall survival, although it did increase failure-free survival. Women with high-risk endometrial cancer should be individually counselled about this combined treatment. Continued follow-up is needed to evaluate long-term survival., Funding: Dutch Cancer Society, Cancer Research UK, National Health and Medical Research Council Project Grant and Cancer Australia, L'Agenzia Italiana del Farmaco, and Canadian Cancer Society Research Institute., (Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC-BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

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., (© 2017 Royal Australasian College of Physicians.)

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'., (© 2017 Royal Australasian College of Physicians.)

Aims: Cyclophosphamide was widely used as a single agent prior to the advent of platinum-based regimens for epithelial ovarian cancer, and, in combination with platinum, prior to the adoption of platinum and paclitaxel as standard first-line therapy. As cyclophosphamide currently has no defined role in ovarian cancer we aimed to assess its activity in women with recurrent disease., Methods: A retrospective review was conducted of patients from three centers in Melbourne, Australia who had received oral cyclophosphamide treatment for recurrent ovarian cancer. The primary end-point was response rate to oral cyclophosphamide (150 mg p.o. day 1-14) based on Gynecologic Cancer InterGroup (GCIG) CA125 and/or Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Secondary end-points included overall and progression-free survival and toxicity., Results: In all, 26 patients were identified and 23 patients were evaluable for response. The median number of prior chemotherapy regimens was three (range 1-6). The response rate to oral cyclophosphamide was 44% with 10 of the 23 patients achieving a partial response (PR) based on GCIG (CA125) criteria. The median number of cycles received was three (range 1-16). Cyclophosphamide showed activity both in patients with platinum-sensitive (seven of 13 PR) and resistant or refractory disease (three of 10 PR). There was no grade 3 or 4 toxicity but two patients ceased cyclophosphamide due to less severe non-hematological toxicity., Conclusion: Single agent oral cyclophosphamide is active and well tolerated in recurrent ovarian cancer. Further investigation of oral cyclophosphamide in patients with platinum-sensitive and platinum-resistant disease is warranted., (© 2013 Wiley Publishing Asia Pty Ltd.)

Objective: The aim of this study is to determine the frequency of geriatric assessment in patients aged over 70 years in Australian medical oncology clinics., Material and Methods: This was a multicentre audit in two parts: a retrospective file review of initial consultations with an oncologist and prospective audit of case presentations at multidisciplinary meetings (MDMs). Patients aged over 70 years presenting to a medical oncology clinic or being discussed at an MDM were eligible. Data was collected at six oncology centres in Victoria, NSW and Canberra from October 2009 to March 2010., Results: Data was collected from 251 file reviews and 108 MDM discussions in a total of 304 patients. Median age was 76 years (range 70-95). The geriatric assessment (GA) domains most frequently assessed during an initial consultation were the presence of comorbidities (92%), social situation-living alone or with someone (80%), social supports (63%), any mention of at least one Activity of Daily Living (ADL) (50%) and performance status (49%). Less frequently assessed were any Instrumental Activity of Daily Living (IADL) (26%), presence of a geriatric syndrome (24%), polypharmacy (29%) and creatinine clearance (11%). Only one patient had all components of ADLs and IADLs assessed. During MDMs all the geriatric domains were comparatively less frequently assessed. No patients had all ADL and IADL components discussed formally in an MDM., Conclusion: This is the first multicentre audit that reveals the low rates of GA in Australian medical oncology practice and describes the GA domains considered important by oncology clinicians., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objectives: Physical activity has been infrequently measured objectively in non-small cell lung cancer (NSCLC). We aimed to investigate levels of physical activity, functional and patient reported outcomes at diagnosis and over six months in participants with recently diagnosed NSCLC and compare results with both physical activity guidelines and outcomes of similar-aged healthy individuals., Methods: This prospective observational study assessed 50 individuals from three Australian tertiary hospitals with stage I-IIIB NSCLC at diagnosis, then 10 weeks and six months later. Thirty five healthy individuals without cancer were assessed once. Outcome measures included tri-axial accelerometery (number of steps per day), six minute walk distance (6MWD), muscle strength and questionnaires including health-related quality of life (HRQoL)., Results: Individuals with NSCLC were engaged in significantly less physical activity than similar-aged healthy individuals, with 60% not meeting physical activity guidelines. At diagnosis they had worse quadriceps strength, nutritional status and HRQoL. Over six months, participants with NSCLC experienced decline in self-reported physical activity, 6MWD and muscle strength, and worsening symptoms., Conclusion: At diagnosis individuals with NSCLC engage in less physical activity, are weaker and more depressed than healthy individuals and their self-reported physical activity declines over six months. Future studies are required to investigate the efficacy of interventions to increase physical activity., (Crown Copyright © 2013. Published by Elsevier Ireland Ltd. All rights reserved.)

The current consensus guidelines were developed to standardize the clinical approach to the management of neutropenic fever in adult cancer patients throughout Australian treating centres. The three areas of clinical practice covered by the guidelines, the process for developing consensus opinion, and the system used to grade the evidence and relative strength of recommendations are described. The health economics implications of establishing clinical guidance are also discussed., (© 2011 The Authors. Internal Medicine Journal © 2011 Royal Australasian College of Physicians.)

Purpose: Many new cancer treatments are available only at significant financial cost to the patient. We previously reported that Australian medical oncologists commonly do not discuss unsubsidized, expensive anticancer drugs (EACD) because of concern about causing distress. We argued that this position was not consistent with modern ethical principals but wanted to seek the community viewpoint., Methods: A cross-sectional telephone survey of the Australian general public was performed. Respondents' views were sought about three hypothetical scenarios in which they were diagnosed with incurable cancer and an EACD treatment (out-of-pocket cost US$25,000) was available., Results: Responses were obtained from 1,255 respondents (response rate, 43%). One hundred thirty-seven (11%) had a prior cancer diagnosis. Ninety-one percent of respondents wanted to be told by their doctor about an EACD that could improve survival by an additional 4 to 6 months, with 51% prepared to pay for it. People were more willing to pay if the drug could improve quality of life (71%) or if there was no effective standard treatment (76%). Sixty-eight percent believed the government should pay. Cost would be a significant financial burden for 31% of those willing to pay. Those more likely to want to be informed were younger, employed, better-educated, or had higher income levels (P < .05). Responses did not vary with the person's personal experience of cancer. Of the 9% who did not wish to be informed, half of these were concerned about the information causing distress., Conclusion: The Australian general public wants to be informed about EACD as potential treatment options, even if they are not willing or readily able to pay for them.