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Purpose: Research has consistently demonstrated that psychological capital (PsyCap) is an important predictor of various employee outcomes. Despite this, there is a paucity of knowledge regarding antecedents of PsyCap and the boundary conditions that influence PsyCap relationships. This study aimed to address these gaps by investigating how ethical leadership (EL) influences employee PsyCap, and in turn, predicts a range of desirable and undesirable employee attitudes. Furthermore, the study examined the moderating role of length of the leader-follower relationship (LLR) and organisational identification in these relationships in a novel moderated-mediation model. Design/methodology/approach: Data were collected from 269 full-time employees in Australia via an online survey across two time-points. Findings: The results show that PsyCap mediates the relationship between EL and employee attitudes. The results also indicate that LLR moderates these relationships, whereby these relationships are strengthened as LLR increases. Originality/value: This study responds to calls for further investigation of antecedent and outcome variables related to PsyCap, as well as moderators of the relationships between PsyCap and antecedent and outcome variables. The findings also extend the application of social exchange theory to the context of EL and PsyCap. [ABSTRACT FROM AUTHOR]

Background and Objectives A multifaceted construct called occupational communion (OC), defined as a sense of belonging based on social interaction at work, has been proposed to understand why care workers were positively engaged in their jobs over time, even though they were very demanding. Rich qualitative data on the multiple aspects of OC in care work exist, but a valid measure does not. Research Design and Methods We applied a mixed-method systematic scale development process to measure OC. Aged and dementia care workers in Australia (76%) and other countries participated in a focus group and online surveys (N = 2,451). We also used interview data from our prior study. The study involved 3 components: (1) scale development and design; (2) pilot test validation with exploratory factor analysis; and (3) confirmatory validation via confirmatory factor analysis. The third component assessed convergent and discriminant validity using measures of communion, self-efficacy, work engagement, job and life satisfaction, intention to leave, positive and negative affect, and mood. Results We developed a 28-item Occupational Communion Scale (OCS) with good internal consistency (composite reliability = 0.75–0.91) across 6 factors: (1) "natural" carer, (2) psychological need to care, (3) connection with clients, (4) connection with coworkers, (5) desire for more connection, and (6) blurred boundaries. All validity measures correlated with OC and work engagement, self-efficacy, and positive affect showed the strongest association. Discussion and Implications The OCS can be used to design and evaluate interventions addressing aged care workforce engagement, social connections and well-being, and care outcomes. [ABSTRACT FROM AUTHOR]

This sub-study of the Australian Genomics Cardiovascular Genetic Disorders Flagship sought to conduct the first nation-wide audit in Australia to establish the current practices across cardiac genetics clinics. An audit of records of patients with a suspected genetic heart disease (cardiomyopathy, primary arrhythmia, autosomal dominant congenital heart disease) who had a cardiac genetics consultation between 1st January 2016 and 31 July 2018 and were offered a diagnostic genetic test. This audit included 536 records at multidisciplinary cardiac genetics clinics from 11 public tertiary hospitals across five Australian states. Most genetic consultations occurred in a clinic setting (90%), followed by inpatient (6%) and Telehealth (4%). Queensland had the highest proportion of Telehealth consultations (9% of state total). Sixty-six percent of patients had a clinical diagnosis of a cardiomyopathy, 28% a primary arrhythmia, and 0.7% congenital heart disease. The reason for diagnosis was most commonly as a result of investigations of symptoms (73%). Most patients were referred by a cardiologist (85%), followed by a general practitioner (9%) and most genetic tests were funded by the state Genetic Health Service (73%). Nationally, 29% of genetic tests identified a pathogenic or likely pathogenic gene variant; 32% of cardiomyopathies, 26% of primary arrhythmia syndromes, and 25% of congenital heart disease. We provide important information describing the current models of care for genetic heart diseases throughout Australia. These baseline data will inform the implementation and impact of whole genome sequencing in the Australian healthcare landscape. • We describe the current models of care for genetic heart diseases throughout Australia • Genetic testing identified a causative variant in 29% of cases • Data will inform the implementation and impact of whole genome sequencing in Australian healthcare [ABSTRACT FROM AUTHOR]

Background: It has previously been shown that there is a significant demographic variation in sexual health literacy (SHL) in university-level students in Tasmania, Australia.Aims: The aim of this study was to evaluate the effect of statistical adjustment for sexuality-related attitudes on this demographic variation in SHL.Methods: Iterated principal-factor analysis was used to evaluate latent variable grouping of responses to 21 attitudinal questions regarding sexuality and sexual behaviour. Linear regression was used to evaluate the distribution and determinants of attitudinal patterns and thence the relationship of these patterns to SHL.Results: Three patterns - conservative, anti-persons-living-with-HIV and sexually responsible - were identified as explaining variation in sexual attitudes; the former two being associated with significantly lower SHL and the latter associated with significantly higher SHL. Adjustment for these patterns significantly attenuated much of the differences in SHL by birthplace/ethnicity and religion, including among South and South-East Asian and Protestant, Islamic and Hindu students. However, some differences in SHL persisted, suggesting they are partly or fully independent of the attitudinal questions.Conclusions: As hypothesised, differences in attitude significantly explained much of the demographic differences in SHL found previously. These results suggest that sexual education and orientation efforts need to bear cultural framing in mind to enhance uptake by students. [ABSTRACT FROM AUTHOR]

Background For select women with early endometrial cancer, particularly nulliparous women, nonsurgical options may be considered. There is increasing experience using progestogens, but little is known about the long-term outcomes and safety of such treatment. Aims To present the cancer and pregnancy outcomes of women with greater than five years follow-up after progestogen treatment for early endometrial cancer. Methods Ten women who underwent greater than six months of continuous progestogen therapy for early endometrial cancer were included in the study. All were managed by a gynaecological oncologist at a major tertiary centre in Melbourne, Australia. The histology of each subsequent curette was recorded, as was the timing and histology of hysterectomy (if relevant), and the results of any subsequent pregnancies. Results All ten women showed histological regression of cancer with no cases of recurrence on follow-up curette. Four of ten women have undergone hysterectomy with one case of occult disease persistence in a woman noncompliant with therapy. The mean follow-up time was 89 months (range 62-142 months), there were no deaths and no woman was lost to follow-up. All four women attempting pregnancy were successful. There were eight pregnancies and five live births. Conclusions This form of treatment appears to be successful and safe in the long term with good pregnancy outcomes. However, it is not standard and should be supervised in a specialised gynaecological oncology unit. [ABSTRACT FROM AUTHOR]

Aims and objectives: Social and cultural factors are identified that impact on complementary therapy use among Australia-born and immigrant women diagnosed with gynaecological cancer. Methods: A qualitative study design including in-depth interviews with women diagnosed with gynaecological cancer (N=53) and participant observation was conducted. Results: Approximately one-third of women utilized complementary and alternative medicine, with this being determined by current health concerns and health beliefs related to the efficacy of different modalities. Four types of complementary therapy users emerged: consequential, therapeutic, informed and exploratory. Conclusion: There was a relatively low uptake of complementary treatments. Choice was influenced by women's socio-demographic background, clinical and personal history, lack of personal experiences of gynaecological cancer among study participants' kin and friends, and lack of popular alternative literature on such cancer. Copyright © 2005 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

To assess the clinical and economic impacts of the use of liquid based cytology (LBC) in the Australian average risk population from the perspective of the public health care budget. Concerns over the evaluation of medical technologies in Australia, which are assessed by the Medicare Services Advisory Committee (MSAC), have been raised recently. We report on the evaluation of LBC, which although being widely adopted in other parts of the world, has, despite substantial uptake in the private sector in Australia, been rejected for public funding by MSAC. We used the health economic model developed by MSAC, but populated the model with the best available international data, sourced from a published review article. The economic model considered the clinical benefits and the costs arising from a biennial cervical screening programme. Net costs divided by life years saved is the cost per life year saved and this is reported as the incremental cost effectiveness. Populating the MSAC model with data on test performance showed that one type of LBC (ThinPrep) ‘dominates’ the conventional Pap smear in the screening of average risk women in the Australian setting. The health economic model created by MSAC predicts that ThinPrep dominates the conventional Pap as a screening test for cervical cancer. An additional 2240 high-grade lesions could be detected, resulting in 480 life years gained and delivering an expected saving to the health care system of $5 536 000 per annum if liquid based cytology replaced the conventional Pap. [ABSTRACT FROM AUTHOR]

Drawing on in-depth interviews with patients and participant observation notes from a cancer support group and outpatients department, we analyse the experiences of Australian-born and immigrant women with gynaecological cancer to describe cancer diagnosis disclosures from the patients' perspectives and examine women's treatment decision-making. Data suggest that most women did not question the surgeon's recommendation and assumed a passive role in treatment decision-making. The contextual factors which impacted on this pattern were the unavailability of an alternative biomedical treatment path, the perception of the metropolitan hospital as a centre of clinical excellence with extensive experience in treating women with gynaecological cancer, and lay understandings of the nature of gynaecological cancer as 'a killer'. We also discuss the circumstances under which a few women took on the role of primary decision-maker. [ABSTRACT FROM AUTHOR]

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.)

Sharing genomic variant interpretations across laboratories promotes consistency in variant assertions. A landscape analysis of Australian clinical genetic-testing laboratories in 2017 identified that, despite the national-accreditation-body recommendations encouraging laboratories to submit genotypic data to clinical databases, fewer than 300 variants had been shared to the ClinVar public database. Consultations with Australian laboratories identified resource constraints limiting routine application of manual processes, consent issues, and differences in interpretation systems as barriers to sharing. This information was used to define key needs and solutions required to enable national sharing of variant interpretations. The Shariant platform, using both the GRCh37 and GRCh38 genome builds, was developed to enable ongoing sharing of variant interpretations and associated evidence between Australian clinical genetic-testing laboratories. Where possible, two-way automated sharing was implemented so that disruption to laboratory workflows would be minimized. Terms of use were developed through consultation and currently restrict access to Australian clinical genetic-testing laboratories. Shariant was designed to store and compare structured evidence, to promote and record resolution of inter-laboratory classification discrepancies, and to streamline the submission of variant assertions to ClinVar. As of December 2021, more than 14,000 largely prospectively curated variant records from 11 participating laboratories have been shared. Discrepant classifications have been identified for 11% (28/260) of variants submitted by more than one laboratory. We have demonstrated that co-design with clinical laboratories is vital to developing and implementing a national variant-interpretation sharing effort. This approach has improved inter-laboratory concordance and enabled opportunities to standardize interpretation practices., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Symptomatic methotrexate-related central neurotoxicity (MTX neurotoxicity) is a severe toxicity experienced during acute lymphoblastic leukemia (ALL) therapy with potential long-term neurologic complications. Risk factors and long-term outcomes require further study. We conducted a systematic, retrospective review of 1,251 consecutive Australian children enrolled on Berlin-Frankfurt-Münster or Children's Oncology Group-based protocols between 1998-2013. Clinical risk predictors for MTX neurotoxicity were analyzed using regression. A genome-wide association study (GWAS) was performed on 48 cases and 537 controls. The incidence of MTX neurotoxicity was 7.6% (n=95 of 1,251), at a median of 4 months from ALL diagnosis and 8 days after intravenous or intrathecal MTX. Grade 3 elevation of serum aspartate aminotransferase (P=0.005, odds ratio 2.31 [range, 1.28-4.16]) in induction/consolidation was associated with MTX neurotoxicity, after accounting for the only established risk factor, age ≥10 years. Cumulative incidence of CNS relapse was increased in children where intrathecal MTX was omitted following symptomatic MTX neurotoxicity (n=48) compared to where intrathecal MTX was continued throughout therapy (n=1,174) (P=0.047). Five-year central nervous system relapse-free survival was 89.2 4.6% when intrathecal MTX was ceased compared to 95.4 0.6% when intrathecal MTX was continued. Recurrence of MTX neurotoxicity was low (12.9%) for patients whose intrathecal MTX was continued after their first episode. The GWAS identified single-nucletide polymorphism associated with MTX neurotoxicity near genes regulating neuronal growth, neuronal differentiation and cytoskeletal organization (P<1x10-6). In conclusion, increased serum aspartate aminotransferase and age ≥10 years at diagnosis were independent risk factors for MTX neurotoxicity. Our data do not support cessation of intrathecal MTX after a first MTX neurotoxicity event.

Importance: Widespread adoption of rapid genomic testing in pediatric critical care requires robust clinical and laboratory pathways that provide equitable and consistent service across health care systems., Objective: To prospectively evaluate the performance of a multicenter network for ultra-rapid genomic diagnosis in a public health care system., Design, Setting, and Participants: Descriptive feasibility study of critically ill pediatric patients with suspected monogenic conditions treated at 12 Australian hospitals between March 2018 and February 2019, with data collected to May 2019. A formal implementation strategy emphasizing communication and feedback, standardized processes, coordination, distributed leadership, and collective learning was used to facilitate adoption., Exposures: Ultra-rapid exome sequencing., Main Outcomes and Measures: The primary outcome was time from sample receipt to ultra-rapid exome sequencing report. The secondary outcomes were the molecular diagnostic yield, the change in clinical management after the ultra-rapid exome sequencing report, the time from hospital admission to the laboratory report, and the proportion of laboratory reports returned prior to death or hospital discharge., Results: The study population included 108 patients with a median age of 28 days (range, 0 days to 17 years); 34% were female; and 57% were from neonatal intensive care units, 33% were from pediatric intensive care units, and 9% were from other hospital wards. The mean time from sample receipt to ultra-rapid exome sequencing report was 3.3 days (95% CI, 3.2-3.5 days) and the median time was 3 days (range, 2-7 days). The mean time from hospital admission to ultra-rapid exome sequencing report was 17.5 days (95% CI, 14.6-21.1 days) and 93 reports (86%) were issued prior to death or hospital discharge. A molecular diagnosis was established in 55 patients (51%). Eleven diagnoses (20%) resulted from using the following approaches to augment standard exome sequencing analysis: mitochondrial genome sequencing analysis, exome sequencing-based copy number analysis, use of international databases to identify novel gene-disease associations, and additional phenotyping and RNA analysis. In 42 of 55 patients (76%) with a molecular diagnosis and 6 of 53 patients (11%) without a molecular diagnosis, the ultra-rapid exome sequencing result was considered as having influenced clinical management. Targeted treatments were initiated in 12 patients (11%), treatment was redirected toward palliative care in 14 patients (13%), and surveillance for specific complications was initiated in 19 patients (18%)., Conclusions and Relevance: This study suggests feasibility of ultra-rapid genomic testing in critically ill pediatric patients with suspected monogenic conditions in the Australian public health care system. However, further research is needed to understand the clinical value of such testing, and the generalizability of the findings to other health care settings.

Background: Adenocarcinoma in situ of cervix is increasingly managed by local excision rather than hysterectomy and this study will ascertain if conservative management by excision alone is adequate., Aims: To evaluate the long-term outcomes of conservative management of adenocarcinoma in situ of cervix, particularly in relation to excisional margin status., Materials and Methods: Retrospective analysis of women diagnosed with adenocarcinoma in situ and their management between 1992 and 2010 retrieved from the Victorian Cervical Cytology Registry, Australia. Failure of conservative treatment is defined by histologically proven adenocarcinoma in situ or adenocarcinoma at follow-up after negative excisional margins., Results: adenocarcinoma in situ of the cervix was managed primarily with cold knife cone biopsy or loop electrosurgical excision of the cervix. Most excisions were in one piece (83.4%) with average depth of 16.1 mm and 21.9% had involved excisional margins. Women with adenocarcinoma in situ on any excisional margin were more likely to have residual or recurrent disease (28.7%) compared with negative excisional margins (4.3%). Residual adenocarcinoma in situ was twice as common if adenocarcinoma in situ was present at endocervical (29.6%) and stromal (23.1%) margins compared with an ectocervical margin (13.6%). Cancer incidence at follow-up was 2.3% for women with positive excisional margins compared to 1.3% with negative margins., Conclusions: Women with adenocarcinoma in situ of cervix can be managed with local excisional procedures, best in single pieces to provide the important information on excisional margins. Adenocarcinoma in situ at endocervical and stromal excisional margins needs re-excision or where appropriate, hysterectomy, while negative excisional margins have a low rate of recurrence and can be followed up with test of cure., (© 2019 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Study Aims: The My Kite Will Fly (MKWF) research program is built on the well-documented need for effective clinical communication tools and therapeutic interventions where a child's mother is diagnosed with life-threatening gynecological cancer., Methods: The Dignity Model and Child-Centered approach were two key study foundations in this pilot cohort. Quantitative survey and qualitative semistructured methods were employed to gather data from patient families at three distinct phases: Diagnosis, Treatment, and Palliative care. Participants were identified from patient groups at The Royal Women's Hospital and Peter MacCallum Cancer Center, Melbourne, Australia. A purposive sample (n = 36 children) (24 girls and 12 boys aged between 3 and 12 years) drawn from 19 families completed structured art therapy workbook activities. The principal researcher and a specialist educational assistant undertook cross-case thematic analysis of all interviews and children's drawings., Results: Five central themes were profiled in six illustrative case studies. Interviews with all families (n = 19) showed 86.1% positive evaluation of the MKWF workbook template at diagnosis. During treatments, 66.6% of parents reported better understanding of the chemotherapy process and better communication with younger family members. At palliative care, 97.3% of families reported stabilization of family routines and improved illness coping. Exit interviews with six children and surviving parents (n = 4) showed that the program substantially prepared them for parental bereavement., Conclusions: Results from this pilot cohort confirm the importance of enhanced parent-child communication and stabilized family routines. Current results provide an important platform for future evaluative research among larger patient-family populations across multisite oncology settings.

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.)

Background: To investigate whether variations in primary chemotherapy were associated with survival in a nationally complete cohort of Australian women with epithelial ovarian cancer (EOC)., Material and Methods: All 1192 women diagnosed with invasive EOC in Australia in 2005 were identified through state-based cancer registries. Medical record information including details of primary chemotherapy treatment was obtained and survival data updated in 2012. Those started on standard chemotherapy (carboplatin and paclitaxel given at three-weekly intervals) after primary cytoreductive surgery were included (n = 351) and the relative dose intensity (RDI) was calculated. Time interval between surgery and start of chemotherapy was analysed in weeks. Hazard ratios [HR, 95% confidence interval (CI)] were calculated using multivariable Cox proportional hazards models., Results: Compared to women with RDI of 91-100%, those with RDI of ≤ 70% had significantly poor survival (HRadj = 1.62, 95% CI 1.05-2.49). This association was stronger among women with advanced (FIGO stage III/IV) disease at diagnosis (HRadj = 1.90, 95% CI 1.22-2.96). The interval between primary surgery and chemotherapy was not related to survival (HRadj = 0.98, 95% CI 0.93-1.03 for every week of delay), at least up to a period of five weeks., Conclusion: Our results suggest that RDI of 70% or less was associated with poorer survival, particularly in women with advanced stage EOC. In contrast, the interval duration between primary surgery and chemotherapy was not related to survival, irrespective of disease stage or residual disease. These results provide some reassurance that, at least up until five weeks post-surgery, timing of chemotherapy commencement has a negligible effect on survival.

Background: The ICON7 trial previously reported improved progression-free survival in women with ovarian cancer with the addition of bevacizumab to standard chemotherapy, with the greatest effect in patients at high risk of disease progression. We report the final overall survival results of the trial., Methods: ICON7 was an international, phase 3, open-label, randomised trial undertaken at 263 centres in 11 countries across Europe, Canada, Australia and New Zealand. Eligible adult women with newly diagnosed ovarian cancer that was either high-risk early-stage disease (International Federation of Gynecology and Obstetrics [FIGO] stage I-IIa, grade 3 or clear cell histology) or more advanced disease (FIGO stage IIb-IV), with an Eastern Cooperative Oncology Group performance status of 0-2, were enrolled and randomly assigned in a 1:1 ratio to standard chemotherapy (six 3-weekly cycles of intravenous carboplatin [AUC 5 or 6] and paclitaxel 175 mg/m(2) of body surface area) or the same chemotherapy regimen plus bevacizumab 7·5 mg per kg bodyweight intravenously every 3 weeks, given concurrently and continued with up to 12 further 3-weekly cycles of maintenance therapy. Randomisation was done by a minimisation algorithm stratified by FIGO stage, residual disease, interval between surgery and chemotherapy, and Gynecologic Cancer InterGroup group. The primary endpoint was progression-free survival; the study was also powered to detect a difference in overall survival. Analysis was by intention to treat. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN91273375., Findings: Between Dec 18, 2006, and Feb 16, 2009, 1528 women were enrolled and randomly assigned to receive chemotherapy (n=764) or chemotherapy plus bevacizumab (n=764). Median follow-up at the end of the trial on March 31, 2013, was 48·9 months (IQR 26·6-56·2), at which point 714 patients had died (352 in the chemotherapy group and 362 in the bevacizumab group). Our results showed evidence of non-proportional hazards, so we used the difference in restricted mean survival time as the primary estimate of effect. No overall survival benefit of bevacizumab was recorded (restricted mean survival time 44·6 months [95% CI 43·2-45·9] in the standard chemotherapy group vs 45·5 months [44·2-46·7] in the bevacizumab group; log-rank p=0·85). In an exploratory analysis of a predefined subgroup of 502 patients with poor prognosis disease, 332 (66%) died (174 in the standard chemotherapy group and 158 in the bevacizumab group), and a significant difference in overall survival was noted between women who received bevacizumab plus chemotherapy and those who received chemotherapy alone (restricted mean survival time 34·5 months [95% CI 32·0-37·0] with standard chemotherapy vs 39·3 months [37·0-41·7] with bevacizumab; log-rank p=0·03). However, in non-high-risk patients, the restricted mean survival time did not differ significantly between the two treatment groups (49·7 months [95% CI 48·3-51·1]) in the standard chemotherapy group vs 48·4 months [47·0-49·9] in the bevacizumab group; p=0·20). An updated analysis of progression-free survival showed no difference between treatment groups. During extended follow-up, one further treatment-related grade 3 event (gastrointestinal fistula in a bevacizumab-treated patient), three grade 2 treatment-related events (cardiac failure, sarcoidosis, and foot fracture, all in bevacizumab-treated patients), and one grade 1 treatment-related event (vaginal haemorrhage, in a patient treated with standard chemotherapy) were reported., Interpretation: Bevacizumab, added to platinum-based chemotherapy, did not increase overall survival in the study population as a whole. However, an overall survival benefit was recorded in poor-prognosis patients, which is concordant with the progression-free survival results from ICON7 and GOG-218, and provides further evidence towards the optimum use of bevacizumab in the treatment of ovarian cancer., Funding: The National Institute for Health Research through the UK National Cancer Research Network, the Medical Research Council, and Roche., (Copyright © 2015 Oza et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Few studies have assessed the risk and impact of lymphedema among women treated for endometrial cancer. We aimed to quantify cumulative incidence of, and risk factors for developing lymphedema following treatment for endometrial cancer and estimate absolute risk for individuals. Further, we report unmet needs for help with lymphedema-specific issues., Methods: Women treated for endometrial cancer (n = 1243) were followed-up 3-5 years after diagnosis; a subset of 643 completed a follow-up survey that asked about lymphedema and lymphedema-related support needs. We identified a diagnosis of secondary lymphedema from medical records or self-report. Multivariable logistic regression was used to evaluate risk factors and estimates., Results: Overall, 13% of women developed lymphedema. Risk varied markedly with the number of lymph nodes removed and, to a lesser extent, receipt of adjuvant radiation or chemotherapy treatment, and use of nonsteroidal anti-inflammatory drugs (pre-diagnosis). The absolute risk of developing lymphedema was >50% for women with 15+ nodes removed and 2-3 additional risk factors, 30-41% for those with 15+ nodes removed plus 0-1 risk factors or 6-14 nodes removed plus 3 risk factors, but ≤ 8% for women with no nodes removed or 1-5 nodes but no additional risk factors. Over half (55%) of those who developed lymphedema reported unmet need(s), particularly with lymphedema-related costs and pain., Conclusion: Lymphedema is common; experienced by one in eight women following endometrial cancer. Women who have undergone lymphadenectomy have very high risks of lymphedema and should be informed how to self-monitor for symptoms. Affected women need greater levels of support., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: To describe survival patterns in a nationally complete cohort of Australian women with epithelial ovarian cancer, by sociodemographic and clinical factors., Design, Setting and Participants: All 1192 women diagnosed with invasive epithelial ovarian cancer in 2005 were identified through state-based cancer registries. We obtained detailed information from their medical records in 2009 and updated survival data in 2012., Main Outcome Measures: Crude 3-year, 5-year and 7-year survival rates; 3-year and 5-year conditional survival; and hazard ratios (HRs) for the association of participant and cancer characteristics with survival, from multivariable Cox proportional hazards models., Results: Overall crude 5-year survival was 35% (95% CI, 33%-38%). Conditional survival increased moderately for women who lived beyond a year from diagnosis, although for women alive 2 years after diagnosis, the probability of surviving a further 5 years was still only 53% (95% CI, 49%-57%). Increasing age and disease stage were most strongly associated with poor survival. After adjusting for these, survival was significantly worse for women with carcinosarcomas (HRadj, 2.1 [95% CI, 1.3-3.2]), clear cell (HRadj, 1.7 [95% CI, 1.2-2.3]) and mucinous (HRadj, 2.6 [95% CI, 1.6-4.0]) cancers than for women with serous cancers. Presence of ascites at diagnosis (HRadj, 1.5 [95% CI, 1.3-1.8]), Charlson comorbidity score ≥ 3 (HRadj, 1.5 [95% CI, 1.1-2.1]), relative socioeconomic disadvantage (HRadj, 1.2 [95% CI, 1.1-1.4]) and regional-remote residence (HRadj, 1.2 [95% CI, 1.0-1.4]) were also associated with poorer survival., Conclusions: Along with expected adverse effects of age and stage, we found survival differences by histological subtype, presence of ascites and comorbidities. Whether geographic and socioeconomic differences relate to treatment access or other factors warrants further investigation. Conditional survival estimates confirm the ongoing poor long-term prognosis for women with ovarian cancer, reinforcing the need for prevention and better treatments.

Objective: The aim of this study was to establish a reference 24-hour urine human chorionic gonadotropin (hCG) regression curve in patients with complete hydatidiform mole (CHM) as diagnostic tool in the prediction of persistent trophoblastic disease (PTD)., Methods: From 2004 to 2011, 312 cases suitable for this study were registered at the Hydatidiform Mole Registry of the Royal Women's Hospital Melbourne, Australia. hCG levels of 61 patients diagnosed as having PTD according to FIGO 2000 criteria were compared with the 95th-percentile (p95) of the normal regression curve derived from hCG levels of 251 cases of uneventful CHM., Results: In the test group of 61 patients PTD was diagnosed by FIGO 2000 criteria after a mean (±SD, min.-max.) of 7.6 (±3.4, 3.0-16.7) weeks after evacuation of the mole while in the same group hCG values for the first time exceeded the upper limit of the 95th percentile significantly earlier after 4.5 (±1.9, 2.0-9.9) weeks (P<0.001). However, hCG levels of 14% of the cases of uneventful CHM at least once exceeded the upper limit of p95, showing that one single value above p95 is not accurate enough for the diagnosis of PTD., Conclusions: The normal 24-hour urine hCG regression curve may be used as a tool in the follow-up of an individual case of CHM after evacuation. At least one hCG level exceeding the upper limit of p95 within 11weeks after evacuation could be added to the current FIGO criteria, in order to diagnose PTD early, but the lack of it may also prevent unnecessary treatment., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: To quantitatively assess and compare the quality of life (QoL) of women with a self-reported diagnosis of lower limb lymphedema (LLL), to women with lower limb swelling (LLS), and to women without LLL or LLS following treatment for endometrial cancer., Methods: 1399 participants in the Australian National Endometrial Cancer Study were sent a follow-up questionnaire 3-5 years after diagnosis. Women were asked if they had experienced swelling in the lower limbs and, if so, whether they had received a diagnosis of lymphedema by a health professional. The 639 women who responded were categorized as: Women with LLL (n=68), women with LLS (n=177) and women without LLL or LLS (n=394). Multivariable-adjusted generalized linear models were used to compare women's physical and mental QoL by LLL status., Results: On average, women were 65 years of age and 4 years after diagnosis. Women with LLL had clinically lower physical QoL (M=41.8, SE=1.4) than women without LLL or LLS (M=45.1, SE=0.8, p=.07), however, their mental QoL was within the normative range (M=49.6; SE=1.1 p=1.0). Women with LLS had significantly lower physical (M=41.0, SE=1.0, p=.003) and mental QoL (M=46.8; SE=0.8, p<.0001) than women without LLL or LLS (Mental QoL: M=50.6, SE=0.8)., Conclusion: Although LLL was associated with reductions in physical QoL, LLS was related to reductions in both physical and mental QoL 3-5 years after cancer treatment. Early referral to evidence-based lymphedema programs may prevent long-term impairments to women's QoL., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Importance: Lentigo maligna (LM) is a clinical, pathologic, and therapeutic challenge with a higher risk of local recurrence than other types of melanoma correctly treated and also carries the cosmetically sensitive localization of head and neck., Objective: To determine whether in vivo reflectance confocal microscopy (RCM) mapping of difficult LM cases might alter patient care and management., Design: Analysis of LM and LM melanoma (LMM) in a series of patients with large facial lesions requiring complex reconstructive surgery and/or recurrent or poorly delineated lesions at any body sites were investigated., Settings: Two tertiary referral melanoma centers in Sydney, Australia., Participants: Thirty-seven patients with LM (including 5 with LMM) were mapped with RCM. Fifteen patients had a recurrent LM, including 9 with multiple prior recurrences. The LM was classified amelanotic in 10 patients, lightly pigmented in 9, and partially pigmented in 18., Interventions: The RCM images were obtained in 4 radial directions (allowing for anatomic barriers) for LM margin delineation using an RCM LM score previously described by our research team., Main Outcome Measures: Differences in the margin of LM as determined by RCM vs dermoscopy vs histopathologic analysis., Results: Seventeen of 29 patients (59%) with dermoscopically visible lesions had subclinical (RCM-identified) disease evident more than 5 mm beyond the dermoscopy margin (ie, beyond the excision margin recommended in published guidelines). The RCM mapping changed the management in 27 patients (73%): 11 patients had a major change in their surgical procedure, and 16 were offered radiotherapy or imiquimod treatment as a consequence of the RCM findings. Treatment was surgical in 17 of 37 patients. Surgical excision margins (based on the RCM mapping) were histopathologically involved in only 2 patients, each of whom had an LM lesion larger than 6 cm., Conclusions and Relevance: In vivo RCM can provide valuable information facilitating optimal patient care management.

Introduction: Malignant transformation in an ovarian dermoid cyst occurs in 1% to 2% of cases. Our knowledge about this tumor type is limited and largely based on case reports. We aimed to collate and analyze the cumulative experience of how these patients have been managed in an effort to identify the most appropriate treatment strategies., Methods: A survey was sent to the members of the Gynaecologic Cancer Intergroup. Data collected included age, symptoms, stage, extent of surgery, chemotherapy and radiotherapy details, response to treatment, progression, survival, and salvage therapy., Results: Data on 33 patients whose conditions were diagnosed between 1979 and 2007 were received from 10 centers in Australia, Canada, Germany, and Austria. The mean age was 49 years. All 15 patients with stage I disease and most of the patients with stages II and III were optimally debulked. Four patients with stage I disease had fertility-sparing surgery with good outcomes. Chemotherapy was not routinely given after surgery and did not seem to be effective. Platinum-based regimens were most commonly used. At relapse, 2 patients had a sustained remission after secondary surgery for relapsed disease. Second-line chemotherapy and radiotherapy were infrequently prescribed. Patients with stage I disease had a good outcome, with all but 2 alive and well at a minimum of 12 months of follow-up., Conclusions: Most patients undergo optimal debulking surgery. Fertility-sparing surgery may be a reasonable option in selected patients. Stage I patients have a good prognosis. There is no standard adjuvant treatment, but platinum-based regimens are most commonly used. However, regardless of treatment received, patients with advanced disease do poorly.

Background: Cervical cancer and its precursors still remain an important cause of morbidity and mortality despite adequate screening programs. It is now established practice in Australia that a Pap smear without an endocervical component, which is otherwise negative, does not warrant an earlier repeat smear. This study aims to determine if the lack of an endocervical component in women with previously treated high-grade abnormalities of the cervix increases the risk of subsequent cytological abnormalities., Method: Data were retrieved from an electronic database in the Oncology and Dysplasia Unit at The Royal Women's Hospital in Melbourne, Australia. Women who underwent treatment for high-grade cervical abnormalities from 2000-2004 were included in the study. Women with negative cytology immediately after their operations were first identified, and the incidence of subsequent cytological abnormalities was calculated and then separated according to their endocervical status., Results: Of the 1260 women in the study population, seven developed high-grade abnormalities (six with an endocervical component and one without) and 107 developed low-grade abnormalities (98 with an endocervical component and nine without)., Conclusion: The lack of an endocervical component was not statistically significantly associated with a higher incidence of either high-grade or low-grade abnormalities. Therefore, women who have had previous treatments for high-grade abnormalities do not need to have earlier repeat smears or intervention if the cytology lacks an endocervical component.

Carcinoma of the cervix and its precursor, high-grade cervical intraepithelial neoplasia (CIN2/3), are associated with persistent oncogenic Human papillomavirus (HPV) infection, particularly HPV 16 and 18. HPV genotype distribution varies with severity of cervical disease, patient demographics such as age, as well as geographical location. In this study, HPV genotype prevalence was determined, using the Roche Linear Array genotyping test, among a cohort of 1,676 women being managed with ablative or excisional treatment following colposcopically directed biopsies, who were referred initially due to cytological abnormalities. HPV genotype prevalence, including presence of single and multiple infections was assessed against both histological diagnosis and age. Overall, 83.9% of women were identified as HPV positive, comprising of 32.2% single and 51.7% multiple HPV infections. Of those with an available histological diagnosis at time-of-treatment (n = 899), HPV positivity increased significantly with disease severity: 62.4% (normal), 77.6% (CIN1), 92.6% (CIN2), and 97.9% (> or =CIN3) (P < 0.006). Similarly, a significant increase in high-risk (HR) HPV detection was observed with severity of disease (P < 0.005). The five most prevalent genotypes were HPV 16 (35.1%), 31 (12.6%), 51 (11.1%), 52 (9.9%), and 18 (8.5%). HPV 16 was the only genotype to demonstrate a significant increase in prevalence with increasing severity of histological or cytological disease (P < 0.0001). Multiple HPV infections, including multiple HR-HPV infections, declined significantly with age (P < 0.02). These findings provide the largest dataset of HPV genotype prevalence rates within Australian women, though are not representative of the general population., (Copyright 2009 Wiley-Liss, Inc.)

Objective: Human chorionic gonadotrophin (hCG) follow-up data were analysed retrospectively in all patients registered in the Hydatidiform Mole Registry at the Royal Women's Hospital, Melbourne from January 1992 to January 2001 to determine the risk of persistent trophoblast disease following partial molar pregnancy and to review the present follow-up protocol of patients suffering from partial hydatidiform molar pregnancy (PHM)., Methods: Demographic factors were determined for all 344 cases with a review diagnosis of PHM, included age, history of previous hydatidiform mole, gestation length, hCG levels and compliance with follow-up., Findings: Six of the 344 patients diagnosed with PHM required treatment with single-agent methotrexate and folinic acid rescue. All six patients achieved and maintained a complete biochemical remission after chemotherapy. hCG regression assays were analysed for 235 patients: 225 patients had at least one normal hCG measurement during follow-up, of whom 152 (64.7%) patients obtained normal values within 2 months after evacuation. All patients obtained normal levels within 32 weeks after evacuation of the partial hydatidiform mole. Only 63 (25.6%) patients completed the recommended follow-up program. No patient who achieved normal hCG levels required chemotherapy because of a recurrent gestational trophoblastic tumour., Recommendations: This study indicates that 1.7% of all partial mole pregnancy patients needed treatment for malignant sequelae. In contrast, no patient diagnosed with partial mole had a biochemical or clinical relapse after achieving normal levels of hCG, consistent with previous studies. Patients who have had a partial hydatidiform mole should be followed by hCG assays until normal levels are achieved and then follow-up can be safely discontinued.

This qualitative study investigated women's participation in decisions regarding treatment of gynaecological cancer. Thirty women, receiving health care in two tertiary hospitals in Australia, were interviewed face-to-face. For women with gynaecological cancer, the most influential factors in treatment decisions are still the surgeon's recommendation and fear of dying from cancer.

The detection and successful treatment of cancers is dependent on timely presentation with abnormal and often subtle symptoms. In this article, we draw on research conducted with Australian immigrant women in 2001-02 who experienced delays in diagnosis of gynecological cancer. Data from in-depth interviews with women with gynecological cancer indicated a common trajectory of an "illness career" whereby the search for diagnosis was often painful and lengthy, either because women normalized the abnormal signs or because their experiences of bodily abnormality, pain, and dysfunction contrasted with medical explanations. This delay was sometimes exacerbated by structural barriers. As a result, diagnosis was often protracted, during which time women presented with symptoms that were dismissed or resulted in the misdiagnosis, with a resultant loss of confidence in clinical services.