ORCID Profile
0000-0002-3087-2788
Current Organisation
University of Adelaide
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Publisher: Elsevier BV
Date: 07-2018
DOI: 10.1016/J.YGYNO.2018.04.006
Abstract: Although endometrial cancer (EC) is associated with relatively good survival rates overall, women diagnosed with high-risk subtypes have poor outcomes. We examined the relationship between lifestyle factors and subsequent all-cause, cancer-specific and non-cancer related survival. In a cohort of 1359 Australian women diagnosed with incident EC between 2005 and 2007 pre-diagnostic information was collected by interview at recruitment. Clinical and survival information was abstracted from women's medical records, supplemented by linkage to the Australian National Death Index. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific survival (EC death vs. non-EC death) associated with each exposure, overall and by risk group (low-grade endometrioid vs. high-grade endometrioid and non-endometrioid). After a median follow-up of 7.1 years, 179 (13%) women had died, with 123 (69%) deaths from EC. As expected, elevated body mass index (BMI), diabetes and the presence of other co-morbidities were associated with a significantly increased risk of all-cause and non-cancer related death. Women with diabetes had higher cancer-specific mortality rates (HR 2.09, 95% CI 1.31-3.35), particularly those who had were not obese (HR 4.13, 95% CI 2.20-7.76). The presence of ≥2 other co-morbidities (excluding diabetes) was also associated with increased risk of cancer-specific mortality (HR 3.09, 95% CI 1.21-7.89). The patterns were generally similar for women with low-grade and high-grade endometrioid/non-endometrioid EC. Our findings demonstrate the importance of diabetes, other co-morbidities and obesity as negative predictors of mortality among women with EC but that the risks differ for cancer-specific and non-cancer related mortality.
Publisher: Informa UK Limited
Date: 31-07-2016
Publisher: Informa UK Limited
Date: 06-06-2007
Publisher: Informa UK Limited
Date: 29-07-2016
Publisher: Routledge
Date: 17-04-2021
Publisher: Informa UK Limited
Date: 19-05-2011
Publisher: Oxford University Press (OUP)
Date: 02-05-2012
DOI: 10.1093/IRAP/LCS007
Publisher: Informa UK Limited
Date: 03-2010
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2015
Publisher: Routledge
Date: 12-12-2016
Publisher: Informa UK Limited
Date: 03-1999
Publisher: Routledge
Date: 27-09-2006
Publisher: Informa UK Limited
Date: 02-2005
Publisher: Informa UK Limited
Date: 07-2002
Publisher: Springer Science and Business Media LLC
Date: 03-2000
Publisher: Wiley
Date: 04-2002
Publisher: Informa UK Limited
Date: 10-11-2022
Publisher: University of California Press
Date: 10-1997
DOI: 10.2307/2645614
Publisher: Informa UK Limited
Date: 03-2001
Publisher: American Association for Cancer Research (AACR)
Date: 14-12-2014
DOI: 10.1158/1078-0432.CCR-14-1292
Abstract: Purpose: Low-grade serous ovarian carcinomas (LGSC) are Ras pathway-mutated, TP53 wild-type, and frequently associated with borderline tumors. Patients with LGSCs respond poorly to platinum-based chemotherapy and may benefit from pathway-targeted agents. High-grade serous carcinomas (HGSC) are TP53-mutated and are thought to be rarely associated with borderline tumors. We sought to determine whether borderline histology associated with grade 2 or 3 carcinoma was an indicator of Ras mutation, and we explored the molecular relationship between coexisting invasive and borderline histologies. Experimental Design: We reviewed & ,200 patients and identified 102 serous carcinomas with adjacent borderline regions for analyses, including candidate mutation screening, copy number, and gene expression profiling. Results: We found a similar frequency of low, moderate, and high-grade carcinomas with coexisting borderline histology. BRAF/KRAS alterations were common in LGSC however, we also found recurrent NRAS mutations. Whereas borderline tumors harbored BRAF/KRAS mutations, NRAS mutations were restricted to carcinomas, representing the first ex le of a Ras oncogene with an obligatory association with invasive serous cancer. Coexisting borderline and invasive components showed nearly identical genomic profiles. Grade 2 cases with coexisting borderline included tumors with molecular features of LGSC, whereas others were typical of HGSC. However, all grade 3 carcinomas with coexisting borderline histology were molecularly indistinguishable from typical HGSC. Conclusion: Our findings suggest that NRAS is an oncogenic driver in serous ovarian tumors. We demonstrate that borderline histology is an unreliable predictor of Ras pathway aberration and underscore an important role for molecular classification in identifying patients that may benefit from targeted agents. Clin Cancer Res 20(24) 6618–30. ©2014 AACR.
Publisher: Springer Science and Business Media LLC
Date: 10-08-2014
DOI: 10.1038/S41467-019-11862-X
Abstract: Mucinous ovarian carcinoma (MOC) is a unique subtype of ovarian cancer with an uncertain etiology, including whether it genuinely arises at the ovary or is metastatic disease from other organs. In addition, the molecular drivers of invasive progression, high-grade and metastatic disease are poorly defined. We perform genetic analysis of MOC across all histological grades, including benign and borderline mucinous ovarian tumors, and compare these to tumors from other potential extra-ovarian sites of origin. Here we show that MOC is distinct from tumors from other sites and supports a progressive model of evolution from borderline precursors to high-grade invasive MOC. Key drivers of progression identified are TP53 mutation and copy number aberrations, including a notable licon on 9p13. High copy number aberration burden is associated with worse prognosis in MOC. Our data conclusively demonstrate that MOC arise from benign and borderline precursors at the ovary and are not extra-ovarian metastases.
Publisher: Elsevier BV
Date: 2015
DOI: 10.1016/J.YGYNO.2014.11.006
Abstract: 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 in iduals. Further, we report unmet needs for help with lymphedema-specific issues. 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. 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. 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.
Publisher: Informa UK Limited
Date: 09-2004
Publisher: Elsevier BV
Date: 05-2014
DOI: 10.1016/J.YGYNO.2014.03.003
Abstract: 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. 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. 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). 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.
Publisher: Informa UK Limited
Date: 17-12-2014
Publisher: Routledge
Date: 07-08-2007
Publisher: Wiley
Date: 26-10-2008
DOI: 10.1002/IJC.23017
Abstract: Chronic inflammation has been proposed as the possible causal mechanism that explains the observed association between certain risk factors, such as the use of talcum powder (talc) in the pelvic region and epithelial ovarian cancer. To address this issue we evaluated the potential role of chronic local ovarian inflammation in the development of the major subtypes of epithelial ovarian cancer. Factors potentially linked to ovarian inflammation were examined in an Australia-wide case-control study comprising 1,576 women with invasive and low malignant potential (LMP) ovarian tumours and 1,509 population-based controls. We confirmed a statistically significant increase in ovarian cancer risk associated with use of talc in the pelvic region (adjusted odds ratio 1.17, 95% CI: 1.01-1.36) that was strongest for the serous and endometrioid subtypes although the latter was not statistically significant (adjusted odds ratios 1.21, 95% CI 1.03-1.44 and 1.18, 95% CI 0.81-1.70, respectively). Other factors potentially associated with ovarian inflammation (pelvic inflammatory disease, human papilloma virus infection and mumps) were not associated with risk but, like others, we found an increased risk of endometrioid and clear cell ovarian cancer only among women with a history of endometriosis. Regular use of aspirin and other nonsteroidal anti-inflammatory drugs was inversely associated with risk of LMP mucinous ovarian tumours only. We conclude that on balance chronic inflammation does not play a major role in the development of ovarian cancer.
Publisher: American Medical Association (AMA)
Date: 28-03-2017
Abstract: Standard treatment for endometrial cancer involves removal of the uterus, tubes, ovaries, and lymph nodes. Few randomized trials have compared disease-free survival outcomes for surgical approaches. To investigate whether total laparoscopic hysterectomy (TLH) is equivalent to total abdominal hysterectomy (TAH) in women with treatment-naive endometrial cancer. The Laparoscopic Approach to Cancer of the Endometrium (LACE) trial was a multinational, randomized equivalence trial conducted between October 7, 2005, and June 30, 2010, in which 27 surgeons from 20 tertiary gynecological cancer centers in Australia, New Zealand, and Hong Kong randomized 760 women with stage I endometrioid endometrial cancer to either TLH or TAH. Follow-up ended on March 3, 2016. Patients were randomly assigned to undergo TAH (n = 353) or TLH (n = 407). The primary outcome was disease-free survival, which was measured as the interval between surgery and the date of first recurrence, including disease progression or the development of a new primary cancer or death assessed at 4.5 years after randomization. The prespecified equivalence margin was 7% or less. Secondary outcomes included recurrence of endometrial cancer and overall survival. Patients were followed up for a median of 4.5 years. Of 760 patients who were randomized (mean age, 63 years), 679 (89%) completed the trial. At 4.5 years of follow-up, disease-free survival was 81.3% in the TAH group and 81.6% in the TLH group. The disease-free survival rate difference was 0.3% (favoring TLH 95% CI, -5.5% to 6.1% P = .007), meeting criteria for equivalence. There was no statistically significant between-group difference in recurrence of endometrial cancer (28/353 in TAH group [7.9%] vs 33/407 in TLH group [8.1%] risk difference, 0.2% [95% CI, -3.7% to 4.0%] P = .93) or in overall survival (24/353 in TAH group [6.8%] vs 30/407 in TLH group [7.4%] risk difference, 0.6% [95% CI, -3.0% to 4.2%] P = .76). Among women with stage I endometrial cancer, the use of total abdominal hysterectomy compared with total laparoscopic hysterectomy resulted in equivalent disease-free survival at 4.5 years and no difference in overall survival. These findings support the use of laparoscopic hysterectomy for women with stage I endometrial cancer. clinicaltrials.gov Identifier: NCT00096408 Australian New Zealand Clinical Trials Registry: CTRN12606000261516.
Publisher: AMPCo
Date: 09-2014
DOI: 10.5694/MJA14.00132
Abstract: To describe survival patterns in a nationally complete cohort of Australian women with epithelial ovarian cancer, by sociodemographic and clinical factors. 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. 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. 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. 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.
Publisher: Cambridge University Press (CUP)
Date: 09-2004
DOI: 10.1017/S030574100400058X
Abstract: Since 1989, Taipei has attempted to capitalize on the systemic changes in East Central Europe. It achieved its goal of winning diplomatic allies among the post-communist states only in 1999, when Macedonia recognized the Republic of China (ROC) hoping that Taipei's generosity would resolve its economic problems. In order to showcase the effectiveness of its assistance, Taipei resorted to economic diplomacy and offered Skopje loans, humanitarian and technical assistance. Yet, the Macedonian–Taiwanese partnership ended in 2001. This report will argue that Taipei failed to become a viable alternative to the People's Republic of China (PRC) as Skopje's economic and diplomatic partner because of China's clout in international affairs and its own reluctance to shower Macedonia with developmental assistance. Instead of showcasing Taiwan's ability to maintain a diplomatic ally through a pro-active economic foreign policy, the failed Macedonian project underlined the limited effectiveness of the ROC's economic diplomacy and the perennial problem of the ROC diplomacy: a successful international isolation by the PRC.
Publisher: Pacific Affairs
Date: 12-2012
DOI: 10.5509/2012854701
Publisher: Oxford University Press (OUP)
Date: 05-2017
DOI: 10.1093/FPA/ORW022
Publisher: Elsevier BV
Date: 11-2017
DOI: 10.1016/J.YGYNO.2017.08.011
Abstract: To determine endometrial cancer (EC) risk according to family cancer history, including assessment by degree of relatedness, type of and age at cancer diagnosis of relatives. Self-reported family cancer history was available for 1353 EC patients and 628 controls. Logistic regression was used to quantify the association between EC and cancer diagnosis in ≥1 first or second degree relative, and to assess whether level of risk differed by degree of relationship and/or relative's age at diagnosis. Risk was also evaluated for family history of up to three cancers from known familial syndromes (Lynch, Cowden, hereditary breast and ovarian cancer) overall, by histological subtype and, for a subset of 678 patients, by EC tumor mismatch repair (MMR) gene expression. Report of EC in ≥1 first- or second-degree relative was associated with significantly increased risk of EC (P=3.8×10 The strongest predictor of EC risk was closer relatedness and younger EC diagnosis age in ≥1 relative. Associations remained significant irrespective of proband MMR status, and after excluding MMR pathogenic variant carriers, indicating that Lynch syndrome genes do not fully explain familial EC risk.
Publisher: Public Library of Science (PLoS)
Date: 15-03-2011
Publisher: University of California Press
Date: 20-10-2005
DOI: 10.1016/J.POSTCOMSTUD.2005.09.001
Abstract: Taking into account recently published evidence on Taiwan’s relations with the Soviet Union during the Cold War, this article examines the official and secret contacts between Moscow and Taipei from 1949 to 1988. It argues that despite some consideration given to a possible cooperation, Cold War hostility suited Taiwan and the Soviet Union more than collaboration. Taipei resorted to the ‘Soviet card’ in the 1970s to hinder Sino—American rapprochement, but never abandoned anti-Sovietism as the foundation of its diplomacy. The Soviet Union, for its part, prioritized normalization of relations with China and avoided rapprochement with the ROC, which could have only further strained ties with the PRC and accelerated the formation of the Sino—US united front against Moscow.
No related grants have been discovered for Czeslaw Tubilewicz.