Direct oral anticoagulants (DOACs) use for prolonged venous thromboembolism prophylaxis following surgery for gynaecological malignancies in Australia and New Zealand - A clinician survey.

BACKGROUND: Current international guidelines recommend 28 days of enoxaparin as venous thromboembolism (VTE) prophylaxis after surgery for gynaecologic cancer. Direct oral anticoagulants (DOACs) have been investigated as an alternative to enoxaparin for post-operative VTE prophylaxis. High-quality evidence to demonstrate safety and efficacy is lacking. AIMS: We aim to investigate the current practice regarding VTE prophylaxis among gynaecological oncologists in Australia and New Zealand following laparotomy for gynaecological malignancy, in particular the use of DOACs for VTE prophylaxis. MATERIALS AND METHODS: Sixty-seven practising gynaecologic oncologists (GO) were identified through Royal Australia and New Zealand College of Obstetricians and Gynaecologists database and emailed online surveys that asked about VTE prophylaxis practice and views of DOACs in this setting. Data were then collected through Survey Monkey and evaluated. RESULTS: The majority (77.1%) routinely prescribed 28 days of enoxaparin following laparotomy for gynaecological malignancies. In clinical circumstance such as laparoscopy for gynaecological malignancies and surgery for vulva malignancies, there was variation in thromboprophylaxis practices. No GO reported routine use of DOACs in any clinical circumstance. There were 56% of GOs who used a DOAC in their practice at some point. Barriers to routine use of DOACs in current practice included insufficient evidence (68%), issue with cost (40.4%) and concerns about safety (29.7%). CONCLUSIONS: Enoxaparin prescribed for 28 days remains the current clinical practice in preventing VTE following laparotomy for gynaecological malignancy. The main barrier to routine DOAC use as post-operative thromboprophylaxis is a lack of evidence which reflects the need for a larger prospective study.

Effects of Resveratrol on In Vivo Ovarian Cancer Cells Implanted on the Chorioallantoic Membrane (CAM) of a Chicken Embryo Model.

Ovarian cancer poses a significant threat to patients in its advanced stages, often with limited treatment options available. In such cases, palliative management becomes the primary approach to maintaining a reasonable quality of life. Therefore, the administration of any medication that can benefit patients without a curative option holds potential. Resveratrol, a natural compound known for its in vitro anticancer activities, has generated contrasting results in vivo and human studies. In this study, we aimed to assess the anticancer effects of resveratrol on ovarian cancer cells grown on the chorioallantoic membrane (CAM) of chicken embryos. Two ovarian cancer cell lines, OVCAR-8 and SKOV-3, were cultured in collagen scaffolds for four days before being implanted on the CAM of chicken embryos on day 7. Different doses of resveratrol were applied to the CAM every two days for six days. Subsequently, CAM tissues were excised, fixed, and subjected to histological analysis. Some CAM tumours were extracted to analyse proteins through Western blotting. Our findings indicate that specific doses of resveratrol significantly reduce angiogenic activities, pNF-κB levels, and SLUG protein levels by using immunohistochemistry. These results suggest that resveratrol may have the potential to impact the behaviour of ovarian cancer CAM tumours, thereby warranting further consideration as a complementary treatment option for women with incurable ovarian cancer.

Shifting incidence and survival of epithelial ovarian cancer (1995-2014): A SurvMark-2 study.

The aim of the study is to provide a comprehensive assessment of incidence and survival trends of epithelial ovarian cancer (EOC) by histological subtype across seven high income countries (Australia, Canada, Denmark, Ireland, New Zealand, Norway and the United Kingdom). Data on invasive EOC diagnosed in women aged 15 to 99 years during 1995 to 2014 were obtained from 20 cancer registries. Age standardized incidence rates and average annual percentage change were calculated by subtype for all ages and age groups (15-64 and 65-99 years). Net survival (NS) was estimated by subtype, age group and 5-year period using Pohar-Perme estimator. Our findings showed marked increase in serous carcinoma incidence was observed between 1995 and 2014 among women aged 65 to 99 years with average annual increase ranging between 2.2% and 5.8%. We documented a marked decrease in the incidence of adenocarcinoma "not otherwise specified" with estimates ranging between 4.4% and 7.4% in women aged 15 to 64 years and between 2.0% and 3.7% among the older age group. Improved survival, combining all EOC subtypes, was observed for all ages combined over the 20-year study period in all countries with 5-year NS absolute percent change ranging between 5.0 in Canada and 12.6 in Denmark. Several factors such as changes in guidelines and advancement in diagnostic tools may potentially influence the observed shift in histological subtypes and temporal trends. Progress in clinical management and treatment over the past decades potentially plays a role in the observed improvements in EOC survival.

Potential drug repurposing of ruxolitinib to inhibit the JAK/STAT pathway for the treatment of patients with epithelial ovarian cancer.

AIM: This review aimed to describe the potential for therapeutic targeting of the JAK/STAT signaling pathway by repurposing the clinically-approved JAK inhibitor ruxolitinib in the patients with epithelial ovarian cancer (OC) setting. METHODS: We reviewed publications that focus on the inhibition of the JAK/STAT pathway in hematological and solid malignancies including OC. RESULTS: Preclinical studies showed that ruxolitinib effectively reduces OC cell viability and metastasis and enhances the anti-tumor activity of chemotherapy drugs. There are a number of recent clinical trials exploring the role of JAK/STAT inhibition in solid cancers including OC. Early results have not adequately supported efficacy in solid tumors. However, there are preclinical data and clinical studies supporting the use of ruxolitinib in combination with both chemotherapy and other targeted drugs in OC setting. CONCLUSION: Inflammatory conditions and persistent activation of the JAK/STAT pathway are associated with tumourigenesis and chemoresistance, and therapeutic blockade of this pathway shows promising results. For women with OC, clinical investigation exploring the role of ruxolitinib in combination with chemotherapy agents or other targeted therapeutics is warranted.

Predicting regression of cervical intraepithelial neoplasia grade 2 in women under 25 years.

BACKGROUND: A number of retrospective and prospective studies have documented substantial rates of regression in cervical intraepithelial neoplasia grade 2 lesions in young women. Initial observational management of cervical intraepithelial neoplasia grade 2 is increasingly accepted as appropriate for women under 25 years of age with screen-detected abnormalities and is included in a number of clinical guidelines. However, there has been a paucity of large prospective studies on observational management with strict inclusion criteria. A number of important questions remain, specifically regarding the clinical variables that are associated with the risk of progression or persistence of disease. To investigate these factors and to ensure that young women with cervical intraepithelial neoplasia grade 2 undergoing observational management were being managed in a well-monitored and an appropriately informed fashion, we conducted a large, multicenter prospective study on observational management of cervical intraepithelial neoplasia grade 2 in women under 25 years. OBJECTIVE: This study aimed to determine the regression rates and clinical, cytologic, and pathologic predictors of regression of cervical intraepithelial neoplasia grade 2 in women under 25 years undergoing observational management over 24 months. STUDY DESIGN: This study was a multicenter prospective study on observational management of cervical intraepithelial neoplasia grade 2 (ie, repeat colposcopy, cytology, and cervical biopsy every 6 months) for up to 24 months. A total of 615 consenting women under 25 years with newly-diagnosed, biopsy-proven cervical intraepithelial neoplasia grade 2 were recruited (from 2010 to 2016) through 16 hospital-based colposcopy units in New Zealand and Australia. RESULTS: At completion, 326 women had confirmed regression, 156 had persistent high-grade cervical intraepithelial neoplasia grade 2 or 3 or adenocarcinoma in situ, and 24 had unconfirmed regression (ie, first regression at the 24-month follow-up). A total of 109 women did not complete the protocol (41 because of delayed follow-up, 41 lost to follow-up, 22 elected treatment, 4 refused a biopsy, and 1 died of an unrelated cause). Confirmed regression was observed in 53% (326 of 615) of all women enrolled in the study and, when missing data were imputed, it was estimated that 64% of women (95% confidence interval, 60%-68%) would have experienced regression. Similarly, lesions regressed in 64% (326 of 506) of women who completed the observational protocol. Based on a multivariable analysis, detection of human papillomavirus 16 in a liquid-based cytology sample at the time of initial colposcopy decreased the chance of regression by 31% (risk ratio, 0.69; 95% confidence interval, 0.56-0.86; P<.001). In addition, at initial colposcopy, low-grade or normal colposcopic impression, later year of diagnosis, low-grade or normal cytology, and being a nonsmoker were all independently associated with an increased chance of regression. CONCLUSION: More than half of women under 25 years with cervical intraepithelial neoplasia grade 2 will regress to cervical intraepithelial neoplasia grade 1 or normal within 24 months without destructive treatment. The absence of human papillomavirus 16 is the most important predictor of regression.

Use of direct oral anticoagulants for postoperative venous thromboembolism prophylaxis after surgery for gynecologic malignancies.

Venous thromboembolism is a preventable cause of postoperative mortality in patients undergoing surgery for malignancy. Current standard of care based on international guideline recommends 28 days of extended thromboprophylaxis after major abdominal and pelvic surgery for malignancies with unfractionated heparin or low molecular weight heparin. Direct oral anticoagulants have been approved for the treatment of venous thromboembolism in the general population. This regimen has a significant advantage over other types of anticoagulation regimens, particularly being administered by non-parenteral routes and without the need for laboratory monitoring. In this review, we evaluate the role of direct anticoagulation and provide an update on completed and ongoing clinical trials.

Complete pathological response following levonorgestrel intrauterine device in clinically stage 1 endometrial adenocarcinoma: Results of a randomized clinical trial.

PURPOSE: Intrauterine levonorgestrel (LNG-IUD) is used to treat patients with endometrial adenocarcinoma (EAC) and endometrial hyperplasia with atypia (EHA) but limited evidence is available on its effectiveness. The study determined the extent to which LNG-IUD with or without metformin (M) or weight loss (WL) achieves a pathological complete response (pCR) in patients with EAC or EHA. PATIENTS AND METHODS: This phase II randomized controlled clinical trial enrolled patients with histologically confirmed, clinically stage 1 FIGO grade 1 EAC or EHA; a body mass index > 30 kg/m2; a depth of myometrial invasion of less than 50% on MRI; a serum CA125 ≤ 30 U/mL. All patients received LNG-IUD and were randomized to observation (OBS), M (500 mg orally twice daily), or WL (pooled analysis). The primary outcome measure was the proportion of patients developing a pCR (defined as absence of any evidence of EAC or EHA) after 6 months. RESULTS: From December 2012 to October 2019, 165 patients were enrolled and 154 completed the 6-months follow up. Women had a mean age of 53 years, and a mean BMI of 48 kg/m2. Ninety-six patients were diagnosed with EAC (58%) and 69 patients with EHA (42%). Thirty-five participants were randomized to OBS, 36 to WL and 47 to M (10 patients were withdrawn). After 6 months the rate of pCR was 61% (95% CI 42% to 77%) for OBS, 67% (95% CI 48% to 82%) for WL and 57% (95% CI 41% to 72%) for M. Across the three treatment groups, the pCR was 82% and 43% for EHA and EAC, respectively. CONCLUSION: Complete response rates at 6 months were encouraging for patients with EAC and EHA across the three groups. TRIAL REGISTRATION: U.S. National Library of Medicine, NCT01686126.

A phase 2 study of anastrozole in patients with oestrogen receptor and/progesterone receptor positive recurrent/metastatic granulosa cell tumours/sex-cord stromal tumours of the ovary: The PARAGON/ANZGOG 0903 trial.

BACKGROUND: Hormonal therapies are commonly prescribed to patients with metastatic granulosa cell tumours (GCT), based on high response rates in small retrospective studies. Aromatase inhibitors (AIs) are reported to have high response rates and an accepted treatment option. We report the results of a phase 2 trial of an AI in recurrent/metastatic GCTs. METHODS: 41 patients with recurrent ER/PR + ve GCT received anastrozole 1 mg daily until progression or unacceptable toxicity. The primary endpoint was clinical benefit rate (CBR) at 12 weeks, evaluated by RECIST1.1 criteria. Secondary endpoints included progression-free survival (PFS), CBR duration, quality of life and toxicity. RESULTS: The CBR at 12 weeks in 38 evaluable patients was 78.9%, which included one (2.6%; 95% CI: 0.5-13.5%) partial response and 76.3% stable disease. Two additional patients without measurable disease were stable, based on inhibin. Median PFS was 8.6 m (95% CI 5.5-13.5 m). There were delayed responses observed after 12 weeks with a total of 4 pts. (10.5%; 95% CI 4.2%-24.1%) with a RECIST partial response; 23 (59%) patients were progression-free at 6 months. The adverse effects were predominantly low grade. CONCLUSIONS: This is the first prospective trial of hormonal therapy in GCTs. Although there was a high CBR, the objective response rate to anastrozole was much lower than the pooled response rates of >70% to AIs reported in most retrospective series and case reports. PARAGON demonstrates the importance of prospective trials in rare cancers and the need to reconsider the role of AIs as single agents in GCTs.

Reaching under-screened/never-screened indigenous peoples with human papilloma virus self-testing: A community-based cluster randomised controlled trial.

BACKGROUND: Indigenous women in the high-income countries of Canada, Australia, New Zealand and USA, have a higher incidence and mortality from cervical cancer than non-Indigenous women. Increasing cervical screening coverage could ultimately decrease cervical cancer disparities. AIMS: To increase cervical screening for under-screened/never-screened Maori women. MATERIALS AND METHODS: This study was a cluster randomised controlled trial. Inclusion criteria were women aged 25-69, last screened ≥4 years ago, in Northland, New Zealand. The intervention arm was the offer of a human papilloma virus (HPV) self-test and the control arm was the usual offer of standard care - a cervical smear. The primary outcome was rate of cervical screening in the intervention group compared to control in Maori, the Indigenous peoples of New Zealand. Six primary care clinics were randomly allocated to intervention or control. RESULTS: Of 500 eligible Maori women in the intervention arm, 295 (59.0%) were screened. Of 431 eligible Maori women in the control arm, 94 (21.8%) were screened. Adjusting for age, time since last screen, deprivation index, Maori women in the intervention arm were 2.8 times more likely to be screened than women in the control arm (95% CI: 2.4-3.1, P-value <0.0001). CONCLUSIONS: Offer of HPV self-testing could potentially halve the number of under-screened/never-screened Maori women and decrease cervical morbidity and mortality. These results may be generalisable to benefit Indigenous peoples facing similar barriers in other high-income countries.

Extracellular biophysical environment: Guilty of being a modulator of drug sensitivity in ovarian cancer cells.

The roles of the extracellular biophysical environment in cancer are barely studied. This study considers the possibility that cell-like topography of a cancer cell environment may influence chemo-responses. Here, a novel bioimprinting technique was employed to produce cell-like topography on the polystyrene substrates used for cell culture. In this work, we have shown that extracellular biophysical cues generated from the topography alter the chemosensitivity of ovarian cancer cells. The three-dimensionality of the bioimprinted surface altered the cell-surface interaction, which consequently modulated intracellular signalling and chemoresponses. Sensitivity to platinum was altered more than that to paclitaxel. The effect was largely mediated through the integrin/focal adhesion system and the Rho/ROCK pathway. Moreover, the results provided evidence that biophysical cues also modulate MAPK signalling associated with chemo-resistance in ovarian cancer. Therefore, the novel findings from of this study revealed for the first time that the effects of the biophysical environment, such as substrate topography, influences ovarian cancer cell responses to clinical drugs. These observations suggest that a full clinical understanding of ovarian cancer will include biophysical aspects of tumour microenvironment.

Excisional treatment comparison for in situ endocervical adenocarcinoma (EXCISE): A phase 2 pilot randomized controlled trial to compare histopathological margin status, specimen size and fragmentation after loop electrosurgical excision procedure and cold knife cone biopsy.

OBJECTIVE: Adenocarcinoma in situ (AIS) of the cervix is a precursor to cervical adenocarcinoma. When AIS is detected by cervical screening an excision biopsy is mandatory to exclude invasion. We aimed to compare margins status, specimen size and fragmentation after loop electrosurgical excision procedure (LEEP) and 'cold knife cone biopsy' (CKC). METHODS: The EXCISE Trial was an investigator-initiated, multicenter, open-label, parallel-group, phase 2, randomized study. Patients were enrolled at seven hospitals in Australia and New Zealand. We randomly assigned women aged ≥18 to ≤45 years with screen detected AIS to LEEP or CKC. Co-primary endpoints were margin status, specimen size and fragmentation. Analysis was by intention-to-treat. RESULTS: Between August 2, 2017 and September 6, 2019, 40 patients were randomly assigned 2:1 to LEEP or CKC. Margin status was evaluable in 36 cases. The proportion of patients with involved margins did not differ between groups. 25 of 26 LEEP and all 14 CKC biopsies were excised as single specimens (p = 1·00). There were no differences in specimen dimensions. Patients in the CKC group had more post-operative complications (64.3% compared to 15.4% for LEEP p = ·00). There were no differences in grade three complications (p = ·65). CONCLUSIONS: LEEP was not associated with a greater likelihood of positive margins, specimen fragmentation or smaller excision compared to CKC when performed according to a standardized protocol. However, the study was not powered to establish non-inferiority of LEEP and a definitive phase 3 trial to compare margin status and rates of treatment failure after LEEP and CKC is warranted.

Exploring variations in ovarian cancer survival by age and stage (ICBP SurvMark-2): A population-based study.

OBJECTIVE: The study aims to evaluate the differences in ovarian cancer survival by age and stage at diagnosis within and across seven high-income countries. METHODS: We analyzed data from 58,161 women diagnosed with ovarian cancer during 2010-2014, followed until 31 December 2015, from 21 population-based cancer registries in Australia, Canada, Denmark, Ireland, New Zealand, Norway, and United Kingdom. Comparisons of 1-year and 3-year age- and stage-specific net survival (NS) between countries were performed using the period analysis approach. RESULTS: Minor variation in the stage distribution was observed between countries, with most women being diagnosed with 'distant' stage (ranging between 64% in Canada and 71% in Norway). The 3-year all-ages NS ranged from 45 to 57% with Australia (56%) and Norway (57%) demonstrating the highest survival. The proportion of women with 'distant' stage was highest for those aged 65-74 and 75-99 years and varied markedly between countries (range:72-80% and 77-87%, respectively). The oldest age group had the lowest 3-year age-specific survival (20-34%), and women aged 65-74 exhibited the widest variation across countries (3-year NS range: 40-60%). Differences in survival between countries were particularly stark for the oldest age group with 'distant' stage (3-year NS range: 12% in Ireland to 24% in Norway). CONCLUSIONS: International variations in ovarian cancer survival by stage exist with the largest differences observed in the oldest age group with advanced disease. This finding endorses further research investigating international differences in access to and quality of treatment, and prevalence of comorbid conditions particularly in older women with advanced disease.

Evaluation of guidelines for observational management of cervical intraepithelial neoplasia 2 in young women.

BACKGROUND: A high rate of regression in young women with cervical intraepithelial neoplasia grade 2 has been recorded. However, there are few prospective data by which to evaluate management guidelines. OBJECTIVE: This study evaluates the American Society for Colposcopy and Cervical Pathology recommendations for follow-up of young women with cervical intraepithelial neoplasia 2 using data created by a large prospective multicenter study of observational management. MATERIALS AND METHODS: Participants were 616 women under 25 years with biopsy-diagnosed cervical intraepithelial neoplasia 2 following a referral to colposcopy for an abnormal smear with no previous high-grade abnormality. The protocol included colposcopy, cytology, and colposcopically directed biopsy at the initial visit and at 6- and 12-month follow-ups visits, and these data were analyzed. Histology from the corresponding cervical biopsy was treated as the reference diagnostic test. For young women with cervical intraepithelial neoplasia 2, we aimed to determine the following: (1) the ability of colposcopy to identify women with cervical intraepithelial neoplasia 3 or worse at 6 months; and (2) the ability of colposcopy, cytology, and a combination of cytology and colposcopy to identify residual high-grade abnormalities at 12 months. In addition, although not specified in the guidelines, we investigated the ability of high-risk human papillomavirus positivity alone or with cytology as a co-test to identify residual high-grade abnormalities at 12 months. RESULTS: At 6 months, cervical intraepithelial neoplasia 3+ colposcopic appearance identified only 28% (95% confidence interval, 18-40%) of women diagnosed with cervical intraepithelial neoplasia 3. At 12 months, a high-grade colposcopic appearance identified only 58% (95% confidence interval, 48-68%) of women with residual histological cervical intraepithelial neoplasia 2 or 3. At 12 months, high-grade cytology identified only 58% (95% confidence interval, 48-68%) of women with cervical intraepithelial neoplasia 2 or 3. However, the combination of either high-grade cytology or colposcopic appearance proved substantially more sensitive (81%; 95% confidence interval, 72-88%). High-risk human papillomavirus positivity at 12 months was a sensitive (96%; 95% confidence interval, 89-99%) indicator of persisting high-grade histology. However, this sensitivity came at the expense of specificity (52%; 95% confidence interval, 45-58%). A co-test of high-risk human papillomavirus positivity or high-grade cytology at 12 months provided a high sensitivity (97%; 95% confidence interval, 90-99%) but low specificity (51%; 95% confidence interval, 45%-58%). CONCLUSION: Colposcopy and cytology are limited in their ability to exclude persistent high-grade abnormality for young women undergoing observational management for cervical intraepithelial neoplasia 2. We recommend biopsy for all women at 12 months. High-risk human papillomavirus positivity is a sensitive indicator of persistent abnormality and should be considered in those not having a biopsy.

Exploring international differences in ovarian cancer treatment: a comparison of clinical practice guidelines and patterns of care.

INTRODUCTION: The International Cancer Benchmarking Partnership demonstrated international differences in ovarian cancer survival, particularly for women aged 65-74 with advanced disease. These findings suggest differences in treatment could be contributing to survival disparities. OBJECTIVE: To compare clinical practice guidelines and patterns of care across seven high-income countries. METHODS: A comparison of guidelines was performed and validated by a clinical working group. To explore clinical practice, a patterns of care survey was developed. A questionnaire regarding management and potential health system-related barriers to providing treatment was emailed to gynecological specialists. Guideline and survey results were crudely compared with 3-year survival by 'distant' stage using Spearman's rho. RESULTS: Twenty-seven guidelines were compared, and 119 clinicians completed the survey. Guideline-related measures varied between countries but did not correlate with survival internationally. Guidelines were consistent for surgical recommendations of either primary debulking surgery or neoadjuvant chemotherapy followed by interval debulking surgery with the aim of complete cytoreduction. Reported patterns of surgical care varied internationally, including for rates of primary versus interval debulking, extensive/'ultra-radical' surgery, and perceived barriers to optimal cytoreduction. Comparison showed that willingness to undertake extensive surgery correlated with survival across countries (rs=0.94, p=0.017). For systemic/radiation therapies, guideline differences were more pronounced, particularly for bevacizumab and PARP (poly (ADP-ribose) polymerase) inhibitors. Reported health system-related barriers also varied internationally and included a lack of adequate hospital staffing and treatment monitoring via local and national audits. DISCUSSION: Findings suggest international variations in ovarian cancer treatment. Characteristics relating to countries with higher stage-specific survival included higher reported rates of primary surgery; willingness to undertake extensive/ultra-radical procedures; greater access to high-cost drugs; and auditing.

Low-grade serous ovarian carcinoma: A comprehensive literature review.

BACKGROUND: Low-grade serous ovarian carcinoma (LGSOC) is a unique entity with clinical and molecular characteristics distinct from high-grade serous ovarian carcinoma (HGSOC). To date the majority of research has focused on the more common HGSOC, with treatment recommendations often extrapolated to LGSOC. Women with LGSOC are typically diagnosed younger and have indolent and relatively chemoresistant disease. Recently there have been major research advances in LGSOC. AIMS: This systematic review describes the epidemiological, clinical and molecular characteristics of LGSOC, with advances in research and novel treatment options also discussed. MATERIALS AND METHODS: A 10-year comprehensive systematic review of peer-reviewed literature was conducted, with a total of 132 abstracts read, 89 articles reviewed and 49 included in this review. RESULTS: This review highlights the clinical and molecular features of LGSOC, current and traditional treatment options and areas of current research into targeted agents. CONCLUSIONS: Our growing knowledge about LGSOC as a distinct clinical and molecular entity from HGSOC has led to the investigation of more targeted and tailored therapies as their clinical course, optimal management and therapeutic targets differ. There is a need for ongoing collaborative research to provide better treatment options for these patients.

The extracellular topographical environment influences ovarian cancer cell behaviour.

The importance of the biophysical cellular environment in cancer development has been increasingly recognised but so far has been only superficially studied. Here we investigated the effect of cell-like substrate topography on ovarian cancer cell behaviour and potential underlying signalling pathways. We observed changes in cell morphology in response to substrate topography, which implies modification of structure-function associations. Differences in focal adhesion signalling and Rho/ROCK activity suggested their involvement in the biomechanically-driven cellular responses. Cell-like topography was also shown to modulate the MAPK pathway and hence potentially regulate cell proliferation. The selective regulation of the cells by the mechanotransduction pathways that we noted has wide ranging implications for understanding cancer development. We established that the physical architecture of cell culture substrate is sufficient to influence cancer cell behaviour, independent of genetic composition or biochemical milieu.

Pathological process has a crucial role in sentinel node biopsy for vulvar cancer.

OBJECTIVES: To report the interim findings of an audit of the outcomes of sentinel node (SN) biopsy performed as a replacement for groin node dissection in women with early stage vulvar cancer in routine clinical practice in Australia and New Zealand. METHODS: A prospective multi-center study in 8 participating centers. Eligible patients had squamous cell carcinomas clinically restricted to the vulva <4 cm in diameter. SN procedures and pathological assessment were to be performed in accordance with the methods published by the GROINSS-V collaboration [1]. RESULTS: 130 women with apparent early stage vulvar cancer were enrolled. Seventeen women subsequently did not meet the eligibility criteria and were excluded. SNs were identified in 111/113 of the remaining women. Twenty-two women had positive nodes. Sixteen of these women had at least 12 months follow up and 7 (44%) had recurrent disease. Eighty-nine women had only negative nodes. Seventy-four of these women had at least 12 months follow up and 6 (8%) had recurrent disease (including 2 [2.7%] with recurrence in the groin). On subsequent review of the two women with negative SNs who had groin recurrences, it was found that the recommended pathology protocol had not been followed. In both cases, SN metastases were identified following serial sectioning of the nodes. CONCLUSIONS: SN biopsy is feasible in routine clinical practice. However, undetected metastases in a removed SN may be associated with groin recurrence. To ensure patient safety, strict adherence to the pathology protocol is an essential component in the utilization of the sentinel lymph node technique in vulvar cancer.

PARAGON: A Phase II study of anastrozole in patients with estrogen receptor-positive recurrent/metastatic low-grade ovarian cancers and serous borderline ovarian tumors.

OBJECTIVE: Treatment options are limited for patients with recurrent/metastatic low-grade ovarian cancers (LGOCs) and serous borderline ovarian tumors (SBOTs) as response rates to chemotherapy are low. A subset of patients appears to derive clinical benefit from antiestrogens, but most studies have been retrospective and clinical benefit rates (CBR) remain uncertain. The primary aim of PARAGON was to prospectively investigate the CBR of anastrozole, an aromatase inhibitor, in patients with estrogen receptor (ER) and/or progesterone receptor (PR) positive LGOC and SBOT. METHODS: Post-menopausal women with ER-positive and/or PR-positive recurrent/metastatic LGOCs and SBOTs and evaluable disease by RECIST v1.1 or GCIG CA125 criteria were treated with anastrozole 1 mg daily until progression or unacceptable toxicity. RESULTS: Thirty-six patients were enrolled. Clinical benefit at 3 months (primary endpoint) was observed in 23 patients (64%, 95% CI 48%-78%) and was similar at 6 months (61%, 95% CI 43%-75%). The median duration of clinical benefit was 9.5 months (95% CI 8.3-25.8). Best study response was partial response by RECIST in 5 patients (14%), stable disease in 18 patients (50%) with progressive disease in 13 patients (36%). Median PFS was 11.1 months (95% CI 3.2-11.9). Anastrozole was well-tolerated. Patients with evidence of clinical benefit at 3 months reported less pain, fatigue, and improved physical and role functioning as early as 1 month of commencing treatment. CONCLUSIONS: Anastrozole was associated with a CBR of 61% of patients with recurrent ER-positive and/or PR-positive LGOC or SBOT for at least 6 months with acceptable toxicity.

Trends in the overall survival rates in women with advanced ovarian cancer in a single tertiary centre in New Zealand.

BACKGROUND: Survival rates for women diagnosed with ovarian cancer are much poorer than other gynaecological cancers and greatly depend on stage at diagnosis. A recent publication showed that unlike some other developed countries, there has been no improvement in the five-year survival rate for those diagnosed with ovarian cancer in New Zealand. AIM: To compare the five-year survival rate of women diagnosed with advanced ovarian cancer in a single tertiary hospital during two 36-month time periods 10 years apart. MATERIALS AND METHODS: An observational retrospective review of patient clinical notes, including all women diagnosed with stage three or four ovarian cancer between 2000 and 2002 (Cohort 1) and 2010-2012 (Cohort 2). Eligible patients were identified through the Regional Gynaecology Oncology database. Clinical notes were reviewed to compare the five-year survival rate between these two time periods and look at changes in patterns of care over time. RESULTS: Eighty-three women were diagnosed in 2000-2002 and 125 women in 2010-2012. There was no difference in five-year survival between cohorts (21.7% vs 23.2%, P = 0.80). Mean age at diagnosis did not differ between cohorts (62.1 years vs 63.5 years, P = 0.43); however, there were more women with stage four cancer in Cohort 2 (14% vs 30%, P = 0.01). In Cohort 2, more women were treated with neoadjuvant chemotherapy (20% vs 34%, P = 0.04) or chemotherapy only (6% vs 18%, P = 0.01). CONCLUSION: Five-year overall survival in women diagnosed with advanced ovarian cancer in our centre has not changed over the last 10 years.

Acceptability of self-taken vaginal HPV sample for cervical screening among an under-screened Indigenous population.

BACKGROUND: Human papillomavirus (HPV), the causative agent of cervical cancer, can be screened for using self-collected vaginal samples (self-testing). This may overcome barriers to screening for Maori women who suffer a greater burden of cervical disease than New Zealand European women. AIMS: This study aimed to explore the potential acceptability of HPV self-testing for never/under-screened (self-reported no cervical screen in 4+ years, aged 25+) Maori women by Kaupapa Maori (by, with and for Maori) mixed methods, involving hui (focus groups/interviews) and survey. MATERIALS AND METHODS: Community-based researchers ran hui with women in four regions (N = 106) and supported hui participants to collect survey data (N = 397). Healthcare providers (HCPs) were also interviewed (N = 17). Hui data were thematically analysed. Survey data were analysed by age group, rural/urban, primary health organisation (PHO) enrolment, and time since last cervical screen. RESULTS: Most survey participants were PHO-enrolled (87.15%) and attended regularly (71.79%), but did not attend regular cervical screening. A desire for bodily autonomy, including whakama (embarrassment/shyness/reticence), was the most frequently cited barrier. Three in four women reported being likely/very likely to do an HPV self-test. Nine in ten women reported being likely/very likely to attend follow up if they receive a positive HPV test result. Women and HCPs in the hui emphasised the importance of health literacy, cultural competence and empathetic support. CONCLUSION: The findings indicate that with a culturally competent introduction of HPV self-testing, many currently never/under-screened Maori women would be willing to be screened and followed up if necessary. HPV self-testing has the potential to save lives.