Lessons from the renewal of the National Cervical Screening Program in Australia.

OBJECTIVES: Australia was one of the first countries to make the transition from cytology-based to HPV-based cervical screening.This analysis of the national program's transition to a new model looks at the lessons learnt that can provide valuable insights to other settings. Type of program: Australia's National Cervical Screening Program (NCSP). METHODS: Following an extensive policy review, in December 2017 the NCSP transitioned from 2-yearly cytology-based screening in women from age 18, to 5-yearly primary HPV screening from age 25. RESULTS: Some changes were more complex than initially anticipated. Building and implementing the National Cancer Screening Register was a more demanding and specialised project than expected. Regulatory requirements for self-collection were unexpectedly onerous, because self-collection was not formally included as an intended use by HPV test manufacturers. This delayed the rollout of a key measure to improve participation and equity. Colposcopy demand was expected to increase substantially but exceeded expectations. Uncertainty about appropriate clinical management or testing outside guideline recommendations may have contributed to the excess demand, highlighting the importance of training providers in the rationale for guidelines as well as the content. LESSONS LEARNT: Although the changes were evidence based, there were nevertheless some concerns among women and healthcare providers, especially about the longer interval and later starting age for screening. These could have been reduced through earlier and more extensively delivered information to healthcare providers, who play a key role in addressing community concerns. Improved coordination of stakeholder support between government and nongovernment organisations may also have extended both the reach and credibility of communication about the program changes. Transitioning a well-established program is challenging, not only because of the changes required, but also because the existing program must continue to function until the transition. Delays may be hard to avoid, but early communication will enable better forward planning, especially by service providers. Since delays can reduce wider confidence in the changes, proactive communication is critical. Achieving high and equitable screening coverage is a key element if Australia and other countries are to succeed in eliminating cervical cancer as a public health problem. Improving screening program confidence and participation remain important ongoing work. Lessons from Australia will provide valuable insights for other countries making similar changes.

Pathways to a cancer-free future: A protocol for modelled evaluations to maximize the future impact of interventions on cervical cancer in Australia.

OBJECTIVE: Australia's HPV vaccination and HPV-based cervical screening programs are changing the landscape in cervical cancer prevention. We aim to identify areas which can make the biggest further impact on cervical cancer burden. This protocol describes the first stage of a program of work called Pathways-Cervix that aims to generate evidence from modelled evaluations of interventions across the cervical cancer spectrum. METHODS: Based on evidence from literature reviews and guidance from a multi-disciplinary Scientific Advisory Committee (SAC), the most relevant evaluations for prevention, diagnosis and treatment were identified. RESULTS: Priority evaluations agreed by the SAC included: increasing/decreasing and retaining vaccination uptake at the current level; vaccinating older women; increasing screening participation; methods for triaging HPV-positive women; improving the diagnosis of cervical intraepithelial neoplasia (CIN) and cancer; treating cervical abnormalities and cancer; and vaccinating women treated for CIN2/3 to prevent recurrence. Evaluations will be performed using a simulation model, Policy1-Cervix previously used to perform policy evaluations in Australia. Exploratory modelling of interventions using idealised scenarios will initially be conducted in single birth cohorts. If these have a significant impact on findings then evaluations with more realistic assumptions will be conducted. Promising strategies will be investigated further by multi-cohort simulations predicting health outcomes, resource use and cost outcomes. CONCLUSIONS: Pathways-Cervix will assess the relative benefits of strategies and treatment options in a systematic and health economic framework, producing a list of 'best buys' for future decision-making in cervical cancer control.

Primary HPV testing versus cytology-based cervical screening in women in Australia vaccinated for HPV and unvaccinated: effectiveness and economic assessment for the National Cervical Screening Program.

BACKGROUND: Australia's National Cervical Screening Program currently recommends cytological screening every 2 years for women aged 18-69 years. Human papillomavirus (HPV) vaccination was implemented in 2007 with high population coverage, and falls in high-grade lesions in young women have been reported extensively. This decline prompted a major review of the National Cervical Screening Program and new clinical management guidelines, for which we undertook this analysis. METHODS: We did effectiveness modelling and an economic assessment of potential new screening strategies, using a model of HPV transmission, vaccination, natural history, and cervical screening. First, we evaluated 132 screening strategies, including those based on cytology and primary HPV testing. Second, after a recommendation was made to adopt primary HPV screening with partial genotyping and direct referral to colposcopy of women positive for HPV16/18, we evaluated the final effect of HPV screening after incorporating new clinical guidelines for women positive for HPV. Both evaluations considered both unvaccinated and vaccinated cohorts. FINDINGS: Strategies entailing HPV testing every 5 years and either partial genotyping for HPV16/18 or cytological co-testing were the most effective. One of the most effective and cost-effective strategies comprised primary HPV screening with referral of women positive for oncogenic HPV16/18 direct to colposcopy, with reflex cytological triage for women with other oncogenic types and direct referral for those in this group with high-grade cytological findings. After incorporating detailed clinical guidelines recommendations, this strategy is predicted to reduce cervical cancer incidence and mortality by 31% and 36%, respectively, in unvaccinated cohorts, and by 24% and 29%, respectively, in cohorts offered vaccination. Furthermore, this strategy is predicted to reduce costs by up to 19% for unvaccinated cohorts and 26% for cohorts offered vaccination, compared with the current programme. INTERPRETATION: Primary HPV screening every 5 years with partial genotyping is predicted to be substantially more effective and potentially cost-saving compared with the current cytology-based screening programme undertaken every 2 years. These findings underpin the decision to transition to primary HPV screening with partial genotyping in the Australian National Cervical Screening Program, which will occur in May, 2017. FUNDING: Department of Health, Australia.

Splenic Artery Embolization in Blunt Trauma: A Single-Center Retrospective Comparison of the Use of Gelatin Sponge Versus Coils.

OBJECTIVE: The purpose of this study was to compare the efficacy of gelatin sponge with that of coils for splenic artery embolization in the treatment of blunt splenic injury. MATERIALS AND METHODS: A single-center retrospective review was performed with the records of 63 patients (45 men, 18 women; mean age, 45.5 years; range, 16-84 years) with blunt splenic injury treated at a tertiary care trauma center by splenic artery embolization with gelatin sponge (n = 30 patients) or metallic coils (n = 33 patients) between 2005 and 2014. The two groups had comparable median American Association for the Surgery of Trauma grades of IV and comparable angiographic appearances regarding active extravasation and pseudoaneurysm formation at preembolization splenic arteriography (p = 0.32). Clinical outcomes and procedure-related outcomes were evaluated. RESULTS: The success rates were similar in the two groups: splenic artery embolization failed in 6.6% (2/30) of patients in the gelatin sponge group and 12.1% (4/33) in the coil embolization group (p = 0.45; 95% CI, -30.1% to 19.2%). Major complications occurred in six patients (20.0%) in the gelatin sponge group and in six patients (18.1%) in the coil group (p = 0.85; 95% CI, -23.0% to 26.6%). Minor complications occurred in three patients (10.0%) in the gelatin sponge group and seven patients (21.2%) in the coil group (p = 0.21; 95% CI, -35.4% to 14.0%). Procedure time was significantly shorter in the gelatin sponge group (median, 32 minutes; interquartile range, 18-48 minutes) than in the coil group (median, 53 minutes; interquartile range, 30-76 minutes) (p = 0.01). CONCLUSION: Splenic artery embolization with gelatin sponge appears to be as effective and as safe as coil embolization and can be completed in a shorter time.

Cervical cancer in women under 25 years of age in Queensland, Australia: To what extent is the diagnosis made by screening cytology?

INTRODUCTION: The current Australian National Cervical Screening Program (NCSP) involves biennial, cytology-based screening of women from the age of 18 years. From December, 2017 this will change to a five-yearly human papilloma virus-based screening commencing at age 25. There is some concern that the new program may delay the opportunistic detection of cervical cancers in women under 25 years. AIM: (1) To review all cases of invasive cervical cancer in Queensland women under the age of 25 over the last 28 years. (2) To determine symptoms and screening history prior to diagnosis. METHODS: A retrospective cohort study was undertaken at the Queensland Centre for Gynaecological Cancer (QCGC) and the Queensland Cancer Registry (QCR) of all women aged between 13 and 25 years diagnosed with cervical cancer in Queensland between 1984 and 2012. Demographic data and symptoms prior to diagnosis were extracted from the QCGC and QCR databases. RESULTS: A total of 56 women aged 13-25, were diagnosed with cervical cancer and treated at the QCGC between 1984 and 2012. The commonest reason for the diagnosis of cancer was investigation of abnormal symptoms (n = 22, 39%) rather than routine Pap smear abnormalities (n = 15, 26%). CONCLUSIONS: Consistent with the world literature, there is a very low incidence of cervical cancer in women under 25 years of age, irrespective of the age of commencement of screening, or the screening interval. Our study lends some support to the proposed commencement age of 25 years in the new NCSP.

Lower serum magnesium is associated with vascular calcification in peritoneal dialysis patients: a cross sectional study.

BACKGROUND: Coronary artery calcification (CAC) is highly prevalent among dialysis patients and is associated with increased cardiovascular and all cause mortality. Magnesium (Mg) inhibits vascular calcification in animal and in-vitro studies but whether the same effect occurs in humans is uncertain. METHODS: A single centre cross-sectional study of 80 prevalent peritoneal dialysis (PD) patients; on PD only for a minimum of 3 months. A radiologist blinded to patient status calculated their abdominal aortic calcification (AAC) scores on lateral lumbar spine radiographs, a validated surrogate for CAC. RESULTS: Eighty patients provided informed consent and underwent lumbar spine radiography. The mean serum Mg was 0.8 mmol/L (standard deviation 0.2) and mean AAC score 8.9 (minimum 0, maximum 24). A higher serum Mg level was associated with a lower AAC score (R 2 = 0.06, unstandardized coefficient [B] = -7.81, p = 0.03), and remained after adjustment for age, serum phosphate, serum parathyroid hormone, low-density lipoprotein cholesterol, smoking history, and diabetes (model adjusted R 2 = 0.36, serum Mg and AAC score B = -11.44, p = 0.00). This translates to a 0.1 mmol/L increase in serum Mg being independently associated with a 1.1-point decrease in AAC score. CONCLUSIONS: Our findings suggest that Mg may inhibit vascular calcification. If this association is replicated across larger studies with serial Mg and vascular calcification measurements, interventions that increase serum Mg and their effect on vascular calcification warrant further investigation in the PD population.

Effect of Total Laparoscopic Hysterectomy vs Total Abdominal Hysterectomy on Disease-Free Survival Among Women With Stage I Endometrial Cancer: A Randomized Clinical Trial.

Importance: 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. Objective: To investigate whether total laparoscopic hysterectomy (TLH) is equivalent to total abdominal hysterectomy (TAH) in women with treatment-naive endometrial cancer. Design, Setting, and Participants: 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. Interventions: Patients were randomly assigned to undergo TAH (n = 353) or TLH (n = 407). Main Outcomes and Measures: 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. Results: 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). Conclusions and Relevance: 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. Trial Registration: clinicaltrials.gov Identifier: NCT00096408; Australian New Zealand Clinical Trials Registry: CTRN12606000261516.

Optimal Management Strategies for Primary HPV Testing for Cervical Screening: Cost-Effectiveness Evaluation for the National Cervical Screening Program in Australia.

BACKGROUND: Several countries are implementing a transition to HPV testing for cervical screening in response to the introduction of HPV vaccination and evidence indicating that HPV screening is more effective than cytology. In Australia, a 2017 transition from 2-yearly conventional cytology in 18-20 to 69 years to 5-yearly primary HPV screening in 25 to 74 years will involve partial genotyping for HPV 16/18 with direct referral to colposcopy for this higher risk group. The objective of this study was to determine the optimal management of women positive for other high-risk HPV types (not 16/18) ('OHR HPV'). METHODS: We used a dynamic model of HPV transmission, vaccination, natural history and cervical screening to determine the optimal management of women positive for OHR HPV. We assumed cytology triage testing was used to inform management in this group and that those with high-grade cytology would be referred to colposcopy and those with negative cytology would receive 12-month surveillance. For those with OHR HPV and low-grade cytology (considered to be a single low-grade category in Australia incorporating ASC-US and LSIL), we evaluated (1) the 20-year risk of invasive cervical cancer assuming this group are referred for 12-month follow-up vs. colposcopy, and compared this to the risk in women with low-grade cytology under the current program (i.e. an accepted benchmark risk for 12-month follow-up in Australia); (2) the population-level impact of the whole program, assuming this group are referred to 12-month surveillance vs. colposcopy; and (3) the cost-effectiveness of immediate colposcopy compared to 12-month follow-up. Evaluation was performed both for HPV-unvaccinated cohorts and cohorts offered vaccination (coverage ~72%). FINDINGS: The estimated 20-year risk of cervical cancer is ≤1.0% at all ages if this group are referred to colposcopy vs. ≤1.2% if followed-up in 12 months, both of which are lower than the ≤2.6% benchmark risk in women with low-grade cytology in the current program (who are returned for 12-month follow-up). At the population level, immediate colposcopy referral provides an incremental 1-3% reduction in cervical cancer incidence and mortality compared with 12-month follow-up, but this is in the context of a predicted 24-36% reduction associated with the new HPV screening program compared to the current cytology-based program. Furthermore, immediate colposcopy substantially increases the predicted number of colposcopies, with >650 additional colposcopies required to avert each additional case of cervical cancer compared to 12-month follow-up. Compared to 12-month follow-up, immediate colposcopy has an incremental cost-effectiveness ratio (ICER) of A$104,600/LYS (95%CrI:A$100,100-109,100) in unvaccinated women and A$117,100/LYS (95%CrI:A$112,300-122,000) in cohorts offered vaccination [Indicative willingness-to-pay threshold: A$50,000/LYS]. CONCLUSIONS: In primary HPV screening programs, partial genotyping for HPV16/18 or high-grade triage cytology in OHR HPV positive women can be used to refer the highest risk group to colposcopy, but 12-month follow-up for women with OHR HPV and low-grade cytology is associated with a low risk of developing cervical cancer. Direct referral to colposcopy for this group would be associated with a substantial increase in colposcopy referrals and the associated harms, and is also cost-ineffective; thus, 12-month surveillance for women with OHR HPV and low-grade cytology provides the best balance between benefits, harms and cost-effectiveness.

Computed Tomography and Magnetic Resonance Imaging in the Differentiation of Osteoporotic Fractures From Neoplastic Metastatic Fractures.

Determining whether a low-intensity vertebral fracture in an older person, particularly one with a history of cancer, is due to osteoporosis (OP) or is the result of a metastasis, is a not infrequent clinical problem that has important prognostic and therapeutic implications. The 2 types of fracture are usually indistinguishable on plain radiographs and require higher order imaging for diagnosis. Magnetic resonance imaging is the modality of choice because of its unique ability to depict the bone marrow, which becomes transiently edematous in an acute OP fracture. Preservation of at least part of the normal marrow signal, the visualization of a fracture line parallel to the end plates, the presence of an intravertebral cleft, lack of pedicle involvement, and no extra-osseous mass all favor a benign OP fracture. Absence of the preceding signs, particularly if there is complete replacement of the normal bone marrow and a convex posterior contour of the vertebral body, favors a fracture of malignant origin. Non-routine magnetic resonance sequences using diffusion-weighted imaging and/or chemical shift imaging may be helpful in difficult cases.

Outpatient uterine artery embolization for symptomatic fibroids: short- and long-term single institution-based outcomes.

OBJECTIVE: To assess the short- and long-term efficacy and safety of uterine artery embolization (UAE) in the management of uterine fibroids, and to assess patient satisfaction with this procedure when performed on an outpatient basis. METHODS: One hundred one patients who had undergone UAE for symptomatic uterine fibroids in the past five years were interviewed over the telephone, using a standard uterine fibroid symptom and quality-of-life questionnaire. The severity of post-procedural pain, occurrence of adverse reactions, complications, need for subsequent hysterectomy or myomectomy, and overall patient satisfaction were also recorded. RESULTS: UAE resulted in a mean 39.1 point improvement in fibroid symptom scores and a mean rise of health-related quality of life score to 93.6, which is near normal. The mean pain score was highest (3.7/10) on the first night after the procedure. Ten patients returned to the hospital in the first 48 hours after UAE, but of these only one required admission because of sepsis. The only other major complication was spontaneous fibroid expulsion in one patient. Fourteen patients remained hypermenorrheic, 78 had regained normal or light menses, five reported spotting, and four became amenorrheic. Six patients underwent subsequent hysterectomy and one a subsequent myomectomy. Six patients found the procedure less than satisfactory. CONCLUSION: UAE is a safe, effective, and durable alternative to hysterectomy and myomectomy in women with symptomatic fibroids who wish to avoid surgery. It can be performed safely on an outpatient basis.

Improved surgical safety after laparoscopic compared to open surgery for apparent early stage endometrial cancer: results from a randomised controlled trial.

AIM: To compare Total Laparoscopic Hysterectomy (TLH) and Total Abdominal Hysterectomy (TAH) with regard to surgical safety. METHODS: Between October 2005 and June 2010, 760 patients with apparent early stage endometrial cancer were enroled in a multicentre, randomised clinical trial (LACE) comparing outcomes following TLH or TAH. The main study end points for this analysis were surgical adverse events (AE), hospital length of stay, conversion from laparoscopy to laparotomy, including 753 patients who completed at least 6 weeks of follow-up. Postoperative AEs were graded according to Common Toxicity Criteria (V3), and those immediately life-threatening, requiring inpatient hospitalisation or prolonged hospitalisation, or resulting in persistent or significant disability/incapacity were regarded as serious AEs. RESULTS: The incidence of intra-operative AEs was comparable in either group. The incidence of post-operative AE CTC grade 3+ (18.6% in TAH, 12.9% in TLH, p 0.03) and serious AE (14.3% in TAH, 8.2% in TLH, p 0.007) was significantly higher in the TAH group compared to the TLH group. Mean operating time was 132 and 107 min, and median length of hospital stay was 2 and 5 days in the TLH and TAH group, respectively (p<0.0001). The decline of haemoglobin from baseline to day 1 postoperatively was 2g/L less in the TLH group (p 0.006). CONCLUSIONS: Compared to TAH, TLH is associated with a significantly decreased risk of major surgical AEs. A laparoscopic surgical approach to early stage endometrial cancer is safe.

Risk factors to predict the incidence of surgical adverse events following open or laparoscopic surgery for apparent early stage endometrial cancer: results from a randomised controlled trial.

AIMS: To identify risk factors for major adverse events (AEs) and to develop a nomogram to predict the probability of such AEs in patients who have surgery for apparent early stage endometrial cancer. METHODS: We used data from 753 patients who were randomised to either total laparoscopic hysterectomy or total abdominal hysterectomy in the LACE trial. Serious adverse events that prolonged hospital stay or postoperative adverse events (using common terminology criteria 3+, CTCAE V3) were considered major AEs. We analysed pre-surgical characteristics that were associated with the risk of developing major AEs by multivariate logistic regression. We identified a parsimonious model by backward stepwise logistic regression. The six most significant or clinically important variables were included in the nomogram to predict the risk of major AEs within 6weeks of surgery and the nomogram was internally validated. RESULTS: Overall, 132 (17.5%) patients had at least one major AE. An open surgical approach (laparotomy), higher Charlson's medical co-morbidities score, moderately differentiated tumours on curettings, higher baseline Eastern Cooperative Oncology Group (ECOG) score, higher body mass index and low haemoglobin levels were associated with AE and were used in the nomogram. The bootstrap corrected concordance index of the nomogram was 0.63 and it showed good calibration. CONCLUSIONS: Six pre-surgical factors independently predicted the risk of major AEs. This research might form the basis to develop risk reduction strategies to minimise the risk of AEs among patients undergoing surgery for apparent early stage endometrial cancer.

Metastatic lung cancer involving the vulva: two new cases and literature review.

Two new cases of metastatic lung cancer involving the vulva are presented. Metastasis from primary lung cancer is a rare cause of a vulval tumour and may require special immunohistochemical stains to determine whether the vulval tumour is primary or secondary. Awareness of the possibility of metastatic disease involving the vulva is of importance as the patient's prognosis is dependent on an accurate diagnosis and palliative treatment where appropriate.

Sonographic patterns of benign thyroid nodules: verification at our institution.

OBJECTIVE: The objective of our study was to apply the sonographic criteria for the diagnosis of benign thyroid nodules described by Bonavita et al. to our patient referral population. MATERIALS AND METHODS: We performed a retrospective review of the sonographic features of 811 thyroid nodules that had undergone fine-needle aspiration biopsy in our radiology department from July 2005 to July 2009 and that had conclusive cytologic results. We determined the percentage of nodules that exhibited strictly the four benign sonographic patterns described by Bonavita et al. and the accuracy of those patterns in the prediction of benign cytologic findings. RESULTS: Sixty-six nodules (8.1%) showed a spongiform pattern and all were benign; 28 nodules (3.5%) showed the pattern described as "cyst with colloid clot" and all were benign; 14 nodules (1.7%) showed a "giraffe" pattern and all were proven to be Hashimoto thyroiditis; and eight nodules (1%) showed the "white knight" pattern and all were Hashimoto thyroiditis. Of the 121 nodules in our series with malignant cytologic features, none exhibited any of these four benign patterns. CONCLUSION: The four sonographic patterns described by Bonavita et al., when applied strictly, were 100% specific for benignity. However in our referral population, the application of these patterns would have eliminated the need for only 14% of biopsies, in contrast with 61% of biopsies in the population studied by Bonavita et al.

A resource allocation metric for thyroid biopsies.

PURPOSE: The aim of this study was to assess the adequacy of departmental resource allocation to ultrasound-guided biopsies of the thyroid gland. METHODS: The numbers of image-guided breast, prostate, and thyroid biopsies performed in the authors' radiology department over a 12-month period in 2009 were determined. The predicted deaths in Canada from breast, prostate, and thyroid cancer over the same period were obtained from the Canadian Cancer Society. The number of biopsies performed on each organ was divided by the expected mortality from the respective cancer. RESULTS: Approximately 2,400 breast biopsies, 910 prostate biopsies, and 610 thyroid biopsies were performed. Using mortality as a measure of cancer burden, the biopsy/cancer burden ratio for thyroid cancer was 7 times that for breast cancer and 15 times that for prostate cancer. CONCLUSION: The skewed ratio in favor of thyroid biopsies supports concerns that current trends in the investigation of thyroid nodules may represent an overconsumption of health resources.

Quality of life after total laparoscopic hysterectomy versus total abdominal hysterectomy for stage I endometrial cancer (LACE): a randomised trial.

BACKGROUND: This two-stage randomised controlled trial, comparing total laparoscopic hysterectomy (TLH) with total abdominal hysterectomy (TAH) for stage I endometrial cancer (LACE), began in 2005. The primary objective of stage 1 was to assess whether TLH results in equivalent or improved quality of life (QoL) up to 6 months after surgery compared with TAH. The primary objective of stage 2 was to test the hypothesis that disease-free survival at 4.5 years is equivalent for TLH and TAH. Here, we present the results of stage 1. METHODS: Between Oct 7, 2005, and April 16, 2008, 361 participants were enrolled in the QoL substudy at 19 centres across Australia, New Zealand, and Hong Kong; 332 completed the QoL analysis. Randomisation was done centrally and independently from other study procedures via a computer-generated, web-based system (providing concealment of the next assigned treatment), using stratified permuted blocks of three and six patients. Patients with histologically confirmed stage I endometrioid adenocarcinoma and Eastern Cooperative Oncology Group performance status less than 2 were randomly assigned to TLH (n=190) or TAH (n=142), stratified by histological grade and study centre. Patients and study personnel were not masked to treatment assignment. QoL was measured at baseline, 1 and 4 weeks (early), and 3 and 6 months (late) after surgery, using the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire. The primary endpoint was the difference between groups in QoL change from baseline at early and late timepoints (a 5% difference was considered clinically significant). Analysis was done according to the intention-to-treat principle. Patients for both stages of the trial have now been recruited and are being followed up for disease-specific outcomes. The LACE trial is registered with ClinicalTrials.gov, number NCT00096408. FINDINGS: Eight of 332 patients (2.4%) had treatment conversion-seven from TLH to TAH and one from TAH to TLH (patient preference). In the early phase of recovery, patients who had TLH reported significantly greater improvement in QoL from baseline compared with those who had TAH, in all subscales apart from emotional and social wellbeing. Improvements in QoL up to 6 months after surgery continued to favour TLH, except in the emotional and social wellbeing measures of FACT and the visual analogue scale of the EuroQoL five dimensions (EuroQoL-VAS). Operating time was significantly longer in the TLH group (138 min [SD 43]) than in the TAH group (109 min [34]; p=0.001). Although the proportion of intraoperative adverse events was similar between groups (TAH eight of 142 [5.6%] vs TLH 14 of 190 [7.4%]; p=0.53); postoperatively, twice as many patients in the TAH group experienced adverse events of grade 3 or higher (33 of 142 [23.2%] vs 22 of 190 [11.6%] in the TLH group; p=0.004). Postoperative serious adverse events occurred more in the TAH group (27 of 142 [19.0%]) than in the TLH group (16 of 190 [7.9%]; p=0.002). INTERPRETATION: QoL improvements from baseline during early and later phases of recovery, and the adverse event profile, favour TLH compared with TAH for treatment of stage I endometrial cancer. FUNDING: Cancer Council Queensland, Cancer Council New South Wales, Cancer Council Victoria, Cancer Council Western Australia; NHMRC project grant 456110; Cancer Australia project grant 631523; The Women and Infants Research Foundation, Western Australia; Royal Brisbane and Women's Hospital Foundation; Wesley Research Institute; Gallipoli Research Foundation; Gynetech; TYCO Healthcare, Australia; Johnson and Johnson Medical, Australia; Hunter New England Centre for Gynaecological Cancer; Genesis Oncology Trust; and Smart Health Research Grant QLD Health.

Malignant transformation within ovarian dermoid cysts: an audit of treatment received and patient outcomes. an Australia New Zealand gynaecological oncology group (ANZGOG) and gynaecologic cancer intergroup (GCIG) study.

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.