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 individual patients who have surgery for apparent early stage endometrial cancer. Methods: We used data from 753 patients who were randomized 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 analyzed 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 6 weeks 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 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 minimize the risk of AEs among patients undergoing surgery for apparent early stage endometrial cancer

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

A clinicopathological review of 33 patients with vulvar melanoma identifies c-KIT as a prognostic marker

Vulvar melanoma is the second most common vulvar cancer. Patients with vulvar melanoma usually present with the disease at a late stage and have a poor prognosis. The prognostic predictors reported in the literature are not unequivocal and the role of lichen sclerosus and c-KIT mutations in the aetiology of vulvar melanoma is unclear. Breslow staging currently seems to be the most adequate predictor of prognosis. We thus performed a clinicopathological and literature review to identify suitable predictors of prognosis and survival and investigated the expression of c-KIT (by immunohistochemistry) in patients with vulvar melanoma (n=33) from the Gynaecological Cancer Centres of the Royal Hospital for Women (Sydney, Australia) and John Hunter Hospital (Newcastle, Australia). Our series of 33 patients fitted the expected clinical profile of older women: delayed presentation, high stage, limited response to treatment and poor prognosis. We identified 3 patients (9.1%) with lichen sclerosus associated with melanoma in situ, although no lichen sclerosus was found in the areas of invasive melanoma. No patient had vulvar nevi. We identified a) Breslow's depth, b) an absence of any of the pathological risk factors, such as satellitosis, in-transit metastasis, lymphovascular space invasion (LVSI) and dermal mitosis, c) removal of inguino-femoral lymph nodes, d) lateral margin of <1 cm, and e) c-KIT expression as valuable prognostic predictors for disease-free survival. We conclude that c-KIT expression is, apart from Breslow's depth, another valuable predictor of prognosis and survival. Lichen sclerosus may be associated with vulvar melanoma

Open-source, fully-automated hybrid cardiac substructure segmentation: development and optimisation

Abstract: Radiotherapy for thoracic and breast tumours is associated with a range of cardiotoxicities. Emerging evidence suggests cardiac substructure doses may be more predictive of specific outcomes, however, quantitative data necessary to develop clinical planning constraints is lacking. Retrospective analysis of patient data is required, which relies on accurate segmentation of cardiac substructures. In this study, a novel model was designed to deliver reliable, accurate, and anatomically consistent segmentation of 18 cardiac substructures on computed tomography (CT) scans. Thirty manually contoured CT scans were included. The proposed multi-stage method leverages deep learning (DL), multi-atlas mapping, and geometric modelling to automatically segment the whole heart, cardiac chambers, great vessels, heart valves, coronary arteries, and conduction nodes. Segmentation performance was evaluated using the Dice similarity coefficient (DSC), mean distance to agreement (MDA), Hausdorff distance (HD), and volume ratio. Performance was reliable, with no errors observed and acceptable variation in accuracy between cases, including in challenging cases with imaging artefacts and atypical patient anatomy. The median DSC range was 0.81–0.93 for whole heart and cardiac chambers, 0.43–0.76 for great vessels and conduction nodes, and 0.22–0.53 for heart valves. For all structures the median MDA was below 6 mm, median HD ranged 7.7–19.7 mm, and median volume ratio was close to one (0.95–1.49) for all structures except the left main coronary artery (2.07). The fully automatic algorithm takes between 9 and 23 min per case. The proposed fully-automatic method accurately delineates cardiac substructures on radiotherapy planning CT scans. Robust and anatomically consistent segmentations, particularly for smaller structures, represents a major advantage of the proposed segmentation approach. The open-source software will facilitate more precise evaluation of cardiac doses and risks from available clinical datasets. Graphical abstract: [Figure not available: see fulltext.]

Feasibility of multi-atlas cardiac segmentation from thoracic planning CT in a probabilistic framework

Toxicity to cardiac and coronary structures is an important late morbidity for patients undergoing left-sided breast radiotherapy. Many current studies have relied on estimates of cardiac doses assuming standardised anatomy, with a calculated increase in relative risk of 7.4% per Gy (mean heart dose). To provide individualised estimates for dose, delineation of various cardiac structures on patient images is required. Automatic multi-atlas based segmentation can provide a consistent, robust solution, however there are challenges to this method. We are aiming to develop and validate a cardiac atlas and segmentation framework, with a focus on the limitations and uncertainties in the process. We present a probabilistic approach to segmentation, which provides a simple method to incorporate inter-observer variation, as well as a useful tool for evaluating the accuracy and sources of error in segmentation. A dataset consisting of 20 planning computed tomography (CT) images of Australian breast cancer patients with delineations of 17 structures (including whole heart, four chambers, coronary arteries and valves) was manually contoured by three independent observers, following a protocol based on a published reference atlas, with verification by a cardiologist. To develop and validate the segmentation framework a leave-one-out cross-validation strategy was implemented. Performance of the automatic segmentations was evaluated relative to inter-observer variability in manuallyderived contours; measures of volume and surface accuracy (Dice similarity coefficient (DSC) and mean absolute surface distance (MASD), respectively) were used to compare automatic segmentation to the consensus segmentation from manual contours. For the whole heart, the resulting segmentation achieved a DSC of 0.944 +0.024, with a MASD of .726 + 1.363 mm. Quantitative results, together with the analysis of probabilistic labelling, indicate the feasibility of accurate and consistent segmentation of larger structures, whereas this is not the case for many smaller structures, where a major limitation in segmentation accuracy is the interobserver variability in manual contouring.</p

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

Background: The two-stage Total Laparoscopic Hysterectomy (TLH) versus Total Abdominal Hysterectomy (TAH) for stage I endometrial cancer (LACE) randomised controlled trial was initiated in 2005. The primary objective of stage 1 was to assess whether TLH results in equivalent or improved QoL up to 6 months after surgery compared to 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. Results addressing the primary objective of stage 1 of the LACE trial are presented here. Methods: The first 361 LACE participants (TAH n= 142, TLH n=190) were enrolled in the QoL substudy at 19 centres across Australia, New Zealand and Hong Kong, and 332 completed the QoL analysis. Randomisation was performed 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 3 and 6, and assigned patients with histologically confirmed stage 1 endometrioid endometrial adenocarcinoma and ECOG performance status <2 to TLH or TAH stratified by histological grade and study centre. No blinding of patients or study personnel was attempted. 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 the groups in QoL change from baseline at early and late time points (a 5% difference was considered clinically significant). Analysis was performed according to the intention-to-treat principle using generalized estimating equations on differences from baseline for the early and late QoL recovery. The LACE trial is registered with clinicaltrials.gov (NCT00096408) and the Australian New Zealand Clinical Trials Registry (CTRN12606000261516). Patients for both stages of the trial have now been recruited and are being followed up for disease-specific outcomes. Findings: The proportion of missing values at the 5%, 10% 15% and 20% differences in the FACT-G scale was 6% (12/190) in the TLH and 14% (20/142) in the TAH group. There were 8/332 conversions (2.4%, 7 of which were from TLH to TAH). In the early phase of recovery, patients undergoing TLH reported significantly greater improvement of QoL from baseline compared to TAH in all subscales except the emotional and social well-being subscales. Improvements in QoL up to 6 months post-surgery continued to favour TLH except for the emotional and social well-being of the FACT and the visual analogue scale of the EuroQoL five dimensions (EuroQoL-VAS). Length of operating time was significantly longer in the TLH group (138±43 mins), than in the TAH group at (109±34 mins; p=0.001). While the proportion of intraoperative adverse events was similar between the treatment groups (TAH 8/142, 5.6%; TLH 14/190, 7.4%; p=0.55), postoperatively, twice as many patients in the TAH group experienced adverse events of CTC grade 3+ than in the TLH group (33/142, 23.2% and 22/190, 11.6%, respectively; p=0.004). Postoperative serious adverse events occurred more frequently in patients who had a TAH (27/142, 19.0%) than a TLH (15/190, 7.9%) (p=0.002). Interpretation: QoL improvements from baseline during early and later phases of recovery, and the adverse event profile significantly favour TLH compared to TAH for patients treated for Stage I endometrial cancer

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

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

A clinicopathological review of 33 patients with vulvar melanoma identifies c-KIT as a prognostic marker

Vulvar melanoma is the second most common vulvar cancer. Patients with vulvar melanoma usually present with the disease at a late stage and have a poor prognosis. The prognostic predictors reported in the literature are not unequivocal and the role of lichen sclerosus and c-KIT mutations in the aetiology of vulvar melanoma is unclear. Breslow staging currently seems to be the most adequate predictor of prognosis. We thus performed a clinicopathological and literature review to identify suitable predictors of prognosis and survival and investigated the expression of c-KIT (by immunohistochemistry) in patients with vulvar melanoma (n=33) from the Gynaecological Cancer Centres of the Royal Hospital for Women (Sydney, Australia) and John Hunter Hospital (Newcastle, Australia). Our series of 33 patients fitted the expected clinical profile of older women: delayed presentation, high stage, limited response to treatment and poor prognosis. We identified 3 patients (9.1%) with lichen sclerosus associated with melanoma in situ, although no lichen sclerosus was found in the areas of invasive melanoma. No patient had vulvar nevi. We identified a) Breslow’s depth, b) an absence of any of the pathological risk factors, such as satellitosis, in-transit metastasis, lymphovascular space invasion (LVSI) and dermal mitosis, c) removal of inguino-femoral lymph nodes, d) lateral margin of >1 cm, and e) c-KIT expression as valuable prognostic predictors for disease-free survival. We conclude that c-KIT expression is, apart from Breslow’s depth, another valuable predictor of prognosis and survival. Lichen sclerosus may be associated with vulvar melanoma