The current and potential future role of peritonectomy and hyperthermic intraperitoneal chemotherapy (HIPEC) for treatment of advanced epithelial ovarian cancer in Australia

Background and Aims: Ovarian cancer is the most common cause of death due to gynaecological malignancy. Most cases (70%) present as advanced disease (stage III/IV), where cancer has spread to peritoneal surfaces. Standard treatment is optimal cytoreductive surgery and intravenous platinum-based chemotherapy, with selective use of targeted treatments. However, peritonectomy (extended cytoreductive surgery) and hyperthermic intraperitoneal chemotherapy (HIPEC) is being increasingly used. This thesis aims to investigate the current and potential future role of peritonectomy and HIPEC in treating advanced ovarian cancer in Australia. Methods: A review of literature on the treatment of primary and recurrent epithelial ovarian cancer, and a systematic review of the use of cytoreductive surgery and HIPEC for this disease, were performed. A survey of Australian gynaecological oncologists was conducted to determine changes in surgical practices for ovarian cancer over the past decade. A retrospective review of 41 cases of peritonectomy with/without HIPEC for ovarian cancer in the largest Australian centre was undertaken. The attitudes of gynaecological oncologists towards this treatment were investigated with an online survey. A multicentre Australian phase II clinical trial of HIPEC for the treatment of primary ovarian cancer was developed, and a grant application was submitted to the Medical Research Future Fund (NHMRC). Results: There is good evidence for the use of extended cytoreductive surgery, but a paucity of quality studies of HIPEC, for treatment of ovarian cancer. Australian gynaecological oncologists report a lack of surgical training and abilities, but increased neoadjuvant chemotherapy use, for treating advanced disease. In an Australian centre performing peritonectomy and HIPEC there were good outcomes for primary ovarian cancer, but poorer results for recurrent disease, primarily due to a lack of strict selection criteria. Gynaecological oncologists report concerns around potential toxicities and effectiveness of HIPEC and indicate a need for quality clinical trials. This knowledge was used to design HyNOVA, a randomised multicentre trial comparing HIPEC with normothermic chemotherapy (NIPEC) for stage III ovarian cancer. HyNOVA received NHMRC funding and commenced in 2022. Conclusion: This thesis has produced new knowledge about peritonectomy and HIPEC for the treatment of ovarian cancer and will help define its future role through an Australian clinical trial, HyNOVA

Exploring international differences in ovarian cancer care: a survey report on global patterns of care, current practices, and barriers

OBJECTIVE: Although global disparities in survival rates for patients with ovarian cancer have been described, variation in care has not been assessed globally. This study aimed to evaluate global ovarian cancer care and barriers to care. METHODS: A survey was developed by international ovarian cancer specialists and was distributed through networks and organizational partners of the International Gynecologic Cancer Society, the Society of Gynecologic Oncology, and the European Society of Gynecological Oncology. Respondents received questions about care organization. Outcomes were stratified by World Bank Income category and analyzed using descriptive statistics and logistic regressions. RESULTS: A total of 1059 responses were received from 115 countries. Respondents were gynecological cancer surgeons (83%, n=887), obstetricians/gynecologists (8%, n=80), and other specialists (9%, n=92). Income category breakdown was as follows: high-income countries (46%), upper-middle-income countries (29%), and lower-middle/low-income countries (25%). Variation in care organization was observed across income categories. Respondents from lower-middle/low-income countries reported significantly less frequently that extensive resections were routinely performed during cytoreductive surgery. Furthermore, these countries had significantly fewer regional networks, cancer registries, quality registries, and patient advocacy groups. However, there is also scope for improvement in these components in upper-middle/high-income countries. The main barriers to optimal care for the entire group were patient co-morbidities, advanced presentation, and social factors (travel distance, support systems). High-income respondents stated that the main barriers were lack of surgical time/staff and patient preferences. Middle/low-income respondents additionally experienced treatment costs and lack of access to radiology/pathology/genetic services as main barriers. Lack of access to systemic agents was reported by one-third of lower-middle/low-income respondents. CONCLUSIONS: The current survey report highlights global disparities in the organization of ovarian cancer care. The main barriers to optimal care are experienced across all income categories, while additional barriers are specific to income levels. Taking action is crucial to improve global care and strive towards diminishing survival disparities and closing the care gap

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

Gene expression profiling of mucinous ovarian tumors and comparison with upper and lower gastrointestinal tumors identifies markers associated with adverse outcomes.

PURPOSE: Advanced-stage mucinous ovarian carcinoma (MOC) has poor chemotherapy response and prognosis and lacks biomarkers to aid stage I adjuvant treatment. Differentiating primary MOC from gastrointestinal (GI) metastases to the ovary is also challenging due to phenotypic similarities. Clinicopathologic and gene-expression data were analyzed to identify prognostic and diagnostic features. EXPERIMENTAL DESIGN: Discovery analyses selected 19 genes with prognostic/diagnostic potential. Validation was performed through the Ovarian Tumor Tissue Analysis consortium and GI cancer biobanks comprising 604 patients with MOC (n = 333), mucinous borderline ovarian tumors (MBOT, n = 151), and upper GI (n = 65) and lower GI tumors (n = 55). RESULTS: Infiltrative pattern of invasion was associated with decreased overall survival (OS) within 2 years from diagnosis, compared with expansile pattern in stage I MOC [hazard ratio (HR), 2.77; 95% confidence interval (CI), 1.04–7.41, P = 0.042]. Increased expression of THBS2 and TAGLN was associated with shorter OS in MOC patients (HR, 1.25; 95% CI, 1.04–1.51, P = 0.016) and (HR, 1.21; 95% CI, 1.01–1.45, P = 0.043), respectively. ERBB2 (HER2) amplification or high mRNA expression was evident in 64 of 243 (26%) of MOCs, but only 8 of 243 (3%) were also infiltrative (4/39, 10%) or stage III/IV (4/31, 13%). CONCLUSIONS: An infiltrative growth pattern infers poor prognosis within 2 years from diagnosis and may help select stage I patients for adjuvant therapy. High expression of THBS2 and TAGLN in MOC confers an adverse prognosis and is upregulated in the infiltrative subtype, which warrants further investigation. Anti-HER2 therapy should be investigated in a subset of patients. MOC samples clustered with upper GI, yet markers to differentiate these entities remain elusive, suggesting similar underlying biology and shared treatment strategies

CCNE1 and survival of patients with tubo-ovarian high-grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study

BACKGROUND: Cyclin E1 (CCNE1) is a potential predictive marker and therapeutic target in tubo-ovarian high-grade serous carcinoma (HGSC). Smaller studies have revealed unfavorable associations for CCNE1 amplification and CCNE1 overexpression with survival, but to date no large-scale, histotype-specific validation has been performed. The hypothesis was that high-level amplification of CCNE1 and CCNE1 overexpression, as well as a combination of the two, are linked to shorter overall survival in HGSC. METHODS: Within the Ovarian Tumor Tissue Analysis consortium, amplification status and protein level in 3029 HGSC cases and mRNA expression in 2419 samples were investigated. RESULTS: High-level amplification (>8 copies by chromogenic in situ hybridization) was found in 8.6% of HGSC and overexpression (>60% with at least 5% demonstrating strong intensity by immunohistochemistry) was found in 22.4%. CCNE1 high-level amplification and overexpression both were linked to shorter overall survival in multivariate survival analysis adjusted for age and stage, with hazard stratification by study (hazard ratio [HR], 1.26; 95% CI, 1.08-1.47, p = .034, and HR, 1.18; 95% CI, 1.05-1.32, p = .015, respectively). This was also true for cases with combined high-level amplification/overexpression (HR, 1.26; 95% CI, 1.09-1.47, p = .033). CCNE1 mRNA expression was not associated with overall survival (HR, 1.00 per 1-SD increase; 95% CI, 0.94-1.06; p = .58). CCNE1 high-level amplification is mutually exclusive with the presence of germline BRCA1/2 pathogenic variants and shows an inverse association to RB1 loss. CONCLUSION: This study provides large-scale validation that CCNE1 high-level amplification is associated with shorter survival, supporting its utility as a prognostic biomarker in HGSC

Factors determining diabetes care outcomes in patients with type 1 diabetes after transition from pediatric to adult health care: a systematic review

Background The transition of young adults with type 1 diabetes from pediatric to adult health care usually takes place at the end of secondary schooling, at a time when they are also experiencing multiple life transitions. Diabetes self-care management will often be of low priority for young people as they adjust to new routines involved with further study, employment and relationships. Failure to transition successfully may result in loss to medical follow-up, deterioration in diabetes control and development of short and long term diabetes complications. Objectives The primary focus of this systematic review was to identify the best available evidence of factors that determine diabetes care outcomes for young adults with type 1 diabetes after transition from pediatric to adult health care services. Data synthesis Where data were available, it has been pooled and presented as a forest plot in the review results. Studies with textual data results or where synthesis is inappropriate are presented as a narrative summary. Results Forty-one studies that potentially met the criteria for inclusion in the review were identified by the search strategy, of which 13 met the inclusion criteria. Factors identified to assist transition in the review studies related to either structured or unstructured interventions. The results of this review demonstrate that when a structured program is in place to assist the transition from pediatric to adult diabetes services, young people are less likely to require hospitalization for acute diabetes complications and more likely to attend appointments at the adult diabetes service. Conclusions The evidence identified from this review is suggestive that a structured transition intervention employing a dedicated health professional to support and coordinate the process is more likely to prevent loss to follow-up, maintain clinic attendance, have a positive impact on diabetes control, reduce hospital admissions, and be a more cost effective and positive experience for patients than an unstructured or usual care model

):e2511408 Public Health Res Pract

Key points • A performance monitoring framework to track implementation (reach) and impacts (change in organisational practices) was introduced in NSW • Linking targets with senior executive performance indicators increased accountability to achieve targets • Significant reach and impact were achieved in early childhood education and care and primary school settings between 2008 and 2014 • Monitoring state-wide program implementation has potential for application in a broad range of health policy areas Abstract The allocation of a significant amount of new funding for health promotion in Australia through the National Partnership Agreement on Preventive Health (2009-14) created a unique opportunity to implement a comprehensive approach to the prevention of chronic diseases and demonstrate significant health improvements. Building on existing health promotion infrastructure in Local Health Districts, the NSW Ministry of Health adopted a scaled-up state-wide capacity-building model, designed to alter policies and practices in key children's settings to increase healthy eating and physical activity among children. NSW also introduced a performance monitoring framework to track implementation and impacts. This paper describes the model that NSW developed for monitoring state-wide programs in the Children's Healthy Eating and Physical Activity Program and presents the model's application to early childhood education and care and primary school settings, including current results. This approach to monitoring the scaling up of program implementation at the state-wide level has potential for more widespread application in other policy areas in NSW

):e2511408 Public Health Res Practice

Key points • A performance monitoring framework to track implementation (reach) and impacts (change in organisational practices) was introduced in NSW • Linking targets with senior executive performance indicators increased accountability to achieve targets • Significant reach and impact were achieved in early childhood education and care and primary school settings between 2008 and 2014 • Monitoring state-wide program implementation has potential for application in a broad range of health policy areas Abstract The allocation of a significant amount of new funding for health promotion in Australia through the National Partnership Agreement on Preventive Health (2009-14) created a unique opportunity to implement a comprehensive approach to the prevention of chronic diseases and demonstrate significant health improvements. Building on existing health promotion infrastructure in Local Health Districts, the NSW Ministry of Health adopted a scaled-up state-wide capacity-building model, designed to alter policies and practices in key children's settings to increase healthy eating and physical activity among children. NSW also introduced a performance monitoring framework to track implementation and impacts. This paper describes the model that NSW developed for monitoring state-wide programs in the Children's Healthy Eating and Physical Activity Program and presents the model's application to early childhood education and care and primary school settings, including current results. This approach to monitoring the scaling up of program implementation at the state-wide level has potential for more widespread application in other policy areas in NSW

Health outcomes for youth with type 1 diabetes at 18 months and 30 months post transition from pediatric to adult care

Aims: To identify (a) determinants of glycated haemoglobin (HbA1c) at 18 and 30 months following transition in young people with Type 1 diabetes mellitus (T1DM) to a youth-specific diabetes service; and to (b) evaluate the impact of the service on acute admissions with diabetic ketoacidosis (DKA) over a 14-year period. Methods: An audit of records of youth with T1DM referred from paediatric services to the multidisciplinary transition service at Westmead Hospital, from 2001 to 2012, and followed-up to 2014. Results: Data from 439 adolescents and young adults (Median age: 18) were analysed. The recommended standard of glycaemic control, HbA1c \u3c 7.5% (58 mmol/mol), was achieved by 23% at baseline, 22% at 18-months, and 20% at 30-month. After adjusting for lag time ( \u3e 3 months) and diabetes duration ( \u3e 7 years), glycaemic control at first visit predicted subsequent glycaemic control at 18-month and 30-month follow-up. From 2001 to 2014, only 8.6% were lost to follow-up; admissions and readmissions for DKA reduced from 72% (32/47) to 4% (14/340) (p \u3c 0.001). Furthermore, mean length of stay (LOS) significantly decreased from 6.56 to 2.36 days (p \u3c 0.001). Conclusions: Continuing engagement with the multidisciplinary transition service prevented deterioration in HbA1c following transition. Age-appropriate education and regular follow-up prevents DKA admissions and significantly reduced admission LOS