Prognostic Role of Histological Tumor Regression in Patients Receiving Neoadjuvant Chemotherapy for High-Grade Serous Tubo-ovarian Carcinoma.

OBJECTIVE: Our objective was to validate the prognostic role of the chemotherapy response score (CRS), which has been proposed for measuring tumor response to neoadjuvant chemotherapy in patients with high-grade serous tubo-ovarian carcinoma, in predicting progression-free survival (PFS) and overall survival (OS). METHODS: A retrospective cohort study was conducted of patients with advanced high-grade serous tubo-ovarian carcinoma diagnosed between January 1, 2010, and December 31, 2014, and treated with neoadjuvant chemotherapy. Treatment-related tumor regression was determined according to the 3-tier CRS, and results were compared with standard clinicopathological variables. Survival analysis was performed using Cox proportional hazards models and the log-rank test. RESULTS: Seventy-one patients were eligible for analysis. Median OS was 25.5 months. Fifty-eight patients (82%) had disease recurrence and 32 (45%) had died at study census. Of the 71 patients, 19, 29, and 23 patients had a CRS of 1, 2, and 3, respectively. On univariate analysis, the CRS significantly predicted PFS (hazard ratio [HR], 3.77; 95% confidence interval [CI], 1.83-7.78; P = 0.000) and OS (HR, 2.81; 95% CI, 1.16-6.79; P = 0.022). In a multivariate model, the CRS was significantly associated with PFS (HR, 2.81; 95% CI, 1.16-6.79; P = 0.022) but not with OS (HR, 2.39; 95% CI, 0.47-3.08; P = 0.079). Patients with CRS of 1 and 2 combined were twice as likely to progress during the study period compared with patients with a CRS of 3 (HR, 2.0; 95% CI, 1.06-3.78; P = 0.032; median PFS, 16 vs 26 months). No significant association was observed for OS (CRS 1/2 vs 3; HR, 1.57; 95% CI, 0.68-3.65; P = 0.291). CONCLUSIONS: In this study, the CRS showed independent prognostic significance for PFS but not for OS.

Risk of persistent or recurrent neoplasia in conservatively treated women with cervical adenocarcinoma in situ with negative histological margins.

INTRODUCTION: Conservative treatments including cold knife cone biopsy (CKC) or loop electrosurgical excision procedure (LEEP) are fertility-preserving alternatives to hysterectomy. The risks of persistent cervical neoplasia in women with negative surgical margins following conservative treatment of adenocarcinoma-in-situ (AIS) are uncertain. This study aims to investigate the risk of persistent or recurrent cervical neoplasia [AIS, adenocarcinoma and/or high-grade cervical squamous intraepithelial neoplasia (CIN)] and compliance with follow-up recommendations in conservatively treated women with AIS and negative histopathological margins. MATERIAL AND METHODS: A retrospective, population-based study of Western Australian women treated by CKC or LEEP for AIS between 2001 and 2012. Histopathology reports were reviewed for demographic information, treatment procedures and clinicopathological factors. Primary outcomes were the diagnosis of cervical neoplasia during follow-up (defined as <12 months) and surveillance (≥12 months) periods. RESULTS: The cohort comprised 360 women, with 175 (48.6%) initially treated by CKC and 185 (51.4%) treated by LEEP. The median patient age at time of excisional treatment was 30.0 years (range 18-64 years) and the median follow-up time was 3.9 years (range six months to 12.2 years). During the follow-up and surveillance periods, seven (1.9%) women were diagnosed with CIN 2/3, 10 (2.8%) with AIS, and one (0.3%) with cervical adenocarcinoma, despite their initial excision specimens having negative histological margins. CONCLUSION: In this study, there was a low but significant risk of persistent or recurrent cervical neoplasia in women who had initial conservative management of AIS with negative histopathological margins.

Risk of persistent and recurrent cervical neoplasia following incidentally detected adenocarcinoma in situ.

BACKGROUND: Adenocarcinoma in situ of the uterine cervix is a precursor to cervical adenocarcinoma and may coexist with both adenocarcinoma and high-grade squamous dysplasia (cervical intraepithelial neoplasia 2 and 3). Up to 60% of adenocarcinoma in situ lesions are detected incidentally following excisional biopsies performed for the treatment of cervical intraepithelial neoplasia 2/3. To date there are no data regarding risk factors for persisting or progressive cervical neoplasia in these patients. OBJECTIVE: We sought to investigate patient outcomes following incidentally detected cervical adenocarcinoma in situ after loop electrosurgical excision procedure or cold knife cone biopsy performed for the treatment of high-grade cervical intraepithelial neoplasia. STUDY DESIGN: We conducted a retrospective, population-based cohort study of Western Australian patients with an incidental diagnosis of adenocarcinoma in situ from 2001 through 2012. Primary outcomes were persistent or recurrent cervical intraepithelial neoplasia 2/3 and or adenocarcinoma in situ, and invasive adenocarcinoma during follow-up (<12 months) and surveillance (≥12 months) periods. RESULTS: The cohort comprised 298 patients, with 228 (76.5%) treated initially by loop electrosurgical excision procedure and 70 (23.5%) treated by cold knife cone biopsy. The mean age was 31.2 (range 18-68) years and the median length of follow-up was 2.4 (range 0.3-12.2) years. Overall, 11 (3.7%) patients had cervical intraepithelial neoplasia 2/3, 23 (7.7%) had adenocarcinoma in situ, and 3 (1.0%) had adenocarcinoma diagnosed during the follow-up and surveillance periods. Age >30 years, pure adenocarcinoma in situ lesions, and larger lesions (>8 mm) were associated with a greater risk of disease persistence or recurrence. CONCLUSION: Following the incidental detection of adenocarcinoma in situ, age >30 years, pure adenocarcinoma in situ lesions, and lesions >8 mm were significantly associated with disease persistence/recurrence. In younger women, incidentally detected adenocarcinoma in situ that coexists with cervical intraepithelial neoplasia 2/3 and is <8 mm extent with clear margins may not require reexcision.

Spontaneous regression of CIN2 in women aged 18-24 years: a retrospective study of a state-wide population in Western Australia.

INTRODUCTION: CIN2 has a high rate of spontaneous regression in young women and may be managed conservatively in appropriately selected patients. This study aimed to investigate health outcomes in women aged 18-24 years with biopsy-confirmed CIN2. MATERIAL AND METHODS: A retrospective cohort study of Western Australian women aged 18-24 years diagnosed with CIN2 on cervical biopsy from 1 January 2001 to 31 December 2010. Women who had not received treatment at ≥4 months following CIN2 diagnosis were classified as managed 'conservatively'. Subsequent cervical cytology and/or biopsy test results were used to report lesion regression (absence of dysplasia or an epithelial lesion of lower grade than CIN2) and disease persistence (CIN2, CIN3 or ACIS). RESULTS: Follow-up data were available for 2417 women of whom 924 (38.2%) were 'conservatively' managed. In all, 152 (16.4%) conservatively managed women had a lesion more severe than CIN2 detected within 24 months of initial diagnosis, of which 144 were CIN3 and eight were ACIS. There was no statistically significant association between rates of regression and patient age, Socio-economic Indexes for Areas or Accessibility/Remoteness Index of Australia indices. The 2-year regression rate for CIN2 was estimated to be 59.5% (95%CI 0.5-0.6) in this cohort of women. CONCLUSION: In conservatively managed young women with CIN2 there was a high rate of spontaneous disease regression. Thus, excisional or ablative treatments may be avoided in selected patients who receive appropriate counseling and who are able to comply with more intensive and prolonged follow-up requirements.

Risk of high-grade cervical dysplasia and gynaecological malignancies following the cytologic diagnosis of atypical endocervical cells of undetermined significance: a retrospective study of a state-wide screening population in Western Australia.

BACKGROUND: In 2006, Australia adopted a revised cervical cytology terminology system, known as the Australian Modified Bethesda System (AMBS). One substantial change in the AMBS was the introduction of the diagnostic category of atypical endocervical cells (AEC) of undetermined significance. AIM: The aim of this study was to investigate the incidence of histologically confirmed high-grade cervical dysplasia (cervical intra-epithelial neoplasia (CIN) grades 2 and 3 and adenocarcinoma in situ (ACIS)), cervical carcinoma and endometrial carcinoma in women presenting with AEC on cervical cytology. METHODS: A seven-year retrospective study examining clinical outcomes of women with AEC on a screening cervical smear. Cytology and histology results were extracted from the Western Australia Cervical Screening Registry, and time-to-event analysis was used to predict the odds of having or developing in situ and invasive neoplasia. RESULTS: AEC was reported in index smears from 0.093% (584/622754) women during the study period. No follow-up was available in 35 AEC cases. Sixty-five of the remaining 549 women (11.8%) had, or developed, high-grade cervical dysplasia within five years of their index AEC diagnosis. Endometrial cancer was diagnosed in 21 women and cervical cancer in four women during the follow-up period. CONCLUSION: Cytologic demonstration of AEC requires careful gynaecologic evaluation, particularly in younger women who may be found to have either high-grade squamous (CIN) or glandular (ACIS) lesions, while in older women, the possibility of endometrial neoplasia needs to be considered.

The human papillomavirus Test of Cure: A lesson on compliance with the NHMRC guidelines on screening to prevent cervical cancer.

BACKGROUND: In Australia, high-risk human papillomavirus (HR HPV) testing is recommended for follow-up of women treated for a high-grade squamous intra-epithelial lesion (HSIL). The sensitivity of HR HPV testing is critical to identify women at risk of further high-grade cervical disease. In Australia, this management protocol is known as the 'Test of Cure' (ToC). AIM: To conduct a population-based study investigating practitioners' compliance with ToC. MATERIALS AND METHODS: Women treated for an HSIL between the five-year period 01 Jan 2006 to 31 Dec 2010 were identified and followed up for at least a 27-month period. Proportions and relative odds were determined for women entering and completing the ToC management pathway within recommended time frames. RESULTS: There were 5,194 women identified as 'eligible' to enter the ToC management pathway. Of these, 1,916 (37%) were managed with annual Pap smears and never had a HR HPV test performed. There were 1,296 (25%) women who entered the ToC management pathway within recommended time frames, and a further 1,978 (38%) women entered outside of the recommended time frames. Overall, 961 women completed the ToC and were classified as 'cured' and were eligible to return to two-yearly Pap smears. Women's demographic information was significantly associated with ToC commencement, specifically, age and year of treatment, and Index of Relative Socioeconomic Disadvantage. CONCLUSION: Overall, a significant number of Australian women did not enter (~37%) and complete (~50%) the ToC management pathway. The challenge remains to advocate its use to practitioners to ensure women are returned to the population screening interval in a timely manner.

Utilisation of co-testing (human papillomavirus DNA testing and cervical cytology) after treatment of CIN: - a survey of GPs' awareness and knowledge.

BACKGROUND: Patients have an increased risk of persistent/recurrent cervical disease if they received treatment for a high-grade squamous intraepithelial lesion (HSIL). Consequently, understanding whether co-testing (human papillomavirus [HPV] DNA testing and cervical cytology) is fully utilised by general practitioners (GPs) is paramount. METHODS: After consultation with key stakeholders, an anonymous, self-completion questionnaire was developed and disseminated to GPs who had provided cervical cytology. RESULTS: Responses were received from 745 GPs (30.9% response rate). A significant number (34.3%) of GPs were unaware of the use of co-testing (HPV DNA testing and cervical cytology) for the management of patients after HSIL treatment. Additionally, the majority of GPs reported they did not 'always' receive a clear follow-up plan for patients after treatment of an HSIL. DISCUSSION: GPs require further support and education to ensure successful adoption of co-testing (HPV DNA testing and cervical cytology), specifically, for patients treated for an HSIL.

The role of general practitioners in the continued success of the National Cervical Screening Program.

BACKGROUND: As the gateway to healthcare for Australian women, general practitioners (GPs) are critical to the success of the National Cervical Screening Program (NCSP). Despite an enviable record - halving the incidence and mortality of cervical cancer - in 2010-2011 more than 2.7 million women did not comply with the recommended 2-yearly screening interval. OBJECTIVE: General practice strategies are presented to assist GPs in encouraging all women, in particular, high-risk and vulnerable women, to participate in cervical screening. DISCUSSION: GPs play a crucial part in addressing the demographic, psychosocial and healthcare barriers that prevent women's participation in cervical screening. Encouraging uptake of the human papillomavirus vaccine and educating all patients on the importance of continued participation in cervical screening is essential for further decreasing the prevalence of this disease through early detection and treatment of cervical abnormalities.

An individual-based versus group-based exercise and counselling intervention for improving quality of life in breast cancer survivors. A feasibility and efficacy study.

BACKGROUND: Cancer and its treatments produce lingering side-effects that undermine the quality of life (QOL) of survivors. Exercise and psycho-therapies increase QOL among survivors, however, research is needed to identify intervention characteristics most associated with such improvements. OBJECTIVE: This research aimed to assess the feasibility of a 9 week individual or group based exercise and counselling program, and to examine if a group based intervention is as effective at improving the QOL of breast cancer survivors as an individual-based intervention. METHODS: A three group design was implemented to compare the efficacy of a 9 week individual (IEC n = 12) and group based exercise and counselling (GEC n = 14) intervention to a usual care (UsC n = 10) group on QOL of thirty-six breast cancer survivors. RESULTS: Across all groups, 90% of participants completed the interventions, with no adverse effects documented. At the completion of the intervention, there was a significant difference between groups for change in global QOL across time (p < 0.023), with IEC improving significantly more (15.0 points) than the UsC group (1.8 points). The effect size was moderate (0.70). Although the GEC improved QOL by almost 10.0 points, this increase did not reach significance. Both increases were above the minimally important difference of 7-8 points. CONCLUSION: These preliminary results suggest a combined exercise and psychological counseling program is both a feasible and acceptable intervention for breast cancer survivors. Whilst both the individual and group interventions improved QOL above the clinically important difference, only the individual based intervention was significant when compared to UsC.