Health-related quality of life and pelvic floor dysfunction in advanced-stage ovarian cancer survivors: associations with objective activity behaviors and physiological characteristics.

PURPOSE: Little is known about the relationship between health-related quality of life (HRQoL), pelvic floor dysfunction (PFD), and modifiable lifestyle and physiological factors for ovarian cancer survivors (OCS). The primary aim of the study was to compare post-treatment advanced-stage OCS with age-matched controls on measures of HRQoL and PFD. The secondary aim was to examine associations between HRQoL, PFD, objective activity behaviors, physical function, and body composition in OCS. METHODS: Twenty advanced-stage OCS and 20 controls completed questionnaires assessing HRQoL (SF-36) and PFD (Australian Pelvic Floor Questionnaire), and underwent objective assessments of activity behavior (7-day accelerometry), physical function (400-m walk, repeated chair rise, 6-m usual-pace walk, one-repetition maximum chest press, and single-leg extension), and body composition (dual-energy x-ray absorptiometry). RESULTS: Compared to controls, OCS had worse physical HRQoL (- 4.3 median difference, p = 0.013), but equivalent self-reported PFD, indicated by combined bladder, bowel, and pelvic organ prolapse symptoms (0.89 mean difference, p = 0.277). In OCS, physical HRQoL was significantly negatively associated with PFD (r = 0.468, p = 0.043). Decreased physical HRQoL and increased PFD were significantly associated with less moderate-to-vigorous physical activity in ≥ 10-min bouts (ρ = 0.627, p = 0.003; ρ = - 0.457, p = 0.049), more sedentary time (r = - 0.449, p = 0.047; r = 0.479, p = 0.038), and slower 400-m walk time (ρ = - 0.565, p = 0.022; ρ = 0.504, p = 0.028). CONCLUSIONS: Post-treatment advanced-stage OCS have decreased physical HRQoL, which is associated with modifiable factors such as worse PFD, less moderate-to-vigorous physical activity, more sedentary time, and decreased objective physical function. This highlights the need for ongoing supportive care and multidisciplinary interventions after first-line ovarian cancer treatment.

Do Groin Drains Reduce Postoperative Morbidity in Women Undergoing Inguinofemoral Lymphadenectomy for Vulvar Cancer?

OBJECTIVE: Sentinel lymph node biopsy has been widely adopted in the surgical management of women with early-stage vulvar cancer, but many patients require inguinofemoral lymphadenectomy (IFL). Following IFL, many surgeons drain the groin to prevent lymphocyst formation despite a lack of evidence to support this practice. Our objective was to investigate whether groin drains after IFL are associated with reduced postoperative morbidity in women undergoing surgery for vulvar cancer. METHODS: A retrospective cohort study of women diagnosed as having primary vulvar cancer who underwent vulvectomy/radical local excision and unilateral or bilateral IFL was conducted. Cases were ascertained from the weekly outcome reports of a statewide tertiary gynecologic oncology tumor board. Data including postoperative outcomes were abstracted from medical records. Patients were stratified into 1 of 2 groups according to whether a groin drain had been used. RESULTS: Seventy-one patients were included. Inguinal drains were used in 48 patients (67.6%) and 23 patients (32.4%) did not have their groin wound(s) drained. The most common postoperative complications recorded were wound infection (59.2%), groin lymphocyst (32.4%), and cellulitis (25.4%). The mean length of hospital admission was 11.5 days (2-40 days). Compared with patients in whom inguinal drains were placed, those in the "no drain" group had a significantly lower incidence of postoperative groin cellulitis (8.7% vs 25.4% P = 0.039). No significant differences were observed between patients in the "drain" and "no drain" groups in lymphocyst formation, wound infection, return to the operating room, duration of hospital stay, readmission post-discharge, and lower-limb lymphedema. CONCLUSIONS: In this study of patients undergoing inguinofemoral dissection for primary vulvar cancer, postoperative cellulitis occurred less frequently in patients without an inguinal drain. The incidence of other postoperative complications was no different whether or not a groin drain was used. Prospective studies may be warranted.

Activity Behaviors and Physiological Characteristics of Women With Advanced-Stage Ovarian Cancer: A Preliminary Cross-sectional Investigation.

OBJECTIVES: Ovarian cancer (OC) survivors experience many disease and treatment adverse effects. However, the impact of OC and its treatment on objective activity behaviors and physiological status have not been examined. The purpose of this study was to compare objectively measured activity behaviors and physiological characteristics of advanced-stage OC survivors to age-matched controls. METHODS: Twenty stage III-IV OC survivors and 20 controls completed assessments of activity behaviors (7-day accelerometry), physical function (400-meter walk as indicator of cardiorespiratory fitness, repeated chair rise, 6-meter walking tests), muscle strength (1-repetition maximum and handgrip), body composition (dual-energy x-ray absorptiometry), and musculoskeletal morphology (peripheral quantitative computed tomography). RESULTS: Compared with controls, OC survivors spent more time/day in prolonged sedentary bouts (P = 0.039, r = 0.32), had lower cardiorespiratory fitness (P = 0.041, r = 0.33) and upper body strength (P = 0.023, r = 0.37), had higher areal bone mineral content (P = 0.047, r = 0.33) and volumetric trabecular density (P = 0.048, r = 0.31), but were not different in other measures of body composition nor in muscle morphology (P > 0.050). Only 20% (n = 4) of OC survivors accrued 150 minutes/week or greater moderate and vigorous physical activity (MVPA) time in 10-minute bouts or greater. Moderate and vigorous physical activity time/day in 10-minute bouts or greater was strongly associated with cardiorespiratory fitness (P = 0.001, ρ = -0.702) and lower extremity function (P = 0.019, ρ = -0.519) and moderately associated with muscle cross-sectional area (P = 0.035, ρ = 0.473). CONCLUSIONS: Posttreatment OC survivors spent more time in prolonged sedentary bouts and had lower cardiorespiratory fitness and upper body strength compared with controls. Moderate and vigorous physical activity was associated with physical function and muscle cross-sectional area. Future studies should test the efficacy of exercise interventions to increase MVPA, reduce sedentary behavior, and increase cardiorespiratory fitness and muscle strength in OC survivors.

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.

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.

Genetic analysis of heterogeneous subsets of circulating tumour cells from high grade serous ovarian carcinoma patients.

Circulating tumour cells (CTCs) are heterogenous and contain genetic information from the tumour of origin. They bear specific intra- and extra-cellular protein markers aiding in their detection. However, since these markers may be shared with other rare cells in the blood, only genetic testing can confirm their malignancy. Herein, we analyse different CTC subsets using single cell whole genome DNA sequencing to validate their malignant origin. We randomly selected putative CTCs identified by immunostaining that were isolated from 4 patients with high grade serous ovarian cancer (HGSOC) and one with benign cystadenoma. We specifically targeted CTCs positive for epithelial (CK/EpCAMpos), mesenchymal (vimentinpos), and pseudoendothelial (CK/EpCAMpos plus CD31pos) markers. We isolated these cells and performed whole genome amplification (WGA) and low-pass whole-genome sequencing (LP-WGS) for analysis of copy number alterations (CNA). Of the CK/EpCAMpos cells analysed from the HGSOC patients, 2 of 3 cells showed diverse chromosomal CNAs. However, the 4 pseudoendothelial cells (CK/EpCAMpos plus CD31pos) observed in the HGSOC cases did not carry any CNA. Lastly, two of the clusters of vimentin positive cells sequenced from those found in the benign cystadenoma case had CNA. Despite the low number of cells analysed, our results underscore the importance of genetic analysis of putative CTCs to confirm their neoplastic origin. In particular, it highlights the presence of a population of CK/EpCAMpos cells that are not tumour cells in patients with HGSOC, which otherwise would be counted as CTCs.

Multi-Marker Immunofluorescent Staining and PD-L1 Detection on Circulating Tumour Cells from Ovarian Cancer Patients.

Detection of ovarian cancer (OC) circulating tumour cells (CTCs) is primarily based on targeting epithelial markers, thus failing to detect mesenchymal tumour cells. More importantly, the immune checkpoint inhibitor marker PD-L1 has not been demonstrated on CTCs from OC patients. An antibody staining protocol was developed and tested using SKOV-3 and OVCA432 OC cell lines. We targeted epithelial (cytokeratin (CK) and EpCAM), mesenchymal (vimentin), and OC-specific (PAX8) markers for detection of CTCs, and CD45/16 and CD31 were used for the exclusion of white blood and vascular endothelial cells, respectively. PD-L1 was used for CTC characterisation. CTCs were enriched using the Parsortix™ system from 16 OC patients. Results revealed the presence of CTCs in 10 (63%) cases. CTCs were heterogeneous, with 113/157 (72%) cells positive for CK/EpCAM (epithelial marker), 58/157 (37%) positive for vimentin (mesenchymal marker), and 17/157 (11%) for both (hybrid). PAX8 was only found in 11/157 (7%) CTCs. In addition, 62/157 (39%) CTCs were positive for PD-L1. Positivity for PD-L1 was significantly associated with the hybrid phenotype when compared with the epithelial (p = 0.007) and mesenchymal (p = 0.0009) expressing CTCs. Characterisation of CTC phenotypes in relation to clinical outcomes is needed to provide insight into the role that epithelial to mesenchymal plasticity plays in OC and its relationship with PD-L1.