Value of prediction models in determining treatment strategies in patients with advanced stage epithelial ovarian cancer

This thesis aims to evaluate the value of prediction models in determining treatment strategies in patients with advanced stage epithelial ovarian cancer (EOC). The background of treatment and treatment decisions in these heterogeneous patient population is described in the first chapter. Chapter 2 investigates the accuracy of an offhand clinical assessment of irresectable disease and proposes a predictive model of suboptimal cytoreduction based on computed tomography (CT) scan and clinical parameters. Chapter 3 evaluates the incidence and causes of postoperative mortality after cytoreductive surgery for EOC. Chapter 4 aims to identify predictive parameters and generate a predictive model of 30-day morbidity. Chapter 5 concerns development of a predictive model of prognosis in patients with advanced stage EOC. Finally, chapter 6 discusses the content of this thesis and recommendations for further research are suggested

The feasibility of folate receptor alpha- and HER2-targeted intraoperative fluorescence-guided cytoreductive surgery in women with epithelial ovarian cancer: A systematic review

Background: Epithelial ovarian cancer (EOC) is often diagnosed late, with a 5-year relative survival of 30.2% for patients with metastatic disease. Residual disease following cytoreductive surgery is an important predictor for poor survival. EOC is characterized by diffuse peritoneal metastases and depositions of small size, challenging a complete resection. Targeted fluorescence imaging is a technique to enhance tumor visualization and can be performed intraoperatively. Folate receptor alpha (FRα) and human epidermal growth factor receptor 2 (HER2) are overexpressed in EOC in 80% and 20% of the cases, respectively, and have been previously studied as a target for intraoperative imaging. Objective: To systematically review the literature on the feasibility of FRα and HER2 targeted fluorescence-guided cytoreductive surgery (FGCS) in women with EOC. Methods: PubMed and Embase were searched for human and animal studies on FGCS targeting either HER2 or FRα in either women with EOC or animal models of EOC. Risk of bias and methodological quality were assessed with the SYRCLE and MINORS tool, respectively. Results: All animal studies targeting either FRα or HER2 were able to detect tumor deposits using intraoperative fluorescence imaging. One animal study targeting HER2 compared conventional cytoreductive surgery (CCS) to FGCS and concluded that FGCS, either without or following CCS, resulted in statistically significant less residual disease compared to CCS alone. Human studies on FGCS showed an increased detection rate of tumor deposits. True positives ranged between 75%–77% and false positives between 10%–25%. Lymph nodes were the main source of false positive results. Sensitivity was 85.9%, though only reported by one human study. Conclusion: FGCS targeting either HER2 or FRα appears to be feasible in both EOC animal models and patients with EOC. FGCS is a promising technique, but further research is warranted to validate these results and particularly study the survival benefit

Introducing a novice surgeon to an experienced robotic gynaecological oncology team: An observational cohort study on the impact of a structured curriculum on outcomes of cervical cancer surgery

Objective: To evaluate the effect on patient outcomes when introducing a novice robotic surgeon, trained in accordance with a structured learning curriculum, to an experienced robotic surgery team treating cervical cancer patients. Methods: Patients with early-stage cervical cancer who were treated with primary robot-assisted surgery between 2007 and 2019 were retrospectively included. In addition to the 165 patients included in a former analysis, we included a further 61 consecutively treated patients and divided all 226 patients over three groups: early learning phase of 61 procedures without structured training (group 1), experienced phase of 104 procedures (group 2), and the 61 procedures during introduction of a novice with structured training (group 3). Risk-adjusted cumulative sum (RA-CUSUM) analysis was performed to assess the learning curve effect. Patient outcomes between the groups were compared. Results: Based on RA-CUSUM analysis, no learning curve effect was observed for group 3. Regarding surgical outcomes, mean operation time in group 3 was significantly shorter than group 1 (p < 0.001) and similar to group 2 (p = 0.96). Proportions of intraoperative and postoperative adverse events in group 3 were not significantly different from the experienced group (group 2). Regarding oncological outcomes, the 5-year disease-free survival, disease-specific survival, and overall survival in group 3 were not significantly different from the experienced group. Conclusions: Introducing a novice robotic surgeon, who was trained in accordance with a structured learning curriculum, resulted in similar patient outcomes as by experienced surgeons suggesting novices can progress through a learning phase without compromising outcomes of cervical cancer patients

TOPical Imiquimod treatment of high-grade Cervical intraepithelial neoplasia (TOPIC trial): Study protocol for a randomized controlled trial

Background: Cervical intraepithelial neoplasia (CIN) is the premalignant condition of cervical cancer. Whereas not all high grade CIN lesions progress to cervical cancer, the natural history and risk of progression of individual lesions remain unpredictable. Therefore, high-grade CIN is currently treated by surgical excision: large loop excision of the transformation zone (LLETZ). This procedure has potential complications, such as acute haemorrhage, prolonged bleeding, infection and preterm birth in subsequent pregnancies. These complications could be prevented by development of a non-invasive treatment modality, such as topical imiquimod treatment. The primary study objective is to investigate the efficacy of topical imiquimod 5 % cream for the treatment of high-grade CIN and to develop a biomarker profile to predict clinical response to imiquimod treatment. Secondary study objectives are to assess treatment side-effects, disease recurrence and quality of life during and after different treatment modalities. Methods/design: The study design is a randomized controlled trial. One hundred fort

Small Cell Carcinoma of the Ovary, Hypercalcemic Type (SCCOHT):Patient Characteristics, Treatment, and Outcome—A Systematic Review

Background: Small-cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare aggressive ovarian malignancy mainly affecting children, adolescents, and young adults. Since the discovery of mutations in the SMARCA4 gene in 2014, SCCOHT has become the subject of extensive investigation. However, international uniform treatment guidelines for SCCOHT are lacking and the outcome remains poor. The aim of this systematic review is to generate an overview of all reported patients with SCCOHT from 1990 onwards, describing the clinical presentation, genetic characteristics, treatment, and outcome. Methods: A systematic search was performed in the databases Embase, Medline, Web of Science, and Cochrane for studies that focus on SCCOHT. Patient characteristics and treatment data were extracted from the included studies. Survival was estimated using Kaplan–Meier’s methodology. To assess the difference between survival, the log-rank test was used. To quantify the effect of the FIGO stage, the Cox proportional hazard regression model was estimated. The chi-squared test was used to study the association between the FIGO stage and the surgical procedures. Results: Sixty-seven studies describing a total of 306 patients were included. The median patient age was 25 years (range 1–60 years). The patients mostly presented with non-specific symptoms such as abdominal pain and sometimes showed hypercalcemia and elevated CA-125. A great diversity in the diagnostic work-up and therapeutic approaches was reported. The chemotherapy regimens were very diverse, all containing a platinum-based (cisplatin or carboplatin) backbone. Survival was strongly associated with the FIGO stage at diagnosis. Conclusions: SCCOHT is a rare and aggressive ovarian cancer, with a poor prognosis, and information on adequate treatment for this cancer is lacking. The testing of mutations in SMARCA4 is crucial for an accurate diagnosis and may lead to new treatment options. Harmonization and international collaboration to obtain high-quality data on diagnostic investigations, treatment, and outcome are warranted to be able to develop international treatment guidelines to improve the survival chances of young women with SCCOHT.</p

Fertility-sparing surgery and fertility preservation in cervical cancer: The desire for parenthood, reproductive and obstetric outcomes

Objective: To evaluate the desire for parenthood and reproductive outcomes of young cervical cancer survivors who underwent fertility-sparing surgery or fertility preservation procedures for invasive cervical cancer. Methods: All women <45 years who underwent fertility-sparing treatment for invasive cervical cancer in a tertiary referral center in the Netherlands between January 2009 and January 2020 were identified. Fertility-sparing treatment options included Vaginal Radical Trachelectomy (VRT) for patients with early-stage disease and fertility preservation techniques (FP) when requiring Radical Hysterectomy (RH) or chemoradiotherapy. Data on reproductive intentions – and outcomes were retrieved from medical files and questionnaires. Results: 75 patients were identified of whom 34 underwent VRT, 9 RH and 32 had (chemo)radiotherapy. 26 patients started FP of whom 23 (88.5%) successfully preserved fertility through cryopreservation of embryos, oocytes and ovarian tissue. After a median follow-up of 49 months, 5 patients developed recurrent disease and died. Reproductive outcomes were retrieved in 58 patients. 89.6% maintained their desire for parenthood after cancer treatment. Following VRT, we report a pregnancy rate of 61.9% among the patients attempting conception (n = 24). 15 patients conceived 21 pregnancies which resulted in 15 live-births, yielding a live-birth rate of 75.0%. Following RH or (chemo)radiotherapy, 3 surrogate pregnancies were established (21.4%) using frozen-thawed material with good neonatal outcomes. Conclusion: Many cervical cancer survivors maintain the desire to become parents eventually. In early-stage disease, VRT shows good reproductive outcomes without compromising oncological safety. For those requiring gonadotoxic treatment fertility preservation and gestational surrogacy provides a promising alternative for achieving a biological offspring