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Objective: To assess the association between pretreatment thrombocytosis, anemia, and leukocytosis and overall survival (OS) of advanced-stage EOC. Furthermore, to develop nomograms using established prognostic factors and pretreatment hematologic parameters to predict the OS of advanced EOC patients. Methods: Advanced-stage EOC patients treated between January 1996 and January 2010 in eastern Netherlands were included. Survival outcomes were compared between patients with and without pretreatment thrombocytosis (≥450,000 platelets/µL), anemia (hemoglobin level of <7.5 mmol/L), or leukocytosis (≥11.0 × 109 leukocytes/L). Three nomograms (for ≤3-, ≥5-, and ≥10-year OS) were developed. Candidate predictors were fitted into multivariable logistic regression models. Multiple imputation was conducted. Model performance was assessed on calibration, discrimination, and Brier scores. Bootstrap validation was used to correct for model optimism. Results: A total of 773 advanced-stage (i.e., FIGO stages IIB–IV) EOC patients were included. The median [interquartile range, IQR] OS was 2.3 [1.3–4.2] and 3.0 [1.4–7.0] years for patients with and without pretreatment thrombocytosis (p < 0.01). The median OS was not notably different for patients with and without pretreatment leukocytosis (p = 0.58) or patients with and without pretreatment anemia (p = 0.07). The final nomograms comprised established predictors with either pretreatment leukocyte or platelet count. The ≥5- and ≥10-year OS models demonstrated good calibration and adequate discrimination with optimism-corrected c-indices [95%-CI] of 0.76 [0.72–0.80] and 0.78 [0.73–0.83], respectively. The ≤3-year OS model demonstrated suboptimal performance with an optimism-corrected c-index of 0.71 [0.66–0.75]. Conclusions: Pretreatment thrombocytosis is associated with poorer EOC survival. Two well-performing models predictive of ≥5-year and ≥10-year OS in advanced-stage EOC were developed and internally validated. [ABSTRACT FROM AUTHOR]

Simple Summary: There has been a growing interest in the interplay between the immune system and the prognosis of epithelial ovarian cancer (EOC). It has become clear that EOC has the ability to escape destruction by the immune system by creating a highly immunosuppressive microenvironment in the abdominal cavity. The first case of an advanced-stage EOC patient who experienced the complete disappearance of her cancer following sepsis without undergoing cancer treatment was reported in 2018. Sepsis has the ability to both activate and suppress the immune system, presenting potential beneficial as well as detrimental effects. It is still unclear what impact sepsis has on the prognosis of advanced-stage EOC. This study's aim was to assess the impact of sepsis on the oncologic outcomes of advanced-stage EOC patients. Of 215 OC patients, a total of 18 advanced-stage EOC patients experienced sepsis. Their survival outcomes were compared with 3988 unmatched and 54 matched patients from the Netherlands Cancer Registry (NCR). The overall and progression-free survival was similar between the sepsis and (un)matched patients from the NCR. Our study suggests that sepsis and its subsequent immune response, overall, does not substantially influence the prognosis of EOC patients. Objective: The sepsis-induced inflammatory response may potentially affect malignant cells. Recently, a case of spontaneous regression of a histologically confirmed International Federation of Gynecology and Obstetrics (FIGO) stage IIIC epithelial ovarian cancer (EOC) following sepsis was reported. The aim of our study was to assess the impact of sepsis on the oncologic outcomes of advanced-stage EOC patients. Methods: Gynecologic oncologic patients admitted to the Intensive Care Unit of three oncologic centers between 2006 and 2019 were identified and patients who experienced sepsis following advanced-stage EOC diagnosis were selected. Survival outcomes were compared with advanced-stage EOC patients from the Netherlands Cancer Registry (NCR). To correct for case-mix differences, propensity score matching using 1:3 nearest neighbor matching was conducted after which survival analyses were repeated. Results: A total of 18 of 215 patients with advanced-stage EOC experienced sepsis. Sepsis patients had similar distributions of patient, tumor, and treatment characteristics to 3988 patients from the NCR cohort. A total of 3 of 18 patients died from the complications of sepsis. While the remaining patients initially responded to treatment, 14/15 patients relapsed. The median (IQR) overall survival was 31 (24–44) and 35 (20–60) months for the sepsis and unmatched NCR cohort (p = 0.56), respectively. The median (IQR) progression-free survival was 16 (11–21) and 16 (11–27) months (p = 0.90), respectively. Survival outcomes did not differ following propensity matching (overall survival of 31 (24–44) vs. 36 (20–56) months, p = 0.40; progression-free survival of 16 (11–21) and 16 (12–21) months, p = 0.72). Conclusion: In this observational study, the occurrence of sepsis did not affect the oncologic and survival outcomes of advanced-stage EOC patients. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To study the influence of a regional collaboration in epithelial ovarian cancer care on staging procedures, debulking results, and survival. METHODS: In an effort to optimize epithelial ovarian cancer treatment, a regional collaboration was introduced in the Netherlands in 2000. Gynecologic oncologists from the university center conducted surgery in community hospitals when ovarian cancer was considered based on the risk-of malignancy index or clinical suspicion. The National Cancer Registry registered 1,554 patients with epithelial ovarian cancer diagnosed in 11 participating Dutch hospitals between 1996 and 2010. Surgical procedures were compared during three periods (1996-1999, 2000-2004, and 2005-2009). Log-rank tests compared Kaplan-Meier survival curves of progression-free and overall survival before (1996-2000) and during the start of the collaboration (2001-2005). RESULTS: Staging was adequate for 139 patients (23.0%) before collaboration, and this proportion increased during the study periods to 32.1% and 62.1% (P<.01), when gynecologic oncologists more often staged cancer in patients (36.7% compared with 54.7% and 80.6%; P<.01). For 1,197 patients with advanced stage disease (stage lib or greater), the proportion of debulking procedures with an optimal (residual volume less than1 cm) as well as a complete result (no residuals) increased during the 14-year study period from 57.4% to 76.5% (P<.01) and from 24.1% to 43.4% (P<.01), respectively. Survival rates were similar before and during the start of the collaboration. In multivariable analysis, the treatment variables completeness of debulking, chemotherapy, and gynecologic oncologist attendance were independent prognostic factors for overall survival, as were age, stage, and tumor grade. CONCLUSIONS: After regional collaboration, gynecologic oncologists attended more surgeries and surgical outcomes improved, but progress in survival could not be demonstrated. Regional collaboration improved care for ovarian cancer patients. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The aim of this study was to describe trends in survival and therapy in advanced stage epithelial ovarian cancer (EOC) in the Netherlands and to determine if changes in therapy affected survival. Methods: All EOC patients diagnosed in the Netherlands during 1989–2009 were selected from the Netherlands Cancer Registry. Differences in treatment over time were tested by the Cochran-Armitage trend test. Multivariable relative survival analyses were performed to test whether changes in treatment are associated with survival. Results: 23,399 EOC patients were diagnosed, of whom 15,892 (67.9%) in advanced stage (stage ≥2b). In advanced stage patients, the proportion receiving (neo-)adjuvant chemotherapy and optimal debulking (residuals <1cm) increased over time in all age groups. In elderly patients (≥75years) a stable proportion (approximately 28%) did not receive any treatment. Five-year relative survival in advanced stage patients increased from 18% in 1989–1993 to 28% in 2004–2009. In the multivariable model survival improved over time (relative excess risk (RER) of 2004–2009 was 0.71, 95% CI 0.67–0.75 compared to 1989–1993). This RER attenuated to 0.85 (95% CI 0.80–0.90) and 0.91 (95% CI 0.83–0.99) with inclusion of treatment variables in the model (surgery with chemotherapy or optimal surgery with chemotherapy, respectively). This suggests that the improvement was mainly, although not entirely, caused by changes in treatment. Conclusion: Treatment in advanced stage EOC patients in the Netherlands improved over the last two decades; more patients received (neo)adjuvant chemotherapy and underwent optimal debulking surgery. Changes in treatment led to partial improvement of survival in EOC patients. [Copyright &y& Elsevier]

Background: Contradicting results regarding ovarian cancer prognosis in women with endometriosis have been reported in the literature. Owing to the small sample size of previous studies, larger studies are required to elucidate the role of endometriosis in ovarian cancer prognosis.Objective: This study aimed to evaluate the survival rate in women with ovarian cancer with or without histologically proven endometriosis in a Dutch population-based cohort.Study Design: All women with ovarian cancer diagnosed between 1990 and 2015 were identified from the Netherlands Cancer Registry. We linked these women with the Dutch nationwide registry of histopathology and cytopathology (Pathologisch-Anatomisch Landelijk Geautomatiseerd Archief) to identify all women with histologically proven endometriosis. We compared the prognosis of patients with ovarian cancer with and without histologically proven endometriosis. Primary outcome was the overall survival with subgroup analyses stratified by histologic ovarian cancer subtype and stage. Multivariable Cox proportional hazard analysis was used to estimate hazard ratios with 95% confidence intervals.Results: We included 32,419 patients with ovarian cancer, of whom 1979 (6.1%) had histologically proven endometriosis. The median age of histologic endometriosis diagnosis was 53 years (interquartile range, 46-62). Of all women with ovarian cancer and endometriosis, 81.2% received a diagnosis of synchronous endometriosis and ovarian cancer. The endometriosis cohort was younger at ovarian cancer diagnosis, had more favorable tumor characteristics, and more often had surgical treatment for ovarian cancer than the women without endometriosis. These variables were included in the multivariable model as confounders. Women with histologically proven endometriosis had a significantly better prognosis in both crude and adjusted analyses (hazard ratio, 0.46; 95% confidence interval, 0.43-0.49; P<.0005, and adjusted hazard ratio, 0.89; 95% confidence interval, 0.83-0.95; P<.05, respectively).Conclusion: Women with ovarian cancer and histologically proven endometriosis had longer overall survival than women with ovarian cancer without endometriosis, even after adjustment for confounders. Future studies on ovarian cancer treatment and prognosis should consider stratifying by endometriosis status to elucidate its role. Furthermore, women diagnosed as having ovarian cancer and concurrent endometriosis should be explained the role of endometriosis in ovarian cancer survival. [ABSTRACT FROM AUTHOR]

Introduction: Epithelial ovarian cancer (EOC) patients undergoing splenectomy during cytoreductive surgery represent a small subgroup of patients. Splenic metastases or technical reasons due to extensive upper abdominal disease may require a splenectomy. It has been hypothesized that as the spleen's antitumor immunologic functions may inhibit cancer growth, splenectomy may promote the growth of residual disease as observed in other cancer types of murine studies. The few studies assessing the impact of splenectomy on the oncologic outcomes of advanced stage EOC patients have reported inconsistent results. It remains unclear whether splenectomy during cytoreductive surgery is justified to achieve complete cytoreduction. The aim of this study was to assess the impact of a splenectomy on perioperative outcomes and survival of advanced stage EOC patients., Material and Methods: In this nationwide population-based study, all consecutive patients diagnosed with FIGO stage IIIC and IV EOC between 1 January 2008 and 31 December 2015 were identified from the Netherlands Cancer Registry. Patients who underwent cytoreductive surgery combined with platinum-based chemotherapy as primary treatment were selected. Differences in clinicopathologic characteristics between splenectomy and non-splenectomy patients were assessed. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier survival curves and log-rank tests. Cox proportional hazards models were used to adjust for covariates that influence survival., Results: A total of 3911 patients were identified: 99 splenectomy and 3812 non-splenectomy patients. Splenectomy patients were more likely to undergo extensive surgery or surgical reintervention, to receive intraperitoneal chemotherapy, intraoperative and postoperative blood transfusion, to experience postoperative infections, and to be admitted to an intensive care unit (all p < 0.002). No significant differences in PFS or OS were observed between splenectomy vs non-splenectomy patients after adjusting for covariates., Conclusions: Although advanced stage EOC patients who undergo splenectomy during cytoreductive surgery have less favorable perioperative outcomes, no adverse impact of splenectomy on the survival of advanced stage EOC patients was observed. Splenectomy during cytoreductive surgery seems to be justified to achieve complete cytoreduction in advanced stage EOC patients., (© 2021 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Objective: Assessing the association between endometriosis and/or adenomyosis and ovarian cancer., Methods: We identified all women with histological proven endometriosis (51,544 women) and/or adenomyosis (85,015 women) from the Dutch pathology database (1990-2015) and matched with women with a benign dermal nevus (132,654 women). Histology results for ovarian cancer were retrieved. We estimated crude and age-adjusted incidence rate ratios (IRR) for ovarian cancer., Results: We found 1017 (2.0%), 1284 (1.5%) and 471 (0.4%) ovarian cancer cases in the endometriosis, adenomyosis and nevus cohort, respectively. The age-adjusted IRRs were 19.75 (95% CI 16.70-23.35) in the endometriosis cohort and 5.93 (95% CI 4.91-7.16) in the adenomyosis cohort. The highest IRRs were found for endometrioid and clear cell ovarian cancer subtypes. Excluding the first year of follow-up did not result in a significant IRR for ovarian cancer overall but resulted in a statistically significant age-adjusted IRR of 3.92 (95% CI 2.19-7.01) for clear cell ovarian cancer and 2.39 (95% CI 1.28-4.45) for endometrioid ovarian cancer in the endometriosis cohort. Additionally, we found a statistically significant age-adjusted IRR of 2.51 (95% CI 1.29-4.90) for endometrioid ovarian cancer in the adenomyosis cohort., Conclusion: We found an increased ovarian cancer incidence in both histological proven endometriosis and adenomyosis. This increased incidence was largest for endometriosis. Excluding the first year of follow-up resulted in an increased incidence for endometrioid ovarian cancer in both cohorts and clear cell ovarian cancer in the endometriosis cohort. This study shows that gynecologist should also be aware of an increased ovarian cancer incidence in women with adenomyosis., Competing Interests: Declaration of competing interest The authors report no conflict of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The aim of this study was to evaluate the adequacy of family history taking in epithelial ovarian cancer (EOC) patients and to identify factors that determine adequacy. Furthermore, the validity of family history taking was assessed by comparison with self-administered questionnaires. Medical records of all 1,112 EOC patients registered by the nation-wide cancer registry and diagnosed in eleven Dutch hospitals between 1996 and 2006 were reviewed. Adequate family history taking was defined as a written notification of the presence or absence of relatives with breast or ovarian cancer. Factors that were correlated with family history taking were identified using univariable and multivariable logistic regression. 147 patients filled in a postal questionnaire. An adequate family history was taken in 41% of all cases. Younger age, an academic hospital and having undergone surgery and/or chemotherapy were associated with adequate family history taking. The comparison with self-administered questionnaires showed a disagreement in 64% mainly due to missing data in medical records. Documentation on family history is either absent or inadequate in the medical records in the majority of EOC patients. These data urge for better uptake of hereditary cancer risk assessment. Different strategies for this assessment like improved family history taking and genetic testing in EOC patients should be explored.

Patients with double primary cancer (DPC) of the ovary and endometrium are considered to have a better prognosis than patients with only epithelial ovarian cancer (EOC). The aim of this study was to clarify the difference in prognosis by comparing clinicopathologic characteristics and survival. From the population-based database of the nationwide Netherlands Cancer Registry, women diagnosed between 1996 and 2006 with EOC were identified. Within this database of all EOC patients in 11 hospitals, the DPC patients were identified. Differences in characteristics between EOC-only and DPC patients were tested using Pearson χ tests and t-tests. Differences in overall survival were analyzed by Kaplan-Meier survival analyses and log-rank tests. Multivariable Cox regression analyses were performed to study the factors that influence survival. Among 1105 EOC patients, 29 (2.6%) DPC patients were identified. DPC patients were more often premenopausal (P<0.01), in the early stage of disease (P<0.01), and more often had low-grade endometrioid tumors. Overall survival was better for DPC patients (P=0.004), but after stratification for stage the overall survival was similar. In multivariable analysis, DPC patients did not show a favorable prognosis after adjustment for age, disease stage, histology, tumor grade, and residual tumor after surgery. DPC patients seem to constitute a prognostically favorable group among EOC patients; however, after correction for age, stage, histology, tumor grade, and residue, survival is similar. This study shows how important it is for clinicians to distinguish DPC from metastatic diseases.

Introduction: Routine follow-up is standard medical practice in ovarian cancer patients treated with curative intent. However, no strong evidence exists indicating that prognosis is improved. The objective of this study was to evaluate the routine follow-up schedule for ovarian cancer patients regarding the adherence to the Dutch protocol, the detection of recurrences, and the follow-up's impact on overall survival., Methods: All 579 consecutive patients diagnosed with epithelial ovarian, primary peritoneal, or fallopian tube cancer in 4 Dutch hospitals between 1996 and 2006 were selected. Only patients in complete clinical remission after primary treatment were studied. Compliance to the Dutch follow-up guideline was assessed in a random sample of 68 patients. Of the 127 patients with recurrence, the mode of recurrence detection was addressed. Survival time since primary treatment was calculated using the Kaplan-Meier method., Results: The patients received more follow-up visits than was recommended according to the guideline. The cumulative 5-year risk of recurrence was 55% (95% confidence interval [CI], 43%-67%). The survival of patients with recurrent ovarian cancer detected asymptomatically at a routine visit (n = 51) tended to be better compared with patients with symptomatic detection at a routine (n = 31) or diagnosed after an interval visit (n = 31). The median survival times were 44 (95% CI, 38-64), 29 (95% CI, 21-38), and 33 months (95% CI, 19-61), respectively (P = 0.08). The median time from primary treatment to recurrence was similar for the 3 groups: 14, 10, and 11 months, respectively (P = 0.26)., Conclusions: Follow-up in line with (inter)national guidelines yields a seemingly longer life expectancy if the recurrence was detected asymptomatically. However, this result is expected to be explained by differences in tumor biology and length-time bias.