Maaike A. van der Aa

Confirmation of the utility of the CA-125 elimination rate (KELIM) as an indicator of the chemosensitivity in advanced-stage ovarian cancer in a “real-life setting”

The modeled CA-125 ELIMination rate constant K (KELIM) has been validated as a marker of response to chemotherapy in >12,000 patients with advanced epithelial ovarian carcinoma (EOC) treated in first-line setting enrolled in >12 clinical trials. Patient KELIM is calculable online https://www.biomarker-kinetics.org/presentation. The objective was to investigate the prognostic value of KELIM in a large real-life national cancer registry with non-selected patients. We investigated 4,025 EOC patients from the Netherlands Cancer Registry treated with neoadjuvant chemotherapy (NACT) ± followed by interval debulking surgery (IDS). Patient KELIM values were calculated in patients with ≥ 3 CA-125 measurements during NACT. KELIM was standardized with a pre-specified cut-off and scored as unfavorable/favorable (<1.0/≥1.0). KELIM's prognostic value regarding radiological response, completeness of IDS, progression-free survival (PFS), and overall survival (OS) was assessed using univariate/multivariate analyses. The data from 1,582 patients treated with heterogeneous chemotherapy regimens and sequences were assessable. KELIM was prognostic for radiological response and the likelihood of complete IDS after NACT (odds ratio=2.59; 95% confidence interval [CI]=2.04-3.29). Moreover, KELIM was independently associated with PFS (hazard ratio [HR]=0.76; 95% CI=0.66-0.87), and OS (HR=0.79; 95% CI=0.69-0.91). Combining KELIM with the completeness of the IDS resulted in 3 prognostic groups (satisfactory, intermediate, and poor) with significant OS differences, namely a good, intermediate, and poor survival respectively. The value of KELIM, as a pragmatic indicator of response to chemotherapy, was maintained in a large real-life population-based cohort, highlighting its applicability in routine conditions.

Patient Voices: What Can We Learn From the Covid‐19 Pandemic About Follow‐Up Care in Gynaecologic Oncology?

ABSTRACT Purpose To explore women's experiences with follow‐up care after gynaecological cancer during the Covid‐19 pandemic and identify key elements of aftercare from their perspective. Methods A qualitative study was performed, including five focus group discussions and two individual interviews with 20 participants diagnosed with ovarian ( n  = 5), cervical ( n  = 6), endometrial ( n  = 5) or vulvar cancer ( n  = 4) who received follow‐up care during the Covid‐19 pandemic in the Netherlands. Transcripts underwent thematic analysis, guided by the framework of the Picker Principles of Patient‐Centred Care. Results Five themes were generated: (1) continuity of care, (2) absence of family members and carers, (3) meeting my needs, (4) managing my needs and (5) the cancer survivor narrative. The main changes experienced during the Covid‐19 pandemic were the introduction to remote healthcare and the absence of family members. An interconnection between themes was found, highlighting that providing a designated, always accessible contact person can be a catalyst for the improvement of information provision and healthcare guidance. Conclusions In conclusion, this study highlights the need for personalised and patient‐centred follow‐up that promotes patient empowerment, and how this can be provided by a designated contact person. Findings emphasise the importance of tailored support, involvement of family members, addressing information gaps, and overcoming barriers to self‐management. Lastly, the findings provide direction on how to approach follow‐up care in the future. Patient Contribution This study was done in close collaboration with the patient advocacy group Olijf; their significant input in both the design and conduct of the study is invaluable. Olijf's involvement ensured that the research remained patient‐centred and aligned with the real‐life concerns and priorities of those affected by gynaecological cancers. The participants in this study, all of whom are gynaecological cancer survivors, played an important role by sharing their experiences, and we extend our gratitude to them. Their insights were critical in shaping the findings of this research.

Incidence and predictors of peritoneal metastases of gynecological origin: a population-based study in the Netherlands

Peritoneal metastases (PM) are a challenge in gynecological cancers, but its appearance has never been described in a population-based study. Therefore, we describe the incidence of PM and identify predictors that increase the probability of peritoneal spread. All ovarian, endometrial and cervical cancer patients diagnosed in the Netherlands between 1989 and 2015 were identified from the Netherlands Cancer Registry and stratified for PM. Crude and age-adjusted incidence over time was calculated. Independent predictors for PM were identified using uni- and multivariable analyses. The 94,981 patients were diagnosed with ovarian, endometrial or cervical cancer and respectively 61%, 2% and 1% presented with PM. Predictors for PM in ovarian cancer were: age between 50 and 74 years (odds ratio [OR]=1.19; 95% confidence interval [CI]=1.08-1.32), other distant metastases (OR=1.25; 95% CI=1.10-1.41), poor differentiation grade (OR=2.00; 95% CI=1.73-2.32) and serous histology. Predictors in endometrial cancer were lymph node metastases (OR=2.32; 95% CI=1.65-3.26), other distant metastases (OR=1.38; 95% CI=1.08-1.77), high-grade tumors (OR=1.95; 95% CI=1.38-2.76) and clear cell (OR=1.49; 95% CI=1.04-2.13) or serous histology (OR=2.71; 95% CI=2.15-3.42). In cervical cancer, the risk is higher in adenocarcinoma than in squamous cell carcinoma (OR=4.92; 95% CI=3.11-7.79). PM are frequently seen in patients with ovarian cancer. In endometrial and cervical cancer PM are rare. Histological subtype was the strongest predictive factor for PM in all 3 cancers. Better understanding of predictive factors for PM and thus the biological behavior is of paramount importance.

Short‐term surgical complications after radical hysterectomy—A nationwide cohort study

AbstractIntroductionCentralization has, among other aspects, been argued to have an impact on quality of care in terms of surgical morbidity. Next, monitoring quality of care is essential in identifying areas of improvement. This nationwide cohort study was conducted to determine the rate of short‐term surgical complications and to evaluate its possible predictors in women with early‐stage cervical cancer.Material and methodsWomen diagnosed with early‐stage cervical cancer, 2009 FIGO stages IB1 and IIA1, between 2015 and 2017 who underwent radical hysterectomy with pelvic lymphadenectomy in 1 of the 9 specialized medical centers in the Netherlands, were identified from the Netherlands Cancer Registry. Women were excluded if primary treatment consisted of hysterectomy without parametrial dissection or radical trachelectomy. Women in whom radical hysterectomy was aborted during the procedure, were also excluded. Occurrence of intraoperative and postoperative complications and type of complications, developing within 30 days after surgery, were prospectively registered. Multivariable logistic regression analysis was used to identify predictors of surgical complications.ResultsA total of 472 women were selected, of whom 166 (35%) developed surgical complications within 30 days after radical hysterectomy. The most frequent complications were urinary retention with catheterization in 73 women (15%) and excessive perioperative blood loss &gt;1000 mL in 50 women (11%). Open surgery (odds ratio [OR] 3.42; 95% CI 1.73‐6.76), chronic pulmonary disease (OR 3.14; 95% CI 1.45‐6.79), vascular disease (OR 1.90; 95% CI 1.07‐3.38), and medical center (OR 2.83; 95% CI 1.18‐6.77) emerged as independent predictors of the occurrence of complications. Body mass index (OR 0.94; 95% CI 0.89‐1.00) was found as a negative predictor of urinary retention. Open surgery (OR 36.65; 95% CI 7.10‐189.12) and body mass index (OR 1.15; 95% CI 1.08‐1.22) were found to be independent predictors of excessive perioperative blood loss.ConclusionsShort‐term surgical complications developed in 35% of the women after radical hysterectomy for early‐stage cervical cancer in the Netherlands, a nation with centralized surgical care. Comorbidities predict surgical complications, and open surgery is associated with excessive perioperative blood loss.

Impact of patient characteristics on primary treatment approach of endometrial cancer: a population-based study in the Netherlands

The incidence of endometrial cancer is rising worldwide, with increasing numbers of elderly patients with substantial comorbidity. We aimed to provide insight into the primary treatment strategies, trends, and outcomes for patients with endometrial cancer in the Netherlands across different periods, and to evaluate the influence of patient characteristics on treatment approaches within these periods. All patients diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage I to III endometrial cancer between 1995 and 2022 were identified in the Netherlands Cancer Registry. Data on histology, FIGO stage, primary treatment, Charlson comorbidity index, body mass index, and outcome were collected and analyzed. Patients were evaluated in 6 5-year cohorts to observe possible trends in treatment choices and outcomes over time, based on patient and tumor characteristics. A total of 43,443 patients were included. Most patients were diagnosed with endometrioid histology (89%, n = 38,751) and early-stage disease (FIGO I-II, 87%, n = 38,077). An increase in endometrial cancer incidence and survival was observed over time, along with a shift toward more non-endometrioid endometrial cases. A primary surgical approach was performed in 95% (n = 41,107) of patients. Among those receiving non-surgical management, curative treatment was reported in only 4% (n = 88). Most patients unfit for surgery either received no treatment (n = 1053, 2%) or were treated with hormonal therapy (n = 840, 2%). Over time, we observed increased use of hormonal therapy as a non-surgical treatment. Patients who did not undergo surgery were older, more often had a body mass index >30 kg/m Incidence and survival in patients with endometrial cancer increased between 1999 and 2022. Patients unfit for surgery most often received no treatment or palliative hormonal therapy. Curative radiotherapy is not often used in patients unfit for surgery and should be considered for this group of patients.

Radical hysterectomy or chemoradiotherapy for clinically early-stage cervical cancer with suspicious lymph nodes on imaging: a retrospective cohort study

The optimal treatment of clinically early-stage cervical cancer with suspicious lymph nodes on pretreatment imaging is unclear. Therefore, we aimed to compare surgery (i.e., radical hysterectomy and pelvic lymphadenectomy±adjuvant therapy) with primary chemoradiotherapy as treatment strategies in this patient group regarding recurrence-free, overall survival and toxicity. Women diagnosed between 2009-2017 with the International Federation of Gynecology and Obstetrics (2009) stage IA-IIA and suspicious nodes based on radiologic assessment of pretreatment imaging were retrospectively selected from the Netherlands Cancer Registry. Cox proportional hazard was used to estimate survival and logistic regression for toxicity. Inverse probability weighting was used to correct for confounding. Grade ≥2 surgery-related (≤30 days) and grade ≥3 chemotherapy or radiotherapy-related (≤6 months) toxicity were collected. Missing data were imputed. Of 330 patients included, 131 (40%) received surgery (followed by adjuvant therapy in 54%) and 199 (60%) chemoradiotherapy. Pathological nodal status was known in 100% of the surgery group and 32% (n=63) of the chemoradiotherapy group, of whom 43% (56/131) and 89% (56/63), respectively, had metastases. After adjustment for confounders, the recurrence-free survival (hazard ratio [HR]=0.67; 95% confidence interval [CI]=0.34-1.31) and overall survival (HR=0.75; 95% CI=0.38-1.47) were not significantly different between both groups, while surgery was associated with more toxicity (odds ratio=2.82; 95% CI=1.42-5.60), mainly surgery-related. In patients with clinically early-stage cervical cancer and suspicious nodes on imaging, surgery and primary chemoradiotherapy yielded comparable results in terms of survival, whereas surgery might be associated with more (surgery-related) short-term toxicity.

Effect of uterine manipulator on oncologic outcome in early-stage, low-grade endometrial cancer.

To evaluate the influence of intrauterine manipulators on oncological outcomes in early-stage, low-grade endometrioid endometrial cancer. This retrospective, nationwide population-based study included all women International Federation of Gynecology and Obstetrics stage I, low-grade endometrioid endometrial cancer who underwent total laparoscopic hysterectomy between January 2010 and December 2020 in the Netherlands. Patient data were identified from the Netherlands Cancer Registry. Data regarding hospital manipulator preferences were retrieved through an online survey. Patients were categorized based on hospital manipulator preference. Main outcome measures were recurrence of cancer, disease-free survival, overall survival, site of recurrence, and manipulator preference according to the type of hospital. Survival analyses were performed using univariable and multivariable Cox regression analysis. Of the total study population (N = 5205), 1524 (29.3%) patients underwent surgery in hospitals that preferred no intrauterine manipulators and 3681 (70.7%) in hospitals that demonstrated a preference for intrauterine manipulators. Cancer recurrence was seen in 195 patients, 49 (3.2%) in the non-intrauterine group and 146 (4.0%) in the intrauterine group. (p =.78) After adjusting for potential confounders, the type of uterus manipulator did not affect disease-free survival (HR 0.93, 95% CI 0.78 to 1.11) and overall survival (HR 0.90, 95% CI 0.75 to 1.09). Intrauterine manipulators were not associated with higher recurrence rates in early-stage, low-grade endometrioid endometrial cancer.