Publications by authors named "Toon Van Gorp"

79 Publications

Experience with PlasmaJet™ in debulking surgery in 87 patients with advanced-stage ovarian cancer.

J Surg Oncol 2021 Mar 26;123(4):1109-1114. Epub 2021 Jan 26.

Division of Gynecologic Oncology, University Hospital Leuven, Leuven Cancer Institute, KU Leuven, Leuven, Belgium.

Objective: The aim was to evaluate the effectiveness and safety of PlasmaJet™ in cytoreductive surgery in patients with advanced-stage ovarian cancer.

Methods: All patients between September 2013 and January 2018 undergoing surgical cytoreduction for advanced-stage ovarian cancer with the help of PlasmaJet™ were identified and analyzed retrospectively.

Results: Eighty-seven patients diagnosed with advanced-stage ovarian cancer underwent surgery with PlasmaJet™. Primary debulking surgery was performed in 15 cases. Fifty-seven patients underwent interval debulking after neoadjuvant chemotherapy. Secondary and tertiary debulking was done in, respectively, 11 and three patients, and one patient underwent quaternary debulking using PlasmaJet™. In all 87 patients but one, complete resection of all macroscopic disease was obtained. PlasmaJet™ was used to remove carcinomatosis on the peritoneum, bowel serosa, intestinal mesentery, and lesions in the upper abdomen (diaphragm and liver surface). No damage to the bladder or ureter was noted in relation to the use of PlasmaJet™. Three patients developed a bowel leakage postoperatively. In one of these patients, PlasmaJet™ was used to treat tumoral implants in the affected region.

Conclusions: Our series suggests that the use of PlasmaJet™ is efficient and safe in obtaining complete resection of all macroscopic tumoral lesions in advanced-stage ovarian cancer.
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http://dx.doi.org/10.1002/jso.26385DOI Listing
March 2021

A phase III, randomized, double blinded trial of platinum based chemotherapy with or without atezolizumab followed by niraparib maintenance with or without atezolizumab in patients with recurrent ovarian, tubal, or peritoneal cancer and platinum treatment free interval of more than 6 months: ENGOT-Ov41/GEICO 69-O/ANITA Trial.

Int J Gynecol Cancer 2020 Dec 14. Epub 2020 Dec 14.

GEICO (Grupo Español de Investigación en Cáncer de Ovario), Madrid, Spain.

Background: Platinum based chemotherapy is the treatment of choice for ovarian cancer patients with a platinum treatment free interval of >6 months. Niraparib is an oral poly (ADP-ribose) polymerase inhibitor approved as maintenance therapy after a response to platinum rechallenge, regardless of BRCA status. Atezolizumab is a humanized monoclonal antibody targeting programmed death-ligand 1 (PD-L1). A combination of poly (ADP-ribose) polymerase inhibitor and anti-PD-L1/programmed cell death protein 1 (PD-1) has shown synergy in preclinical models and promising clinical activity.

Primary Objective: To determine whether the addition of atezolizumab to carboplatin based chemotherapy and to subsequent maintenance with niraparib improves progression free survival compared with placebo in patients with recurrent disease and a platinum treatment free interval of >6 months.

Trial Design: The Atezolizumab and NIraparib Treatment Association (ANITA) trial is a GEICO (Grupo Español de Investigación en Cáncer de Ovario) led phase III, randomized, double-blinded, multicenter European Network for Gynecological Oncological Trials (ENGOT) study. Patients will be randomized to arm A (control arm) consisting of platinum based chemotherapy (investigator's choice) plus a placebo of atezolizumab followed by maintenance niraparib plus a placebo of atezolizumab, or to arm B (experimental arm) consisting of platinum based chemotherapy (investigator's choice) plus atezolizumab followed by maintenance niraparib plus atezolizumab.

Major Inclusion/exclusion Criteria: Inclusion criteria are women aged over 18 years, diagnosed with relapsed high grade serous, endometrioid, or undifferentiated ovarian, fallopian tube, or primary peritoneal carcinoma. Patients are eligible if they received no more than two previous lines of chemotherapy, relapsed ≥6 months after the last platinum containing regimen, and have at least one measurable lesion according to the response evaluation criteria in solid tumors, version 1.1.

Primary Endpoint: The primary endpoint for this study is progression free survival.

Sample Size: Approximately 414 patients will be recruited and randomized in a 1:1 ratio, with the aim of demonstrating a benefit in progression free survival for the experimental arm with a hazard ratio of O.7, using a two sided alpha of 0.05 and a power of 80%.

Estimated Dates For Completing Accrual And Presenting Results: The trial was launched in the fourth quarter of 2018 and is estimated to close in the second quarter of 2021. Mature results for progression free survival are expected to be presented by 2023.

Trial Registration: Clinicaltrials.gov NCT03598270.
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http://dx.doi.org/10.1136/ijgc-2020-001633DOI Listing
December 2020

No influence of sarcopenia on survival of ovarian cancer patients in a prospective validation study.

Gynecol Oncol 2020 Dec 2;159(3):706-711. Epub 2020 Oct 2.

Department of Gynecology, the Netherlands Cancer Institute, Plesmanlaan 121, 1066CX Amsterdam, the Netherlands. Electronic address:

Objective: Decrease in skeletal muscle index (SMI) during neoadjuvant chemotherapy (NACT) has been associated with worse outcome in patients with advanced ovarian cancer. To validate these findings, we tested if a decrease in SMI was a prognostic factor for a homogenous cohort of patients who received NACT in the randomized phase 3 OVHIPEC-trial.

Methods: CT-scans were performed at baseline and after two cycles of neoadjuvant chemotherapy in stage III ovarian cancer patients. The SMI (skeletal muscle area in cm divided by body surface area in m) was calculated using SliceOMatic software. The difference in SMI between both CT-scans (ΔSMI) was calculated. Cox-regression analyses were performed to analyze the independent effect of a difference in SMI (ΔSMI) on outcome. Log-rank tests were performed to plot recurrence-free (RFS) and overall survival (OS). The mean number of adverse events per patient were compared between groups using t-tests.

Results: Paired CT-scans were available for 212 out of 245 patients (87%). Thirty-four of 74 patients (58%) in the group with a decrease in ΔSMI and 73 of 138 of the patients (53%) in the group with stable/increase in ΔSMI had died. Median RFS and OS did not differ significantly (p = 0.297 and p = 0.764) between groups. Patients with a decrease in SMI experienced more pre-operative adverse events, and more grade 3-4 adverse events.

Conclusion: Decreased SMI during neoadjuvant chemotherapy was not associated with worse outcome in patients with stage III ovarian cancer included in the OVHIPEC-trial. However, a strong association between decreasing SMI and adverse events was found.
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http://dx.doi.org/10.1016/j.ygyno.2020.09.042DOI Listing
December 2020

Cancer Surveillance in Healthy Carriers of Germline Pathogenic Variants in : A Review of Secondary Prevention Guidelines.

J Oncol 2020 20;2020:9873954. Epub 2020 Jun 20.

Department of General Medical Oncology, University Hospitals Leuven, Leuven, Belgium.

Germline pathogenic alterations in the breast cancer susceptibility genes 1 () and 2 () are the most prevalent causes of hereditary breast and ovarian cancer. The increasing trend in proportion of cancer patients undergoing genetic testing, followed by predictive testing in families of new index patients, results in a significant increase of healthy germline 2 mutation carriers who are at increased risk for breast, ovarian, and other -related cancers. This review aims to give an overview of available screening guidelines for female and male carriers of pathogenic or likely pathogenic germline variants per cancer type, incorporating malignancies that are more or less recently well correlated with . We selected guidelines from national/international organizations and/or professional associations that were published or updated between January 1, 2015, and February 1, 2020. In total, 12 guidelines were included. This review reveals several significant discordances between the different guidelines. Optimal surveillance strategies depend on accurate age-specific cancer risk estimates, which are not reliably available for all -related cancers. Up-to-date national or international consensus guidelines are of utmost importance to harmonize counseling and proposed surveillance strategies for carriers.
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http://dx.doi.org/10.1155/2020/9873954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7322604PMC
June 2020

Para-aortic lymph node surgical staging in locally-advanced cervical cancer: comparison between robotic versus conventional laparoscopy.

Int J Gynecol Cancer 2020 04 19;30(4):466-472. Epub 2020 Feb 19.

Gynecological Oncology, KU Leuven University Hospitals Leuven, Leuven, Flanders, Belgium

Objective: With the expansion of the use of minimally invasive surgical techniques within the field of gynecological oncology, a robot assisted procedure seems to be an attractive technique for para-aortic lymph node sampling. The aim of this study was to compare robotic versus conventional laparoscopic para-aortic lymphadenectomy in patients with locally advanced cervical cancer.

Methods: In this monocentric retrospective study, we included patients with locally-advanced cervical cancer (International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IB2-IVA or IB1 with suspicious pelvic lymph nodes), who underwent a para-aortic lymphadenectomy up to the inferior mesenteric artery between December 1994 and December 2016 (robotic technique starting from December 2012).

Results: A total of 217 patients were included in the study (robotic, n=55 vs laparoscopic, n=162). When comparing conventional laparoscopic versus robotic para-aortic lymphadenectomy, the median age was 48 versus 49 years and the median body mass index was 24.4 vs 24.7 kg/m, respectively. In the robotic or laparoscopic group, 85% and 83% were squamous carcinomas, respectively. Patients who underwent a robotic procedure had a higher American Society of Anesthesiologists (ASA) score (ASA2: 62% vs 56%, ASA3: 20% vs 2%, p<0.001), more prior major abdominal surgery (18% vs 6%, p=0.016), less estimated blood loss (median, 25 mL vs 62.5 mL, p<0.001), more para-aortic lymph nodes removed (11 vs 6, p<0.001), shorter postoperative stay (1.8 vs 2.3 days, p=0.002), and a higher, but non-significant, rate of metastatic para-aortic lymph nodes (13% vs 5%, p=0.065) compared with the laparoscopic procedure, respectively. There was no difference in complication rates between the two approaches. The most frequent complications were grade I and grade II according to the Clavien Dindo classification. No difference was observed in progression-free survival between robotic and laparoscopic para-aortic lymphadenectomy after 2 years (both groups 66%) (p=0.472). Also, 2 year overall survival was similar between the groups (77% vs 81% for robotic vs conventional laparoscopy group, respectively) (p=0.749).

Conclusion: Robotic para-aortic lymphadenectomy in patients with locally-advanced cervical cancer resulted in better perioperative outcomes and similar survival outcomes when compared with a conventional laparoscopic approach.
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http://dx.doi.org/10.1136/ijgc-2019-000961DOI Listing
April 2020

Short-term surgical complications after radical hysterectomy-A nationwide cohort study.

Acta Obstet Gynecol Scand 2020 07 6;99(7):925-932. Epub 2020 Feb 6.

Department of Research & Development, Netherlands Comprehensive Cancer Organization (IKNL), Utrecht, the Netherlands.

Introduction: Centralization 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 Methods: Women 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.

Results: A 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 >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.

Conclusions: Short-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.
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http://dx.doi.org/10.1111/aogs.13812DOI Listing
July 2020

What do we need to know about anatomy in gynaecology: A Delphi consensus study.

Eur J Obstet Gynecol Reprod Biol 2020 Feb 16;245:56-63. Epub 2019 Dec 16.

Department of Obstetrics and Gynaecology, Maastricht University Medical Centre+, the Netherlands; GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre+, Maastricht, the Netherlands; Department of Obstetrics and Gynaecology, Radboud Medical Centre, the Netherlands.

Objective: Determination of the anatomical structures that should be taught to ensure safe and competent practice among general gynaecologists.

Study Design: A two-round Delphi survey, face-to-face meeting in focus groups and an individual interview. Participants were medical doctors and trainees from gynaecology, surgery, urology and radiology from academic, non-academic teaching and non-academic, non-teaching hospitals in the Netherlands. Relevant structures were collected from gynaecology surgery atlas based on most common gynaecological surgeries and diseases. These structures were supplemented and critically viewed in focus groups followed by a Delphi survey. In the Delphi survey gynaecologist and trainee's gynaecology from all over the Netherlands scored the items on a Likert scale between 1 (not relevant) and 5 (highly relevant). Consensus was defined when ≥ 70 % of the panellist scored the item as relevant or very relevant and the average rating was ≥ 4. Main outcome was clinically relevant anatomical structures.

Results: Consensus on 86 clinically relevant anatomical structures divided by nine categories.

Conclusions: This study identified a core list of anatomical structures that are relevant to the safe and competent practice of general gynaecologists and that can be used to guide gynaecology postgraduate education. This is the first step in a much wider and complex process of becoming a competent gynaecologist.
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http://dx.doi.org/10.1016/j.ejogrb.2019.11.015DOI Listing
February 2020

Organoids of epithelial ovarian cancer as an emerging preclinical in vitro tool: a review.

J Ovarian Res 2019 Nov 8;12(1):105. Epub 2019 Nov 8.

Division of Gynecologic Oncology, Department of Gynecology and Obstetrics, University Hospitals Leuven, Herestraat 49, 3000, Leuven, European Union, Belgium.

Epithelial ovarian cancer (EOC) remains the most lethal gynecological cancer in developed countries, indicating the need for further research. Although current cancer models prove useful, they have major limitations. Organoids, a novel in vitro 3D cell culture technique, derived from stem cells, could provide a bridge between the current preclinical platforms. However, this technique is still in its early stages. After conducting a systematic literature search, only sixteen manuscripts concerning ovarian related organoids could be retrieved.In this review, we discuss current tumor models, including organoids and provide a comprehensive review about organoids of ovarian tissue. Potential future applications are addressed, proving organoids to be an interesting platform for modeling tumorigenesis, drug testing and screening and other applications. Recent advancements could usher in a new era of highly personalized medicine in EOC.
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http://dx.doi.org/10.1186/s13048-019-0577-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6839218PMC
November 2019

Sarcopenia and ovarian cancer survival: a systematic review and meta-analysis.

J Cachexia Sarcopenia Muscle 2019 12 7;10(6):1165-1174. Epub 2019 Aug 7.

Department of Obstetrics and Gynecology, Division of Gynaecological Oncology, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium.

Background: Sarcopenia is the loss of skeletal muscle mass and function that occurs with advancing age and certain diseases. It is thought to have a negative impact on survival in cancer patients. Routine computed tomography imaging is often used to quantify skeletal muscle in cancer patients. Sarcopenia is defined by a low skeletal muscle index (SMI). Skeletal muscle radiation attenuation (SMRA) is used to define muscle quality. The primary aim of this meta-analysis was to study the association between sarcopenia or SMRA and overall survival (OS) or complications in patients with ovarian cancer.

Methods: Medline, Embase, CINAHL, and PEDro databases were searched from inception to 15 February 2019. Studies evaluating the prognostic effect of SMI and SMRA on ovarian cancer survival or surgical complications were included. Risk of bias and study quality were evaluated with the Quality in Prognosis Studies Instrument (QUIPS) according to the modified Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework.

Results: The search strategy yielded 4262 hits in all four databases combined. Ten and eight studies were included for qualitative and quantitative analysis, respectively. Meta-analysis revealed a significant association between the SMI and OS [0.007; hazard ratio (HR): 1.11, 95% confidence interval (CI): 1.03-1.20]. SMRA was also significantly associated with OS (P < 0.001; HR: 1.14, 95% CI: 1.08-1.20). Association between the SMI and surgical complications had borderline statistical significance (0.05; HR: 1.23, 95% CI: 1.00-1.52). The risk of bias assessed with QUIPS was high in all studies. The quality of the evidence was very low.

Conclusions: Whereas our meta-analysis indicated that a low SMI and low SMRA are associated with survival in ovarian cancer patients, the low quality of the source data precludes drawing definitive conclusions.
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http://dx.doi.org/10.1002/jcsm.12468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6903439PMC
December 2019

Trends in incidence, treatment and survival of borderline ovarian tumors in the Netherlands: a nationwide analysis.

Acta Oncol 2019 Jul 28;58(7):983-989. Epub 2019 May 28.

a Department of Research , Netherlands Comprehensive Cancer Organisation (IKNL) , Utrecht , The Netherlands.

Population-based data on borderline ovarian tumors (BOTs) are scarce and information regarding recent trends in incidence, treatment and survival is lacking. The purpose of this study was to analyze these trends in the Netherlands and to assess the risk of developing a subsequent invasive ovarian tumor. All consecutive patients diagnosed with BOTs between 1993 and 2016 ( = 7113) were identified from the Netherlands Cancer Registry (NCR). Annual age-adjusted incidence rates were calculated. Relative survival (RS) analyses and multivariable analyses estimating excess mortality were conducted. Patients with a subsequent invasive ovarian tumor were identified by the NCR. Age-adjusted incidence increased from 2.1/100,000 person-years in 1993 to 4.2/100,000 in 2011, after 2011 the incidence declined. The proportion of bilateral tumors decreased over time from 16% in 1993-1998 to 11% in 2005-2010 and remained stable onwards. Survival improved over time (excess mortality ratio 2011-2016 1993-1998: 0.25; 95%CI: 0.13-0.47). Five-year RS increased from 91% in 1993-1998 to 98% in 2011-2016 and 10-year RS from 88% in 1993-1998 to 96% in 2005-2010. Fewer patients were treated with chemotherapy (4.4% in 1993-1998 0.7% in 2011-2016). During a median follow-up time of 8 years, 0.9% developed a subsequent invasive ovarian carcinoma. The incidence of BOTs increased over time from 1993 until 2010 but declined since 2011. This decline may be partly due to changes in the classification of gynecological tumors, as serous BOTs are now more often diagnosed as low grade serous ovarian cancers. Survival is high and has improved since 1993. The risk of a subsequent invasive ovarian carcinoma seems low.
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http://dx.doi.org/10.1080/0284186X.2019.1619935DOI Listing
July 2019

Economic evaluation of an expert examiner and different ultrasound models in the diagnosis of ovarian cancer.

Eur J Cancer 2018 09 26;100:55-64. Epub 2018 Jun 26.

Department of Obstetrics and Gynaecology, Maastricht University Medical Center+ (MUMC+), Maastricht, The Netherlands; GROW: School for Oncology and Developmental Biology, P. Debyelaan 25, 6202 AZ, Maastricht, The Netherlands. Electronic address:

The Risk of Malignancy Index (RMI) is commonly used to diagnose adnexal masses. The aim of the present study was to determine the cost-effectiveness of the RMI compared with subjective assessment (SA) by an expert and the following novel ultrasound models: Cost-effectiveness and budget impact analyses were performed from a societal perspective. A decision tree was constructed, and short-term costs and effects were examined in women with adnexal masses. Sensitivity, specificity and the costs of diagnostic strategies were incorporated. Incremental cost-effectiveness ratios were expressed as costs/additional percentage of correctly diagnosed patients. Probabilistic and deterministic sensitivity analyses were performed. Effectiveness was highest for SA (90.7% [95% confidence interval = 77.3-100]), with a cost saving of 5.0% (-€398 per patient [-€1403 to 549]) compared with the RMI. The costs of SR + SA were the lowest (€7180 [6072-8436]), resulting in a cost saving of 9.0% (-€709 per patient [-€1628 to 236]) compared with the RMI, with an effectiveness of 89.6% (75.8-100). SR + SA showed the highest probability of being the most cost-effective when willingness-to-pay was <€350 per additional percentage of correctly diagnosed patients. The RMI had low cost-effectiveness probabilities (<3%) and was inferior to SA, SR + SA and LR2. Budget impact in the Netherlands compared with that of the RMI varied between a cost saving of €4.67 million for SR + SA and additional costs of €3.83 million when implementing ADNEX (cut-off: 10%). The results were robust when tested in sensitivity analyses. Although SA is the best strategy in terms of diagnostic accuracy, SR + SA might be preferred from a cost-effectiveness perspective.
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http://dx.doi.org/10.1016/j.ejca.2018.05.003DOI Listing
September 2018

Centralization of ovarian cancer in the Netherlands: Hospital of diagnosis no longer determines patients' probability of undergoing surgery.

Gynecol Oncol 2018 01 10;148(1):56-61. Epub 2017 Nov 10.

Department of Research, Netherlands Comprehensive Cancer Organization (IKNL), Utrecht, The Netherlands.

Objective: Surgical care for advanced stage epithelial ovarian cancer (EOC) patients has been centralized in the Netherlands since 2012. We evaluated whether the likelihood for patients to undergo surgery depends on the hospital of initial diagnosis before and after centralization of surgical care.

Methods: Patients with EOC FIGO stage IIB-IV, diagnosed in the Netherlands between 2000 and 2015, were identified from the Netherlands Cancer Registry. Multilevel multivariate logistic regression was used to study the association between hospital of diagnosis and patients' likelihood of undergoing surgery in subsequent time periods. Furthermore, changes in overall survival were analyzed by multivariable Cox regression models.

Results: 15,314 EOC patients were selected from the NCR. Hospital of diagnosis was identified as a significant level for patients' likelihood of undergoing surgery in 2000-2005 (LR test p<0.001), as well as in 2006-2011 (LR test p=0.002) but not in 2012-2015 (LR test p=0.127). Patients who underwent surgery in 2012-2015 had a better survival when compared to 2006-2011 (HR 0.90(0.84-0.96)).

Conclusion: This study shows that centralization of surgical care resolved the variation between hospitals in the probability to undergo cytoreductive surgery for patients with advanced EOC. Since centralization was established in 2012, the decision to operate patients seems solely attributable to patient and tumor characteristics. This supports the growing evidence in favor of centralizing (surgical) treatment for complex and heterogeneous diseases such as EOC.
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http://dx.doi.org/10.1016/j.ygyno.2017.11.009DOI Listing
January 2018

Simple Rules, Not So Simple: The Use of International Ovarian Tumor Analysis (IOTA) Terminology and Simple Rules in Inexperienced Hands in a Prospective Multicenter Cohort Study.

Ultraschall Med 2017 Dec 23;38(6):633-641. Epub 2017 Aug 23.

GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre (MUMC+), Maastricht, Netherlands.

Objectives:  To analyze how well untrained examiners - without experience in the use of International Ovarian Tumor Analysis (IOTA) terminology or simple ultrasound-based rules (simple rules) - are able to apply IOTA terminology and simple rules and to assess the level of agreement between non-experts and an expert.

Methods:  This prospective multicenter cohort study enrolled women with ovarian masses. Ultrasound was performed by non-expert examiners and an expert. Ultrasound features were recorded using IOTA nomenclature, and used for classifying the mass by simple rules. Interobserver agreement was evaluated with Fleiss' kappa and percentage agreement between observers.

Results:  50 consecutive women were included. We observed 46 discrepancies in the description of ovarian masses when non-experts utilized IOTA terminology. Tumor type was misclassified often (n = 22), resulting in poor interobserver agreement between the non-experts and the expert (kappa = 0.39, 95 %-CI 0.244 - 0.529, percentage of agreement = 52.0 %). Misinterpretation of simple rules by non-experts was observed 57 times, resulting in an erroneous diagnosis in 15 patients (30 %). The agreement for classifying the mass as benign, malignant or inconclusive by simple rules was only moderate between the non-experts and the expert (kappa = 0.50, 95 %-CI 0.300 - 0.704, percentage of agreement = 70.0 %). The level of agreement for all 10 simple rules features varied greatly (kappa index range: -0.08 - 0.74, percentage of agreement 66 - 94 %).

Conclusion:  Although simple rules are useful to distinguish benign from malignant adnexal masses, they are not that simple for untrained examiners. Training with both IOTA terminology and simple rules is necessary before simple rules can be introduced into guidelines and daily clinical practice.
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http://dx.doi.org/10.1055/s-0043-113819DOI Listing
December 2017

Cost-effectiveness of laparoscopy as diagnostic tool before primary cytoreductive surgery in ovarian cancer.

Gynecol Oncol 2017 09 20;146(3):449-456. Epub 2017 Jun 20.

Department of Gynecology, Center for Gynecologic Oncology Amsterdam, Academic Medical Center, PO Box 22660, 1100 DD Amsterdam, The Netherlands. Electronic address:

Objective: To evaluate the cost-effectiveness of a diagnostic laparoscopy prior to primary cytoreductive surgery to prevent futile primary cytoreductive surgery (i.e. leaving >1cm residual disease) in patients suspected of advanced stage ovarian cancer.

Methods: An economic analysis was conducted alongside a randomized controlled trial in which patients suspected of advanced stage ovarian cancer who qualified for primary cytoreductive surgery were randomized to either laparoscopy or primary cytoreductive surgery. Direct medical costs from a health care perspective over a 6-month time horizon were analyzed. Health outcomes were expressed in quality-adjusted life-years (QALYs) and utility was based on patient's response to the EQ-5D questionnaires. We primarily focused on direct medical costs based on Dutch standard prices.

Results: We studied 201 patients, of whom 102 were randomized to laparoscopy and 99 to primary cytoreductive surgery. No significant difference in QALYs (utility=0.01; 95% CI 0.006 to 0.02) was observed. Laparoscopy reduced the number of futile laparotomies from 39% to 10%, while its costs were € 1400 per intervention, making the overall costs of both strategies comparable (difference € -80 per patient (95% CI -470 to 300)). Findings were consistent across various sensitivity analyses.

Conclusion: In patients with suspected advanced stage ovarian cancer, a diagnostic laparoscopy reduced the number of futile laparotomies, without increasing total direct medical health care costs, or adversely affecting complications or quality of life.
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http://dx.doi.org/10.1016/j.ygyno.2017.06.019DOI Listing
September 2017

Psoas muscle area is not representative of total skeletal muscle area in the assessment of sarcopenia in ovarian cancer.

J Cachexia Sarcopenia Muscle 2017 Aug 16;8(4):630-638. Epub 2017 May 16.

Department of Obstetrics and Gynaecology, Maastricht University Medical Centre, PO Box 5800, Maastricht, 6202 AZ, The Netherlands.

Background: Computed tomography measurements of total skeletal muscle area can detect changes and predict overall survival (OS) in patients with advanced ovarian cancer. This study investigates whether assessment of psoas muscle area reflects total muscle area and can be used to assess sarcopenia in ovarian cancer patients.

Methods: Ovarian cancer patients (n = 150) treated with induction chemotherapy and interval debulking were enrolled retrospectively in this longitudinal study. Muscle was measured cross sectionally with computed tomography in three ways: (i) software quantification of total skeletal muscle area (SMA); (ii) software quantification of psoas muscle area (PA); and (iii) manual measurement of length and width of the psoas muscle to derive the psoas surface area (PLW). Pearson correlation between the different methods was studied. Patients were divided into two groups based on the extent of change in muscle area, and agreement was measured with kappa coefficients. Cox-regression was used to test predictors for OS.

Results: Correlation between SMA and both psoas muscle area measurements was poor (r = 0.52 and 0.39 for PA and PLW, respectively). After categorizing patients into muscle loss or gain, kappa agreement was also poor for all comparisons (all κ < 0.40). In regression analysis, SMA loss was predictive of poor OS (hazard ratio 1.698 (95%CI 1.038-2.778), P = 0.035). No relationship with OS was seen for PA or PLW loss.

Conclusions: Change in psoas muscle area is not representative of total muscle area change and should not be used to substitute total skeletal muscle to predict survival in patients with ovarian cancer.
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http://dx.doi.org/10.1002/jcsm.12180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5566632PMC
August 2017

Laparoscopy to Predict the Result of Primary Cytoreductive Surgery in Patients With Advanced Ovarian Cancer: A Randomized Controlled Trial.

J Clin Oncol 2017 Feb 28;35(6):613-621. Epub 2016 Dec 28.

Marianne J. Rutten, Hannah S. van Meurs, Roelien van de Vrie, Christiana A. Naaktgeboren, Guus Fons, Brent C. Opmeer, Anje M. Spijkerboer, Patrick M.M. Bossuyt, Gemma G. Kenter, and Marrije R. Buist, Academic Medical Center, Amsterdam; Katja N. Gaarenstroom, Leiden University Medical Center, Leiden; Toon van Gorp, Maastricht University Medical Center, Maastricht; Henk G. Ter Brugge, Isala Hospital, Zwolle; Ward Hofhuis, Sint Franciscus Gasthuis, Rotterdam; Henk W.R. Schreuder, University Medical Center Utrecht; Maarten van Haaften, Diakonessenhuis, Utrecht; Henriette J.G. Arts, University Medical Center Groningen, Groningen; Petra L.M. Zusterzeel, Radboud University Medical Center, Nijmegen; Johanna M.A. Pijnenborg and M. Caroline Vos, Elisabeth-Tweesteden Hospital, Tilburg; Mirjam J.A. Engelen, Atrium Medical Center, Heerlen; Erik A. Boss, Máxima Medical Center, Veldhoven; Kees G. Gerestein, Meander Medical Center, Amersfoort; Eltjo M.J. Schutter, Medical Spectrum Twente, Enschede, the Netherlands; and Ben Willem Mol, The Robinson Research Institute, University of Adelaide; The South Australian Health and Medical Research Institute, Adelaide, Australia.

Purpose To investigate whether initial diagnostic laparoscopy can prevent futile primary cytoreductive surgery (PCS) by identifying patients with advanced-stage ovarian cancer in whom > 1 cm of residual disease will be left after PCS. Patients and Methods This multicenter, randomized controlled trial was undertaken within eight gynecologic cancer centers in the Netherlands. Patients with suspected advanced-stage ovarian cancer who qualified for PCS were eligible. Participating patients were randomly assigned to either laparoscopy or PCS. Laparoscopy was used to guide selection of primary treatment: either primary surgery or neoadjuvant chemotherapy followed by interval surgery. The primary outcome was futile laparotomy, defined as a PCS with residual disease of > 1 cm. Primary analyses were performed according to the intention-to-treat principle. Results Between May 2011 and February 2015, 201 participants were included, of whom 102 were assigned to diagnostic laparoscopy and 99 to primary surgery. In the laparoscopy group, 63 (62%) of 102 patients underwent PCS versus 93 (94%) of 99 patients in the primary surgery group. Futile laparotomy occurred in 10 (10%) of 102 patients in the laparoscopy group versus 39 (39%) of 99 patients in the primary surgery group (relative risk, 0.25; 95% CI, 0.13 to 0.47; P < .001). In the laparoscopy group, three (3%) of 102 patients underwent both primary and interval surgery compared with 28 (28%) of 99 patients in the primary surgery group ( P < .001). Conclusion Diagnostic laparoscopy reduced the number of futile laparotomies in patients with suspected advanced-stage ovarian cancer. In women with a plan for PCS, these data suggest that performance of diagnostic laparoscopy first is reasonable and that if cytoreduction to < 1 cm of residual disease seems feasible, to proceed with PCS.
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http://dx.doi.org/10.1200/JCO.2016.69.2962DOI Listing
February 2017

Correspondence: Premature Stop of the SOCceR Trial, a Multicenter Randomized Controlled Trial on Secondary Cytoreductive Surgery: Netherlands Trial Register Number: NTR3337.

Int J Gynecol Cancer 2017 01;27(1)

Department of Obstetrics and Gynecology Radboud University Medical Centre Nijmegen, the Netherlands Department of Obstetrics and Gynecology Maastricht University Medical Centre Maastricht, the Netherlands and GROW, School for Oncology and Developmental Biology Maastricht University Maastricht, the Netherlands Department of Obstetrics and Gynecology Maastricht University Medical Centre Maastricht, the Netherlands GROW, School for Oncology and Developmental Biology Maastricht University Maastricht, the Netherlands Department of Obstetrics and Gynecology Radboud University Medical Centre Nijmegen, the Netherlands Department of Obstetrics and Gynecology Maastricht University Medical Centre Maastricht, the Netherlands GROW, School for Oncology and Developmental Biology Maastricht University Maastricht, the Netherlands Department of Obstetrics and Gynecology Radboud University Medical Centre Nijmegen, the Netherlands.

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http://dx.doi.org/10.1097/IGC.0000000000000841DOI Listing
January 2017

Comparison of Intraoperative γ-Probe Imaging and Postoperative SPECT/CT in Detection of Sentinel Nodes Related to the Ovary.

J Nucl Med 2017 Feb 13;58(2):243-245. Epub 2016 Oct 13.

Department of Radiology and Nuclear Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands.

Tracer injection into ovarian ligaments has been shown to detect sentinel nodes (SNs) in patients with ovarian cancer. To determine the possibility that SNs are missed, this feasibility study compared their detection during surgery with their detection on postoperative SPECT/CT.

Methods: In 8 patients (with either ovarian or endometrial cancer), after a staging lymphadenectomy including resection of SNs related to the ovary, SPECT/CT was performed within 24 h.

Results: SPECT/CT identified hotspots in 4 patients at sites where SNs were resected. In 6 patients, additional sites were found, mainly in the pelvic region.

Conclusion: Discrepancies between the γ-probe and SPECT/CT may be due to missed SNs during surgery, but with respect to pelvic hotspots, in most cases they are more probably related to remnants of tracer at injection sites. With respect to sites where SNs were resected, remaining hotspots may have been caused by residual lymphatic flow after resection.
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http://dx.doi.org/10.2967/jnumed.116.183426DOI Listing
February 2017

Perioperative changes in serum CA125 levels: a prognostic factor for disease-specific survival in patients with ovarian cancer.

J Gynecol Oncol 2017 Jan 12;28(1):e7. Epub 2016 Sep 12.

Department of Obstetrics and Gynecology, Maastricht University Medical Centre, Maastricht, The Netherlands.

Objective: In patients with advanced stage epithelial ovarian cancer (EOC) the volume of residual tumor after debulking is known as prognostic factor for survival. We wanted to examine the relationship between postoperative decline in serum CA125 and residual disease after cytoreductive surgery and evaluate perioperative changes in serum CA125 levels as predictor for disease-specific survival.

Methods: A retrospective study was conducted of patients with FIGO stage IIb-IV EOC treated with cytoreductive surgery, followed by chemotherapy between 1996 and 2010 in three hospitals in the Southeastern region of the Netherlands. Data were analyzed with the use of multilevel linear regression and Cox-proportional hazard regression models.

Results: A postoperative decline in serum CA125 level of ≥80% was associated with complete primary cytoreduction (p=0.035). Univariate analyses showed favorable associations with survival for both the degree of decline in serum CA125 and residual tumor after primary cytoreduction. In multivariate analyses the decline in serum CA125 but not the outcome of surgery remained significantly associated with better survival (HR(50%-79%)=0.52 [95% CI: 0.28-0.96] and HR(≥80%)=0.26 [95% CI: 0.13-0.54] vs. the serum CA125 decline of <50% [p<0.001]).

Conclusion: The current study, although hampered by possible biases, suggests that the perioperative decline in serum CA125 is an early biomarker that predicts disease-specific survival in patients who underwent primary cytoreductive surgery for advanced stage EOC. If confirmed prospectively, the perioperative change in serum CA125 could be a better marker for residual tumor volume after primary cytoreductive surgery (and therewith disease-specific survival) than the surgeons' estimation of residual tumor volume.
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http://dx.doi.org/10.3802/jgo.2017.28.e7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5165075PMC
January 2017

The impact of lymph node dissection and adjuvant chemotherapy on survival: A nationwide cohort study of patients with clinical early-stage ovarian cancer.

Eur J Cancer 2016 10 15;66:83-90. Epub 2016 Aug 15.

Maastricht University Medical Centre, Department of Obstetrics and Gynaecology, Maastricht, The Netherlands; Maastricht University Medical Centre, GROW - School for Oncology and Developmental Biology, Maastricht, The Netherlands. Electronic address:

Introduction: To establish the impact of lymph node dissection and chemotherapy on survival in patients with early-stage epithelial ovarian cancer (EOC).

Methods: All Dutch patients with International Federation of Gynaecology and Obstetrics (FIGO) stage I-IIA and IIIA1 EOC between 2000 and 2012 were included. Data concerning age, stage, tumour grade, histological subtype, hospital type, lymph node dissection, adjuvant chemotherapy and survival were extracted from the Netherlands Cancer Registry.

Results: Of 3658 patients included, 1813 (49.6%) had lymph nodes removed. Relative survival of patients with lymph node dissection (including those with lymph node metastases) was significantly better than that of patients without, also after correcting for stage, tumour grade, histology and age (89% and 82%, respectively; relative excess risk [RER], 0.64; 95% confidence interval [CI]: 0.52-0.78). There was a positive correlation between the number of removed lymph nodes and overall survival (after excluding patients with lymph node metastases). Of patients with stage I-IIA EOC who had ≥10 lymph nodes removed, there was no difference in relative survival between those who received chemotherapy and those who did not (RER, 0.51; 95% CI: 0.15-1.64). This was also true for a subgroup of patients with high-risk features (stage IC and IIA and/or tumour grade 3 and/or clear cell histology [RER, 0.90; 95% CI: 0.46-1.99]).

Conclusion: Adequate dissection of at least 10 but preferably ≥20 lymph nodes should be standard procedure for the staging of early-stage EOC. Adjuvant chemotherapy after an adequate lymph node dissection does not seem to contribute to a better relative survival.
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http://dx.doi.org/10.1016/j.ejca.2016.07.015DOI Listing
October 2016

Predictive criteria for MRI-based evaluation of response both during and after radiotherapy for cervical cancer.

J Contemp Brachytherapy 2016 Jun 1;8(3):181-8. Epub 2016 Jul 1.

GROW, School for Oncology and Developmental Biology, Maastricht; Department of Radiology, Maastricht University Medical Centre.

Purpose: For cervical carcinoma, the presence of persistent disease after radiotherapy (RT) is a significant predictor for survival. To date, no standard protocol is available to evaluate a response. This study was performed to assess magnetic resonance imaging (MRI) to evaluate presence of local residual disease during and after RT for Federation of Gynecology and Obstetrics (FIGO) stage Ib1-IVa cervical cancer.

Material And Methods: Forty-two patients were included. Patients underwent MRI before external beam RT, at final intracavitary brachytherapy (BCT) and 2-3 months after completion of RT. Two blinded radiologists (observer 1: experienced, observer 2: less experienced) scored the likelihood of residual tumor. Magnetic resonance imaging was evaluated by means of (a) 'subjective' visual evaluation of T2 weighted MRI images, and (b) 'objective' visual evaluation of T2 weighted MRI images according to predefined imaging criteria.

Results: Seven patients had residual disease. Area under the receiver operating characteristics curve (AUC) for 'subjective' visual assessment was 0.79/0.75 (observer 1/observer 2) after RT and 0.75/0.43 at final BCT. The combined 'objective' MRI criteria (isointense, nodular, and irregular) resulted in improved prediction of residual tumor (AUCs of 0.91/0.85 after RT). For the less experienced observer, the MRI criteria set significantly improved prediction of residual tumor compared to 'subjective' visual assessment. Observer dependency decreased, kappa of 0.41 compared to 0.84 for the MRI criteria set after RT.

Conclusion: Compared to 'subjective' visual assessment, predefined 'objective' MRI criteria increase diagnostic performance and decrease observer dependency for assessing residual tumor after RT in cervical cancer.
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http://dx.doi.org/10.5114/jcb.2016.61065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4965503PMC
June 2016

Loss of skeletal muscle during neoadjuvant chemotherapy is related to decreased survival in ovarian cancer patients.

J Cachexia Sarcopenia Muscle 2016 09 7;7(4):458-66. Epub 2016 Mar 7.

Department of Obstetrics and Gynaecology Maastricht University Medical Centre 6202 AZ Maastricht The Netherlands; GROW School for Oncology and Developmental Biology Maastricht University 6200 MD Maastricht The Netherlands.

Background: Malnutrition, weight loss, and muscle wasting (sarcopenia) are common among women with advanced ovarian cancer and have been associated with adverse clinical outcomes and survival. Our objective is to investigate overall survival (OS) related to changes in skeletal muscle (SM) for patients with advanced ovarian cancer treated with neoadjuvant chemotherapy and interval debulking.

Methods: Ovarian cancer patients (n = 123) treated with neoadjuvant chemotherapy and interval debulking in the area of Maastricht (the Netherlands) between 2000 and 2014 were included retrospectively. Surface areas of SM and adipose tissue were defined on computed tomography at the level of the third lumbar vertebra. Low SM at baseline and SM changes during chemotherapy were compared with Kaplan Meier curves, and Cox-regression models were applied to test predictors of OS.

Results: Median OS for patients who lost SM (n = 83) was 916 ± 99 days, which was significantly different from median OS for patients who maintained or gained SM (n = 40), which was 1431 ± 470 days (P = 0.004). Loss of SM was also a significant predictor of OS in multivariable Cox-regression analysis (hazard ratio 1.773 (95%CI: 1.018-3.088), P = 0.043). Low baseline SM did not influence survival.

Conclusions: Patients with ovarian cancer have a worse survival when they lose SM during neoadjuvant chemotherapy. Evaluation of low SM at a specific time point is not prognostic for OS. External and prospective validation of these findings is imperative. Nutritional, pharmacological, and/or physical intervention studies are necessary to establish whether SM impairment can be prevented to prolong ovarian cancer survival.
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http://dx.doi.org/10.1002/jcsm.12107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4782251PMC
September 2016

Prediction of incomplete primary debulking surgery in patients with advanced ovarian cancer: An external validation study of three models using computed tomography.

Gynecol Oncol 2016 Jan 24;140(1):22-8. Epub 2015 Nov 24.

Department of Obstetrics and Gynecology, Maastricht University Medical Center, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands; GROW School for Oncology and Developmental Biology, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands.

Objective: To test the ability of three prospectively developed computed tomography (CT) models to predict incomplete primary debulking surgery in patients with advanced (International Federation of Gynecology and Obstetrics stages III-IV) ovarian cancer.

Methods: Three prediction models to predict incomplete surgery (any tumor residual >1cm in diameter) previously published by Ferrandina (models A and B) and by Gerestein were applied to a validation cohort consisting of 151 patients with advanced epithelial ovarian cancer. All patients were treated with primary debulking surgery in the Eastern part of the Netherlands between 2000 and 2009 and data were retrospectively collected. Three individual readers evaluated the radiographic parameters and gave a subjective assessment. Using the predicted probabilities from the models, the area under the curve (AUC) was calculated which represents the discriminative ability of the model.

Results: The AUC of the Ferrandina models was 0.56, 0.59 and 0.59 in model A, and 0.55, 0.60 and 0.59 in model B for readers 1, 2 and 3, respectively. The AUC of Gerestein's model was 0.69, 0.61 and 0.69 for readers 1, 2 and 3, respectively. AUC values of 0.69 and 0.63 for reader 1 and 3 were found for subjective assessment.

Conclusions: Models to predict incomplete surgery in advanced ovarian cancer have limited predictive ability and their reproducibility is questionable. Subjective assessment seems as successful as applying predictive models. Present prediction models are not reliable enough to be used in clinical decision-making and should be interpreted with caution.
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http://dx.doi.org/10.1016/j.ygyno.2015.11.022DOI Listing
January 2016

Surgery for Recurrent Epithelial Ovarian Cancer in the Netherlands: A Population-Based Cohort Study.

Int J Gynecol Cancer 2016 Feb;26(2):268-75

*Department of Obstetrics and Gynecology, Radboud University Medical Center, Nijmegen; †Department of Obstetrics and Gynecology, Maastricht University Medical Centre; and ‡GROW, School for Oncology and Developmental Biology, Maastricht University, Maastricht; and §Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands.

Objective: The value of secondary cytoreductive surgery (SCS) in patients with recurrent epithelial ovarian cancer is controversial. The aim of this population-based study was to investigate the role of SCS in the Netherlands.

Methods: Data of 408 patients who underwent SCS between 2000 and 2013 were retrospectively collected from 38 Dutch hospitals. Survival after complete and incomplete SCS was estimated by Kaplan-Meier curves. Factors associated with overall survival (OS) were explored with Cox regression.

Results: Median OS after SCS was 51 months (95% confidence interval [95% CI], 44.8-57.2). Complete SCS was achieved in 295 (72.3%) patients, with an OS of 57 months (95% CI, 49.0-65.0) compared with 28 months (95% CI, 20.8-35.2) in patients with incomplete SCS (log-rank test; P < 0.001). Nonserous histology (HR 0.65; 95% CI 0.45-0.95), a long progression free interval (hazard ratio [HR], 0.29; 95% CI, 0.07-1.18), a good performance status (HR, 0.68; 95% CI, 0.49-0.94), SCS without preoperative chemotherapy (HR, 0.72; 95% CI, 0.51-1.01), and complete SCS (HR, 0.46; 95% CI, 0.33-0.64) were prognostic factors for survival.

Conclusions: This population-based retrospective study showed that there might be a role for SCS in recurrent epithelial ovarian cancer especially when complete SCS can be accomplished. However, before adopting SCS as a standard treatment modality for recurrent epithelial ovarian cancer, results of 3 ongoing prospectively randomized trials are needed.
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http://dx.doi.org/10.1097/IGC.0000000000000598DOI Listing
February 2016

Understanding Lymphatic Drainage Pathways of the Ovaries to Predict Sites for Sentinel Nodes in Ovarian Cancer.

Int J Gynecol Cancer 2015 Oct;25(8):1405-14

*Department of Obstetrics and Gynecology, Maastricht University Medical Center, Maastricht; †Department of Anatomy and Embryology, Leiden University Medical Center, Leiden; ‡GROW-School for Oncology and Developmental Biology, Maastricht; and §Computer Graphics and Visualization, Department of Intelligent Systems, Delft University of Technology, Delft, the Netherlands.

Objective: In ovarian cancer, detection of sentinel nodes is an upcoming procedure. Perioperative determination of the patient's sentinel node(s) might prevent a radical lymphadenectomy and associated morbidity. It is essential to understand the lymphatic drainage pathways of the ovaries, which are surprisingly up till now poorly investigated, to predict the anatomical regions where sentinel nodes can be found. We aimed to describe the lymphatic drainage pathways of the human ovaries including their compartmental fascia borders.

Methods: A series of 3 human female fetuses and tissues samples from 1 human cadaveric specimen were studied. Immunohistochemical analysis was performed on paraffin-embedded transverse sections (8 or 10 μm) using antibodies against Lyve-1, S100, and α-smooth muscle actin to identify the lymphatic endothelium, Schwann, and smooth muscle cells, respectively. Three-dimensional reconstructions were created.

Results: Two major and 1 minor lymphatic drainage pathways from the ovaries were detected. One pathway drained via the proper ligament of the ovaries (ovarian ligament) toward the lymph nodes in the obturator fossa and the internal iliac artery. Another pathway drained the ovaries via the suspensory ligament (infundibulopelvic ligament) toward the para-aortic and paracaval lymph nodes. A third minor pathway drained the ovaries via the round ligament to the inguinal lymph nodes. Lymph vessels draining the fallopian tube all followed the lymphatic drainage pathways of the ovaries.

Conclusions: The lymphatic drainage pathways of the ovaries invariably run via the suspensory ligament (infundibulopelvic ligament) and the proper ligament of the ovaries (ovarian ligament), as well as through the round ligament of the uterus. Because ovarian cancer might spread lymphogenously via these routes, the sentinel node can be detected in the para-aortic and paracaval regions, obturator fossa and surrounding internal iliac arteries, and inguinal regions. These findings support the strategy of injecting tracers in both ovarian ligaments to identify sentinel nodes.
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http://dx.doi.org/10.1097/IGC.0000000000000514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5106084PMC
October 2015

Investigating the performance and cost-effectiveness of the simple ultrasound-based rules compared to the risk of malignancy index in the diagnosis of ovarian cancer (SUBSONiC-study): protocol of a prospective multicenter cohort study in the Netherlands.

BMC Cancer 2015 Jun 26;15:482. Epub 2015 Jun 26.

Department of Obstetrics and Gynecology, Maastricht University Medical Centre (MUMC+), P. Debyelaan 25, 6202 AZ, Maastricht, The Netherlands.

Background: Estimating the risk of malignancy is essential in the management of adnexal masses. An accurate differential diagnosis between benign and malignant masses will reduce morbidity and costs due to unnecessary operations, and will improve referral to a gynecologic oncologist for specialized cancer care, which improves outcome and overall survival. The Risk of Malignancy Index is currently the most commonly used method in clinical practice, but has a relatively low diagnostic accuracy (sensitivity 75-80% and specificity 85-90%). Recent reports show that other methods, such as simple ultrasound-based rules, subjective assessment and (Diffusion Weighted) Magnetic Resonance Imaging might be superior to the RMI in the pre-operative differentiation of adnexal masses.

Methods/design: A prospective multicenter cohort study will be performed in the south of The Netherlands. A total of 270 women diagnosed with at least one pelvic mass that is suspected to be of ovarian origin who will undergo surgery, will be enrolled. We will apply the Risk of Malignancy Index with a cut-off value of 200 and a two-step triage test consisting of simple ultrasound-based rules supplemented -if necessary- with either subjective assessment by an expert sonographer or Magnetic Resonance Imaging with diffusion weighted sequences, to characterize the adnexal masses. The histological diagnosis will be the reference standard. Diagnostic performances will be expressed as sensitivity, specificity, positive and negative predictive values and likelihood ratios.

Discussion: We hypothesize that this two-step triage test, including the simple ultrasound-based rules, will have better diagnostic accuracy than the Risk of Malignancy Index and therefore will improve the management of women with adnexal masses. Furthermore, we expect this two-step test to be more cost-effective. If the hypothesis is confirmed, the results of this study could have major effects on current guidelines and implementation of the triage test in daily clinical practice could be a possibility.

Trial Registration: ClinicalTrials.gov: registration number NCT02218502.
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http://dx.doi.org/10.1186/s12885-015-1319-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4489120PMC
June 2015

Natural history of high-grade cervical intraepithelial neoplasia: a review of prognostic biomarkers.

Expert Rev Mol Diagn 2015 Apr 21;15(4):527-46. Epub 2015 Feb 21.

GROW, School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands.

The natural history of high-grade cervical intraepithelial neoplasia (CIN) is largely unpredictable and current histopathological examination is unable to differentiate between lesions that will regress and those that will not. Therefore, most high-grade lesions are currently treated by surgical excision, leading to overtreatment and unnecessary complications. Prognostic biomarkers may differentiate between lesions that will regress and those that will not, making individualized treatment of high-grade CIN possible. This review identifies several promising prognostic biomarkers. These biomarkers include viral genotype and viral DNA methylation (viral factors), human leukocyte antigen-subtypes, markers of lymphoproliferative response, telomerase amplification and human papillomavirus-induced epigenetic effects (host factors) and Ki-67, p53 and pRb (cellular factors). All identified biomarkers were evaluated according to their role in the natural history of high-grade CIN and according to established criteria for evaluation of biomarkers (prospective-specimen-collection, retrospective-blinded-evaluation [PROBE] criteria). None of the biomarkers meets the PROBE criteria for clinical applicability and more research on prognostic biomarkers in high-grade CIN is necessary.
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http://dx.doi.org/10.1586/14737159.2015.1012068DOI Listing
April 2015

External validation of two prediction models of complete secondary cytoreductive surgery in patients with recurrent epithelial ovarian cancer.

Gynecol Oncol 2015 May 10;137(2):210-5. Epub 2015 Feb 10.

Department of Obstetrics and Gynecology, Maastricht University Medical Centre, Maastricht, The Netherlands; GROW, School for Oncology and Developmental Biology, Maastricht University, P. Debyelaan 25, 6229 HA Maastricht, The Netherlands.

Objective: The purpose of this study was to validate the performance of two prediction models, the AGO score and the Tian model, of complete secondary cytoreductive surgery (SCS) in patients with recurrent epithelial ovarian cancer. The predictive value of both models for survival controlled for the outcome of SCS was analyzed and known predictive factors for complete SCS were tested.

Methods: A population-based database with 408 patients, who underwent SCS between 2000 and 2013 in 38 Dutch hospitals, was used. The validation cohorts for the AGO score and the model of Tian contained 273 (66.9%) and 257 (63.0%) patients, respectively.

Results: The AGO score and Tian model showed a positive predictive value for complete SCS of 82.0% and 80.3% respectively, and a false negative rate of 68.5% and 55.6% respectively. A positive AGO score had no significant association with overall survival (HR 0.73; 95% CI 0.51-1.06) whereas the low risk score of the Tian model did (HR 0.62; 95% CI 0.41-0.93). A good performance status (OR 0.60; 95% CI 0.33-1.10) and the absence of ascites (OR 0.18; 95% CI 0.08-0.41) were prognostic factors for complete SCS.

Conclusions: Both the AGO score and the model of Tian showed a high positive predictive value for complete SCS but also relatively high false negative rates. However, before the two prediction models can be applied in daily clinical practice the usefulness of SCS itself has to be proven first by the three ongoing randomized controlled trials: DESKTOP III trial, the GOG 213 trial and the Dutch SOCceR trial.
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http://dx.doi.org/10.1016/j.ygyno.2015.02.004DOI Listing
May 2015

Costs, effectiveness, and workload impact of management strategies for women with an adnexal mass.

J Natl Cancer Inst 2015 Jan 16;107(1):322. Epub 2014 Dec 16.

Division of Gynecologic Oncology (LJH), and Department of Obstetrics and Gynecology (LJH, ERM), Department of Medicine (MD, LHC), Duke University Medical Center, Durham, NC; Duke Cancer Institute, Durham, NC (LJH, ERM); St. Francis Hospital, Columbus, GA (GPS); Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, San Antonio Military Medical Center, Fort Sam Houston, TX (JCB); Division of Gynaecological Oncology, Department of Obstetrics and Gynaecology, Universitaire Ziekenhuizen Leuven, Katholieke Universiteit Leuven, Leuven, Belgium (TVG); Division of Gynaecological Oncology, Department of Obstetrics and Gynaecology, MUMC., GROW - School for Oncology and Developmental Biology, Maastricht, the Netherlands (TVG).

Background: We compared the estimated clinical outcomes, costs, and physician workload resulting from available strategies for deciding which women with an adnexal mass should be referred to a gynecologic oncologist.

Methods: We used a microsimulation model to compare five referral strategies: 1) American Congress of Obstetricians and Gynecologists (ACOG) guidelines, 2) Multivariate Index Assay (MIA) algorithm, 3) Risk of Malignancy Algorithm (ROMA), 4) CA125 alone with lowered cutoff values to prioritize test sensitivity over specificity, 5) referral of all women (Refer All). Test characteristics and relative survival were obtained from the literature and data from a biomarker validation study. Medical costs were estimated using Medicare reimbursements. Travel costs were estimated using discharge data from Surveillance, Epidemiology and End Results-Medicare and State Inpatient Databases. Analyses were performed separately for pre- and postmenopausal women (60 000 "subjects" in each), repeated 10 000 times.

Results: Refer All was cost-effective compared with less expensive strategies in both postmenopausal (incremental cost-effectiveness ratio [ICER] $9423/year of life saved (LYS) compared with CA125) and premenopausal women (ICER $10 644/YLS compared with CA125), but would result in an additional 73 cases/year/subspecialist. MIA was more expensive and less effective than Refer All in pre- and postmenopausal women. If Refer All is not a viable option, CA125 is an optimal strategy in postmenopausal women.

Conclusions: Referral of all women to a subspecialist is an efficient strategy for managing women with adnexal masses requiring surgery, assuming sufficient capacity for additional surgical volume. If a test-based triage strategy is needed, CA125 with lowered cutoff values is a cost-effective strategy.
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http://dx.doi.org/10.1093/jnci/dju322DOI Listing
January 2015