Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Symptoms and General Pathology

Rare Diseases

Carcinoma

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Cysts

Ovarian Cysts

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Ovarian Cancer

Ovarian Epithelial Cancer

All patients included will undergo an ultrasound scan in which both the RMI and simple ultrasound-based rules are applied. This scan will take place in the hospital of inclusion. For 80% of all patients, this will be the only intervention.

If the simple ultrasound-based rules, used in the first ultrasound scan, yield an inconclusive result (approx. 20% of all patients), patients are refered to the center hospital to undergo a second ultrasound (by an expert) and a DW-MRI scan. Furthermore, these group of patients will be asked to give an extra blood sample in order to perform translational research and validate new biomarkers in the diagnosis of ovarian cancer.

All patients will undergo an ultrasound by a general gynaecologist at the moment of inclusion. Based on this ultrasound, the gynaecologist will use both the RMI and the simple rules to predict the chance of malignancy.

Ultrasound by general gynaecologist

Patients in which the simple rules yield an inconclusive result (about 20% of all patients) will undergo a second ultrasound scan. This scan is performed by an expert in gynaecological ultrasound.

Ultrasound by an expert ultrasonographist

Patients in which the simple rules yield an inconclusive result (about 20% of all patients) will undergo a diffusion weighted MRI.

DW-MRI

Patients in which the simple rules yield an inconclusive result (about 20% of the patients) will be asked for an extra blood sample. We will use these materials to perform translational research and validate new biomarkers in the diagnosis of ovarian cancer.

Give blood sample

Evelyne MJ Meys, LLM, BsC

Toon van Gorp, MD, PhD

This study is performed to compare the diagnostic performance and cost-effectiveness of different diagnostic methods for differentiating benign from malignant adnexal (ovary or Fallopian tube) masses: the Risk of Malignancy Index (RMI) will be compared with a two-step triage test called "simple ultrasound-based rules" supplemented -if necessary- with either subjective assessment by an expert sonographer or Diffusion Weighted - Magnetic Resonance Imaging (DW-MRI). The investigators will test the hypothesis that this two-step triage test will have better diagnostic accuracy than the RMI and therefore will improve the management of women with adnexal masses.

Estimating whether an adnexal mass is malignant or not is essential in the preoperative management of adnexal masses. Recognizing cancer means treatment is not delayed and appropriate staging or debulking surgery can be carried out after referral to specialized surgical centers. Vice versa, benign lesions may be managed conservatively or with minimal invasive surgery in non-centre hospitals. This will limit morbidity and will avoid unnecessary costs: laparoscopic surgery offers lower estimated blood loss, shorter hospital stay, and fewer postoperative complications with an improved quality of life and faster return to normal functioning.

There are several methods to distinguish benign from malignant adnexal masses. The commonly used method in clinical practice is the Risk of Malignancy Index (RMI). The RMI is an easy to use scoring system recommended by many national guidelines concerning the management of ovarian masses, including the national guideline in the Netherlands. The RMI combines ultrasound variables, menopausal status and serum CA125 into a score used to predict the risk of ovarian cancer before surgery. However, the reported sensitivity and specificity of RMI at a cut-off value of 200 are relatively low; 75-80% and 85-90%, respectively.

Another method called 'simple ultrasound-based rules' (simple rules), uses different morphological ultrasound features of adnexal masses (without including menopausal status or serum CA125 measurement). It includes five simple ultrasound-based rules to predict malignancy (M-rules) and five rules to predict a benign tumor (B-rules). If both or none of the M- and B-rules are met (20% of the patients) the test is inconclusive. Recent reports show that simple rules might be superior to the RMI. In adnexal masses for which the simple ultrasound rules yield an inconclusive result, subjective assessment of Gray-scale and color Doppler ultrasound images by an experienced ultrasound examiner can be used as a second stage test to achieve an optimal diagnostic performance. Subjective assessment by an expert sonographer is superior to any scoring system or mathematical model when classifying adnexal masses as benign or malignant. However, it is not feasible and efficient that every patient would undergo an expert ultrasonography. Therefore, this method is better used as a second stage test.

Another option is to use Diffusion Weighted - Magnetic Resonance Imaging (DW-MRI) as a second stage test, when the simple rules yield an inconclusive result. The use of MRI - when interpret by specialized radiologists- also seems to be superior to RMI in the preoperative identification of adnexal masses.

The Risk of Malignancy Index (RMI) is the current standard in differentiating benign from malignant adnexal masses. The simple ultrasound-based rules as a first stage triage test followed by either subjective assessment by an experienced ultrasound examiner or DW-MRI in case the simple rules are inconclusive, is the test of comparison. Both the RMI and the simple rules will be performed in the regional hospitals and MUMC+ by general gynaecologists during the same ultrasound scan. Only when the simple rules are inconclusive the patient will be referred to the MUMC+ for a second stage test. From previous publications it can be deducted that this will be in approximately 20% of patients. Approximately 80% of patients will not need any additional second stage test.

The histology of the surgically removed adnexal masses is the clinical reference standard.

Study Into a New Diagnostic Tool (Simple Ultrasound-based Rules) in Patients With Adnexal Masses

Regional Study Into the Performance and Cost-effectiveness of Simple Ultrasound-based Rules Compared to the Currently Used Risk of Malignancy Index in the Diagnosis of Ovarian Cancer

Sensitivity is defined as the percentage of women with ovarian cancer diagnosed with a malignancy by respectively the RMI and the two-step test. Specificity is defined as the percentage of correctly diagnosed benign masses.

The positive likelihood ratio is calculated by dividing the sensitivity by 100 minus the specificity. The negative likelihood ratio is calculated as the sensitivity minus 100 divided by the specificity.

The positive predictive value is defined as the percentage of patients with a positive test result by respectively RMI and simple rules having malignant disease. The negative predictive value is defined as the percentage of patients with a negative test result having benign disease.

The economic evaluation will explore the potential cost-effectiveness of RMI versus the triage test. Incremental cost-effectiveness will be expressed as the costs per correct diagnosis (i.e. either true positive or false negative for malignancy based on histology) including the costs of surgical management following diagnosis. The analysis will take a hospital perspective including all costs from inclusion up to hospital discharge following surgery. As not all data necessary for comparison between the diagnostic strategies will be collected empirically and surgical management will be based on RMI, a simple decision analytic model will be constructed. The comparative sensitivity, specificity and costs of the diagnostic strategies including surgical management for the diagnostic work up of patients with at least one pelvic mass that is suspected to be of ovarian origin, will explicitly be incorporated in the model.

A budget impact analysis will be performed according to the ISPOR guidelines. The BIA addresses the financial stream of consequences related to the uptake and diffusion of the triage test to assess affordability. The budget impact will depend on both the costs of the diagnostic strategies, the effect in terms of correct diagnosis, as well as potential future levels of uptake of the triage test. All these elements which determine the potential budget impact will be addressed in this study.

Laurentius Hospital Roermond

St.Jans Gasthuis Weert

VieCuri Medical Centre

Orbis Medical Centre

Maastricht University Medical Center

The ADNEX model includes nine parameters; Age, CA-125 level, Oncology center (yes/no), and 6 ultrasound features which are maximal diameter of the lesion, maximal diameter of the largest solid part, more than 10 locules (yes/no), number of papillary projections (0/1/2/3/more than 3), acoustic shadow, and ascites

Assesment of Different NEoplasias in the adenexa model

The RMI was measured as follows; Menopausal status (score is 3 as all patients were postmenopausal X Ultrasound score is based on assessment of 5 features and with the presence of one feature, the score is 1 while if more than one feature is present, the score is 3; the five ultrasound features are the presence of solid components, multilocularity, bilaterality, ascites, and metastases X CA - 125 level

Risk of malignancy index

Histopathologic examination of all excised specimens was done as this is the gold standard test for detecting ovarian malignancy

Histopathologic examination

Amr H El-Shalakany, M.D.

Kareem M Labib, M.D.

Hassan Morsi, PhD

Mortada Elsayed, M.D.

Ovarian cancer is the second most common gynecologic malignancy. In 2008, it was the seventh leading cause of cancer deaths in women worldwide. Estimating the risk of malignancy is essential in the management of adnexal masses and several mathematical models and scoring systems have been developed to be used for discrimination between benign and malignant adnexal masses. Knowledge of the specific type of adnexal pathology before surgery is likely to improve patient triage with high accuracy, and it also makes it possible to optimize treatment. The correct identification of stage I cancer is particularly important

Ovarian cancer (OC) is the third most common gynecological malignancy worldwide and carries the highest mortality. OC has an incidence of 11.7 - 12.1 per 100,000 in the USA and Europe, with slightly lower rates of disease in Asia and the Middle East. Most patients (60%) are diagnosed with advanced disease which is associated with significant mortality. The most important factor for survival is the stage at diagnosis and nowadays there isn't a proven effective screening strategy. It is necessary to identify the best tool to detect early-stage disease. To reduce the diagnostic dilemma between benign and malignant ovarian masses, a formula-based scoring system known as the risk of malignancy index (RMI) was introduced in 1990, which was termed RMI 1. RMI is a combined parameter that is simple, specific, and highly sensitive for the evaluation of adnexal masses. It is a product of ultrasound findings (U), the menopausal status (M), and serum CA-125 levels (RMI = U X M XCA-125). The original RMI (RMI-1) was modified in 1996 as (RMI 2) and again in 1999 known as (RMI 3), and the last modification was in 2009 by adding the tumor size (S) to the equation and calling it RMI 4. A systematic review of diagnostic studies concluded that the RMI I was the most effective for women with suspected ovarian malignancy.

Malignant tumors benefit from management in specialized oncology centers, but borderline malignancies, stage I primary invasive tumors, and advanced primary invasive tumors might require different surgical approaches. To optimize patient triage without operating on all masses, diagnostic models can be used to estimate the likelihood of malignancy and hence to plan treatment for patients. The International Ovarian Tumor Analysis Group (IOTA) has developed a multi-tumor prediction model, Assessment of Different NEoplasias in the adneXa (ADNEX) model, which is used to describe in detail the characteristics of adnexal masses. ADNEX model can not only distinguish the probability of benign and malignant AMs, but also distinguish between borderline ovarian tumors, stage I ovarian cancer, stage II-IV ovarian cancer, and secondary metastatic ovarian cancers, which includes three clinical features and six ultrasound features

Screening for Ovarian Malignancy

Assessment of Different Neoplasias in the Adenxa Model Versus Risk of Malignancy Index as a Tool for Predicting Ovarian Malignancy in Postmenopausal Ovarian Cysts

The diagnostic performance of the ADNEX model for differentiating between benign and malignant ovarian tumors was assessed at a threshold of 10%. The diagnostic performance was expressed as Area Under Receiver Operating Characteristic Curve (AUC)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Study Into a New Diagnostic Tool (Simple Ultrasound-based Rules) in Patients With Adnexal Masses	NCT02218502	Ovarian Carcino... Ovarian Cancer Ovarian Mass Ovarian Cyst	Ultrasound by g... Ultrasound by a... DW-MRI Give blood samp...	18 Years -	Maastricht University Medical Center
Screening for Ovarian Malignancy	NCT06348784	Early Detection...	Assesment of Di... Risk of maligna... Histopathologic...	40 Years -	Ain Shams Maternity Hospital

Spots Global Cancer Trial Database for risk of malignancy index