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

NCT02218502 | Terminated DMC

• 1 other identifier: NL44181.068.13
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Ovarian Carcinoma; Ovarian Cancer; Ovarian Mass; Ovarian Cyst

Keywords

Ovarian cancer; Diagnosis; Risk of Malignancy Index; RMI; Ultrasound; Simple ultrasound-based rules; DW-MRI; Subjective assessment

Outcome Measures

Primary Outcomes (5)

• Sensitivity and specificity

  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.

  This analysis will take place after completing the inclusion of patients (approx. 2 years)

• Likelihood ratios

  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.

  This analysis will take place after completing the inclusion of patients (approx. 2 years)

• positive and negative predictive values

  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.

  This analysis will take place after completing the inclusion of patients (approx. 2 years)

• cost-effectiveness

  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.

  This analysis will take place after completing the inclusion of patients (approx. 2 years)

• Budget Impact Analysis (BIA)

  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.

  This analysis will take place after completing the inclusion of patients (approx. 2 years)

Study Arms (2)

If simple rules are conclusive

OTHER

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.

Other: Ultrasound by general gynaecologist

If simple rules are inconclusive

OTHER

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.

Other: Ultrasound by general gynaecologist; Other: Ultrasound by an expert ultrasonographist; Other: DW-MRI; Other: Give blood sample

Interventions

Ultrasound by general gynaecologist OTHER

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.

If simple rules are conclusive; If simple rules are inconclusive

Ultrasound by an expert ultrasonographist OTHER

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.

If simple rules are inconclusive

DW-MRI OTHER

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

If simple rules are inconclusive

Give blood sample OTHER

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.

If simple rules are inconclusive

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female patient;
• Diagnosed in one of the participating centers with at least one pelvic mass that is suspected to be of ovarian origin;
• Are to undergo surgery in order to obtain a final histological diagnosis;
• years of age or older.

You may not qualify if:

• Pregnant patients;
• Patients aged under 18 years;
• Patients in whom the surgery does not take place, or takes place more than 120 days after RMI and simple ultrasound-based rules are performed;
• Patients with a prior bilateral oophorectomy;
• Patients with insufficient or missing data;
• Patients who do not give or are incapable of giving an informed consent;
• Patients who are not able or willing to travel to the center hospital for additional diagnostic procedures.

Sponsors & Collaborators

• Maastricht University Medical Center: lead
• Laurentius Hospital Roermond: collaborator
• St.Jans Gasthuis Weert: collaborator
• VieCuri Medical Centre: collaborator
• Orbis Medical Centre: collaborator

Study Sites (5)

Maastricht University Medical Centre (MUMC+)

Maastricht, Netherlands

Location

Laurentius Ziekenhuis Roermond

Roermond, Netherlands

Location

Orbis Medical Sittard

Sittard, 6162 BG, Netherlands

Location

VieCuri Venlo

Venlo, Netherlands

Location

St.Jans Gasthuis Weert

Weert, Netherlands

Location

Related Publications (11)

• Weber S, McCann CK, Boruta DM, Schorge JO, Growdon WB. Laparoscopic surgical staging of early ovarian cancer. Rev Obstet Gynecol. 2011;4(3-4):117-22.

  PMID: 22229064 BACKGROUND

• Timmerman D, Ameye L, Fischerova D, Epstein E, Melis GB, Guerriero S, Van Holsbeke C, Savelli L, Fruscio R, Lissoni AA, Testa AC, Veldman J, Vergote I, Van Huffel S, Bourne T, Valentin L. Simple ultrasound rules to distinguish between benign and malignant adnexal masses before surgery: prospective validation by IOTA group. BMJ. 2010 Dec 14;341:c6839. doi: 10.1136/bmj.c6839.

  PMID: 21156740 BACKGROUND

• Timmerman D, Testa AC, Bourne T, Ameye L, Jurkovic D, Van Holsbeke C, Paladini D, Van Calster B, Vergote I, Van Huffel S, Valentin L. Simple ultrasound-based rules for the diagnosis of ovarian cancer. Ultrasound Obstet Gynecol. 2008 Jun;31(6):681-90. doi: 10.1002/uog.5365.

  PMID: 18504770 BACKGROUND

• Van Gorp T, Veldman J, Van Calster B, Cadron I, Leunen K, Amant F, Timmerman D, Vergote I. Subjective assessment by ultrasound is superior to the risk of malignancy index (RMI) or the risk of ovarian malignancy algorithm (ROMA) in discriminating benign from malignant adnexal masses. Eur J Cancer. 2012 Jul;48(11):1649-56. doi: 10.1016/j.ejca.2011.12.003. Epub 2012 Jan 5.

  PMID: 22226481 BACKGROUND

• Valentin L, Jurkovic D, Van Calster B, Testa A, Van Holsbeke C, Bourne T, Vergote I, Van Huffel S, Timmerman D. Adding a single CA 125 measurement to ultrasound imaging performed by an experienced examiner does not improve preoperative discrimination between benign and malignant adnexal masses. Ultrasound Obstet Gynecol. 2009 Sep;34(3):345-54. doi: 10.1002/uog.6415.

  PMID: 19585547 BACKGROUND

• Dodge JE, Covens AL, Lacchetti C, Elit LM, Le T, Devries-Aboud M, Fung-Kee-Fung M; Gynecology Cancer Disease Site Group. Preoperative identification of a suspicious adnexal mass: a systematic review and meta-analysis. Gynecol Oncol. 2012 Jul;126(1):157-66. doi: 10.1016/j.ygyno.2012.03.048. Epub 2012 Apr 6.

  PMID: 22484399 BACKGROUND

• Tingulstad S, Hagen B, Skjeldestad FE, Halvorsen T, Nustad K, Onsrud M. The risk-of-malignancy index to evaluate potential ovarian cancers in local hospitals. Obstet Gynecol. 1999 Mar;93(3):448-52.

  PMID: 10074998 BACKGROUND

• Tingulstad S, Hagen B, Skjeldestad FE, Onsrud M, Kiserud T, Halvorsen T, Nustad K. Evaluation of a risk of malignancy index based on serum CA125, ultrasound findings and menopausal status in the pre-operative diagnosis of pelvic masses. Br J Obstet Gynaecol. 1996 Aug;103(8):826-31. doi: 10.1111/j.1471-0528.1996.tb09882.x.

  PMID: 8760716 BACKGROUND

• Jacobs I, Oram D, Fairbanks J, Turner J, Frost C, Grudzinskas JG. A risk of malignancy index incorporating CA 125, ultrasound and menopausal status for the accurate preoperative diagnosis of ovarian cancer. Br J Obstet Gynaecol. 1990 Oct;97(10):922-9. doi: 10.1111/j.1471-0528.1990.tb02448.x.

  PMID: 2223684 BACKGROUND

• Mauskopf JA, Sullivan SD, Annemans L, Caro J, Mullins CD, Nuijten M, Orlewska E, Watkins J, Trueman P. Principles of good practice for budget impact analysis: report of the ISPOR Task Force on good research practices--budget impact analysis. Value Health. 2007 Sep-Oct;10(5):336-47. doi: 10.1111/j.1524-4733.2007.00187.x.

  PMID: 17888098 BACKGROUND

• Meys EM, Rutten IJ, Kruitwagen RF, Slangen BF, Bergmans MG, Mertens HJ, Nolting E, Boskamp D, Beets-Tan RG, van Gorp T. 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. doi: 10.1186/s12885-015-1319-5.

  PMID: 26111920 DERIVED

MeSH Terms

Conditions

Ovarian Neoplasms; Ovarian Cysts; Disease

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Cysts; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Evelyne MJ Meys, LLM, BsC

  Maastricht University Medical Center

  STUDY DIRECTOR

• Toon van Gorp, MD, PhD

  Maastricht University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: CARE PROVIDER
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2014
• First Posted: August 18, 2014
• Study Start: September 1, 2014
• Primary Completion: September 1, 2015
• Study Completion: October 1, 2015
• Last Updated: March 28, 2017

Record last verified: 2017-03

Locations

NL (5)