MYometrial Lesion UltrasouNd And mRi

MYometrial Lesion UltrasouNd And mRi

Sponsors

Lead sponsor: Catholic University of the Sacred Heart

Collaborator: Prof. Antonia Testa
Dr. Daniela Romualdi
Dr. Francesca Ciccarone

Source Catholic University of the Sacred Heart
Brief Summary

A monocentric prospective observational study aimed at assessing the accuracy of a diagnostic algorithm to pre-operatively identify uterine sarcomas..

Primary Aim:To assess the accuracy of a diagnostic algorithm in identifing patients with uterine sarcomas in women with at least one > =3 cm myometrial lesion.

Detailed Description

INTRODUCTION

Uterine sarcomas are rare malignant tumors arising from the mesenchymal tissues of the uterus including the endometrial stroma, uterine muscle and connective tissue. They represent 1% of female genital tract malignancies and 3-7% of all uterine malignances with a worldwide annual incidence of 1.55-1.95 per 100.000 women. Malignant mesenchimal tumors include: uterine leiomyosarcoma (LMS), endometrial stromal sarcoma (ESS), and undifferentiated uterine sarcoma (UUS), and other (eg adenosarcoma, epithelioid sarcoma, STUMP). , The mean age at diagnosis is approximately 60 years old. However, uterine sarcomas have been diagnosed in women as young as 20 years old . The prevalence of sarcoma in women undergoing hysterectomy or myomectomy for a myometrial mass, is approximately 0.001 percent (1 in 1000) (Parker 94), with a range from 0.005 (1 in 2000) to 0.28 percent (1 in 352). , The discrimination between benign and malignant myometrial lesions is clinically relevant to plan the optimal management (surgery versus medical treatment) and to define the most appropriate surgical approach.

However, the diagnosis of uterine sarcomas is a challenge and no validated clinical or radiological criteria can accurately distinguish benign from malignant myometrial tumors.

In particular, data on the ultrasound features of uterine sarcomas are scarce and they are mainly based on retrospective case series. The role of CT(Computed Tomography) has generally been limited to identify extrauterine disease, including local spread within the pelvis and metastatic disease. MRI (Magnetic Resonance Imaging) )represents an accurate diagnostic imaging modality in the assessment of gynecological pathologies with high soft tissue contrast, large field-of-view and multiplanar imaging capabilities; however, no accurate diagnostic criteria have been validated to discriminate between benign and malignant myometrial lesions.

To the best of our knowledge, no large prospective studies have been carried on to assess a diagnostic algorithm to predict the malignant histology of myometrial lesions.

PURPOSES AND OBJECTIVES OF THE CLINICAL TRIAL

Primary aim:

To assess the accuracy of a diagnostic algorithm in identifing patients with uterine sarcomas in women with at least one >3 cm myometrial lesion.

Secondary aims:

1. To describe the clinical history of patients with myometrial lesions, assessed on ultrasound, and conservately managed.

2. To assess the accuracy of subjective assessment of an experienced ultrasound examiner in detecting uterine sarcomas in women with at least one >3 cm myometrial lesion.

3. To compare clinical and ultrasound characteristics of patients with benign myometrial lesion versus those with uterine sarcomas, histologically confirmed.

4. To compare clinical and Magnetic Resonance (MR) characteristics of patients with benign myometrial lesions versus those with uterine sarcomas, histologically confirmed.

5. To compare the accuracy of the subjective assessment of an ultrasound examiner versus that of a MR reader in detecting uterine sarcomas in women triaged for surgery ("Orange group").

EXPERIMENTAL DESIGN

- Type of study: Monocentric, prospective, observational study

- Setting: Department of Woman and Child Health, Fondazione Policlinico Universitario A. Gemelli, IRCSS, Roma.

- Estimated study period: Three years for the enrollment and additional two years for the completion of follow-up.

STUDY POPULATION SAMPLE SIZE

The prevalence of uterine sarcomas in patients operated on for myometrial lesions reported in literature varies from of 0.5/1000 to 28 /1000 (ref) whereas no data are available regarding the prevalence of sarcomas in non operated patients with a myometrial lesion. In a six months experience of a clinical center, within the gynecological oncological unit, dedicated to the management of women with atypical myometrial lesions 323 patients with a myometrial lesion >3cm were observed. 113 of them (35.0%) were triaged to surgery on the basis of clinical symptoms and morphological features and 5/113 (4.4%) resulted to be uterine sarcomas at histology.

Sample size was calculated according to one study group design. Considering the prevalence in literature regarding the whole population (1/1000) and the prevalence observed in this preliminary experience in our Institution (44/1000), and assuming an α type 1 error = 0.05, and a β type II error = 0.2 (power 80%), a total of 3076 patients is required. Taking into account a dropout rate around 10%, a final sample size of 3418 patients is planned. Considering the number of patients addressing to our Institution for myometrial lesion, the estimated enrollment period will be three years. The end of the study will be set when the last enrolled patient not triaged to surgery will be followed up for at least two years.

IDENTIFICATION PARAMETERS

A myometrial lesion with the largest diameter >3 cm represents the target lesion. In case of multiple myometrial lesions with similar ultrasound morphology, the largest tumor will be selected as target lesion. In case of multiple myometrial lesions with different ultrasound morphology, the "target lesion" will be identified by the ultrasound examiner on the basis of the parameters subjectively considered suspicious for malignancy.

WITHDRAWAL PROCEDURES

The patient may choose not to take part in this study. The patient may choose to have US revaluation or surgery without enrolling in this study. The patient may choose to receive other therapy, if available. In all cases, the woman receive appropriate medical care, including treatment for bleeding, pain or other symptoms.

SUBJECT TREATMENT

All women enrolled in the study will be managed according to the following algorithm (Figure 1. Clinical and Diagnostic Algorithm).

Patients will be assessed by a Green Card (Figure 2. Green Card) to check the eventual presence of at least one of the following clinical and/or ultrasound characteristics:

- Maximum size of the lesion ≥ 5cm;

- Symptoms (abdominal and/or pelvic pain, sensation of pressure, abdominal distension, infertility (>12 months), two or more abortions;

- Largest diameter rapid growth (Growth >30% per year);

- Irregular cystic areas;

- Color Score 4.

- If no Green Card criteria is fulfilled (Negative Green Criteria), the patient will receive an annual telephone follow up for 2 years.

- If one or more Green Card criteria is present (Positive Green Criteria), a dedicated clinical and ultrasound paper form (Appendix 1. MYLUNAR Paper Form) will be fulfilled in order to check the presence of the criteria described in the Orange Card (Figure 3. Orange Card):

- Anamnestic and clinical characteristics:

- Age ≥ 45 years old

- Symptoms (abnormal uterine bleeding; abdominal and/or pelvic pain; sensation of pressure; Abdominal distension)

- LDH (Lactate dehydrogenase) > 250 UI/L (if known)

- Ultrasound characteristics:

- Maximum size of the lesion ≥ 8cm

- Largest diameter rapid growth (Growth >30% per year)

- Irregular margins of the lesion

- Presence of irregular cystic areas

- Absence of acoustic shadow

- Color Score 4

- "Cooked" aspect

- If at least two Orange Card criteria (including at least one ultrasound parameter) are present (Positive Orange Criteria), the patient will be examined by means of Magnetic Resonance (MRI) within 15 days and triaged to surgery (to be performed within 30 days since the enrollment in the study). A dedicated MRI paper form will be fulfilled (Appendix 2. MRI Paper Form) Histology of the target myometrial lesion will be considered as the gold standard parameter.

- In case of "negative Orange Criteria" (i.e. no Orange Card criteria, or only one Orange Card criteria, or only Orange clinical criteria) the patient will be scheduled for longitudinal follow up at 6, 12 and 24 months. At each follow-up visit, a transvaginal ultrasound examination will be performed (using the MYLUNAR Paper Form) and the patient will be re-evaluated according to the Orange Card. In case of "positive Orange Criteria" the patient will be triaged to MRI and surgery. Eventual treatment for the myometrial lesion during the study period will be recorded and the outcome of these patients will be described separately.

Overall Status Recruiting
Start Date March 12, 2018
Completion Date March 12, 2023
Primary Completion Date March 12, 2021
Study Type Observational
Primary Outcome
Measure Time Frame
Myometrial Lesion March 2018 -March 2023
Enrollment 3000
Condition
Intervention

Intervention type: Diagnostic Test

Intervention name: Ultrasound

Description: Intervention: Diagnostic Test Ultrasound Ultrasound investigating the following characteristics: Maximum size of the lesion ≥ 8cm; Largest diameter rapid growth (Growth >30% per year); Irregular margins of the lesion; Presence of irregular cystic areas; Absence of acoustic shadow; Color Score 4; "Cooked" aspect; ]

Intervention type: Diagnostic Test

Intervention name: MRI

Description: Diagnostic Test: MRI; MRI investigating the following carachteristics: TARGET LESION Maximum diameter; Borders; Signal intensity on T2WI; Heterogeneity on T2WI; Cystic alteration(s); Cystic alteration(s) borders; Hemorrhage; T2 dark" area(s); Flow voids; Signal intensity on DWI(b-1000); ADC value; ≥ 1,23 Signal intensity on contrasted images Intensity [relative to myometrium] (Hyper- / Hypo- / Iso- intense) Heterogeneity (Homogeneous / Heterogeneous) Unenhanced area(s) Presence (Present / Absent) Location (Central / None or non-central) 1 Tumour - myometrium contrast ratio on T2WI [SItumour - SImyometrium / SImyometrium]

Arm group label: ORANGE

Eligibility

Sampling method: Probability Sample

Criteria:

Inclusion Criteria:

- Consecutive patients admitted to our Department for transvaginal ultrasound examination, in whom a myometrial lesion > 3cm in size is detected.

- Informed consent form signed by the patient.

Exclusion Criteria:

- Patients undergoing medical treatment for myometrial lesion;

- Patients previously treated with hormonal therapy including estroprogestin in the last six months;

- Patients previously treated by embolization

Gender: Female

Minimum age: N/A

Maximum age: N/A

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Giovanni Scambia, Professor Principal Investigator Fondazione Policlinico Agostino Gemelli
Overall Contact

Last name: Francesca Ciccarone, M.D.

Phone: 00390630154979

Email: [email protected]

Location
facility status contact Fondazione Policlinico Agostino Gemelli Francesca Ciccarone, M.D. 00390630154979 [email protected]
Location Countries

Italy

Verification Date

October 2019

Responsible Party

Responsible party type: Principal Investigator

Investigator affiliation: Catholic University of the Sacred Heart

Investigator full name: Prof. Giovanni Scambia

Investigator title: Professor

Keywords
Has Expanded Access No
Arm Group

Arm group label: WHITE

Description: If no Green Card criteria is fulfilled (Negative Green Criteria), the patient will receive an annual telephone follow up for 2 years.

Arm group label: GREEN

Description: Patients will be assessed by a Green Card to check the eventual presence of at least one of the following clinical and/or ultrasound characteristics. If one or more Green Card criteria is present (Positive Green Criteria), a dedicated clinical and ultrasound paper form will be fulfilled in order to check the presence of the criteria described in the Orange Card In case of "negative Orange Criteria" (no Orange Card criteria, or only one Orange Card criteria, or only Orange clinical criteria) the patient will be scheduled for longitudinal follow up at 6, 12 and 24 months. At each follow-up visit, a transvaginal ultrasound examination will be performed (using the MYLUNAR Paper Form) and the patient will be re-evaluated according to the Orange Card. In case of "positive Orange Criteria" the patient will be triaged to MRI and surgery. Eventual treatment for the myometrial lesion during the study period will be recorded and the outcome of these patients will be described separately.

Arm group label: ORANGE

Description: - If at least two Orange Card criteria (including at least one ultrasound parameter) are present (Positive Orange Criteria), the patient will be examined by means of Magnetic Resonance (MRI) within 15 days and triaged to surgery (to be performed within 30 days since the enrollment in the study). A dedicated MRI paper form will be fulfilled Histology of the target myometrial lesion will be considered as the gold standard parameter.

Acronym MYLUNAR
Patient Data Undecided
Study Design Info

Observational model: Cohort

Time perspective: Prospective

Source: ClinicalTrials.gov