The Role of Pre-Surgical Tru - Cut Biopsy in the Management of Atypical Myometrial Lesions (MYSTR)

July 22, 2024 updated by: Charles University, Czech Republic
The Tru-cut biopsy (TCB) for targeting pelvic tumors is well established in gynecologic oncology. However, its reliability for differentiating of uterine sarcoma in "myoma-like" uterine lesions has been confirmed by only a few studies, which were either retrospective or provided only pilot result on the limited number of prospectively enrolled patients (N=34). Proving that preoperative TCB can provide accurate information about the histological nature of the tumor would have great impact for setting an adequate tailored oncologically safe approach, especially in patients with sonographically atypical lesions. Additionally, the biopsy should be safe, with transcervical, transuterine cavity ("in organ" biopsy) approaches preferred to avoid the risk of needle canal contamination if sarcoma is diagnosed. The purpose of this study is to evaluate the accuracy of the Tru-cut biopsy (TCB) of sonographically atypical myometrial lesions as a complementary diagnostic method in the preoperative management of patients scheduled for uterus preserving procedure or hysterectomy. Additionally, we aim to assess the impact of this procedure on patients´ quality of life and clinical management. MYSTR is a single arm, prospective, multicentric cohort study.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

A total of 250 patients is planned to be enrolled, accounting for an estimated 15% dropout rate. Study data will be collected and managed using REDCap (Research Electronic Data Capture) open-source platform, which allows for the secure collection of research data via a web-based interface. REDCap was developed by Vanderbilt University in Nashville, Tennessee, is used by Charles University in Prague under a standing agreement to allow the usage of REDCap for academic and research purposes. The REDCap platform environment is compliant with 21 CFR Part 11, FISMA, HIPAA, and GDPR.

Patients will be identified at each of the participating site. If a patient meets all inclusion criteria, she will be informed about the study and asked to sign an informed consent (ICF). All patients referred for TCB will have their blood count and baseline coagulation parameters checked prior to performing the biopsy to eliminate bleeding complications. All patients will undergo a standard-of-care ultrasound examination with a focus on the description of the fibroid with atypical features according to the MUSA statement and/or Basel sarcoma scale score (BSS). A patient will be included in the study if she will meet one or more of the following MUSA criterion: irregular tumor borders, cystic areas in the lesion (as a sign of central necrosis), nonuniform echogenicity, moderate-to-abundant intralesional vascularity and an absence of calcifications, and/or BSS total score ≥ 1.

The patient will be further referred to MRI imaging (optional) and will undergo TCB within 4 weeks after US exam. In selected centers which will decide to participate in this optional part of the trial, all patients with ≥ 1 MUSA criterion and/or BSS total score ≥ 1 based on the US examination will be referred for MRI imaging. Images will be acquired with 3T MRI. The sequences parameters (Sagittal T2, Coronal T2, Axial T2, Axial DWI, Axial T1 3D DIXON, Axial Perfusion T1 3D, Axial T1 3D DIXON post contrast) will be evaluated in accordance with European Society of Urogenital Radiology (ESUR) guidelines. Two experienced readers in gynecologic oncology imaging will review all MRI images and calculate the MRI score.

The tru-cut biopsy is performed as an out-patient procedure without the need of any anesthesia in lithotomic position. Using an automatic biopsy gun and 18-gauge disposable core tissue biopsy needle four tissue cylinder samples are taken from the tumor. If the localization of the lesion and anatomical conditions allow, the transcervical approach without breaking the continuity of the perimetrium is preferred. If the lesion is localized in the uterine doom, or targetable by the uterine cavity, the transcervical canal approach is feasible and should be considered. If both above-described methods are not feasible, a transvaginal approach is also possible. In all cases transvaginal US is used for correct navigation. Patients will be observed for 30 minutes following the biopsy and then discharged. Other follow up of the patients will be done 24 hours and two weeks after the procedure via phone with the assessment of the patient´s pain, overall experience, and eventual complications.

Intraoperative and early post-procedural complications will be evaluated, and adverse events will be assessed on the 14th post-TCB day according to the Clavien-Dindo Surgical complications classification. Pain will be assessed during the TCB, 30 minutes after the procedure, and after 24 hours using the Numeric rating scale (NRS). Overall experience will be assessed using questionnaire: FACIT-TS-G (Version 4) 30 minutes after the procedure.

Specimen evaluation will be conducted at each participating site by dedicated, experienced pathologist according to standard diagnostic procedures. The biological nature of spindle cell leiomyocellular tumors will be determined according to Table 2 (modified from the WHO classification of female genital tumors 2020).

If necessary, immunohistochemical or molecular examination will be used. For smooth muscle lesions the gene mutation status of PTEN, pRb, TP53, MTAP, ATRX, and DAXX will be analyzed. In lesions of other histological types, RNA next-generation sequencing will be performed, optionally accompanied by immunohistochemical examination. These examinations are routinely performed as a part of standardized diagnostic procedures and will not be covered by the project's expenses. Histology findings from other than the main sight that will fail to meet the characteristics of conventional leiomyoma (either from TCB or definitive histology result) will undergo a second evaluation at the main site by a senior gyneco-pathologist. Following samples will be stored in biobanks at each respective institution: tumor sample DNA (isolated from one snap-frozen TCB sample); representative formalin-fixed paraffin-embedded (FFPE) tumor tissue block and representative FFPE non-tumor myometrial tissue block (both harvested during curative surgery). All samples will be collected with the intention to be used for future translational and exploratory research, including studies that aim to evaluate the association between biomarkers and clinical-surgical-pathological characteristics. All samples will be stored in the biobank at the respective institution. Participation in the translatory part is not obligatory for the trial participation but is highly recommended. A separate consent form will be provided to the patient to obtain permission for all biological material storage and future translational studies. Based on the histology result obtained from the TCB, patients will be categorized into three groups. Subsequent clinical management will be determined according to the appropriate group:

Subgroup 1: Patients with a typical benign histological result of TCB will undergo elective surgery within 8 weeks from receiving the results, with a preference of a minimally invasive approach, i.e., most often laparoscopic myomectomy or laparoscopic hysterectomy.

Subgroup 2: Patients with an atypical histological result of TCB (i.e., other than conventional leiomyoma but with no signs of malignancy) will undergo elective surgery within 6 weeks from receiving the results, with a preference of laparoscopy but excluding unprotected power morcellation of pathological tissue.

Uncontained morcellation will be used strictly for tumors with benign TCB histology and nonsuspicious perioperative appearance of resected uterine tumor. Contained morcellation technique will be strictly preferred for all other tumors, i.e., with non-standard TCB histology and/or atypical or suspicious perioperative appearance, or standard TCB histology and atypical or suspicious perioperative appearance.

Subgroup 3: Patients with a histological result from the TCB that are clearly malignant or suspicious for malignancy undergo open surgery, specifically abdominal hysterectomy. In cases of women with incomplete reproductive plans, open resection of the tumor may be performed after detailed consultation with the oncogynecological team and the patient, a secondary hysterectomy may be added based on the result of definitive histology. The procedure should be done as soon as possible, with a maximum interval between the result of TCB histology and elective surgery no more than 3 weeks.

In cases of tumors without penetration through the uterine serosa (according to US and perioperatively) and without requiring morcellation for the specimen evacuation, total laparoscopic hysterectomy can be performed.

Subgroup 4: In case of invalid TCB histology result, the patient will undergo contained morcellation during laparoscopic procedure or open surgery within 4 weeks after the TCB.

The definitive histology results from the surgery will be evaluated using the same histopathological criteria as in TCB histology. Definitive histology will be compared with the histological results from the pre-surgical TCB.

For the primary endpoint analysis, the accuracy of the histological results from TCB will be established using the definitive postoperative histological results as a reference standard.

The sample size of 217 patients with sonographically atypical myometrial lesions was calculated to establish the accuracy of the diagnostic method, with the degree of estimate precision of 0.07, 95% confidence and 80% power; assuming ratio between patients with/ without atypical lesion as per final pathology of 23:77, as based on the retrospective database data. Considering a possible dropout or unavailability of data in 15% of the patients, the final sample size reaches 250 patients. Analysis was computed using PASS 13 Power Analysis and Sample Size Software (2014). NCSS, LLC. Kaysville, Utah, USA, ncss.com/software/pass.

If this trial proves the accuracy of TCB of myometrial lesion, it could provide a new diagnostic tool and significantly impact the clinical practice.

A positive study outcome could establish level A evidence for a change of international standards and implement prehabilitation into a routine clinical practice. On a national level, the study aims to standardize and improve the care for gynecological patients with sonographic atypical myometrial lesions. A primary endpoint final analysis is intended for publication in a top medical journal. The study could also provide prospective genomic characterization analyses of myometrial tumors as well as the exploratory analysis of the reliability of individual imaging methods in the preliminary selection of patients with atypical myometrial findings.

Study Type

Observational

Enrollment (Estimated)

250

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Czechia
      • Praha, Czechia, 12800
        • General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Probability Sample

Study Population

  • Age ≥ 18 years
  • Women indicated for uterus-preserving surgery (tumour resection) or hysterectomy for myometrial lesion ('myoma-like' uterine tumour(s))

Description

Inclusion Criteria:

  • Signed informed consent
  • Age ≥ 18 years
  • Women indicated for uterus-preserving surgery (tumour resection) or hysterectomy for myometrial lesion ('myoma-like' uterine tumour(s))
  • USG finding of atypical myometrial lesion/s a

Exclusion Criteria:

patient 's refusal

  • age < 18 years
  • ongoing pregnancy
  • inability to perform TCB /contraindications for TCB (trombocytopenia, coagulopathy, PID, colpitis) or definitive surgery (myomectomy or hysterectomy)
  • USG finding of more than 2 atypical lesion/s with a diameter ≤ 20 mm and ≥ 100 mm
  • inability to perform any of the 3 core needle biopsy approaches (transvervical, trans uterine cavity, transvaginal) because of anatomical, localization issues. The percutaneous transabdominal biopsy is not allowed
  • Polymyomatous uterus that may not be examined adequately with routine transvaginal ultrasound
  • myoma (which would be subject to TCB) type 7 according to FIGO classification 16
  • history of conservative hormonal therapy less than 3 months prior to study enrolment
  • history of conservative therapy via uterine artery embolisation or laparoscopic uterine artery occlusion
  • history of pregnancy less than one year prior to study enrollment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Tru cut biopsy
A single arm, prospective, multicentric cohort study. A total of 250 patients is planned to be enrolled, accounting for an estimated 15% dropout rate.
Procedure: tru cut biopsy
Proving that preoperative TCB could provide accurate information about the histological nature of the tumor would have great impact for setting an adequate, tailored, oncologically safe treatment approach.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of accuracy
Time Frame: 3 years
Accuracy is defined as the concordance of the results of preoperative histology from TCB with the result of definitive histology from the operative specimen
3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of adequately performed TCBs
Time Frame: 3 years
defined as the number of TCBs with adequate encroachment of the lesion with bioptic needle (by the US) and sufficient tissue sample for the histopathological analysis to the total number of TCBs.
3 years
Number of complications
Time Frame: 3 years
number of complications after TCB divided by the number of patients. Intraoperative and early post-procedural complications will be assessed using a questionnaire. Adverse events will be assessed 14th post-TCB day according to the Clavien-Dindo Surgical complications classification
3 years
Pain associated with TCB
Time Frame: 24 hours
Assessment of patient´s pain during, 30 minutes after, and 24 hours after the procedure using the Numeric rating scale (NRS)
24 hours
Comparison of the preoperative MRI examination to US imaging
Time Frame: 3 years
Testing the superiority of either approach, sensitivity and specificity of the MRI imaging when compared to US examination will be analyzed
3 years
Patient satisfaction with the diagnostic MRI and TCB
Time Frame: 3 years
1 questionnaire: Patient experience of the diagnostic modalities will be assessed using developed and validated Patient Satisfaction Questionnaire
3 years
Impact of TCB on clinical management
Time Frame: 3 years
the change of clinical management of patients with uterine "myoma-like" tumors caused by the TCB histology results (frequency of open surgeries and rate of necessary use of contained morcellation during laparoscopic myomectomy or hysterectomy)
3 years
Frequency of non-standard histological findings
Time Frame: 3 years
the frequency of atypical histological findings (other than conventional leiomyoma) from the results of definitive histology in the group of women with sonographically atypical initial findings
3 years
Validation of the US markers of atypical myometrial lesions
Time Frame: 3 years
External validation of the MUSA statement and/or Basel sarcoma scale score (BSS), correlation of respective imaging score and final pathology result
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Charles University, Czech Republic

Investigators

  • Principal Investigator: Kristyna Hlinecka, Charles University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

October 1, 2024

Primary Completion (Estimated)

January 1, 2027

Study Completion (Estimated)

June 1, 2028

Study Registration Dates

First Submitted

December 3, 2023

First Submitted That Met QC Criteria

July 22, 2024

First Posted (Actual)

July 25, 2024

Study Record Updates

Last Update Posted (Actual)

July 25, 2024

Last Update Submitted That Met QC Criteria

July 22, 2024

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NW24J-03-00025

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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