CEH-EUS for Differentiating GISTs and Leiomyomas: A Multicenter Prospective Self-Controlled Study

Not yet recruiting

• Conditions: Submucosal Tumor; Gastrointestinal Stromal Tumor (GIST); Leiomyoma

• Registration Number: NCT07106411
• Lead Sponsor: Huazhong University of Science and Technology

Brief Summary

The investigators conduct a prospective, multicenter diagnostic trial primarily aimed at evaluating the value of contrast-enhanced harmonic endoscopic ultrasound (CEH-EUS) in differentiating gastrointestinal stromal tumors (GISTs) from leiomyomas, as well as its predictive utility in the risk stratification of GISTs.

Detailed Description

This study adopts a prospective, multicenter, self-controlled (pre-post) design. Patients with upper gastrointestinal subepithelial lesions (SELs) detected under white-light endoscopy will be consecutively enrolled. Each patient will first undergo endoscopic ultrasound (EUS) examination, during which lesion characteristics-including tumor size, margins, internal echogenicity, and originating layer-will be recorded. The contrast-specific extended pure harmonic detection (ExPHD) mode will then be activated, the mechanical index (MI) will be set to 0.3, and 2.4 mL of contrast agent (SonoVue) will be injected intravenously, followed by a 5 mL saline flush. Real-time dynamic imaging will be recorded for 120 seconds, capturing the arterial, venous, and delayed phases.

Histopathological results from surgical or endoscopic resection will serve as the reference standard. The diagnostic performance of EUS and contrast-enhanced EUS (CE-EUS) for differentiating gastrointestinal stromal tumors (GISTs) from leiomyomas and for predicting GIST risk stratification will be compared.

Patients meeting the inclusion criteria will be consecutively recruited. The primary outcome indicators are the sensitivity of CEH-EUS versus EUS in the differential diagnosis between GIST and leiomyoma, as well as in risk stratification of GIST. A prospective, self-controlled design will be used, with a type I error (α) of 0.05 (two-sided) and type II error (β) of 0.20, yielding a power of 0.80. Based on prior studies, the sensitivity of CEH-EUS for differentiating GISTs from leiomyomas is 87%, while that of EUS is approximately 72%-73%. Using McNemar's test for paired binary data (e.g., the same subject evaluated by two methods for positive diagnosis), the minimum sample size required for GIST patients is 121. Given that GISTs account for 67%-68% of all SELs, the required combined sample size of GIST and leiomyoma cases is 178. Accounting for an estimated 20% dropout rate, the final minimum sample size is 222 cases. For the GIST risk stratification analysis, prior studies report a sensitivity of 93% for CEH-EUS and 80% for EUS. McNemar's test was again used for sample size estimation. To meet the statistical requirements, 110 low-risk GIST cases are needed. Considering that low-risk GISTs comprise about 70% of all GISTs, and factoring in a 20% dropout rate, the total number of prospectively enrolled GIST patients required is 196. Since the risk stratification task requires a larger sample size and GISTs are the target of both diagnostic and stratification objectives, the final planned total sample size is 288 patients with GISTs or leiomyomas, which satisfies the statistical requirements for all primary study endpoints.

The study team will screen patients based on inclusion and exclusion criteria, ensure that all necessary examinations are completed to confirm eligibility, and obtain written informed consent from all prospective participants before conducting any study-related procedures.

This is a purely observational study. No additional interventions will be performed on participants, nor will they incur any extra costs. Patient access to optimal diagnostic or therapeutic options will not be affected. The primary potential risk is the breach of patient privacy. A strict data security and monitoring plan will be implemented, and participants will be informed that their data will be used for clinical research purposes.

The diagnostic performance of EUS and CE-EUS in differentiating GISTs from leiomyomas and in risk stratification of GISTs will be compared, with histopathological diagnosis serving as the gold standard. Diagnostic performance will be evaluated using paired analysis. All statistical tests will be two-sided, with significance defined as P \< 0.05. Continuous variables will be presented as mean ± standard deviation, and categorical variables as counts and percentages.(1) Diagnostic performance: Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and area under the curve (AUC) will be calculated for both CEH-EUS and EUS as interpreted by expert endoscopists. To address class imbalance (e.g., GIST vs. other lesions), F1-score (harmonic mean) and balanced accuracy will also be computed. (2) Continuous variables: Comparisons with baseline will be performed using paired t-tests, analysis of variance (ANOVA), or rank-sum tests, as appropriate to data distribution. (3) Categorical variables: Group comparisons will use Chi-square tests (including Cochran-Mantel-Haenszel Chi-square) or Fisher's exact test. (4) Baseline comparability: Demographic and baseline characteristics will be compared using independent t-tests or Chi-square tests to assess balance between groups. (5) Effectiveness analysis: The primary effectiveness endpoint is the diagnostic accuracy for upper gastrointestinal subepithelial lesions. Differences in proportions and the Youden index will be compared using approximate Z-tests or Chi-square tests, with adjustment for center effects. (6) Statistical software: All statistical analyses will be performed using SPSS version 26.0.

Study Timeline

• Status Verified: 2025-07
• Study First Submitted: 2025-07-30
• Study First Submitted QC: 2025-07-30
• Last Update Submitted: 2025-07-30
• Study Start: 2025-08-01
• Study First Posted: 2025-08-06
• Last Update Posted: 2025-08-06
• Primary Completion: 2026-06
• Study Completion: 2026-10-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 288

Inclusion Criteria

• Age ≥18 years and ≤ 85 years;

• Subepithelial lesion in the gastrointestinal tract identified under white-light endoscopy and scheduled for CEH-EUS examination to determine the nature of the lesion;

• EUS image quality meets the following quality control standards:

  1. Equipment requirements: EU-ME2 processor (Olympus, Tokyo, Japan) and GF-UCT260 / GF-UE260 echoendoscope (Olympus, Tokyo, Japan);
  2. Image acquisition: Five EUS still images clearly displaying the lesion and surrounding structures, including maximum lesion diameter, originating layer, Doppler signals, and internal echo characteristics; a 15-second video clearly demonstrating the lesion without any artificial annotations (e.g., scale, needle, Doppler signal, elastography, etc.);
  3. CEH-EUS procedure: Use of extended pure harmonic detection (Ex-PHD) mode with mechanical index (MI) adjusted to 0.3; 2.4 mL of SonoVue contrast agent is injected via the elbow vein within 2-3 seconds, followed by a 5 mL saline flush; real-time dynamic image acquisition continues for 120 seconds, and video recording is collected.

• Patients with GIST confirmed by surgical or endoscopic resection pathology, and patients with leiomyoma confirmed by surgical resection, EUS-guided tissue sampling, or other biopsy techniques;

• Written informed consent is obtained.

Exclusion Criteria

• Age <18 years or >85 years;
• Hemoglobin level ≤8.0 g/dL;
• Known allergy or hypersensitivity to ultrasound contrast agents;
• Pregnant women;
• Severe cardiopulmonary dysfunction that precludes tolerance of endoscopic ultrasound examination;
• Inability to provide written informed consent (e.g., due to psychiatric disorders or substance abuse).

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Diagnostic accuracy of CE-EUS and EUS for differentiating GIST from leiomyoma	Within 1 month after final histopathological diagnosis	The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall diagnostic accuracy of CE-EUS and conventional EUS will be calculated based on histopathological diagnosis as the gold standard.
Accuracy of CE-EUS and EUS in predicting malignant potential (risk stratification) of gastrointestinal stromal tumors	Within 1 month after final histopathological diagnosis	The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall diagnostic accuracy of CE-EUS and conventional EUS will be calculated based on histopathological diagnosis as the gold standard.

Secondary Outcome Measures

Name	Time	Method
Quantitative TIC Parameter Analysis for Differential Diagnosis and Risk Stratification	Within 1 month after histopathological diagnosis	TIC-based quantitative CEH-EUS parameters will be measured and evaluated for their ability to distinguish GIST from leiomyoma and to predict GIST risk stratification, compared against final histopathology.
Comparison of CEH-EUS Imaging Characteristics Between GIST and Leiomyoma	Within 1 month after histopathological diagnosis	Contrast-enhancement patterns and perfusion characteristics will be recorded and compared between histologically confirmed GISTs and leiomyomas.
Correlation of CEH-EUS Perfusion Parameters with Tumor Type and Risk Classification	Within 1 month after histopathological diagnosis	CEH-EUS perfusion parameters such as enhancement intensity, wash-in rate, and wash-out rate will be analyzed for correlation with tumor type (GIST vs. leiomyoma) and with GIST risk levels based on NIH criteria.

Trial Locations

Locations (1)

Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology; 🇨🇳 Wuhan, Hubei, China