Application of Contrast-enhanced Ultrasound in Monitoring Soft Tissue Sarcoma Response to Neoadjuvant Radiotherapy

April 9, 2026 updated by: Thomas Jefferson University

This pilot study will evaluate the feasibility of applying CEUS as imaging guidance for planning RT and predicting RT response. The investigators will determine if US-CT/MRI fusion is feasible and if tumor vascularity and pressure from CEUS can be used to reflect/predict the RT response.

The investigators will perform CEUS three times: before the first neoadjuvant RT fraction, halfway through RT, and between the completion of RT and surgery. The fusion will be performed using previously acquired CT/MRI or on-site cone-beam CT with Bmode US. Once the fusion is successful, CEUS will be performed and panoramic 2D images (mimicking 3D) will be collected for the whole tumor. If the fusion is not feasible or successful, the investigators will perform CEUS side by side with CT/MRI and collect images. The investigators will quantify tumoral vascularity comparing Bmode area/volume (total tumor) and contrast-enhanced area/volume (vascular region) at each time point. Subharmonic amplitudes in the tumor area/volume will be quantified to estimate tumoral pressure (known to be the same level as interstitial fluid pressure (IFP)). Quantified vascularity and pressure at each time point will be compared with the tumor size change at later study points as well as the histological outcome after the surgery.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is an open-label, non-randomized, human trial that will be conducted at one clinical site, Thomas Jefferson University. Our subjects will be patients with localized STS scheduled for neoadjuvant RT based upon the recommendations of our multidisciplinary sarcoma tumor board.

All subjects will have an unenhanced (baseline) conventional US followed by CEUS study with infusion of ultrasound contrast agent (Definity; Lantheus Medical Imaging). The investigators will collect the study data at three time points: 1) prior to the first RT fraction, 2) middle of RT (e.g., any day on 3rd week of 5 week-long RT), and 3) between the completion of RT and surgery.

The ultrasound contrast administration will be an intravenous infusion of 2 vials of Definity/50ml saline will be administered as an IV infusion via a peripheral vein (preferably the antecubital vein), with infusion rates of 4 to 10 ml/min (titrated to effect) through an 18-22 gauge angiocatheter. During the contrast infusion, CEUS data will be collected.

On the study visit, the investigators first perform conventional US including Doppler imaging using a C2-9VN probe (with embedded electromagnetic sensors) on Loqiq E10 (GE HealthCare) to locate the whole tumor and select the planes for fusion. The US scanner has dedicated fusion software, and the investigators will load the pre-obtained CT/MRI (most recent CT/MRI by standard of care) on US scanner and fuse it with real-time US by selecting references points under the magnetic field created by an electromagnetic transmitter near a subject. Once the fusion is done (if the fusion fails or unsatisfactory, the investigators will perform CEUS alone), the investigators will start the infusion UCA, Definity (3 ml of Definity suspended in 50 ml saline) via a peripheral vein (preferably the antecubital vein), with infusion rates of 4 to 10 ml/min (titrated to effect) through an 18-22 gauge angiocatheter. The dosage was selected based on our previous work in monitoring breast tumor IFP in humans. Conventional CEUS images will be collected as 2D movie clips sweeping over 3D tumor volume during infusion. Then, the investigators will turn on SHAPE mode. The investigators will determine the optimum SHAPE settings (where the subharmonic signal changed the most, which will vary among subjects) for each subject and infusion will be stopped during this process. With restarting the infusion, the SHAPE data will be collected with individually determined acoustic power, which allows us to compare the pressure between subjects independently of an operator and other imaging settings. Another set of SHAPE data will be acquired at the same acoustic output power setting with no UCA after roughly 5 minutes (to allow for clearance of bubbles).

Study Type

Interventional

Enrollment (Estimated)

10

Phase

  • Early Phase 1

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 Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Recruiting
        • Thomas Jefferson University Hospital
        • Contact:
        • Principal Investigator:
          • Kibo Nam, PhD

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

No

Description

Inclusion Criteria:

  • Individuals must meet all of the following inclusion criteria in order to be eligible to participate in the study:

    • Provide signed and dated informed consent form
    • Willing to comply with all study procedures and be available for the duration of the study
    • Male or female, Male or female, aged ≥18 years of age
    • Patients with pathologically confirmed STS (Trunk and extremity sarcoma only)

    • Scheduled for neoadjuvant RT for STS

      o Both standard and hypofractionation schedules are permitted.

    • Willing to comply with all study procedures and be available for the duration of the study

Exclusion Criteria:

  • An individual who meets any of the following criteria will be excluded from participation in this study:

    • Pregnancy or lactation
    • Known allergic reactions to any component of Definity
    • Has STS that is too large for ultrasound imaging (e.g. its short axis is larger than 10 cm at the depth of 2 cm)
    • Has other primary cancers requiring systemic treatment.
    • Has metastatic disease at presentation
    • Had prior RT to the area

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

  • Primary Purpose: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: CEUS with Definity
Patients will first undergo baseline ultrasound imaging over the whole tumor and then will receive an administration of ultrasound contrast agent. The ultrasound contrast administration will be an intravenous infusion of 2 vials of Definity/50ml saline will be administered as an IV infusion via a peripheral vein (preferably the antecubital vein), with infusion rates of 4 to 10 ml/min (titrated to effect) through an 18-22 gauge angiocatheter. During the contrast infusion, CEUS data will be collected.
Drug: Definity
Definity will be administered as an IV infusion via a peripheral vein (preferably the antecubital vein), with infusion rates of 4 to 10 ml/min (titrated to effect) through an 18 to 22 gauge angio-catheter.
Other Names:
  • Perflutren Lipid Microsphere
  • Definity RT
Diagnostic test: Contrast-Enhanced Ultrasound
Contrast-enhanced ultrasound (CEUS) imaging will be performed after baseline ultrasound imaging of the tumor. During intravenous infusion of ultrasound contrast agent, CEUS data will be collected as 2D movie clips sweeping over the tumor volume. CEUS imaging will be performed at three study timepoints: prior to the first radiotherapy fraction, during radiotherapy, and after completion of radiotherapy prior to surgery.
Other Names:
  • CEUS

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Success of US-CT/MRI fusion
Time Frame: From Baseline to Post-Radiotherapy prior to Surgery, Approximately 3 months

It will be treated as a binary outcome and summarized with a proportion and presented with a Clopper-Pearson exact 95% confidence interval at the visit level and at the patient level (where success at every visit relates success for the patient).

The investigators will evaluate the US-CT/MRI fusion qualitatively (by a radiologist) either Success or Fail at each time point (3 time points in total). The investigators will consider Success for a patient if more than 50% success rate from three time points.
From Baseline to Post-Radiotherapy prior to Surgery, Approximately 3 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluation of Tumor Size
Time Frame: From Baseline to Post-Radiotherapy prior to Surgery, Approximately 3 months

The tumor area/volume with/without enhancement from CEUS will be compared with those from CTs or MRIs using data plots; by computing Pearson's correlation coefficients; and by computing and presenting in a table their respective means ± standard deviations as well as the respective means and 95% confidence intervals for the differences between CEUS and CT or MRI modalities.

The investigators will report the mean ± standard deviation from CEUS and CT/MRI and the difference between two imaging modality in mean ± standard deviation.
From Baseline to Post-Radiotherapy prior to Surgery, Approximately 3 months
Evaluation of RECIST Response
Time Frame: Prior to Surgery
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by standard of care imaging (e.g., CT/MRI): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. The investigators will evaluate the RECIST response assessed by standard of care imaging is consistent with the RECEIST response assessed by CEUS.
Prior to Surgery
Correlation with Histological Outcome After Surgery
Time Frame: After Surgery
The residual tumor area/volume quantified using 2D conventional CEUS clips will be also compared with histology outcomes (necrosis and viable tumor areas) using correlation coefficients. The investigators will evaluate if the viable/non-viable lesions identified by histology are correlated with the lesion vascularity and pressure quantified from CEUS.
After Surgery

Collaborators and Investigators

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

Sponsor

Thomas Jefferson University

Investigators

  • Principal Investigator: Kibo Nam, PhD, Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University

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 (Actual)

March 23, 2026

Primary Completion (Estimated)

May 1, 2027

Study Completion (Estimated)

May 1, 2027

Study Registration Dates

First Submitted

February 18, 2026

First Submitted That Met QC Criteria

February 20, 2026

First Posted (Actual)

February 27, 2026

Study Record Updates

Last Update Posted (Actual)

April 14, 2026

Last Update Submitted That Met QC Criteria

April 9, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • iRISID-2025-1257
  • JT 46327 (Other Identifier: JeffTrial Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

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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