IVIM & OLINK in Sarcoma

Prospective Study of Image and Blood-derived Biomarkers to Predict Metastasis in Soft-tissue Sarcomas

The hypoxia > metastasis axis suggests that a DWI-based biomarker of hypoxia incorporating IVIM may be able to predict metastasis in STS patients, ultimately enabling stratification for personalized treatments at the time of diagnostic (MR) imaging, without adding an excessive burden to the patient or clinical workflow (typical DWI/IVIM sequences can be acquired acquired in approximately 5 minutes).

Study Overview

• Status: Recruiting
• Conditions: Soft Tissue Sarcoma
• Intervention / Treatment: Radiation: Radiotherapy; Other: Surgery

Detailed Description

Tumour hypoxia has been implicated as a major driver in STS metastatic dissemination. Despite this, patients are not routinely assessed for hypoxia, largely due to the cost and difficulty involved. PET hypoxia imaging using Fluorine-18-labelled nitroimidazole-based agents such as fluoroazomycin arabinoside (FAZA) provide non-invasive in vivo quantification of hypoxia [5], including in STS. The expense and unproven clinical value of these agents and the long times between their injection and PET scanning (typically, two hours) has limited the uptake of PET-hypoxia imaging as a routine screening modality. In contrast, magnetic resonance imaging (MRI) is standard for diagnosis of STS and is a routine part of the radiation therapy workflow due to its superior contrast between tumour and surrounding normal tissue. In addition, diffusion-weighted magnetic resonance imaging (DWI) can quantify physiological tumour properties such as cellularity and perfusion that may provide information about tumour biology, including hypoxia.

Hypoxia results from the interplay between oxygen demand (oxygen consumption rate) and supply (perfusion). Hypothesizing that oxygen consumption increases with increasing cellularity, Hompland and colleagues demonstrated that a biomarker derived from IVIM measurements could predict hypoxia in prostate, breast, and cervical cancer patients. An ongoing prospective imaging study of hypoxia in STS patients at Princess Margaret is investigating the capacity of FAZA to image hypoxia in STS and develop correlative DWI (IVIM)-based biomarkers of hypoxia on a combined PET/MRI scanner.

• Study Type: Interventional
• Enrollment (Estimated): 145
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: David Shultz, MD; Phone Number: 2121 416-946-4501; Email: david.shultz@rmp.uhn.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, L4W4C2
      • Recruiting
      • University Health Network
      • Contact: David Shultz, MD; Phone Number: 6899 416 946 4501; Email: david.shultz@uhn.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years
• Ability to understand and the willingness to sign a written informed consent document
• Grade 2 or 3 soft tissue sarcoma greater than 5 cm in largest dimension

Exclusion Criteria:

• Contraindication to MRI scan as per current institutional guidelines (for patients requiring MRI)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identify image-derived, plasma-derived biomarkers of hypoxia	Image-derived, plasma-derived biomarkers of hypoxia (such as HIF-1alpha, VEGF, osteopontin) acquired before radiation therapy will be assessed for correlation to distant metastasis-free survival.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival		3 years
Progression-free survival		3 years
Hypoxia in plasma	Correlation between the relative concentration of circulating protein biomarkers of hypoxia detected in plasma using proximity-extension assays to hypoxic fraction as calculated by MR imaging and to distant metastasis-free survival.	3 years
Transcriptomic and proteomic expression profiles in circulating immune cells	Transcriptomic expression (measured using RNA sequencing and reported as normalized read counts) and proteomic expression (measured using OLINK proximity-extension assays and reported as NPX units) will be characterized in circulating immune and tumor cells collected before radiotherapy and correlated with distant metastasis-free survival, overall survival, and progression-free survival.	3 years
Distant-metastasis free survival		3 years

Collaborators and Investigators

• Sponsor: University Health Network, Toronto

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2024
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): November 30, 2027

Study Registration Dates

• First Submitted: July 10, 2023
• First Submitted That Met QC Criteria: July 10, 2023
• First Posted (Actual): July 18, 2023

Study Record Updates

• Last Update Posted (Actual): March 16, 2026
• Last Update Submitted That Met QC Criteria: March 11, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Connective and Soft Tissue; Sarcoma; Therapeutics; Radiotherapy; Surgical Procedures, Operative
• Other Study ID Numbers: 23-5436

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No