PET/MR Pre- and Post Radiotherapy for Cardiopulmonary Dysfunction Evaluation

Exploratory Evaluation of Simultaneous Cardiac PET/MR, Metabolomic Markers and Circulating DNA as Possible Prognostic Markers in Identifying Patients Developing Transient or Permanent Cardiopulmonary Dysfunctions After Radiotherapy

Radiotherapy (RT) is a well-known and established therapy or adjuvant therapy for the treatment of thoracic cancer It uses a high energy radiation from x-rays, gamma rays and other charged particles that assist in damaging the cancer DNA.

PET/MR as imaging biomarkers for cardiopulmonary dysfunction with a focus on Pulmonary hypertension (PH).

Despite the measures taken to reduce the total radiation dose and to limit the radiation to normal tissues, there is evidence of transient or permanent radiotherapy induced myocardial and pulmonary dysfunction leading to PH in patients who receive radiotherapy above a certain threshold of received dose.

To be able to Demonstrate correlation of combined PET/MR and plasma metabolomics markers in patients at risk of developing cardiopulmonary disfunction after RT.

Study Overview

• Status: Recruiting
• Conditions: Pulmonary Hypertension
• Intervention / Treatment: Drug: PET/MR with 18F-FDG

Detailed Description

RT is a well-known and established therapy or adjuvant therapy for the treatment of thoracic malignancies (breast cancer, lung cancer, lymphoma and others). It usually uses high energy radiation from x-rays, gamma rays or other charged particles to induce DNA damage in malignant cells. Despite the measures taken to reduce the total radiation dose and to limit the radiation to normal tissues, the signs and symptoms of radiation induced cardiopulmonary dysfunction (RICPD) still persist. However, in the majority of cases, it remains unclear which cardiopulmonary damage is the main /leading cause for the clinical symptoms the patients are experiencing.

Hybrid PET/MRI is a promising technique that allows for truly simultaneous molecular, anatomic and functional imaging of the cardiopulmonary system. The simultaneity is an important aspect in this proposed study since only parameters measured at the same time in PET and MR can be used for an integrated, multimodality parameter for possible detection and prognostication of the different underlying processes of cardiopulmonary dysfunction after RT. Furthermore, certain PET-uptake of the RV have to be corrected for RV mass which is only possible with concomitant anatomical imaging. MR imaging and PET at different time point are not accurately reflective of the underlying pathophysiological pathways and metabolic state at the specific time points pre- and post radiotherapy. To our knowledge, there are no online publications of its use in the diagnosis and prognostication of cardiopulmonary dysfunction after RT and specifically PH.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Patrick Veit-Haibach, MD; Phone Number: 6085 416-340-4800; Email: Patrick.Veit-Haibach@uhn.ca
• Study Contact Backup: Name: Andrew Hope, MD; Phone Number: 416-946-2124; Email: Andrew.Hope@rmp.uhn.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Recruiting
      • University Health Network
      • Contact: Patrick Veit-Haibach

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥18 years
• Biopsy or otherwise clinically proven thoracic malignant mass which is intended to be treated with radio(chemo)therapy
• Intention to treat with radio(chemo)therapy with incidental cardiac irradiation of at least 25Gy.
• A negative urine or serum pregnancy test within the two week interval immediately prior to imaging, in women of child-bearing age.
• Ability to provide written informed consent to participate in the study (for all components of the trial: imaging with cardiac PET/MR, blood sampling for plasma metabolomics and circulating DNA).

Exclusion Criteria:

• Contraindication for MR as per current institutional guidelines.
• Contraindication for Gadolinium injection as per current institutional guidelines.
• Inability to lie supine for at least 45 minutes.
• Any patient who is pregnant or breastfeeding.
• Any patient with known hypersensitivity to 18F-FDG.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: One arm / exploratory study; Injection of 18F-FDG.The 18F-FDG cardiac PET-MR scanning visit will take up to 1.5 hours.	Drug: PET/MR with 18F-FDG; (18F) Fluorodeoxyglucose (FDG) will be administered by intravenous injection at a dose of 4-5 MBq/kg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of FDG uptake of heart	FDG uptake of the left and right ventricles of heart will be measured and compared in PETMRI scans	at 4 weeks prior to radiotherapy, and at 6-10 weeks after completion of radiotherapy
Change of FDG uptake of lungs	FDG uptake of left and right ratios within the lungs in PETMRI scans	at 4 weeks prior to radiotherapy, and at 6-10 weeks after completion of radiotherapy
Change of the heart function	MRI of ventricular volumes in PETMRI scans	at 4 weeks prior to radiotherapy, and at 6-10 weeks after completion of radiotherapy
Change of the lung perfusion	Percentage of the perfused/ventilated lung segments will be evaluated and compared pre and post therapy by SPECT scans	before radiotherapy and up to 16 weeks after completion of radiotherapy

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Investigators: Principal Investigator: Patrick Veit-Haibach, MD, University Health Network, Toronto

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2021
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: March 17, 2021
• First Submitted That Met QC Criteria: May 19, 2021
• First Posted (Actual): May 26, 2021

Study Record Updates

• Last Update Posted (Estimated): December 7, 2023
• Last Update Submitted That Met QC Criteria: December 6, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Hypertension, Pulmonary; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; Fluorodeoxyglucose F18
• Other Study ID Numbers: 18-5879

Drug and device information, study documents

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