Measurement of Head and Neck Tumor Hypoxia With PET-MRI (EF5NECK)

Simultaneous PET-MRI for Comparison of Advanced DW-MRI Techniques and EF5-PET in the Detection of Hypoxia in Head and Neck Cancer

This study is designed to evaluate the performance of advanced magnetic resonance (MR) imaging in the assessment of tumor hypoxia using [18F]EF5 positron emission tomography (PET) as a reference in head and neck cancer patients. Low oxygen level or hypoxia contributes to radiotherapy resistance. Therefore, a clinically applicable method to detect tumor hypoxia is of great importance.

Study Overview

• Status: Recruiting
• Conditions: Head and Neck Cancer
• Intervention / Treatment: Diagnostic test: PET-MRI

Detailed Description

This is a non-randomized prospective study which aims to compare [18F]EF5 PET data and MR imaging data acquired with simultaneous PET/MR imaging. Hypoxic tumor tends to be more aggressive than its non-hypoxic counterpart since hypoxia promotes invasive tumor growth and metastatic spread of the disease. The detrimental effect of hypoxia on outcome of radiotherapy (RT) is especially important in head and neck cancer.

EF5 is a comprehensively studied hypoxia-avid compound, which is utilized in radiolabeled form in [18F]EF5 PET imaging detecting tumor hypoxia. IVIM (intra-voxel incoherent motion) is novel technique based on diffusion-weighted MRI (DWI), which allows for the distinction between tissue perfusion and diffusion without the need for intravenous contrast agent. This study aims to investigate the potential of novel MRI techniques for tumor hypoxia assessment in HNC.

The specific aims of the current study are:

1. To characterize the voxel-level relationship between diffusion characteristics in tumor tissue, as measured with DW-MRI, and tumor hypoxia, as measured with [18F]EF5-PET, leveraging the state-of-the-art simultaneous MRI/PET measurement;
2. To employ IVIM-based modeling of DW-MRI signal using multiple b-values to optimize the diffusion metrics that most closely predict tumor hypoxia, and compare those with the perfusion metrics from DCE;
3. To develop models based on novel radiophenotypic analyses of MRI data (radiomics) and machine learning algorithms to find MRI patterns that best predict tumor hypoxia at the patient sample level.

The only intervention for participating subjects is an additional [18F]EF5-PET/MR scan, which is not used for any clinical purposes. All study subjects will undergo standard diagnostic and treatment procedures according to clinical routine.

A standard dose of about 300 MBq of the radiotracer [18F]EF5 will be administered intravenously via an upper extremity vein. About 180 min after tracer injection, radioactivity will be followed in the neck area with the PET/MRI device for about 20 min. [18F]EF5 uptake will be modeled as standard uptake value (SUV), and tumor-to-background ratios (TBR) will be calculated.

The MRI protocol will include anatomical sequences covering the primary tumor as well as the neck for lymph node metastases. Several DW-MRI methods will also be employed. In total, MRI experiments will be completed in about 1 hour.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jussi Hirvonen, MD, PhD; Phone Number: 0035823130000; Email: jussi.hirvonen@tyks.fi
• Study Contact Backup: Name: Antti Silvoniemi, MD, PhD; Phone Number: 0035823130000; Email: antti.silvoniemi@tyks.fi

Study Locations

• Finland
  • G102881
    • Turku, G102881, Finland, 20521
      • Recruiting
      • Turku University Hospital
      • Contact: Jussi Hirvonen, MD, PhD; Phone Number: 0035823130000; Email: jussi.hirvonen@tyks.fi
      • Contact: Antti Silvoniemi, MD, PhD; Phone Number: 0035823130000; Email: antti.silvoniemi@tyks.fi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age: 18 to 80 years old
• Sex: male or female
• Language spoken: Finnish or Swedish
• Performance status: Karnofsky score 70 or better or WHO performance status 2 or better
• Mental status: Patients must be able to understand the meaning of the study
• Diagnosis: Histological, cytological and clinical findings are consistent with squamous cell carcinoma of the head and neck (oral cavity, pharynx or larynx)
• Primary tumor diameter as determined clinically or from contrast enhanced CT or MRI scan must be at least 20 mm
• Patients with nodal neck metastases of head and neck cancer are eligible
• Informed consent: The patient must sign the appropriate Ethical Committee (EC) approved informed consent documents in the presence of the designated staff
• Gravidity: Patient, if female, must not be pregnant or lactating at the time of the study

Exclusion Criteria:

• Any previously known contraindication of MR Imaging (including but not limited to metallic implants or foreign bodies, pacemakers or other cardiac implantable electronic devices, MR-incompatible prosthetic heart valves, contrast allergy, claustrophobia)
• Prior Medical History: Patient must have no history of serious haematologic, cardiovascular, liver or kidney disease. Since none of these is an absolute contraindication for inclusion final judgement will be left to the investigators.
• Prior Therapy: Patient must have no history of previous chemotherapy, biological therapy, immunotherapy, radiotherapy or major surgery for treatment of head and neck cancer
• Infections: Patient must not have an uncontrolled serious infection
• Advanced disease: Patient is not eligible for curative cancer treatment due to advanced disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: PET-MRI; Simultaneous 18F-EF5 PET and DW-MRI	Diagnostic test: PET-MRI; Simultaneous PET-MRI measurement

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PET-MRI correlation	Voxel level correlation of DW-MRI and PET estimates	1 day

Collaborators and Investigators

• Sponsor: Turku University Hospital
• Investigators: Principal Investigator: Jussi Hirvonen, MD, PhD, Radiologist

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 8, 2022
• Primary Completion (ANTICIPATED): May 1, 2026
• Study Completion (ANTICIPATED): October 1, 2026

Study Registration Dates

• First Submitted: February 8, 2022
• First Submitted That Met QC Criteria: February 8, 2022
• First Posted (ACTUAL): February 18, 2022

Study Record Updates

• Last Update Posted (ACTUAL): February 18, 2022
• Last Update Submitted That Met QC Criteria: February 8, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Signs and Symptoms, Respiratory; Head and Neck Neoplasms; Hypoxia
• Other Study ID Numbers: T255/2021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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