Hyperpolarized 13C Pyruvate MRI for Early Immune Evaluation in Cervical Cancer Patients At Baseline and CCRT Therapy

NCT04951921CompletedPHASE2INTERVENTIONAL

Summary

In this single armed, single-center, case-controlled study, the investigators will conduct a prospective trial and integrate the most advanced imaging technology to medical practice, attempting to solve the problem detected by radiomics approach. The investigators plan a 3-year project with non-randomized, single group assignment observational study design. Thirty participants with diagnosed LACC that are to receive CCRT are to be recruited for this prospective single institutional study from Chang Gung Memorial Hospital at Linkou (CGMH). Standard-of-care MRI/CT that is required for staging will be the first line screening method. A tumor biopsy and routine blood test will be obtained at the time of the initial clinic visit. Participants eligible for this study will receive two investigative exams-MRF, CEST, DNP-MRI MRI and Metabolomics, at baseline and the 2-week during CCRT. The new imaging methods being tested are MRF and CEST without contrast enhancement, and DNP-MRI which provides quantitative measurement of the metabolism occurring within cancer cells. It also involves injection of a contrast agent-Hyperpolarized pyruvate (13C) Injection. The participants will be injected with the study drug at a dose of 0.43 ml/kg and then receive MRI scan.

Key Facts

Lead Sponsor

Chang Gung Memorial Hospital

Enrollment

6

Start Date

2021-07-15

Completion Date

2024-07-31

Study Type

INTERVENTIONAL

Official Title

Precision Medicine Imaging for Cervical Cancer: Integrating MR Fingerprinting, Dynamic Nuclear Polarization (DNP)-MRI and Artificial Intelligence Radiomics

Interventions

Hyperpolarized 13C Pyruvate

Conditions

Cervical Cancer

Eligibility

Age Range

20 Years+

Sex

FEMALE

Inclusion Criteria:

1. Histologically confirmed carcinoma of the uterine cervix.
2. Age ≥ 20 years.
3. Clinical International Federation of Gynecology and Obstetrics (FIGO) stage IB2-IV.
4. Tumor diameter ≥ 4 cm, verified by MRI or CT.
5. Scheduled curative-intent non-surgical treatment.

Exclusion Criteria:

1. Contraindication to MRI study (e.g. claustrophobia, cardiac pacemaker, metal implants in pelvis).
2. Inadequate marrow, liver and renal functions.
3. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
4. Pregnant or breast-feeding women.

Outcome Measures

Primary Outcomes

MRI size measurement of the primary tumor

Tumor size measurement by regular MRI

Time frame: Change from baseline in tumor size at 3 months

Secondary Outcomes

Recurrent rate

Follow-up recurrent rate

Time frame: Follow-up for 5 years

Locations

Chang Gung Memorial Hospital, Taoyuan, Taiwan

Linked Papers

2024-04-10

Hyperpolarized [1-13C]-pyruvate MRS evaluates immune potential and predicts response to radiotherapy in cervical cancer

Abstract Background Monitoring pyruvate metabolism in the spleen is important for assessing immune activity and achieving successful radiotherapy for cervical cancer due to the significance of the abscopal effect. We aimed to explore the feasibility of utilizing hyperpolarized (HP) [1-13C]-pyruvate magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) to evaluate pyruvate metabolism in the human spleen, with the aim of identifying potential candidates for radiotherapy in cervical cancer. Methods This prospective study recruited six female patients with cervical cancer (median age 55 years; range 39–60) evaluated using HP [1-13C]-pyruvate MRI/MRS at baseline and 2 weeks after radiotherapy. Proton (1H) diffusion-weighted MRI was performed in parallel to estimate splenic cellularity. The primary outcome was defined as tumor response to radiotherapy. The Student t-test was used for comparing 13C data between the groups. Results The splenic HP [1-13C]-lactate-to-total carbon (tC) ratio was 5.6-fold lower in the responders than in the non-responders at baseline (p = 0.009). The splenic [1-13C]-lactate-to-tC ratio revealed a 1.7-fold increase (p = 0.415) and the splenic [1-13C]-alanine-to-tC ratio revealed a 1.8-fold increase after radiotherapy (p = 0.482). The blood leukocyte differential count revealed an increased proportion of neutrophils two weeks following treatment, indicating enhanced immune activity (p = 0.013). The splenic apparent diffusion coefficient values between the groups were not significantly different. Conclusions This exploratory study revealed the feasibility of HP [1-13C]-pyruvate MRS of the spleen for evaluating baseline immune potential, which was associated with clinical outcomes of cervical cancer after radiotherapy. Trial registration ClinicalTrials.gov NCT04951921, registered 7 July 2021. Relevance statement This prospective study revealed the feasibility of using HP 13C MRI/MRS for assessing pyruvate metabolism of the spleen to evaluate the patients’ immune potential that is associated with radiotherapeutic clinical outcomes in cervical cancer. Key points • Effective radiotherapy induces abscopal effect via altering immune metabolism. • Hyperpolarized 13C MRS evaluates patients’ immune potential non-invasively. • Pyruvate-to-lactate conversion in the spleen is elevated following radiotherapy. Graphical Abstract

Linked Investigators

Gigin Lin