Clinical trial NCT01874548: MR Metabolic Biomarkers for Cervical Cancer
Official title: Magnetic Resonance Study on Metabolism Biomarkers for Cervical Cancer.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Uterine Cervical Neoplasms
Keywords: Autophagy
Cancer metabolism
Cervical cancer
Diffusion weighted imaging
Human papillomavirus
Magnetic resonance spectroscopy.
Lead sponsor: Chang Gung Memorial Hospital
Sponsor class: OTHER
First posted: 2013-06-11
Enrollment: 136
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients in a tertiary referral center.

Brief summary: The purposes of this study are: (1) to develop magnetic resonance (MR) imaging and spectroscopy as surrogate biomarkers for altered cancer metabolism in cervical cancer; (2) to understand the function of human papillomavirus (HPV) infection and autophagy (a cellular catabolic degradation response to stress) in the metabolic alterations in cervical cancer.

Detailed description: In the first part of this project, we aim to identify the differences in cancer metabolism between normal and cervical cancer. Conventional MR study plus magnetic resonance spectroscopy (MRS) and diffusion weighted imaging (DWI) sequences will be carried out on 30 eligible surgical candidates for pretreatment clinical assessment. Metabolites in cancer tissue will be collected during operation and analyzed using high resolution MRS, and compared with control group comprising 30 patients with normal cervical tissue. The primary endpoint of this part is to identify different MRS profiles between normal and cancer subjects. We will investigate the underlying biological mechanism between these two groups by evaluating status of HPV infection and autophagy. In the second part, we aim to understand cancer metabolism in cervical cancers infected by different types of HPV. We plan to enroll another 30 surgical candidates and complete the data regarding clinical MRS/DWI and tissue high resolution MRS. Together with the 30 cancer subjects in part one there will be in total 60 cancer subjects for analysis. The primary endpoint of this part is to compare MRS profiles from cancer tissue infected with different HPV genotypes, particularly HPV type 16 and HPV type 18. The secondary endpoint is to correlate the tissue MRS profiles with the in vivo MRS/DWI measured by clinical MR scanner. In the third part of this project, we aim to investigate cancer metabolism under combined chemoradiation therapy (CCRT). We plan to enroll 60 patients primarily treated with CCRT and collect the data using clinical MR and tissue high-resolution MRS. Tissue MRS profiles will be correlated with the HPV, E6/E7 and autophagy.

The advance in knowledge of this project is to unwire the complex relationship among cancer metabolism, HPV infection and autophagy in cervical cancer. The clinical impact is the development of MR biomarkers for cancer metabolism and autophagy, both play important roles in the resistance to cancer therapy. The inherited non-invasiveness and non-radiation nature makes MR technique an ideal platform for clinical usage.

Eligibility criteria: Inclusion Criteria:

* be able to give informed consent.
* female patients between 20 and 80 years of age.
* biopsy proven newly diagnosed cervical cancer clinical stage International Federation of Gynecology and Obstetrics (FIGO) Ib and above.
* patients must be willing to undergo standard treatment such as surgery or chemo-radiation therapy.

Exclusion Criteria:

* patients who are judged to be noncompliant to treatment or not accessible for follow up.
* patients with contraindications to magnetic resonance imaging (MRI) scanning, such as claustrophobia, cardiac pacemaker, metal implants in field of view, or unable to cooperate for MRI study due to mental status.

Primary outcomes:
measure: the amounts of metabolites in uterine cervical tissue
timeFrame: up to 8 weeks of magnetic resonance imaging and spectroscopy exam
Secondary outcomes:
Other outcomes:
Locations:
city: Guishan
country: Taiwan
facility: Department of Radiology, Chang Gung Memorial Hospital
state: Taoyuan
Study officials:
affiliation: Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital
name: Gigin Lin, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lin G, Lai CH, Tsai SY, Lin YC, Huang YT, Wu RC, Yang LY, Lu HY, Chao A, Wang CC, Ng KK, Ng SH, Chou HH, Yen TC, Hung JH. 1 H MR spectroscopy in cervical carcinoma using external phase array body coil at 3.0 Tesla: Prediction of poor prognostic human papillomavirus genotypes. J Magn Reson Imaging. 2017 Mar;45(3):899-907. doi: 10.1002/jmri.25386. Epub 2016 Jul 19.