PET and MRI in Prognosis Prediction of NPC

1. Background: Nasopharyngeal carcinoma (NPC) has a higher local tumor control rate but a higher incidence of distant metastasis compared with squamous cell carcinomas of other regions of the head and neck. Thus, it's usually considered a distinct study group. A reliable clinical prognostic factor for NPC patients is still lacking. Positron emission tomography (PET) with 2- [fluorine- 18]fluoro-2-deoxy-D-glucose (18F-FDG)/computed tomography (CT) has been used extensively for diagnosis and assessment of prognosis in NPC in recent years. Several PET-derived imaging parameters such as standardized uptake value (SUV), metabolic tumor volume (MTV), or total lesion glycolysis (TLG) have been proposed as potential prognosticators in NPC. MRI functional parameters also play a role to assess the cellular or molecular change of head and neck cancer. Diffusion-weighted MR imaging (DWI) is a technique, which can quantify the diffusion of water molecules in tissues using apparent diffusion coefficient (ADC). ADC is inversely correlated with cellular density. Dynamic contrast-enhanced perfusion MR imaging (DCE-MRI) is another MRI technique based on sequential imaging obtained during the passage of a contrast of agent through the tissue. It enables probing the microvascular environment in the tumor tissue. Integrated PET/MRI is a new imaging modality, which can simultaneously acquire PET and MRI images. Traditionally, PET and MRI images were acquired on different dates and were fused by commercial software. Problems caused by a separate system include SUV or MRI parameters were reported to be different if the scans were acquired on different days. Simultaneous acquisition of PET and MRI images would solve these problems.
2. Aim: The investigators conduct this prospective study to investigate the roles of integrated PET/MRI imaging parameters for predicting treatment outcomes and prognosis in patients with NPC.
3. Study design:

Patients: All patients receive whole-body 18F-FDG PET/MRI following 18F-FDG-PET/CT on the same day. For tumor staging, the 7th edition of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) cancer staging system is used. The patients with stage I disease are treated with definitive radiation therapy alone, while patients with stage II-IVB are treated with concurrent chemoradiotherapy. Patients with metastatic disease (stage IVC) are treated with standard platinum-based chemotherapy.

18F-FDG PET/CT: All study patients fast for at least 6 h before 18F-FDG PET/CT imaging. Scans are performed using a Biograph mCT scanner (Siemens Medical Solutions, Malvern, PA, USA) consisting of a four-ring PET scanner (axial field-of-view [FOV] = 22.1 cm, transaxial FOV = 70 cm) and a 40-section CT scanner.

Whole-body 18F-FDG PET/MRI: PET/MRI is performed on a Biograph mMR (Siemens Healthcare, Erlangen, Germany) following the PET/CT scan on the same day. The PET/MRI system is equipped with 3-T magnetic field strength, total imaging matrix coil technology covering the entire body with multiple integrated radiofrequency surface coils, and a fully functional PET system with avalanche photodiode technology embedded in the magnetic resonance gantry.

Image interpretation: The PET/CT and PET/MRI data sets are evaluated on dedicated workstations (Syngo.via, Siemens Healthcare, Erlangen, Germany). The readers interpret the (1) MR images from PET/MRI, (2) 18F-FDG PET/MRI images, and (3) 18F-FDG PET/CT images independently. They are aware of the study protocol but are blinded to the results from the other imaging modalities. Imaging parameters including SUV, MTV, TLG, ADC, Ktrans, Ve, and Vp are calculated.

Statistical analysis: Overall survival (OS) and recurrence-free survival (RFS) serves as the main outcome measures. OS is calculated from the date of diagnosis to the date of death or censored at the date of the last follow-up for surviving patients. RFS is defined as the time between the end of treatment and the date of recurrence (tumor relapse or death) or censored at the date of the last follow-up. The cutoff values for the clinical variables and imaging parameters in survival analysis are determined using the log-rank test based on the RFS and OS rates observed in the entire study cohort. Survival curves are plotted using the Kaplan-Meier method. The effect of each individual variable is initially evaluated using univariate analysis. Cox regression models are used to identify the predictors of survival. Two-tailed P values < 0.05 are considered statistically significant.