Usefulness of Integrated PET/MRI in Oropharyngeal Squamous Cell Carcinoma Evaluation
Condition: Oropharyngeal Cancer
MeSH terms: Carcinoma, Squamous Cell; Oropharyngeal Neoplasms; Squamous Cell Carcinoma of Head and Neck
Study type: Observational

Summary: 
      Head and neck cancer (HNC) continues to be a significant health care problem in Taiwan and
      oropharyngeal squamous cell carcinoma (SCC) is the common subtype. With the concern of organ
      preservation in recent years, concurrent chemoradiation is the major treatment modality for
      oropharyngeal SCC, while endoscopy with biopsy serves as the main diagnostic tools. With the
      advance of MRI technology, whole body MRI is now possible, and functional techniques become
      more feasible in the head and neck region, including diffusion-weighted imaging (DWI) which
      comprises of monoexponential DWI, intravoxel incoherent motion (IVIM) model and Kurtosis
      (biexponential or non-Gaussian fitting), and dynamic contrast-enhanced perfusion weighted MRI
      (DCE-PWI) become feasible. Therefore, MRI can evaluate distant site status of HNC in the
      single examination session and provide biologic information of tumors. Positron emission
      tomography/CT (PET/CT) is another common imaging modality to evaluate HNC, because of its
      ability to provide whole-body anatomic and metabolic information.

      Integrated PET/MRI is a novel imaging technology that combines PET and MRI in one single
      scanner. In this 3-year prospective study, the investigators will take the advantages of
      integrated PET/MRI scanner with DWI (including monoexponential, kurtosis and IVIM modes) and
      DCE-PWI to evaluate our 160 patients with oropharyngeal SCC subjected to chemoradiation.
      Non-contrast chest CT will also be performed on the same day. The investigators aim to
      determine whole-body staging/restaging accurately, to predict treatment response and
      prognosis, and to determine necessity of noncontrast chest CT. The investigators expect that
      this project will offer the validation of usefulness of integrated PET/MRI in tumor
      staging/restaging of oropharyngeal SCC and resultant clinical impact. The role of noncontrast
      chest CT in the workup with our PET/MRI protocol can be defined. It will also provide
      evidence about how and to what extent the various simultaneously acquired MRI and PET
      functional parameters can help prediction of treatment response and prognosis of
      oropharyngeal SCC subjected to chemoradiation, which are important in timely modification of
      treatment regimen.
    

Detailed description: 
      In this three-year prospective project, a total of 160 patients with histologically proven
      oropharyngeal SCC subjected to chemoradiation will be enrolled. Exclusion criteria include
      previous head or neck malignant tumor, a second malignant tumor, distant metastasis,
      contraindications to MRI (renal insufficiency, cochlear implant, cardiac pacemaker, or
      intracranial aneurysmal ferromagnetic clips), and serum glucose level >200 mg/dl. Each
      enrolled patients will undergo detail clinical examination, including human papillomavirus
      test. The participants will undergo low dose chest CT on the same day before PET/MRI. In the
      posttreatment period, baseline whole body MRI will be obtained 3 months after chemoradiation.
      Thereafter, the participants will then be followed up also with alternative extend-field CT
      and whole body MRI by every 6 months. If tumor recurrenceis confirmed or highly suspected,
      PET/MRI will also be performed for tumor re-staging.

      The three-years planning Adequate cases number and follow-up duration are essential for
      statistical analysis and outcome determination of oropharyngeal SCC treated with
      chemoradiation. The investigators plan to accomplish this study in 3 years.

      In the first year, the works of the this project in the first year will design the data bank
      categories, set up the workflow and optimize the imaging protocols, determine the diagnostic
      capability of MRI component, PET component, integrated PET/MRI in tumor staging, determinate
      any added diagnostic value of noncontrast chest CT in integrated PET/MRI, and study the early
      treatment response and the patterns of residual tumor.

      In the second year, the investigators will continue to the first-year works, and further
      include the following works to determinate incidence and predictors of treatment failure of
      oropharyngeal SCC, and to study the patterns of treatment response and early recurrence. In
      the third year, the investigators will continue to do previous work and will also get
      sufficient sample size to perform statistical analysis of the relationship between the
      imaging parameters and patient outcomes, attain comprehensive imaging about patterns of tumor
      recurrence and posttreatment changes/complications, investigate to what extent biologic
      imaging parameters may affect outcome and patient selection for chemoradiation, and analysis
      the accuracy, pitfalls and cost effectiveness of the PET/MRI alone and PET/MRI with
      noncontrast chest CT in evaluating in patients with oropharyngeal SCC.

      PET/MRI data will be acquired on the integrated PET/MRI scanner , which acquires simultaneous
      PET and MR data with a 3.0-T magnet. The examination protocol will combined a whole-body scan
      with a dedicated examination of the head and neck area. All participants will fast for 6 h
      before the scan. At 50-70 min post injection of 370 MBq of FDG, the patient will be placed on
      the PET/MRI scanner bed. After fast-view T1-weighted MR localizer sequence for scout imaging
      and Dixon VIBE sequence for attenuation correction, a whole-body PET scan will be performed
      in 5 bed positions to cover from the head to the proximal thigh, with an acquisition time of
      4 min per bed position. Simultaneously, whole body MR image acquisition will be performed for
      the corresponding 5 bed positions with the axial HASTE sequence and coronal STIR sequence as
      well as the sagittal T1-weighted Turbo spine echo(TSE) and STIR sequence.

      Afterwards, regional PET and MRI images will be simultaneously performed. Regional PET will
      be performed with an acquisition time of 10 min, while a dedicated MRI of the head and neck
      region will be acquired in the axial and coronal projections with T1-weighted TSE sequence
      and T2-weighted TSE sequence with fat saturation. Axial DWI will be performed using a single
      shot spin-echo echo-planar technique with modified Stejskal-Tanner diffusion gradient pulsing
      scheme. A total of 10 b values will be used for the reconstruction of IVIM and kurtosis
      imaging, which are: 0, 20, 40, 80, 100, 200, 400, 800, 1200, 1500 sec/mm2. DCE-PWI at the
      head and neck region will be acquired by using a 3D T1-weighted spoiled gradient-echo
      sequence. A spatial saturation slab will be implanted inferior to the acquired region to
      minimize the inflow effect from the carotid arteries. Before the contrast agent
      administration, baseline longitudinal relaxation time values will be calculated from image
      acquired with different flip angles. Then, the dynamic series will be acquired using the same
      sequence with a 15° flip angle, after intravenous administration of paramagnetic contrast
      agent at 3 ml/s. Thereafter, dedicated regional MRI will be obtained with T1-weighted TSE
      sequence with fat saturation in the axial and coronal projections. Finally, whole body axial
      VIBE with fat saturation will be performed. The total acquisition time is about 42 min, and
      the mean in-room time for PET/MR will be approximately 60 min.

      Non-enhanced low-dose chest CT Spiral low-dose chest CT without contrast material enhancement
      will be performed before PET/MRI on the same examination day. Acquisition parameters include
      peak voltage of 120 kVp, mAs of 50, collimation of 64x0.5 mm and reconstruction interval of
      3-mm.

      Data analysis Readers are aware that patients have oropharyngeal SCC, and they will be
      blinded to the results of other studies and to PET/MR data. The PET, MRI and chest CT images
      will be first interpreted independently. All images will be then reviewed together and
      compared. A checklist of various distributions of tumor extension, nodal spread and distant
      metastasis will be recorded. The clinical and imaging findings will be discussed jointly by
      the Head-and-Neck research team. Endoscopic biopsy, ultrasonographic guided fine needle
      aspiration or CT-guided biopsy will be performed in any lesions suspicion for malignancy if
      possible. If biopsy of the lesion of interest is not feasible, or yields a negative result,
      close clinical and imaging follow-up will be pursued. All participants will be followed up
      for at least 12 months. The clinical and functional imaging data will be collected and
      analyzed for predicting treatment response and prognosis. For the diffusion MRI, regions of
      interest will be manually placed on the lesions on ADC map to encompass as much of the solid
      tumor area as possible. The signal intensities measured on the images acquired at different
      b-values S(b) will be numerically fitted against the model, S(b)=S0 e-b*ADC, where S0 and Sb
      are signal intensities at different b values, For IVIM imaging, the relationship between
      signal intensities and b values can be expressed by the equation: Sb/S0 = (1-f )．exp(-bD) +
      f．exp[-b( D + D＊)] where f is a microvascular volume fraction representing the fraction of
      the diffusion linked to microcirculation, D represents pure diffusion coefficient, and D* is
      perfusion-related incoherent microcirculation. For the DKI, the relationship between signal
      intensities and b values can be expressed by the equation: ln[S(b)] = ln[S(0)] - b x Dapp +
      1/6b2 x Dapp2 x Kapp where S is the signal intensity (arbitrary units), b is the b-value
      (s/mm2), Dapp is the apparent diffusion coefficient (10-3 mm2/s), and Kapp is the apparent
      kurtosis coefficient denoting thedeviation from a Gaussian distribution. We will also perform
      monoexponential fitting by using Kapp=0 in the equation, yielding ADCmono. For the DCE-PWI
      MRI, the change in contrast agent concentration over time, Ct(t), will be determined in each
      voxel in the tumor, and the compartmental tracer kinetic model will be applied to each voxel
      by using an arterial input function, Cp(t), measured in each individual: Ct (t)=VpCp(t) +
      Ktrans ∫0 t Cp(t' ) exp(Ktrans(t-t') /Ve )dt' where t' is the time (in minutes) as an
      integration variable, and Cp(t') is the concentration of contrast agent in the blood plasma
      as a function of time.

      For PET imaging parameters, SUV and MTV of the target lesions will be measured from
      attenuation-corrected 18F-FDG PET images by drawing the boundaries drawn large enough to
      include the lesions. An SUV threshold of 2.5 will be used to delineate the MTV. The TLG is
      calculated as the product of the mean SUV and the MTV.
    

Intervention name(s): PETMRI
Intervention type(s): Diagnostic Test
Intervention description(s): PET/MRI data will be acquired on the integrated PET/MRI scanner. After fast-view T1-weighted MR localizer sequence for scout imaging and Dixon VIBE sequence for attenuation correction, a whole-body PET scan will be performed to cover from the head to the proximal thigh, with an acquisition time of 4 min per bed position. Simultaneously, whole body MR image acquisition will be performed with the axial HASTE sequence and coronal STIR sequence as well as the sagittal T1-weighted Turbo spine echo and STIR sequence. Afterwards, regional PET and MRI images will be simultaneously performed. DWI will be performed using a single shot spin-echo echo-planar technique. A total of 10 b values will be used for the reconstruction of IVIM and kurtosis imaging. DCE-PWI will be acquired by using a 3D T1-weighted spoiled gradient-echo sequence. Thereafter, dedicated regional MRI will be obtained. Finally, whole body axial VIBE with fat saturation will be performed.
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Patients in a tertiary referral center
      
Keywords: Oropharyngeal cancer; integrated PET/MR