Peroperative assessment of tumor resection margins using high-resolution PET/CT in oral carcinoma, a feasibility clinical trial.

The treatment of choice for cancer of the oral cavity is surgical excision followed by adjuvant radiotherapy and/or chemotherapy. The choice for adjuvant treatment depends on the presence of cancer cells in the surgical specimen’s margins and/or the regional lymph nodes. It should be noted that tumor-infiltrated margins and lymph nodes result in a significantly increased locoregional recurrence rate which is associated with a significant reduction in overall survival [1]. The current gold standard for assessing surgical margins and lymph nodes is histopathology of the resected specimens. Unfortunately, the histopathological conclusion is known only several days after the surgery. Hence, identifying the margin status during surgery would be of interest, thereby allowing a broader resection of the primary tumor if necessary. The current standard of practice is to perform frozen section analysis of samples taken from the resection cavity, but this is both time consuming and prone to sampling bias. To overcome these limitations, we propose using high-resolution 18F-fluorodeoxyglucose (FDG) PET/CT (positron emission tomography/computed tomography) imaging for immediate peroperative margin assessment of the excised specimens [2]. The applied CT system achieves spatial resolution of 50 μm while the PET system has a sub-millimeter spatial resolution of 0.85 mm and sensitivity of 12%. This high sensitivity PET allows for both short scan time and imaging of very low concentrations of radiotracer, which is especially important for peroperative imaging. In addition, this method has the advantage of providing 3D images of the full specimen in contrast to the two-dimensional histopathological assessment of the specific histological slices. A recent proof-of-concept study in breast conserving surgery for early stage breast cancer evaluated the use of this very high-resolution PET/CT-scanner and found a sensitivity and specificity of 88% and 80% respectively for invasive ductal carcinomas. The aim of the current study is to further evaluate the feasibility of high-resolution 18F-FDG-PET/CT for intraoperative margin assessment of resected squamous cell carcinomas of the head and neck region and compare the results to the gold standard. A standard clinical dose of 18F-FDG will be administered intravenously in the operating room following anesthesia. Tumor excision will start at least 45-60 minutes post-injection. The surgical specimen will be oriented for histopathological evaluation. Lymphadenectomy is performed as per local protocol and made identifiable per neck region. Both primary tumor and lymphadenectomy samples will be imaged using high resolution PET/CT. A margin sample is considered positive when the distance between the contour of the tumor and margin of the specimen is less than 5mm. a lymph node is identified as positive when focal 18F-FDG uptake is visualized. After finalizing the imaging protocol, the surgical specimens are sent for standard histopathological assessment. The sensitivity and specificity of both methods will be calculated and compared.