The aim of this study was to assess the diagnostic value of integrated whole body positron emission tomography/contrast-enhanced CT (PET/CECT) as a one step examination in the initial staging of oral and oropharyngeal squamous cell carcinoma (OOSCC). Seventy three consecutive OOSCC patients who underwent PET/CECT for initial staging and tumour resection and neck dissection as primary treatment, were included. For each PET/CECT result, the contribution of fluorine-18 fluorodeoxyglucose ( 18 F-FDG)-uptake and radiologic criteria was assessed. PET/CECT results were correlated to histological specimens obtained with tumour resection and neck dissection. For detecting the primary tumour PET/CECT showed a sensitivity of 96% and for detecting cervical metastases a sensitivity and specificity of 89% and 81%, respectively. In the clinically N0 subgroup ( n = 37), PET/CECT showed a sensitivity and specificity of 64% and 81%, respectively. In five of six patients PET/CECT detected a second primary tumour. The results show that the use of diagnostic PET/CECT as a one step examination is a reliable alternative for PET/CT in combination with a separate diagnostic CT in patients with OOSC for initial staging. The need for treatment of the neck in the clinically negative neck should not be based on PET/CECT results only, due to the risk of missing a small metastasis.
Accurate initial staging of head and neck squamous cell carcinoma (HNSCC) is essential for adequate treatment planning and prognosis . Although radiological imaging modalities such as CT, MRI, and ultrasound with or without fine needle aspiration provide a much more accurate staging than physical examination only, there is still a need for improvement .
Positron emission tomography (PET) with the radiopharmaceutical fluorine-18 fluorodeoxyglucose ( 18 F-FDG) has been shown to be complementary to CT and MRI, or even to demonstrate a greater accuracy than anatomical imaging methods in the initial staging of HNSCC . 18 F-FDG PET may offer advantages over anatomic imaging in the assessment of primary tumours and cervical metastases, as it can detect both without anatomical deformation. The advantage of whole-body 18 F-FDG PET is its high sensitivity in detecting distant metastases and second primary tumours in any part of the body in a single diagnostic modality .
The use of 18 F-FDG PET has been reported to have a significant impact on patient management in HNSCC patients who are initially staged by conventional imaging modalities, by providing adequate staging of local and regional disease, identifying distant metastases and synchronous malignancies and, thereby, avoiding non-beneficial treatment . CT and MRI remain the first choice for staging HNSCC. The main reasons are the lack of spatial resolution and the poor delineation of anatomic landmarks by 18 F-FDG PET. For staging and treatment planning anatomical imaging is required to determine the site and extent of the primary tumour and its relationship with surrounding anatomical structures. 18 F-FDG PET is thought to be a complementary rather than an alternative diagnostic tool for staging HNSCC .
The introduction of integrated PET/CT makes it possible to acquire PET and CT sequentially in a single imaging session, providing excellent spatial resolution with fusion of anatomic and metabolic data. In head and neck cancer, PET/CT has been shown to be of value given the anatomy and the presence of normal structures with variable intensity 18 F-FDG-uptake, for example lymphoid tissue, salivary glands, and muscles . Usually PET/CT is performed without a contrast-enhanced diagnostic CT component and the results are rarely validated by histological examination of neck dissection specimens.
The aim of this study was to evaluate the value of integrated PET/contrast-enhanced CT (PET/CECT) in the initial staging of oral and oropharyngeal squamous cell carcinoma (OOSCC). For each PET/CECT result, the separate contribution of its radiologic criteria and focal pathologic 18 F-FDG-uptake was assessed.
Patients and methods
All patients with a primary diagnosed OOSCC between July 2005 and June 2009, who underwent tumour resection and neck dissection as primary treatment, were included in the study. The patients underwent a whole-body 18 F-FDG PET/CECT for initial staging. The study population consisted of 73 consecutive patients. There were 25 women and 48 men, with a median age of 63 years.
PET/CT acquisition and processing
A Biograph 6 LSO HI-REZ hybrid PET/CT scanner was used (Siemens Medical Systems Inc, Hoffman Estates, IL, USA). Patients had a carbohydrate restricted diet for one day before the PET/CT investigation, to decrease the uptake in the myocardium . In order to provide a useful bowel distension, whilst avoiding PET artefacts induced by the contrast material, a solution containing 0.2% locust bean gum and 2.5% mannitol was used as an oral contrast agent . The patients fasted for 6 h prior to the injection of 4 MBq/kg body weight of 18 F-FDG, with a maximum of 333 MBq. Ninety minutes after 18 F-FDG administration, data acquisition of the fully optimized diagnostic CT began, with intravenous administration of 120 ml Optiray 300. A three-dimensional total-body PET was acquired, with the patient in a supine position, with the arms upwards. The field of investigation included the skull base to the upper legs in seven 3-min bed positions. In addition, a 6-min bed position with the arms downwards was made of the head and neck area. Attenuation correction was based on CT data. The CT parameters were 95 kV (Q ref. mAs care dose 4D), slice thickness varied from 0.6, 1.25, 3.0 to 5.0 mm, collimation was 6 mm × 1 mm and pitch 1.33.
PET images were reconstructed iteratively using ordered-subset expectation maximization software. PET, CT and fused PET/CT images were displayed as non-corrected and attenuation-corrected images and in a rotating maximum-intensity projection.
All studies were interpreted and reviewed with knowledge of the patient’s clinical history. PET/CECT scans were assessed by two experienced reviewers, a nuclear medicine physician and a radiologist. A site of increased 18 F-FDG uptake was defined as negative and unrelated to cancer when it was located in an area of the physiologic biodistribution of the tracer or in a known non-malignant process. A focus of increased 18 F-FDG uptake, with intensity higher than that of surrounding tissues in areas unrelated to physiologic processes, was defined as positive. Besides the visual interpretation of the tracer uptake, SUV calculations were used to consider malignancy. A cervical lymph node was considered positive on the PET images if the SUVmax was significantly higher than lymph nodes of the same size/diameter or the SUV was higher than 3.5. The CECT component of the PET/CT was classified as negative or positive for malignancy. Cervical lymph nodes were considered metastatic if central necrosis or irregular contrast enhancement were present, if their axial diameter was >1.0 cm, a round shape, or a cluster of three or more lymph nodes of borderline size . Both, the nuclear medicine physician and the radiologist, made a separate report of their findings concerning the primary tumour, the presence of cervical metastases and second primary tumours.
Surgical procedure and histology
All patients underwent surgical resection of the primary tumour and neck dissection. Bilateral neck dissection was performed in patients with a primary tumour involving the midline and those in whom, on clinical or radiological examination, enlarged or positive lymph nodes were present. All lymph nodes in the histological specimen were studied on an individual basis. From each lymph node the largest diameter was measured. All lymph nodes were cut in one or more 2 mm slices, depending on the size of the lymph node, and all slices were examined for the presence or absence of tumour.
Reference standard/statistical analysis
PET/CT findings were validated by histological specimens obtained during tumour resection and neck dissection. If no bilateral neck dissection was performed, the contralateral neck was evaluated during patient follow-up. Data were analysed with the SPSS statistical package (SPSS Windows, version 16.0). Sensitivity and specificity of PET/CECT were calculated for detecting the primary tumour, cervical metastases per neck side and for distant disease. In each PET/CECT finding, the contribution of the CT and PET criteria was assessed.