15 Integrated FDG-PET/CT for Head and Neck Malignancies Abstract Fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is now used routinely for the guidance of initial staging and for posttreatment monitoring as well as for the localization of an unknown primary in head and neck cancer patients. Along with qualitative image review, the semiquantitative parameter, standardized uptake value (SUV), allows not only assessment of a treatment response, but also provides prognostic information. In particular, one of the greatest utilities of FDG-PET/CT for head and neck malignancies is its high negative predictive value after treatment. Keywords: head and neck, fluorodeoxyglucose, PET/CT Fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) provides in vivo functional information on the metabolic behavior of various tissues. It has proven to be very useful for head and neck (H&N) malignancies. When integrated with computed tomography (CT) as FDG-PET/CT, valuable combined functional and anatomical information is provided, which assists in the appropriate clinical management of patients. Also, by combining PET with CT, more accurate anatomic lesion localization and size measurements can be made than with PET alone. In most cases, PET/CT allows metabolically active malignancy to be differentiated from benign entities. The patient should refrain from eating or drinking (water permitted) 6 to 8 hours prior to FDG injection. Typically, between 10 and 20 mCi (370–740 MBq) of FDG are administered intravenously (IV), and the patient is then placed in a quiet room with his or her eyes closed during what is termed the FDG “uptake period.” During this time, the patient is discouraged from reading, chewing, or talking. Approximately 1 hour after FDG administration, PET/CT imaging of the patient is acquired from the top of the head to the midthighs (occasionally extending to the soles of the feet in patients with tumors such as melanoma and myeloma). At some institutions, a second dedicated H&N PET/CT acquisition is acquired about 30 minutes later from the base of the skull through the aortic arch. This second set of images should be acquired with a higher matrix to improve visualization of H&N abnormalities and allow a longer uptake period for tumor accumulation of FDG. This second acquisition may also help differentiate between malignant and inflammatory or infectious conditions (i.e., uptake in benign conditions may peak early on, while malignancies frequently have gradually increasing uptake over time).1 Placing the head at a slightly greater tilt (increasing the degree of neck extension) during the second acquisition may also assist in visualization of oral cavity abnormalities when there is excessive dental artifact in the region. Depending upon the institution, the CT portion of the examination will be performed with or without (more common) IV contrast enhancement. In the majority of cases, the CT portion of PET/CT is performed without IV contrast and used mainly for attenuation correction and localization purposes. The PET scan is attenuation corrected by utilizing coefficients obtained from scaling the CT numbers to the PET energy level of 511 keV.2 It has been demonstrated that IV contrast does not interfere significantly with semiquantitative evaluation known as SUV. FDG is the most commonly utilized radiopharmaceutical for oncology imaging. It is a positron-emitting radionuclide with fluorine-18 (F-18) substituted for a hydroxyl group on the glucose molecule. FDG is essentially a “radioactive sugar,” or glucose analog, which is taken up physiologically by various tissues in the body and, to a greater degree, by tumor cells. Once FDG enters a cell, it is trapped within that cell after initial phosphorylation by hexokinase without further metabolism. Essentially, FDG accumulates in the cells as FDG-6-phosphate and cannot enter glycolysis at this point. Given that tumor cells, in general, have a higher glucose utilization than nonmalignant tissues, there is an elevated amount of FDG trapped in these cells, and therefore greater radioactivity. Thus, the areas of increased radioactivity accumulation are visualized as “hot spots” when viewing FDG-PET images. If a region of interest (ROI) is drawn around any given “hot spot,” an SUV can be calculated as an estimation of the metabolic activity within that specific tissue area or ROI. SUV is a semiquantitative measure of the metabolic activity of body tissues and corrects for the variability of FDG uptake related to differences in patient size and the dose of the injected FDG.3 In general, the SUV is the ratio of the radioactivity concentration in the ROI (drawn on images on a computer monitor) divided by the whole-body concentration of the injected radioactivity: SUV = (ROI radioactivity concentration)/(whole − body injected radioactivity concentration) The SUV is especially useful in monitoring response to therapy, as the uptake at one time point can be compared to the uptake in that same tissue at a subsequent time point. PET-reconstructed resolution is typically about 4 to 6 mm; therefore, evaluation of the metabolic activity of lesions below this size is not reliable. Newer time-of-flight (TOF) PET systems provide improved resolution, contrast, and signal-to-noise ratio.4 Accurate TNM (t umor size, n ode involvement, and m etastasis status) staging at the time of initial diagnosis is of utmost important in accurate treatment planning. An important benefit of FDG-PET and PET/CT in this aspect derives from the whole-body approach, thereby not only assessing the primary tumor, but also evaluating for nodal and/or distant metastases. FDGPET has been reported to have higher sensitivity (87 compared to 62%) and specificity (89 compared to 73%) than CT for initial staging.5 Integrated FDG-PET/CT has even higher sensitivity and specificity at greater than 90% each for this purpose.6 The literature suggests that FDG-PET/CT is at least as sensitive as anatomic imaging (i.e., CT or MRI) in detecting primary H&N malignancies (especially oral cancers), but may be somewhat lacking in providing assessment of the tumor extent and involvement of adjacent structures. Therefore, it is not routinely utilized clinically for this purpose. Contrast-enhanced MRI or CT typically provides greater anatomic soft-tissue details for this purpose. MRI is also superior to both FDG-PET/CT and CT alone for providing information on possible perineural involvement of tumor. On the other hand, when IV contrast is given for the CT portion, FDG PET/CT, it may be the most practical single imaging study for management/surgical planning purposes by providing acceptable anatomic detail combined with functional information. This obviates the need to have the patient schedule two separate imaging sessions. In the case of biopsy-proven cervical neck nodal metastases with an unknown primary H&N malignancy, FDG-PET/CT has been shown to successfully localize the primary malignancy in about 30 to 50% of cases when other imaging modalities do not.7,8 A recent meta-analysis determined the overall sensitivity, specificity, and accuracy of FDG-PET/CT for detecting an unknown primary H&N malignancy as 82.5, 80.2, and 81.4%, respectively, without a significant difference between PET alone and combined PET/CT. The most common histological tumor type for unknown primary detection in these cases was squamous cell carcinoma (SCC; 68.6%), with the most common primary location being the tonsils at 21.6%9,10 ( FDG-PET/CT has been shown to play a role in both pretreatment evaluations of possible nodal metastases and posttreatment monitoring. In the preoperative setting, FDG PET/CT yields a statistically significant improvement in detecting and predicting true pathologic cervical nodal metastasis in general (p = 0.005), and when occurring only in the contralateral neck (p = 0.013), as compared to CT or MRI, with sensitivity and specificity above 80%.11,12 Regarding patients with clinically negative nodal disease, FDGPET/CT is about twice as sensitive as conventional imaging (CT or MRI) in the detection of occult nodal metastases, thereby having a significant impact on treatment planning.13,14 Fig. 15.1 This patient had biopsy-proven squamous cell carcinoma metastasis to a right neck node. The primary malignancy was unknown. A subsequent FDG-PET/CT scan showed uptake in the known right neck metastatic node (green arrows) and also localized the primary malignancy to the left tonsillar pillar (blue arrows). It is recommended that FDG-PET/CT imaging be delayed for 10 to 12 weeks after completion of therapy, particularly after surgery or radiation treatment, in order to allow posttreatment inflammation to resolve and therefore to obtain higher diagnostic accuracy. This is true not only for nodal evaluation but also for the primary tumor. The high negative predictive value (NPV) of posttreatment FDG-PET/CT imaging is one of its greatest assets in directing management. If neck nodes are not metabolically active after treatment, they do not likely contain viable tumor. Therefore, if a postradiotherapy FDG-PET/CT scan is negative, neck dissection can be avoided with high confidence. FDG-PET/CT offers a whole-body imaging approach, and therefore a single image acquisition to evaluate for possible distant metastatic disease; it has been shown to be very reliable for this purpose. Rohde et al15 performed a recent prospective cohort study for head-to-head comparison of three imaging approaches for detection of distant metastases in patients with oral, pharyngeal, or laryngeal squamous cell cancer: (1) combined chest X-ray and H&N MRI (CXR/MRI), (2) combined chest CT and H&N MRI (CHCT/MRI), and (3) FDG-PET/CT. The study evaluated a total of 307 patients. FDG-PET/CT was shown to have a much higher detection rate for distant metastatic disease in this patient population as compared to the other two imaging approaches—CXR/MRI detected distant disease in 1% of patients, CHCT/MRI in 4%, and FDG-PET/CT in 8%. The most common site for distant metastasis was the lung (72% of cases). In addition, FDG-PET/CT was superior for the detection of synchronous carcinomas, with the most common site being a second H&N malignancy (20% of cases; Anatomical response criteria applied to FDG PET/CT are commonly based upon the World Health Organization (WHO) or Response Evaluation in Solid Tumors (RECIST). On the other hand, the European Organization for Research and Treatment of Cancer (EORTC) Response Criteria incorporates FDG uptake and tumor metabolic response based upon SUV calculations and is broken down into categories of complete metabolic response (complete resolution of FDG uptake in the tumor), partial metabolic response (15 to > 25% SUV reduction), progressive metabolic disease (increase of tumor SUV of > 25%), and stable metabolic disease (increase in SUV of < 25% or decrease of < 15%). A more recent approach to response assessment is the Hopkins criteria, which assign a score of 1 through 5 based upon the visual assessment of tumor FDG uptake pattern and intensity. A score of 1, 2, or 3 is considered negative for residual disease and scores of 4 or 5 are considered positive for residual disease. There are two methods for incorporating FDG-PET data into radiation treatment planning: (1) PET images are fused with separately acquired radiotherapy planning CT images or (2) acquired integrated PET/CT images are used directly. When integrated PET/CT images are to be used directly for radiotherapy, images are acquired with the patient in the planned treatment position (frequently with the patient positioned on a flat radiotherapy treatment bed mounted to the PET/CT bed) and allows for more accurate target volume delineation. Automatic delineation of the tumor can be performed by using a specified SUV cutoff value to separate target from background uptake. In order to minimize motion caused by patient respiration, “4D” PET/CT (which incorporates respiratory motion correction) can be utilized, or, when possible, the patient can be instructed to inhale deeply and then hold his/her breath during the acquisition over the thoracic field of view (“breath-hold” technique).
15.1 Introduction
15.2 Technique
15.2.1 Fluorodeoxyglucose Dose and Administration
15.2.2 Image Acquisition
15.2.3 Intravenous Contrast
15.3 Fluorodeoxyglucose Mechanism of Uptake
15.4 Standardized Uptake Value
15.5 Lesion Size and Positron Emission Tomography Resolution
15.6 Indications for FDG-PET or FDG-PET/CT
15.6.1 TNM Staging
Primary Tumor
Tumor Extent
Unknown Primary
Fig. 15.1).
Nodal Metastases
Pretherapy Evaluation
Posttherapy Evaluation
Distant Metastases
Fig. 15.2).
15.6.2 Treatment Monitoring/Response
15.6.3 Radiation Therapy Planning
Methods
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