13
Head and Neck Cancer

Eugene C. Lin and Abass Alavi

Cervical Metastasis, Unknown Primary

Clinical Indication: B

1. Although reported sensitivities vary, positron emission tomography (PET) can be useful for identifying the primary tumor in patients presenting with metastasis to cervical nodes (Figs. 13.1, 13.2, and 13.3).
   
2. In addition, PET can identify unsuspected distant metastases and define regional disease in N2 (nodes > 3 cm but < 6 cm) patients.
   
3. It is best to perform PET after physical examination and panendoscopy are negative. In one study the risk of subsequent primary tumor was < 6% if both PET and panendoscopy were negative.¹

Accuracy/Comparison to Other Modalities

1. The reported sensitivities of PET are variable (8 to 46%),2,3 and a substantial incidence of false-positive results has been reported. The results may be improved with PET/computed tomography (CT), which identified the primary site in 68% of patients in one study.⁴
   
   
   
   • PET may have poor sensitivity for occult tonsillar cancer.⁵
   
   
2. However, PET overall is more accurate than conventional imaging.³

Pearls/Pitfalls

1. The main areas to search for primary tumors are the nasopharynx, base of tongue (Fig. 13.1), tonsils (Fig. 13.2), and pyriform sinuses (Fig. 13.3).
   
2. Primary tumors that are not identified by PET are generally superficial with a depth < 4 mm.⁶

Staging

Clinical Indication: B

1. Although PET is more accurate than CT or magnetic resonance imaging (MRI) for nodal staging, it cannot replace these modalities for tumor (T) staging. Although clinically proven primary tumors are visualized by PET in the majority of cases, PET does not have the resolution to evaluate local spread.
   
2. Specific uses of PET
   
   
   
   1. N0 neck. Nodal staging in the N0 (clinically node negative) neck, particularly in patients with oral or oropharyngeal cancer where the probability of occult nodal metastases is higher
      
      
      

      
      

      Fig. 13.1 Primary tumor localization: tongue base. Axial positron emission tomography/computed tomography scan in a patient with a malignant right neck node demonstrates uptake in the primary tumor in the right tongue base (arrow).

      
      
      
      
      • The sensitivity of PET in this setting is variable, ranging from 33 to 67%.7–9
        
      • In patients with T4 (stage 2 of tumor growth) disease, false-negative results are more likely, and PET is less helpful.
        
      • PET is more helpful in patients with T1 to T3 disease. The use of PET in this population can reduce the probability of occult neck metastases to < 15%.
        
      • PET is insensitive compared with sentinel node biopsy, but specificity is high.
        
      • One potential use of PET is to perform sentinel node biopsy if PET is negative and neck dissection if PET is positive. This may reduce the number of unnecessary neck dissections.¹⁰
      
      
   2. Detecting distant metastases
      
      
      
      • PET can detect distant metastases, particularly in the mediastinum, bone marrow, and liver (Fig. 13.4).
        
      • PET is particularly useful for detecting mediastinal disease in stage III and IV cancer.
      
      
   3. Detection of synchronous lesions.^11,12 PET can detect additional tumors in the lung (Fig. 13.5) and aerodigestive tract (Fig. 13.6). The overall incidence of coincidental secondary primary tumors is 3 to 8%.
      
      
      

      
      

      Fig. 13.2 Primary tumor localization: tonsil. Axial positron emission tomography/computed tomography scan in a patient with a malignant left neck node demonstrates uptake in the primary tumor in the left tonsil (arrow).

      
      
      
      
      • Coincidental lung lesions. PET has an accuracy of 80% for such lung lesions.
        
        
        

        
        

        Fig. 13.3 Primary tumor localization: pyriform sinus. Coronal positron emission tomography computed tomography scan in a patient with a malignant right neck node demonstrates uptake in the primary tumor in the right pyriform sinus (arrow).

        
        
        
        

        
        

        Fig. 13.4 Metastastic head and neck cancer. Coronal positron emission tomography/computed tomography scan in a patient with head and neck cancer demonstrates metastases to the left neck nodes and the liver.

        
        

        A PET scan, which includes the thorax, will detect lung lesions not seen on chest x-ray. However, in general, CT is more sensitive than PET for lung lesions.

        
        
        
        

        
        

        Fig. 13.5 Synchronrous lung cancer. Coronal positron emission tomography scan in a patient with a right parotid malignancy (arrow) demonstrates a synchronous left upper lobe lung cancer (open arrow) with mediastinal metastases and another nodule in the left apex. Uptake in the thyroid (arrowheads) is nonspecific but related to thyroiditis in this patient.

        
        
        
        

        
        

        Fig. 13.6 Synchronous colon cancer. Coronal positron emission tomography scan in a patient with head and neck cancer with metastatic cervical nodes also demonstrates a synchronous sigmoid carcinoma (arrow).

      
      
   4. Prognosis. Pretreatment tumor standardized uptake value (SUV) is an independent prognostic factor.13

Accuracy/Comparison with Other Modalities

1. PET versus CT/MRI.14 See Table 13.1.
   
2. PET is more sensitive than CT and MRI and more specific than CT, MRI, and ultrasound (US).¹¹
   
3. Bone metastases. PET may be more sensitive than a bone scan for bone metastases in endemic nasopharyngeal carcinoma.¹⁶

Pearls/Pitfalls

1. Knowledge of the common sites and incidence of cervical metastases for different primary tumors is helpful in interpretation of PET scans.17
   

   
   

   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   

   Table 13.1 Sensitivity and Specificity of Positron Emission Tomography Compared with Other Imaging Modalities in the Staging of Head and Neck Cancer

   	Sensitivity %	Specificity %
   PET	87–90	80–93
   CT/MRI	61–97	21–100

   
   

   Abbreviations: CT, computed tomography; MRI, magnetic resonance imaging; PET, positron emission tomography.

   
   
   
   
   1. Oral cavity tumors have high incidence of metastases despite being clinically node negative.
      
   2. Laryngeal tumors have a low incidence of metastases even in advanced stages of disease.
      
   3. Supraglottic larynx tumors often spread to nodes bilaterally (Fig. 13.7).
      
   4. Nasopharyngeal tumors often spread to nodes bilaterally and to the posterior triangle (Fig. 13.8).
   
   
2. Scan volume. It is helpful to include the abdomen and pelvis in the scan volume because of the possibility of coincidental tumors and distant metastases.
   
   
   

   
   

   Fig. 13.7 Metastastic supraglottic cancer. Coronal positron emission tomography/computed tomography scan demonstrates a supraglottic cancer with metastases to bilateral neck nodes. Supraglottic cancers have a propensity for bilateral nodal metastases.

   
   
   
   

   
   

   Fig. 13.8 Metastatic nasopharyngeal cancer. Coronal positron emission tomography/computed tomography scan demonstrates a large left nasopharyngeal cancer with metastases to bilateral neck nodes. Nasopharyngeal cancers have a propensity for bilateral nodal metastases.

   
   
3. Bone invasion. In patients with oral cancer, PET does not improve identification of bone infiltration compared with CT.¹⁸
   
4. SUV. The use of size-based SUV cutoffs may be helpful for nodal staging. In one study, SUV cutoffs of 1.9, 2.5, and 3.0 for lymph nodes < 10 mm, 10 to 15 mm, and > 15 mm yielded a 79% sensitivity and 99% specificity for nodal staging.¹⁹
   
5. Dedicated head and neck protocol. The use of a dedicated head and neck PET protocol (longer acquisition, higher count study reconstructed with smaller pixels) improves detection of disease in small nodes.²⁰ However, SUVs with a dedicated protocol are significantly higher than with a standard protocol. Thus, SUVs from a dedicated PET study cannot be compared with those from a standard PET.

Recurrence

Clinical Indication: A

Accuracy

1. Overall. Sensitivity 84 to 100%, specificity 61 to 93%21
   
2. By region²²
   
   
   
   1. Local. Sensitivity 97%, specificity 79%
      
   2. Regional. Sensitivity 92%, specificity 95%
      
   3. Distant. Sensitivity 94%, specificity 96%²²
   
   
3. PET is sensitive and specific for disease at regional and distant sites. specificity is lower in the head and neck region due to false-positive results from inflammation related to infection or other processes.²² The primary value of PET is its high negative predictive value.²³
   
4. If PET is negative, no biopsy is needed.
   
5. If PET is positive and biopsy is negative, a follow-up scan should be performed. Decreased activity on the follow-up scan indicates that the initial result was likely false-positive due to an inflammatory process.²⁴

Comparison with Other Modalities25

1. Other radionuclides. PET is more sensitive than sestamibi, tetrofosmin, or thallium; specificity is comparable. However, sestamibi or tetrofosmin combined with CT is comparable to PET (Table 13.2).^25,26
   
2. MRI.²⁷ See Table 13.3.

Pearls

1. SUV. SUV cutoffs of 3.0 to 3.2 have been used to detect recurrence.22,28 However, an increasing SUV on dual time point PET imaging is of greater value than a single SUV measurement.
   
2. Radiation has minimal effect on FDG uptake in normal structures. There is mildly increased uptake, mostly in muscle, in the early postradiation period, which is related to inflammation.

Pitfalls

1. Tumor stunning. A delay in PET imaging for at least 4 months after radiation can be helpful in avoiding false-negative results from presumed tumor “stunning.”29
   
2. Laryngeal uptake. Laryngeal uptake of FDG can be noted normally, particularly in the posterior portion (see Chapter 6).
   
   
   
   1. It is better to use asymmetry of uptake rather than absolute uptake in the larynx as a criterion of abnormality.
      
   2. Anterior uptake is more suggestive of a malignant process than uptake in posterior structures.
      
   3. However, laryngeal uptake may be asymmetric due to postoperative changes or vocal cord paralysis.
   
   
3. Postoperative. False-positive results are particularly unavoidable when evaluating for recurrence. Besides the typical physiologic areas of uptake, abnormal patterns of uptake can be seen from postoperative distortion of normal anatomy or as a result of postsurgical or therapeutic inflammation. How ever, reconstruction hardware typically does not interfere with interpretability. Osteotomy sites do have slightly greater (25% on average) uptake, but less than that seen in tumor.³⁰ PET/CT can be used in free flap cases with acceptable levels of accuracy.

Therapy Response/Prognosis31

Clinical Indication: B

1. Evaluation of residual disease following radiotherapy or chemoradiotherapy. PET is useful in evaluating therapy response in preoperative induction chemoradiotherapy, chemoradiotherapy protocols that are aimed at organ preservation, and definitive radiotherapy.11,12
   
   
   
   1. Postchemoradiotherapy. In patients with head and neck squamous cell cancer, chemoradiotherapy regimens that attempt to preserve organ function (e.g., larynx and tongue) often achieve regional control at the primary site. However, residual tumor is more likely if cervical nodal disease (particularly N2 or N3) is present, even if there is a clinical complete response. In patients with advanced nodal disease, posttreatment neck dissection can often reduce regional recurrence. The role of PET in predicting the need for posttreatment neck dissection is controversial. PET/CT does appear to be superior to contrast-enhanced CT for predicting persistent disease in the neck.³² Some data suggest that PET is a reliable predictor of the absence of residual tumor after chemoradiotherapy in the N positive neck,³³ but this is not supported by some studies.³⁴
      
   2. Postradiotherapy. There is controversy over the role of neck dissection after definitive radiation therapy for advanced neck disease. One study suggests that PET/CT is more accurate than CT in assessing therapy response in this setting.³⁵ Limited data suggest that if there is no residual lymphadenopathy and a negative PET, neck dissection can be withheld.³⁶ However, if there is substantial residual lymphadenopathy (> 2 cm) and a negative PET, further studies are required before withholding neck dissection.³⁷
   
   
2. Prognosis. PET is helpful for both early and late prediction of outcome.
   

   
   

   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   
   

   Table 13.4 Sensitivity and specificity of Positron Emission Tomography Compared with Other Imaging Modalities in the Evaluation of Therapy Response

   	Sensitivity %	Specificity %
   PET/CT	77	93
   CT	92	47

   
   

   Abbreviations: CT, computed tomography; PET, positron emission tomography.

   
   
   
   
   1. Primary tumor. High SUV (> 10) in the primary tumor is correlated with poor prognosis.³⁸
      
   2. Nodes. Nodal SUV does not predict prognosis.³⁹
      
   3. Early prediction. Low levels of tumor metabolic activity after 1 cycle of chemotherapy or radiation predict complete remission and longer survival.
      
   4. Late prediction. High SUV after treatment predicts local recurrence and decreased survival.

Accuracy/Comparison with Other Modalities

Postradiotherapy.35 See Table 13.4.

Pitfalls

1. PET has a limited clinical value in assessing response to postoperative adjuvant chemoradiotherapy.
   
   
   
   1. Postsurgical inflammatory reactions can cause false-positive results and therefore render subsequent response assessment inaccurate.
      
   2. Microscopic residual disease cannot be detected.
   
   
2. As in all settings, there should be a substantial time interval between radiotherapy and PET imaging. Typically, false-negative results are more commonly seen if imaging is performed early after radiation. Some studies suggest that a 4- or 8-week delay is adequate3536 for evaluating therapy response, but other studies suggest 12 weeks or longer.³⁷ If postradiotherapy neck dissection is being considered, PET may be more valuable if it can be accurately performed earlier after therapy (within 12 weeks), as fibrosis can increase the technical difficulty and morbidity of delayed neck dissection.40
   
3. Osteoradionecrosis can cause false-positive results.⁴¹

Radiotherapy Planning

Clinical Indication: B

Potential applications of PET in radiotherapy planning are42

1. Coregistration of PET and treatment planning CT
   
2. Detection of additional/distant disease by PET
   
3. Gross tumor volume assessment: gross tumor volume assessment by PET is closer to the surgical specimen than CT or MRI, although all imaging modalities overestimate tumor extension.

Characterization of Head and Neck Tumors

Clinical Indication: D

1. Parotid lesions. PET cannot distinguish between benign and malignant parotid tumors.43 Warthin tumors and pleomorphic adenomas can have fluorodeoxyglucose (FDG) uptake. High-grade salivary gland tumors tend to have more uptake than lower grade tumors, but there is substantial overlap.⁴⁴ PET and PET/CT may be superior to CT for staging patients’ known salivary gland malignancies.^44–46
   
2. Cystic neck masses. PET/CT may not be accurate in identifying malignancy in adults with cystic neck masses.⁴⁷

PET/CT

1. The use of PET/CT compared with PET alone will decrease the fraction of equivocal lesions by 53%, greatly improve lesion localization (see Fig. 8.1, p. 89), slightly improve accuracy, and change management in 18% of cases.^11,12
   
2. Particular attention must be paid to the possibility of mislocalization on PET/CT studies due to movement of the head between the CT and PET studies (see Figs. 8.6, p. 92 and 8.7, p. 93).
   
3. If PET/CT or fusion with CT or MRI is not available, potential anatomical landmarks that can be used to aid in localization include the tonsils, palate, tongue, floor of mouth, salivary glands, mandible, and cervical spine.

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