Oncology—Head, Neck, and Thy

Oncology—Head, Neck, and Thyroid

I. HEAD AND NECK

Head and neck cancers are increasing in incidence and are associated with excess alcohol ingestion and tobacco use. The most common histology is squa- mous cell carcinoma. Prognosis depends on the stage of disease. Cervical lymph nodes represent the major lymph drainage of the head and neck. In 1–5% of patients with cervical lymph node metastases, the site of the head and neck primary tumor remains unknown despite thorough diagnostic evaluation.

Most primary head and neck malignancies are discernible through com- plete office examination. Diagnostic evaluation includes fine-needle aspiration of the neck mass, chest roentgenography, computed tomography (CT), and/or magnetic resonance imaging (MRI) of the head and neck, followed by panen- doscopy and biopsies. The primary tumor will be detected in approximately 40% of patients. Approximately 80% of cancers are located in the base of the tongue or tonsillar fossa. Management options depend on the extent of disease and may be multimodal including surgery and radiation therapy for early dis- ease and chemotherapy for advanced disease. Functional imaging with FDG PET has been shown to be useful in the detection of the primary tumor site in patients with metastatic cervical adenopathy, initial staging of disease, differ- entiation of post-therapy changes from residual and recurrent disease, moni- toring of tumor response to therapy, detection of synchronous lung lesions, and in prognostication (Fig. 1).

Unique preparation attributes in this group of patients include potential oral administration of diazepam (5–10 mg orally) given 30 min to 1 h prior to intravenous FDG injection to reduce physiologic skeletal muscle uptake that may mimic or obscure nodal disease. Patients are also instructed not to chew, talk, and move head or dry–swallow excessively during the FDG uptake phase.

Drinking a glass of water prior to imaging will diminish the retained salivary activity in the mouth and upper esophagus. Comfortable ambient temperature will reduce tracer uptake in brown fat. Dental implants and non-removable bridgework can cause artifacts in attenuation-corrected images using either the Ge-68 transmission source or the CT scan obtained with a hybrid PET/CT imaging system. Examination of the non-attenuation-corrected PET images helps in the recognition of this artifact in patients undergoing PET of the head and neck. Furthermore, one should also be aware of the physiologic distribu- tion of FDG in the head and neck. Palatine tonsils and adenoids may display relatively high symmetric hypermetabolism, especially in children and young adults. FDG localizations in the normal laryngeal tissue and the salivary glands are symmetric and low, with benign lesions typically displaying only slight increases in FDG uptake.

Squamous cell carcinoma is highly FDG avid. PET with FDG complements anatomic imaging modalities such as CT and MRI in accurately detecting the presence and extent of primary tumor and regional nodal metastases, especial- ly in borderline or normal-sized nodes. Unsuspected distant metastases may also be detected which may lead to significant changes in treatment options.

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PET has been shown to be useful in localizing the site of unknown primary tumor in 20–35% of patients with metastatic cervical lymphadenopathy and an occult head and neck tumor leading to treatment-related implications on up to 25% of these patients. However, false-positive results may result due to inflammation or infection and small or superficial (submucosal) tumors may be missed.

The biggest advantage of PET over conventional imaging modalities is in

the evaluation of patients after treatment for detection of residual or recurrent

disease (Figs. 2, 3). The treatment-related anatomic alterations and edema

reduce the accuracy of CT and MRI in the post-therapy setting. FDG PET has

been shown to be more sensitive and specific than both CT and MRI in this

clinical setting. The timing of PET scanning after therapy is an important fac-

tor to improve the specificity of PET in differentiating acute post-therapy

inflammatory changes from tumor. Whole-body PET scanning approximately

six weeks after completion of a combined treatment regimen with radiation

and chemotherapy can reliably identify locoregional residual cancer and distant

metastases or secondary tumors in patients with advanced-stage disease which

may then lead to changes in clinical management. The timing is, however, more

critical after head and neck radiation therapy, since this form of treatment

induces an intense inflammatory reaction. PET scanning after a delay of at least

12 weeks from the completion of radiation therapy seems to be the optimal

Figure 1: A 44-year-old woman with nasopharyngeal squamous cell carcinoma. PET-CT

demonstrates intense hypermetabolism in the primary tumor. There was no evidence of

regional and distant metastatic disease.

time as it allows early assessment for response while reducing the false-positive results.

A decline in FDG accumulation has been shown to be correlated with favorable treatment response, improved local control, and longer survival.

Lesions that demonstrate persistent high FDG uptake indicate resistant disease that may require modification of the therapeutic approach. FDG PET in the early phase of treatment of HNSCC is associated with In other clinical scenar- ios, FDG-PET can contribute to the detection of residual/early recurrent tumors, leading to potential institution of salvage therapy and prevention of unnecessary tissue samplings which may aggravate injury.

The clinical experience with PET-CT in the imaging evaluation of patients with head and neck cancer is currently limited. However, PET-CT appears to be superior to PET, and probably also to PET and CT viewed side by side. In par- ticular, PET-CT may be widely used for treatment planning for radiation therapy. PET-CT has the potential for reducing tissue misses, to minimize the dose of ionizing radiation applied to non-target areas, and to incorporate both anatomic and metabolic features of cancer into the three-dimensional confor- mal radiation therapy planning, which may then affect treatment outcome favorably. The exact clinical utility of the other PET radiotracers such as C-11 methionine, C-11 tyrosine, and Cu-62 ATSM (diacetyl-bis(N(4)-methylth- iosemicarbazone) also remain to be established.

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Figure 2: A 75-year-old male with recurrent squamous cell carcinoma treated initially with total laryngectomy and partial pharyngectomy followed by radiation therapy.

PET-CT shows a large hypermetabolic soft tissue mass in the oropharynx which involves

the right lateral and posterior oropharyngeal wall as well as the tongue base.

A

B

Figure 3: An 8-year-old male with tongue carcinoma treated with partial glossectomy

and partial supraglottic laryngectomy followed by radiation. A. Pre-therapy PET-CT

shows intense focal hypermetabolism in the primary at the tongue base. B. Post-therapy

PET-CT demonstrates treatment-related anatomic changes but no evidence for residual

or recurrent tumor.

II. THYROID CANCER

The usual presentation of thyroid cancer is a palpable nodule or a cervical lymph node discovered on physical examination. Dominant nodules in multi- nodular goiter, nodules that are increasing in size, and thyroid nodules in men convey greater risk for cancer. The prognosis of thyroid cancer is affected by many factors including gender, age, histology, and extent of disease. Thyroid carcinomas arise from follicular epithelium (papillary, follicular, anaplastic) or from parafollicular cells (medullary). Rare thyroid cancers include lymphoma and squamous cell carcinoma. Initial diagnosis is usually made by needle aspiration or biopsy.

The normal thyroid gland typically demonstrates no or low FDG accumu- lation. Focal hypermetabolism may indicate benign autonomous nodules or otherwise unknown malignancy (Figs. 4, 5). Overexpression of GLUT1 on the cell membrane of thyroid neoplasms has been shown to be closely related to more aggressive biological behavior. In patients with thyroid cancer, the stan- dard therapy is thyroidectomy followed by radioiodine (I-131) ablation.

Patients are followed for evidence of recurrent or metastatic disease based on serial physical examination and monitoring of serum thyroglobulin (Tg) level.

It has been noted that occasionally the diagnostic radioiodine scan may be neg- ative in view of high clinical suspicion for disease (e.g., high Tg level or abnor- mal physical findings). In these situations, other nuclear studies have been employed using Tc-99m tetrofosmin, Tc-99m sestamibi, In-111 octreotide, thallium-201, and FDG. While well-differentiated thyroid cancer may show low FDG uptake and good iodine avidity, poorly differentiated malignancy and

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Figure 4: Multinodular Goiter. FDG-PET/CT in a patient with bilateral follicular adenomas does not show abnormal FDG uptake.

Figure 5: Papillary Cancer. FDG-PET/CT of a 0.7-cm papillary cancer of the thyroid.

tumors such as anaplastic carcinoma and Hurthle cell carcinoma tend to demonstrate high FDG accumulation and no iodine accumulation (“flip-flop”

phenomenon) (Figs. 6–10).

Many studies have now documented the diagnostic utility of FDG PET in localizing the non-iodine avid metastases in up to 70% of patients and it is most

A B

C

Figure 6: A 21-year-old man with thyroid cancer who presented with fracture of the left

fibula. A. Neck MRI shows right thyroid lobe mass. B. Left lower extremity radiograph

shows lytic lesions in the fibula. C. PET shows focal hypermetabolism corresponding to

the primary tumor in the neck and the metastatic lesions in the left fibula with an

additional unsuspected lesion in the right distal femur.

promising at Tg levels of >10 µg/L. The localization of disease may be amenable to local surgical or radiotherapeutic intervention without resort to systemic therapy. Earlier studies showed that the efficacy of FDG PET in localizing disease may not depend on the presence of high serum thyroid-stimulating hormone (TSH) level. However, recent reports indicate that endogenous TSH stimulation or exogenous recombinant TSH (rhTSH) stimulation improves the detectability of occult thyroid metastases with FDG PET in comparison with scans performed on TSH suppression. FDG PET has also been shown to have prognostic utility. Patients with positive PET studies, high rates of FDG accumulation in the lesions, and overall high volume of FDG-avid disease (>125 ml) have reduced survival in comparison to those patients without these findings. In patients with medullary thyroid cancer, FDG PET has been shown to be the most sensitive and specific single modality for localizing metastases in the clinical setting of increased serum calcitonin level. Recent studies have also demonstrated the utility of the combined PET-CT imaging systems for the diagnosis and anatomic localization of recurrent and metasta- tic thyroid cancer.

In summary, with the recent support of the Center for Medicare and Medicaid Services, it is expected that FDG PET will continue to have a growing role in the imaging assessment of patients with thyroid cancer, specifically in thyroidectomized patients with rising serum Tg levels and negative radioiodine scan.

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Figure 7: A male patient with history of thyroid cancer s/p total thyroidectomy who

presents with elevated serum thyroglobulin level. Whole-body I-131 radioiodine scan is

negative (left panel) while sagittal PET (middle panel) shows a focal hypermetabolic

lesion in the lumbar spine corresponding to a paravertebral lesion on lumbar spine MRI

(right panel). Excisional biopsy demonstrated recurrent thyroid cancer.

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Figure 8: Papillary Cancer Pulmonary Metastases. Twenty-two years after papillary thyroid cancer, a 35-year-old woman presented for recurrent cancer in neck nodes. A. A whole body scan after therapy with iodine-131 showed several pulmonary metastases.

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