Differentiated Thyroid Cancers

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The two primary types of differentiated thyroid cancers are papillary and follicular. Several variants exist and include a follicular variant of papillary carcinoma, a tall cell variant of papillary carcinoma and a Hurthle cell carcinoma which is a variant of follicular carcinoma. The latter two subtypes are more ominous lesions.

Primary surgery is the initial treatment approach. The surgical therapeutic decisions are based on prognostic variables. At Memorial Sloan-Kettering Cancer Center, those patients who are felt to be at high risk are assessed based on "GAMES," for example: (1) Grade: high, (2) Age: > 45 years, (3) Metastasis: positive, (4) Extracapsular extension: positive, (5) Size > 4 cm.89 The patients at low risk do well irrespective of the extent of surgery. The surgical goal is to remove all gross disease that is clinically detectable. The different operations represent the variations in the volume of the thyroid gland that is resected and include partial thyroidectomy and total thyroidectomy. Partial thyroidectomy encompasses the following procedures: (1) lumpectomy, (2) lobectomy, (3) isthmec-tomy, (4) lobectomy and isthmectomy, and (5) near-

total thyroidectomy. Shah and colleagues.90 reviewed the Memorial Sloan-Kettering Cancer Center experience of 931 previously untreated patients in a matched pair analysis to evaluate the extent of surgical resection necessary for differentiated thyroid cancer clinically confined to one lobe. They noted that a large (> 4 cm) primary tumor size and presence of extra-thyroidal extension were associated with a poor prognosis. However, multifocal lesions were not associated with an adverse prognosis. The presence of microscopic disease in the contralateral thyroid lobe was found to have very few clinical consequences with respect to overall survival. In this review, 73 patients > 45 years of age who had undergone a lobec-tomy for a thyroid cancer confined to one lobe were stratified for significant prognostic factors and matched with 73 other similar patients who had undergone a total thyroidectomy. The 20-year survival rate was roughly equivalent at around 80 percent for both arms. It was concluded that patients at low risk89 undergoing lobectomy were likely to do as well as those who underwent a total thyroidectomy. A lobec-tomy with isthmectomy is felt to be the minimal surgical procedure that could be considered in a patient with a solitary thyroid nodule. However, if a patient is felt to need postoperative RAI, then a total thyroidec-tomy should be performed.

The issue of regional lymph nodes needs to be addressed surgically as well. Papillary thyroid cancers are at high risk for cervical node metastasis while follicular thyroid cancers are at a relatively low risk for this process. The surgical approach is one of conservatism. For papillary carcinomas with an N0 neck, one can consider a central compartment clean-out versus monitoring the patient. If the primary lesion is greater than 2 cm and/or there is extra-thyroidal extension, one can consider a central compartment resection—removing the highest risk lymph nodes. For follicular carcinomas with an N0 neck, monitoring the patient can be justified. However if the patient has palpable neck nodes, central compartment and neck dissections involving levels II through V are warranted. If gross lymphadenopa-thy is present in the superior mediastinal lymph nodes, dissection at that level is necessary as well.

Postoperative radioactive iodine (I—131) should be considered but is not required for all cases. To be ther apeutic, the I—131 must be well concentrated in any residual normal or malignant thyroid cell. Uptake varies by histology: papillary and follicular: 60 to 90 percent; Hurthle cell: 36 percent. Also, locally-invasive thyroid cancer in contrast to lymph node recurrence many times will not concentrate RAI.91 This emits a beta particle with a 2 mm zone of effective irradiation. Its use is to: (1) ablate residual normal thyroid tissue, and (2) treat the residual cancer.

I—131 indications include: (1) high postoperative risk for microscopic disease in the thyroid bed and regional lymph nodes (eg, extensive extracapsular extension in the adjacent tissues), (2) postoperative macroscopic residual disease (thyroid bed and lymph nodes), (3) gross disease: recurrent primary or nodal disease or unresectable primary or nodal disease (4) persistently elevated thyroglobulin without clinical evidence of disease, and (5) metastatic disease: lung, bone (iodine uptake is only approximately 50 percent overall and is rather low for bone metastasis).

Contraindications for I—131 include: (1) low-risk papillary carcinoma: age < 40 to 45 years, size < 1.0 to 1.5 cm, no clinical evidence for nodal metastasis, and (2) low-risk follicular carcinoma: age < 40 to 45 years, size < 2.5 cm, no clinical evidence for nodal metastasis, minimal invasiveness.

The use of postoperative external beam radiation therapy is controversial but there is data to support its use.9293 However, there are no phase III, controlled randomized studies available. Thyroid carcinomas are not any more or less curable than squamous cell carcinomas of equivalent volume when treated by external beam radiation.9 With adequate doses (5,000 to 5,400 cGy for elective nodal irradiation/ 6,300 cGy or more for high-risk disease) and contemporary complex treatment planning using CT-PET fusion (Figures 21-12A and B) and intensity-modulated radiation therapy (IMRT), the efficacy of external beam radiation therapy may become more substantiated.

Figure 21-12. CT-PET fusion technique using IMRT treatment planning for a locore-gionally recurrent differentiated thyroid cancer. (A, B).

Possible indications for external beam radiation therapy92,93 include: (1) postoperative high risk for microscopic disease in the thyroid bed and regional lymph nodes (eg, locally-advanced disease with extracapsular tumor extension),91,94-97 (2) postoperative macroscopic residual disease (thyroid bed and nodes,91,94,96,97 (3) gross disease: recurrent primary or nodal disease or unresectable primary or nodal dis-ease,96-98 (4) poor uptake of RAI with above high-risk features,96 (5) persistent/recurrent disease after RAI therapy,99 (6) persistently elevated thyroglobulin with no evidence of disease, and (7) metastatic disease: brain metastasis, painful bone metastasis.98

At Memorial Sloan-Kettering Cancer Center, our initial treatment volume includes the thyroid bed, cervical-retropharyngeal nodes (up to the mas-toid tip-mandibular rim level), supraclavical nodes and superior mediastinal nodes (down to around the level just above the carina or at the angle of Louis. IMRT is employed as a recent evaluation of our experience comparing two-dimensional, three-dimensional and IMRT plans (Figures 21-13 A to D) revealed a more homogenous dose distribution and improved sparing of adjacent vital organs, particularly the spinal cord, with IMRT.100 Elective nodal irradiation is taken to a dosage of 5,000 to 5,400 cGy. High-risk primary and nodal sites are administered 6,300 cGy and may go up to 7,000 cGy for gross disease as a cone down which is based on our current research using PET scan fusion with the CT simulation scans for treatment planning. Often we consider planned postoperative I-131 and then external beam radiation therapy 6 weeks later for selected high-risk patients.

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