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مخاطبین : رزیدنتهای محترم داخلی و فلوهای محترم غدد

مختصر و مفید  از:
UPTODATE 21.2

Overview of the management of differentiated thyroid cancer
CLASSIFICATION — Thyroid follicular epithelial-derived cancers are divided into three categories:
• Papillary cancer
• Follicular cancer
• Anaplastic cancer
Papillary and follicular cancers are considered differentiated cancers. Most anaplastic (undifferentiated) cancers appear to arise from differentiated cancers.
Staging — Formal disease staging is based upon applying the individual TNM (Tumor Node Metastasis) descriptors in the AJCC (American Joint Commission on Cancer) staging scheme . Since the AJCC staging system is designed to risk stratify based upon disease specific mortality and may not accurately predict the risk of recurrence/persistentdisease in thyroid cancer, the ATA thyroid cancer management guidelines have proposed a novel clinic-pathologic staging system:
low (papillary thyroid cancer confined to thyroid),
intermediate (regional metastases, worrisome histologies, extrathyroidal extension, or vascular invasion), or
high risk (gross extrathyroidal extension or distant metastases) of recurrence

TREATMENT —
Guidelines — American Thyroid Association in 2009 for management of DTC provide clear recommendations for use of surgery, radioiodine, and thyroid hormone therapy . Our approach is consistent with the American Thyroid Association Guidelines .
Surgery —
We recommend total thyroidectomy if the primary tumor is at least 1.0 to 2.0 cm in diameter, or if extrathyroidal extension or metastases are present.

This recommendation may differ in the following circumstances:
• We suggest unilateral lobectomy and isthmusectomy when the tumor is less than 1.0 cm in diameter and confined to one lobe of the gland.
• We suggest regional neck dissection in patients with papillary cancer only if there is clinical evidence (on exam or preoperative ultrasound) of nodal involvement.

recommend therapeutic neck dissection in patients with clinical evidence (exam or ultrasound) of nodal involvement
In addition, the ATA suggests that prophylactic central neck dissection may be performed in patients with advanced PTC (>4 cm and/or extrathyroidal extension) even in the absence of clinical evidence of nodal involvement
The guideline from the National Comprehensive Cancer Network only recommends central neck dissection in the presence of grossly positive metastasis .
• Patients with invasion of neck structures such as the esophagus, trachea, or strap muscles should have a more extensive resection.
• Radioiodine therapy — Radioiodine is the most effective adjuvant treatment for PTC , in the form of 131-iodine (131-I). Radioiodine causes cytotoxicity by the emission of short path-length (1 to 2 mm) beta radiation.
• the IV contrast used for CT scans contains a large iodine load and may interfere with RAI scanning and therapy for several months.
Radioiodine has three uses in the post-thyroidectomy treatment of patients with differentiated thyroid cancer:
 adjuvant ablation of residual thyroid tissue and possible microscopic residual cancer,
 imaging for possible metastatic disease,
 treatment of known residual or metastatic thyroid cancer.
Thyroid hormone suppression —
BY levothyroxine therapy for all patients to prevent hypothyroidism and to minimize potential TSH stimulation of tumor growth.
Our recommendations for initial thyroid hormone suppression therapy are as follows:
• For stage I and II disease without distant metastases —TSH AT 0.1 to 2.0 mU/L.
• For stage II disease with distant metastases, stage III, and IV disease — the serum TSH 0.8 cm in diameter or, possibly, larger nodes in the lateral compartments, especially if they are increasing in size or are significantly FDG PET positive.
we recognize that aggressive surgical resection of small volume disease in the central or lateral neck does not have a proven benefit in terms of improving overall survival.
Therefore, it is important to ensure that the risk of persistent low level disease outweighs the risk of surgical resection in patients with potentially stable low volume disease.
Although many patients will still have measurable serum thyroglobulin levels after surgery, indicating a persistence of minimal disease, intraoperative ultrasonography and/or pre-operative ultrasound-guided placement of hook needles may help guide the operation [ 27 ].
Surgery is usually followed by a stimulated thyroglobulin determination, radioiodine scanning, and radioiodine therapy if there is persistent radioiodine uptake.
However, if the patient had a rhTSH-stimulated radioiodine scan before such surgery and if gross recurrent disease failed to concentrate radioiodine before surgery, there is likely no role for postoperative imaging and therapy. Recurrent disease that is FDG avid (positive on FDG PET scanning) is unlikely to respond to even high dose RAI therapy .
Extensive disease —
Recurrence within the thyroid bed may be associated with soft tissue, laryngeal, tracheal, or esophageal invasion, which may require more extensive resection; imaging studies with contrast-enhanced CT or MRI may be valuable to detect such locally extensive disease.
Other options for treating recurrent/metastatic disease include the following:
• Radioiodine, if scans demonstrate uptake
• External radiotherapy
• Percutaneous ethanol injection of cervical nodal metastases
• Radiofrequency ablation of cervical, osseous, and pulmonary metastases are alternatives for patients who are poor surgical candidates and whose metastases do not concentrate radioiodine, but expertise in these treatment modalities is not widely available
• Palliative embolization of bone metastases may reduce symptoms or be used prior to surgery
Patients who develop distant metastases during long-term follow-up are treated like those with metastases found at the time of initial treatment; however, radioiodine therapy may be less effective in these patients

Rarely, surgery may be considered for patients with single distant metastases, including patients with a single bone metastasis [ 33 ] or limited pulmonary metastases .
Systemic chemotherapy or palliative external radiotherapy may be considered for patients with either local or distant recurrence, or when radioiodine fails to control local growth and spread of disease.
LONG-TERM FOLLOW-UP —
Most recurrences of DTC occur within the first five years after initial treatment,
All patients should have periodic physical examinations and testing as described below. The biochemical tests may be performed while the patient is taking thyroxine.
Imaging —
If there is clinical or other evidence of recurrence, other tests that may be indicated to identify the sites of disease include radioiodine imaging (on a low iodine diet with TSH stimulation as above), ultrasonography , CT or MR imaging, skeletal x-rays, or skeletal radionuclide imaging . Ultrasonography has been particularly useful at identifying malignant cervical lymph nodes,
Ultrasonographic lymph node characteristics most consistent with malignancy are a cystic appearance, microcalcifications, loss of hilum, and peripheral vascularization .
In patients with evidence of distant metastases, FDG-PET scanning may provide useful prognostic information
The use of rhTSH before FDA-PET scan significantly increases the number of lesions detected.
FDG-PET may complement 131-I scanning . FDG-PET was more likely to be positive in 131-I negative patients .
Serum thyroglobulin measurements —
Compared with normal thyroid tissue, most thyroid cancers have a reduced capacity to transport and organify iodide.
when TSH are high, approximately 60 % of DTC take up enough iodide to be detected by radioiodine imaging, and over 90 % synthesize and secrete thyroglobulin.
If initial surgery and thyroid remnant ablation are successful, the serum Tg should be very low (10 ng/mL) without surgically resectable disease may lead to hormone withdrawal, a diagnostic radioiodine scan, and administration of a therapy dose if the scan indicates pathologic uptake.
• Patients with Stage III or IV disease with a negative evaluation at 6 to 12 months should undergo measurement of Tg before and after rhTSH injections and usually a diagnostic radioiodine scan — pathologic uptake on the scan leads to hormone withdrawal and repeat 131-I therapy.
• Patients with detectable Tg or evidence of small suspicious lesions by ultrasound should undergo measurement of Tg and a diagnostic radioiodine scan following thyroid hormone withdrawal, with administration of a therapy dose if the scan indicates pathologic uptake.
If significant uptake is seen within the thyroid bed, one more treatment with 100 to 150 mCi (5550 MBq) of 131-I is often given to complete the ablation in patients at risk for recurrence.
Generally, we are reluctant to continue to re-treat thyroid bed uptake in the absence of clear evidence of residual cancer that can respond to the therapy. If there is uptake outside of the thyroid bed, we give doses of 131-I appropriate to the site of uptake.
A single negative scan/thyroglobulin combination may be sufficient in Stage III or IV patients, and lower risk patients with negative Tg may not require follow-up scanning at all.
Years 2 to 10 — Clinical examination, measurements of serum free thyroxine, TSH, and Tg annually; neck ultrasonography every one to two years or less frequently in low-risk patients with no evidence of disease; radioiodine imaging if serum Tg increases or there is other evidence of recurrence.
Years 11 to 20 — Clinical examination and measurements of serum free thyroxine, TSH, and thyroglobulin annually; neck ultrasonography every one to three years or less frequently in low-risk patients with no evidence of disease; radioiodine imaging if serum Tg increases or there is other evidence of recurrence.
Years 21+ — Clinical examination and measurements of serum free thyroxine, TSH, and thyroglobulin annually; neck ultrasonography every three to five years or less frequently in low-risk patients with no evidence of disease; radioiodine imaging if serum Tg increases or there is other evidence of recurrence.
• SUMMARY AND RECOMMENDATIONS — Once the diagnosis of DTC is established, several treatment options may be considered, depending upon the extent of the disease, the patient’s age, and the presence of comorbid conditions.

Surgical therapy
• Surgery is the primary mode of therapy for patients with DTC . For most patients with papillary or follicular cancer, we suggest total thyroidectomy if the primary tumor is > 1.0 cm in diameter, there is extrathyroidal extension of tumor, metastases, or if there is a history of exposure to ionizing radiation of the head and neck.
• Radioiodine ablation —
• We currently recommend postoperative radioiodine ablation for all patients with known distant metastases, gross extrathyroidal extension of the tumor regardless of tumor size, or primary tumor >4 cm even in the absence of other high risk features .
• We also suggest radioiodine ablation for select patients with tumor size 1 to 4 cm confined to the thyroid, who have documented lymph node metastases or other high risk features (eg, vascular invasion, more aggressive histologic subtypes, such as tall cell, columnar cell, insular, or poorly differentiated histologies) when the combination of age, tumor size, lymph node status, and individual histology predicts an intermediate to high risk of recurrence or death from thyroid cancer
• In the absence of a proven benefit on either disease free survival or recurrence, we suggest AGAINST radioiodine ablation for patients with unifocal tumors <1 cm without other high risk features or for patients with multifocal cancer when all foci are <1 cm in the absence of other high risk features .
Levothyroxine suppression
• For high risk patients (Stage III and IV disease), we recommend full levothyroxine suppression therapy (TSH <0.1 mU/L) .
• For low-risk patients (Stage I and II disease), we suggest levothyroxine suppression of TSH to slightly below the lower half of the reference range (0.1 to 2.0 mU/L)

The presence of heart disease or low bone density may necessitate a lower level of TSH suppression with smaller doses of thyroxine. The dose also may be decreased to allow the TSH to rise into the normal range in low risk patients who remain disease-free for 5 to 10 years after primary therapy.
• Progressive disease
• For patients with progressive disease, we suggest enrollment in a clinical trial. If unavailable, we suggest treatment with a tyrosine kinase inhibitor
• Follow-up
Patients with DTC require long-term follow up with physical examinations, biochemical testing (including serum thyroglobulin measurements), radioiodine imaging, and ultrasound.

تصویر پروفایل نویسنده:دکتر علی میرزاپور
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