Σάββατο 31 Δεκεμβρίου 2016

RISK FACTORS FOR LYMPH NODE RECURRENCE IN THYROID CANCER

In patients with cervical lymph node metastases after thyroidectomy for papillary thyroid carcinoma, patient age and rapid growth of lymph node metastases are better predictors of outcome than tumor size at initial surgery or lymph node size at recurrence.
Chisato Tomoda, MD, from the Ito Hospital, Tokyo, Japan, and colleagues reported the findings of their retrospective analysis in an article published in Thyroid (2016;26:1706-1711).
"The study shows that for papillary thyroid cancer patients with lymph node recurrence, 10-year and 15-year disease-specific survival (DSS) rates after initial surgery were 96.1% and 90.1%, respectively, while 10-year and 15-year DSS rates after diagnosis of lymph node recurrence were 84.7% and 72.6%, respectively," the researchers say.
The study reveals a correlation between advanced age and disease-specific survival after initial treatment (= .0106), but not with primary tumor size at initial surgery.
In addition, recurrent lymph node growth of more than 3 mm per year showed a significant direct correlation with disease-specific survival after lymph node recurrence, but lymph node size of more than 1.5 cm at the start of the observation period did not.
"Recurrent lymph node growth of more than 3 mm per year could be related to mortality," Dr Tomoda and colleagues report, noting that patients with rapid growth of lymph node metastases were more likely to be 45 years of age or older and to have larger lymph node size at study entry.
A 3-mm increase in size of the largest lymph node — when there were multiple metastases — was chosen for the study because it is the smallest size change that can be reproducibly determined by high-resolution ultrasound, the researchers explain.
The velocity of lymph node metastasis growth after thyroidectomy could be "very helpful for deciding how best to manage individual patients with lymph node recurrence," they suggest. "Intervention for recurrent metastatic lymph nodes should be discussed in detail with each patient."
Fine needle aspiration biopsy and surgical intervention should be considered in cases of suspicious lymph node recurrence, they recommend.
For the purposes of this study, features such as marked hypoechogenicity, microcalcifications, margins that were microlobulated and irregular, and a shape that was taller than wide were considered "suspicious."
The retrospective review included 83 consecutive patients with papillary thyroid carcinoma and at least one lymph node on postoperative ultrasound during follow-up at Ito Hospital between October 2003 and January 2014.
There were 15 men and 68 women with a median age of 50.6 years.
Almost half (48.2%) of patients had undergone total thyroidectomy and all received central neck dissection, including 10 (12.0%) who underwent massive extrathyroid extension. The median number of lymph nodes dissected per patient was five.
Following diagnosis of lymph node recurrence by ultrasound-guided fine-needle aspiration biopsy or thyroglobulin titer in the washout of the needle, researchers used serial ultrasound studies every 3 to 6 months to monitor for size changes
The median lymph node size at the start of the observation period was 1.3 cm.
After a median follow-up of 86 months, analysis showed that 17 of 83 patients (20.5%) had an increase in lymph node size of at least 3 mm.
Of these patients, 8.4% (7 of 83) had an increase of at least 5 mm, whereas 39.7% (33 of 83) resolved.
Distant metastases were present in 11 of 83 patients in lung (n = 9), bone (n = 2), brain (n = 1), and skin (n = 1).
Ten patients with distant metastases underwent ablation and/or therapeutic doses of radioiodine, and 44 patients with distant metastases, extra-thyroidal massive invasion, or a second recurrence underwent selective postoperative thyrotropin suppression therapy.
The therapeutic approach for patients with rapidly growing recurrent lymph node metastasis may include surgical resection, with or without thyrotropin suppressive therapy with thyroid hormone, radioactive iodine therapy, external beam radiation therapy, and/or tyrosine kinase inhibitors (TKIs), Dr Tomoda and colleagues say.
"Theoretically, there may be benefit derived from removing these lymph nodes to prevent de novo distant metastases as well, although this has not been proven," they note.
"We have to understand the risks and benefits of each therapy, including observation, depending on the recurrence site and patient-related factors," they write, adding that the National Comprehensive Cancer Network panel recommends surgery for locoregional recurrent disease.
Patients with a recurrent metastatic lymph node with evidence of invasion or a high risk of probable invasion into the internal jugular vein, carotid artery, esophagus, or recurrent laryngeal nerve would be considered candidates for surgical removal, Dr Tomoda and colleagues say.
They add that surgery "has been reported to have no impact on overall survival" and risk of iatrogenic vocal cord paralysis should be discussed.
For patients with unresectable, locoregional disease that doesn't respond to radioiodine, guidelines by the National Comprehensive Cancer Network suggest that outcomes can be improved with the use of external radiation therapy.
TKI initiation should only be considered after careful weighing of the pros and cons, including increased risk of cutaneous alterations, aerodigestive fistulas, and carotid rupture, the researchers say.
The authors have reported no relevant financial relationships. 
Thyroid. 2016;26:1706-171

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