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Background Following total thyroidectomy ( TT) for papillary thyroid cancer ( PTC), pathological assessment can occasionally reveal incidental perithyroidal lymph nodes ( LNs) with occult metastases. These cN0pN1a patients often receive radioactive iodine ( RAI) therapy for this indication alone . The aim of this study was to determine the central compartment nodal recurrence-free survival in patients treated without RAI compared to those who received RAI treatment. Methods An institutional database of 3664 previously untreated patients with differentiated thyroid cancer operated between 1986 and 2010 was reviewed. A total of 232 pT1-3 patients managed with TT and no neck dissection were subsequently found to have incidental level 6 LNs on pathology. Patients with other indications for RAI, such as extrathyroidal extension and close or positive margins, were excluded. One hundred and four patients remained for analysis. Kaplan-Meier method was used to determine central neck LN recurrence-free survival ( RFS). Results The median age of the cohort was 40 years (range 17-83). The median follow-up was 53 months (range 1-211). The median number of positive LNs removed and maximum LN diameter were 1 (range 1-8) and 5 mm (range 1-16 mm), respectively. A total of 67 (64%) patients had adjuvant RAI and 37 (36%) did not. Patients with vascular invasion ( P = 0·01), LNs >2 mm ( P = 0·07) and >2 positive nodes ( P = 0·06) were more likely to be selected for adjuvant RAI therapy. Patients without RAI therapy had similar 5-year central neck LN RFS compared to those treated with RAI: 96·2% vs 94·6%, respectively ( P = 0·92). Conclusion There is no difference in the 5-year central compartment nodal recurrence-free survival in patients treated without RAI compared to those who received RAI treatment. [ABSTRACT FROM AUTHOR]

Background: The recent overdiagnosis of subclinical, low-risk papillary thyroid cancer (PTC) coincides with a growing national interest in cost-effective health care practices. The aim of this study was to measure the relative cost-effectiveness of disease surveillance of low-risk PTC patients versus intermediate- and high-risk patients in accordance with American Thyroid Association risk categories.Methods: Two thousand nine hundred thirty-two patients who underwent thyroidectomy for differentiated thyroid cancer between 2000 and 2010 were identified from the institutional database; 1845 patients were excluded because they had non-PTC cancer, underwent less than total thyroidectomy, had a secondary cancer, or had <36 months of follow-up. In total, 1087 were included for analysis. The numbers of postoperative blood tests, imaging scans and biopsies, clinician office visits, and recurrence events were recorded for the first 36 months of follow-up. Costs of surveillance were determined with the Physician Fee Schedule and Clinical Lab Fee Schedule of the Centers for Medicare and Medicaid Services.Results: The median age was 44 years (range, 7-83 years). In the first 36 months after thyroidectomy, there were 3, 44, and 22 recurrences (0.8%, 7.8%, and 13.4%) in the low-, intermediate-, and high-risk categories, respectively. The cost of surveillance for each recurrence detected was US $147,819, US $22,434, and US $20,680, respectively.Conclusions: The cost to detect a recurrence in a low-risk patient is more than 6 and 7 times greater than the cost for intermediate- and high-risk PTC patients. It is difficult to justify this allocation of resources to the surveillance of low-risk patients. Surveillance strategies for the low-risk group should, therefore, be restructured. [ABSTRACT FROM AUTHOR]

Background: In most staging systems, 45 years of age is used to differentiate low risk thyroid cancer from high risk thyroid cancer. However, recent studies have questioned both the precise 45 year age point and the concept of using a binary cut off as accurate predictors of disease specific mortality. Methods: A cohort of 3664 thyroid cancer patients that received surgery and adjuvant treatment at Memorial Sloan Kettering Cancer Center (MSKCC) from the years 1985 to 2010 were analyzed to determine the significance of age at diagnosis as a categorical variable at a variety of age cutoffs (5 year intervals between 30 and 70 years of age). The unadjusted and adjusted hazard ratio for the association between disease-specific survival and age was determined using a Cox proportional hazards model adjusted for other predictive variables sex, histology, and pathological T, N, and M status. Furthermore, predictive nomograms of disease-specific mortality were created and validated on an external dataset of 4551 patients to evaluate the impact of age at diagnosis as both a categorical and continuous variable. Results: In the MSKCC cohort, with a median follow-up time of 54 months (range 1-332), there were 59 deaths from thyroid cancer with a 10 year disease-specific survival of 96%. Adjusted hazard ratios for all age cutoffs from age 30 to age 70 years were significant. There was no specific cutoff age which risk stratifies patients with differentiated thyroid cancer (DTC). Categorizing age into five strata (<40, 40-49, 50-59, 60-69 and >70 years) showed a 37-fold increase in hazard ratio from age <40 years to age >70 years. A predictive nomogram using age as a continuous variable with other predictive variables had a high concordance index of 96%. Validation on the external cohort had a concordance index of 73%. Conclusions: Mortality from DTC increases progressively with advancing age. There is no specific cutoff age which risk stratifies patients with DTC. A predictive nomogram using age as a continuous variable may be a more appropriate tool for stratifying patients with DTC and for predicting outcome. [ABSTRACT FROM AUTHOR]

Background: In contrast to other head and neck cancers, the impact of histological thyroid specimen margin status in differentiated thyroid cancer (DTC) is not well understood. The aim of this study was to investigate the prognostic value of margin status on local recurrence in DTC. Method: The records of 3664 consecutive patients treated surgically for DTC between 1986 and 2010 were identified from an institutional database. Patients with less than total thyroidectomy, unresectable or gross residual disease, or M1 disease at presentation and those with unknown pathological margin status were excluded from analysis. In total, 2616 patients were included in the study; 2348 patients (90%) had negative margins and 268 patients (10%) had positive margins. Microscopic positive margin status was defined as tumor present at the specimen's edge on pathological analysis. Patient, tumor, and treatment characteristics were compared by Pearson's chi-squared test. Local recurrence free survival (LRFS) was calculated for each group using the Kaplan Meier method. Results: The median age of the cohort was 48 years (range 7-91 years) and the median follow-up was 50 months (range 1-330 months). Age, sex, and histology types were similar between groups. As expected, patients who had positive margins were more likely to have larger tumors ( p<0.001), extrathyroidal extension (ETE) ( p<0.001), multicentric disease ( p<0.001), or nodal disease ( p<0.001) and were more likely to receive adjuvant radioactive iodine therapy ( p<0.001) as well as external beam radiotherapy ( p<0.001). The LRFS at 5 years for patients with positive margins status was slightly poorer compared with patients with negative margins (98.9% vs. 99.5%, p=0.018). Twelve patients developed local recurrence-8/2348 (0.34%) patients with negative margins and 4/263 (1.52%) patients with positive margins. Univariate predictors of LRFS were sex ( p=0.006), gross ETE (<0.001), and positive margins ( p=0.018). However, when controlling for presence of gross ETE on multivariate analysis, microscopic positive margin status was not an independent predictor of LRFS ( p=0.193). Conclusion: Patients with resectable, M0 disease that undergo total thyroidectomy have an excellent five year LRFS of 99.4%. Microscopic positive margin status was not a significant predictor for local failure after adjusting for ETE or pathological tumor (pT) stage. [ABSTRACT FROM AUTHOR]

Background: Vascular invasion (VI) is an important predictor of distant metastasis and possible radioactive iodine (RAI) benefit in follicular, Hürthle cell, and poorly differentiated thyroid carcinomas, but its role in well-differentiated papillary thyroid cancer (WDTC) remains unclear. Methods: Archived pathological material of all differentiated thyroid carcinoma patients undergoing primary surgical treatment at Memorial Sloan-Kettering Cancer Center between 1986 and 2003 was reviewed by two dedicated thyroid pathologists. Only WDTCs were included in the present study. Standard statistical methods were used to assess the relationship between VI and outcomes of interest, including 10-year disease-specific survival (DSS), regional recurrence-free survival (RRFS), and distant recurrence-free survival (DRFS). Results: VI was present in 47 of 698 WDTC (6.7%). VI was significantly associated with tumor size >4.0 cm, extrathyroidal extension, distant metastasis, and RAI treatment. On univariate analysis, VI was predictive of decreased 10-year DRFS, but not DSS or RRFS. On multivariate analysis, VI was not an independent predictor of DRFS. Univariate survival analysis of 422 RAI-naïve WDTC showed that both size >4 cm and VI were predictors of outcome, but only size remained independently predictive on multivariate analysis. Conclusion: The presence of VI is not an independent predictor of outcome in WDTC. [ABSTRACT FROM AUTHOR]

Background: Levothyroxine suppression of thyrotropin (TSH) is broadly applied to patients with thyroid cancer despite lack of consensus on the optimal TSH concentration necessary to reduce cancer recurrence while minimizing toxicity from subclinical hyperthyroidism. The objectives of this study were to examine the beneficial effects and the cardiac and skeletal toxicity of TSH suppression in well-differentiated thyroid carcinoma (DTC). Methods: A total of 771 patients (569 women) at ATA low or intermediate risk of recurrence, with a mean age of 48±14 years, and undergoing total thyroidectomy at a tertiary care center between 2000 and 2006 were followed for a median of six and a half years. They were divided into a suppressed TSH group (median TSH ≤0.4 mIU/L) and a nonsuppressed group (median TSH >0.4 mIU/L). Structural recurrence of thyroid cancer, postoperative atrial fibrillation (AF), and osteoporosis were examined in the two groups. Osteoporosis was only examined in women. Results: A total of 43/771 (5.6%) patients recurred, 29/739 (3.9%) patients were diagnosed with postoperative osteoporosis, and 17/756 (2.3 %) were diagnosed with postoperative AF. Despite similar rates of recurrence (HR 1.02, p=0.956 [CI 0.54-1.91]), patients treated to a median TSH ≤0.4 mIU/L were at increased postoperative risk of a composite outcome of AF and osteoporosis (HR 2.1, p=0.05 [CI 1.001-4.3]) compared to those not suppressed. A differential risk of AF alone (HR 0.78, p=0.63 [CI 0.3-2.1]) was not detected, but postoperative osteoporosis was increased among women with a suppressed TSH compared to those not suppressed (HR 3.5, p=0.023 [CI 1.2-10.2]). The increased risk of postoperative osteoporosis disappeared when the patient's median TSH was maintained around 1 mIU/L. Conclusion: TSH suppression significantly increases the risk of postoperative osteoporosis without changing tumor recurrence in ATA low- and intermediate-risk patients with DTC. Future interventions should focus on avoiding harm in indolent disease. [ABSTRACT FROM AUTHOR]

Background: The aim of our study was to determine central compartment lymph node (LN) characteristics predictive of outcomes in patients with differentiated thyroid cancer (DTC) and pathologically confirmed positive central LNs, in the absence of lateral neck disease or distant metastases at presentation. Methods: An institutional database of 3664 previously untreated patients with DTC operated between 1986 and 2010 was reviewed. Six hundred patients with central compartment nodal disease on histopathology were identified. Patient demographics, number of positive LNs, size of largest LN, and presence of extranodal spread (ENS) were recorded for each patient. Variables predictive of recurrence-free survival (RFS) were identified using the Kaplan-Meier method. Univariate analysis was carried out by the log-rank test and multivariable analysis was carried out using cox proportional hazard model. Results: The median age of the cohort was 41 years (range 12-91 years). The median follow-up was 61 months (range 1-330 months). Neck recurrence occurred in 43 patients. Recurrence occurred in the central neck in 11 patients, lateral neck in 27 patients, and both compartments in five patients. Factors predictive of neck RFS on univariate analysis were higher T stage ( p=0.007), increased number of positive LNs, increased LN diameter, and presence of ENS ( p=0.001). Multivariable analysis of LN characteristics showed that the only statistically significant predictor of neck recurrence was the presence of ENS. Neck RFS at five years for patients with and without ENS was 84.7% and 94.5% respectively ( p=0.001). Conclusion: The LN feature most predictive of neck recurrence appears to be the presence of ENS in the positive central neck. [ABSTRACT FROM AUTHOR]

Background: The American Thyroid Association guidelines recommend the routine use of radioactive iodine for remnant ablation (RRA) in all T3 or greater primary tumors, and selective use in patients with intrathyroidal disease >1 cm, or evidence of nodal metastases. The guidelines recognize that there is conflicting and inadequate data to make firm recommendations for most patients. The aim of this study was to analyze our institutional experience of the use of RRA in the management of papillary thyroid cancer, with a particular focus on outcomes for those patients selected not to receive RRA. Methods: We retrospectively reviewed 1129 consecutive patients who underwent total thyroidectomy at the Memorial Sloan-Kettering Cancer Center between 1986 and 2005. Of these, 490 were pT1-2 N0, 193 pT1-2 N1, and 444 pT3-4. Details on recurrence and disease-specific survival were recorded by the Kaplan-Meier method and compared using the log-rank test. Results: The five-year disease-specific survival and recurrence-free survival in the pT1/T2 N0, pT1-2 N1, and pT3-4 were 100% and 92%, 100% and 92%, and 98% and 87% respectively. Low-risk patients who were managed without RRA (who tended to have limited primary disease, pT1-2, and low-volume metastatic disease in the neck, pT1-2 N1-fewer than five nodes, all <1 cm greatest dimension) had five-year recurrence-free survival of >97%. In the group with advanced local tumors (pT3-4), those patients who did not receive RRA (who tended to have pT3 N0 disease) had five-year recurrence-free survival of >90%. Conclusion: Following appropriate surgical management, the majority of patients with low-risk local disease and even some patients with more advanced-stage (pT3) tumors or regional metastases have low rates of recurrence and high rates of survival when managed without RRA. [ABSTRACT FROM AUTHOR]