Is a Prophylactic Central Compartment Neck Dissection Required in Papillary Thyroid Carcinoma Patients with Clinically Involved Lateral Compartment Lymph Nodes?

BACKGROUND: The 2015 American Thyroid Association guidelines state that a prophylactic central compartment neck dissection (PCND) should be considered for patients with papillary thyroid carcinoma (PTC) and clinically involved lateral neck lymph nodes (cN1b). The purpose of our study was to determine the rate of central neck recurrence in select cN1b patients, with no evidence of clinically involved central compartment lymph nodes, treated without a PCND. METHODS: After institutional review board approval, adult PTC patients with cN1b disease who were treated with a total thyroidectomy and lateral neck dissection were identified from an institutional database of 6259 patients who underwent initial surgery for well-differentiated thyroid carcinoma from 1986 to 2015. Patients with gross extrathyroidal extension, distant metastases, or no preoperative imaging were excluded. Patients with evidence of clinically involved central compartment lymph nodes, on preoperative imaging or intraoperative evaluation, also were excluded. A total of 152 cN1b patients were included and categorized into non-PCND and PCND groups. Central neck recurrence-free probability (CNRFP) was calculated using the Kaplan-Meier method and log-rank tests. RESULTS: One hundred three patients (67.8%) did not have a PCND. With a median follow-up of 65 months, the 5- and 10-year CNRFP was 98.4% in the non-PCND group and 93.6% in the PCND group (p = 0.133). CONCLUSIONS: Select PTC patients with cN1b disease but no evidence of clinically involved central compartment lymph nodes, on preoperative imaging and intraoperative evaluation, appear to have a low rate of central neck recurrence. These patients may not require or benefit from a PCND.

Management and outcome of clinically evident neck recurrence in patients with papillary thyroid cancer.

BACKGROUND: The aim of this study was to report our incidence of clinically evident neck recurrence, salvage neck management and subsequent outcomes in patients with papillary thyroid cancer. This is important to know so that patients with thyroid cancer can be properly counselled about the implications of recurrent disease and subsequent outcome. METHODS: An institutional database of 3664 patients with thyroid cancer operated between 1986 and 2010 was reviewed. Patients with nonpapillary histology and gross residual disease and those with distant metastases at presentation or distant metastases prior to nodal recurrence were excluded from the study. Of these, 99 (3.0%) patients developed clinically evident nodal recurrence. Details of recurrence and subsequent therapy were recorded for each patient. Subsequent disease-specific survival (sDSS), distant recurrence-free survival (sDRFS) and nodal recurrence-free survival (sNRFS) were determined from the date of first nodal recurrence using the Kaplan-Meier method. RESULTS: Of the 99 patients, 59% were female and 41% male. The median age was 41 years (range 5-91). The majority of patients had pT3/4 primary tumours (63%) and were pN+ (78%) at initial presentation. The median time to clinically evident nodal recurrence was 28 months (range: 3-264). Nodal recurrence occurred in the central neck in 15 (15%) patients, lateral neck in 74 (75%) patients and both in 10 (10%) patients. After salvage treatment, the 5-year sDSS was 97.4% from time of nodal recurrence. The 5-year sDRFS and sNRFS were 89.2% and 93.7%, respectively. CONCLUSION: In our series, isolated clinically evident nodal recurrence occurred in 3.0% of patients. Such patients are successfully salvaged with surgery and adjuvant therapy with sDSS of 97.4% at 5 years.

Plasma phospholipid fatty acid profile confirms compliance to a novel saturated fat-reduced, monounsaturated fat-enriched dairy product intervention in adults at moderate cardiovascular risk: a randomized controlled trial.

BACKGROUND: Dairy products are a major contributor to dietary SFA. Partial replacement of milk SFA with unsaturated fatty acids (FAs) is possible through oleic-acid rich supplementation of the dairy cow diet. To assess adherence to the intervention of SFA-reduced, MUFA-enriched dairy product consumption in the RESET (REplacement of SaturatEd fat in dairy on Total cholesterol) study using 4-d weighed dietary records, in addition to plasma phospholipid FA (PL-FA) status. METHODS: In a randomised, controlled, crossover design, free-living UK participants identified as moderate risk for CVD (n = 54) were required to replace habitually consumed dairy foods (milk, cheese and butter), with study products with a FA profile typical of retail products (control) or SFA-reduced, MUFA-enriched profile (modified), for two 12-week periods, separated by an 8-week washout period. A flexible food-exchange model was used to implement each isoenergetic high-fat, high-dairy diet (38% of total energy intake (%TE) total fat): control (dietary target: 19%TE SFA; 11%TE MUFA) and modified (16%TE SFA; 14%TE MUFA). RESULTS: Following the modified diet, there was a smaller increase in SFA (17.2%TE vs. 19.1%TE; p < 0.001) and greater increase in MUFA intake (15.4%TE vs. 11.8%TE; p < 0.0001) when compared with the control. PL-FA analysis revealed lower total SFAs (p = 0.006), higher total cis-MUFAs and trans-MUFAs (both p < 0.0001) following the modified diet. CONCLUSION: The food-exchange model was successfully used to achieve RESET dietary targets by partial replacement of SFAs with MUFAs in dairy products, a finding reflected in the PL-FA profile and indicative of objective dietary compliance. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02089035 , date 05-01-2014.

Role of RAI in the management of incidental N1a disease in papillary thyroid cancer.

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.

Nodal metastases in thyroid cancer: prognostic implications and management.

The significance of cervical lymph node metastases in differentiated thyroid cancer has been controversial and continues to evolve. Current staging systems consider nodal metastases to confer a poorer prognosis, particularly in older patients. Increasingly, the literature suggests that characteristics of the metastatic lymph nodes such as size and number are also prognostic. There is a growing trend toward less aggressive treatment of low-volume nodal disease. The aim of this review is to summarize the current literature and discuss prognostic and management implications of lymph node metastases in differentiated thyroid cancer.

Cost-effectiveness analysis of papillary thyroid cancer surveillance.

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.

Increasing diagnosis of subclinical thyroid cancers leads to spurious improvements in survival rates.

BACKGROUND: Survival rates are commonly used to measure success in treating cancer, but can be misleading. Modern diagnostic practices can lead to the appearance of improving cancer survival, as tumors are diagnosed earlier (lead-time bias) or as an increasing proportion are slow-growing (length bias), whereas the actual burden of cancer deaths is unchanged. Increasingly, more subclinical thyroid cancers are being diagnosed. The objective of the current study was to determine whether thyroid cancer survival rates have been affected by this phenomenon. METHODS: The authors analyzed survival data from patients with thyroid cancer who were treated at Memorial Sloan Kettering Cancer Center (MSKCC) from 1950 to 2005, and United States population-based incidence, prevalence, and survival data from 1973 to 2009 in the Surveillance, Epidemiology, and End Results data set. RESULTS: US thyroid cancer incidence has increased 3-fold from 1975 to 2009. Over time, the proportion of thyroid cancers that are subcentimeter in size has increased from 23% (1983) to 36% (2009). At MSKCC, this percentage rose from 20% (1950) to 35% (2005). The incidence rates of large tumors (>6 cm) and distant metastasis have not changed. In the United States, 10-year relative survival improved from 95.4% to 98.6% (1983-1999). At MSKCC, 10-year disease-specific survival improved from 91.1% to 96.1% (1950-2005). However, when stratified by tumor size and stage, no changes in survival outcomes were observed. US thyroid cancer mortality rates have remained stable (1975-2009). CONCLUSIONS: Modern medical practices increasingly uncover small, asymptomatic thyroid cancers. Survival rates appear improved, but this finding is spurious, attributable instead to shifts in the characteristics of disease being diagnosed. Relying on survival rates to measure success in treating thyroid cancer may reinforce inappropriately aggressive management. Treatment decisions in thyroid cancer should be made based on mortality, not survival data.

Level 7 disease does not confer worse outcome than level 6 disease in differentiated thyroid cancer.

BACKGROUND: Level 7 nodal disease increases patients from N1a to N1b in the American Joint Committee on Cancer (AJCC) TNM classification of differentiated thyroid cancers (DTCs). This results in upstaging of patients older than 45 years of age from stage III to IV. Our objective was to determine if patients with level 7 disease had poorer outcome in comparison to patients with isolated level 6 disease. METHODS: A total of 599 patients with DTC limited to the central neck (level 6 and 7) were identified from an institutional database. Patients with N1b disease due to lateral compartment (level 1-5) involvement or M1 disease were excluded. Fifty-seven patients had positive level 7 disease, and 542 patients had nodal disease limited to level 6. Disease-specific survival (DSS) and recurrence-free survival (RFS) were calculated for each group. RESULTS: Median age was 41 years (range 12-91) and follow-up was 61 months (range 1-330). There were no disease-specific deaths at 5 years. Among patients with level 6 disease at presentation, there were 42 nodal recurrences, and among patients with level 7 disease, there were two recurrences. There were no differences in overall RFS between patients with level 6 or 7 disease (5-year RFS 90.7 vs. 98.2 %, respectively; p = 0.096). CONCLUSIONS: Our results suggest that N1b disease due to level 7 disease does not confer worse DSS or RFS compared with patients with level 6 disease only. Classifying all central neck disease (levels 6 and 7) into the N1a category, and reserving the N1b classification only for patients with lateral neck disease may be more reflective of prognosis.

Lateral Neck Lymph Node Characteristics Prognostic of Outcome in Patients with Clinically Evident N1b Papillary Thyroid Cancer.

PURPOSE: To identify lateral lymph node (LN) characteristics predictive of outcome in papillary thyroid cancer patients with clinically evident nodal disease. METHODS: A total of 438 patients with lateral neck metastases from papillary thyroid cancer were identified from an institutional database of 3,664 differentiated thyroid cancers. The number of positive LNs, size of the largest LN, number of positive LNs to total number of LNs removed (LN burden), and presence of extranodal spread (ENS) were recorded. Cutoffs for continuous variables were determined by receiver operating characteristic curves. LN variables predictive of recurrence free survival and disease-specific survival (DSS) were identified by the Kaplan-Meier method and the Cox proportional hazard model. RESULTS: The median age was 41 years (range 5-86 years). The median follow-up was 65 months (range 1-332 months). Fifty-nine patients developed disease recurrence; these were local in five, regional in 40, and distant in 30 patients. Fifteen patients died of disease. Receiver operating characteristic cutoffs were >10 positive LNs and a LN burden >17 %. No lateral LN characteristics were predictive of DSS. In patients <45 years old, univariate predictors of recurrence were >10 positive nodes (p = 0.049) and LN burden >17 % (p < 0.001). In patients ≥45 years old, >10 positive nodes, LN burden >17 %, and presence of ENS were predictive of recurrence (p = 0.019, p = 0.019, and p = 0.029, respectively). CONCLUSIONS: LN burden >17 % (1 positive LN in 6 LNs removed) in the lateral neck is predictive for recurrence in patients of all ages, whereas ENS is also prognostic for recurrence in older patients.

Level VII is an important component of central neck dissection for papillary thyroid cancer.

BACKGROUND: Therapeutic central neck dissection (CND) is an accepted part of the management of papillary thyroid carcinoma (PTC), while prophylactic CND remains controversial. Regardless of the indication for CND, the lower anatomic border of the central compartment, specifically the inclusion or otherwise of level VII, is not always clearly defined in the literature. This study aimed to determine if the routine inclusion of level VII lymph node dissection as part of CND confers increased utility in the detection of macrometastatic lymph nodes compared with level VI dissection alone. METHOD: This was a prospective cohort study of patients undergoing CND for PTC at a tertiary referral center. All patients received either a prophylactic or therapeutic CND. The CND specimens were divided by the surgeon into level VI and level VII at the level of the suprasternal notch and submitted separately for histopathology. Criteria for macroscopic lymph node disease were taken from the American Joint Committee on Cancer (AJCC) recommendations for breast cancer. RESULTS: A total of 45 patients with PTC underwent total thyroidectomy and routine CND, at a tertiary referral center; 77 % of the therapeutic CND group had positive level VI lymph nodes, and 38 % had positive level VII lymph nodes. Of the prophylactic CND group, 50 % of patients had positive level VI nodes and 16 % has positive level VII nodes detected. All patients with positive level VII lymph nodes in the prophylactic CND group had macrometastatic disease. Temporary hypocalcemia rate was 31 % in the therapeutic group and 6 % in the prophylactic CND group. One patient experienced permanent hypoparathyroidism. There was no vascular injury or recurrent laryngeal nerve palsy in either group. CONCLUSIONS: CND incorporating both level VI and level VII can be undertaken safely through a cervical incision with no increased risk of permanent complications of hypoparathyroidism or recurrent laryngeal nerve injury. Failure to include level VII as part of CND will leave significant macrometastatic nodal disease behind in both therapeutic and prophylactic dissections. As level VII is in direct anatomic continuity with the pretracheal level VI nodes, it should be routinely included as part of every CND.

Does macroscopic extrathyroidal extension to the strap muscles alone affect survival in papillary thyroid carcinoma?

BACKGROUND: Macroscopic extrathyroidal extension to structures adjacent to the thyroid gland is one of the most important predictors of survival in papillary thyroid carcinoma. However, the prognostic significance of macroscopic extrathyroidal extension to strap muscles alone is unknown. The aim of this study is to determine the impact on survival in patients with macroscopic extrathyroidal extension to strap muscles alone compared to those with no macroscopic extrathyroidal extension and macroscopic extrathyroidal extension involving other adjacent structures. METHODS: After institutional review board approval, adult papillary thyroid carcinoma patients were identified from an institutional database of 6,259 patients undergoing initial surgery for well-differentiated thyroid carcinoma from 1986 to 2015. Patients were classified as having no macroscopic extrathyroidal extension, macroscopic extrathyroidal extension to strap muscles alone, or macroscopic extrathyroidal extension to other adjacent structures. Disease-specific survival was calculated using the Kaplan-Meier method and groups were compared using the log-rank test. A P value < .05 was considered statistically significant and significant factors were used in a Cox proportional hazard model to predict disease-specific survival. RESULTS: There were 5,880 patients included in the analysis; 5,485 patients (93.3%) in the no macroscopic extrathyroidal extension group, 179 (3.0%) in the macroscopic extrathyroidal extension to strap muscles alone group and 216 (3.7%) in the macroscopic extrathyroidal extension involving other adjacent structures group. With a median follow-up of 64 months, the estimated 10-year disease-specific survival for patients with no macroscopic extrathyroidal extension, macroscopic extrathyroidal extension to strap muscles alone, and macroscopic extrathyroidal extension involving other adjacent structures were 98.9%, 95.7%, and 83.7%, respectively (P < .0001). In the ≥55-year-old cohort, the estimated 10-year disease-specific survival for patients with no macroscopic extrathyroidal extension, macroscopic extrathyroidal extension to strap muscles alone, and macroscopic extrathyroidal extension involving other adjacent structures were 97.6%, 89.3%, and 68.1%, respectively (P <.0001). After controlling for pathological nodal stage and distant metastasis stage, extent of extrathyroidal extension remained an independent predictor of disease-specific survival; patients with macroscopic extrathyroidal extension to strap muscles alone had a 3.3-fold increased likelihood of a disease-specific death compared to no macroscopic extrathyroidal extension patients (hazard ratio 3.294; 95% confidence interval 1.076-10.086, P < .0368). CONCLUSION: In our study, patients aged ≥55 years with papillary thyroid carcinoma and macroscopic extrathyroidal extension to strap muscles alone appear to have an increased likelihood of a disease-specific death compared to patients with no macroscopic extrathyroidal extension.

Should multifocality be an indication for completion thyroidectomy in papillary thyroid carcinoma?

BACKGROUND: Multifocality in papillary thyroid carcinoma is common. The aim of this study is to determine whether patients with multifocal disease, treated with lobectomy alone, have an increased risk of contralateral lobe papillary thyroid carcinoma, regional recurrence, and poorer survival. METHODS: After institutional review board approval, papillary thyroid carcinoma patients managed from 1986 to 2015 with lobectomy alone were identified from an institutional database. Papillary thyroid carcinoma patients with pT3 to T4 classification, nodal disease, or distant metastases were excluded. After excluding 40 patients who underwent an immediate completion thyroidectomy, 849 were included in the analysis; 619 (72.9%) had unifocal disease and 230 (27.1%) had multifocal disease. Contralateral lobe papillary thyroid carcinoma-free probability, regional recurrence-free probability, disease-specific survival, and overall survival were calculated using the Kaplan-Meier method. RESULTS: With a median follow-up of 58 months, unifocal disease and multifocal disease patients had similar rates of contralateral lobe papillary thyroid carcinoma, regional recurrence, and overall survival (10-year contralateral lobe papillary thyroid carcinoma-free probability 98.6% vs 97.8%; regional recurrence-free probability 99.5% vs 99.4%; overall survival 91.6% vs 93.1%, respectively). There were no disease-related deaths. CONCLUSION: Select multifocal disease patients, managed with lobectomy alone, have rates of contralateral lobe papillary thyroid carcinoma, regional recurrence, and overall survival comparable to unifocal disease patients. Multifocal disease should not be an indication for completion thyroidectomy.

The effect of different meals on the absorption of stable isotope-labelled phylloquinone.

Few studies have investigated the absorption of phylloquinone (vitamin K1). We recruited twelve healthy, non-obese adults. On each study day, fasted subjects took a capsule containing 20 microg of 13C-labelled phylloquinone with one of three meals, defined as convenience, cosmopolitan and animal-oriented, in a three-way crossover design. The meals were formulated from the characteristics of clusters identified in dietary pattern analysis of data from the National Diet and Nutrition Survey conducted in 2000-1. Plasma phylloquinone concentration and isotopic enrichment were measured over 8 h. Significantly more phylloquinone tracer was absorbed when consumed with the cosmopolitan and animal-oriented meals than with the convenience meal (P = 0.001 and 0.035, respectively). Estimates of the relative availability of phylloquinone from the meals were: convenience meal = 1.00; cosmopolitan meal = 0.31; animal-oriented meal = 0.23. Combining the tracer data with availability estimates for phylloquinone from the meals provides overall relative bioavailability values of convenience = 1.00, cosmopolitan = 0.46 and animal-oriented = 0.29. Stable isotopes provide a useful tool to investigate further the bioavailability of low doses of phylloquinone. Different meals can affect the absorption of free phylloquinone. The meal-based study design used in the present work provides an approach that reflects more closely the way foods are eaten in a free-living population.

A critical analysis of the prognostic performance of the 8th edition American Joint Committee on Cancer staging for metastatic cutaneous squamous cell carcinoma of the head and neck.

BACKGROUND: The 8th edition AJCC staging of cutaneous squamous cell carcinoma of the head and neck (cSCCHN) incorporated extranodal extension (ENE) for the first time. This study compared the prognostic performance of the 7th and 8th edition staging for cSCCHN with nodal metastases. METHODS: Retrospective analysis of 96 patients with metastatic cSCCHN, comparing the ability of staging systems to predict disease-specific and overall survival (OS) using the proportion of variation explained and Harrell's C-index. RESULTS: In AJCC8, the N classification was upstaged in 77% of patients due to the presence of ENE and 88% of patients were classified as TNM stage IV. AJCC8 was inferior to AJCC7 in predicting disease-specific survival for both N and TNM stages, and OS by TNM stage. CONCLUSIONS: The majority of patients with metastatic cSCCHN have ENE and are classified as TNM stage IV based on the 8th edition staging, resulting in poor prognostic performance.

Number of nodal metastases and prognosis in metastatic cutaneous squamous cell carcinoma of the head and neck.

BACKGROUND: Existing prognostic systems for metastatic cutaneous squamous cell carcinoma of the head and neck (cSCCHN) do not discriminate between the number of involved nodes beyond single versus multiple. This study aimed to determine if the number of metastatic lymph nodes is an independent prognostic factor in metastatic cSCCHN and whether it provides additional prognostic information to the American Joint Committee on Cancer (AJCC) staging. METHODS: We retrospectively analysed 101 patients undergoing curative intent treatment for metastatic cSCCHN to parotid and/or neck nodes by surgery +/- radiotherapy at Liverpool Hospital, Sydney, Australia. The impact of number of nodal metastases on disease-free survival (DFS) and risk of distant metastases was assessed using multivariate Cox regression. RESULTS: The mean number of nodal metastases was 2.5 (range 1-12). On multivariate analysis, increasing number of nodal metastases significantly predicted reduced DFS (hazard ratio 1.17; 95% confidence interval 1.05-1.30; P = 0.004), with a 17% increased risk of recurrence or death for each additional node. This remained significant in multivariate models adjusted for AJCC 8th edition nodal and TNM stages. Number of nodal metastases was also associated with risk of distant metastatic failure (hazard ratio 1.21; 95% confidence interval 1.05-1.39; P = 0.009). CONCLUSION: Increasing number of nodal metastases is associated with decreased DFS and increased risk of distant metastases in metastatic cSCCHN, with a cumulative risk increase with each additional node. It provides additional prognostic information to the AJCC staging, which may be improved by incorporating information on the number of nodal metastases beyond the current single versus multiple distinction.

Stage migration with the new American Joint Committee on Cancer (AJCC) staging system (8th edition) for differentiated thyroid cancer.

BACKGROUND: Tumor, node, and metastasis staging in thyroid carcinoma is important for assessing prognosis. However, patients with stage III or IV disease have an overall survival rate of 90%. The change to 55 years of age as the cutoff will create stage migration and many patients will be downstaged. METHODS: We reviewed our database of 3,650 patients to analyze the impact of the new American Joint Committee on Cancer staging system. There were 994 men (27%) and 2,656 women (73%). The median age was 46 years. Patients were staged using both 7th and 8th editions, with a cutoff of 55 years of age and new definitions of T3 and T4, and nodal staging. RESULTS: Of 3,650 patients, 1,057 (29%) were downstaged. There were 104 (10%) who went from stage IV to I, 109 (10%) who went from stage IV to stage II, and 68 (6%) who went to stage III. There were 218 (21%) who went from stage III to I, 347 (33%) who went from stage III to stage II, and 211 (20%) who went from stage II to I. The overall disease-specific and relapse-free survival was analyzed and showed better stratification with the new staging system. CONCLUSION: The new staging system reflects more appropriately the biology of thyroid cancer and will have significant impact on the management of thyroid cancer.

Previous External Beam Radiation Treatment Exposure Does Not Confer Worse Outcome for Patients with Differentiated Thyroid Cancer.

BACKGROUND: Radiation exposure, especially in childhood, is known to increase the risk for the development of thyroid cancer. However, the prognosis of patients with thyroid cancer with a history of radiation treatment exposure remains unclear. METHODS: One hundred and sixteen patients with a previous history of radiotherapy in the head and neck region were identified from an institutional database of 3664 patients with differentiated thyroid cancer treated between 1986 and 2010. Using the Kaplan-Meier method, disease-specific survival and recurrence-free survival were compared between patients with (RT; n = 116) and without (No RT; n = 3509) a prior history of radiation exposure. RESULTS: The median ages of the RT and No RT cohorts were 52 and 47 years. The median follow-up for both groups was 54 months. Patients who had a prior history of radiation treatment exposure were more likely to be male (38.8% vs. 26.9%; p = 0.005) and older than 45 years of age (67.2% vs. 53.9%; p = 0.005). Other patient, tumor, and treatment characteristics were similar between the groups. There was no difference in the five-year disease-specific survival of the RT and No RT patients (97.4% vs. 98.7%; p = 0.798). The five-year recurrence-free survival was also similar between the RT and No RT patients (97.8% vs. 94.9%; p = 0.371). CONCLUSION: The findings suggest that differentiated thyroid cancer patients with a history of prior radiation treatment exposure have similar outcomes to those with no history of head and neck radiation exposure.

Operative management of locally advanced, differentiated thyroid cancer.

BACKGROUND: The majority of differentiated thyroid cancer tends to present with limited locoregional disease, leading to excellent long-term survival after operative treatment. Even patients with advanced local disease may survive for long periods with appropriate treatment. The aim of this study is to present our institutional experience of the management of locally advanced differentiated thyroid cancer and to analyze factors predictive of outcome. METHODS: We reviewed our institutional database of 3,664 previously untreated patients with differentiated thyroid cancer operated between 1986 and 2010. A total of 153 patients had tumor extension beyond the thyroid capsule that invaded the subcutaneous soft tissues, recurrent laryngeal nerve, larynx, trachea, or esophagus. Details on extent of operation and adjuvant therapy were recorded. Disease-specific survival and locoregional recurrence-free probability were determined by the Kaplan-Meier method. Factors predictive of outcome were determined by multivariate analysis. RESULTS: The median age of the 153 patients with tumor extension beyond the thyroid capsule was 55 years (range 11-91 years). Eighty-nine patients (58.2%) were female. Twenty-three patients (15.0%) were staged as M1 at presentation, and 122 (79.7%) had pathologically involved lymph nodes. The most common site of extrathyroidal extension was the recurrent laryngeal nerve (51.0%) followed by the trachea (46.4%) and esophagus (39.2%). Sixty-three patients (41%) required resection of the recurrent laryngeal nerve due to tumor involvement. After surgery, 20 patients (13.0%) had gross residual disease (R2), 63 (41.2%) had a positive margin of resection (R1), and 70 (45.8%) had complete resection with negative margins (R0). With a median follow-up of 63.9 months, 5-year, disease-specific survival, when stratified by R0/R1/R2 resection, was 94.4%, 87.6%, and 67.9%, respectively (P = .030). The data do not demonstrate a statistical difference in survival between R0 versus R1 (P = .222). The 5-year distant recurrence-free probability for M0 patients was 90.8%, 90.3%, and 70.7% (P = .410). The locoregional recurrence-free probability was 85.8% for R0 patients and 85.5% for R1 patients (P = .593). CONCLUSION: With an appropriate operative strategy, patients with locally advanced thyroid cancer with an R0 or R1 resection have excellent survival outcome.

Pattern of neck recurrence after lateral neck dissection for cervical metastases in papillary thyroid cancer.

BACKGROUND: The objective of this study was to determine the rate and pattern of nodal recurrence in patients who underwent a therapeutic, lateral neck dissection (LND) for papillary thyroid cancer (PTC) with clinically evident cervical metastases and to determine if there was any correlation between the extent of initial dissection and the rate and pattern of neck recurrence. METHODS: A total of 3,664 patients with PTC treated between 1986 and 2010 at Memorial Sloan Kettering Cancer Center were identified from our institutional database. Tumor factors, patient demographics, extent of initial LND, and adjuvant therapy were recorded. Patterns of recurrent lateral neck metastases by level involvement were recorded and outcomes calculated using the Kaplan-Meier method. RESULTS: A total of 484 patients had an LND for cervical metastases; 364 (75%) had a comprehensive LND (CLND) and 120 (25%) had a selective neck dissection (SND). The median duration of follow-up was 63.5 months. As expected, patients with CLND had a greater number of nodes removed as well as a greater number of positive nodes (P < .001). There was no difference in overall lateral neck recurrence-free status (CLND 94.4% vs SND 89.4%, P = .158), but in the dissected neck, the ipsilateral lateral neck recurrence-free status was superior in the CLND patients (97.7% vs 89.4%, P < .001). CONCLUSION: Patients with clinically evident neck metastases from PTC managed by CLND have lesser rates of recurrence in the dissected neck compared with patients managed by SND. SND should only be done in highly selected cases with small volume disease.

Effectiveness of routine ultrasonographic surveillance of patients with low-risk papillary carcinoma of the thyroid.

BACKGROUND: Over the last 15 years, there has been a change in clinical practice for the detection of recurrence in all patients with papillary thyroid cancer (PTC). In the past, recurrence was detected by clinical examination supplemented with fine-needle aspiration cytology; however, routine neck ultrasonography (US) and measurements of serum thyroglobulin were introduced for follow-up in 2000 and are now used widely for recurrence surveillance. The aim of this study was to describe the effectiveness of this changing trend in the use of routine surveillance ultrasonography for the detection of recurrence in low-risk PTC at a single institution. METHODS: Patients undergoing total thyroidectomy for PTC between January 2000 and December 2010 were identified from an institutional database. Of these, 752 (43.1%) were categorized as low risk by the risk stratification of the American Thyroid Association and included for analysis. The number of US examinations per patient per year of follow-up was then determined. The number of recurrences and deaths from disease was recorded similarly. RESULTS: The median age was 48 years (range, 16-83) and the median follow-up was 34 months (range, 1-148). Between 2003 and 2012, the number of US examinations per patient-year of follow-up increased by 5.3-fold. Over the same time period, 3 structural recurrences (clinically evident neck masses or nodes) were detected with no disease-related deaths. CONCLUSION: At our institution, the annual rate of neck US examination increased by 5.3-fold per low-risk PTC patients between 2003 and 2012. Despite this increase, only 3 structural recurrences were detected. The routine use of neck US for surveillance of low-risk PTC patients requires review.