Cause-specific mortality in patients with mucoepidermoid carcinoma of the major salivary glands.

BACKGROUND: The objective of this study was to determine the incidence and cause of disease-specific death in patients with mucoepidermoid carcinoma (MEC) affecting the major salivary glands. METHODS: A total of 94 patients with MEC treated at Memorial Sloan-Kettering Cancer Center between 1985 and 2009 were identified from a preexisting database of 451 patients with major salivary gland cancer. Patient, tumor, and treatment characteristics were recorded from a retrospective analysis of patient charts. There were 49 males (52 %), and the median age was 57 years (range, 9-89 years). Of the 94 patients, 49 % had low, 22 % had intermediate, and 28 % had high-grade carcinoma. Overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) were calculated using the Kaplan-Meier method. Cause of death was determined by chart review. Predictors of DSS were identified by univariate analysis. RESULTS: With a median follow-up of 59 months (range, 1-257), the 5-year OS, DSS, and RFS for all patients were 76 %, 83 %, and 79 %, respectively. DSS was significantly poorer for high-grade MEC compared with low/intermediate-grade MEC (5-year DSS 37 % vs 100 %, P < .001). There were 9 disease-specific deaths. The cause of death in 7 patients was distant metastatic disease with locoregional recurrence accounting for death in only 2 patients. CONCLUSION: Outcome in patients with mucoepidermoid cancers of the major salivary glands is generally good. Mortality occurs almost exclusively in patients with high-grade tumors. The cause of death in the majority of patients is distant metastatic disease rather than locoregional recurrence.

Thyroid isthmusectomy for well-differentiated thyroid cancer.

BACKGROUND: The American Thyroid Association guidelines do not mention isthmusectomy as an appropriate procedure for thyroid cancer. Despite this, a small number of patients present with lesions isolated to the thyroid isthmus, which can be excised without exploring the trachyesophageal grooves or total thyroidectomy. This study was designed to analyze outcomes in patients treated with isthmusectomy for small well-differentiated thyroid cancer (WDTC) at our institution. METHODS: Nineteen patients with WDTC managed by isthmusectomy were identified from a database of 1,810 patients (1%) with WDTC managed by surgery in Memorial Sloan Kettering Cancer Center from 1986-2005. Demographic, surgical, pathological, and outcomes data were analyzed. RESULTS: Six patients were men and 13 were women. The median age was 46 (range, 28-83) years. All patients had a solitary nodule confined to the thyroid isthmus. The median size of lesion was 1 (range, 0.4-3) cm. Eighteen patients had a pathologically T1 lesion (pT1), and one patient had a pT2 lesion. Two patients had papillary carcinoma detected in perithyroid lymph nodes (pN1a). There were no complications of recurrent laryngeal nerve palsy or hypocalcaemia. With a median follow-up of 124 (range, 53-276) months, the 10-year disease-specific survival was 100% and 100% local and regional 10-year recurrence-free survival. CONCLUSIONS: Our results suggest that isthmusectomy alone may be sufficient treatment for selected patients with small WDTC limited to the isthmus. This procedure has the benefit of avoiding dissection of the recurrent laryngeal nerve and parathyroid glands, thus limiting postoperative complications.

Surgical management of metastases to the thyroid gland.

BACKGROUND: Metastases to the thyroid gland are uncommon, with rates reported between 0.02% and 1.4% of surgically resected thyroid specimens. Our goal was to present our experience with surgical management of metastases to the thyroid gland. METHODS: Twenty-one patients with metastatic disease to the thyroid were identified from a database of 1,992 patients with thyroid cancer who had surgery during 1986-2005. Patient, tumor, treatment, and outcome details were recorded by analysis of charts. The median age at time of surgery was 68 (range, 39-83) years; 12 were men and 9 were women. RESULTS: All patients were managed by surgery, including lobectomy in ten patients, total thyroidectomy in six, completion thyroidectomy in two, and subtotal thyroidectomy in one. In two patients, the thyroid lesion was found to be unresectable at the time of surgery. Histopathology revealed renal cell carcinoma in ten, malignant melanoma in three, gastrointestinal adenocarcinoma in three, breast cancer in one, sarcoma in one, and adenocarcinoma from an unknown primary site in three patients. Seventeen patients have died. The cause of death in all 17 was widespread metastatic disease from their respective primary tumors. The median survival from surgery to death or last follow-up was 26.5 (range, 2-114) months. CONCLUSIONS: In patients with metastases to the thyroid gland, local control of metastatic disease in the central compartment of the neck can be successfully achieved with minimal morbidity with surgical resection in selected patients.

Nomogram for selecting thyroid nodules for ultrasound-guided fine-needle aspiration biopsy based on a quantification of risk of malignancy.

BACKGROUND: Our aim through this study was to develop a statistical tool to quantify risk of malignancy in thyroid nodules based on clinical, biochemical, and ultrasound features, which could be used to select which nodules require ultrasound-guided fine-needle aspiration. METHODS: Clinical records, biochemical profiles, pathology reports, and ultrasound images were reviewed. Multivariate logistic regression was used to rank variables in their ability to predict malignancy. RESULTS: In all, 190 nodules were reviewed. The final diagnoses were papillary carcinoma in 105 patients (66%), other carcinoma in 8 patients (5%), and benign thyroid pathology in 45 patients (29%). After exclusions, 182 nodules remained for analysis on a per nodule basis. The 8 variables with highest predictive value were: age; thyroid-stimulating hormone; and ultrasound size, shape, echo texture, calcification, margin, and vascularity. The nomogram had a concordance index of 75%. CONCLUSION: We produced a nomogram able to accurately predict the need to perform ultrasound-guided fine-needle aspiration on a thyroid nodule based on biochemical, clinical, and ultrasound features.

Thyroid lobectomy for treatment of well differentiated intrathyroid malignancy.

BACKGROUND: There remains controversy over the type of surgery appropriate for T1T2N0 well differentiated thyroid cancers (WDTC). Current guidelines recommend total thyroidectomy for all but the smallest lesions, despite previous evidence from large institutions suggesting that lobectomy provides similar excellent results. The objective of this study was to report our experience of T1T2N0 WDTC managed by either thyroid lobectomy or total thyroidectomy. METHODS: Eight hundred eighty-nine patients with pT1T2 intrathyroid cancers treated surgically between 1986 and 2005 were identified from a database of 1810 patients with WDTC. Total thyroidectomy was carried out in 528 (59%) and thyroid lobectomy in 361 (41%) patients. Overall survival (OS), disease-specific survival (DSS) and recurrence-free survival (RFS) were determined by the Kaplan-Meier method. Factors predictive of outcome by univariate and multivariate analysis were determined using the log rank test and Cox proportional hazards method respectively. RESULTS: With a median follow-up of 99 months, the 10-yr OS, DSS, and RFS for all patients were 92%, 99%, and 98% respectively. Univariate analysis showed no significant difference in OS by extent of surgical resection. Multivariate analysis showed that age over 45 yr and male gender were independent predictors for poorer OS, whereas T stage and type of surgery were not. Comparison of the thyroid lobectomy group and the total thyroidectomy group showed no difference in local recurrence (0% for both) or regional recurrence (0% vs 0.8%, P = .96). CONCLUSION: Patients with pT1T2 N0 WDTC can be safely managed by thyroid lobectomy alone.

Undetectable thyroglobulin after total thyroidectomy in patients with low- and intermediate-risk papillary thyroid cancer--is there a need for radioactive iodine therapy?

BACKGROUND: The efficacy of radioactive iodine therapy (RAI) in patients who have an undetectable thyroglobulin (Tg) level after total thyroidectomy in well-differentiated papillary thyroid cancer (PTC) is questionable. The objectives of this study were to report the risk of recurrence in patients with PTC who had an undetectable Tg level after total thyroidectomy managed with postoperative RAI and without RAI. METHODS: After approval by the institutional review board, 751 consecutive patients who had total thyroidectomy for PTC as well as postoperative Tg measurement were identified from our institutional database of 1163 patients treated for well-differentiated thyroid carcinoma at Memorial Sloan Kettering Cancer Center between 1999 and 2005. Of these, 424 patients had an undetectable postoperative Tg (defined as a Tg <1 ng/mL) of whom 80 were classified as low, 218 intermediate, and 126 high risk via use of the GAMES (grade, age, distant metastasis, extrathyroidal extension, and size of the neoplasm) criteria. Patient, neoplasm, and treatment characteristics were recorded on the low- and intermediate-risk patients. Recurrence was defined as any structural abnormality on examination or imaging and confirmed by fine-needle aspiration biopsy. Disease-specific survival and recurrence-free survival (RFS) were calculated with the Kaplan-Meier method. Univariate analysis was carried out by the log rank test and multivariate analysis by Cox proportional hazards method. RESULTS: In the low-risk group (n = 80), 35 patients received postoperative RAI and 45 did not. Comparison of patient and tumor characteristics showed patients treated without RAI were more likely to have T1 tumors (82% vs 60%, P = .027). There were no disease-specific deaths in either group. There was 1 neck recurrence in the group that did not receive RAI. Patients managed without RAI had a similar RFS to patients managed with RAI (96% vs 100%, P = .337). In the intermediate risk group (n = 218), 135 were managed with RAI and 83 without. Comparison of patient and tumor characteristics showed patients managed without RAI were more likely to be older patients (≥ 45 years: 90% vs 39%, P < .0005) with smaller tumors (pT1T2: 97% vs 62%, P < .0005) and negative neck disease (N0: 56% vs 30%, P < .0005). There were no disease specific deaths in either group. There were 7 recurrences, of which 6 were in the RAI cohort (5 regional, 1 distant) and 1 in the non-RAI cohort (1 regional). Patients managed without RAI had a similar RFS to patients managed with RAI (97% vs 96%, P = .234). CONCLUSION: Select low- and intermediate-risk group patients who have undetectable Tg after total thyroidectomy for PTC can be managed safely without adjuvant RAI with no increase in risk of recurrence.

Changing trends in well differentiated thyroid carcinoma over eight decades.

INTRODUCTION: The incidence of well differentiated thyroid cancer (WDTC) is rising in the USA. The objective of this study is to present the changes in incidence, presentation, management and outcomes of WDTC within our institution over the past 8 decades. METHODS: 2797 patients managed between 1932 and 2005 at Memorial Sloan Kettering Cancer Center were identified from our institutional database. RESULTS: There has been an increase in the number of patients managed per decade. Although the median age was 45 years, patients managed post-1985 were more likely to be over 45 years (53% versus 44%, p < 0.001). The percentage of women increased from 68% to 72% (p = 0.026), and the percentage of papillary carcinomas also increased, from 78% to 92%, p < 0.001. An increase in early stage tumors was observed with pT1 lesions increasing from 19% to 48%. Patients in the latter cohort were less likely to have thyroid lobectomy (29% versus 72%, p < 0.001). There was a significant change in the use of RRA, with 8% of the early versus 44% of the latter group receiving post-operative RRA (p < 0.001). Since the introduction of risk group stratification disease specific survival (DSS) has not changed significantly. With a median follow up of 90 months, 10 year DSS rates were below 90% in the cohort managed prior to the 1970s, which rose to >95% thereafter (p < 0.001). CONCLUSIONS: Older patients with earlier stage disease present an increasing workload for surgical oncologists. Excellent outcomes remain unchanged despite increasingly aggressive surgical and medical management.

Surgical management of squamous cell carcinoma of the soft palate: factors predictive of outcome.

BACKGROUND: Squamous cell carcinoma of the soft palate (SCCSP) is uncommon. The aim of this study was to report our experience and identify factors predictive of outcome. METHODS: Between 1976 and 2005, 186 patients with SCCSP were treated with curative intent. In all, 150 patients had primary surgery, of whom 112 patients (75%) had cT1/T2 tumors and 103 patients (69%) had cN0 necks. Overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) were determined by the Kaplan-Meier method and factors predictive of outcome were identified. RESULTS: Five-year OS, DSS, and RFS for surgical patients were, respectively, 52%, 71%, and 56%. DSS for cT1T2N0 and cT1T2N+ were 79% and 56%, respectively. For OS and DSS, multivariate analysis showed cN classification was predictive of outcome. For RFS and distant RFS, margin status was a significant predictor, whereas the cT classification was a significant predictor for local RFS. CONCLUSIONS: Outcomes of patients with early-stage SCCSP managed by surgery were excellent. These patients may be suitable for transoral robotic or endoscopic surgical procedures.

The impact of distant metastases at presentation on prognosis in patients with differentiated carcinoma of the thyroid gland.

BACKGROUND: Distant metastases at presentation are rare in well-differentiated thyroid cancer (WDTC). The objective of this study was to report outcomes for patients presenting with distant metastases managed by thyroidectomy and radioactive iodine (RAI) therapy. METHODS: Fifty-two patients with distant metastases from thyroid cancer diagnosed before thyroid surgery (n=32) or on a postoperative RAI scan after thyroid surgery (n=20) were identified from a database of patients with WDTC treated between 1985 and 2005. The median age was 58 years (range 12-83 years), with a male-to-female ratio of 3:2. Forty-seven patients (90%) had total thyroidectomy and two (4%) had thyroid lobectomy, and three patients (6%) were found to be unresectable. Distant metastases were classified into pulmonary and extrapulmonary. Overall survival (OS), disease-specific survival (DSS), and locoregional recurrence-free survival were calculated by the Kaplan-Meier method. Factors predictive of the outcome were determined by univariate and multivariate analyses. RESULTS: Thirty-nine patients (75%) were diagnosed with pulmonary metastases alone and 13 (25%) with extrapulmonary metastases. The sites of extrapulmonary metastases were bone in nine, mediastinum in one, pyriform sinus in one and skin in one, and one patient had synchronous lung, bone, and intracerebral metastases. After thyroid surgery, 47 patients (90%) were treated with RAI alone, and 2 patients had external beam radiation in addition to RAI. With a median follow-up after surgery of 78.5 months, the 5-year OS and DSS were 65% and 68%, respectively. Twenty-nine patients (56%) died during follow-up, of whom 24 (46%) died of thyroid cancer. Six patients (12%) developed recurrent disease in the lateral neck, and three patients (6%) developed recurrence in the thyroid bed. Over 45 years, follicular pathology and extrapulmonary metastases were predictive of lower 5-year DSS (56% vs. 100%, p<0.001; 50% vs. 70%, p=0.004; and 46% vs. 75%, p=0.013, respectively). CONCLUSION: Approximately half of patients with WDTC presenting with distant metastases die of disease within 5 years of initial diagnosis despite thyroid surgery and RAI. Age over 45 years, extrapulmonary metastases, and follicular pathology were significant predictors of the poor outcome.

The impact of microscopic extrathyroid extension on outcome in patients with clinical T1 and T2 well-differentiated thyroid cancer.

OBJECTIVE: To report the impact of microscopic extrathyroid extension (ETE) on outcome in patients with cT1/cT2 well-differentiated thyroid cancer (WDTC), and to determine the effect of extent of surgery and adjuvant radioactive iodine (RAI) treatment on outcome in patients with microscopic ETE. PATIENTS AND METHODS: From an institutional database, we identified 984 patients (54%) who underwent surgery for cT1/T2N0 disease. Of these, 869 patients were pT1/T2 and 115 were upstaged to pT3 based on the finding of microscopic ETE. Disease-specific survival (DSS) and recurrence-free survival (RFS) were analyzed for each group using the Kaplan-Meier method. In the pT3 group, factors predictive of outcome were analyzed by univariate and multivariate analyses. RESULTS: There was no difference in the 10-year DSS (99% vs 100%; P = .733) or RFS (98% vs 95%; P = .188) on comparison of the pT1/pT2 and pT3 cohorts. Extent of surgery and administration of postoperative RAI were not significant for recurrence on univariate or multivariate analysis in the pT3 cohort. CONCLUSION: Outcomes in patients with cT1T2N0 WDTC are excellent and not affected by microscopic ETE. The extent of resection and administration of postoperative RAI in patients with microscopic ETE does not impact survival or recurrence.

Disease-related death in patients who were considered free of macroscopic disease after initial treatment of well-differentiated thyroid carcinoma.

BACKGROUND: Death from well-differentiated thyroid cancer (WDTC) is rare, and over the past century there has been a trend away from local recurrence as the primary cause of death. The objective of our study was to report the cause of death from thyroid cancer in patients with WDTC treated with curative intent with surgery ± adjuvant radioactive iodine. METHODS: An institutional database of 1811 patients with WDTC treated surgically for WDTC between 1986 and 2005 was analyzed and identified 165 (9.4%) who had died. Case records were studied to determine the cause of death in each patient. RESULTS: Of the 165 deaths, 17 (10%) patients were confirmed to have died of thyroid cancer and 6 (4%) died of an unknown cause but had thyroid cancer present at the time of last follow-up. The remaining 142 (86%) died from other causes and were considered free of thyroid cancer at their last follow-up. We therefore identified only 23 cause-specific deaths from the entire cohort (1.3%). Of the 17 patients known to have died of thyroid cancer, all had distant recurrence. Ninety-four percent had pulmonary metastases. Of these, 47% also had bony metastasis at the time of death. Two patients had recurrent disease in the neck at the time of death, but both also had distant disease. Of the six patients (4%) who died of unknown causes but had thyroid cancer at last follow-up, four (67%) had distant disease alone, one (17%) had local and regional recurrence, and one had local and distant recurrence at last follow-up. CONCLUSION: After successful resection of WDTC, we report a low disease-specific death rate (1.3%). In contrast to earlier reports, death caused by central compartment disease in this recent series is very rare, with metastatic disease accounting for almost all fatalities.