Frank L. Palmer

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.

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.

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.

The Results of Selective Use of Radioactive Iodine on Survival and on Recurrence in the Management of Papillary Thyroid Cancer, Based on Memorial Sloan-Kettering Cancer Center Risk Group Stratification

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.

Nomograms for preoperative prediction of prognosis in patients with oral cavity squamous cell carcinoma

This study sought to develop prognostic tools that will accurately predict overall and cancer‐related mortality and risk of recurrence in individual patients with oral cancer based on host and tumor characteristics. These tools would take into account numerous prognosticators beyond those covered by the traditional TNM (tumor–node–metastasis) staging system.

The impact of nodal status on outcome in older patients with papillary thyroid cancer

BACKGROUND The impact of clinically or radiologically detected nodal metastases on survival in patients with papillary thyroid cancer (PTC) is controversial but seems more important and relevant in older patients. The objective of this study was to determine the impact of clinically or radiologically detected nodal metastases on outcome in patients 45 years of age or older. METHODS Retrospective analysis of 834 patients 45 years or older who underwent operation for PTC between 1986 and 2005. RESULTS With a median follow up of 77 months, the 5 year disease-specific survival (DSS) and recurrence-free survival (RFS) were 99% and 94%, respectively. Patients with clinically N+ nodes with pathologic confirmation were stratified into pN0/Nx, pN1a, and pN1b, respectively. Five-year DSS was 100%, 100%, and 91% for pN0/Nx, pN1a, and pN1b disease; P < .001. Patients with pN1b disease had poorer distant RFS compared with pN0/Nx and pN1a patients (84%, 99%, and 99%; P < .001). The presence of pN1b disease was an independent predictor of worse DSS and distant RFS on multivariate analysis, conferring a 10-fold increased risk of distant metastases and death. All cause-specific deaths were due to distant metastases. CONCLUSION Older patients with PTC and N1b disease at presentation have poorer DSS compared with patients with pN0/Nx or N1a disease. The cause of death in these patients is due to distant metastases rather than locoregional recurrence.

An International Multi-Institutional Validation of Age 55 Years as a Cutoff for Risk Stratification in the AJCC/UICC Staging System for Well-Differentiated Thyroid Cancer

BACKGROUND Age is a critical factor in outcome for patients with well-differentiated thyroid cancer. Currently, age 45 years is used as a cutoff in staging, although there is increasing evidence to suggest this may be too low. The aim of this study was to assess the potential for changing the cut point for the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) staging system from 45 years to 55 years based on a combined international patient cohort supplied by individual institutions. METHODS A total of 9484 patients were included from 10 institutions. Tumor (T), nodes (N), and metastasis (M) data and age were provided for each patient. The group was stratified by AJCC/UICC stage using age 45 years and age 55 years as cutoffs. The Kaplan-Meier method was used to calculate outcomes for disease-specific survival (DSS). Concordance probability estimates (CPE) were calculated to compare the degree of concordance for each model. RESULTS Using age 45 years as a cutoff, 10-year DSS rates for stage I-IV were 99.7%, 97.3%, 96.6%, and 76.3%, respectively. Using age 55 years as a cutoff, 10-year DSS rates for stage I-IV were 99.5%, 94.7%, 94.1%, and 67.6%, respectively. The change resulted in 12% of patients being downstaged, and the downstaged group had a 10-year DSS of 97.6%. The change resulted in an increase in CPE from 0.90 to 0.92. CONCLUSIONS A change in the cutoff age in the current AJCC/UICC staging system from 45 years to 55 years would lead to a downstaging of 12% of patients, and would improve the statistical validity of the model. Such a change would be clinically relevant for thousands of patients worldwide by preventing overstaging of patients with low-risk disease while providing a more realistic estimate of prognosis for those who remain high risk.

International collaborative validation of intraneural invasion as a prognostic marker in adenoid cystic carcinoma of the head and neck.

The purpose of this study was to characterize the incidence, pattern of spread, and prognostic correlation of nerve invasion in patients with adenoid cystic carcinoma (ACC).

Factors Predicting Outcome in Malignant Minor Salivary Gland Tumors of the Oropharynx

OBJECTIVES to report our experience in the care of patients with minor salivary gland cancers occurring only in the oropharynx and to determine factors predictive of outcome. DESIGN Retrospective analysis. SETTING memorial Sloan-Kettering Cancer Center. PATIENTS sixty-seven patients with malignant minor salivary gland tumors were identified from a preexisting database of patients with cancers of the oropharynx between January 1985 and December 2005. MAIN OUTCOME MEASURES overall survival, disease-specific survival, and recurrence-free survival were calculated by the Kaplan-Meier method. Factors predictive of outcome were identified by univariate and multivariate analyses. RESULTS the most common histologic types were mucoepidermoid carcinoma in 26 patients (39%), adenoid cystic carcinoma in 16 (24%), adenocarcinoma in 16 (24%), and malignant mixed tumor in 7 (10%). The tumors were located in the base of the tongue in 41 patients (61%), soft palate in 20 (30%), and tonsil in 6 (9%). With a median follow-up time of 86 months (range, 12-249 months), overall outcomes at 5 and 10 years were overall survival, 80% and 53%; disease-specific survival, 87% and 67%; and recurrence-free survival, 69% and 60%, respectively. Tumor recurred in 20 patients (34%); 12 of these patients had locoregional failure and 15 developed distant metastases. Multivariate analyses showed that clinical T stage, anatomic subsite, and margin status were independent predictors for overall survival; T stage and margin status were independent predictors for locoregional recurrence-free survival. CONCLUSION clinical T stage, anatomic subsite, and margin status are independent predictors of outcome of patients with minor salivary gland cancers of the oropharynx.