Long-term local control rates of patients with adenoid cystic carcinoma of the head and neck managed by surgery and postoperative radiation.

OBJECTIVES: To report long-term local control in patients with adenoid cystic cancer (ACC) of the head and neck managed by surgery and identify factors predictive for local failure. STUDY DESIGN: Single-institution retrospective cohort study. METHODS: Eighty-seven patients who had surgery for ACC between 1985 and 2009 were identified. Patient, tumor, and treatment characteristics were recorded. Local recurrence-free survival (LRFS) was recorded by the Kaplan-Meier method. Predictors of local control were identified. RESULTS: The median age was 54 years. Seventy-two (83%) patients had perineural invasion, 61 (70%) had close/positive margins, and 58 (67%) had pT 1T2. Fifty-nine (68%) patients had postoperative radiation therapy (PORT). With a median follow-up of 85 months, the 10-year LRFS was 78.7%. There were 14 local recurrences. On multivariable analysis, pathological tumor (T)3T4 stage and no PORT were independent predictors for local failure. Patients with no PORT had a 13-fold increased risk of local failure compared to patients treated with PORT (P = 0.003) after adjusting for stage. CONCLUSION: After adjusting for T stage, patients who do not get PORT are more likely to have local recurrence. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:2265-2269, 2017.

Patient Reflections on Decision Making for Laryngeal Cancer Treatment.

Objective To describe the reflections of patients treated for laryngeal cancer with regard to treatment-related decision making. Study Design Cross-sectional survey-based pilot study. Setting Single-institution tertiary care cancer center. Subjects/Methods Adults with laryngeal carcinoma were eligible to participate (N = 57; 46% treated surgically, 54% nonsurgically). Validated surveys measuring decisional conflict and regret explored patients' reflections on their preferences and priorities regarding treatment-related decision making for laryngeal cancer and how patient-reported functional outcomes, professional referral patterns, and desired provider input influenced these reflections. Results When considering the level of involvement of surgeons, radiation oncologists, and medical oncologists in their care, patients were more likely to believe that the specialist whom they saw first was the most important factor in deciding how to treat their cancer (Fisher's exact, ~χ2 = 16.2, df = 6, P = .02). Patients who were treated for laryngeal cancer who reported worse voice-related quality of life recalled more decisional conflict ( P = .01) and experienced more decisional regret ( P < .001). Of the patients for whom speech was a top priority prior to treatment, better voice-related quality of life overall scores were correlated with less decision regret about treatment decisions ( P < .02). Of the patients for whom eating and drinking were top priorities prior to treatment, better MD Anderson Dysphagia Inventory global scores were correlated with less decision regret about treatment decisions ( P < .002). Conclusion Patient priorities and attitudes, coupled with functional outcomes and professional referral patterns, influence how patients reflect on their choices regarding management of laryngeal cancer. Better understanding of these variables may assist in ensuring that patients' voices are integrated into individualized laryngeal cancer treatment planning.

Influence of bone invasion on outcomes after marginal mandibulectomy in squamous cell carcinoma of the oral cavity.

INTRODUCTION: Marginal mandibulectomy (MM) is indicated for oral cavity squamous cell carcinomas (OCSCC) that abut or minimally erode the mandible without gross invasion. Successful implementation of MM is predicated on accurate patient selection and appropriate adjuvant treatment based on well-known host and tumor characteristics. The incidence of microscopically diagnosed bone involvement in MM specimens and its implications on outcomes have however not been reported in large contemporary series. PURPOSE: To report the incidence of bone involvement and analyze its influence on oncologic outcomes in selected patients who underwent MM in treatment of OCSCC. METHOD: A retrospective cohort study was performed on a consecutive series of previously untreated patients requiring MM, at a tertiary care cancer center, between 1985 and 2012 (n = 326). The median age was 64 years and 59% were male. The majority of patients (67%) had a primary tumor of the floor of the mouth or lower alveolus, 80% were clinically staged T1-2, and 31% were clinically N+. Postoperative radiation (PORT) was used in 27% and chemoradiation (POCTRT) in 8% of patients who had microscopic bone invasion. The median follow up period was 55 months and endpoints of interest were local and regional recurrence free (LRFS and RRFS) and disease specific (DSS) survival. RESULTS: Microscopic bone invasion was present in 15% of patients (n = 49). Among these, cortical invasion was present in 32, medullary in 13, and it was not specified in 4. Eight patients had microscopic positive bone margins. Positive bone margins were associated with medullary bone involvement (p < 0.001), floor of mouth and buccal mucosa primary site (p = 0.03), and positive soft tissue margins (p = 0.06). LRFS and DSS were similar in patients without versus with bone invasion (62.8% vs 79.7% and 76.2% vs 66% respectively, p = NS). LRFS were similar in patients with microscopic positive versus negative bone margins, as long as postoperative adjuvant treatment was administered. CONCLUSION: Microscopic bone involvement does not adversely influence outcomes but medullary bone involvement does confer a higher risk of positive bone margins. MM and appropriate adjuvant treatment is an effective strategy for treatment of OCSCC in selected patients with primary tumors adherent to or in proximity to the mandible.

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.

Complete metastasectomy for renal cell carcinoma: Comparison of five solid organ sites.

BACKGROUND AND OBJECTIVES: Patients with metastatic RCC can undergo metastasectomy to improve survival time. Our goal was to provide and compare characteristics and oncological outcomes of RCC patients who underwent complete metastasectomy at a single organ site. METHODS: A total of 138 RCC patients were identified as undergoing complete metastasectomy at a single organ site including adrenal, lung, liver, pancreas, or thyroid. Competing risk regression analysis was used to assess RFS and CSS adjusting for several covariates. RESULTS: In this highly selected cohort, RFS and CSS was 27% and 84% at 5 years following metastasectomy, respectively. Univariate analysis revealed that removal of multiple tumors, younger age, and a shorter interval between nephrectomy and metastasis was associated with worse RFS. Larger tumors and sarcomatoid histology at nephrectomy was associated with worse CSS. We found no evidence that metastases at the time of RCC diagnosis influenced recurrence or survival. Tumor size, number of metastases resected, and time from nephrectomy to first recurrence was significantly different, but recurrence rates were not found to be significantly different, when compared across all organ sites. CONCLUSIONS: These findings inform clinical and surgical management of select RCC patients with isolated metastasis to one of several organ sites. J. Surg. Oncol. 2016;114:375-379. © 2016 Wiley Periodicals, Inc.

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.

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.

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.

Influence of extracapsular nodal spread extent on prognosis of oral squamous cell carcinoma.

BACKGROUND: An objective definition of clinically relevant extracapsular nodal spread (ECS) in head and neck squamous cell carcinoma (SCC) is unavailable. METHODS: Pathologic review of 245 pathologically positive oral cavity SCC neck dissection specimens was performed. The presence/absence of ECS, its extent (in millimeters), and multiple nodal and primary tumor risk factors were related to disease-specific survival (DSS) at a follow-up of 73 months. RESULTS: ECS was detected in 109 patients (44%). DSS was significantly better for patients without ECS than patients with ECS. Time-dependent receiver operator curve (ROC) analysis identified a prognostic cutoff for ECS extent at 1.7 mm. In multivariate analyses, DSS was significantly lower for patients with major ECS compared with patients with minor ECS, but not significantly different between patients with minor ECS and patients without ECS. CONCLUSION: ECS is clinically relevant in oral cavity SCC when it has extended more than 1.7 mm beyond the nodal capsule. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1192-E1199, 2016.

Impact of elective neck dissection on the outcome of oral squamous cell carcinomas arising in the maxillary alveolus and hard palate.

BACKGROUND: Whether elective lymph neck dissection (ELND) is associated with improved survival in oral squamous cell carcinomas (SCC) of the maxillary alveolus/hard palate is not known. METHODS: One hundred ninety-nine patients presenting de novo and receiving treatment for clinically node negative SCC of the maxillary alveolus/hard palate at 2 cancer centers between 1985 and 2011 were analyzed. RESULTS: Forty-two patients (21%) received ELND. Occult nodal metastases were present in 29% of the dissected necks. The ELND group had more T3 to T4 status tumors (62% vs 34%; p < .001) and positive-margin resections (59% vs 38%; p = .019). Patients undergoing ELND experienced lower rates of neck recurrence (6% vs 21%; p = .031), superior 5-year recurrence-free survival (68% vs 45%; p = .026), and overall survival (86% vs 62%; p = .043). ELND was associated with a 2-fold decrease in risk of recurrence in multivariable analysis. CONCLUSION: ELND was associated with lower rates of recurrence and improved survival in SCC of the maxillary alveolus/hard palate. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1688-E1694, 2016.

Defining a Valid Age Cutoff in Staging of Well-Differentiated Thyroid Cancer.

BACKGROUND: Age 45 years is used as a cutoff in the staging of well-differentiated thyroid cancer (WDTC) as it represents the median age of most datasets. The aim of this study was to determine a statistically optimized age threshold using a large dataset of patients treated at a comprehensive cancer center. METHODS: Overall, 1807 patients with a median follow-up of 109 months were included in the study. Recursive partitioning was used to determine which American Joint Committee on Cancer (AJCC) variables were most predictive of disease-specific death, and whether a different cutoff for age would be found. From the resulting tree, a new age cutoff was picked and patients were restaged using this new cutoff. RESULTS: The 10-year disease-specific survival (DSS) by Union for International Cancer Control (AJCC/UICC) stage was 99.6, 100, 96, and 81 % for stages I-IV, respectively. Using recursive partitioning, the presence of distant metastasis was the most powerful predictor of DSS. For M0 patients, age was the next most powerful predictor, with a cutoff of 56 years. For M1 patients, a cutoff at 54 years was most predictive. Having reviewed the analysis, age 55 years was selected as a more robust age cutoff than 45 years. The 10-year DSS by new stage (using age 55 years as the cutoff) was 99.2, 98, 100, and 74 % for stages I-IV, respectively. CONCLUSION: A change in age cutoff in the AJCC/UICC staging for WDTC to 55 years would improve the accuracy of the system and appropriately prevent low-risk patients being overstaged and overtreated.

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.

Nomograms for predicting survival and recurrence in patients with adenoid cystic carcinoma. An international collaborative study.

BACKGROUND: Due to the rarity of adenoid cystic carcinoma (ACC), information on outcome is based upon small retrospective case series. The aim of our study was to create a large multiinstitutional international dataset of patients with ACC in order to design predictive nomograms for outcome. METHODS: ACC patients managed at 10 international centers were identified. Patient, tumor, and treatment characteristics were recorded and an international collaborative dataset created. Multivariable competing risk models were then built to predict the 10 year recurrence free probability (RFP), distant recurrence free probability (DRFP), overall survival (OS) and cancer specific mortality (CSM). All predictors of interest were added in the starting full models before selection, including age, gender, tumor site, clinical T stage, perineural invasion, margin status, pathologic N-status, and M-status. Stepdown method was used in model selection to choose predictive variables. An external dataset of 99 patients from 2 other institutions was used to validate the nomograms. FINDINGS: Of 438 ACC patients, 27.2% (119/438) died from ACC and 38.8% (170/438) died of other causes. Median follow-up was 56 months (range 1-306). The nomogram for OS had 7 variables (age, gender, clinical T stage, tumor site, margin status, pathologic N-status and M-status) with a concordance index (CI) of 0.71. The nomogram for CSM had the same variables, except margin status, with a concordance index (CI) of 0.70. The nomogram for RFP had 7 variables (age, gender, clinical T stage, tumor site, margin status, pathologic N status and perineural invasion) (CI 0.66). The nomogram for DRFP had 6 variables (gender, clinical T stage, tumor site, pathologic N-status, perineural invasion and margin status) (CI 0.64). Concordance index for the external validation set were 0.76, 0.72, 0.67 and 0.70 respectively. INTERPRETATION: Using an international collaborative database we have created the first nomograms which estimate outcome in individual patients with ACC. These predictive nomograms will facilitate patient counseling in terms of prognosis and subsequent clinical follow-up. They will also identify high risk patients who may benefit from clinical trials on new targeted therapies for patients with ACC. FUNDING: None.

Individualized Risk Estimation for Postoperative Complications After Surgery for Oral Cavity Cancer.

IMPORTANCE: Postoperative complications after head and neck surgery carry the potential for significant morbidity. Estimating the risk of complications in an individual patient is challenging. OBJECTIVE: To develop a statistical tool capable of predicting an individual patient's risk of developing a major complication after surgery for oral cavity squamous cell carcinoma. DESIGN, SETTING, AND PARTICIPANTS: Retrospective case series derived from an institutional clinical oncologic database, augmented by medical record abstraction, at an academic tertiary care cancer center. Participants were 506 previously untreated adult patients with biopsy-proven oral cavity squamous cell carcinoma who underwent surgery between January 1, 2007, and December 31, 2012. MAIN OUTCOMES AND MEASURES: The primary end point was a major postoperative complication requiring invasive intervention (Clavien-Dindo classification grades III-V). Patients treated between January 1, 2007, and December 31, 2008 (354 of 506 [70.0%]) comprised the modeling cohort and were used to develop a nomogram to predict the risk of developing the primary end point. Univariable analysis and correlation analysis were used to prescreen 36 potential predictors for incorporation in the subsequent multivariable logistic regression analysis. The variables with the highest predictive value were identified with the step-down model reduction method and included in the nomogram. Patients treated between January 1, 2007, and December 31, 2008 (152 of 506 [30.0%]) were used to validate the nomogram. RESULTS: Clinical characteristics were similar between the 2 cohorts for most comparisons. Thirty-six patients in the modeling cohort (10.2%) and 16 patients in the validation cohort (10.5%) developed a major postoperative complication. The 6 preoperative variables with the highest individual predictive value were incorporated within the nomogram, including body mass index, comorbidity status, preoperative white blood cell count, preoperative hematocrit, planned neck dissection, and planned tracheotomy. The nomogram predicted a major complication with a validated concordance index of 0.79. Inclusion of surgical operative variables in the nomogram maintained predictive accuracy (concordance index, 0.77). CONCLUSIONS AND RELEVANCE: A statistical tool was developed that accurately estimates an individual patient's risk of developing a major complication after surgery for oral cavity squamous cell carcinoma.

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.

Survival from Differentiated Thyroid Cancer: What Has Age Got to Do with It?

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.

Microscopic Positive Margins in Differentiated Thyroid Cancer Is Not an Independent Predictor of Local Failure.

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.

Undetectable Thyroglobulin Levels in Poorly Differentiated Thyroid Carcinoma Patients Free of Macroscopic Disease After Initial Treatment: Are They Useful?

BACKGROUND: Predictive role of undetectable thyroglobulin (Tg) in patients with poorly differentiated thyroid carcinoma (PDTC) is unclear. Our goal was to report on Tg levels following total thyroidectomy and adjuvant RAI in PDTC patients and to correlate Tg levels with recurrence. METHODS: Forty patients with PDTC with no distant metastases at presentation (M0) and managed by total thyroidectomy and adjuvant RAI were identified from a database of 91 PDTC patients. Of these, 31 patients had Tg values recorded and formed the basis of our analysis. A nonstimulated Tg level <1 ng/ml was used as a cutoff point for undetectable Tg levels. Association of patient and tumor characteristics with Tg levels was examined by χ (2) test. Recurrence-free survival (RFS) stratified by postop Tg level was calculated by Kaplan-Meier method and compared by log-rank test. RESULTS: Twenty patients had undetectable Tg (<1 ng/ml) and 11 had detectable Tg (≥1 ng/ml; range 2-129 ng/ml) following surgery. After adjuvant RAI, 24 patients had undetectable Tg (<1 ng/ml) and 7 had detectable Tg (≥1 ng/ml; range 1-57 ng/ml). Patients with undetectable Tg were less likely to have pathologically positive margins compared to those with detectable Tg (33 vs. 72 % respectively; p = 0.03). Patients with undetectable Tg levels had better 5-year regional control and distant control than patients with detectable Tg level (5-year regional recurrence-free survival 96 vs. 69 %; p = 0.03; 5-year distant recurrence-free survival 96 vs. 46 %, p = 0.11). CONCLUSION: Postoperative thyroglobulin levels in subset of patients with PDTC appear to have predictive value for recurrence. Patients with undetectable Tg have a low rate of recurrence.