Distant Metastases in Patients with Carcinoma of the Major Salivary Glands.

BACKGROUND: This study aimed to show the incidence of distant metastases (DM) in salivary gland cancer as well as the types of histology most commonly associated with it and to identify factors predictive of DM. METHODS: The study identified 301 patients who underwent surgery for cancer of the major salivary glands at Memorial Sloan-Kettering Cancer center between 1985 and 2009. Clinical, tumor, and treatment characteristics were recorded. Tumors were categorized as low-, intermediate-, and high-risk pathology based on histologic subtype and grade. Factors predictive of distant recurrence-free probability (DRFP) were determined by uni- and multivariable analyses. RESULTS: The primary tumor was parotid in 266 patients (88 %), and 96 tumors (32 %) were clinical T3/T4. For 57 patients (18.9 %), DM developed with a 5-year DRFP of 72.7 %. The most common site of metastasis was the lung (50 %). The clinical predictors were male gender, cT4 stage, cN+ stage, and clinical overall stage. The multivariable analysis of clinical variables showed male gender (p = 0.018), cT4 stage (p < 0.001), and cN+ stage (p = 0.004) to be significant. The pathologic predictors were high-risk and high-grade pathology, vascular invasion, perineural invasion, positive margins, pT4 stage, pN+ stage, and overall stage. The multivariable analysis of pathologic variables showed high-grade pathology (p < 0.001), perineural invasion (p = 0.005), and pN+ stage (p = 0.002) to be significant. CONCLUSIONS: Distant metastases developed in approximately 20 % of the patients with salivary gland cancer. The most common site of metastases was the lung. The significant predictors of DM were cT4, cN+, male gender, high-grade pathology, perineural invasion, and positive nodal disease.

Treatment of the neck in carcinoma of the parotid gland.

PURPOSE: To review our experience in the treatment of the neck in patients with carcinoma of the parotid gland. METHODS: A total of 263 patients were stratified into 3 groups: no neck dissection (NoND), elective neck dissection (END), and therapeutic neck dissection (TND). Clinicopathological characteristics of END and TND versus NoND were compared by Chi square test. Pathological positivity of each neck level was quantified. Neck recurrence-free survival was determined by Kaplan-Meier statistics. RESULTS: There were 232 cN0 and 31 cN+ patients. Of the cN0 patients, 74 had END. All cN+ patients had TND. Of the END group, occult neck metastases were detected in 26 (35 %) patients. The percentage of positivity was 6.7, 28.3, 21.3, 10.8, and 6.7 % for levels I to V, respectively. Compared to the NoND group, the END group was more likely to be over 60 years old, to have cT3T4 disease, and to have disease with more aggressive histology. Of the TND group, pathological positivity was found in 87 %. The percentage of positivity was 51.6, 77, 73, 53, and 40 % for levels I to V, respectively. Patients who had disease-positive necks had a poorer neck recurrence-free survival of 84.8 %. CONCLUSIONS: In patients with cN0 disease, observation of the neck is safe in those who are under 60 years of age with clinical T1 or T2 tumors and who have low-grade histology. END should be carried out in patients with cT3T4 disease or high-grade histology and should involve levels II to IV at a minimum. Patients with cN+ disease commonly have all neck levels involved and therefore should be managed with comprehensive neck dissection.

Postoperative nomograms predictive of survival after surgical management of malignant tumors of the major salivary glands.

OBJECTIVES: The objective of this study was to create a nomogram predictive of survival in salivary gland cancer. METHODS: Clinical, tumor, and treatment characteristics were collected for 301 patients who underwent surgery for salivary gland cancer between 1985 and 2009 at Memorial Sloan Kettering Cancer Centre. Factors predictive of overall survival (OS) and cancer-specific survival (CSS) were determined by univariate analysis. Cox risk regression was used to model OS data. Competing risks regression was used for cancer-specific death. Deaths from other causes were treated as competing risks for cancer-specific death. Predictive nomograms for OS and CSS were then created using stepdown method to select predictors of outcome. RESULTS: The median age was 62 (range 9-89) years. There were 156 (52%) males and 145 (48%) females. Five variables predictive for OS (age, clinical T4 stage, histological grade, perineural invasion, and tumor dimension) were used to generate a parsimonious model, and a nomogram was created to predict 10-year survival probability. The concordance index (CI) for this nomogram was 0.809. Five variables predictive for CSS (histological grade, perineural invasion, clinical T4 stage, positive nodal status, and status of margins) were used to generate a second nomogram predicting CSS. This nomogram had a CI of 0.856. Both nomograms were validated internally by assessing discrimination and calibration. CONCLUSIONS: We have developed the first nomograms to predict prognosis in an individual patient with salivary gland cancer.

ThyroidEx: Development and Preliminary Validation of a Thyroid Surgery Expectations Measure.

OBJECTIVE: To address the lack of validated patient-reported outcome (PRO) instruments that define and quantify patient expectations in thyroid cancer surgery, we developed and initially validated ThyroidEx, a novel disease-specific PRO instrument. STUDY DESIGN: Survey study. SETTING: Single-institution tertiary care cancer center. METHODS: An expert panel drafted an initial set of thyroid cancer-specific concepts, which was used in semistructured concept elicitation interviews with patients with thyroid cancer 4 weeks before and 8 weeks after surgery. Candidate items were generated per patient responses and refined via cognitive interviewing and additional review by the expert panel. The draft ThyroidEx was then preoperatively administered to a separate cohort undergoing thyroid cancer surgery to establish a final item set and initial psychometric evidence. RESULTS: Prospective concept elicitation interviews generated 358 patient-elicited concepts (n = 15 patients). These were then placed into 70 unique subcategories from which 41 items were generated for cognitive interviews with 20 patients preoperatively and 28 postoperatively. After expert panel review, ThyroidEx included 18 items across 2 scales (Expectations and Concerns), with an additional item about beliefs. In the preoperative cohort in phase 2 (n = 67), internal consistency Cronbach's α values ranged from 0.81 to 0.89. Descriptive analysis showed significant differences between patients' concerns and expectations and clinicians' perceptions. CONCLUSION: Defining expectations represents an important modifier in the measurement of PROs. Preliminary validation of ThyroidEx revealed incongruent expectations between expert opinion and patients. Future development and implementation of ThyroidEx may affect preoperative consultation and the consent process.

False-positive FNA due to highly sensitive BRAF assay.

OBJECTIVE: False-positive BRAF analysis on fine-needle aspiration (FNA) has rarely been reported in the literature but may become more common with the advent of assays that can detect the BRAF V600E mutation in only 2% of otherwise wild-type thyroid cells. We present the case of an indeterminate BRAF-positive FNA that showed no evidence of cancer on final surgical pathology. METHODS: Case report and literature review. RESULTS: An 87-year-old female with an indeterminate 1.7-cm nodule but BRAF-positive cytology underwent thyroid lobectomy. Final pathology revealed a benign adenomatoid nodule. An area rich in tumor cells from the nodule was identified, labeled, and microdissected for molecular testing, which demonstrated only wild-type BRAF, at the analytical limit of the assay. CONCLUSION: Increasingly sensitive BRAF assays using dual-priming oligonucleotide-based multiplex polymerase chain reaction analysis can detect the BRAF V600E mutation when present in only 2% of a population of wild-type cells. This increases the risk of false-positive results, particularly in cases of indeterminate FNA. Clinicians must caution patients in these circumstances that BRAF molecular testing may not have a 100% positive predictive value.

A predictive nomogram for recurrence of carcinoma of the major salivary glands.

IMPORTANCE: This nomogram quantifies the risk of recurrence in patients with carcinoma of the major salivary glands. It may facilitate patient counseling on prognosis and may help guide management and posttreatment surveillance in these patients. OBJECTIVES: To identify factors predictive of recurrence after primary surgical treatment of carcinoma of the major salivary glands and create a nomogram that could be used to predict the risk of recurrence in an individual patient. DESIGN Retrospective case series. SETTING Single institution tertiary care cancer center. PATIENTS: After institutional review board approval, 301 patients with previously untreated malignant salivary gland tumors treated at our institution between the years 1985 and 2009 were identified. Among the 301 patients, the median age was 62 (range, 9-89) years and 156 (52%) were male. Patient, tumor, and treatment characteristics were recorded from a retrospective analysis of patient medical charts. MAIN OUTCOMES AND MEASURES: Overall mortality was calculated using the Kaplan-Meier method. Disease-specific mortality and recurrence risk were estimated with cumulative incidence rate. Factors predictive of recurrence were identified using univariate analysis. A Cox proportional hazard model was used to select predictors for the predictive nomogram. RESULTS: With a median follow-up of 43 (range, 1-264) months, the 5-year overall mortality, disease-specific mortality, and recurrence rate were 30%, 28%, and 33%, respectively. There were 70 recurrences (18 local, 12 regional, and 56 distant). The 5 variables most predictive for recurrence were age, grade, vascular and perineural invasion, and nodal metastasis. These variables were selected to generate the nomogram, which had a high concordance index of 0.85. CONCLUSIONS AND RELEVANCE: We introduce a clinically useful nomogram that quantifies the risk of recurrence in carcinomas of the major salivary gland. By quantifying risk for an individual patient, this would enable the clinician to give more accurate prognostic information to the patient resulting in better patient counseling.

Selective use of radioactive iodine in intermediate-risk papillary thyroid cancer.

OBJECTIVE To describe the outcomes with the selective use of radioactive iodine (RAI) in patients who are at intermediate risk of death from papillary thyroid cancer, focusing on 2 subgroups: patients older than 45 years with low-risk tumors and patients younger than 45 years with high-risk tumors. DESIGN Retrospective case review. SETTING Tertiary referral US cancer center. PATIENTS The study incluced 532 consecutive patients who were surgically treated between 1986 and 2005. INTERVENTIONS All patients underwent total thyroidectomy; 307 also received RAI. MAIN OUTCOME MEASURES Disease-specific survival (DSS) and recurrence-free survival (RFS). RESULTS Of 344 patients older than 45 years with low-risk tumors, 148 (43%) received RAI and 196 (57%) were selected not to receive RAI. The patients who were treated without RAI were more likely to be female and have pT1N0 disease. The 5-year DSS and RFS were 100% and 98%, respectively. The presence of nodal metastases predicted poorer 5-year RFS within this group (99% vs 91%; P = .004). Of 188 patients younger than 45 years with high-risk tumors, 159 (85%) received RAI, and only 29 (15%) were selected not to receive RAI. The 5-year DSS and RFS for these patients were 100% and 95%, respectively. The presence of nodal metastases predicted poorer 5-year RFS within this group (100% vs 86%; P = .02). CONCLUSION Our study shows that the subgroup of patients who are older than 45 years with tumors that are smaller than 4 cm in greatest dimension and confined to the thyroid gland and who do not have nodal metastases can safely be treated without RAI.