Samantha Tam

Mutation status among patients with sinonasal mucosal melanoma and its impact on survival

Background:Sinonasal mucosal melanoma (SNMM) comprises <1% of all melanomas and lacks well-characterised molecular markers. Our aim was to determine the frequencies of common mutations and examine their utility as molecular markers in a large series of primary SNMMs.Methods:SNMM patients seen at our institution from August 1991 through July 2016 were identified. Genomic DNA was extracted from 66 formalin-fixed paraffin-embedded tumours and screened for mutations by direct sequencing. We investigated the association of mutations with clinicopathological features and survival outcomes.Results:Overall, 41% (27 out of 66) of the SNMMs harboured mutations. BRAF and KIT mutations were identified in 8% (five patients) and 5% (three patients) of SNMMs, respectively, whereas NRAS mutations were detected in 30% (20 patients) of SNMMs. Mutation rates in these oncogenes were similar between SNMMs located in the paranasal sinuses and those in the nasal cavity (30% and 13%, respectively, P=0.09). In a multivariate analysis, patients with negative margins had significantly better overall survival (hazard ratio 5.43, 95% confidence interval 1.44–21.85, P=0.01) and disease-specific survival (hazard ratio 21.9, 95% confidence interval 3.71–180, P=0.0004). The mutation status of the tumours showed no association with survival outcomes.Conclusions:In SNNM, mutation status does not affect survival outcomes, but NRAS mutations are relatively frequent and could be targeted in this disease by MEK inhibitors.

Role of Adjuvant Treatment in Sinonasal Mucosal Melanoma

Purpose Sinonasal mucosal melanoma (SNMM) is a locally aggressive tumor. This study aimed to define the role of adjuvant treatment and its association with survival outcomes of SNMM. Methods This retrospective study investigated 152 patients with SNMM treated between 1991 and 2016 in MD Anderson Cancer Center. Patients were divided into the following treatment groups: surgery alone, surgery with postoperative radiotherapy (PORT), surgery with postoperative chemoradiation (POCRT), and induction chemotherapy followed by surgery and PORT. Overall survival (OS), disease‐specific survival, and relapse‐free survival were compared. Survival between the groups was compared using univariate and multivariate analyses. Results The median follow‐up was 28 months (range: 2‐220 months). Five‐year OS rates were 39, 42, 47, and 27% for the surgery only, PORT, POCRT, and neoadjuvant chemotherapy groups, respectively (log rank p = 0.73). Distant metastasis was the most common form of treatment failure and occurred in 59 (39%) patients. Five‐year distant metastasis rates were 51, 45, and 58% for patients treated with surgery alone, PORT, and POCRT, respectively (log rank p = 0.21) but unable to be estimated in the neoadjuvant chemotherapy group due to low OS rates. Multivariate analysis demonstrated tumor site (hazard ratio [HR] = 2.32, 95% confidence interval [CI] = 1.24‐4.15) and smoking status (HR = 1.77, 95% CI = 1.02‐3.1) to be significant prognostic factors for survival. Conclusion Tumor site and smoking status were significant prognosticators in SNMM. A high rate of distant metastatic disease suggests that further investigation into novel, systemic therapies is required to improve outcomes in this disease entity.

Adjuvant External Beam Radiotherapy in Locally Advanced Differentiated Thyroid Cancer

Importance As incidence of differentiated thyroid cancer rises, treatment paradigms have become increasingly defined. Despite this, locally advanced disease continues to be challenging to manage. Postoperative therapy in the form of radioactive iodine (RAI) is generally recommended, but the role of external beam radiation therapy (EBRT) is less well defined. Objective To investigate the role of EBRT in locally advanced differentiated thyroid cancer. Design, Setting, and Participants For this retrospective cohort study, patients treated surgically for T4a differentiated thyroid cancer at the University of Texas MD Anderson Cancer Center from January 2000 through December 2015 were recruited, and 88 patients were included for analysis. Exposures Adjuvant treatment with RAI alone or both RAI and EBRT. Main Outcomes and Measures Disease-free survival (DFS), defined as the time from primary surgery to locoregional or distant recurrence or death due to any cause. Kaplan-Meier survival analysis was completed. Univariate and multivariate analysis was completed with Cox proportional hazards model to determine predictors of DFS. Results A total of 88 patients (44 women [50%]; mean [SD] age, 58.2 [15.3] years) were included in the analysis. Median (range) follow-up was 117 (12-164) months. Forty-four patients (50%) underwent RAI alone and 44 patients (50%) underwent RAI with adjuvant EBRT. Patients undergoing RAI alone did not receive EBRT owing to invasion into the recurrent laryngeal nerve only (n = 14 [32%]) or invasion into the tracheal perichondrium and/or esophageal muscularis only (n = 18 [41%]). Five-year DFS was 43% in those undergoing RAI alone, compared with 57% in those undergoing RAI and EBRT (effect size = 14%; 95% CI, −7% to 33%). Patients undergoing RAI alone had an increased rate of locoregional failure (effect size = −32%; 95% CI, −47% to −16%), with those undergoing RAI treatment alone, for minimal tracheal perichondrium and/or esophageal muscularis invasion having worse locoregional control than those with recurrent laryngeal nerve invasion only (effect size = 49%; 95% CI, 20% to 71%). Age (adjusted hazard ratio [adjusted HR], 1.02/y; 95% CI, 1.00 to 1.05) and esophageal invasion (adjusted HR, 2.30; 95% CI, 1.16 to 4.60) were independent predictors of worse DFS. Conclusions and Relevance The addition of EBRT to RAI results in good disease control in locally advanced differentiated thyroid cancer, particularly in patients with tracheal or esophageal invasion treated with aggressive surgical resection. Increased age and presence of esophageal invasion were independent predictors of poor disease control.

Patterns of Treatment Failure in Patients with Sinonasal Mucosal Melanoma

BackgroundHead and neck mucosal melanoma is a locally aggressive tumor with a high recurrence rate. The paranasal sinuses and nasal cavity are the most common primary tumor sites.ObjectiveThe purpose of this retrospective study was to identify independent predictors of outcome in sinonasal mucosal melanoma (SNMM) and characterize the patterns of treatment failure.MethodsThis study included 198 patients with SNMM who had been treated at The University of Texas MD Anderson Cancer Center from 1 January 1991 through 31 December 2016. The survival outcomes included overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), local recurrence-free survival, and distant metastasis-free survival. A stepwise regression analysis was used to assess associations in the multivariate models.ResultsThe 5-year OS, DSS, and DFS rates were 38, 58, and 27%, respectively. Independent predictors of poor OS and DSS were the paranasal sinuses as the primary tumor site [hazard ratio (HR) 1.73, 95% confidence interval (CI) 1.11–2.66; and HR 2.12, 95% CI 1.21–3.74, respectively] and the presence of distant metastases at presentation (HR 4.53, 95% CI 2.24–7.83; and HR 3.6, 95% CI 1.12–7.1). Recurrence occurred in 96 patients (48%). The most common cause of treatment failure was distant metastasis in 69 of 198 patients (35%), followed by local [36 (18%)] and regional [22 (11%)] recurrence.ConclusionThe most common cause of treatment failure in SNMM is distant metastasis. The tumor site and the presence of metastatic disease at presentation were the only independent predictors of survival. These data can be used to inform quality improvement efforts and the counseling of high-risk SNMM patients.

Medical care cost of oropharyngeal cancer among Texas patients

Background: The incidence of oropharyngeal cancer is rising rapidly, with the majority of cases being attributable to human papillomavirus (HPV). Despite the availability of a vaccine, rates of HPV vaccination among Texas youth are low. The healthcare cost of oropharyngeal cancer in Texas is unknown. The aims of this study were to estimate the first 2-year cost of treating new cases of oropharyngeal cancer and determine the predictors of oropharyngeal cancer treatment cost in Texas. Methods: This study included a retrospective cohort of 467 Texas patients with commercial insurance claims data with oropharyngeal cancer diagnosed from 2011 to 2014 and a control group of 467 noncancer patients obtained with propensity score matching. Total healthcare cost during the first 2 years after the index date was measured. A generalized linear model was used to identify predictors of monthly cost during the 2 years after the index date. Results: The mean differential adjusted healthcare cost for oropharyngeal cancer cases was

Association of Lymph Node Density With Survival of Patients With Papillary Thyroid Cancer

139,749 in the first 2 years. The mean adjusted monthly cost in the first 2 years was

Age-Structured Population Modeling of HPV-related Cervical Cancer in Texas and US

6,693 for cases and

The epidemiology of oral human papillomavirus infection in healthy populations: A systematic review and meta-analysis

870 for controls. Age, comorbidity, mental health, prediagnostic healthcare cost, and time index were significant predictors of monthly cost. Conclusions: Medical care cost was about

Incompletely treated malignancies of the major salivary gland: Toward evidence-based care

140,000 in the first 2 years after diagnosis of oropharyngeal cancer among commercially insured patients in Texas. Impact: The cost estimates provide important parameters for development of decision-analytic models to inform decision makers about the potential value of initiatives for increasing the HPV immunization rate in the state. Cancer Epidemiol Biomarkers Prev; 26(9); 1443–9. ©2017 AACR.

Approaches to regional lymph node metastasis in patients with head and neck mucosal melanoma

Importance Lymph node metastases are common in papillary thyroid cancer (PTC), yet the impact of nodal metastases on survival remains unclear. Lymph node density (LND) is the ratio between the number of positive lymph nodes excised and the total number of excised lymph nodes. Lymph node density has been suggested as a prognostic factor in many types of cancer. Objective To evaluate the prognostic role of LND in PTC. Design, Setting, and Participants This cohort study reviewed medical records of patients with PTC who were treated at the University of Texas MD Anderson Cancer Center between January 1, 2000, and December 31, 2015. Survival and recurrence outcomes were calculated by using the Kaplan-Meier method. Significant variables on univariate analysis were subjected to a Cox proportional hazards regression multivariate model. Main Outcomes and Measures Primary study outcome was disease-specific survival (DSS); other measurements included overall survival (OS). Results The study cohort included data for 2542 patients (1801 [71%] male; median age, 48 years [range, 18-97 years]) with a median follow-up of 55 months (range, 4-192 months). The 10-year disease-specific survival rate was 98% for patients with LND of 0.19 or less, compared with 90% for those with LND greater than 0.19 (effect size, 8%; 95% CI, 4%-15%). The 10-year overall survival was 87% for patients with LND of 0.19 or less, compared with 79% for patients with LND greater than 0.19 (effect size, 8%; 95% CI, 3%-15%). Multivariable analysis revealed that LND greater than 0.19 was independently associated with an adverse DSS (hazard ratio [HR], 4.11; 95% CI, 2.11-8.97) and OS (HR, 1.96; 95% CI, 1.24-4.11). Subgroup analysis of patients with 18 or more lymph nodes analyzed revealed that LND greater than 0.19 remained a significant marker for DSS (HR, 2.94; 95% CI, 1.36-9.81) and OS (HR, 2.26; 95% CI, 1.12-5.34). Incorporating LND into the current American Joint Committee on Cancer staging system successfully stratified risk groups compared with the traditional TNM staging system. Conclusions and Relevance This single-institute study demonstrates the reproducibility of LND as a predictor of outcomes in PTC. Lymph node density can potentially assist in identifying patients with poorer survival who may benefit from more aggressive adjuvant therapy.