Prevalence of pituitary hormone dysfunction following radiotherapy for sinonasal and nasopharyngeal malignancies.

BACKGROUND: There are limited studies and no surveillance protocols on pituitary dysfunction for adults who underwent anterior skull base radiation. METHODS: Cross-sectional study of 50 consecutive patients with sinonasal or nasopharyngeal cancer who underwent definitive radiotherapy. The mean radiation doses, prevalence of pituitary dysfunction, and associated factors were calculated. RESULTS: Pituitary hormone levels were abnormal in 23 (46%) patients, including 6 (12%) with symptomatic abnormalities requiring treatment. The most common hormonal abnormality was hyperprolactinemia (30%), central hypothyroidism (8%) and central hypogonadism (6%). Patients with abnormal pituitary hormone values received higher mean radiation doses to the pituitary gland (1143 cGy, P = 0.04), pituitary stalk (1129 cGy, P = 0.02), optic chiasm (1094 cGy, P = 0.01), and hypothalamus (900 cGy, P = 0.01). CONCLUSIONS: Nearly half of the patients had abnormal pituitary function, including over a tenth requiring treatment. There may be a dose-dependent association between hormonal dysfunction and radiation.

Neoadjuvant chemotherapy for locoregionally advanced squamous cell carcinoma of the paranasal sinuses.

BACKGROUND: Squamous cell carcinoma is the most common type of sinonasal malignancy. Despite improvements in surgical resection and adjuvant therapy, which are considered the standard of care, the outcome for patients with locoregionally advanced disease remains poor. The objective of this study was to investigate the role of induction chemotherapy in patients with locoregionally advanced sinonasal squamous cell carcinoma and to determine the oncologic outcomes in those patients. METHODS: The study included 123 consecutive patients with previously untreated, locoregionally advanced (stage III and IV) sinonasal squamous cell carcinoma who were treated with curative intent at The University of Texas MD Anderson Cancer Center between 1988 and 2017 with induction chemotherapy followed by definitive local therapy. Patient demographics, tumor staging, treatment details, and oncologic outcomes were reviewed. The outcomes of this study included response to induction chemotherapy, recurrence, organ preservation, and survival. RESULTS: The median follow-up was 32.6 months (range, 12.4-240 months). Of the 123 patients, 110 (89%) had T4 disease, and 13 (11%) had T3 disease. Lymph node metastasis at the time of presentation was observed in 36 patients (29.3%). The overall stage was stage IV in 111 patients (90.2%) and stage III in 12 patients (9.8%). The chemotherapy regimen consisted of the combination of a platinum and taxanes in most cases (109 patients; 88.6%), either as a doublet (41 patients) or in combination with a third agent, such as 5-fluorouracil (34 patients), ifosfamide (26 patients), or cetuximab (8 patients). After induction chemotherapy, 71 patients (57.8%) achieved at least a partial response, and 6 patients had a complete response. Subsequent treatment after induction chemotherapy was either: 1) definitive chemoradiation or radiation followed by surgical salvage for any residual disease, or 2) surgery followed by adjuvant radiation or chemoradiation. Overall, 54 patients (49.5%) underwent surgical resection. The 2-year overall and disease-free survival rates for the whole cohort were 61.4% and 67.9%, respectively. The rate of orbital preservation was 81.5%. The recurrence rate was 26.8% (33 patients), and distant metastases occurred in 8 patients (6.5%). Patients who had at least a partial response or stable disease had significantly better overall and disease-free survival than those who had progressive disease (P = .028 and P = .021, respectively). CONCLUSIONS: The current results indicate that a high proportion of patients with sinonasal squamous cell carcinoma achieved a favorable response to induction chemotherapy. The data suggest that response to induction chemotherapy is associated with an improved outcome and a good chance of organ preservation. The oncologic outcomes in this cohort with locally advanced (mostly T4) disease are better than those historically reported in the literature. Further study of induction chemotherapy in patients with advanced sinonasal squamous carcinoma is warranted.

Evaluating Perineural Spread to the Intratemporal Facial Nerve on Magnetic Resonance Imaging.

OBJECTIVES: To determine the sensitivity and specificity of magnetic resonance imaging (MRI) for the detection of perineural spread (PNS) along the intratemporal facial nerve (ITFN) in patients with head and neck cancers. STUDY DESIGN: Case series with chart review. SETTING: Tertiary care center. SUBJECTS AND METHODS: We included 58 patients with head and neck malignancies who underwent sacrifice of the ITFN between August 1, 2002, and November 30, 2015. Demographics, preoperative facial nerve function, prior oncologic treatment, and timing between MRI and surgery were recorded. Histopathology slides and preoperative MRI were reviewed retrospectively by a neuropathologist and a neuroradiologist, respectively, both blinded to clinical data. The mastoid segment of the facial nerve (referred to as the descending facial nerve [DFN]) and stylomastoid foramen (SMF) were evaluated separately. A grading system was devised when radiographically assessing PNS along the DFN. RESULTS: Histopathologic evidence of PNS was found in 21 patients (36.2%). The sensitivity and specificity of MRI in detecting PNS to the DFN were 72.7% and 87.8%, respectively. MRI showed higher sensitivity but slightly lower specificity when evaluating the SMF (80% and 82.8%, respectively). Prior oncologic treatment did not affect the false-positive rate ( P = .7084). Sensitivity was 100% when MRI was performed within 2 weeks of surgery and was 62.5% to 73.3% when the interval was greater than 2 weeks. This finding was not statistically significant (SMF, P = .7076; DFN, P = .4143). CONCLUSION: MRI shows fair to good sensitivity and good specificity when evaluating PNS to the ITFN.

Induction Chemotherapy Response as a Guide for Treatment Optimization in Sinonasal Undifferentiated Carcinoma.

PURPOSE: Multimodal therapy is a well-established approach for the treatment of sinonasal undifferentiated carcinoma (SNUC); however, the optimal sequence of the various treatments modalities is yet to be determined. This study aimed to assess the role of induction chemotherapy (IC) in guiding definitive therapy in patients with SNUC. METHODS: Ninety-five previously untreated patients diagnosed with SNUC and treated between 2001 and 2018 at The University of Texas MD Anderson Cancer Center were included in the analysis. Patients were treated with curative intent and received IC before definitive locoregional therapy. The primary end point was disease-specific survival (DSS). Secondary end points included overall and disease-free survival, disease recurrence, and organ preservation. RESULTS: A total of 95 treatment-naïve patients were included in the analysis. For the entire cohort, the 5-years DSS probability was 59% (95% CI, 53% to 66%). In patients who had partial or complete response to IC, the 5-year DSS probabilities were 81% (95% CI, 69% to 88%) after treatment with definitive concurrent chemoradiotherapy (CRT) after IC and 54% (95% CI, 44% to 61%) after definitive surgery and postoperative radiotherapy or CRT after IC (log-rank P = .001). In patients who did not experience at least a partial response to IC, the 5-year DSS probabilities were 0% (95% CI, 0% to 4%) in patients who were treated with concurrent CRT after IC and 39% (95% CI, 30% to 46%) in patients who were treated with surgery plus radiotherapy or CRT (adjusted hazard ratio of 5.68 [95% CI, 2.89 to 9.36]). CONCLUSION: In patients who achieve a favorable response to IC, definitive CRT results in improved survival compared with those who undergo definitive surgery. In patients who do not achieve a favorable response to IC, surgery when feasible seems to provide a better chance of disease control and improved survival.

Frequent PTEN loss and differential HER2/PI3K signaling pathway alterations in salivary duct carcinoma: Implications for targeted therapy.

BACKGROUND: Patients with advanced primary and recurrent salivary duct carcinoma (SDC), a rare and lethal malignancy, have limited therapeutic options. Novel small-molecule agents aimed at targeting critical signaling associated with SDC tumorigenesis may lead to new therapeutic options for patients with these tumors. The human epidermal growth factor receptor 2 (HER2)/phosphoinositide 3-kinase (PI3K) axis, an important oncogenic pathway, has been targeted for therapy in several solid tumors. Currently, little is known about the role and clinical implications of alterations of the HER2/PI3K pathway in patients with SDC. METHODS: The authors investigated the clinicopathologic features, genetic alterations, and expression of key members of the HER2/PI3K pathway in 43 primary tumors and conducted in vitro functional and targeted drug-response analyses on cell lines derived from salivary epithelial carcinomas. RESULTS: In primary tumors, loss of phosphatase and tensin homolog (PTEN) expression was identified in 22 of 43 tumors (51%), overexpression of HER2 was observed in 12 of 43 tumors (28%), and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations were identified in 12 of 43 tumors (28%). Phosphorylated protein kinase B (p-AKT) was highly expressed in most tumors. Most tumors (70%) displayed mutually exclusive alterations of PI3K members, whereas 8 tumors (19%) had 2 or more concurrent abnormalities. In vitro studies demonstrated a direct association between PTEN loss and PI3K pathway activation and evidence of response to combined PI3Kα and PI3Kß and/or pan-PI3K inhibitors. CONCLUSIONS: The current analyses reveal frequent PTEN loss and mutually exclusive alterations of key PI3K pathway members in SDC and demonstrate in vitro evidence of a response to pan-PI3K inhibitors. These results provide a framework for a biomarker-based substratification of patients with SDC in future targeted therapy. Cancer 2018;124:3523-32. © 2018 American Cancer Society.

Basal cell carcinoma of the temporal bone and external auditory canal.

OBJECTIVES/HYPOTHESIS: To review the presenting features, treatment, and outcomes for patients with basal cell carcinoma (BCC) involving the temporal bone or external auditory canal (EAC). STUDY DESIGN: Retrospective case series. METHODS: Presenting characteristics, treatment strategies, and outcomes for patients with BCC involving the temporal bone or EAC were reviewed. Main outcome measures included rates of overall and disease-free survival at 5 years. RESULTS: Forty-two patients met the inclusion criteria (mean age, 67 years). The most common presenting symptoms were hearing loss (15 patients, 36%) and otorrhea (11 patients, 26%). The 5-year overall survival rate was 78%, and the 5-year disease-free survival rate was 77%. Patients who had undergone surgery elsewhere and presented with facial weakness had significantly worse overall survival (P = .004). Ten patients (24%) underwent sacrifice of at least a portion of the facial nerve at the time of their initial procedure at our institution. Two patients (5%) developed regional nodal disease. There was a trend toward better disease-free survival for patients who received adjuvant radiation therapy after surgery at our institution (P = .06). CONCLUSIONS: BCC originating from or extending to the temporal bone can exhibit a wide range of behavior, ranging from superficial lesions readily managed with surgery to extensive locally invasive tumors with propensity for recurrence, treated with multimodality therapy. BCC may be associated with better prognosis than other temporal bone malignancies. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:1425-1430, 2018.

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

BACKGROUND: Mucosal melanomas in the head and neck region are most often located in the nasal cavity and paranasal sinuses. To the authors' knowledge, the prognostic effects of lymph node metastasis in patients with sinonasal mucosal melanoma (SNMM) have not been established. Therefore, the objective of the current study was to determine the effects of lymph node metastasis on survival. METHODS: The current study included 198 patients with SNMM who had been treated between 1985 and 2016 at The University of Texas MD Anderson Cancer Center in Houston. Patients' clinical and pathologic lymph node statuses were evaluated and characterized. A multivariate analysis was used to assess the associations between regional spread and survival outcomes. RESULTS: Therapeutic neck dissection was performed in 23 patients with SNMM (11.6%). Regional disease recurrence occurred in 7 of the patients who had lymph node metastasis at the time of presentation (30.4%) and in 30 of those who had N0 disease at the time of presentation (17.1%) (P = .15). Metastasis to the contralateral lymph nodes was present in 7 patients (3.5%). The 5-year disease-specific survival rate was 66% in patients with lymph node spread compared with 45% in patients with N0 status (P = .04, log-rank test). A multivariate analysis demonstrated that distant metastasis was the only variable found to be independently associated with both overall survival (hazard ratio, 2.96; 95% confidence interval, 1.54-6.95 [P = .01]) and disease-specific survival (hazard ratio, 3.32; 95% confidence interval, 1.79-7.14 [P = 0.01]). CONCLUSIONS: The results of the current study demonstrated that lymph node status in patients with SNMM was not a significant predictor of outcome. This finding, together with the low incidence of lymph node metastases in patients with SNMM, suggests that elective treatment of the neck should be highly selective in this patient population. Cancer 2018;124:514-20. © 2017 American Cancer Society.

Long-Term Outcomes of Lateral Neck Dissection in Patients with Recurrent or Persistent Well-Differentiated Thyroid Cancer.

BACKGROUND: Well-differentiated thyroid carcinoma (WDTC) has a high predilection for regional metastatic spread. Rates for WDTC lateral neck recurrence are reported to be as high as 24% in patients after initial thyroidectomy, lateral neck surgery, and adjuvant radioactive (RAI) iodine treatment. The objective of the study was to evaluate the efficacy, safety, and long-term outcome of comprehensive lateral neck dissection (LND) of levels II-V for recurrent or persistent WDTC in a tertiary referral center. METHODS: This study retrospectively analyzed the standardized approach of LND for recurrent WDTC in the lateral neck compartment. Survival was analyzed by Cox regression analysis. RESULTS: Three hundred and seven patients underwent 429 LND for cytopathology-confirmed lateral neck recurrent WDTC at the University of Texas MD Anderson Cancer Center between 1994 and 2012. The vast majority (90%) of patients were originally treated elsewhere. Multilevel lateral neck dissection had been originally performed in 80% of patients, with 17% having undergone at least two previous operations. Two hundred and sixty-seven (87%) patients had previous RAI. The most common levels of recurrence were levels III and IV (33% and 33%, respectively). Postoperative complications were seen in 7% of patients. Median follow-up was 7.2 years. In-field lateral neck control was 96% at 10 years. Overall lateral neck regional control, overall survival (OS), and disease-specific survival (DSS) at 10 years was 88%, 78%, and 91%, respectively. When stratifying by age (<24 years, 24-50 years, and >50 years), OS and DSS was significantly better in patients <50 years (OS: p < 0.001; DSS: p < 0.001). However, there was worse overall lateral neck control in the younger group (<24 years; p = 0.04). Regional recurrence after salvage LND occurred within a median time interval of 20.0 months (2.9-121.3 months), of which 2% (8/429) developed in-field lateral neck recurrences. Of those with any lateral neck recurrence after salvage LND, 24/30 (80%) patients successfully underwent another LND, resulting in an ultimate 98% lateral neck regional control rate. CONCLUSIONS: Expert comprehensive LND of levels II-V is associated with few perioperative complications and results in very high in-field regional control rate and ultimate lateral neck control in recurrent/persistent WDTC.

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.

Influence of timing, radiation, and reconstruction on complications and speech outcomes with tracheoesophageal puncture.

BACKGROUND: We evaluated the impact of radiation, reconstruction, and timing of tracheoesophageal puncture (TEP) on complications and speech outcomes. METHODS: Retrospective review identified 145 patients who underwent TEP between 2003 and 2007. RESULTS: Ninety-nine patients (68%) had primary and 46 (32%) had secondary TEP, with complications occurring in 65% and 61%, respectively (p = .96). Twenty-nine patients (20%) had major complications (18 primary and 11 secondary; p = .42). Ninety-four patients (65%) had pre-TEP radiation, 39 (27%) post-TEP radiation, and 12 (8%) no radiation. With patients grouped by TEP timing and radiation history, there was no difference in complications, fluency, or TEP use. With mean 4.7-year follow-up, 82% primary and 85% secondary used TEP for primary communication (p = .66). Free-flap patients used TEP more commonly for primary communication after secondary versus primary TEP (90% vs 50%; p = .02). CONCLUSION: Primary and secondary tracheoesophageal speakers experience similar high rates of complications. Extent of pharyngeal reconstruction, rather than radiation, may be more important in selection of TEP timing. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1765-1771, 2016.

Complications of tympanostomy tubes in head and neck cancer patients.

PURPOSE: To assess myringotomy plus tympanostomy tube (MTT) complication rates in head and neck cancer (HNC) patients with otitis media (OM). MATERIALS AND METHODS: We performed a retrospective review of 182 HNC patients with OM treated between January 2000 and October 2007 for demographic data and data about MTT-related complications, tumor type and outcomes following MTT. RESULTS: We identified OM in 35 nasopharyngeal (NP), 34 paranasal sinus (PNS), and 24 larynx cancer patient ears; of these, 29 (83%), 31 (91%), and 22 (92%), respectively, were treated with MTT. Of the 29 NP cancer patient ears treated with MTT, 13 (45%) received MTT before radiotherapy; complications included otorrhea in 11 ears (38%), otorrhea with perforation in 3 ears (10%), and cholesteatoma in 1 ear (3%). Of the 31 PNS cancer patient ears treated with MTT, 17 (55%) received MTT before radiotherapy; complications included otorrhea in 10 ears (32%) and otorrhea with perforation in 3 ears (10%). All 22 laryngeal cancer patient ears were treated with MTT before radiotherapy; 5 ears (23%) developed chronic otorrhea. Patients with pre-existing eustachian tube dysfunction had significantly higher rates of tympanostomy tube otorrhea (p=.009). CONCLUSIONS: The complication rates of OM in the setting of NP or PNS cancer were not significantly different regardless of intervention timing in relation to radiotherapy. Laryngectomy patients had a high rate of tympanostomy sequelae after radiotherapy. MTT for OM has high complication rates in HNC patients.

Association of TERT Promoter Mutation, But Not BRAF Mutation, With Increased Mortality in PTC.

CONTEXT: Papillary thyroid carcinoma (PTC) carrying the BRAF mutation has been reported to be associated with high recurrence and potentially increased mortality. PTC carrying the TERT promoter mutation has been associated with older age, recurrence, and aggressive disease. OBJECTIVE: The objective of this study was to determine the association of BRAF and TERT promoter gene alterations with recurrence and survival in a high-risk population. DESIGN: Genomic DNA was analyzed for the BRAF mutation from 256 persistent/recurrent PTC (p/rPTC; 202 new, 54 previously reported) and for the TERT promoter mutation and polymorphism (242 p/rPTC). Two-tailed Fisher exact tests or the Pearson χ(2) test were performed for the associations between mutations and other variables. Overall and disease-free survivals were compared by log rank tests on Kaplan-Meier plots and by Cox regression analysis. TERT promoter constructs were tested in PTC cell lines to determine their activities in these cells. RESULTS: BRAF V600E mutation was identified in 235 of 256 (91.8%), TERT promoter mutation at -124 was detected in 77 of 242 (31.8%), and TERT promoter polymorphism at -245 was found in 113 of 242 (46.7%) p/rPTC patients. A significant difference in survival was found in p/rPTC patients with the TERT promoter mutation, which also displayed increased activity in vitro as compared to the nonmutated promoter sequence. No association was noted between the BRAF mutation or TERT promoter polymorphism and recurrence or survival. A drawback of our study could be the limited number of patients with nonmutated BRAF (21 of 256 [8.2%]). CONCLUSIONS: Mutation in the TERT promoter, but not in BRAF, was associated with decreased survival in 19 (24.7%) p/rPTC patients who died of disease and in 38 (49.4%) p/rPTC patients who died at last contact. The presence or absence of the BRAF mutation and TERT promoter polymorphism, however, was not significantly correlated with survival.

Sialendoscopy for Patients with Radioiodine-Induced Sialadenitis and Xerostomia.

BACKGROUND: We examined outcomes in patients treated for radioactive iodine-induced sialadenitis (RAIS) and xerostomia with sialendoscopy. METHODS: Data was prospectively collected for all patients undergoing sialendoscopy for RAIS from a single institution. Interventional details and intraoperative findings were recorded. Qualitative data were obtained through patient examination, telephone interviews, and use of a standard quality of life questionnaire, Xerostomia Questionnaire. Quantitative data were obtained from patients who underwent sialometry. RESULTS: Twenty-six patients (24 women and 2 men; median age, 43 years; age range, 19-57 years) underwent interventional sialendoscopy after conservative management of symptoms proved unsuccessful. Sialadenitis was present in 25 patients and xerostomia in 22 patients. Mucus plugging in the duct of the gland was the most common finding (22 patients) followed by stenosis (18 patients), inflammation (eight patients), and erythema (eight patients). Median follow-up time was 23.4±12.1 months. Sixteen patients (64%) reported complete resolution; seven (28%), partial resolution; one (4%), no change in symptoms; and one (4%), regression in RAIS-related symptoms. Patients subjectively noted the following regarding their xerostomia symptoms: seven (31.8%) had complete resolution; 10 (45.5%), partial resolution; four (18.2%), no change; and one (4.5%), regression. Statistical analysis of the available sialometry data revealed a statistically significant difference in saliva production at 6 months following sialendoscopy for unstimulated saliva production (p=0.028). CONCLUSION: Sialendoscopy is an effective treatment option for the management of RAIS and xerostomia refractory to conservative therapy and medical management. Patients in our cohort report durable improvement in symptoms after intervention.

An audit and feedback system for effective quality improvement in head and neck surgery: Can we become better surgeons?

BACKGROUND: An evaluation system was established for measuring physician performance. This study was designed to determine whether an initial evaluation with surgeon feedback improved subsequent performance. METHODS: After an evaluation of an initial cohort of procedures (2004-2008), surgeons were given risk-adjusted individual feedback. Procedures in a postfeedback cohort (2009-2010) were then assessed. Both groups were further stratified into high-acuity procedure (HAP) and low-acuity procedure (LAP) groups. Negative performance measures included the length of the perioperative stay (2 days or longer for LAPs and 11 days or longer for HAPs); perioperative blood transfusions; a return to the operating room within 7 days; and readmission, surgical site infections, and mortality within 30 days. RESULTS: There were 2618 procedures in the initial cohort and 1389 procedures in the postfeedback cohort. Factors affecting performance included the surgeon, the procedure's acuity, and patient comorbidities. There were no significant differences in the proportions of LAPs and HAPs or in the prevalence of patient comorbidities between the 2 assessment periods. The mean length of stay significantly decreased for LAPs from 2.1 to 1.5 days (P = .005) and for HAPs from 10.5 to 7 days (P = .003). The incidence of 1 or more negative performance indicators decreased significantly for LAPs from 39.1% to 28.6% (P < .001) and trended downward for HAPs from 60.9% to 53.5% (P = .081). CONCLUSIONS: Periodic assessments of performance and outcomes are essential for continual quality improvement. Significant decreases in the length of stay and negative performance indicators were seen after feedback. Therefore, an audit and feedback system may be an effective means of improving quality of care and reducing practice variability within a surgical department.

Risk Factors and Prognosis for Myoepithelial Carcinoma of the Major Salivary Glands.

BACKGROUND: The clinical behavior and treatment outcomes of salivary gland myoepithelial carcinoma have yet to be clearly defined. The current study investigated risk factors and prognoses for this tumor. METHODS: A retrospective review of the medical records for 32 patients with myoepithelial carcinoma of the major salivary glands was performed. Their clinical parameters were assessed to identify correlations with local-regional recurrence, distant metastasis, and survival. RESULTS: The 5-year survival rate was 71 %. Of the reviewed patients, 41 % had local-regional recurrences, and 22 % had distant metastases. Age of 60 years or younger was a predictive factor for distant metastasis. Patients with neck lymph nodes clinically positive for carcinoma had shorter overall survival durations than those with nodes negative for carcinoma. CONCLUSIONS: Myoepithelial carcinoma of the major salivary glands is characterized by a high incidence of local-regional recurrence and distant metastasis. Adjuvant therapy is indicated for selected patients with high-risk disease.

Radiation-associated malignancies of the ear canal and temporal bone.

OBJECTIVES/HYPOTHESIS: To examine our experience with surgically treated radiation-associated malignancy (RAM) of the temporal bone. STUDY DESIGN: Retrospective chart review. METHODS: Thirteen patients treated surgically for temporal-bone RAM during 1999 to 2012 were identified. Demographics, symptoms at presentation with RAM, interval between initial radiotherapy and diagnosis of RAM, pathologic features of RAM, treatment, and recurrence and survival were obtained from medical records. RESULTS: Ten patients had squamous cell carcinoma; three had sarcoma. The mean period between completion of radiotherapy and diagnosis of RAM was 13.38 years (range, 4.5-33.3 years). Three-year overall and disease-free survival rates were 59.8% and 42.3%, respectively. Seven patients (54%) had RAM limited to the external auditory canal (LEAC); six had RAM extending beyond it (EEAC). The mean age was 66.5 years for LEAC patients versus 41.1 years for EEAC patients (P = .0161). Compared to patients with EEAC disease, patients with LEAC disease were more likely to have negative margins (100% vs. 33%; P = .021) and less likely to have postoperative adjuvant therapy (0% vs. 67%; P = .0209). The 3-year disease-specific survival was significantly better for patients with LEAC disease versus EEAC (log rank P = .023). CONCLUSIONS: To our knowledge, this is the largest reported series of surgically treated RAM of the ear canal or temporal bone. This study highlights the need for vigilance for RAM in patients treated with head and neck radiation. LEVEL OF EVIDENCE: 4. Laryngoscope, 125:1198-1204, 2015.

Recurrence of cutaneous melanoma of the head and neck after negative sentinel lymph node biopsy.

BACKGROUND: Sentinel lymph node biopsy remains controversial for cutaneous melanoma of the head and neck (CMHN). Incidence and factors associated with recurrence after negative sentinel lymph node biopsy have not been well delineated. METHODS: Characteristics of 204 patients with head and neck melanoma who had a negative sentinel lymph node biopsy were studied. Main outcomes were overall survival and disease-free survival. RESULTS: Recurrence developed in 45 patients (22%) with a median time to recurrence of 20.1 months. Five-year overall survival was 91.8% for patients without recurrence and 57.0% for those with recurrence. The overall regional recurrence rate was 8.8% (n = 18) and was associated with Breslow thickness >2 mm and scalp location of the primary tumor. The false omission rate was 3.4%. CONCLUSION: For CMHN, regional recurrence after negative sentinel lymph node biopsy occurs at acceptably low rates relative to other sites, although it is associated with adverse survival.

Sinonasal adenocarcinoma: a 16-year experience at a single institution.

BACKGROUND: Adenocarcinoma is a rare tumor of the sinonasal tract. The purpose of this study was to characterize a single institution's experience with this malignancy. METHODS: Retrospective review was performed of patients with adenocarcinoma of the sinonasal tract from 1993 to 2009. Demographic data, disease presentation, treatment, and survival rates were collected and evaluated. RESULTS: We identified 66 patients with sinonasal adenocarcinoma; 48 were men and 18 women. Average age at time of diagnosis was 57.1 years (range, 20-88 years), and median follow-up was 55.3 months (range, 1-238 months). The ethmoid sinus (38%) and nasal cavity (36%) were the most common sites of origin. Nasal obstruction (36%), epistaxis (30%), and nasal discharge (21%) were the most common presenting symptoms. Fifty-one percent of patients presented with T1 or T2 tumors. Surgery was the primary form of treatment in 81% of patients. Twenty-six percent of surgical patients underwent an endoscopic tumor resection. Adjuvant radiation was utilized in 50% of patients and chemotherapy in 10%. Recurrence was seen in 24 patients (37%): 29% recurred locally and 7.6% recurred distantly. The overall 5-year survival was 65.9%. Survival was decreased significantly in patients with T4 tumors (p < .05), high-grade histology (p < .05), and sphenoid sinus involvement (p < .05). Survival was not affected by surgical approach between endoscopic and open approaches (p = .76). CONCLUSION: Sinonasal adenocarcinomas are commonly identified in the sinonasal cavity and are associated with a relatively favorable prognosis, despite a substantial local failure rate of 30%. Advanced-stage tumors, sphenoid sinus and skull base invasion, and high-grade histology portend poor prognosis. In our experience, endoscopic resection was not associated with adverse outcomes and suggests that this minimally invasive approach can provide acceptable oncologic outcomes in selected patients.

Optimization of long-term outcomes for patients with esthesioneuroblastoma.

BACKGROUND: Esthesioneuroblastoma is a rare cancer of the anterior cranial base that arises in the region of the olfactory rootlets. The purpose of this study was to review the long-term outcomes of patients diagnosed with esthesioneuroblastoma (ENB) treated at a single institution to determine factors associated with improved disease control and survival. METHODS: A retrospective review of 70 patients with ENB treated at the University of Texas MD Anderson Cancer Center between 1992 and 2007 was undertaken. Survival and recurrence was analyzed and compared using the Kaplan-Meier method and log-rank statistics. RESULTS: Seventy patients were reviewed. The majority (77%) had T3 or T4 disease at presentation, 38% identified as modified Kadish stage C or D. Ninety percent of patients received surgical resection as part of their treatment, and 66% received postoperative radiation or chemoradiation. The median follow-up was 91.4 months (7.6 years). Forty-eight percent of patients developed recurrent disease and the median time to recurrence was 6.9 years. Overall and disease-specific median survival was 10.5 and 11.6 years, respectively. Patients who were treated with surgery alone had a median disease-specific survival of 87.9 months, whereas those who were treated with surgery and postoperative radiation had a median disease-specific survival of 218.5 months (p = .047). CONCLUSION: Patients with ENB can achieve favorable long-term survival, even if disease is locally advanced. Survival is improved considerably when surgical resection is followed by postoperative radiation. However, recurrence rates and mortality remain high, and therefore long-term observation in these patients is warranted.

MicroRNA profiling of salivary adenoid cystic carcinoma: association of miR-17-92 upregulation with poor outcome.

BACKGROUND: Salivary adenoid cystic carcinoma (ACC) is a rare relentlessly progressive malignant tumor. The molecular events associated with ACC tumorigenesis are poorly understood. Variable microRNAs (miRNA) have been correlated with tumorigenesis of several solid tumors but not in ACC. To investigate the association of miRNAs with the development and/or progression of ACC, we performed a comparative analysis of primary ACC specimens and matched normal samples and a pooled salivary gland standard and correlated the results with clinicopathologic factors and validated selected miRNAs in a separate set of 30 tumors. METHODS: MiRNA array platform was used for the identification of target miRNAs and the data was subjected to informatics and statistical interrelations. The results were also collected with the MYB-NFIB fusion status and the clinicopathologic features. RESULTS: Differentially dysregulated miRNAs in ACC were characterized in comparison to normal expression. No significant differences in miRNA expression were found between the MYB-NFIB fusion positive and -negative ACCs. Of the highly dysregulated miRNA in ACC, overexpression of the miR-17 and miR-20a were significantly associated with poor outcome in the screening and validation sets. CONCLUSION: Our study indicates that the upregulation of miR-17-92 may play a role in the biology of ACC and could be potentially targeted in future therapeutic studies.