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.

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.

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.

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.

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.

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.

An evolution in demographics, treatment, and outcomes of oropharyngeal cancer at a major cancer center: a staging system in need of repair.

BACKGROUND: In this retrospective review, the authors examined demographic/clinical characteristics and overall survival in patients with squamous cell carcinoma of the oropharynx at a tertiary cancer center, and they report the characteristics that influenced any observed survival trends over time. METHODS: The study included 3891 newly diagnosed, previously untreated patients who presented at the authors' institution between 1955 and 2004. RESULTS: Over time, patients presented at younger ages and were more likely to have base of tongue or tonsil tumors and to be never-smokers or former smokers. Patients who were diagnosed between 1995 and 2004 were almost half as likely to die as those who were diagnosed before 1995 (hazard ratio, 0.6; 95% confidence interval, 0.6-0.8). In both multivariable and recursive partitioning survival analyses, the TNM staging system predicted the survival of patients who received treatment before 1995 but did not predict the survival patients treated during the period from 1995 to 2004. CONCLUSIONS: Survival among patients with squamous cell carcinoma of the oropharynx improved substantially over the past 50 years. The main contributing factors were changes in clinical characteristics, in particular surrogates for positive human papillomavirus status. The current TNM staging system for squamous cell carcinoma of the oropharynx is inadequate. The incorporation of human papillomavirus status and perhaps smoking status into the TNM system is encouraged.

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.

Prognostic factors in mucoepidermoid carcinoma of the salivary glands.

BACKGROUND: Mucoepidermoid carcinoma (MEC) is the most common malignancy of the major salivary glands. Prior reports noted histological grade and tumor stage as consistently important prognostic factors. This study reviewed the experience of patients with MEC at the University of Texas MD Anderson Cancer Center to determine the impact of clinical and pathologic findings on disease outcomes. METHODS: A retrospective clinical review was performed of patients with salivary gland MEC treated at a tertiary cancer center from 1990 to 2007. RESULTS: A total of 125 patients were included. The 5-year overall survival and disease-free survival of all patients were 79.3% and 76.5%, respectively. Patients with low- and intermediate-grade disease had significantly better overall survival and disease-free survival than patients with high-grade disease, but no difference in survival rates was found between low- and intermediate-grade disease. Pathologic results of positive lymph nodes, extracapsular lymph node spread, and perineural invasion were all found to be poor prognostic indicators. On multivariate analysis, advanced disease stage and perineural invasion were found to be the most significant prognostic factors. CONCLUSIONS: Patients with either low- or intermediate-grade tumors uniformly have favorable local control and survival. High histological grade, advanced stage, perineural invasion, positive surgical margins, and submandibular location all portend for poor outcomes in MEC. Further advances in therapy are needed to improve outcomes for high-grade and advanced-stage disease.

Quantitative promoter hypermethylation analysis of cancer-related genes in salivary gland carcinomas: comparison with methylation-specific PCR technique and clinical significance.

PURPOSE: To compare the methylation status of tumor-associated genes by quantitative pyrosequencing and qualitative methylation-specific PCR (MSP) techniques and to correlate the results with clinicopathologic features and patients outcome to determine which method might have greater clinical utility. EXPERIMENTAL DESIGN: The hypermethylation status of the retinoid acid receptor beta2 (RARbeta2), RAS association domain family 1A (RASSF1A), O(6)-methylguanine-DNA methyltransferase (MGMT), and E-cadherin genes was analyzed in five salivary carcinoma cell lines and 69 human salivary gland carcinoma specimens by pyrosequencing and MSP techniques. The two datasets were compared by linear regression. Correlations between methods and with clinicopathologic characteristics were assessed by Pearson's chi(2) test or the two-tailed Fisher exact test, as applicable, using cutoff points determined from the regression curves and empirical fitting. We also investigated the effect of demethylating agents on methylated genes in cell lines to assess their effect on the expression of these genes. RESULTS: Overall, regression analysis indicated high degrees of correlation of the two methods for measurement of methylation for the RARb2, RASSF1A, and MGMT genes (adjusted R(2) = 0.319, 0.835, and 0.178; P < 0.001, <0.001, and 0.0002, respectively) among the 69 tumors tested. However, the pyrosequencing technique yielded four more instances of methylation above background levels than MSP for RARbeta2 and three more for RASSF1. Methylation of either RARbeta2 and RASSF1A alone or both by pyrosequencing were correlated with tumor type (P = 0.027, 0.014, and 0.012, respectively). Methylation of RARbeta2 alone and in combination with RASSF1A by pyrosequencing were also significantly correlated with tumor grade (P = 0.014 and 0.011, respectively) and 3-year survival (P = 0.002 and 0.004, respectively). The survival curves of patients who had hypermethylation at both RARbeta2 and RASSF1A were significantly lower than those of patients who had hypermethylation at neither or just for the RASSF1A (P = 0.008 and 0.007, respectively). 5-Azadeoxycytidine treatment of methylated cell lines led to the reactivation of RARbeta2 expression in only one of the five cell lines. CONCLUSIONS: (a) Although the methylation status of RARb2, RASSF1A, and MGMT genes by both techniques were significantly correlated, pyrosequencing is generally more sensitive and its results correlate better with the clinical variables than those of MSP. (b) The methylation level of the RARbeta2 and/or RASSF1A by pyrosequencing is significantly associated with aggressive tumor phenotypes and patients survival.

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.

Swallowing outcomes after radiotherapy for laryngeal carcinoma.

OBJECTIVE: To describe swallowing physiology and functional outcomes at select intervals after definitive radiotherapy for laryngeal carcinoma. We also examined associations among patient, tumor, and treatment characteristics and swallowing outcomes. DESIGN: Retrospective review. SETTING: The University of Texas M. D. Anderson Cancer Center, Houston. PATIENTS: This study cohort included 40 patients who underwent definitive radiotherapy for laryngeal carcinoma (from February 2001 to June 2004). MAIN OUTCOME MEASURES: Modified barium swallow (MBS) studies were performed for 32 patients at 3 test intervals following irradiation: less than 6 months, 6 to 11 months, and 12 or more months. We recorded the presence or absence of aspiration (sensate or silent), 5 pharyngeal phase disorders, and 2 structural abnormalities. We also recorded pretreatment dysphagia complaints, feeding tube dependency, T classification, disease site, mucositis grade, and radiotherapy schedule with or without chemotherapy. RESULTS: Eighty-four percent of patients (27 of 32) referred for MBS studies after undergoing radiotherapy aspirated; 44% (12 of 27) did so silently. Silent aspiration was more prevalent during MBS studies conducted 1 or more years after radiotherapy. Pharyngeal phase disorders were observed more frequently than structural abnormalities (P < .01). Most patients required a feeding tube (78% [31 of 40]); however, 52% of the tubes (16) were eventually removed. We found no significant association between the occurrence of aspiration and disease site, T classification, treatment regimen, or pretreatment variables (P > .05). Pretreatment and posttreatment levels of feeding tube dependency were significantly associated (P = .03). Patient-reported dysphagia before treatment did not predict posttreatment swallowing outcomes (P > .05). CONCLUSIONS: Dysphagia is a common outcome after laryngeal preservation with radiotherapy. Contrary to expectations, few parameters that we measured were significantly associated with swallowing outcomes in our study.

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.

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.

Primary tracheal malignant neoplasms: the University of Texas MD Anderson Cancer Center experience.

BACKGROUND: Primary malignant neoplasms of the trachea are very rare and data relating to them are limited. This study was conducted to review the presentation, management, and outcomes of primary tracheal cancers at our institution, a large multidisciplinary cancer center. STUDY DESIGN: Retrospective chart review was conducted for all patients found to have a pathologic diagnosis of primary tracheal malignancy. RESULTS: Since 1945, 74 patients were diagnosed with primary tracheal cancers. Among these, 34 (45.9%) were squamous cell carcinomas, 19 (25.7%) were adenoid cystic carcinomas, and 21 (28.4%) were of other histologic types. Presenting symptoms were most frequently dyspnea (55.4%), hemoptysis (48.6%), cough (41.9%), and hoarseness (35.1%). Most patients (77.3%) were former or current smokers, particularly those with squamous cell carcinoma (93.3%). For the entire group of 74 patients, the 5-year disease-specific mortality rate was 72.9% and the 5-year all-cause mortality rate was 79.3%. Patients who had adenoid cystic carcinoma and those with cervical primaries had better rates of disease-specific and overall survival than others (p = 0.036 and 0.006 for the former patient group and p = 0.006 and 0.030 for the latter patient group). Among patients with incident disease treated at our institution (n = 45), those undergoing primary operation with adjuvant radiotherapy appeared to have better disease-specific and overall survival rates compared with those undergoing primary radiotherapy with or without chemotherapy (p = 0.0002 and 0.0003, respectively). Although those undergoing operation and receiving radiotherapy did better than those undergoing operation alone, the difference was not statistically significant. CONCLUSIONS: Primary tracheal cancers are very rare, and our results should be viewed with caution, given that our population comprised a small heterogeneous group treated over a 60-year period. Although squamous cell carcinoma was the most common pathology in smokers, adenoid cystic carcinoma was more prevalent among nonsmokers. Operation with adjuvant postoperative radiotherapy is recommended for most patients.

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.

Matched-pair analysis of survival of never smokers and ever smokers with squamous cell carcinoma of the head and neck.

PURPOSE: To compare survival rates between patients with squamous cell carcinoma of the head and neck (SCCHN) without a history of smoking (never smokers) and those with a current or previous history of smoking (ever smokers). PATIENTS AND METHODS: Fifty never smokers with newly diagnosed SCCHN were matched to 50 ever smokers according to sex, age, tumor site, overall stage, nodal stage, and treatment. Survival analysis was performed using Kaplan-Meier estimates. Matched-pair survival was compared using the Cox proportional hazards model. RESULTS: The never smokers had a greater overall survival (P =.020), disease-specific survival (P =.022), and recurrence-free survival (P =.016). Furthermore, matched-pair analysis demonstrated smoking was associated with a significant increase in risk of overall death (relative risk [RR] = 3.50; 95% CI, 1.14 to 10.77; P =.029), risk of death owing to disease (RR = 3.98; 95% CI, 1.11 to 14.33; P =.034), and risk of disease recurrence (RR = 3.29; 95% CI, 1.18 to 9.14; P =.023). Smoking was associated with three-fold increases in risk for overall death, death owing to disease, and recurrence after adjustment for cancer-associated symptom severity and alcohol use, but the 95% CI for these adjusted risk estimates each included the null. CONCLUSION: Survival differed significantly between never smokers and ever smokers with SCCHN. These results are not substantively explained by differences in cancer-associated symptoms or alcohol use, but the CIs are wide and some imprecision remains. Regardless, possible fundamental differences in SCCHN between ever smokers and never smokers may exist, and further molecular characterization of these tumors is needed to determine whether biologic differences needing targeted therapies exist.

Functional outcomes after circumferential pharyngoesophageal reconstruction.

OBJECTIVE: To determine functional speech and swallowing outcomes, morbidity, and complication rates after reconstruction of circumferential pharyngoesophageal defects using a jejunal versus an anterolateral thigh (ALT) flap. STUDY DESIGN: Retrospective analysis. METHODS: We reviewed the medical records of 58 patients with circumferential pharyngoesophageal defects, 27 with ALT flap reconstruction, and 31 with jejunal interposition. We compared complication rates, intensive care unit (ICU) and hospital stays, nutritional intake, number of tracheoesophageal punctures (TEPs) performed, TE speech fluency, and functional use. Modified barium swallow studies assessed swallowing physiology. RESULTS: Patient characteristics were similar. Total flap loss occurred in one (3.7%) patient with an ALT flap and two (6.5%) patients with jejunal interposition (P = 1.000), fistula in two (7.4%) ALT patients and one (3.2%) jejunal patient (P = .5931), and anastomotic stricture in four (15%) ALT patients and six (19.4%) jejunal patients (P = .7371). ICU and hospital stays were greater for jejunal patients (P = .001, <.001, respectively). TEPs were performed in eight jejunal patients and nine ALT patients. Eighty-nine percent of ALT patients and 63% of jejunal patients were fluent, whereas 78% of ALT patients and 25% of jejunal patients used TE speech to communicate. Ninety-one percent of ALT patients and 73% of jejunal patients resumed oral intake (P = .151). The most common causes of dysphagia were impaired tongue base retraction (62% jejunum) and disordered motility (62% jejunum, 67% ALT). CONCLUSIONS: For circumferential pharyngoesophageal reconstruction, the ALT flap results in similar complication rates, but shorter ICU and hospital stays, and better speech and swallowing compared with jejunal reconstruction.