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Background Sinonasal papilloma has a tendency toward local destruction, recurrence, and malignant transformation. This study aimed to unravel mechanisms in the malignant transformation of sinonasal papillomas using RNA-seq. Methods The cohort consisted of 37 consecutive patients; tumor histology included a continuum spectrum (sinonasal papillomas/dysplastic/carcinomas-in-situ/invasive squamous cell carcinomas). These were microdissected and RNA was subjected to whole-transcriptome shotgun sequencing. Results RNA-seq and pathway analysis showed that the highest expressed genes/potential drivers were development- and differentiation-related genes. The protein expression of six highly upregulated genes (HOXA9, EN1, DUX4, CA9, CD1a, and CK5/6) validated the RNA-seq results. HOXA9 and CA9 were found to be expressed in most of the carcinoma samples but were largely negative in papillomas; all of the CA9-negative carcinomas were recurrent. Conclusions We conclude that sinonasal carcinomas arising from papillomas are mainly defined by overexpressed developmental/homeobox genes, which provide the potential for transformation/plasticity, along with differentiation and proliferation behavior of neoplastic cells. Our results support HOXA9 and CA9 as biomarkers for carcinomas, with CA9 emerging as a predictive marker of recurrence.

Background Depth of invasion (DOI) in oral cavity cancer is important in determining prognosis. This study aims to determine optimal cut-points of DOI for detection of occult disease and survival. Methods A retrospective cohort study was completed of previously untreated early stage lateral oral tongue cancer. DOI cut-points were computed. Multiple logistic regression and multivariate Cox proportional hazards models were used to assess predictors of occult nodal disease and overall survival (OS) and disease-specific survival (DSS). Results Occult nodal disease was found in 55 (26%) of the 212 patients. DOI of 7.25 mm was most predictive for occult nodal disease and 8 mm for OS and DSS. DOI was an independent predictor of OS and DSS. Conclusion The optimal DOI cut-point for detection of occult nodal metastasis was 7.25 and 8 mm for OS and DSS at 5 years. DOI is an independent predictor of OS and DSS.

We evaluated the impact of radiation, reconstruction, and timing of tracheoesophageal puncture (TEP) on complications and speech outcomes.Retrospective review identified 145 patients who underwent TEP between 2003 and 2007.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).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.

This study assessed outcomes of patients with hypopharyngeal carcinoma treated with organ-preservation therapy utilizing intensity-modulated radiation therapy (IMRT).The medical records of 98 patients treated with definitive IMRT +/- chemotherapy from 2001 to 2013 for nonmetastatic hypopharyngeal cancer were retrospectively reviewed.Patients were treated to doses of 66 to 72 Gy. Eighty-three patients (85%) received chemotherapy. With median follow-up of 35 months, 2-year overall survival (OS), locoregional control, progression-free survival (PFS), and laryngectomy-free survival rates were 74%, 77%, 67%, and 65%, respectively. Functional laryngeal preservation rate was 76% at 2 years. N3 disease correlated with worse OS (p.01). Concurrent chemotherapy correlated with improved locoregional control (p = .03) and complete response to induction chemotherapy correlated with improved OS and PFS (p = .02). Actuarial 2-year and 5-year grade 3 treatment toxicities were 17% and 21%, respectively.Favorable disease outcomes and functional laryngeal preservation rates can be achieved with IMRT for patients with hypopharyngeal cancer. © 2016 Wiley Periodicals, Inc. Head Neck 38: E2091-E2099, 2016.

The purpose of this study was to present our evaluation of the clinical and functional outcomes after salvage total laryngectomy (STL).We conducted a retrospective review of 218 patients who underwent STL between 1994 and 2014.Seventy percent of patients originally had T1 or T2, N0 tumors and 73% had definitive external-beam radiotherapy (EBRT) alone. A majority utilized tracheoesophageal prosthesis (77%) and were gastrostomy free (80%) at last follow-up. The 5-year disease control and overall survival (OS) rates were 65% and 57%, respectively. Patients with a disease-free interval after initial treatment2 years were more likely to develop a recurrence (p = .001) and die of disease (p = .032) after STL. The disease-free interval after EBRT impacted disease control (p.001), with 5-year disease control of 92% for5-year disease-free interval and 60% for2-year disease-free interval.Most patients remain disease-free after STL, achieve intelligible tracheoesophageal speech, and maintain an oral diet. Delayed recurrence after initial treatment portends better survival and may indicate a distinct biological profile. © 2016 Wiley Periodicals, Inc. Head Neck 38: E1962-E1968, 2016.

Mucoepidermoid carcinoma arises from major or minor salivary glands, making up 10% of salivary gland tumors. Intraosseous mucoepidermoid carcinomas are rare, and make up only 2% to 3% of all mucoepidermoid carcinomas. The t(11;19) and its CRTC1-MAML2 fusion gene transcript have been identified in mucoepidermoid carcinoma and are associated with a subset of mucoepidermoid carcinomas. The extent to which the transcript influences disease features and patient survival is unclear.We conducted a retrospective analysis of records for clinical features, surgical interventions, and prognoses. Reverse transcriptase-polymerase chain reaction (RT-PCR) and fluorescence in situ hybridization (FISH) used to assess the t(11;19) fusion gene in intraosseous mucoepidermoid carcinoma.Twenty-five patients with intraosseous mucoepidermoid carcinoma treated between 1998 and 2013 were identified. The t(11;19) fusion gene transcript CRTC1-MAML2 manifested in 9 intraosseous mucoepidermoid carcinomas, whereas is was not detected in another 9 intraosseous carcinomas. Although the incidence of this fusion in mucoepidermoid carcinoma varies, it is generally accepted that more than 50% of this entity manifest the CRTC1-MAML2.Intraosseous mucoepidermoid carcinoma diagnosis should be based on clinical and pathologic manifestations and complete resection is the first choice for patient treatment. The need for neck dissection and adjuvant treatment are debatable. Radiotherapy may improve prognosis and may be recommended in the postoperative period. Primary intraosseous mucoepidermoid carcinoma can manifest the fusion transcript in a subset of tumors. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1312-E1317, 2016.

The purpose of this study was for us to determine National Comprehensive Cancer Network (NCCN) guideline-compliance of multidisciplinary conference (MDC) recommendations and actual treatment received, and to determine this impact on patient outcomes.We conducted a retrospective review of patients presented at MDC between January 1, 2006, and December 31, 2006, with previously untreated incident cancers.We identified 232 patients, for whom MDC recommendations were NCCN guideline-compliant in 201 (86.6%). Actual treatment was NCCN guideline-compliant in 170 of 197 patients (86.3%). Adherence of MDC recommendations to NCCN guidelines was associated with superior overall survival (hazard ratio [HR] = 0.69; 95% confidence interval [CI] = 0.33-1.39; p = .3), as was guideline-compliance of actual treatment (HR = 0.6; 95% CI = 0.64-1.07; p = .07); congruence between MDC recommendations and actual treatment conferred a statistically significant overall survival benefit (HR = 0.49; 95% CI = 0.27-0.89; p = .02).Our findings argue for patient-centered application of NCCN guidelines. Prospective evaluation will enable more timely identification of systematic NCCN guideline deviations that quality improvement interventions may address. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1820-E1825, 2016.

Conflicting results are reported regarding the impact of neck dissection on radiation-associated dysphagia. The purpose of this study was to reexamine this question specific to oropharyngeal intensity-modulated radiotherapy (IMRT).Three hundred forty-nine patients with oropharyngeal cancer treated with bilateral IMRT with systemic therapy (induction and/or concurrent) were reviewed. Chronic dysphagia was defined by aspiration, stricture, pneumonia, and/or gastrostomy dependence ≥12 months post-IMRT.Selective neck dissection was performed after IMRT in 75 patients (21%). Overall, 41 patients (12%) developed chronic dysphagia. Neck dissection did not increase the rate of chronic dysphagia (9% neck dissection; 12% no neck dissection; p = .464) or gastrostomy duration (p = .482). On multivariate analysis, age (odds ratio [OR] per 5-year = 1.25; 95% confidence interval [CI] = 1.04-1.51), baseline abnormal diet (OR = 2.78; 95% CI = 1.31-5.88), and IMRT dose (OR per 5-Gy = 5.11; 95% CI = 1.77-14.81) significantly predicted dysphagia.In the setting of selective neck dissection for residual adenopathy after IMRT, neck dissection did not impact dysphagia. © 2015 Wiley Periodicals, Inc. Head Neck 38: 886-893, 2016.

Quality assessment is a major tool for evaluation of health care delivery. In head and neck surgery, the University of Texas MD Anderson Cancer Center (MD Anderson) has defined quality standards by publishing benchmarks.We conducted an analysis of 360 head and neck surgeries performed at the AC Camargo Cancer Center (AC Camargo). The procedures were stratified into low-acuity procedures (LAPs) or high-acuity procedures (HAPs) and outcome indicators where compared to MD Anderson benchmarks.In the 360 cases, there were 332 LAPs (92.2%) and 28 HAPs (7.8%). Patients with any comorbid condition had a higher incidence of negative outcome indicators (p = .005). In the LAPs, we achieved the MD Anderson benchmarks in all outcome indicators. In HAPs, the rate of surgical site infection and length of hospital stay were higher than what is established by the benchmarks.Quality assessment of head and neck surgery is possible and should be disseminated, improving effectiveness in health care delivery. © 2015 Wiley Periodicals, Inc. Head Neck 38: 1002-1007, 2016.

The health care industry, including consumers, providers, and payers of health care, recognize the importance of developing meaningful, patient-centered measures. This article describes our experience using an existing electronic medical record largely based on free text formats without structured documentation, in conjunction with tumor registry abstraction techniques, to obtain and analyze data for use in clinical improvement and public reporting.We performed a retrospective analysis of 2467 previously untreated patients treated with curative intent who presented with laryngeal, pharyngeal, or oral cavity cancer in order to develop a system to monitor and report meaningful outcome metrics of head and neck cancer treatment. Patients treated between 1995 and 2006 were analyzed for the primary outcomes of survival at 1 and 2 years, the ability to speak at 1 year posttreatment, and the ability to swallow at 1 year posttreatment.We encountered significant limitations in clinical documentation because of the lack of standardization of meaningful measures, as well limitations with data abstraction using a retrospective approach to reporting measures. Almost 5000 person-hours were required for data abstraction, quality review, and reporting, at a cost of approximately $134,000. Our multidisciplinary teams document extensive patient information; however, data is not stored in easily accessible formats for measurement, comparison, and reporting.We recommend identifying measures meaningful to patients, providers, and payers to be documented throughout the patients' entire treatment cycle, and significant investment in the improvements to electronic medical records and tumor registry reporting in order to provide meaningful quality measures for the future.

Mesenchymal malignancies of salivary origin are rare and are histologically diverse. We reviewed our experience with these tumors, as well as the published literature, with an emphasis on treatment modalities and prognosis.We identified 17 patients treated for malignant mesenchymal cell tumors at The University of Texas MD Anderson Cancer Center between 1990 and 2007. We compared our results to the literature from January 1990 to July 2010.Tumors were located primarily in the parotid gland and were primarily T1 tumors (5 cm). All patients were treated with surgical resection, and 13 patients were given adjuvant therapy. Seven patients (41%) had recurrence, and 4 developed distant metastases. The overall 5-year and 10-year survival rates were 42% and 20%, respectively.Our case series and literature review show that sarcomas of the salivary glands have a high rate of recurrence and are associated with a poor prognosis.

Background Cutaneous squamous cell carcinoma (CSCC) is the second most common nonmelanoma skin cancer. Most of the approximately 250,000 cases occurring annually in the United States are small, nonaggressive, and cured by excision alone. However, a subset of these tumors which are defined by poorly differentiated histology, large tumor size, invasion of adjacent structures, and/or regional metastases can prove resistant to treatment despite adjuvant radiotherapy and can have an increased risk of recurrence and nodal metastasis. Novel therapeutic approaches are necessary to improve the outcomes for patients with aggressive CSCC. Methods We analyzed the effect of targeted therapy on the growth and survival of CSCC cell lines using an anti-insulin-like growth factor-I receptor (IGF-IR) antibody, A12, alone or in combination with an anti-epidermal growth factor receptor (EGFR) antibody, cetuximab, both in vitro and in vivo in an athymic nude mouse model of CSCC. Results Treatment with A12 and cetuximab inhibited the signaling pathways of IGF-IR and EGFR and inhibited proliferation and induced apoptosis of squamous cell carcinoma (SCC) cell lines in vitro. Immunohistochemical staining revealed decreased proliferating cell nuclear antigen (PCNA), microvessel density, and increased apoptosis within the treated tumor xenografts. In addition, the administration of A12, alone or in combination with cetuximab inhibited the growth of tumors by 51% and 92%, respectively, and significantly enhanced survival in the nude mouse model of CSCC (p = .044 and p < .001, respectively). Conclusion These data suggest that dual treatment with monoclonal antibodies to the EGFR and IGF-IR may be therapeutically useful in the treatment of CSCC. © 2010 Wiley Periodicals, Inc. Head Neck, 2011

Background. Epithelial salivary gland neoplasms are rare in children. Malignant tumors account for 30% to 50% of cases in the pediatric age group, with mucoepidermoid carcinoma as the most common histology. Methods. A retrospective medical record review was con- ducted from 1953 to 2007 to identify patients with mucoepider- moid carcinoma at the age of 18 years or younger at the time of diagnosis. Forty-nine patients were identified. Their medical records were examined for presentation, treatment, pathologic features, and outcomes. Results. Forty-nine pediatric patients with mucoepidermoid carcinoma were identified. The parotid gland (49%) and oral cavity (35%) were the most common subsites. Nodal meta- stasis was seen in 24% of patients. All patients underwent surgery, and 11 patients (22%) were treated with radiation therapy. The 5-year overall survival was 98%, the 10-year over- all survival was 94%, and 10% of patients developed recurrence. Conclusion. Mucoepidermoid carcinoma in children carries a favorable prognosis and can be successfully treated with surgery alone in most cases. V C 2011 Wiley Periodicals, Inc.* Head Neck 33: 1769-1773, 2011

Background. Our goal was to determine the impact of reconstructive microsurgery on the treatment of advanced oral cavity cancers. Methods. We reviewed 484 patients undergoing resection of T3-4 oral cavity squamous cell cancers from 1980 to 2004. To examine how reconstructive microsurgery affects outcomes, we compared 135 patients treated prior to the introduction of free tissue transfer and 349 patients treated after the introduc- tion of free tissue transfer. Results. Cancers treated after the introduction of free flaps included a significantly higher proportion of T4 compared to T3 lesions and significantly more advanced N classification lesions. Although cancers were more advanced, survival and recurrence rates were maintained and the rate of positive path- ologic margins decreased significantly. In addition, fistula and tracheostomy dependence rates decreased and rates of intelli- gible speech increased. Conclusion. Reconstructive microsurgery contributes to improved oncologic outcomes in addition to better function and lower morbidity in oral cavity cancer treatment. V C 2009 Wiley Periodicals, Inc. Head Neck 31: 1289-1296, 2009

Background. Radiation-induced xerostomia is a fre- quent and usually permanent side effect of radiation therapy for head and neck cancer. We summarize recent developments in the prevention and treatment of radiation-induced xerostomia. Methods. The Medline database was searched for articles published within the past 10 years on the prevention and treat- ment of postirradiation xerostomia. Proceedings of recent impor- tant national meetings and government Web registries of clinical trials and therapeutic agents were also consulted. Priority was given to randomized controlled trials but, because of the scar- city of such trials, small open trials were included in this review. No other predetermined selection criteria were used, although articles exploring the effects of xerostomia and its treatment on quality of life were considered of special interest. Results. A variety of preventive approaches for postirradia- tion xerostomia exist, involving more conformal radiation delivery technology, radioprotective agents, and even preirradiation sur- gical techniques. Therapeutic interventions include supportive care, saliva supplementation, and the use of procholinergic sali- vary secretagogues. Conclusions. Radiation-induced xerostomia constitutes a significant morbidity after orofacial irradiation. Careful preventive techniques, meticulous supportive care, and new preventive and therapeutic agents may prove useful in combination. V C 2006 Wiley Periodicals, Inc. Head Neck 29: 58-63, 2007

Background. Completion cervical lymphadenec- tomy is usually performed after excisional biopsy of nodal metastases from melanoma. Radiation (XRT) might be effective for some patients in lieu of formal lymph node dissection. Methods. Thirty-six patients with parotid or cervical node metastases from melanoma were treated with excision of nodal disease and postoperative XRT without formal lymph node dissection. Radiation was delivered to the primary site (if known), the site of nodal excision, and the undissected ipsilateral neck. Results. With a median follow-up of 5.3 years, the disease recurred within the regional basin in two patients and at dis- tant sites in 14 patients. The actuarial 5-year regional control and distant metastasis - free survival rates were 93% and 59%, respectively. Two patients had a clinically significant side effect develop. Conclusions. The results of this study suggest that selected patients may receive regional XRT after local excision of nodal disease from melanoma in lieu of formal lymph node dissection. A 2005 Wiley Periodicals, Inc. Head Neck 27: 718 - 721, 2005

Background. The purpose of this study was to determine the preoperative accuracy of preservation of the retropharyngeal fat plane on magnetic resonance (MR) images in predicting the absence of fixation or extension of head and neck carcinomas to the prevertebral space. Methods. The MR images of 75 patients with T3 or T4 primary pharyngeal or laryngeal cancers seen over a 5-year period and treated at our Head and Neck Cancer Center were retrospectively reviewed. The MR images were independently and blindly evaluated by two head and neck radiologists for preservation of the retropharyngeal fat plane between the tumor and prevertebral musculature. In cases in which the fat was preserved, the prevertebral muscle complex was assessed for the presence of T2 hyperintensity and enhancement. All patients underwent panendoscopy, surgery, or both. Results. Forty of 75 patients had preservation of the retropharyngeal fat plane between the tumor and the prevertebral compartment on T1-weighted images. In all 40 cases, the prevertebral muscles had a normal appearance on T2-weighted and enhanced MR images. Intraoperative assessment revealed absence of fixation of tumor to the prevertebral fascia in 39 of 40 cases, and these tumors were resectable. Conclusion. In patients with advanced head and neck carcinomas, preservation of the fat between the tumor and the prevertebral musculature on unenhanced T1-weighted images reliably predicts absence of prevertebral space fixation. © 2004 Wiley Periodicals, Inc. Head Neck27: 95–100, 2005

Objective This article investigates the effect of patient age on postoperative pathway length of stay (LOS) for head and neck surgery. Aggregate clinical results for 43 patients, enrolled in the CCP from June 1996–July 1997, are described. Patient age, comorbid status, and postoperative complications are analyzed with respect to impact on LOS. Setting Tertiary level academic medical center with an operative otorhinolaryngology volume of approximately 1200 cases per year. Patients Forty-three patients undergoing head and neck resection with primary closure, local flap, or free flap closure were enrolled on CCP from June 1996–July 1997. Length of stay, frequency of selected aggregated comorbidities, and frequencies of complications are analyzed with nonparametric statistics. A pre-pathway group of 87 consecutive patients is used for comparison. Main Outcome Measures Length of stay and age. Results Median actual LOS post-pathway for the patients enrolled in the first year of the pathway was 8 days. This met the CCP target and improved on pre-pathway LOS by 5 days (p < .001). The average LOS increased 25% from 8 days to 10 days for patients older than 65 years of age (p = .036, Mann–Whitney U test). Presence of a comorbidity and a complication concomitantly was statistically associated with increased LOS though not with advancing age (p = .003). Conclusions The CCP-reported performance improvement achieved by this pathway suggests improved resource use, and improved patient outcomes are achieved for postoperative care of head and neck surgery patients. Our experience suggests that advancing age creates a clinically significant increase in resource use represented by our finding of increasing LOS. This finding warrants further investigation. © 2002 Wiley Periodicals, Inc. Head Neck 24: 545–548, 2002

Standard treatment of locally advanced laryngeal, hypopharyngeal, and some oropharyngeal cancers includes total laryngectomy. In an attempt to preserve the larynx through induction chemotherapy, we conducted two consecutive phase II studies. From March 1986 to February 1991, 64 patients with advanced untreated but resectable head and neck cancer who would require total laryngectomy were enrolled on one of two cisplatin-based induction regimens: cisplatin-bleomycin-5-fluorouracil (PBF) in 31 patients and cisplatin-5-fluorouracil (PF) in 33; all received definitive radiotherapy. Surgery was reserved for patients who achieved less than a partial response to chemotherapy and patients with residual or recurrent disease after sequential chemotherapy plus radiotherapy. Overall complete plus partial response rates to both cisplatin-based regimens were comparable. The combined PF and PBF overall response rates were 75% for laryngeal cancer, 78% for hypopharyngeal cancer, and 75% for oropharyngeal cancer. Complete response rates after radiotherapy were 88%, 83%, and 50%, respectively. Neutropenia (

Occult thyroid cancer is an occasional incidental finding during surgery for other indications and is usually considered of minor clinical significance; however, the appropriate approach for incidentally found metastatic thyroid cancer is less clear especially when it occurs in the context of another malignancy that has more aggressive potential. Among 2,855 patients treated for squamous cancer of the tongue at The University of Texas M. D. Anderson Cancer Center, eight patients had coexisting differentiated thyroid cancer metastatic to cervical lymph nodes which was found incidentally during regional lymph node dissection. The eight patients included three women and five men with a median age of 47 years (range, 32-62 years); tumors were of the papillary variety in four patients and follicular in the other four. In one patient, no gross or microscopic primary tumor could be identified after thyroidectomy; in another patient, no gross tumor was evident, but whole organ section revealed an area of fibrosis consistent with a primary lesion. Two patients had primary lesions less than 1 cm in maximal diameter. In four patients who had no surgery, physical exam and radiologic evaluation failed to show any intrathyroidal lesions. Clinically relevant thyroid cancer did not develop in any of those patients during the duration of documented follow-up (1-15 years). Three patients died of progressive tongue cancer, one patient of unrelated pulmonary disease, and four patients remain alive without evidence of disease for 1 to 15 years of available follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)