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BACKGROUND: The study objective is to identify risk factors associated with fatigue among long-term OPC survivors. METHODS: This cross-sectional study included disease-free OPC survivors treated curatively between 2000 and 2013 who were surveyed from September 2015 to July 2016. The outcome variable was patient-reported fatigue. Multivariable logistic regression was used to identify factors associated with moderate to severe fatigue. RESULTS: Among 863 OPC survivors, 17.4% reported moderate to severe fatigue. Self-reported thyroid problems (OR: 2.01; p = 0.003), current cigarette smoking at time of survey (OR: 3.85; p = 0.001), late lower cranial neuropathy (OR: 3.44; p = 0.002), and female sex (OR: 1.91; p = 0.010) were concurrent risk factors of reporting moderate to severe fatigue. Ipsilateral intensity-modulated radiotherapy (OR: 0.18; p = 0.014) was associated with lower risk of reporting moderate to severe fatigue. CONCLUSIONS: Our study identified thyroid problems, smoking, and late lower cranial neuropathy as associated with moderate to severe fatigue. These findings should be further validated in prospective studies to address fatigue among OPC survivors.

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 Optimal treatment and prognostic factors affecting long-term survival in patients with sinonasal adenoid cystic carcinoma (ACC) have yet to be clearly defined. Methods We conducted a retrospective review of patients treated with curative intent from 1980-2015 at MD Anderson Cancer Center. Results One hundred sixty patients met inclusion criteria, including 8 who were treated with radiotherapy alone. Median follow-up time was 55 months. The 5-year overall survival (OS) and disease-free survival (DFS) rates were 67.0% and 49.0%, respectively. The 10-year OS and DFS rates were 44.8% and 25.4%, respectively. Factors that portended for poor survival on multivariate analysis were recurrent disease, any solid type histology, epicenter in the sinus cavity, the presence of facial symptoms, or the original disease not treated with surgery. There was no association between surgical margin status or nodal status and survival. Conclusion In this large cohort of patients with sinonasal ACC with extended follow-up, long-term survival is better than reported in prior literature. Future research should target patients with adverse risk factors.

Background The purpose of this study was to characterize decisional regret and its association with symptom burden in a large cohort of oropharyngeal carcinoma (OPC) survivors. Methods A cross-sectional survey was administered to 1729 OPC survivors. Survey items included a multisymptom inventory and a validated decisional regret inventory. Associations between regret and symptom scores were analyzed to determine and rank symptom drivers of decisional regret. Results Nine hundred seventy-two patients responded reporting a low level of decisional regret overall, although 15.5% communicated “moderate to strong” regret. Overall symptom score and treatment group were statistically significant predictors of decisional regret. Relative to other symptoms, difficulty swallowing and feeling sad were the strongest drivers of decisional regret. Conclusion OPC survivors provide a robust description of their long-term outcomes with 15.5% expressing “moderate to high” regret that was significantly associated with late symptom burden and multimodality treatment. Difficulty swallowing was the strongest driver of decisional regret.

The American College of Radiology (ACR) Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer-reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. Here, we present the Appropriateness Criteria for cancers arising in the nasal cavity and paranasal sinuses (maxillary, sphenoid, and ethmoid sinuses). This includes clinical presentation, prognostic factors, principles of management, and treatment outcomes. Controversies regarding management of cervical lymph nodes are discussed. Rare and unusual nasal cavity cancers, such as esthesioneuroblastoma and sinonasal undifferentiated carcinomas, are included. © 2016 American College of Radiology. Head Neck, 2016 © 2016 Wiley Periodicals, Inc. Head Neck 39: 407-418, 2017.

Juvenile angiofibroma is an uncommon, benign, locally aggressive vascular tumor. It is found almost exclusively in young men. Common presenting symptoms include nasal obstruction and epistaxis. More advanced tumors may present with facial swelling and visual or neurological disturbances. The evaluation of patients with juvenile angiofibroma relies on diagnostic imaging. Preoperative biopsy is not recommended. The mainstay of treatment is resection combined with preoperative embolization. Endoscopic surgery is the approach of choice in early stages, whereas, in advanced stages, open or endoscopic approaches are feasible in expert hands. Postoperative radiotherapy (RT) or stereotactic radiosurgery seem valuable in long-term control of juvenile angiofibroma, particularly those that extend to anatomically critical areas unsuitable for complete resection. Chemotherapy and hormone therapy are ineffective. The purpose of the present review was to update current aspects of knowledge related to this rare and challenging disease. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1033-1045, 2017.

Treatments for head and neck squamous cell carcinoma (HNSCC) are associated with toxicities that lead to emergency department presentation.We utilized data from an ongoing prospective cohort of newly diagnosed, previously untreated patients (N = 298) with HNSCC to evaluate the association between clinical and epidemiologic factors and risk for and frequency of emergency department presentation. Time to event was calculated from the date of treatment initiation to emergency department presentation, date of death, or current date. Frequency of emergency department presentation was the sum of emergency department visits during the follow-up time.History of hypertension, normal/underweight body mass index (BMI), and probable depression predicted increased risk for emergency department presentation. BMI and severe pain were associated with higher frequency of emergency department presentations.Clinical and epidemiologic factors can help predict patients with HNSCC who will present to the emergency department. Such knowledge may improve treatment-related patient outcomes and quality of life. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1195-1204, 2017.

The sinonasal cavities are rare locations for metastases. Metastases to these locations are usually solitary and produce similar symptoms to those of a primary sinonasal tumor. Nasal obstruction and epistaxis are the most frequent symptoms. The maxillary sinus is most frequently involved. The most common primary tumor sites to spread to this region originate in the kidney, breast, thyroid, and prostate, although any malignancy could potentially lead to a metastasis to the paranasal sinuses. The patient's prognosis is usually poor because of the fact that the sinonasal metastasis is usually associated with widespread disseminated disease. In the majority of patients, palliative therapy is the only possible treatment option. Nevertheless, whenever possible, surgical excision either alone or combined with radiotherapy may be useful for palliation of symptoms and, rarely, to achieve prolonged survival. This review considers the most interesting cases reported in the literature that presents metastases to the sinonasal cavities. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1847-1854, 2016.

We analyzed local control and early ocular toxicity after eye-sparing management of lacrimal gland carcinoma.For consecutive patients with lacrimal gland carcinoma treated during 2007 to 2014, we reviewed tumor characteristics, treatment details, ocular toxic effects, and recurrence.Twenty patients, median age 55 years, were treated for lacrimal gland carcinoma during the study period; 11 had globe-sparing surgery. Seven patients had adenoid cystic carcinoma, 2 had carcinoma ex pleomorphic adenoma, and 1 each had high-grade and low-grade adenocarcinoma. Ten patients underwent postoperative radiotherapy, median 60 Gy (range, 52-64 Gy), 6 with concurrent chemotherapy. At a median of 30 months after radiation, all patients had dry eye syndrome, and 1 patient had severe corneal and conjunctival damage leading to enucleation. All 11 patients were disease free at last contact, median follow-up after surgery of 33 months.An eye-sparing approach with surgery followed by adjuvant radiotherapy or chemoradiotherapy is feasible for selected patients with lacrimal gland carcinoma and is associated with a reasonable locoregional control and ocular toxicity profile. © 2016 Wiley Periodicals, Inc. Head Neck 38:1258-1262, 2016.

The primary treatment for head and neck adenoid cystic carcinoma (ACC) is surgery. Infrequently, however, ACC's propensity for perineural and base of skull invasion can preclude definitive surgical management. We present our experience with proton radiation therapy (RT) and concurrent platinum-based chemotherapy.Nine patients with unresectable node-negative, nonmetastatic head and neck ACC received definitive proton RT and concurrent cisplatin. Outcomes and toxicities were recorded. A systematic review of the literature was performed.Median follow-up was 27 months (range, 9.2-48.3 months). Four patients achieved complete response at the primary site, and an additional 4 patients achieved stabilization of local disease. Only 1 patient developed local disease progression. Four patients had 5 acute grade 3 (G3) toxicities, and 1 patient developed a chronic G4 optic nerve disorder.Our preliminary results suggest proton RT and concurrent chemotherapy is a definitive treatment option for select patients with head and neck ACC. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1472-E1480, 2016.

Sinonasal undifferentiated carcinoma (SNUC) is a rare and aggressive cancer. Despite multimodal therapy, the prognosis in SNUC remains poor, and new therapies are needed. Thus, the purpose of this study was to explore potential therapeutic targets in SNUC.Using the human-derived SNUC MDA8788-6 cell line, we performed whole genome single nucleotide polymorphism (SNP) analysis to identify copy number changes in this line. Protein expression levels were evaluated by Western blotting. Cell growth inhibition was assessed by methylthiazol tetrazolium (MTT) and clonogenic assays. The mouse flank model was used to examine the effect of growth inhibition in vivo.The ERBB2 gene was highly amplified and cell extracts showed human epidermal growth factor receptor 2 (HER2) was overexpressed and phosphorylated in MDA8788-6. Lapatinib effectively inhibited the HER2 signaling pathway in our SNUC cell line. HER2 inhibition successfully suppressed the cell growth of MDA8788-6 cells both in vitro and in vivo.Targeting HER2 may be a promising avenue for the development of novel therapies for SNUC. © 2016 Wiley Periodicals, Inc. Head Neck 38: E1926-E1934, 2016.

The purpose of this study was to assess outcomes of patients with orbital carcinomas treated with orbital exenteration and intensity-modulated radiation therapy (IMRT).Twenty-nine patients were treated with orbital exenteration and postoperative IMRT between 2002 through 2011; their medical records were retrospectively reviewed.Adenoid cystic carcinoma represented the most common histology (41%) followed by squamous cell carcinoma (21%). Perineural invasion (PNI) was identified in 22 patients (76%). The median radiation dose was 60 Gy (range, 60-70). Seven patients (24%) received neck radiation. The median follow-up was 43 months (range, 5-102 months). Five-year local control, overall survival (OS), and disease-free survival rates were 83%, 60%, and 55%, respectively. PNI (p = .01) and especially involvement of a named nerve (p = .001) significantly correlated with worse OS.Favorable disease control rates for orbital carcinomas are achievable with IMRT after orbital exenteration even for patients with advanced disease. Toxicity for the contralateral eye was minimal. © 2015 Wiley Periodicals, Inc. Head Neck 38: E580-E587, 2016.

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.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.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).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.

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.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.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).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.

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.

Little is known about the molecular signature of the rare tumor sinonasal squamous cell carcinoma (SNSCC). The purpose of this study was to comprehensively assess various molecular biomarkers in SNSCC.We chose 13 markers for this study, which have been known as prognostic markers in head and neck squamous cell carcinoma. Expression of these markers was examined by either in situ hybridization or immunohistochemical methods on tissue microarrays made from 70 SNSCC specimens and 28 matched-pair normal tissues from patients who underwent surgical resection at our institution. Expression data were correlated with patient clinicopathologic parameters and survival.Of the 13 markers, only epidermal growth factor receptor (EGFR) protein expression was associated with significantly shorter disease-free survival (DFS; p = .01307). EGFR expression was also associated with shorter overall survival (OS), but the difference was not statistically significant.Targeted inhibition of tumor EGFR expression may be a new approach to treating SNSCC.

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 As a first step toward developing effective strategies to control symptoms associated with head and neck cancer (HNC) and its treatment, we sought to describe the pattern of symptoms experienced before radiation therapy. Methods Subjects completed the MD Anderson Symptom Inventory–Head and Neck Module before beginning radiation therapy. Results In all, 270 patients participated. Symptom severity and interference varied between treatment-naive patients and those with prior treatment. Cluster analyses revealed that 33% of patients had high symptom burden. Symptoms most often rated moderate-to-severe were fatigue, sleep disturbance, distress, pain, and problems chewing and swallowing. Poorer performance status, higher T classification, and receipt of previous treatment correlated with higher symptom burden. Conclusions A substantial proportion of patients were experiencing high symptom burden. Because few interventions currently exist for several of the most problematic symptoms, research in symptom reduction that targets the pattern of symptoms described here is greatly needed. © 2012 Wiley Periodicals, Inc. Head Neck 35: 1490–1498, 2013

Background Sinonasal hemangiopericytomas are rare low-grade sarcomas. The role of endoscopic management has not been adequately studied. Methods This study was conducted through retrospective medical chart review of patients seen with sinonasal hemangiopericytomas at 2 institutions over a 19-year period. Demographic, clinicopathological, and surgical information was analyzed with descriptive statistics. Results Thirteen patients with a diagnosis of sinonasal hemangiopericytomas were treated. The most common symptoms were obstruction (69%) and epistaxis (35%). All tumors were localized in the nasal cavity, and half had extension to 1 or more sinuses. Resection was performed endoscopically in 6 patients. Median intraoperative blood loss was 500 mL; median operative time was 165 minutes. Two patients received postoperative radiation. There were no recurrences with a median follow-up of 25 months. Three patients presented with recurrences, 2 local and 1 distant, up to 13 years after primary tumor removal. Conclusion Surgery for sinonasal hemangiopericytomas can be challenging; both endoscopic and open approaches may be used to treat these highly vascular tumors. © 2011 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. Palatal obturators and microvascular free flaps are both used to treat patients with maxillectomy defects, however, the optimal technique remains controversial. Methods. A retrospective analysis of 113 patients undergoing maxillectomy for cancer was performed. Seventy-three patients received an obturator and 40 patients were reconstructed with a free flap. Results. Speech intelligibility and postoperative diet were comparable between the obturator and free flap groups, except in cases of extensive (>50%) palatal defects, where free flap reconstruction was superior in both aspects (p = .019 and p = .043, respectively). The average time for presenting with a local recurrence in advanced cancer involving the palate was comparable in both groups (p = .33). Conclusion. Moderate-sized maxillectomy defects involving the palate can be successfully treated with either an obturator or free flap reconstruction. Extensive defects have a better functional outcome with free flaps. Evidence does not suggest that free flap reconstructions delay diagnosis of local recurrences. © 2009 Wiley Periodicals, Inc. Head Neck, 2009

Background The anti-cancer gene, E1A, can be complexed to a lipid carrier, DC-Cholesterol:DOPE, to form tgDCC-E1A, which can be injected directly into tumors. Methods Twenty-four patients with recurrent, unresectable, head and neck cancer were treated with intratumoral injections of tgDCC-E1A over 8 weeks. Tumor response was assessed using CT scans. Time to progression and overall survival were calculated. Results Intratumoral tgDCC-E1A was well tolerated in all patients. No significant toxicities related to tgDCC-E1A were reported. One patient (4.2%) had a complete response, two patients (8.3%) had minor response, and seven patients (29.2%) had stable disease by two-dimensional cross-products on blinded CT scans. The median time to progression was 8.6 weeks (range, 3.3–43.7 weeks), and median survival was 4.6 months (range, 1.3–15.6 months). Conclusions Intratumoral injections of tgDCC-E1A were safe and well tolerated. Modest tumor response was observed. Further development of tgDCC-E1A is warranted in combination with other treatment modalities. © 2002 Wiley Periodicals, Inc.