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Objective Primary repair of posteriorly located anterior skull base (ASB) dural defects following cranial trauma is made difficult by narrow operative corridors and adherent dura mater. Inadequate closure may result in continued cerebrospinal fluid (CSF) leak and infectious sequelae. Here, we report surgical outcomes following the use of nonpenetrating titanium microclips as an adjunctive repair technique in traumatic anterior skull base dural defects extending from the olfactory groove to the tuberculum sellae. Methods All trauma patients who underwent a bifrontal craniotomy from January 2013 to October 2019 were retrospectively reviewed. Patients with ASB defects located at posterior to the olfactory groove were analyzed. Patients with isolated frontal sinus fractures were excluded. All patients presented with CSF leak or radiographic signs of dural compromise. Patients were divided according to posterior extent of injury. Patient characteristics, imaging, surgical technique, and outcomes are reported. Results A total of 19 patients who underwent a bifrontal craniotomy for repair of posteriorly located ASB dural defects using nonpenetrating titanium microclips were included. Defects were divided by location: olfactory groove (10/19), planum sphenoidale (6/19), and tuberculum sellae (3/19). No patients demonstrated a postoperative CSF leak. No complications related to the microclip technique was observed. Clip artifact did not compromise postoperative imaging interpretation. Conclusion Primary repair of posteriorly located ASB dural defects is challenging due to narrow working angles and thin dura mater. Use of nonpenetrating titanium microclips for primary repair of posteriorly located dural defects is a reasonable adjunctive repair technique and was associated with no postoperative CSF leaks in this cohort.

Objective Esthesioneuroblastoma (ENB) is a rare malignancy of the sinonasal tract and its infrequency has confounded efforts at clearly describing the survival trends associated with this neoplasm over the years. In this study, we reviewed survival trends in ENB and investigated the impact of treatment extent and modality on patient outcomes. Methods We accessed the Surveillance, Epidemiology, and End Result (SEER) program to identify ENB cases from 1998 to 2016. A χ2 test was used to compare the categorical covariates and a t test or Mann-Whitney U test was utilized for continuous variables. The impact of prognostic factors on survival was computed using a Kaplan-Meier analysis and multivariate Cox proportional hazards model. We divided ENB patients into 4 periods including 1998–2002, 2003–2007, 2008–2012, and 2013–2016, and investigated survival trends using the Kaplan-Meier curve and log-rank test. Results ENB patients who underwent biopsy alone were associated with older age, larger tumor diameter, increased rates of tumor extension, nodal/distant metastases, and advanced stages as compared with patients undergoing tumor resection. Our results also demonstrated that surgical resection and adjuvant radiotherapy could confer survival advantages, whereas chemotherapy was associated with reduced survival in patients with ENB. Over the past 2 decades, surprisingly, there has been no change in survival rates for patient with ENB (P = 0.793). Conclusions Despite advanced diagnostic studies and modernized treatment approaches, ENB survival has remained unchanged over the years, calling for improved efforts to develop appropriate individualized interventions for this rare tumor entity. Our results also confirmed that surgery and adjuvant radiotherapy is associated with improved patient survival whereas the use of chemotherapy should be considered carefully.

Background Orbital cavernous hemangiomas (OCH) are the most common adult orbital tumor and represent an ideal index lesion for endonasal orbital tumor surgery. In order to standardize outcomes reporting, an anatomic-based staging system was developed. Methods An international, multidisciplinary panel of 23 experts in orbital tumor surgery was formed. A modified Delphi method was used to develop the cavernous hemangioma exclusively endonasal resection (CHEER) staging system with a total of 2 rounds being completed. Results Tumors medial to a plane along the long axis of the optic nerve may be considered amenable for an exclusively endonasal resection. In select cases, tumors may extend inferolaterally if the tumor remains below a plane from the contralateral naris through the long axis of the optic nerve (ie, plane of resectability [POR]). This definition reached consensus with 91.3% of panelists in agreement. Five stages were designed based on increasing technical resection difficulty and potential for morbidity. Stages were based on the relationship of the tumor to the extraocular muscles, the inferomedial muscular trunk of the ophthalmic artery (IMT), and orbital foramina. Staging by anatomic location also reached consensus with 87.0% of panelists in agreement. Size was not included in the staging system due to the lack of agreement on the contribution of size to resection difficulty. Conclusion Endoscopic orbital tumor surgery is a nascent field with a growing, yet heterogeneous, body of literature. The CHEER staging system is designed to facilitate international, high-quality, standardized studies establishing the safety, efficacy, and outcomes of endonasal resection of OCH.

Dopamine agonist-induced cerebrospinal fluid (CSF) rhinorrhea is an uncommon treatment-related complication arising in 6.1% of prolactinoma patients treated with dopamine agonists. Locally invasive prolactinomas may create CSF fistulae through formation of dural and osseous skull base defects. Tumor shrinkage secondary to dopamine agonist therapy unmasks skull base defects, thus inducing CSF rhinorrhea. In these cases, repair of the leak may be achieved through collaborative surgical intervention by rhinologists and neurosurgeons. Multiple variables have been investigated as potential contributors to the risk of CSF rhinorrhea development in medically treated prolactinoma patients, with little consensus.The primary aim of our study was the characterization of risk factors for CSF rhinorrhea development following dopamine agonist treatment.A systematic review of the literature was conducted to identify cases of CSF rhinorrhea following dopamine agonist treatment of prolactinoma. The clinical history, radiographic findings and treatment outcomes are discussed.Fifty-four patients with dopamine agonist-induced CSF rhinorrhea were identified across 23 articles published from 1979 to 2019. Description of diagnostic imaging [computed tomography (CT)/magnetic resonance imaging (MRI)] was not provided for 18/54 subjects. For the 36 cases that described prolactinoma appearance on CT or MRI, invasion of the cavernous sinuses was reported in 13 (36.1%) and invasion of the sphenoid sinus was reported in 18 (50%).Based on our systematic review, we propose that CT findings of osseous erosion of the sella or the anterior skull base may predict dopamine agonist-induced CSF rhinorrhea. We recommend obtaining a thin-slice CT of the sinuses in cases with MRI evidence of sphenoid involvement.

Objectives/hypothesis To evaluate the impact of age on patient-reported quality of life (QOL) following endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS). Study design Prospective cohort study. Methods Six hundred thirty-six patients with CRS were recruited from 11 otolaryngologic practices and completed the sinonasal-specific, 22-item Sino-Nasal Outcome Test-22 (SNOT-22) and general health-related EuroQol 5-Dimension (EQ-5D) questionnaires at baseline and 12 and 24 months after ESS. Patients were grouped chronologically to determine whether age at time of ESS was associated with clinical outcomes. Results Ages ranged from 18 to 80 years (mean ± standard deviation = 48.5 ± 14.4). Improvement was observed in postoperative SNOT-22 scores at 12 and 24 months for all decades of life. Similar improvements were observed for EQ-5D-based health utility value (HUV) scores in all decades of life, except for the eldest cohort (ages 70-80, N = 33), who did not exceed the minimal clinically important difference at either 12 or 24 months following ESS. In regression analysis, age was not associated with sinonasal-specific outcomes (change in SNOT-22 scores) at 12 (P = .507) or 24 months (P = .955). In general health-related outcomes, however, age was significantly associated with change in EQ-5D-based HUV scores from baseline to 12 months following ESS after adjusting for patient demographics, comorbidities, and surgical history (P = .049). Conclusions This study demonstrates that ESS for adult CRS sufferers offers improved QOL outcomes through the eighth decade of life. The impact of comorbidities on QOL needs to be carefully considered when assessing older patients for sinus surgery. Level of evidence 2b Laryngoscope, 128:2681-2687, 2018.

Background: Basilar invagination (BI) is a complex condition characterized by prolapse of the odontoid into the brain stem/upper cervical cord. This lesion is often associated with Chiari malformations, and rheumatoid arthritis (RA). Treatment options for BI typically include cervical traction, an isolated anterior transoral odontoidectomy, anterior endonasal odontoidectomy, an isolated posterior fusion, or combined anterior/ posterior surgical approach. Case Description: A 45-year-old female with a Chiari I malformation and RA underwent a combined posterior C0-C5 posterior decompression/fusion, followed by an anterior odontoidectomy (i.e. endoscopic/endonasal under neuronavigation). Postoperatively, the patient’s symptoms and neurological signs resolved. Conclusion: BI in was successfully managed with a combined posterior C0-C5 decompression/fusion followed by an anterior endoscopic/endonasal odontoidectomy performed under neuronavigation.

Background Treatment of head and neck cancer is complex, and a multidisciplinary clinic may improve the coordination of care. The value of a head and neck multidisciplinary clinic has not yet been established in oropharyngeal squamous cell carcinoma (SCC). Methods A retrospective review was conducted of Veterans Affairs patients with oropharyngeal SCC undergoing concurrent chemoradiation before and after implementation of the head and neck multidisciplinary clinic. Results Fifty-two patients before and 54 patients after multidisciplinary clinic were included in this study. Age, tobacco use, and p16+ status were similar between groups. With multidisciplinary clinic, time to treatment decreased, and utilization of supportive services, including speech pathology, dentistry, and nutrition increased. The 5-year disease-specific survival rate increased from 63% to 81% (p = .043) after implementation of the multidisciplinary clinic. Multivariate analysis showed that disease stage (p = .016), p16 status (p = .006), and multidisciplinary clinic participation (p = .042) were predictors of disease-specific survival. Conclusion Implementation of a multidisciplinary clinic improved care coordination and disease-specific survival in patients with oropharyngeal SCC. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1106-1112, 2017.

To provide a comprehensive overview of the emerging role of periostin, an extracellular matrix protein, as a key component in the development, diagnosis, and treatment of patients with chronic rhinosinusitis.Medline database.A state of the art review was performed targeting English-language studies investigating the role of periostin in cardiopulmonary, neoplastic, and inflammatory diseases, with emphasis on recent advances in the study of periostin in chronic rhinosinusitis.Periostin has emerged as a novel biomarker and therapeutic target for numerous human pathologies, including cardiac, pulmonary, and neoplastic disease. The upregulation of periostin in chronic rhinosinusitis suggests the potential for similar roles among patients with sinonasal disease.Chronic rhinosinusitis is a widespread disease with major clinical and societal impact. A critical limitation in the current treatment of patients with chronic rhinosinusitis is the absence of clinically relevant biomarkers to guide diagnosis and treatment selection. A review of the literature supports a likely role of periostin as a biomarker of chronic rhinosinusitis, as well as a novel therapeutic target in the future treatment of patients with sinonasal disease.

Background Sleep impairment is highly prevalent in patients with chronic rhinosinusitis (CRS). Although endoscopic sinus surgery (ESS) has been shown to improve overall patient-reported sleep quality, the postoperative impact on individual sleep symptoms remains unclear. Methods Patients with medically-recalcitrant CRS who elected to undergo ESS were prospectively enrolled into a multi-institutional, observational cohort study. Sleep-related symptom severity and treatment outcomes were assessed using the sleep domain questions within the 22-item Sino-Nasal Outcome Test (SNOT-22). Results A total of 334 participants met criteria and were followed postoperatively for an average of 14.5 ± 4.9 months (mean ± standard deviation [SD]). Mean SNOT-22 sleep domain scores improved from 13.7 ± 6.8 to 7.7 ± 6.6 (p < 0.001). Significant mean relative improvements were reported for “difficulty falling asleep” (45%; p < 0.001), “waking up at night” (40%; p < 0.001), “lack of a good night's sleep” (43%; p < 0.001), “waking up tired” (40%; p < 0.001), and “fatigue” (42%; p < 0.001) scores. A total of 66% of study participants reported postoperative improvement in “lack of a good night's sleep,” “waking up tired,” and “fatigue”; 62% reported improvement in “waking up at night”; and 58% reported improvement in “difficulty falling asleep.” Conclusion Patients with CRS report significant and sustained improvements following ESS in common sleep-related symptoms as assessed by the SNOT-22 sleep domain. Despite these significant improvements, some degree of persistent postoperative sleep impairment was reported. Further study is necessary to determine what factors are associated with continued sleep dysfunction after sinus surgery.

Background The Brief Smell Identification Test (BSIT) is an abbreviated version of the Smell Identification Test (SIT) used to assess olfactory function. Although the BSIT can be efficiently administered in under 5 minutes, the accuracy of the BSIT in relation to the SIT in patients with chronic rhinosinusitis (CRS) is unknown. Methods Patients with CRS were recruited as part of an ongoing multi-institutional observational cohort study. A total of 183 participants provided both BSIT and SIT olfactory function scores during initial enrollment. Linear associations between BSIT and SIT scores were evaluated using Pearson's correlation coefficients (rp). The sensitivity, specificity, and accuracy of BSIT scores were determined using SIT scores as the “gold standard.” Results A strong bivariate linear association was found between BSIT and SIT scores (rp = 0.893; p < 0.001) for all participants. A significantly lower proportion of patients were identified as having abnormal olfaction using the BSIT compared to the SIT (47% vs 68%, respectively; p < 0.001). Using the currently defined score of ≤8 as a cut-point for abnormal olfactory function, the BSIT demonstrated a sensitivity of 63% and specificity of 88% with an overall accuracy of 71%. Increasing the cut-point to ≤9 resulted in an increased sensitivity of 86%, a specificity of 76%, and an improved overall accuracy of 83%. Conclusion In patients with CRS, BSIT scores strongly correlate with SIT scores; however, the BSIT underestimates olfactory dysfunction as defined by the suggested cut-point of ≤8. Increasing the cut-point to ≤9 increased the sensitivity and accuracy of the BSIT.

PHACES syndrome is a neurocutaneous disorder characterized by the presence of segmental hemangiomas with associated anomalies of the posterior fossa, cerebral vasculature, cardiovascular system, eyes, and ventral or midline structures. We present the first case of propranolol-responsive congenital trigeminal and facial nerve palsies secondary to an intracranial hemangioma in a patient with PHACES syndrome.

Severe anterior septal deviation and resultant nasal obstruction represent a difficult surgical task to correct. The goal of surgery is to straighten the anterior dorsal and caudal struts, while maintaining nasal tip and midvault support. This study presents a novel extracorporeal septoplasty technique to straighten the crooked anterior septum.To describe the novel anterior septal transplant technique, which consists of complete resection of the caudal septum and reconstruction with extended spreader grafts and a columellar strut, without a separate caudal septal replacement graft.This study was a retrospective case series at a tertiary academic referral center. Participants were sequential adult patients undergoing anterior septal transplant from January 1, 2008, to December 31, 2015.Patient-reported nasal obstruction using Nasal Obstruction Symptom Evaluation (NOSE) scores and objective photographic analysis. Nasal tip deviation, projection, and rotation were measured. Preoperative and postoperative outcomes were compared. Complications are reported.Seventy-one patients (mean age, 46 years [age range, 16-72 years]; 48 [67.6%] female and 23 [32.4%] male) were included in the case series. Postoperative NOSE scores (mean [SD], 24.00 [24.58]) were significantly better than preoperative NOSE scores (mean [SD], 72.25 [14.55]) (P .001). A separate cohort of 32 patients (mean age, 42 years [age range, 13-72 years]; 23 [71.9%] female and 9 [28.1%] male) had photographs available for analysis. In the frontal view, nasal deviation improved from a mean (SD) of 2.9 (2.0) degrees before surgery to a mean (SD) of 1.4 (1.7) degrees after surgery (P = .004). In the base view, the deviation was corrected from a mean (SD) of 4.9 (2.8) degrees to a mean (SD) of 1.7 (1.2) degrees (P .001). Tip rotation and projection were unchanged after surgery. Four patients had mild dorsal irregularities after surgery.Anterior septal transplant by the described technique is a safe and effective treatment option for severe anterior septal deviation.4.

Objectives To evaluate practice patterns amongst pediatric otolaryngologists in the management of post-tonsillectomy hemorrhage. Methods A cross-sectional survey of the American Society of Pediatric Otolaryngology membership was administered electronically. The survey contained questions related to practice type, availability of resident and fellow call coverage, and management of different scenarios of post-tonsillectomy hemorrhage. Anonymous responses were collected and tabulated. Results The response rate was 157/443 (35%). For patients presenting with a convincing history of post-tonsillectomy hemorrhage but no clot or bleeding on exam, the most common management was overnight observation (55%) or discharge home with close follow-up (29%). In patients presenting with tonsillar clot but no active bleeding, the most common management was operating room for control (50%), followed by observation (25%) and bedside topical treatment (13%). In the same scenario with a cooperative teenager, bedside topical treatment was most common (45%), followed by operating room for control (27%) and observation (16%). In patients presenting with active tonsillar bleeding, operating room for control was most common (83%) while few (6%) attempted bedside treatment. If the patient was a cooperative teenager, 38% attempted bedside treatment while 52% would still go to the operating room. Conclusions There is substantial variation in the management of post-tonsillectomy hemorrhage amongst the pediatric otolaryngologists. Further studies to determine outcomes associated with differing treatment strategies would be useful in establishing practice recommendations.

Background Lymphomas of the sinonasal tract are a rare and heterogeneous subset of solid sinonasal neoplasms. Objective To characterize, in this case series, presenting symptoms, treatment modalities, and outcomes for patients with sinonasal lymphoma within a single institution. Methods Retrospective patient data were collected from an academic, oncologic center and entered into a repository designed to capture outcomes for sinonasal malignancies. Patient demographics, presenting symptoms, imaging findings, treatment modalities, and health status were retrospectively extrapolated and evaluated by using Kaplan-Meier estimations for survival probability. Results Patients with sinonasal lymphoma with a mean follow-up of 50 months were identified (n = 18). Histologic diagnosis included the following: diffuse large B-cell lymphoma (n = 9), natural killer/T-cell lymphoma (n = 5), follicular lymphoma (n = 1), T-cell lymphoma (n = 1), and lymphoma-not otherwise specified (n = 2). The most frequent presenting symptoms were nasal obstruction (78%), facial pain (72%), facial swelling (50%), and nasal discharge (44%). Treatment before lymphoma diagnosis included antibiotics (83%), oral steroids (22%), decongestants (22%), and topical steroids (11%). Treatment regimens after diagnosis included both chemotherapy (94%) and chemoradiotherapy (56%). Survival rates by lymphoma subtype were 56% for B-cell lymphoma and 40% for natural killer/T-cell lymphoma. Overall, 2- and 5-year survival rates were 67% and 50%, respectively. The combination of chemotherapy and radiation resulted in significantly higher survival rates (p ≤ 0.001) than chemotherapy alone. Conclusion Sinonasal lymphomas are characterized by meager survival rates, which differ by histopathologic subtype. The diagnosis of sinonasal lymphoma is challenging because symptoms frequently parallel those of chronic rhinosinusitis. Increased awareness of these rare malignancies may improve detection and more timely treatment. Clinical trial registration NCT01332136.

As cell-cell interactions among tumor and immune cells are known to contribute to tumor progression, in depth evaluation of tumor-immune heterogeneity will enable biomarker-guided patient stratification and improvement of treatment response. Here we examined head and neck squamous cell carcinomas (HNSCC) to reveal the prognostic significance of leukocytes in tumors with regards to their complexity, effector status and spatial characteristics via multiplex immunohistochemistry and image cytometry. To accomplish this, we examined oropharyngeal HNSCC (N = 38), where lymphoid, myeloid, and hypo-inflamed leukocyte complexity correlated with HPV-status (Tsujikawa et al. Cell Reports, 2017). In the present study, quantitative analysis of cell density and distribution of 14-distinct immune cell lineages (e.g., CD8+ T cells, regulatory T cells, Th1, Th2, Th17, Th0 lymphocytes, B cells, NK cells, CD163+ and CD163- macrophages, mature and immature dendritic cells, mast cells, granulocytes) was analyzed via immune cell density mapping and tissue segmentation algorithms. We revealed tropism of polarized Th1-type cells within tumor nests versus stroma in HPV-associated HNSCC. In addition, Cox regression analysis of cell density and distribution of the 14 immune populations revealed that CD66b+ granulocyte infiltration within tumor nests reflected a negative prognostic indicator for HNSCC outcome. Furthermore, cell-cell proximity analysis in HPV-associated HNSCC further revealed a correlation between PD-L1 positive immune cells, and micro-regionally polarized immune characteristics biased towards Th1, coincident with high density of CD8+ T cells. These results reveal intra-tumor immune heterogeneity is associated with micro-regional immune complexity profiles, and provide insight into in situ immune characteristics that may aid patient stratification for immune therapy going forward. Acknowledgement: This project was supported by the Japan Society for the Promotion of Science Grant-in-Aid for Young Scientists (Start-up, 17H07016), Oregon Clinical and Translational Research Institute (OCTRI), grant number (UL1TR000128) from the National Center for Advancing Translational Sciences (NCATS) at the National Institutes of Health (NIH), and P30 CA069533-17 OHSU Knight Cancer Institute. LMC acknowledges support from the NIH/NCI, DOD BCRP Era of Hope Scholar Expansion Award, Susan G. Komen Foundation, Stand Up To Cancer - Lustgarten Foundation Pancreatic Cancer Convergence Dream Team Translational Research Grant, Breast Cancer Research Foundation, and the Brenden-Colson Center for Pancreatic Health. Citation Format: Takahiro Tsujikawa, Guillaume Thibault, Young Hwan Chang, Edward El Rassi, Daniel R. Clayburgh, David Sauer, Akihito Arai, Molly F. Kulesz-Martin, Motomi Mori, Shigeru Hirano, Paul W. Flint, Lisa M. Coussens. Intra-tumor immune heterogeneity is associated with prognosis of oropharyngeal head and neck squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 220.

Immunoglobulin G4-related disease (IgG4-RD) is an emerging clinicopathologic entity characterized by both IgG4+ plasma cell infiltration and fibrosis in one or more organs, prototypically pancreas or salivary/lacrimal glands. IgG4-RD in the thyroid (IgG4-RTD) is an area of active study, and the relationship between IgG4-RTD and Hashimoto thyroiditis is not fully delineated due to their overlapping histologic features. Retrospective review was performed of all thyroidectomy cases demonstrating lymphocytic inflammation at a single institution over a 4-year period. Approximately half (23/38) of patients had a clinical diagnosis of Hashimoto thyroiditis (HT). Nine of the 38 patients had increased absolute and relative numbers of IgG4+ plasma cells. Patients with a clinical diagnosis of HT had increased lymphoplasmacytic inflammation, but the relative proportion of IgG4+ plasma cells was not increased compared to patients without HT. There was no correlation between IgG4 levels and the amount of fibrosis in patients with or without HT. Patients identified as having the fibrosing variant of HT were not more likely to have increased levels of IgG4+ plasma cells than those without. There is significant morphologic and immunohistochemical overlap between HT and IgG4-RTD. Future studies to identify specific characteristics of IgG4-RTD involving the thyroid are necessary to accurately define this entity.

Importance Periocular necrotizing fasciitis is a rare but potentially devastating disease, accompanied by high rates of morbidity and mortality. Observations We report 5 cases of periocular necrotizing fasciitis resulting in severe vision loss, 3 of which required exenteration to contain the disease and only 1 of which recovered vision. Three cases were caused by group A streptococcus; 1, by methicillin-resistant Staphylococcus aureus ; and 1, by Streptococcus anginosus constellatus . Conclusions and Relevance Providers should maintain a high clinical suspicion for necrotizing fasciitis and distinguish it from more common forms of cellulitis. As seen in these 5 cases, periocular necrotizing fasciitis may cause severe visual loss more often than previously recognized. To our knowledge, this is also the first report of Streptococcus anginosus constellatus causing necrotizing fasciitis.

Introduction. Head and neck squamous cell carcinomas (HNSCCs) account for nearly 600,000 deaths worldwide annually and have limited treatment options. Approximately 20% of HNSCCs harbor amplifications of fibroblast growth factor receptor 1 (FGFR1) on chromosome 8p, however FGFR1 amplification by itself does not predict clinical response to FGFR inhibitors. We hypothesized that FGF2, or basic FGF, ligand expression is a better marker of FGFR activation and predictor of response to FGFR inhibitors. Results. A tissue micro array (TMA) of HNSCC patient biopsies was stained and quantitated for FGF2 expression by Aperio ImageScope software. FGF2 was significantly increased in recurrent tissue samples (p = 0.04). We examined a number of immortalized HNSCC cell lines and found that overexpression of both FGF2 and FGFR1 predicted response to the selective FGFR inhibitor PD173074. FGFR inhibition did not cause apoptosis, but rather induced a G0/G1 arrest and growth inhibition. FGFR inhibition also induced a change in cell morphology, with a significant increase in cell size and adherence. The expression of epithelial-to-mesenchymal transition (EMT) proteins was examined and FGF2-FGFR1 activation was associated with a more mesenchymal phenotype. Accordingly, FGFR inhibition reversed invasiveness as measured using the Incucyte WoundMaker scratch assay, suggesting that HNSCCs with FGF2-FGFR1 activation have more metastatic potential. Invasiveness of these cells in vivo was confirmed using orthotopic injection into the buccal pad of NSG mice. Once primary tumors reached 0.8 cm in size, mice were sacrificed and buccal mucosa, lung, liver, and neck tissue were examined post-mortem. All of the injected animals developed local invasion, and distant metastases in the lungs. 5/7 mice also had metastases in the liver and this model is being used to test the ability of FGFR inhibition to prevent metastasis. The mechanism of autocrine FGF2-FGFR1 activation was further explored and FGF2 was found to be secreted in association with extracellular vesicles (ECVs). Interestingly, inhibition of FGFR reduced secretion of ECVs and FGF2, providing a novel approach to target autocrine and paracrine FGFR1 activation within the tumor. We further tested a number of small molecule inhibitors in combination with PD173074 to look for synergistic combinations of kinase inhibitors and found significant synergy between EGFR and FGFR inhibitors suggesting this combination may be most effective in patients with HNSCC. Conclusions. Increased FGF2 in HNSCC patient samples is correlated with recurrent disease. FGF2-FGFR1 activation increases invasiveness through activation of EMT genes both in vitro, and in an orthotopic model. Inhibition of FGF2-FGFR1 reversed the invasive phenotype in vitro and may be an effective therapeutic strategy to reduce metastases in HNSCC patients. Citation Format: Isabel A. English, Jacqueline Martinez, Edward El Rassi, Mark Schmidt, Ellen Langer, Sophia Bornstein, John Gleysteen, Melissa Wong, Brian Druker, Elie Traer. FGF2 activation of FGFR1 in head and neck squamous cell carcinoma is associated with more invasive disease and can be attenuated by FGFR inhibition. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1631.