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Background Sinonasal undifferentiated carcinoma (SNUC) is a rare, aggressive malignancy with a poor prognosis, and multimodal therapy is the standard of care. We sought to characterize treatment delays in SNUC managed with surgery and adjuvant radiation and to determine the impact on survival using the National Cancer Database (NCDB). Methods This was a retrospective, population-based cohort study of patients with SNUC between 2004 and 2016 in the NCDB. The intervals of diagnosis to surgery (DTS), surgery to radiation (SRT), and radiation duration (RTD) were examined. Recursive partitioning analysis (RPA) was performed to identify the variables with the greatest impact on survival. The association between treatment delay and overall survival (OS) was then assessed using multivariate Cox proportional hazards regression. Results Of 173 patients who met inclusion criteria, 65.9% were male, average age at diagnosis was 56.6 years, and 5-year OS was 48.1%. Median durations of DTS, SRT, and RTD were 18, 43, and 46 days, respectively. Predictors of treatment delay included Black race, government insurance excluding Medicare/Medicaid, and positive margins. RPA-derived optimal thresholds were 29, 28, and 38 days for DTS, SRT and RTD, respectively. On multivariate analysis, positive margins (hazard ratio [HR]: 4.82; 95% confidence interval [CI]: 2.28–10.2) and DTS less than 29 days (HR: 2.41; 95% CI: 1.23–4.73) were associated with worse OS. Conclusion Our results likely reflect the aggressive nature of the disease with surgeons taking more invasive disease to the operating room more quickly. Median treatment intervals described may serve as relevant national benchmarks. [ABSTRACT FROM AUTHOR]

Objectives Although adjuvant radiotherapy may be indicated in patients with sinonasal squamous cell carcinoma (SNSCC) following primary surgery, some patients choose to forgo recommended postoperative radiation therapy (PORT). This study aimed to elucidate factors associated with patient refusal of recommended PORT in SNSCC and examine overall survival. Methods Retrospective analysis of patients with SNSCC treated with primary surgery from the National Cancer Database diagnosed between 2004 and 2016. A multivariable logistic regression model was created to determine the association between clinical or demographic covariates and likelihood of PORT refusal. Unadjusted Kaplan–Meier estimates, log-rank tests, and a multivariable Cox proportional hazard model were used to assess overall survival. Results A total of 2,231 patients were included in the final analysis, of which 1,456 (65.3%) were males and 73 (3.3%) refused recommended PORT. Patients older than 74 years old were more likely to refuse PORT than those younger than 54 (odds ratio [OR] 3.43, 95% confidence interval [CI]: 1.84–6.62). Median survival among the entire cohort, those who received recommended PORT, and those who refused PORT was 83.0 months (95% CI: 74.6–97.1), 83.0 months (95% CI: 74.9–98.2), and 63.6 months (95% CI: 37.3–101.4), respectively. Refusal of PORT was not associated with overall survival (hazard ratio: 0.99, 95% CI: 0.69–1.42). Conclusions PORT refusal in patients with SNSCC is rare and was found to be associated with several patient factors. The decision to forgo PORT is not independently associated with overall survival in this cohort. Further study is required to determine the clinical implications of these findings as the treatment decisions are complex. [ABSTRACT FROM AUTHOR]

Objectives: Myoepithelial carcinoma (MECA) is a rare salivary gland tumor that can occur in the sinonasal cavity with poor outcomes. There are limited data on sinonasal outcomes to guide management. We sought to use the National Cancer Database (NCDB) to better define treatment outcomes in MECA. Methods: We conducted a retrospective analysis of the NCDB from 2004 to 2016 for patients with MECA of the sinonasal cavity. Patient demographic, treatment, and survival information were extracted from the database. Unadjusted Kaplan–Meier estimates, log-rank tests, and a multivariable Cox proportional hazard model were used to assess overall survival (OS). Results: A total of 38 patients were included. The average age was 60.7 ± 18.2 years and male patients represented 47.4% of the cohort. Most patients were White (n = 26, 68.4%) and the majority of patients had either private insurance (n = 20, 52.6%) or Medicare (n = 15, 39.5%). The primary site of most tumors was nasal cavity (n = 19, 50%), followed by maxillary sinus (n = 16, 42.1%). Most tumors were >4 cm (n = 17, 44.7%). The 1-, 5-, and 10-year OS was 89.7% (95% confidence interval [CI]: 80.7%−99.8%), 63.6% (95% CI: 49.4%−82%), and 46.4% (95% CI: 31%−69.5%), respectively. The median survival for the overall cohort was 85.8 months. Medicare insurance was associated with a decreased OS (hazard ratio [HR]: 8.2; 95% CI: 2.88−23.4, P <.001). Patients who underwent surgery had a significant survival benefit (HR: 0.04, 95% CI: 0.01−0.21, P <.001). Discussion: MECA of the sinonasal cavity is a rare tumor with poorly understood behavior. Data from the NCDB suggests that it is a relatively aggressive tumor with surgical management associated with better outcomes. This analysis is limited by the small sample size and further research into optimal treatment regimens is needed. [ABSTRACT FROM AUTHOR]

Background: Chondrosarcomas of the sinonasal cavity and skull base are uncommon malignancies. We sought to provide long‐term outcomes at two tertiary care centers. Methods: Patients with chondrosarcoma treated between 2000 and 2021 were included. The primary outcomes were overall survival (OS) and disease‐specific survival (DSS). Results: Thirty‐eight patients met inclusion criteria. Fourteen patients had sinonasal (36.8%), 7 petroclival (18.4%), and 17 other primary skull base lesions (44.7%). Twenty‐eight patients (73.7%) underwent radiation with an average dose of 67.3 ± 15.1 Gy. Eighteen patients (47.4%) required revision surgery for recurrence. 1, 5, and 10‐year OS were 97.3%, 93.1%, and 74.7%. DSS at 5‐ and 10‐year survival was 95.7%. Adjuvant radiation was associated with improved OS (HR: 0.12; 95% CI: 0.02–0.75, p = 0.023). Conclusion: We present our experience over the last 20 years treating chondrosarcomas. Favorable survival outcomes can be achieved but recurrence requiring repeat resection is common. [ABSTRACT FROM AUTHOR]

Background: Acinic cell carcinoma (ACC) is a salivary gland malignancy that rarely can involve the sinonasal cavity. There are limited outcomes data available to guide management. Objective: We sought to use the National Cancer Database (NCDB) to characterize treatment outcomes in sinonasal ACC. Methods: A retrospective analysis of the NCDB from 2004 to 2016 for patients with ACC involving the sinonasal cavity was conducted. Demographic, treatment, and survival information were obtained. Unadjusted Kaplan-Meier estimates, log-rank tests, and a multivariable Cox proportional hazard model were used to assess overall survival (OS). Results: A total of 28 patients were included in the analysis with an average age of 58.6 ± 15.5 years. Half the patients (n = 14, 50%) were male, mostly white (n = 23, 82.1%), and with private insurance (n = 16, 57.1%). The nasal cavity was the most common subsite (n = 18, 64.3%), followed by the maxillary sinus (n = 5, 17.9%). Most patient received surgery alone (n = 17, 60.7%), with the remaining patients undergoing surgery followed by radiation (n = 8, 28.6%), radiation alone (n = 1, 3.6%), and no treatment (n = 2, 7.1%). The 1-, 5-, and 10-year survival in this cohort was 100% (95% CI: 100%–100%), 84.3% (95% CI: 71.2%–99.7%), and 72.2% (95% CI: 55%–94.8%), respectively. On multivariate analysis, older age was associated with worse OS (hazard ratio (HR): 1.27; 95% CI: 1.11–1.46, P <.001). Disease of the sphenoid sinus correlated with worse survival (HR: 198, 95% CI: 10.4–3,739, P <.001) and large tumor size was associated with worse OS on log-rank test, but not on multivariate analysis. Conclusion: Sinonasal ACC is a rare entity with relatively good long-term outcomes. Older age and primary disease of the sphenoid sinus are associated with worse outcomes. Most patients are treated with surgical resection. Future research is needed to assess the optimal timing and indications for radiation therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Inverted papillomas are benign sinonasal tumors that can recur or become cancerous. The mainstay of treatment is surgical resection. We summarize the biology of inverted papillomas and review surgical outcomes in an effort to define the current treatment strategy. Inverted papillomas (IP) are the most common sinonasal tumor with a tendency for recurrence, potential attachment to the orbit and skull base, and risk of malignant degeneration into squamous cell carcinoma (SCC). While the overall rate of recurrence has decreased with the widespread adoption of high-definition endoscopic optics and advanced surgical tools, there remain challenges in managing tumors that are multiply recurrent or involve vital neurovascular structures. Here, we review the state-of-the-art diagnostic tools for IP and IP-degenerated SCC, contemporary surgical management, and propose a surveillance protocol. [ABSTRACT FROM AUTHOR]

Long‐term survival and recurrence patterns of squamous cell carcinoma arising from inverted papilloma (IP‐SCC) have not been thoroughly investigated. Four electronic databases were searched and primary studies describing overall survival (OS), recurrence, and mean time to recurrence of patients with IP‐SCC were included for review. Our search yielded 662 studies. The 28 studies selected for inclusion identified 663 patients with IP‐SCC. In 596 patients with reported T classification, 439 (73.7%) were T3/T4 on presentation. Of the 650 participants with recurrence data (local, regional, and distant), 155 (23.8%) experienced a recurrence, with an aggregate mean time‐to‐recurrence of 24.3 months. In 565 patients with 5‐year OS rates, the aggregate 5‐year OS was 62%. Based on the literature to date, IP‐SCC is associated with a 5‐year OS rate of 62%. 23.8% of patients experienced recurrence at a mean time of 24.3 months, suggesting the need for long‐term surveillance. [ABSTRACT FROM AUTHOR]

Objective: To evaluate recurrence patterns and survival after recurrence among patients with sinonasal mucosal melanoma (SNMM). Methods: This was a multi‐institutional retrospective review from seven U.S. institutions of patients with SNMM from 1991 to 2022. Recurrence was categorized as local, regional, distant, or multifocal. Kaplan‐Meier tests were used to evaluate disease‐free survival (DFS), overall survival (OS), and post‐recurrence survival (PRS) reported with standard errors (SE) and log‐rank testing used for comparison. Cox‐regression was further used, with hazard ratios (HR) and 95% confidence intervals (CI) reported. Results: Among 196 patients with SNMM, there were 146 patients with recurrence (74.5%). Among all patients, 60‐month DFS (SE) was 15.5% (2.9%), 60‐month OS (SE) was 44.7% (3.7%), mean age ± standard deviation at diagnosis was 69.7 ± 12.5 years, and 54.6% were female. In 26 patients who underwent primary treatment of the neck, 60‐month DFS did not differ from no treatment (p > 0.05). Isolated distant recurrence was most common (42.8%), followed by local (28.3%), multifocal (20.7%), and regional recurrence (8.3%). Among patients with regional recurrence in the neck, there was no 60‐month PRS benefit for patients undergoing salvage neck dissection or radiation (p > 0.05). Among patients with distant recurrence, only immunotherapy was associated with improved 12‐month PRS (HR = 0.32, 95% CI = 0.11–0.92, p = 0.034), and no treatment group was associated with improved 24‐ or 60‐month PRS (p > 0.05). Conclusion: SNMM is associated with a high recurrence rate and poor survival. Primary treatment of the neck was not associated with reduced recurrence, and immunotherapy for treatment of distant recurrence was associated with increased 12‐month PRS. [ABSTRACT FROM AUTHOR]

Background: Non‐steroidal anti‐inflammatory drugs (NSAIDs) have emerged as an alternative to opioids for optimal postoperative pain management. However, the adoption of NSAIDs in sinonasal surgery has been impeded by a theoretical concern for postoperative bleeding. Our objective is to systematically review the efficacy and safety of NSAIDs for patients undergoing sinonasal surgery. Methods: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, CINAHL, and the WHO International Clinical Trials Registry Platform were searched from inception to January 27, 2022. Randomized controlled trials (RCTs) and comparative observational studies in any language were considered. Screening, data extraction, and risk of bias assessment were performed in duplicate. Our outcomes were postoperative pain scores, requirement for rescue analgesia, and postoperative adverse events (epistaxis, nausea/vomiting). Results: Out of 4661 records, 15 RCTs (enrolling 1210 patients) and two observational studies were included. Following endoscopic sinus surgery, there was no difference in pain scores between NSAIDs and non‐NSAIDs groups (standardized mean differences [SMD] 0.44 units better, 95% CI –0.18 to 1.05). Following septorhinoplasty, NSAIDs decreased pain scores compared to non‐NSAID regimens (SMD 1.14 units better, 95% CI 0.61 to 1.67 units better). Overall, NSAIDs reduced the need for rescue medication with a relative risk (RR) of 0.45 (95% CI 0.24 to 0.84). In addition, NSAIDs decreased the risk of nausea with an RR of 0.62 (95% CI 0.42 to 0.91) and did not increase the risk of epistaxis (RR 0.72, 95% CI 0.23‐2.22). Conclusion: Among patients undergoing sinonasal surgery, NSAIDs are beneficial in postoperative pain management and avoidance of postoperative nausea without increasing the risk of postoperative epistaxis. [ABSTRACT FROM AUTHOR]

Background: Succinate, although most famous for its role in the Krebs cycle, can be released extracellularly as a signal of cellular distress, particularly in situations of metabolic stress and inflammation. Solitary chemosensory cells (SCCs) express SUCNR1, the succinate receptor, and modulate type 2 inflammatory responses in helminth and protozoal infections in the small intestine. SCCs are the dominant epithelial source of interleukin‐25, as well as an important source of cysteinyl leukotrienes in the airway, and have been implicated as upstream agents in type 2 inflammation in chronic rhinosinusitis (CRS) and asthma. Methods: In this study, we used scRNAseq analysis, live cell imaging of intracellular calcium from primary sinonasal air‐liquid interface (ALI) cultures from 1 donor, and measure antimicrobial peptide release from 5 donors to demonstrate preliminary evidence suggesting that succinate can act as a stimulant of SCCs in the human sinonasal epithelium. Results: Results from scRNAseq analysis show that approximately 10% of the SCC/ionocyte cluster of cells expressed SUCNR1 as well as a small population of immune cells. Using live cell imaging of intracellular calcium, we also demonstrate that clusters of cells on primary sinonasal ALI cultures initiated calcium‐mediated signaling in response to succinate stimulation. Furthermore, we present evidence that primary sinonasal ALI cultures treated with succinate had increased levels of apical beta‐defensin 2, an antimicrobial peptide, compared to treatment with a control solution. Conclusion: Overall, these findings demonstrate the need for further investigation into the activation of the sinonasal epithelium by succinate in the pathogenesis of CRS. [ABSTRACT FROM AUTHOR]

Background: Sinonasal lymphoma (SL) is a heterogeneous, underrecognized neoplastic disorder with limited outcomes data. We sought to better define outcomes by subtype and treatment at 2 referral centers over the past 2 decades. Methods: Demographics, clinicopathologic data, and treatment outcomes for patients treated for SL were queried from January 1, 2000 to December 31, 2021 at 2 tertiary academic medical centers. Results: Eighty‐four patients were included, with an average age at diagnosis of 63.4 ± 15 years. There were 34 females (40.5%). The majority of patients had an Eastern Cooperative Oncology Group (ECOG) score of <2 (76.2%) and the most common presenting symptom was facial swelling/pain (26.2%). The most common primary site was the nasal cavity (36.9%). Diffuse large B‐cell lymphoma was the most common subtype (46.4%), followed by extranodal NK/T‐cell lymphoma (17.9%). Chemotherapy was the most common treatment strategy (n = 59, 70.2%), followed by radiation therapy (n = 35, 41.7%) and immunotherapy (n = 24, 28.6%). Disease‐specific survival rates at 1, 5, and 10 years were 85.7%, 73.6%, and 58.6%, respectively. Eighteen patients (21.4%) developed recurrence. On multivariate analysis, higher ECOG score (p < 0.0001) and history of head and neck radiation (p = 0.048) were associated with worse survival. Younger age was associated with greater risk of recurrence (p = 0.022) and male sex was associated with more treatment side effects (p = 0.012). Conclusion: This is the largest multi‐institutional analysis of SL characteristics and outcomes. Our work suggests that, although disease control in the first 5 years is reasonable, 10‐year outcomes remain challenging. Further studies are needed to investigate new treatment paradigms and risk stratification. [ABSTRACT FROM AUTHOR]

Background: Management of sinonasal malignancy (SNM) often includes surgical resection as part of the multimodality treatment. Treatment‐related surgical morbidity can occur, yet risk factors associated with complications in this population have not been sufficiently investigated. Methods: Adult patients with histologically confirmed SNM whose primary treatment included surgical resection were prospectively enrolled into an observational, multi‐institutional cohort study from 2015 to 2020. Sociodemographic, disease, and treatment data were collected. Complications assessed included cerebrospinal fluid leak, orbital injury, intracranial injury, diplopia, meningitis, osteoradionecrosis, hospitalization for neutropenia, and subsequent chronic rhinosinusitis. The surgical approach was categorized as endoscopic resection (ER) or open/combined resection (O/CR). Associations between factors and complications were analyzed using Student's t test, Fisher's exact test, and logistic regression modeling. Results: Overall, 142 patients met the inclusion criteria. Twenty‐three subjects had at least 1 complication (16.2%). On unadjusted analysis, adjuvant radiation therapy was associated with developing a complication (91.3% vs 65.5%, p = 0.013). Compared with the ER group (n = 98), the O/CR group (n = 44) had a greater percentage of higher T‐stage lesions (p = 0.004) and more frequently received adjuvant radiation (84.1% vs 64.4%, p = 0.017) and chemotherapy (50.0% vs 30.6%, p = 0.038). Complication rates were similar between the ER and O/CR groups without controlling for other factors. Regression analysis that retained certain factors showed O/CR was associated with increased odds of experiencing a complication (odds ratio, 3.34; 95% confidence interval, 1.06‐11.19). Conclusions: Prospective, multicenter evaluation of SNM treatment outcomes is feasible. Undergoing O/CR was associated with increased odds of developing a complication after accounting for radiation therapy. Further studies are warranted to build upon these findings. [ABSTRACT FROM AUTHOR]