Cancer of the Nasal Cavity, Middle Ear and Accessory Sinuses - 15 Year Comparative Survival and Mortality Analysis by Age, Sex, Race, Stage, Grade, Cohort Entry Time-Period, Disease Duration and Topographic Primary Sites: A Systematic Review of 13,404 Cases for Diagnosis Years 2000-2017: (NCI SEER*Stat 8.3.8).

BACKGROUND: .-Sinonasal malignancies are rare, aggressive, deadly and challenging tumors to diagnose and treat. Since 2000, age-adjusted incidence rates average less than 1 case per 100,000 per year, male and female combined, in the United States. For the entire cohort, 2000-2017, overall median age-onset was 62.6 years. Carcinoma constitutes over 90% of these upper respiratory cancers and most cases are advanced, more than 72% (regional or distant stage) when the diagnosis is made. Composite mortality at 5 years was 108 excess deaths/1000/year with a mortality ratio of 558%, and 41% of deaths occurred in this time frame. As a consequence, observed median survival was approximately 6 years with 5-year cumulative observed survival (P) and relative survival rates (SR) 53% and 60%. This mortality and survival update study follows the World Health Organization International Classification of Diseases for Oncology-3rd Edition (ICD-O-3)1 topographical identification, coding, labeling and listing of 13,404 patient-cases accessible for analysis in the United States National Cancer Institute's Surveillance, Epidemiology and End Results program (NCI SEER Research Data, 18 Registries), 2000-2017 located in 8 primary anatomical sites: C30.0-Nasal cavity, C30.1-Middle ear, C31.0-Maxillary sinus, C31.1-Ethmoid sinus, C31.2-Frontal sinus, C31.3-Sphenoid sinus, C31.8-Overlapping lesion of accessory sinuses, C31.9-Accessory sinus, NOS. OBJECTIVES: .-1) Utilize national population-based SEER registry data for 2000-2017 to update cancer survival and mortality outcomes for 8 ICD-O-3 topographically coded sinonasal primary sites. 2) Discern similarities and contrasts in NCI-SEER case characteristics. 3) Identify current risk pattern outcomes and shifts in United States citizens, 2000-2017. METHODS: .-SEER Research Data, 18 Registries, Nov 2019 Sub (2000-2017)2,3 are used to examine the risk consequences of 13,404 patients diagnosed with sinonasal malignancies, 2000-2017, in this retrospective population-based study employing prognostic data stratified by topography, age, sex, race, stage, grade, 2 cohort entry time-periods (2000-06 & 2007-17), and disease-duration to 15 years. General methods and standard double decrement life table methodologies for displaying and converting SEER site-specific annual survival and mortality data to aggregate average annual data units in durational intervals of 0-1, 0-2, 1-2, 2-5, 0-5, 5-10, and 10-15 years are employed. The reader is referred to the "Registrar Staging Assistant (SEER*RSA)" for local-regional-distant Extent of Disease (EOD) sources used in the development of staging descriptions for the Nasal Cavity and Paranasal Sinuses (maxillary and ethmoid sinuses only) and Summary Stage 2018 Coding Manual v2.0 released September 1, 2020. Cancer staging & grading procedural explanations, statistical significance & 95% confidence levels4 are described in previous Journal of Insurance Medicine articles5,6 and other publications.7,8 Poisson confidence intervals at the 95% level based on the number of observed deaths are used in this study but not displayed here to conserve space on the mortality tables. Excluded were all death certificate only and those alive with no survival time. RESULTS: .-In the SEER 18 registries, a total of 13,404 patient cases (2000-2017) were available for analysis with an incidence of less than one patient per 100,000 people. From this group, analysis for survival and mortality totaled 10,624 patients. Males comprised 59.3% of cases and females 40.7%. Whites represented 80.3% of cases and black, others & unknown patients comprised 19.7%. The most common anatomic site of malignancy was the nasal cavity (49.7%); least common was the frontal sinus (1.2%). From diagnosis, across the span of 8 primary sites, first-year mortality rates q ranged from 14.3% (C30.0-nasal cavity) to 30.2% (C31.8-overlapping sinus) with corresponding excess death rates (EDR) of 118/1000/year and 279/1000/year. For single sites, the 5-year cumulative survival ratio (SR) was highest for the nasal cavity (69.5%) and lowest for overlapping lesions of the accessory sinuses (47.2%) with EDRs of 76 and 169 per 1000 per year respectively Overall, 5-year relative survival (SR) for all sinonasal tract malignancies combined was 60.3%, excess mortality (EDR) 108 per 1000 per year and mortality ratio 558%. CONCLUSIONS: .-The 8 sinonasal cancer primary sites are characterized by a low percentage of cases in the localized stage (28%). Since excess mortality is high even in the localized stage, overall prognosis is very poor for all patients. Excess mortality persists in cancer of the sinonasal tract as long as 10-15 years after diagnosis and treatment. EDR in the 15-year durational-interval, all sinonasal sites combined remained significant at 27.6 per 1000 per year with continuing decrease in cumulative survival ratio (SR) to 43.9%.

Multimodal assessment of high-risk human papillomavirus in sinonasal squamous cell carcinoma.

High-risk human papillomavirus (hrHPV) is an emerging risk factor for sinonasal squamous cell carcinoma (SNSCC). The goal of this study was to assess the prevalence of hrHPV and subtype distribution in SNSCC and correlation with patient and clinical characteristics. This retrospective cohort study included 43 cases diagnosed with incident primary SNSCC at the University of Cincinnati Medical Center from 2010 to 2015. The prevalence of hrHPV was interrogated using a multi-assay approach that included p16 immunohistochemistry (IHC), RNA in-situ hybridization (ISH), and hrHPV DNA sequencing. The association of hrHPV with 5-year overall survival (OS) and 2-year disease-free survival (DFS) was assessed. Fourteen cases (32.6 %) were classified as hrHPV positive, based on the a priori definition of having either a positive RNAScope™ ISH test or hrHPV DNA and p16-positive IHC; 9 cases (20.9 %) were positive for all three tests. All cases that arose from an inverted sinonasal papilloma (ex-ISP) were negative for hrHPV. HPV16 was the most common subtype among hrHPV positive cases (58.8 %), followed by HPV18 (17.6 %). No significant association was observed between hrHPV and OS or DFS after adjusting for potential confounding. hrHPV is prevalent in a sizable fraction of SNSCC. Additional studies are needed to better elucidate the relationship with patient survival outcomes and determine the optimal testing modality for prognostication.

Expression of immune checkpoint molecules TIGIT and TIM-3 by tumor-infiltrating lymphocytes predicts poor outcome in sinonasal mucosal melanoma.

BACKGROUND: Sinonasal mucosal melanoma (SNMM) is a rare but aggressive tumor with a poor prognosis. The co-inhibitory receptors T cell immunoglobulin and mucinodomain containing-3 (TIM-3), lymphocyte activation gene-3 (LAG-3) and T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) are promising new targets in anti-cancer immunotherapy. The expression profiles of these immune checkpoint molecules (ICMs) and potential prognostic implications have not been characterized in SNMM yet. METHODS: Immunohistochemical staining for TIGIT, LAG-3 and TIM-3 was performed on tumor tissue samples from 27 patients with primary SNMM. Associations between ICM expression and demographic parameters, AJCC tumor stage, overall survival, and recurrence-free survival were retrospectively analyzed. RESULTS: SNMM patients with low numbers of TIGIT+ and TIM-3+ tumor infiltrating lymphocytes (TILs) in the primary tumor survived significantly longer than patients with a high degree of TIGIT+ and TIM-3+ TILs. High infiltration with TIM-3+ or TIGIT+ lymphocytes was associated with the higher T4 stage and decreased 5-year survival. CONCLUSION: We identified high densities of TIM-3+ and TIGIT+ TILs as strong negative prognostic biomarkers in SNMM. This suggests that TIM-3 and TIGIT contribute to immunosuppression in SNMM and provides a rationale for novel treatment strategies based on this next generation of immune checkpoint inhibitors. Prospective studies with larger case numbers are warranted to confirm our findings and their implications for immunotherapy.

Topical Application of 5-Fluorouracil for the Treatment of Sinonasal Adenocarcinoma and Inverted Papilloma.

BACKGROUND: Sinonasal tumors represent a rare and heterogeneous group of rhinologic neoplasms. Even with advancements in surgical approaches, mortality rates of patients with sinonasal adenocarcinoma (SNAC) have not significantly improved and persistently high rates of recurrence in certain patients with inverted papilloma (IP) are seen. The use of 5-fluorouracil (5-FU) has been successfully described as an adjuvant treatment of SNAC and in the prevention of IP recurrence. OBJECTIVE: This review aims to present the current evidence on the management of SNAC and IP with topical 5-FU. METHODS: A three-author independent literature review was conducted to identify research involving the use of topical 5-FU for the treatment of SNAC and IP. A total of nine papers on the treatment of SNAC and IP were collected. RESULTS: The earliest study looking at the combination of adjuvant low-dose radiation and topical 5-FU for adenocarcinoma of the ethmoid sinus showed a 5-year survival rate of 100%. A follow-up study evaluating a similar protocol reported adjusted disease-free survival at 2, 5, and 10 years of 96%, 87%, and 74%, respectively. Similar results have been demonstrated for adjuvant 5-FU use following endoscopic resection and have even been described in the novel setting of transcutaneous 5-FU delivery following frontal trephination. Topical 5-FU has also been described in the treatment of aggressive IP. The largest case series described the use of 5-FU for eighteen cases and demonstrated only a single recurrence. CONCLUSION: The use of topical 5-FU currently represents an underutilized therapeutic modality within the treatment of rhinologic neoplasms. Available literature suggests that neoadjuvant use of topical 5-FU can improve survival and decrease recurrence for SNAC and IP. However, the small sample sizes prevent advocation for routine use in the general population and further research on 5-FU is necessary.

Non-intestinal-type adenocarcinoma of the nasal cavity and paranasal sinuses: an analysis of clinical characteristics and prognosis.

BACKGROUND: Non­intestinal adenocarcinoma of the nasal cavity and paranasal sinuses (non­ITAC) is a heterogeneous tumour that has rarely been reported in previous studies. We compared and analysed the symptoms, radiographic and pathological features, treatment methods, and prognosis of patients with low-grade (G1) and high-grade (G3) tumours. METHODS: This was a retrospective study included 22 patients with pathologically confirmed non-ITAC of the nasal cavity and paranasal sinuses who were treated between January 2008 and December 2021 at a single centre. Of these, 11 patients had G1 tumours, and 11 patients had G3 tumours. Clinicopathological features, treatment methods, and survival outcomes were analysed. RESULTS: The median follow-up period was 48.5 months. Nasal congestion was the most common initial symptom, and the nasal cavity was the most frequently involved site. For G1 tumours, the main treatment was simple surgery, 1 and 3­year overall survival (OS) rates were 100 and 88.9%, while the 1 and 3­year local control (LC) rates were 100 and 100%, respectively. For G3 tumours, the main treatments were surgery combined with radiotherapy and/or chemotherapy,1 and 3­year OS rates were 72.7 and 72.7%, while the 1 and 3­year LC rates were 100 and 90.91%, respectively. G3 tumours was associated with significantly shorter overall survival than G1 tumours (P = 0.035). Patients with stage III-IV showed shorter overall survival compared to stage I-II patients (P = 0.035). CONCLUSIONS: Non-ITAC of the nasal cavity and paranasal sinuses may frequently occur in the nasal cavity. The main treatment modality is surgery, supplemented by radiotherapy and chemotherapy. Pathological grade and tumour stage were poor prognostic factors for the disease.

Surgical management of advanced sinonasal cancer: a 10-year mono-institutional experience.

Objective: Endoscopic endonasal surgery is effective in the treatment of sinonasal cancers. However, in cases of well-differentiated locally advanced neoplasms as well as recurrences, the most appropriate treatment is debated. The purpose of this study is to report a mono-institutional experience on craniofacial surgery performed in a tertiary-care referral centre. Methods: This was a retrospective analysis of 90 patients treated with transcranial and/or transfacial resection for sinonasal cancer between 2010 and 2020. Outcome measures included overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS) and recurrence-free survival (RFS). Results: The 5-year OS, DSS and DFS were 48.2%, 60.6% and 28.7%, respectively. Factors correlated with prognosis were pT-classification (p = 0.002), histotype (p = 0.012) and dural involvement (p = 0.004). Independent prognostic factors were orbital apex infiltration (p = 0.03), age (p = 0.002) and adjuvant therapy (p = 0.03). Conclusions: When endoscopic endonasal surgery is contraindicated and chemoradiotherapy is not appropriate, craniofacial and transfacial approaches still represent an option to consider, despite the non-negligible morbidity.

Efficacy and Safety of Postoperative Adjuvant Radiation Therapy in Resected Nasal Cavity and Paranasal Sinus Mucosal Melanoma: A Combined Analysis.

PURPOSE: Mucosal melanoma of the nasal cavity and paranasal sinuses (NPMM) is a highly aggressive disease. The role of postoperative adjuvant radiation therapy is controversial. METHODS AND MATERIALS: A total of 300 patients with NPMM treated between March 2009 and January 2020 were divided into surgery alone (SA; 158 patients) and surgery plus radiation therapy (SR; 142 patients) groups. Postoperative radiation therapy was recommended, with a total dose of 65 to 70 Gy/30 to 35 fractions to the gross tumor volume and 60 Gy/30 fractions to the clinical target volume. The primary endpoint was relapse-free survival. Secondary endpoints included local recurrence-free survival, distant metastasis-free survival, and overall survival. RESULTS: At a median follow-up of 50.0 months, relapse-free survival in the SA and SR groups was 9.8 and 15.2 months (hazard ratio [HR], 0.714; 95% CI, 0.546-0.933; P = .014). Distant metastasis-free survival in the SA and SR groups was 23.8 and 21.3 months (HR, 0.896; 95% CI, 15.7-31.9 vs 13.3-29.3; P = .457). Overall survival in the SA and SR groups was 31.0 and 35.1 months (HR, 0.816; 95% CI, 25.7-36.3 vs 27.1-43.2; P = .178). For patients with stage IVA NPMM, radiation therapy reduced the incidence of relapse by 0.43-fold. CONCLUSIONS: Postoperative radiation therapy played a crucial role in the local control of resected NPMM, especially in patients with stage T4a or IVA disease.

Radiotherapy Results in Locally Advanced Sinonasal Cancer: Turkish Society for Radiation Oncology, Head and Neck Study Group 01-005.

OBJECTIVES: This study aims to examine the treatment outcomes and related factors in locally advanced sinonasal cancer across Turkiye. METHODS: Twelve centers participants of the Turkish Society for Radiation Oncology Head and Neck Study Group attended the study. One hundred and ninety-four patients treated with intensity-modulated radiation therapy between 2001 and 2021 were analyzed retrospectively. The survival analysis was performed using the Kaplan-Meier method. Acute and late toxicity were recorded per Common Toxicity Criteria for Adverse Events V4.0. RESULTS: The median age was 58 years and 70% were male. The majority of tumors were located in maxillary sinus (59%). Most of the patients (%83) had T3 and T4A disease. Fifty-three percent of patients were in stage 4A. Radiotherapy was administered to 80% of the patients in the adjuvant settings. Median 66 Gy dose was administered in median 31 fractions. Chemotherapy was administered concomitantly with radiotherapy in 45% of the patients mostly with weekly cisplatin. No grade ≥4 acute and late toxicity was observed. The median follow-up was 43 months. The 5-year and 10-year overall survival (OS); locoregional recurrence-free survival (LRFS); distant metastasis-free survival (DMFS), and progression-free survival (PFS) rates were 61% and 47%; 69% and 61%; 72%, and 69%, and 56% and 49%, respectively. In the multivariate analysis, several factors demonstrated significant influence on OS, such as performance status, surgery, and lymph node involvement. Moreover, surgery was the key prognostic factor for LRFS. For DMFS, lymph node involvement and surgical margin were found to be influential factors. In addition, performance status and lymph node involvement were identified as significantly affecting PFS. CONCLUSIONS: In our study, the authors obtained promising results with IMRT. Performance status, lymph node involvement, and surgery emerged as the primary factors significantly influencing OS.

Choice of surgery in intestinal-type adenocarcinoma of the sinonasal tract: a long-term comparative study.

PURPOSE: Intestinal-type adenocarcinoma (ITAC) is a rare sinonasal malignancy. Curative treatment requires multidisciplinary approach, with surgical options consist of the endonasal endoscopic approach (EEA) and external surgery (EXTS). Here, we provide the post-operative and survival results from a single-center long-term follow-up. METHODS: We report long-term follow-up of 92 ITAC cases treated between 1998 and 2018, treated with EEA (n = 40) or EXTS (n = 52). Survival estimates, post-operative complications and duration of hospitalization were compared between surgical modalities. RESULTS: Baseline characteristics were similar. A higher number of T4b tumors (16%), and subsequently more tumoral invasion (39%), was present in patients undergoing EXTS compared to EEA (3% and 18%, respectively). No difference in Barnes histology subtypes was noticed. Patients undergoing EEA had a shorter post-operative hospitalization stay versus EXTS (4 versus 7 days). Use of EEA was associated to improved disease-specific survival (DSS; 11.4 versus 4.4 years; HREEA = 0.53), especially for patients with T3-4a tumors (11.4 versus 3.0 years; HREEA = 0.41). Patients with T3-4 stage, tumoral invasion, positive surgical margins, mucinous or mixed histology, and prolonged post-operative hospital stay showed poor local relapse-free, disease-free, overall, and DSS. CONCLUSIONS: Long-term follow-up in locally advanced ITAC demonstrates that resection by EEA is correlated with improved DSS compared to EXTS, especially for T3-4 tumors. No significant differences between both treatment modalities was observed regarding per- and post-operative complications, although hospitalization in patients undergoing EEA was shorter than for patients treated with EXTS. These results confirm that EEA should remain the preferred surgical procedure in operable cases of sinonasal ITAC.

Improved outcomes of localized diffuse large B-cell lymphoma at the Waldeyer ring in comparison to the sinonasal area in the rituximab era.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) of the head-and-neck area primarily involves the Waldeyer ring (WR) and sinonasal area (SN). However, the differential clinical outcomes between patients with WR-DLBCL and those with SN-DLBCL in the rituximab era remain unclear. METHODS: To avoid confounding factors contributed by advanced DLBCL with WR and SN involvement, we assessed the clinical outcomes of patients with stage I/II WR-DLBCL and SN-DLBCL and compared them with those having corresponding stages of DLBCL in the lymph nodes but without other extranodal involvement (LN-DLBCL) in the same period. We compared the patients' clinical characteristics, treatment modalities, event-free survival (EFS), and overall survival (OS) among the three subgroups. RESULTS: We analyzed 67, 15, and 106 patients with WR-DLBCL, SN-DLBCL, and LN-DLBCL, respectively, between January 2000 and December 2019. All patients received front-line rituximab-based regimens, and > 80% received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone-based regimens. More patients with SN-DLBCL had revised International Prognostic Index (R-IPI) score 3 (27%) when compared with those with WR-DLBCL (7%) and those with LN-DLBCL (10%, p = 0.181). Patients with WR-DLBCL, LN-DLBCL, and SN-DLBCL had 5-year EFS and OS rates of 80.7%, 59.5%, and 41.9% (p = 0.021) and 83.7%, 70.8%, and 55.8% (p = 0.032), respectively. Compared to patients with LN-DLBCL, those with WR-DLBCL also had a significantly favorable 5-year EFS rate (p = 0.021) and 5-year OS rate (p = 0.023). Three of the 15 patients with SN-DLBCL experienced lymphoma recurrence in the brain after front-line treatment. In multivariate analyses, R-IPI scores of 1-2 and 3 served as significantly poor prognostic factors for patients with poor EFS and OS. CONCLUSIONS: Compared to patients with LN-DLBCL, patients with WR-DLBCL receiving front-line rituximab-based treatments had favorable clinical outcomes; however, patients with SN-DLBCL had worse clinical outcomes. Further studies on molecular prognostic factors and treatment strategies for SN-DLBCL are warranted.

Development and validation of a nomogram for prognosis of sinonasal adenocarcinoma (a nomogram for sinonasal adenocarcinoma).

BACKGROUND: The incidence of sinonasal adenocarcinoma is low, and there are few studies on survival and prognosis. Therefore, we aim to develop and validate a prognostic model for predicting the overall survival of sinonasal adenocarcinoma and provide guidance for clinical management. METHODS: Patients who were diagnosed as sinonasal adenocarcinoma through Surveillance, Epidemiology, and End Results database between 1975 and 2015 were randomly divided into a training group and validation group. Univariate, multivariate survival analysis was performed to screen independent survival factors. A nomogram was established to predict the overall survival rate of sinonasal adenocarcinoma. Receiver operating characteristic curve and calibration plot were performed to verify the discrimination and accuracy of the model. A decision curve analysis was performed to verify the clinical applicability of the model. RESULTS: A total of 423 patients with sinonasal adenocarcinoma were randomly divided into training group (n = 299) and verification group (n = 124). We established and verified the Nomo map including age, marriage, grade, surgery and tumour size. The c-index of Surveillance, Epidemiology, and End Results stage, T stage and this model are 0.635, 0.626 and 0.803, respectively. The survival rate of the high-risk group scored by this model was lower than that of the low-risk group (P < 0.001). Decision curve analysis shows that the model has advantages in predicting survival rates. CONCLUSION: Our model is considered to be a useful tool for predicting the overall survival of sinonasal adenocarcinoma, with good discrimination and clinical applicability. We hope that this model will help rhinologists to make clinical decisions and manage patients diagnosed with sinonasal adenocarcinoma.

Intragenic NF1 deletions in sinonasal mucosal malignant melanoma.

Mucosal malignant melanoma (MMM) is a rare and aggressive tumor. Despite effective local therapies, tumor recurrence and metastasis remain frequent. The genetics of MMM remain incompletely understood. This study is aimed to identify actionable genetic alterations by next-generation sequencing. Fifteen MMM samples were analyzed by next-generation and Sanger sequencing. Gene copy number alterations were analyzed by MLPA. Mutation status was correlated with pERK, pAKT, and Ki-67 expression and follow-up data. Inactivating mutations and intragenic deletions in neurofibromatosis type-1 (NF1) were identified in 3 and 2 cases, respectively, (in total 5/15, 33%) and activating mutations in NRAS and KRAS (3/15, 20%) cases. Other mutated genes included CDKN2A, APC, ATM, MITF, FGFR1, and FGFR2. BRAF and KIT mutations were not observed. Cases with NF1 alterations tended to have worse overall survival. The mutational status was not associated with pERK, pAKT, or Ki-67 immunostaining. MMM carries frequent gene mutations activating the MAPK pathway, similar to cutaneous melanoma. In contrast, NF1 is the most frequently affected gene. Intragenic NF1 deletions have not been described before and may go undetected by sequencing studies. This finding is clinically relevant as NF1-mutated melanomas have worse survival and could benefit from therapy with immune checkpoint and MEK inhibitors.

Decreasing recurrence and increasing survival rates in patients of ethmoid or sphenoid intestinal-type adenocarcinomas: Systematic review and meta-analysis with 1126 cases.

BACKGROUND: Ethmoid or sphenoid intestinal-type adenocarcinomas (ITACs) form a distinct subtype of sinonasal adenocarcinomas that occur less than 1 case/100,000/yr. They have obvious exposure relationship to hardwood or leather dusts, infrequent metastasis, but a relatively high local-recurrence rate. They locate at sinuses close to vital structures listed as high-risk areas in surgeries. Even in expert hands, a craniofacial resection is associated with non-negligible mortality and morbidity. Management of these tumors, first or recurrent, needs to weigh these consequences versus the survival, regional-recurrence, and distant-recurrence rates. Due to the rareness of ethmoid or sphenoid ITACs, accurate overall survival and local- or regional-recurrence rates across diverse treatments are unclear. The aim of this study is to report the overall statistics of this cancer and the relationship between enrollment year versus age, recurrence, and survival. METHODS: Systemic review and meta-analysis with 1126 cases across various treatments in the literature. RESULTS: Here, we show that patients of ethmoid or sphenoid ITACs had overall local-, regional-, and distant-recurrence rates of 32.2%, 2.2%, and 10.3%, respectively, with a 5-year overall survival rate of 66.2%. The results present a significant correlation between age, local-recurrent rate, or overall survival rate versus enrollment year. CONCLUSION: This suggests that recent patients of ethmoid or sphenoid ITACs may present at an older mean age, have a lower local-recurrence rate, and have a better 5-year survival rate than before. There was a shifting trend of treating ethmoid ITACs from external approach to endoscopic resection. Clinicians may want to weigh mortality and morbidity rates of external surgeries and these data to share or decide a solution.

Extranodal Extension as an Indicator for Sinonasal Squamous Cell Carcinoma Prognosis.

OBJECTIVE: Although extranodal extension (ENE) is a known indicator of poor prognosis for head and neck malignancies, its value as an indicator for sinonasal squamous cell carcinoma (SCC) has not been well characterized. This study seeks to assess the usefulness of ENE as a prognostic marker for sinonasal SCC. STUDY DESIGN: Retrospective database review. SETTING: National Cancer Database from 2010 to 2015. METHODS: The National Cancer Database was queried from 2010 to 2015 for all patients with sinonasal SCC with available ENE status (n = 355). These cases were divided into those with pathologically confirmed ENE (n = 146) and those without ENE (n = 209). Univariate and multivariate analyses were used to examine survival differences and predictors of ENE status. RESULTS: Most patients with ENE were ≥60 years old (61.7%), male (61.6%), and white (83.6%). Patients aged 60 to 69 and 80+ years were more likely to have ENE than those under 60 years (P < .05). Patients with ENE had worse 1-year overall survival than those without ENE (58.2% vs 70.8%, log-rank P = .008). After multivariate regression, however, there was no survival difference detected between ENE-positive and ENE-negative cases (hazard ratio, 1.14 [0.775-1.672], P = .508). CONCLUSION: ENE status did not have a significant effect on survival in patients with sinonasal SCC. Thus, ENE alone may not necessarily be a helpful indicator for sinonasal SCC prognosis.

Survival Outcomes of De Novo vs Inverted Papilloma-Associated Sinonasal Squamous Cell Carcinoma: A Systematic Review and Meta-analysis.

Importance: Overall, the prognosis of sinonasal squamous cell carcinoma (SCC) is poor. This malignancy can arise de novo or from inverted papillomas, but it is unclear whether survival differences between the 2 pathologies exist. Objective: To assess for survival differences between patients with sinonasal de novo SCC (dnSCC) and those with inverted papilloma-associated SCC (IPSCC). Data Sources: A search of Ovid MEDLINE, Embase, Scopus, and the Cochrane Library from inception to January 23, 2020, with cross-referencing of retrieved studies, was performed. Additional data were requested from authors. Study Selection: Inclusion and exclusion criteria were designed to capture studies with survival outcomes of adults with sinonasal SCC who underwent regular treatment. Clinical trials, cohort studies, case-control studies, and case series with more than 10 adults aged 18 years or older with sinonasal SCC were included. Exclusion criteria were studies on non-SCC sinonasal neoplasms, studies without histopathologic diagnoses, non-English language articles, nonhuman animal studies, and abstract-only articles. Two blinded investigators (J.J.L., A.M.P., T.W.E., or N.S.W.) screened each abstract and full text, and a third investigator (J.J.L. or P.P.) adjudicated discrepancies. Of 729 unique citations, 26 studies of 1194 total patients were included. Data Extraction and Synthesis: Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines were followed. The Methodological Index for Nonrandomized Studies (MINORS) criteria were used to assess study quality. Two blinded investigators (J.J.L., A.M.P., T.W.E., or N.S.W.) independently extracted data from each study. Data were pooled using a random-effects model. Main Outcomes and Measures: The primary outcome was overall survival, and secondary outcomes were disease-free and disease-specific survival. Before data collection, it was hypothesized that the dnSCC cohort would have worse survival outcomes than the IPSCC cohort. Results: One study of patients with dnSCC, 12 studies of patients with IPSCC, and 5 studies with both cohorts were included in the meta-analysis of overall survival. The pooled 5-year overall survival rate for 255 patients with dnSCC was 56% (95% CI, 41%-71%; I2 = 83.8%) and for 475 patients with IPSCC was 65% (95% CI, 56%-73%; I2 = 75.7%). Five comparative studies of both cohorts totaling 240 patients with dnSCC and 155 patients with IPSCC were included in another meta-analysis. The pooled overall survival hazard ratio was 1.87 (95% CI, 1.24-2.84; I2 = 0%). Conclusions and Relevance: This systematic review and meta-analysis found that patients with dnSCC had almost a 2-fold increased risk of mortality compared with those with IPSCC. Large, multicenter studies are necessary to validate these findings before considering treatment alterations such as de-escalation based on histopathology.

Survival Outcomes in Sinonasal Poorly Differentiated Squamous Cell Carcinoma.

OBJECTIVE: Sinonasal squamous cell carcinoma (SCC) is rare with no consensus on treatment regimen. Our goal is to analyze treatment outcomes in poorly differentiated SCC (PDSCC) using a large national database. STUDY DESIGN: Retrospective database study. METHODS: The National Cancer Database was queried for sinonasal invasive SCC, grade 3 (poorly differentiated) from 2004 to 2014. Patient demographics and tumor and treatment characteristics were tabulated. Kaplan-Meier (KM) analysis was performed to compare overall survival (OS) between histology subtype and primary site. Multivariable Cox proportional hazards regression was performed for statistical analysis of treatment regimen on OS. RESULTS: A total of 1,074 patients were identified. The maxillary sinus was the most common site (45%). T4 tumors were observed in 50% of patients, with most patients treated at high-volume facilities (77%). In KM analysis, spindle cell SCC histological subtype, primary tumors of the maxillary sinus, and poorly differentiated grade had worse OS. In our Cox-PH model, higher T stage and age were associated with worse OS. Those treated at a high-volume facility and those who underwent surgical resection followed by adjuvant radiation had improved OS. Chemotherapy within the treatment regimen did not confer survival benefit except in surgical patients when positive margins were present, and surgery with adjuvant chemoradiation trended toward improved survival. CONCLUSIONS: Sinonasal PDSCC appears to be best treated at high-volume centers with surgical resection followed by adjuvant radiation. Poorly differentiated grade has worse OS compared to more differentiated tumors. Chemotherapy along with adjuvant radiation may have a role in patients with positive surgical margins. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E1040-E1048, 2021.