Sinonasal mucosal melanoma in The Netherlands between 2001 and 2021: a clinical and epidemiological overview of 320 cases.

PURPOSE: Sinonasal mucosal melanoma (SNMM) is a rare malignancy, characterised by high (local) recurrence rates and poor survival. Comprehensive understanding of tumour etiology is currently lacking, which complicates adequate tumour treatment. Besides examining trends in incidence, this study aims to assess the association between clinical characteristics, treatment practices and patient outcomes, with the objective of establishing a baseline from which SNMM management can be enhanced. METHODS: All newly diagnosed SNMM cases in The Netherlands between 2001 and 2021 were included using data from The Netherlands Cancer Registry (NCR). RESULTS: A total of 320 patients were included. The annual incidence rate for the overall population was stable over the inclusion period with an annual percentage change (APC) of only - 0.01%. The 5-year overall survival (OS) and relative survival (RS) were 24.5 and 32.4%, respectively. Relative survival did not increase over time. The addition of adjuvant radiotherapy to surgery was not associated with a higher OS and RS compared to surgery alone. CONCLUSION: Sinonasal mucosal melanoma is a rare disease with stable incidence rates in the Netherlands between 2001 and 2021. There has been no improvement in survival over the course of the inclusion period. The study reaffirms that adjuvant radiotherapy does not seem to improve patient outcomes. Given the generally poor outcomes for SNMM patients, novel therapeutic options ought to be considered in order to improve care.

Meta-analysis of multi-modality therapies in sinonasal undifferentiated carcinoma-A timely update.

OBJECTIVES: Sinonasal undifferentiated carcinoma (SNUC) is a rare but aggressive tumour with very poor prognosis. There are currently no well-established clinical trials to guide therapy and the impact of various treatment modalities on survival is not well defined. We aim to provide an updated systematic review on current treatment modalities on survival outcomes. DESIGN AND SETTING: Individual patient data were extracted, and survival data pooled in a one-stage meta-analysis. Descriptive statistics were analysed using the Kaplan-Meier method. Patient-level comparisons stratified by treatment modalities, adjusted for demographics, were conducted using shared-frailty Cox regression. PARTICIPANTS AND MAIN OUTCOME MEASURES: Participants include all patients diagnosed with SNUC based on histological evidence. We looked at the overall cumulative survival outcome for different treatment modalities and overall survival by treatment modality in low versus high stage SNUC patients. RESULTS AND CONCLUSION: Seventeen studies were identified, comprising 208 patients from 1993 to 2020. There was no significant difference in cumulative overall survival in low versus high stage patients, and no significant difference in outcomes by treatment modality. The overall cumulative survival of SNUC is 30% at 95 months. Among patients treated with various combinations of treatment modalities, patients with chemoradiotherapy had the highest cumulative survival of 42% at 40 months. Definitive chemoradiotherapy was associated with improved disease survival rate. Regardless of tumour stage, patients should be treated early and aggressively, with no superiority of one treatment regimen over another. Trimodality treatment does not confer survival advantage over bimodality treatment.

High-risk human papillomavirus 16/18 associated with improved survival in sinonasal squamous cell carcinoma.

BACKGROUND: There has been conflicting evidence on the independent prognostic role of human papillomavirus (HPV) status in sinonasal cancer. The objective of this study was to assess whether the survival of patients with sinonasal cancer differs based on various HPV statuses, including HPV-negative, positive for the high-risk HPV-16 and HPV-18 (HPV16/18) subtypes, and positive for other high-risk and low-risk HPV subtypes. METHODS: In this retrospective cohort study, data from the National Cancer Database were extracted from the years 2010-2017 for patients who had primary sinonasal cancer (N = 12,009). The outcome of interest was overall survival based on HPV tumor status. RESULTS: Study included an analytic cohort of 1070 patients with sinonasal cancer who had confirmed HPV tumor status (732 [68.4%] HPV-negative; 280 [26.2%] HPV16/18-positive; 40 [3.7%] positive for other high-risk HPV; and 18 [1.7%] positive for low-risk HPV). HPV-negative patients had the lowest all-cause survival probability at 5 years postdiagnosis (0.50). After controlling for covariates, HPV16/18-positive patients had a 37% lower mortality hazard than HPV-negative patients (adjusted hazard ratio, 0.63; 95% confidence interval [CI], 0.48-0.82). Patients aged 64-72 years (crude prevalence ratio, 0.66; 95% CI, 0.51-0.86) and 73 years and older (crude prevalence ratio, 0.43; 95% CI, 0.31-0.59) presented with lower rates of HPV16/18-positive sinonasal cancer than those aged 40-54 years. In addition, Hispanic patients had a 2.36 times higher prevalence of non-HPV16/18 sinonasal cancer than non-Hispanic White patients. CONCLUSIONS: These data suggest that, for patients with sinonasal cancer, HPV16/18-positive disease may confer a significant survival advantage compared with HPV-negative disease. Other high-risk and low-risk HPV subtypes have survival rates similar to the rates for HPV-negative disease. HPV status might be an important independent prognostic factor in sinonasal cancer that could be used in patient selection and clinical decisions.

The Role of Induction Therapy for Sinonasal Cancers.

OPINION STATEMENT: The role of induction chemotherapy in sinonasal cancers is promising; however, prospective studies with higher grades of evidence are needed. With the currently available literature, the authors would advocate for the use of induction chemotherapy (IC) in locally advanced sinonasal squamous cell carcinoma (T3-T4) for organ preservation and potentially for improved survival outcomes. In sinonasal undifferentiated carcinoma (SNUC), IC should be considered in all patients given its tendency for aggressive invasion and poor outcomes. In SNUC, response to IC may direct the modality of definitive treatment to follow. In responders (partial or complete), chemoradiation therapy should be strongly considered. In non-responders or in those with progression of disease, surgical therapy is favored. For esthesioneuroblastoma, surgical resection with negative margins and adjuvant radiation therapy remains the gold standard. However, IC may be considered for locally advanced disease especially with orbital invasion or in recurrent/distant disease. There is no definite indication for IC in sinonasal adenoid cystic carcinoma or sinonasal adenocarcinoma. Recommendations are summarized in Table 1.

Frailty does not worsen postoperative outcomes in sinonasal squamous cell carcinoma.

PURPOSE: Sinonasal squamous cell carcinoma (SCC) is an aggressive malignancy frequently requiring surgical resection and adjuvant treatment. Frailty is a metric that attempts to estimate a patient's ability to tolerate the physiologic stress of treatment. There is limited work describing frailty in patients with sinonasal cancer. We sought to determine the impact of frailty on postoperative outcomes in patients undergoing treatment for sinonasal SCC. MATERIALS AND METHODS: Cases of patients undergoing surgical resection of sinonasal SCC at two tertiary medical centers were queried. Demographic, treatment, and survival data were recorded. Frailty was calculated using validated indexes, including the American Society of Anesthesiologists (ASA) classification, modified 5-item frailty index (mFI-5), and the Charlson Comorbidity Index (CCI). Primary outcomes included medical and surgical complications, readmission, and length of stay (LOS). RESULTS: 38 patients were included. There were 23 (60.5 %) men and 15 (39.5 %) women with an average age of 59.6 ± 12.1 years. MFI-5 was 0.76 ± 0.54 and CCI was 5.71 ± 2.64. No significant association was noted between frailty measures and postoperative outcomes including 30-day medical complications, 30-day surgical complications, any 30-day complication, and readmission. Increased ASA was noted to be predictive of increased length of stay (Incidence Rate Ratio: 1.80, 95 % confidence interval [CI]: 1.16-2.83, p = 0.009). CONCLUSIONS: We found no association between frailty metrics and worsening surgical or medical postoperative outcomes. This suggests that frailty metrics may not be as relevant for sinonasal surgery even for advanced pathologies, given the more limited physiologic impact of minimally invasive surgery.

Signaling Pathways mTOR and ERK as Therapeutic Targets in Sinonasal Intestinal-Type Adenocarcinoma.

Despite advances in surgery and radiotherapy, the overall prognosis of sinonasal intestinal-type adenocarcinoma (ITAC) is poor, and new treatment options are needed. Recent studies have indicated alterations in cellular signaling pathways that may serve as targets for modern inhibitors. Our aim was to evaluate the frequency of mTOR and ERK pathway upregulation in a retrospective series of 139 ITAC and to test the efficacy and mechanism of action of candidate targeted inhibitors in cell line ITAC-3. An immunohistochemical analysis on p-AKT, p-mTOR, p-S6, p-4E-BP1, and p-ERK indicated, respectively, a 68% and 57% mTOR and ERK pathway activation. In vitro studies using low doses of mTOR inhibitor everolimus and ERK inhibitor selumetinib showed significant growth inhibition as monotherapy and especially as combined therapy. This effect was accompanied by the downregulation of mTOR and ERK protein expression. Our data open a new and promising possibility for personalized treatment of ITAC patients.

Relevance of apparent diffusion coefficient features for a radiomics-based prediction of response to induction chemotherapy in sinonasal cancer.

In this paper, several radiomics-based predictive models of response to induction chemotherapy (IC) in sinonasal cancers (SNCs) are built and tested. Models were built as a combination of radiomic features extracted from three types of MRI images: T1-weighted images, T2-weighted images and apparent diffusion coefficient (ADC) maps. Fifty patients (aged 54 ± 12 years, 41 men) were included in this study. Patients were classified according to their response to IC (25 responders and 25 nonresponders). Not all types of images were acquired for all of the patients: 49 had T1-weighted images, 50 had T2-weighted images and 34 had ADC maps. Only in a subset of 33 patients were all three types of image acquired. Eighty-nine radiomic features were extracted from the MRI images. Dimensionality reduction was performed by using principal component analysis (PCA) and by selecting only the three main components. Different algorithms (trees ensemble, K-nearest neighbors, support vector machine, naïve Bayes) were used to classify the patients as either responders or nonresponders. Several radiomic models (either monomodality or multimodality obtained by a combination of T1-weighted, T2-weighted and ADC images) were developed and the performance was assessed through 100 iterations of train and test split. The area under the curve (AUC) of the models ranged from 0.56 to 0.78. Trees ensemble, support vector machine and naïve Bayes performed similarly, but in all cases ADC-based models performed better. Trees ensemble gave the highest AUC (0.78 for the T1-weighted+T2-weighted+ADC model) and was used for further analyses. For trees ensemble, the models based on ADC features performed better than those models that did not use those features (P < 0.02 for one-tail Hanley test, AUC range 0.68-0.78 vs 0.56-0.69) except the T1-weighted+ADC model (AUC 0.71 vs 0.69, nonsignificant differences). The results suggest the relevance of ADC-based radiomics for prediction of response to IC in SNCs.

Target coverage and local recurrences after radiotherapy for sinonasal cancer in Denmark 2008-2015. A DAHANCA study.

PURPOSE: The study aimed to investigate the pattern of failure and describe compromises in the definition and coverage of the target for patients treated with curatively intended radiotherapy (RT) for sinonasal cancer (SNC). METHODS AND MATERIAL: Patients treated with curatively intended RT in 2008-2015 in Denmark for SNC were eligible for the retrospective cohort study. Information regarding diagnosis and treatment was retrieved from the national database of the Danish Head and Neck Cancer Group (DAHANCA). Imaging from the diagnosis of recurrences was collected, and the point of origin (PO) of the recurrent tumour was estimated. All treatment plans were collected and reviewed with the focus on target coverage, manual modifications of target volumes, and dose to organs at risk (OARs) above defined constraints. RESULTS: A total of 184 patients were included in the analysis, and 76 (41%) relapsed. The majority of recurrences involved T-site (76%). Recurrence imaging of 39 patients was evaluated, and PO was established. Twenty-nine POs (74%) were located within the CTV, and the minimum dose to the PO was median 64.1 Gy (3.1-70.7). The criteria for target coverage (V95%) was not met in 89/184 (48%) of the CTV and 131/184 (71%) of the PTV. A total of 24% of CTVs had been manually modified to spare OARs of high-dose irradiation. No difference in target volume modifications was observed between patients who suffered recurrence and patients with lasting remission. CONCLUSION: The majority of relapses after radical treatment of SNC were located in the T-site (the primary tumour site). Multiple compromises with regards to target coverage and tolerance levels for OARs in the sinonasal region, as defined from RT guidelines, were taken. No common practice in this respect could be derived from the study.

Outcome for sinonasal malignancies: a population-based survey.

PURPOSE: Sinonasal malignancies (SNM) represent a rare and complex group of cancers that includes a wide range of histopathological subtypes. Data from population-based cohorts are scarce but warranted as a basis for randomized controlled treatment trials (RCTs). Our aim was to assess overall and histology subset-specific outcomes for SNM patients treated at a tertiary referral centre. METHODS: A retrospective, population-based, consecutive cohort of patients with SNMs diagnosed from 2001 through 2019 was examined. Outcome was analysed in relation to age, gender, site, stage, histopathology, and treatment. RESULTS: Two-hundred and twenty-six patients were identified, whereof 61% presented with stage IV disease. 80% completed treatment with curative intent, which comprised surgery with neoadjuvant (29%) or adjuvant (37%) radiotherapy, monotherapy with surgery (22%), definitive chemoradiotherapy (7%), or radiotherapy (5%). Median follow-up was 106 months. The 5- and 10-year overall survival rates were 57% and 35%, respectively. Median overall survival was 76 months (esthesioneuroblastoma: 147 months; adenocarcinoma: 117; salivary carcinoma: 88; mucosal melanoma: 69; squamous cell carcinoma: 51, undifferentiated carcinoma: 42; neuroendocrine carcinoma: 9; and NUT-carcinoma 5). The 5- and 10-year disease-free survival rates were 63% and 54%, respectively, and disease-specific survival 83% and 66%. Increasing age, stage IVB, melanoma histopathology, and treatment with definitive chemoradiotherapy emerged as significant independent prognostic risk factors for disease-specific mortality (p ≤ 0.001). CONCLUSION: The results indicate a seemingly good outcome in comparison to previous reports, particularly for mucosal melanoma, adenocarcinoma, and undifferentiated carcinoma. The study provides additional background for future RCTs focusing on histology subset-specific treatment for SNM.

Translational genomics of sinonasal cancers.

The sinonasal cavities harbor a wide variety of histologically distinct cancers, the majority very aggressive with 5-year survival rates between 30-60% and local recurrence as the main cause of death. This is a complex anatomic area, close to structures such the eyes and the brain, which is of special relevance for surgery and postoperative radiotherapy. The low incidence of these rare tumors hampers accumulation of experience with diagnosis and clinical managment as well as knowledge on recurrent genetic aberrations or testing of new treatment strategies. However, recent years have seen a growing number of publications on genetic aberrations providing data that can aid or fine-tune classification and provide molecular targets for treatment with specific inhibitors. In addition, new sinonasal cancer models are created that enable preclinical testing of candidate inhibitor drugs. With more and more novel targeted therapies being developed, options for personalized treatment of sinonasal cancer patients are now opening up.

Management of a Unique Sinonasal Undifferentiated Carcinoma Subtype in the Era of SARS-CoV-2.

The novel coronavirus (SARS-CoV-2) pandemic has influenced the timeliness of care for patients with both common and rare conditions, particularly those affecting high-risk operative sites such as the upper aerodigestive tract. Sinonasal undifferentiated carcinoma (SNUC) represents a rare malignancy of the sinonasal tract, a unique subset of which has never been previously reported in the otolaryngology literature and is characterized by inactivation of the SMARCB (INI-1) tumor suppressor gene. This subtype exhibits a particularly poor prognosis and is characterized pathologically by its rhabdoid appearance. Here we present the case of an individual who was diagnosed with a sinonasal mass during the SARS-CoV-2 pandemic, which was ultimately found to be SMARCB (INI-1)-deficient sinonasal carcinoma. Advanced imaging was deferred in the interest of limiting the patient's exposure to the virus, and expedited operative management was performed which facilitated prompt referral for adjuvant chemoradiation. The SARS-CoV-2 pandemic presents unique challenges, but the work-up of high-risk lesions must be prioritized; this continues to be paramount as SARS-CoV-2 resurges in many cities across the USA.

Prognostic and Therapeutic Implications of Immune Classification by CD8+ Tumor-Infiltrating Lymphocytes and PD-L1 Expression in Sinonasal Squamous Cell Carcinoma.

Sinonasal squamous cell carcinoma (SNSCC) is an aggressive tumor predominantly arising in the maxillary sinus and nasal cavities. Advances in imaging, surgical and radiotherapeutic techniques have reduced complications and morbidity; however, the prognosis generally remains poor, with an overall 5-year survival rate of 30-50%. As immunotherapy may be a new therapeutic option, we analyzed CD8+ tumor-infiltrating lymphocytes (TILs) and the tumor microenvironment immune type (TMIT, combining CD8+ TILs and PD-L1) in a series of 57 SNSCCs. Using immunohistochemistry, tissue samples of 57 SNSCCs were analyzed for expression of CD8 on TILs and of PD-L1 on tumor cells. The results were correlated to the clinical and survival data. In total, 88% (50/57) of the tumors had intratumoral CD8+ TILs; 19% (11/57)-CD8high (>10%); and 39/57 (68%)-CD8low (1-10%). PD-L1 positivity (>5%) was observed in 46% (26/57) of the SNSCCs and significantly co-occurred with CD8+ TILs (p = 0.000). Using univariate analysis, high intratumoral CD8+ TILs and TMIT I (CD8high/PD-L1pos) correlated with a worse survival rate. These results indicate that SNSCCs are immunogenic tumors, similar to head and neck squamous cell carcinomas. Nineteen percent of the cases were both CD8high and PD-L1pos and this subgroup may benefit from therapy with immune checkpoint inhibitors.

[The new national guidelines for the keeping of the Italian Sinonasal Cancer Registry (ReNaTuNS)]. / Il nuovo manuale operativo ReNaTuNS per la gestione dei casi di tumore naso-sinusale.

Sinonasal cancers (SNC) are rare tumours with predominant occupational aetiology associated with exposures to specific carcinogens. In Italy, SNC incidence has been under compulsory surveillance since 2008, through the National Sinonasal Cancer Registry (ReNaTuNS), a nationwide cancer registry coordinated by the National Institute for Insurance Against Accidents at Work (Inail). The ReNaTuNS has a regional structure with local registries, established at Regional Operating Centres (CORs). Currently, seven Italian Regions are active in SNC search and, together with Inail, have recently released a new version of the national guidelines for keeping the Registry (available on the Inail website). The aim of this text is to present the new guidelines, an updating version, and to underline the relevance of this tool in enforcing the role of the ReNaTuNS, considering the high occupational fraction of SNC and the unicity of the Italian Registry, which collects all the information available on occupational exposures of each SNC case registered. It is recommended that the active search for SNC cases and the analysis of exposure become a systematic and well-organized activity to prevent or reduce risks of exposure and to support and improve the efficiency of the compensation and welfare system.

Novel Biomarkers in Sinonasal Cancers: from Bench to Bedside.

PURPOSE OF REVIEW: Sinonasal cancers are a heterogenous group of rare cancers for which histopathological diagnosis can be very challenging and treatment options are limited for advanced disease in particular. Here, we review the candidacy of novel diagnostic and prognostic biomarkers, and therapeutic targets for sinonasal cancers. RECENT FINDINGS: Molecular multidimensional analyses of sinonasal cancers have been lagging behind other major cancers, but there are numerous publications describing the discovery of novel candidate biomarkers, e.g. the methylation classifier, originally developed for brain cancers, and gene expression panels for the prediction of response to induction chemotherapy in sinonasal undifferentiated carcinoma. The most promising biomarkers are summarized and discussed further with regard to their clinical applicability and future potential. Many of the described novel biomarkers for sinonasal cancers will eventually overcome the pitfalls associated with the frequently non-specific immunohistological tests. With comprehensive, multidimensional molecular testing of these tumours in collaborative consortia projects, our better understanding of the molecular mechanisms of sinonasal cancers and their carcinogenesis will determine the most useful diagnostic and prognostic biomarkers, allow stringent multi-institutional validation and guide trials on targeted therapies.

Multimodal Therapy for Sinonasal Malignancies: Updates and Review of Current Treatment.

OPINION STATEMENT: Sinonasal malignancies pose a significant challenge in management due to their low incidence, biologic diversity, and significant symptom burden. Even though surgery remains the primary therapeutic modality, a multi-modality approach has been shown to benefit a significant proportion of patients and its success depends largely on stage and histologic type. Non-surgical approaches such as novel radiation approaches as well as intensification with systemic therapy hold promise in altering the organ preservation rate as well as overall survival for patients. Practice changing randomized trials to test these novel modalities are overdue and desperately needed.

Sinonasal adenocarcinoma following styrene exposure in the reinforced plastics industry.

BACKGROUND: Sinonasal adenocarcinoma is a rare disease expected to have rare causes and potential for strong risk factors as reflected by the strong association with occupational wood dust exposure. High level styrene exposure is a rare and suspected carcinogen, and this study examines the exposure-response relation between occupational styrene exposure, sinonasal adenocarcinoma and other subtypes. METHODS: We followed 73 092 styrene-exposed workers from 1968 to 2011 and identified sinonasal cancers in the Danish Cancer Registry. We modelled cumulative styrene exposure and estimated incidence rates and age, sex and wood-industry adjusted ORs. RESULTS: During 1 585 772 person-years, we observed nine cases of adenocarcinoma, corresponding to a fivefold non-significantly increased OR for estimates of high versus low cumulative styrene exposure (OR 5.11, 95% CI 0.58 to 45.12). The increased risk was confined to exposure received during the recent 15 years. The other histological subtypes showed no increased risk. CONCLUSION: This study suggests increased risk of sinonasal adenocarcinoma following styrene exposure. The observations are, however, few, confounding from wood dust exposure cannot be ruled out, and additional studies are needed before firm conclusions can be drawn.

Sinonasal cancer in the Italian national surveillance system: Epidemiology, occupation, and public health implications.

BACKGROUND: Sinonasal cancer (SNC) is a rare tumor with predominant occupational etiology associated with exposures to specific carcinogens. The aim of this study is to describe SNC cases recorded in Italy in the period 2000-2016. METHODS: Clinical information, occupational history, and lifestyle habits of SNC cases collected in the Italian Sinonasal Cancer Register were examined. Age-standardized rates were estimated. RESULTS: Overall, 1529 cases were recorded. The age-standardized incidence rates per 100 000 person-years were 0.65 in men and 0.26 in women. Occupational exposures were predominant among the attributed exposure settings, primarily to wood and leather dusts. Other putative causal agents included chrome, solvents, tannins, formaldehyde, textile dusts, and pesticides. Many cases had unknown exposure. CONCLUSIONS: Epidemiological surveillance of SNC cases and their occupational history is fundamental for monitoring the occurrence of the disease in exposed workers in industrial sectors generally not considered at risk of SNC as well as in non-occupational settings.

Treatment, outcomes, and demographics in sinonasal sarcoma: a systematic review of the literature.

BACKGROUND: Sarcomas comprise a diverse group of soft tissue mesenchymal malignancies. The sinuses and nasal region are a relatively rare site of sarcomas. METHODS: Retrospective review of the literature on sinonasal sarcomas from 1987-2017. Data were analyzed for demographics, treatment type, stage, and histopathologic type. Kaplan-Meier analysis was used to assess and compare survival. RESULTS: A total of 198 cases of sinonasal sarcoma were identified and analyzed. The median age at diagnosis was 39 years. Overall 5-, 10-, and 20-year survival was 61.3%, 58.9%, and 49.1%, respectively, and disease-free 5-, 10-, and 20-year survival was 53.2%, 49.1%, and 38.3%, respectively. Lymph node metastasis was present at diagnosis in 3.0% of cases, and distant metastasis was present in 3.5% of cases. On univariate analysis T stage, overall stage, treatment type, histopathologic subtype, and presence of distant metastasis significantly affected survival. On multivariate analysis overall stage alone significantly predicted overall survival. Open vs. endoscopic surgery, total radiation dose, and presence of neck metastasis did not significantly affect survival. Combined modality treatment was associated with higher survival rates than single modality therapy. CONCLUSIONS: Sinonasal sarcoma is a relatively rare malignancy. Lower T and overall stage, lack of distant metastasis, and multimodality therapy were associated with improved survival. Certain histopathologic subtypes were associated with poorer survival.

Survival in sinonasal and middle ear malignancies: a population-based study using the SEER 1973-2015 database.

BACKGROUND: The sinuses, nasal cavity, and middle ear represent a rarer location of head and neck malignancy than more common sites such as the larynx and oral cavity. Population-based studies are a useful tool to study the demographic and treatment factors affecting survival in these malignancies. METHODS: Population-based database search of the Survival, Epidemiology, and End Results (SEER) database from 1973 to 2015 for malignancies involving the nasal cavity, paranasal sinuses, and middle ear. Data were analyzed for demographics, treatment type, stage, primary site and histopathologic type. Kaplan-Meier analysis was used to assess and compare survival. RESULTS: A total of 13,992 cases of sinonasal or middle ear malignancy were identified and analyzed. The majority of patients were between ages 50 and 80 at the time of diagnosis. Overall 5-, 10-, and 20-year survival was 45.7%, 32.2%, and 16.4%, respectively. Lymph node metastasis was reported in 4.4% of patients, while distant metastasis was present in 1.5% of cases. On univariate analysis surgical vs. nonsurgical treatment, sex, race, age at diagnosis, T stage, N stage, M stage, AJCC overall stage, primary site, tumor grade, and histopathologic subtype significantly affected survival. On multivariate analysis age, race, sex, primary site, overall AJCC stage, surgical vs. nonsurgical treatment, and T, N, and M stage remained significant predictors of overall survival. CONCLUSIONS: Malignancies of the nasal cavity, paranasal sinuses, and middle ear account for a minority of overall head and neck cancers. The overall 5-, 10-, and 20-year survival for these malignancies is relatively low. Higher T, N, M, and overall stage and higher tumor grade is associated with lower survival. Patients treated with surgery as part of the treatment regimen had higher overall survival. Demographics and primary site also significantly affect survival. Certain histopathologic subtypes were associated with poorer survival.

Customized individual applicators for endocavitary brachytherapy in patients with cancers of the nasal cavity, sinonasal region and nasopharynx.

Brachytherapy has become an established therapeutic regimen for primary, persistent, recurrent and metastatic tumour disease in the head and neck region. This study presents the authors' preliminary experience with intracavitary brachytherapy by means of an individual silicone applicator in the treatment of patients with nasal, sinonasal, orbital and nasopharyngeal cancer. Between January 2001 and January 2013, twenty patients with cancer of the nasal cavity, the paranasal sinuses and nasopharynx underwent surgery and intracavitary brachytherapy with the aid of an individually manufactured silicone applicator in the Department of Otolaryngology, Head and Neck Surgery and in the Department of Radiotherapy and Radiooncology at the Saarland University Medical Center of Homburg, Germany. The tumour was localized in the nasal cavity/paranasal sinuses (15) affecting the orbit twice and the nasopharynx (5). There were 14 patients with squamous cell carcinoma, 2 patients with mixed tumours and one patient with adenocarcinoma, adenoid cystic carcinoma, mucosal melanoma or plasmocytoma. The majority of the patients presented with advanced disease (T3 or T4 tumours). In 18/20 patients, brachytherapy was performed as a boost technique, in the remaining two solely because of a previous radiation series. All surgical interventions were performed endonasally. Three to six weeks after surgery, a cast of the nasal cavity was created under general anaesthesia. Subsequently, an individual brachytherapy silicon applicator with two to four plastic tubes was manufactured. The radiation therapy was applied using the Ir-192 high-dose-rate-afterloading method (total dose 10-20 Gy) in two to five sessions, additionally in 18/20 patients a percutaneous radiotherapy with a total dose of 30-60 Gy was applied. After a mean duration of follow-up of 2 years, 7/20 patients experienced a local progression, 5/19 a regional recurrence in the neck nodes and 4/19 distant metastases. The 2-year survival was 57.3 %. No serious complications were reported. The silicone applicator was well tolerated by all patients. Because of the complexity of the sinonasal anatomy with the finding of mainly advanced tumours, the presented individual silicone brachytherapy applicator has proven to be useful and meaningful for endocavitary brachytherapy of malignancies of the nasal cavities, paranasal sinuses and nasopharynx.