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.

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.

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.

The role of endoscopic resection for selected patients with sinonasal squamous cell carcinoma.

OBJECTIVE: Despite of rapid advances in endoscopic surgery, the gold standard for sinonasal squamous cell carcinoma (SNSCC) surgery has remained the open approach with en-block resection due to the aggressive nature of SNSCC, including frequent recurrence and high mortality rate. For that reason, few studies have focused on SNSCC treated by endoscopic surgery alone. The objective of this study was to evaluate the usefulness of endoscopic surgery for patients with SNSCC. METHODS: A retrospective analysis was performed for 15 consecutive SNSCC patients who underwent endoscopic surgery without an open approach. We carefully selected patients whose tumor attachment sites could be fully visualized and completely resected through an endonasal approach. RESULTS: Of the fifteen patients, 4 patients (27%) were diagnosed with T1, 7 (47%) with T2, 4 (27%) with T3, and no patients with T4a or T4b disease. Four of the 15 (27%) patients showed positive surgical margins. The 5-yr overall survival, disease-specific survival, and local control rate was 72.4%, 79.6%, and 92.9%, respectively. The 5-yr disease-specific survival for T1, T2, and T3 disease was 100% and 75% and 75%, respectively. Patients with negative surgical margins had a better disease-specific survival rate than did those with positive surgical margins (p = 0.0253). CONCLUSION: Endoscopic surgery for patients with SNSCC appears to afford an effective method in selected cases. The achievement of negative surgical margins with a good view of the tumor attachment site was considered to be critical to the management of SNSCC.

Outcomes of Primary Versus Salvage Surgery for Sinonasal Malignancies: A Population-Based Analysis.

OBJECTIVES/HYPOTHESIS: There exists a lack of consensus on the optimal sequence of treatment for many sinonasal malignancies (SNMs). This study compares the overall survival (OS) outcomes for primary surgery (PS) versus salvage surgery (SS) in SNM patients across stage, histology, and primary site. STUDY DESIGN: Retrospective database review. METHODS: The National Cancer Database was queried for all SNM cases treated with multimodal surgical and nonsurgical therapy between 2004 and 2015. Logistic regression identified predictors of SS. Cox proportional hazards models evaluated predictors of mortality, and Kaplan-Meier log-rank test assessed OS outcomes. RESULTS: Our SNM cohort consisted of 3,011 patients (PS = 2,804; SS = 207). SS patients had significantly longer postoperative hospital stays (P = .009) and increased rates of 30-day (P < .001) and 90-day mortality (P < .001) compared to PS. On multivariate logistic regression, predictors of undergoing SS included sinonasal undifferentiated carcinoma histology (odds ratio = 2.72; 95% confidence interval [CI]: 1.16-6.66; P = .024). On multivariate Cox proportional hazards analyses among SS patients, late-stage disease (hazard ratio [HR] = 4.80; 95% CI: 1.46-15.8; P = .01) and positive surgical margins (HR = 2.31; 95% CI: 1.29-4.13; P = .005) portended significantly worse OS. In the propensity score-matched cohort controlling for stage and histology, PS had significantly improved OS compared to SS (P = .007). Compared to SS, PS also had improved OS in subgroup analyses for patients with late-stage disease (P = .026) and squamous cell carcinoma histology (P = .006). CONCLUSIONS: In our SMN cohort, PS resulted in improved OS outcomes compared to SS independent of stage and histology. Consideration may be given to primary surgical resection for SMN whenever feasible, though a targeted, individualized approach is warranted. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:E710-E718, 2021.

Treatment sequence of cetuximab and immune checkpoint inhibitor in head and neck squamous cell carcinoma differentially affects outcomes.

OBJECTIVES: To examine the impact of treatment sequences of Immune checkpoint inhibitor (ICI) and cetuximab on clinical outcomes in patients with recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: Clinicopathologic data were retrospectively collected on patients with R/M HNSCC who received ICI treatment. Association between treatment sequence and clinical outcomes were assessed. RESULTS: A total of 113 patients with R/M HNSCC were analyzed. Patients who had cetuximab prior to ICI had worse overall (HR, 1.83) and progression-free survival (HR, 1.76) compare to those without prior cetuximab. Among patients who had subsequent therapy after ICI, cetuximab-based therapy was associated with a trend toward higher response rate and longer survival than non-cetuximab regimen. CONCLUSION: Our single institution analysis showed that treatment sequence of cetuximab and ICI in R/M HNSCC may affect clinical outcomes. Cetuximab prior to ICI was associated with worse outcomes while the efficacy of cetuximab may be enhanced after ICI therapy.

Carbon ion radiation therapy for sinonasal malignancies: Promising results from 2282 cases from the real world.

The aim of this study is to compare the effectiveness of carbon ion radiation therapy (CIRT), proton radiation therapy (PRT), and photon-based intensity-modulated radiation therapy (IMRT) in the treatment of sinonasal malignancies. We identified studies through systematic review and divided them into three cohorts (CIRT group/PRT group/IMRT group). Primary outcomes of interest were overall survival (OS) and local control (LC). We pooled the outcomes with meta-analysis and compared the survival difference among groups using Chi2 (χ2 ) test. A representative sample of 2282 patients with sinonasal malignancies (911 in the CIRT group, 599 in the PRT group, and 772 in the IMRT group) from 44 observation studies (7 CIRT, 16 PRT, and 21 IMRT) was included. The pooled 3-year OS, LC, distant metastasis-free survival, and progression-free survival rates were 67.0%, 72.8%, 69.4%, and 52.8%, respectively. Through cross-group analysis, the OS was significantly higher after CIRT (75.1%, 95% CI: 67.1%-83.2%) than PRT (66.2%, 95% CI: 57.7%-74.6%; χ2  = 13.374, P < .0001) or IMRT (63.8%, 95% CI: 55.3%-72.3%; χ2  = 23.814, P < .0001). LC was significantly higher after CIRT (80.2%, 95% CI: 73.9%-86.5%) than PRT (72.9%, 95% CI: 63.7%-82.0%; χ2  = 8.955, P = .003) or IMRT (67.8%, 95% CI: 59.4%-76.2%; χ2  = 30.955, P < .0001). However, no significant difference between PRT and IMRT for OS and LC was observed. CIRT appeared to provide better OS and LC for patients with malignancies of nasal cavity and paranasal sinuses. A prospective randomized clinical trial is needed to confirm the superiority of CIRT in the treatment of sinonasal tumors.

Particle beam radiation therapy for sinonasal malignancies: Single institutional experience at the Shanghai Proton and Heavy Ion Center.

BACKGROUND: Sinonasal malignancies (SNM) include malignant neoplasms of various histologies that originate from the paranasal sinuses or nasal cavity. This study reported the safety and efficacy of particle-beam radiation therapy (PBRT) for the treatment of sinonasal malignancies. METHODS AND MATERIALS: One-hundred-and-eleven patients with nonmetastatic sinonasal malignancies received definitive (82.9%) or salvage (31.5%) PBRT. The majority (85.6%) of patients presented with T3/4 disease, and only 19 (17.1%) had R0 or R1 resection. Seventy (63.1%) patients received carbon-ion radiotherapy (CIRT), 37 received proton radiotherapy (PRT) followed by CIRT boost, and 4 received PRT alone. Prognostic factors were analyzed using Cox regression for univariate and multiple regression. Toxicities were reported using the Common Terminology Criteria for Adverse Events (version 4.03). RESULTS: The median follow-up was 20.2 months for the entire cohort. The 2-year local progression-free survival (LPFS), regional progression-free survival (RPFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) rates were 83%, 97.2%, 85.9%, 66%, and 82%, respectively. Re-irradiation and large GTV were the significant factors for OS. Melanoma and sarcoma patients had significantly higher distant metastatic rate, and poorer OS and PFS. Late toxicity occurred in 22 (19.8%) patients, but only 4 (3.6%) patients experienced grades 3-4 late toxicity. CONCLUSIONS: Particle-beam radiation therapy results in excellent local-regional control with extremely low serve toxicities for patients with SNM. Sarcoma and melanoma were featured with a greater risk of death from distant dissemination. Patients who underwent re-irradiation had significantly worse OS. PBRT is feasible and safe in the management of SNM.

Sinonasal Malignant Melanoma.

Sinonasal malignant mucosal melanoma (SNMM) is a rare, aggressive, and capricious tumour accounting for 4% of sinonasal malignancies. Recent studies suggest an increasing frequency. There are few large published series, but all authors report poor outcomes irrespective of treatment of approximately 25% 5-year survival. As a consequence, the American Joint Committee on Cancer (AJCC) have restaged all SNMMs as T3 or greater, irrespective of extent. Surgery remains the principle treatment modality. Survival and recurrence data analysis from a single-centre prospective cohort of 125 cases (all treated surgically with or without radiotherapy) showed 5-year overall survival was 28% and disease-free survival was 23.7%. Local control was achieved for a median of 21 months, with a 5-year disease control rate of 27.7%. However, endoscopically resected cases showed a significant overall survival advantage up to 5 years, confirming that endoscopic resection of SNMM does not adversely affect outcome and may even be beneficial up to 5 years. These findings are supported by other recent series in the literature. Radiotherapy did not improve local control or survival in this study, though there is debate in the literature as to its value. Cervical metastases confer a dramatically worse outcome. Chemotherapy has not previously shown much advantage, but more recently immunologic manipulation with drugs such as ipilimumab have shown promise. Thus far, the mutation status does not appear to affect survival outcomes, but NRAS mutations are relatively frequent and could be targeted in this disease by MEK inhibitors in the future.

Sinonasal Squamous Cell Carcinoma Outcomes: Does Treatment at a High-Volume Center Confer Survival Benefit?

OBJECTIVE: To determine whether treatment of sinonasal squamous cell carcinoma (SCC) at a high-volume facility affects survival. STUDY DESIGN: Retrospective database analysis. SETTING: National Cancer Database (2004-2014). SUBJECTS AND METHODS: The National Cancer Database was queried for sinonasal SCC from 2004 to 2014. Patient demographics, tumor characteristics and classification, resection margins, treatment regimen, and facility case-specific volume-averaged per year and grouped in tertiles as low (0%-33%), medium (34%-66%), and high (67%-100%)-were compared. Overall survival was compared with Cox proportional hazards regression analysis. RESULTS: A total of 3835 patients treated for sinonasal SCC between 2004 and 2014 were identified. Therapeutic options included surgery alone (18.6%), radiotherapy (RT) alone (29.1%), definitive chemoradiation (15.4%), surgery with adjuvant RT (22.8%), and combinations (14.1%) of the aforementioned treatments. Patients who underwent surgery with adjuvant RT had better overall survival (hazard ratio [HR], 0.74; P < .001; 95% CI, 0.63-0.86). As for treatment volume per facility, 7.4% of patients were treated at a low-volume center, 17.5% at a medium-volume center, and 75.1% at a high-volume center. Univariate analysis showed that treatment at a high-volume facility conferred a significantly better overall survival (HR, 0.77; P = .002). Multivariable Cox proportional hazards regression analysis, adjusting for age, sex, tumor classification, and treatment regimen, demonstrated that patients who underwent treatment at a high-volume facility (HR, 0.81; P < .001) had significantly improved survival. CONCLUSION: This study shows a better overall survival for sinonasal SCC treated at high-volume centers. Further study may be needed to understand the effect of case volume on the paradigms of sinonasal SCC management.

Cost-effectiveness analysis of proton beam therapy for treatment decision making in paranasal sinus and nasal cavity cancers in China.

BACKGROUND: Cost-effectiveness is a pivotal consideration for clinical decision making of high-tech cancer treatment in developing countries. Intensity-modulated proton radiation therapy (IMPT, the advanced form of proton beam therapy) has been found to improve the prognosis of the patients with paranasal sinus and nasal cavity cancers compared with intensity-modulated photon-radiation therapy (IMRT). However, the cost-effectiveness of IMPT has not yet been fully evaluated. This study aimed at evaluating the cost-effectiveness of IMPT versus IMRT for treatment decision making of paranasal sinus and nasal cavity cancers in Chinese settings. METHODS: A 3-state Markov model was designed for cost-effectiveness analysis. A base case evaluation was performed on a patient of 47-year-old (median age of patients with paranasal sinus and nasal cavity cancers in China). Model robustness was examined by probabilistic sensitivity analysis, Markov cohort analysis and Tornado diagram. Cost-effective scenarios of IMPT were further identified by one-way sensitivity analyses and stratified analyses were performed for different age levels. The outcome measure of the model was the incremental cost-effectiveness ratio (ICER). A strategy was defined as cost-effective if the ICER was below the societal willingness-to-pay (WTP) threshold of China (30,828 US dollars ($) / quality-adjusted life year (QALY)). RESULTS: IMPT was identified as being cost-effective for the base case at the WTP of China, providing an extra 1.65 QALYs at an additional cost of $38,928.7 compared with IMRT, and had an ICER of $23,611.2 / QALY. Of note, cost-effective scenarios of IMPT only existed in the following independent conditions: probability of IMPT eradicating cancer ≥0.867; probability of IMRT eradicating cancer ≤0.764; or cost of IMPT ≤ $52,163.9. Stratified analyses for different age levels demonstrated that IMPT was more cost-effective in younger patients than older patients, and was cost-effective only in patients ≤56-year-old. CONCLUSIONS: Despite initially regarded as bearing high treatment cost, IMPT could still be cost-effective for patients with paranasal sinus and nasal cavity cancers in China. The tumor control superiority of IMPT over IMRT and the patient's age should be the principal considerations for clinical decision of prescribing this new irradiation technique.

A clinical analysis of sinonasal squamous cell carcinoma: a comparison of de novo squamous cell carcinoma and squamous cell carcinoma arising from inverted papilloma.

Background: Sinonasal squamous cell carcinoma (SCC) is a rare tumor arising either de novo or in association with inverted papillomas (IPs).Objectives: The aim of this study was to investigate and compare the oncological features and prognosis of patients with sinonasal SCCs based on their etiology.Material and methods: The medical records of 117 patients who had been diagnosed with de novo SCC or those arising from IP (IP-SCC) were retrospectively reviewed. In situ hybridization analyses to detect HPV 16/18DNA and p16 immunohistochemistry were also performed in 10 cases with IP-SCC.Results: The three-year disease-specific survival (DSS) rate was higher in cases with T1, 2 and 3 than in cases with T4 in both tumor groups. T4 cases with de novo SCC had a better DSS than those with IP-SCCs. HPV16/18 was not detected in any of the 10 IP-SCCs.Conclusions and significance: T4 cases with de novo SCC tended to have a better DSS than those with IP-SCC. Since some T4 patients with IP-SCC were found to have a highly aggressive disease, careful treatment planning should be performed. High-risk HPV may not play a vital role in the carcinomatous transformation of most IP-SCC cases.