Sinonasal Squamous Cell Carcinoma Patients Research Articles

Induction Chemotherapy for Locoregionally Advanced Sinonasal Squamous Cell Carcinoma

Abstract Background There is emerging evidence to suggest the role of induction chemotherapy (IC) in definitive management of locoregionally advanced sinonasal squamous cell carcinoma (SNSCC). We evaluated the influence of IC on survival and predictors of its use in SNSCC patients. Methods The 2004 to 2017 National Cancer Database was queried for patients with locoregionally advanced SNSCC (T4/M0). Treatments were stratified into seven groups: definitive chemoradiation (CRT), IC with definitive CRT (IC + CRT), IC + CRT with salvage surgery (IC + CRT + Sx), definitive surgery (Sx), IC with definitive surgery (IC + Sx), definitive surgery with adjuvant radiation or CRT (Sx + ATx), or IC + Sx + ATx. Cox proportional-hazards regression assessed overall survival (OS) and logistic regression identified predictors of IC. Results Of 3,162 patients, 1,088 (34.4%) were female with a mean age of 63.4 ± 13.4 years. The 2- and 5-year OS rates were 58.6 and 42.0%, respectively. Compared with CRT, Sx + ATx (hazard ratio [HR]: 0.663; p < 0.001), IC + Sx (HR: 0.606; p = 0.005), or IC + Sx + ATx (HR: 0.468; p = 0.001) exhibited reduced mortality. Among patients who were treated with definitive surgery, those receiving IC had additional OS benefit (all ps < 0.05). Older age (odds ratio [OR]: 0.607; p < 0.001), female sex (OR: 0.759; p = 0.028), Black race (OR: 1.650; p < 0.001, T4b stage (OR: 1.674; p < 0.001), and higher N stage (OR: 1.395; p < 0.001) were predictors of IC. Conclusions IC prior to definitive surgery with or without adjuvant therapy exhibited the highest OS for locoregionally advanced SNSCC. Age, sex, race, and T/N staging were predictors of IC. Multimodal treatment regimens involving surgery as the primary modality may, therefore, provide the greatest therapeutic response.

P16 Overexpression in Sinonasal Squamous Cell Carcinoma: Association with Human Papillomavirus and Prediction of Survival Outcomes

p16 overexpression is often used as a surrogate marker for human papillomavirus (HPV) infection in oropharyngeal squamous cell carcinoma but remains an uncertain diagnostic tool for HPV-related sinonasal squamous cell carcinoma (SNSCC). Our study involved 79 consecutive SNSCC patients who were treated at a tertiary referral university hospital during 2006–2021. We retrospectively examined their clinical characteristics and conducted p16 immunohistochemistry and HPV detection. We found that 12.7% of the patients exhibited p16 overexpression, which was significantly more common in the nasal cavity and increased from 2015 onward. The HPV was a high-risk type and viral loads ranged from 4.2 to 1.6 × 106 copies/ng DNA with genome integration. Five-year overall survival (OS) and five-year relapse-free survival (RFS) rates were 74.6% and 69.9%, respectively. Our multivariate analysis showed that T category (T1–4a) and hemoglobin levels (≥13.7) were significant favorable prognostic factors for OS, while T category, performance status, and p16 overexpression were significantly associated with RFS. In patients with p16 overexpression, OS was 100% and RFS was 90%. Our findings suggest that p16 overexpression is a reliable surrogate marker for transcriptionally active HPV infection and predicts a favorable prognosis.

Feasibility of omitting contralateral neck irradiation in patients with node-negative sinonasal squamous cell carcinoma crossing the midline.

Identifying the lymph node target volume in patients with node-negative sinonasal squamous cell carcinoma (SNSCC) crossing the midline poses a challenge. This study aims to address this. We retrospectively reviewed clinically N0 patients with tumors crossing the midline who received elective neck irradiation (ENI) from two centers between 1999 and 2019. The main endpoint was regional relapse-free survival (RRFS). We included 104 patients: 64 received bilateral ENI, and 40 received ipsilateral-only ENI (median follow-up time was 89.99 and 95.01 months, respectively). At 5 years, the RRFS rates were comparable (57.68% vs. 55.83%, p = 0.372), as were the contralateral RRFS (57.68% vs. 61.62%, p = 0.541). Five-year OS, LRFS, and DMFS showed no significant difference between two groups. Our findings provide preliminary evidence suggesting the potential for avoiding contralateral ENI in SNSCC patients with midline crossing tumors who undergo ipsilateral ENI, covering at least level II. Validation through future prospective studies is necessary.

Can Definitive Radiation Therapy Substitute Surgical Resection in Locally Advanced T3 or T4 Sinonasal Squamous Cell Carcinoma?

This study aimed to compare oncologic outcomes between definitive radiation therapy (RT) and upfront surgical resection in patients with sinonasal squamous cell carcinoma (SCC). Between 2008 and 2021, 155 patients with T1-4b, N0-3 sinonasal SCC were analyzed. The 3-year overall survival (OS), local progression-free survival (LPFS), and overall progression-free survival (PFS) were evaluated using the Kaplan Meier method and compared using a log-rank test. A pattern of regional neck lymph node (LN) failure and treatment-related toxicity profiles were investigated. A total of 63 and 92 patients underwent upfront RT (RT group) and surgical resection (Surgery group), respectively. The RT group included significantly more patients with T3-4 disease than the Surgery group (90.5% vs 39.1%, P < .001). The rates of 3-year OS, LPFS, and PFS in the RT and Surgery groups were 68.6% versus 81.7% (P=.073), 62.3% versus 73.8% (P=.187), and 47.4% versus 66.1% (P=.005), respectively. However, the corresponding rates in patients with T3-4 disease were 65.1% versus 64.8% (P=.794), 57.4% versus 56.8% (P=.351), and 43.2% versus 46.5% (P=.638), respectively, demonstrating no statistically significant differences between the 2 treatment modalities. Among the 133 N0 patients, regional neck LN progression was observed in 17 patients, and the most common sites of regional neck LN failure were ipsilateral levels Ib (9 patients) and II (7 patients). The 3-year neck node recurrence-free rate in cT1-3N0 patients was 93.5%, while that in cT4N0 patients was 81.1% (P=.025). Upfront RT may be considered in selected patients with locally advanced sinonasal SCC, as we have demonstrated similar oncologic outcomes to those of surgery. Prophylactic neck treatment in T4 disease requires further investigation to evaluate its efficacy.

Assessing the Association Between Time to Surgery and Survival in Sinonasal Squamous Cell Carcinoma.

To assess the association between time to surgery (TTS) and survival in sinonasal squamous cell carcinoma patients (SSCC). We queried the 2004-2016 National Cancer Database for all cases of adult SSCC undergoing primary surgical treatment. Patients with missing TTS information were excluded. We conducted a multivariate analysis of patient demographic and clinicopathological characteristics' effect on overall survival (OS) using a Cox proportional hazards model enhanced with cubic spline non-linear approximation. Bootstrapping methods were utilized to detect the aggregate risk of TTS delay on patient OS. A total of 2,881 patients met the inclusion criteria. The majority of patients were male (63.5%), White (86.3%), and over the age of 60 (58.4%). Parametric cubic spline approximation Cox hazard model detected a non-linear association between patient OS and TTS below 30 days with the lowest risk occurring at 18 days and steadily increasing subsequently. To analyze the aggregate risk and identify the optimal TTS cut-off after 30 days of surgical delay, the cohort sample was bootstrapped and dichotomized. The largest increase in aggregated risk was identified at 59 days (Hazards Ratio [HR] = 1.006 [0.839-1.084], p = 0.003). 60 days were used as the optimal TTS cut-off for analyzing the survival rate using the Cox proportional hazard model. Undergoing surgery within 60 days translated to a 14.6% decreased chance of death (HR: 0.854 [0.83-0.96]). Increasing TTS is associated with worse overall survival in patients with SSCC. Our study suggests that surgery should be done within 60 days to achieve optimal survival results. 4 Laryngoscope, 133:3389-3395, 2023.

Abstract 6077: Comprehensive multi-omic characterization of genetic changes associated with sinonasal squamous cell carcinoma progression

Abstract Approximately 50-80% of sinonasal tract cancers are sinonasal squamous cell carcinoma (SNSCC), a rare malignancy which occur in the nasal cavity and maxillary sinus. These lesions possess a propensity for local invasion into adjacent structures including the skull base, brain, and orbit. Owing to relatively mild symptoms during early stages, which resemble benign sinonasal disease, most patients are already in clinically advanced stages when diagnosed. Therefore, despite improvements in endoscopic surgical approaches, radiotherapy and imaging techniques, the 5-year overall survival for advanced SNSCC patients remains poor (~40%). Inverted sinonasal papilloma (IP) is a locally aggressive, benign epithelial neoplasm arising in the paranasal sinuses which has a high recurrence rate and transforms to SNSCC in 10%-25% of cases. As some IP evolve to malignant neoplasms, it has been presumed that they represent an intermediate step in SNSCC progression. However, the current tools for detecting altered epithelial cells, such as clinical examination and histological characteristics, have limited prognostic value for predicting which IP will progress to malignancy, and the link between IP and invasive disease remains unclear. Activating mutations in EGFR and PIK3CA genes as well as loss-of-function mutations in TP53 have been reported in a few very small cohorts of IP and SNSCC lesions, suggesting their role in IP pathogenesis and progression to invasive malignancy. Other observed alterations potentially associated with malignant transition include KRAS mutations, loss of heterozygosity (LOH) at the 9p21 locus (containing p16INK4a), mismatch repair genes deficiency, amplification of FGFR1 and SOX2 genes, as well as NFκB, COX2 and HOXA9 overexpression. While these studies provide a snapshot of molecular changes in SNSCC, genetic alterations critical to the development of SNSCC are poorly understood, and the exact mechanism underlying malignant transformation remains unknown. In this study we have used PandaOmic, a multi-omic data analysis and visualization algorithm, to perform a first comprehensive integrative analysis of WES, mitochondrial sequencing and transcriptomic data obtained from 11 IP lesions, matched invasive SNSCC tumors and histologically normal paranasal sinus epithelium collected from the same patients. Our analysis reveals heterogeneous mutational patterns, gene expression changes and signaling pathways features associated with SNSCC pathogenesis, and provides crucial insights that may aid in the development of novel means of prevention, diagnosis, and treatment of this rare, aggressive and poorly characterized malignancy. Citation Format: Alka Singh, Nikita Babushkin, Michael Korzinkin, Viktoria Sarkisova, Vasudha Mishra, Ari Rosenberg, Mark Lingen, Justin Bishop, Alex Zhavoronkov, Nyall London, Nishant Agrawal, Xuanyao Liu, Evgeny Izumchenko. Comprehensive multi-omic characterization of genetic changes associated with sinonasal squamous cell carcinoma progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6077.

Automated Prediction of Early Recurrence in Advanced Sinonasal Squamous Cell Carcinoma With Deep Learning and Multi-parametric MRI-based Radiomics Nomogram

Preoperative prediction of the recurrence risk in patients with advanced sinonasal squamous cell carcinoma (SNSCC) is critical for individualized treatment. To evaluate the predictive ability of radiomics signature (RS) based on deep learning and multiparametric MRI for the risk of 2-year recurrence in advanced SNSCC. Preoperative MRI datasets were retrospectively collected from 265 SNSCC patients (145 recurrences) who underwent preoperative MRI, including T2-weighted (T2W), contrast-enhanced T1-weighted (T1c) sequences and diffusion-weighted (DW). All patients were divided into 165 training cohort and 70 test cohort. A deep learning segmentation model based on VB-Net was used to segment regions of interest (ROIs) for preoperative MRI and radiomics features were extracted from automatically segmented ROIs. Least absolute shrinkage and selection operator (LASSO) and logistic regression (LR) were applied for feature selection and radiomics score construction. Combined with meaningful clinicopathological predictors, a nomogram was developed and its performance was evaluated. In addition, X-title software was used to divide patients into high-risk or low-risk early relapse (ER) subgroups. Recurrence-free survival probability (RFS) was assessed for each subgroup. The radiomics score, T stage, histological grade and Ki-67 predictors were independent predictors. The segmentation models of T2WI, T1c, and apparent diffusion coefficient (ADC) sequences achieved Dice coefficients of 0.720, 0.727, and 0.756, respectively, in the test cohort. RS-T2, RS-T1c and RS-ADC were derived from single-parameter MRI. RS-Combined (combined with T2WI, T1c, and ADC features) was derived from multiparametric MRI and reached area under curve (AUC) and accuracy of 0.854 (0.749-0.927) and 74.3% (0.624-0.840), respectively, in the test cohort. The calibration curve and decision curve analysis (DCA) illustrate its value in clinical practice. Kaplan-Meier analysis showed that the 2-year RFS rate for low-risk patients was significantly greater than that for high-risk patients in both the training and testing cohorts (p < 0.001). Automated nomograms based on multi-sequence MRI help to predict ER in SNSCC patients preoperatively.

Immunohistochemical p16 expression in the prognosis of patients with sinonasal squamous cell carcinoma.

In sinonasal squamous cell carcinoma (SNSCC), the prognostic relevance of p16INK4a (p16) expression has been reported rarely. This study aims to examine the immunohistochemical expression of p16 and investigate the possibility of p16 as a prognostic factor for SNSCC. The medical records of 173 individuals with SNSCC between 2010 and 2022 were retrospectively reviewed. The researchers examined patients' demographics, p16 status, staging, tumor histological subtypes, treatment details, recurrence, metastasis, and survival outcomes. p16 was found in 22.0% (38/173) of SNSCC patients, and there was no difference between inverted papilloma-SNSCC (19.6%) and de novo SNSCC (23.0%). p16 status did not correlate with all the cases' age, gender, clinical stage, or therapy features. p16-positive patients had a considerably superior 5-year overall survival (OS) rate (80.7% vs. 57.5%, p=0.039) and a slight tendency in progression-free survival (PFS) rate (68.1% vs. 52.0%, p=0.15), except in stage T4b cases. In maxillary sinus lesions, p16-positive SNSCC had a better 5-year OS (87.4% vs. 49.2%, p=0.03) rate and PFS (79.1% vs. 40.7%, p=0.01) rate than p16-negative SNSCC. Among patients without skull base involvement (82.9% vs. 57.7%, p=0.037) or orbital invasion (86.9% vs. 57.3%, p=0.02), p16-positive SNSCC confers benefits in OS rates more than p16-negative SNSCC. Immunohistochemical p16 expression may be a predictive predictor in individuals with maxillary sinus SCC, non-T4b stage, without skull base involvement, and without orbital invasion.

Evaluation of the Prognostic Capacity of a Novel Survival Marker in Patients with Sinonasal Squamous Cell Carcinoma.

Sinonasal squamous cell carcinoma (SNSCC) is a malignant tumor associated with poor survival, and easily obtainable prognostic markers are of high interest. Therefore, we aimed to assess the prognostic value of a novel survival index (SI) combining prognostic values of clinical (T and N classifications and invasion across Ohngren’s line), inflammatory (neutrophil-to-lymphocyte ratio), and nutritional (albumin and body-mass index) markers. All patients with primarily treated SNSCC between 2002 and 2020 (n = 51) were included. Each of the six SI components was stratified into a low- (0) and high-risk (1) categories. Subsequently, the cohort was stratified into low- (SI of 0–2) and high-risk SI groups (SI of 3–6). Overall survival (OS) and disease-free survival (DFS) were compared between patients with low- and high-risk SI. The log-rank test was used to test for statistical significance. Overall, the mortality rate was 41.2% (n = 21), and the recurrence rate was 43.1% (n = 22). We observed significantly better OS in patients with low-risk SI (n = 24/51, 47.1%, mean OS: 7.9 years, 95% confidence interval (CI): 6.3–9.6 years) than in high-risk SI (n = 27/51, 52.9%, mean OS: 3.4 years, 95% CI: 2.2–4.5 years; p = 0.013). Moreover, we also showed that patients with low-risk SI had a longer DFS than patients with high-risk SI (mean DFS: 6.4, 95% CI: 4.8–8.0 vs. mean DFS: 2.4 years, 95% CI 1.3–3.5, p = 0.012). The SI combines the prognostic capacity of well-established clinical, radiologic, inflammatory, and nutritional prognosticators and showed prognostic potential in our cohort of SNSCC patients.

The Role of Salvage in the Management of Patients with Sinonasal Squamous Cell Carcinoma.

Objectives: This paper presents and discusses the rate and outcome of salvage according to various factors for patients with sinonasal squamous cell carcinoma (SNSCC). Methods: Data of 79 patients treated radically due to SNSCC between 2000 and 2016 in the National Cancer Research Institute, Gliwice branch, were analyzed. Surgery was the primary treatment in 63 (79%) of patients. The ratio, type, and effectiveness of salvage was assessed and correlated with prognostic factors. Probabilities of overall survival (OS), local control (LC), nodal control (NC), and locoregional control (LRC) were assessed and compared between the groups. Results: The 5-year LC, NC, and LRC survival rates were 62%, 75%, and 53%, respectively. The 5-year OS rate was 51%. In 34 (43%) patients, treatment failure was reported, and salvage was performed in 17 (50%) of them. It was shown that patients after any salvage had significantly longer 2- and 3-year OS rates when compared to patients with no salvage: 52% vs. 7% and 38% vs. 0%, respectively (p = 0.004). Two- and three-year OS rates for patients after effective and ineffective salvage were 83% vs. 33% and 83% vs. 11%, respectively (p = 0.02). For patients with effective salvage, OS did not differ significantly when compared to the OS of primarily cured patients (p = 0.6). Conclusions: For SNSCC patients after treatment failure, salvage is possible in half of the cases and can improve their overall survival even if not finally successful. Moreover, effective salvage can compensate for the failure and give the same ultimate OS as in primarily cured patients.

NGS-based miRNome identifies miR-449 cluster as marker of malignant transformation of sinonasal inverted papilloma

Objectiveidentification of the miRNA expression profile in sinonasal inverted papilloma (SNIP) as a tool to evaluate the risk of transformation into sinonasal squamous cell carcinoma (SNSCC). Materials and Methodspaired tumour tissues and adjacent normal tissues were obtained from SNIP and SNSCC patients who had undergone surgical resection and used for next-generation sequencing (NGS)-based miRNome analysis. SNIP tissues with concomitant dysplasia (SNIP-DISP) were used as malignant transition samples. By comparing the deregulated miRNAs in SNIP and SNSCC, an miRNA cluster was identified and its physio- and clinical-pathological value was predicted. ResultsNGS identified 54 miRNAs significantly down- and upregulated in SNIP. Among them, the miR-449 cluster was upregulated in SNIP and could differentiate the benign tumour from normal tissue. Notably, the miR-449 cluster was found to be significantly underexpressed in SNSCC, and the cluster markedly changed in SNIP during the malignant transition into SNSCC. miRNA enrichment analysis and GO analysis revealed that miR-449 is involved in apoptotic and cell proliferation pathways. ConclusionsOur findings suggest that miR-449 may be involved in the molecular pathogenesis of SNIP and its malignant transformation into SNSCC. miR-449 might therefore be a useful tumour biomarker in patients with SNIP and may also have the potential to be used as a tool for detecting and monitoring the course of the possible malignant transformation.

Characterization of the tumor immune microenvironment of sinonasal squamous-cell carcinoma.

Treatment and prognosis of sinonasal squamous-cell carcinoma (SNSCC) have not significantly improved despite improvements in radical therapy. Characterization of the tumor immune microenvironment (TiME) may identify patient subgroups associated with disease recurrence, and provide new biomarkers for improved patient stratification and treatment. The TiME was quantitatively evaluated by multiplex immunohistochemistry (mIHC) in archived tissue sections from 38 patients with SNSCC, and were assessed for differences between recurrent (n=20) and nonrecurrent (n=18) groups. Hierarchical clustering analyses were performed to identify phenotypic TiME subgroups within the cohort and were used to compare survival outcomes. Our mIHC analysis revealed increased T-cell populations and decreased myeloid-cell populations in SNSCC patients without recurrent disease, as compared with patients with recurrent disease. Within T-cell subsets, there was a significantly higher percentage of granzyme B+ , T-bet+ , Eomes+ T cells, as well as higher proliferation of CD8+ T cells within the nonrecurrent group relative to the recurrent group. Furthermore, immune-cell complexity profiles of SNSCC revealed hyper- and hypo-T-cell-inflamed, myeloid-inflamed, B-cell-inflamed, and broadly hypoinflamed subtypes not previously identified by gene expression analyses. Our study revealed that presence of either hyper- or hypo-T-cell-inflamed TiME subtypes were associated with increased survival outcomes as compared with broadly hypoinflamed TiME subtypes (p=0.035 and 0.0376, respectively). The TiME of SNSCC reveals distinct subtypes, which may correlate with recurrence and survival outcomes.

Human Papillomavirus and Survival of Sinonasal Squamous Cell Carcinoma Patients: A Systematic Review and Meta-Analysis.

Simple SummaryHuman papillomavirus (HPV) has been associated with multiple cancers in the anogenital and upper aerodigestive tracts. In the head and neck region, HPV-positive cancers are common in oropharynx, with rising incidence and a well-established association with more favorable patient outcomes. However, the relationship with prognosis of sinonasal squamous cell carcinoma (SNSCC) has been much less often studied and is presently unclear. To better elucidate this relationship, we performed a systematic review and meta-analysis of the biomedical literature to determine the aggregate effect across studies. In doing so, we observed significantly better overall survival associated with HPV-positive SNSCC. Therefore, we conclude that HPV testing may be useful for determining patient prognosis and potentially guiding treatment decisions. Human papillomavirus (HPV) is detectable in a subset of sinonasal squamous cell carcinoma (SNSCC), but the impact on patient outcomes is presently unclear due to a modest number of studies with limited statistical power. Therefore, we conducted a systematic review and meta-analysis to better clarify this relationship. A PubMed search was conducted to identify all studies reporting on overall (OS) or disease-free survival (DFS) for SNSCC by HPV status. Hazard ratios (HR) and corresponding 95% confidence intervals (CI) were extracted or, when not provided, indirectly estimated from each manuscript. Summary survival curves for 5-year OS and estimating survival probability by HPV status at pre-specified time intervals from study-specific Kaplan-Meier curves generated 2-year DFS. Log HRs and log CIs were combined across studies to generate summary estimates and a corresponding 95% CIs for OS and DFS. We identified ten unique studies reporting on OS and four for DFS. We observed a significant association between HPV and OS (summary HR = 0.51, 95% CI: 0.38–0.70) with relatively low heterogeneity between studies. These results indicate that HPV is a significant predictor of more favorable survival for SNSCC, and thus may be a useful biomarker for prognostication and, potentially, treatment modulation.

A Comparative Study on Clinico-radiological Differentiation of Sino-nasal Squamous Cell Carcinoma (SCC) and Sino-nasal Non-Hodgkins Lymphoma (NHL).

(1) To compare clinical presentations between sinonasal non-Hodgkins Lymphoma (NHL) and sino-nasal Squamous cell carcinoma (SCC). (2) To compare computed tomographic (CT) scan findings between sino-nasal NHL and sino-nasal SCC. (1) Design: Retrospective Comparative study. (2) Setting: tertiary care hospital. (3) Subjects: patients with histologically proven primary maxillary tumors (NHL and SCC). (4) Method: (a) Patients: medical records between March 2013 to March 2018 were examined and patients with histologically proven primary maxillary tumors (NHL and SCC) were included in the study. (b) CT imaging: unenhanced and contrast enhanced images were obtained for all patients. Unenhanced CT images were reconstructed using bone and soft tissue algorithm. (c) Image Assessment: Predominant growth patterns of the tumors were noted from the CT images. Sino-nasal NHL: 8 men and 3 women; Sino-nasal SCC: 19 men and 5 women. Mean age of the NHL and SCC patients were 66.18y and 64.88y respectively. Nasal obstruction, diplopia/blurred vision, nasal/cheek pain and cranial nerve palsies were significantly more common presentation among sino-nasal NHL patients (p values of 0.0053, 0.0014, 0.0089 and 0.0089 respectively). Permeative growth pattern was significantly higher among NHL patients (54.54%) (p value = 0.026) whereas SCCs showed significant destructive growth pattern (83.33%) (p value = 0.0009). Intra-tumoral necrosis was significantly higher in SCC patients (87.5%) (p value = < 0.0001). Nasal obstruction, diplopia/blurred vision, nasal/cheek pain and cranial nerve palsies were the predominant presenting features in sino-nasal NHL patients. In CT imaging, Sino-nasal SCCs showed predominantly destructive growth pattern and intra-tumoral necrosis whereas permeative growth was predominant feature of sino-nasal NHL.

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

ObjectiveDespite 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. MethodsA 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. ResultsOf 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). ConclusionEndoscopic 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.

Prognostic Factors of Sinonasal Squamous Cell Carcinomas Arising De Novo and From Inverted Papilloma.

The prognostic factors and survival difference between inverted papilloma (IP)-associated sinonasal squamous cell carcinoma (SCC) and de novo SCC are unclear. This study aimed to compare the clinical features and oncologic outcomes in patients with IP-associated SCC and de novo SCC; and additionally, to analyze the prognostic factors of the two types of SCCs. Data from 173 SCC patients treated for IP-associated SCC (n = 89) and de novo SCC (n = 84), were reviewed retrospectively for demographic features, tumor characteristics, treatment modality, and clinical outcomes. 5-year overall survival (OS) and disease free survival (DFS) was analyzed using the Kaplan-Meier method, and Cox proportional hazards model was used to analyze factors influencing prognosis. A higher proportion of IP-associated SCC occurred in frontal and sphenoid sinus compared to de novo SCC. The two groups demonstrated similar 5-year OS and DFS (5-year OS: 63.3% and 55.4%, DFS: 45.4% and 50.1%, respectively). The metachronous tumor had a relatively better prognosis outcome than synchronous tumor and de novo SCC (5-year OS: 73.1%, 54.5% and 55.4%, respectively). Both groups showed similar loco-regional recurrence rates (p > 0.05); however, de novo SCC tumors demonstrated an increased incidence of distant metastasis. Multivariate analysis indicated that age >70 years, advanced tumor stage and surgical margin were independent predictive factors for the risk of mortality (HR 2.047, 1.581 and 1.931, respectively). IP-associated SCCs have an aggressive loco-regional tendency, whereas de novo SCCs have a higher aggressive distant metastatic propensity. Age, tumor stage and surgical positive margin are key factors for poor prognosis and should be routinely taken into consideration during treatment planning and subsequent surveillance.

Prevalence of human papillomavirus in sinonasal squamous cell carcinoma with and without association of inverted papilloma in Eastern China

BackgroundInformation on HPV-associated sinonasal squamous cell carcinoma (SNSCC) is very limited in China. The aim of this study was to determine the prevalence of HPV in a large cohort of SNSCC patients in China.MethodsClinical records and formalin-fixed and paraffin-embedded tumor specimens from 30 SNSCC patients with associated inverted papilloma (IP-SNSCC) and 84 de novo SNSCC (DN-SNSCC) patients were retrieved between 2010 and 2017. HPV status was determined for each specimen using a combination of p16 immunohistochemistry and GP5+/6+ PCR.ResultsImmunohistochemistry for p16 was positive in two IP-SNSCC patients (2/30, 6.7%) and in 16 DN-SNSCC patients (16/84, 19.0%). HPV DNA was detected in six IP-SNSCC patients (6/30, 20%) and in three DN-SNSCC patients (3/84, 3.8%). Expression of p16 was not correlated with the presence of HPV DNA (p = 0.150). Among 18 p16-positive SNSCC patients, only three were HPV DNA-positive. Furthermore, only three of nine HPV DNA-positive tumors exhibited high p16 expression. In IP-SNSCC patients, only one of six HPV DNA-positive tumors exhibited high p16 expression. In DN-SNSCC patients, two of three HPV DNA-positive tumors exhibited high p16 expression. The positive rates for both HPV DNA and p16 in IP-SNSCC patients and DN-SNSCC patients were 3.3 and 2.4%, respectively.ConclusionsImmunostaining for p16 is not a reliable surrogate marker of HPV status in SNSCC. The presence of HPV is rarely detected in DN-SNSCC patients in Eastern China. IP-SNSCC patients frequently lack of p16 overexpression despite the presence of high-risk HPV DNA.

EGFR mutation and HPV infection in sinonasal inverted papilloma and squamous cell carcinoma.

To evaluate the involvement of EGFR signalling and HPV infection in a cohort of inverted sinonasal papilloma (ISP) and sinonasal squamous cell carcinoma (SNSCC) and their value for prognosis and clinical treatment. We analysed 55 ISP, 14 SNSCC associated with ISP (SNSCC-isp) and and 60 SNSCC not associated with ISP (SNSCC-novo) for EGFR gene mutation and copy number gain, protein expression of EGFR and phosporylated EGFR (pEGFR), and HPV-infection and KRAS mutation. Findings were correlated to clinico-pathological and follow-up data. We found EGFR exon 20 mutations in 38% (7/18) ISP, in 50% (6/12) SNSCC-isp and in 5% (1/19) SNSCC-novo. EGFR was expressed in 92% of ISP, while pEGFR was observed in 54% (21/39). SNSCC-isp and SNSCC-novo demonstrated comparable expression of EGFR (57% and 33%) and of pEGFR (44% and 38%). We observed an inverse relation between EGFR exon 20 mutation and pEGFR expression. Four of 39 (10%) ISP carried HPV-16. Oncogenic HPV was detected in 3/12 (25%) SNSSC-isp and in 1/8 (13%) SNSCC-novo. KRAS mutations were not detected in any of the samples. HPV infection was inversely correlated with pEGFR expression but not with EGFR mutation. ISP with EGFR activation by mutation or by phosphorylation had longer ISP-free survival, however, neither EGFR exon 20 mutation, pEGFR expression nor HPV infection demonstrated prognostic value in SNSCC. EGFR exon 20 mutation is frequent in ISP and SNSCC-isp, while activation of EGFR through phosphorylation also plays an important role. Our data indicate that a large proportion of SNSCC patients could benefit from therapy with modern EGFR inhibitors.

A Novel LncRNA, AC091729.7 Promotes Sinonasal Squamous Cell Carcinomas Proliferation and Invasion Through Binding SRSF2.

Long non-coding RNAs (lncRNAs) play important roles in various biological progresses of carcinogenesis. However, the function of lncRNAs in human sinonasal squamous cell carcinoma (SNSCC) remains greatly unclear. In the current study, lncRNA AC091729.7 expression was examined in SNSCC samples by using microarray, RNA in situ hybridization (ISH) and real-time fluorescence quantitative PCR (qRT-PCR). Cell viability, colony-formation, wound-healing, and transwell assays were applied to SNSCC cells. Xenograft mouse models were employed to evaluate the role of AC091729.7 in growth of SNSCC in vivo. Human protein microarray (HuprotTM Protoarray) and RNA immunoprecipitation (RIP) were used for identifying AC091729.7 binding proteins in SNSCC. Results showed AC091729.7 was upregulated and closely connected with the survival of the SNSCC patients. Knockdown of AC091729.7 suppressed SNSCC cell migration, proliferation, invasion in vitro. Furthermore, downregulation of AC091729.7 could inhibit the growth of SNSCC in vivo. Moreover, Human protein microarray and RIP suggested that AC091729.7 directly combine with the serine/arginine rich splicing factor 2 (SRSF2). Our results suggest that in the cell progression of SNSCC, lncRNA AC091729.7 plays a carcinogenic role and serves as a novel biomarker and latent curative target in SNSCC patients.

Prognostic Value Of The Preoperative Neutrophil To Lymphocyte Ratio In Patients With Sinonasal Squamous Cell Carcinoma.

ObjectiveThis study explored the effectiveness of a new inflammatory prognostic system, using preoperative neutrophil to lymphocyte ratio (NLR) to predict the postoperative survival rate of patients with sinonasal squamous cell carcinoma (SSCC).MethodsPatients diagnosed with SSCC who undergone surgically treated without neoadjuvant therapy were included in the study between May 2008 and October 2017. Preoperative NLR is defined as: preoperative neutrophil/postoperative lymphocyte ratio. The prognostic value was uncovered by univariate and multivariate Cox hazards analysis.ResultsA total of 147 patients were included in this study. Through the multivariate analysis, pathological T stage (hazard ratio [HR] 1.719, confidence interval [CI] 1.277–3.642, p<0.001), pathological N stage (HR 1.344, 95% CI 1.015–2.776, p<0.001), and preoperative NLR (HR 1.579, 95% CI 1.217–3.092, p=0.002) were independent risk factor for overall survival (OS). Pathological T stage (HR 1.835, 95% CI 1.141–3.132, <0.001), pathological N stage (HR 1.281, 95% CI 1.169–2.476, p<0.001), and preoperative NLR (HR 1.688, 95% CI 1.162–3.363, p p<0.001) were also independently associated with disease-free survival (DFS). Pathological T stage (HR p<0.001, 95% CI 1.537–3.021, p<0.001), pathological N stage (HR1.571, 95% CI 1.157–2.258, p<0.001), and preoperative NLR (HR 1.509, 95% CI 1.153–3.104, p=0.001) were independent risk factors for disease-specific survival (DSS).ConclusionThe preoperative NLR is considered to be a useful predictor of postoperative survival in SSCC patients.