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Background Squamous cell carcinoma is the most common type of sinonasal malignancy. Despite improvements in surgical resection and adjuvant therapy, which are considered the standard of care, the outcome for patients with locoregionally advanced disease remains poor. The objective of this study was to investigate the role of induction chemotherapy in patients with locoregionally advanced sinonasal squamous cell carcinoma and to determine the oncologic outcomes in those patients. Methods The study included 123 consecutive patients with previously untreated, locoregionally advanced (stage III and IV) sinonasal squamous cell carcinoma who were treated with curative intent at The University of Texas MD Anderson Cancer Center between 1988 and 2017 with induction chemotherapy followed by definitive local therapy. Patient demographics, tumor staging, treatment details, and oncologic outcomes were reviewed. The outcomes of this study included response to induction chemotherapy, recurrence, organ preservation, and survival. Results The median follow-up was 32.6 months (range, 12.4-240 months). Of the 123 patients, 110 (89%) had T4 disease, and 13 (11%) had T3 disease. Lymph node metastasis at the time of presentation was observed in 36 patients (29.3%). The overall stage was stage IV in 111 patients (90.2%) and stage III in 12 patients (9.8%). The chemotherapy regimen consisted of the combination of a platinum and taxanes in most cases (109 patients; 88.6%), either as a doublet (41 patients) or in combination with a third agent, such as 5-fluorouracil (34 patients), ifosfamide (26 patients), or cetuximab (8 patients). After induction chemotherapy, 71 patients (57.8%) achieved at least a partial response, and 6 patients had a complete response. Subsequent treatment after induction chemotherapy was either: 1) definitive chemoradiation or radiation followed by surgical salvage for any residual disease, or 2) surgery followed by adjuvant radiation or chemoradiation. Overall, 54 patients (49.5%) underwent surgical resection. The 2-year overall and disease-free survival rates for the whole cohort were 61.4% and 67.9%, respectively. The rate of orbital preservation was 81.5%. The recurrence rate was 26.8% (33 patients), and distant metastases occurred in 8 patients (6.5%). Patients who had at least a partial response or stable disease had significantly better overall and disease-free survival than those who had progressive disease (P = .028 and P = .021, respectively). Conclusions The current results indicate that a high proportion of patients with sinonasal squamous cell carcinoma achieved a favorable response to induction chemotherapy. The data suggest that response to induction chemotherapy is associated with an improved outcome and a good chance of organ preservation. The oncologic outcomes in this cohort with locally advanced (mostly T4) disease are better than those historically reported in the literature. Further study of induction chemotherapy in patients with advanced sinonasal squamous carcinoma is warranted.

Objectives Sinonasal undifferentiated carcinoma (SNUC) is a rare, highly aggressive cancer. Despite aggressive multimodal therapy, its prognosis remains poor. Because of its locally advanced nature and high propensity for distant metastasis, we frequently use induction chemotherapy before definitive therapy in patients with SNUC. However, about 30% of patients do not respond to induction chemotherapy, and lack of response is associated with a poor survival rate. Therefore, in this study, we performed gene expression analysis of SNUC samples to identify prognostic markers for induction chemotherapy response. Materials and methods Formalin-fixed, paraffin-embedded SNUC tumor samples from previously untreated patients harvested before induction chemotherapy were used. Gene expression was performed using an oncology gene expression panel. Results We identified 34 differentially expressed genes that distinguish the responders from the non-responders. Pathway analysis using these genes revealed alteration of multiple pathways between the two groups. Of these 34 genes, 24 distinguished between these two groups. Additionally, 16 gene pairs were associated with response to induction therapy. Conclusion We identified genes predictive of SNUC response to induction chemotherapy and pathways potentially associated with treatment outcome. This is the first report of identification of predictive biomarkers for response of SNUC to induction chemotherapy, and it may help us develop therapeutic strategies to improve the treatment outcomes of non-responders.

PURPOSE Multimodal therapy is a well-established approach for the treatment of sinonasal undifferentiated carcinoma (SNUC); however, the optimal sequence of the various treatments modalities is yet to be determined. This study aimed to assess the role of induction chemotherapy (IC) in guiding definitive therapy in patients with SNUC. METHODS Ninety-five previously untreated patients diagnosed with SNUC and treated between 2001 and 2018 at The University of Texas MD Anderson Cancer Center were included in the analysis. Patients were treated with curative intent and received IC before definitive locoregional therapy. The primary end point was disease-specific survival (DSS). Secondary end points included overall and disease-free survival, disease recurrence, and organ preservation. RESULTS A total of 95 treatment-naïve patients were included in the analysis. For the entire cohort, the 5-years DSS probability was 59% (95% CI, 53% to 66%). In patients who had partial or complete response to IC, the 5-year DSS probabilities were 81% (95% CI, 69% to 88%) after treatment with definitive concurrent chemoradiotherapy (CRT) after IC and 54% (95% CI, 44% to 61%) after definitive surgery and postoperative radiotherapy or CRT after IC (log-rank P = .001). In patients who did not experience at least a partial response to IC, the 5-year DSS probabilities were 0% (95% CI, 0% to 4%) in patients who were treated with concurrent CRT after IC and 39% (95% CI, 30% to 46%) in patients who were treated with surgery plus radiotherapy or CRT (adjusted hazard ratio of 5.68 [95% CI, 2.89 to 9.36]). CONCLUSION In patients who achieve a favorable response to IC, definitive CRT results in improved survival compared with those who undergo definitive surgery. In patients who do not achieve a favorable response to IC, surgery when feasible seems to provide a better chance of disease control and improved survival.

Objectives/hypothesis Olfactory neuroblastoma (ONB) is a rare sinonasal malignant neoplasm that is known to develop late recurrence. The aim of this study is to evaluate the long-term outcomes of patients with ONB and to determine the factors associated with prognosis. Study design Retrospective study. Methods A retrospective review of the medical records of 139 patients diagnosed with ONB at MD Anderson Cancer Center was performed between 1991 and 2016. Descriptive statistics were calculated, and Kaplan-Meier curves were utilized to assess survival. Results Median follow-up time was 75 months. Overall, 129 patients (92.8%) had surgery as part of their treatment and 82 (58.9%) patients received postoperative radiation therapy (PORT) or concurrent chemoradiotherapy. Endoscopic approaches were utilized for 72 patients, 69.4% of whom had pure endoscopic endonasal approaches. Five-year overall survival and disease-specific survival were 85.6% and 93.4%, respectively. Recurrence rate was 39.6% with a median time to recurrence of 42 months. Among the 31 patients who received elective nodal irradiation (ENI), two patients developed neck recurrence (6.4%) compared with 20 who developed neck recurrence when ENI was omitted (34.4%) (P = .003). Advanced Kadish stage, orbital invasion, intracranial invasion, and presence of cervical lymphadenopathy at the time of presentation were significantly associated with poor survival. Conclusion ONB has an excellent survival. Surgical resection with PORT when indicated is the mainstay of treatment. Endoscopic approaches can be used as a good tool. Elective neck irradiation reduces the risk of nodal recurrence among patients with clinically N0 neck. Despite the excellent survival, recurrence rate remains high and delayed, highlighting the need for long-term surveillance. Level of evidence Level 4 Laryngoscope, 2021.

Background Patients with locoregionally advanced oral cavity squamous cell carcinoma (OCSCC) have a poor survival outcome. Treatment involves extensive surgery, adjuvant radiation, or chemoradiation and results in high morbidity. In this study, the authors' objective was to evaluate their experience with induction chemotherapy (IC) in the treatment of locoregionally advanced OCSCC. Methods A retrospective review of the medical records of all patients with locoregionally advanced (stage III and IV) OCSCC who received IC followed by definitive local therapy was conducted. Outcomes included response to IC and survival. Results In total, 120 patients were included in the study. The overall stage was stage IV in 79.2% of patients. After 2 cycles of IC, 76 patients (63.3%) achieved at least a partial response, including 13 who had a complete response. Stable disease was observed in 30 patients (25%), and 14 patients (11.7%) had progressive disease. Among responders, 16 patients received definitive chemoradiation or radiation therapy, and 60 underwent surgical resection, of whom 15 had less extensive surgery than was originally planned. Overall, organ preservation was achieved in 40.8% of patients who had a favorable response to IC. The 5-year overall and disease-specific survival rates were 51.4% and 66.9%, respectively. Patients who had at least a partial response had better 5-year overall survival (60.1%) and disease-specific survival (78.5%) compared with nonresponders (33.8% and 46.4%, respectively). Conclusions The results demonstrate a response rate to IC in patients with advanced OCSCC similar to what has been observed in patients with cancer in other head and neck subsites. Patients who achieved at least a partial response to IC had a more favorable outcome, with ensuing organ preservation. Further studies are warranted.

Sinonasal malignancies are uncommon, representing 1% of all neoplasms. A wide spectrum of malignant neoplasms arise from the sinonasal and skull base regions; the majority of these tumors are poorly or undifferentiated tumors manifesting overlapping features that result in diagnostic challenges. Sinonasal neuroendocrine carcinoma (SNEC) and sinonasal undifferentiated carcinoma (SNUC) are types of sinonasal neuroendocrine tumor, together with olfactory neuroblastoma. They share overlapping clinical, radiological, and histopathological features, albeit with variability in behavior and prognosis between each other. The literature is at variance regarding the appropriate management strategy of these tumors due to their rarity and difficulty in establishing the correct diagnosis. In recent years progress has been made in the diagnostic techniques and treatment strategies implemented for these tumors. Here we provide a comprehensive review of the recent literature, focusing on the recent advances in histopathological and ancillary diagnosis, and different treatment options for SNEC and SNUC.

Background Aneurysmal bone cysts are rare, benign expansile tumors most commonly involving long bones and vertebrae in patients younger than age 20. Skull base involvement is rare. Aneurysmal bone cysts shares radiological and histological features with other bone tumors, posing a diagnostic challenge. Methods/results We report the case of a 32-year-old man who presented with facial pain, epistaxis, and cranial neuropathies secondary to a massive tumor of the maxillary sinus and anterior skull base. The tumor was originally misdiagnosed as osteosarcoma. However, genomic analysis revealed a rearrangement in the USP6 gene, elucidating a diagnosis of primary aneurysmal bone cysts. The patient was treated with denosumab. Within 5 months, the patient was asymptomatic with CT showing ossification of the tumor. Conclusions This case highlights (1) the utility of genomic analysis in aggressive bone tumors when the diagnosis is unclear and (2) the effectiveness of denosumab as a treatment for aneurysmal bone cysts when surgical resection is unfavorable.

Head and neck mucosal melanoma is a locally aggressive tumor with a high recurrence rate. The paranasal sinuses and nasal cavity are the most common primary tumor sites. The purpose of this retrospective study was to identify independent predictors of outcome in sinonasal mucosal melanoma (SNMM) and characterize the patterns of treatment failure. This study included 198 patients with SNMM who had been treated at The University of Texas MD Anderson Cancer Center from 1 January 1991 through 31 December 2016. The survival outcomes included overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), local recurrence-free survival, and distant metastasis-free survival. A stepwise regression analysis was used to assess associations in the multivariate models. The 5-year OS, DSS, and DFS rates were 38, 58, and 27%, respectively. Independent predictors of poor OS and DSS were the paranasal sinuses as the primary tumor site [hazard ratio (HR) 1.73, 95% confidence interval (CI) 1.11–2.66; and HR 2.12, 95% CI 1.21–3.74, respectively] and the presence of distant metastases at presentation (HR 4.53, 95% CI 2.24–7.83; and HR 3.6, 95% CI 1.12–7.1). Recurrence occurred in 96 patients (48%). The most common cause of treatment failure was distant metastasis in 69 of 198 patients (35%), followed by local [36 (18%)] and regional [22 (11%)] recurrence. The most common cause of treatment failure in SNMM is distant metastasis. The tumor site and the presence of metastatic disease at presentation were the only independent predictors of survival. These data can be used to inform quality improvement efforts and the counseling of high-risk SNMM patients.

Background Mucosal melanomas in the head and neck region are most often located in the nasal cavity and paranasal sinuses. To the authors' knowledge, the prognostic effects of lymph node metastasis in patients with sinonasal mucosal melanoma (SNMM) have not been established. Therefore, the objective of the current study was to determine the effects of lymph node metastasis on survival. Methods The current study included 198 patients with SNMM who had been treated between 1985 and 2016 at The University of Texas MD Anderson Cancer Center in Houston. Patients' clinical and pathologic lymph node statuses were evaluated and characterized. A multivariate analysis was used to assess the associations between regional spread and survival outcomes. Results Therapeutic neck dissection was performed in 23 patients with SNMM (11.6%). Regional disease recurrence occurred in 7 of the patients who had lymph node metastasis at the time of presentation (30.4%) and in 30 of those who had N0 disease at the time of presentation (17.1%) (P = .15). Metastasis to the contralateral lymph nodes was present in 7 patients (3.5%). The 5-year disease-specific survival rate was 66% in patients with lymph node spread compared with 45% in patients with N0 status (P = .04, log-rank test). A multivariate analysis demonstrated that distant metastasis was the only variable found to be independently associated with both overall survival (hazard ratio, 2.96; 95% confidence interval, 1.54-6.95 [P = .01]) and disease-specific survival (hazard ratio, 3.32; 95% confidence interval, 1.79-7.14 [P = 0.01]). Conclusions The results of the current study demonstrated that lymph node status in patients with SNMM was not a significant predictor of outcome. This finding, together with the low incidence of lymph node metastases in patients with SNMM, suggests that elective treatment of the neck should be highly selective in this patient population. Cancer 2018;124:514-20. © 2017 American Cancer Society.

Purpose Sinonasal mucosal melanoma (SNMM) is a locally aggressive tumor. This study aimed to define the role of adjuvant treatment and its association with survival outcomes of SNMM. Methods This retrospective study investigated 152 patients with SNMM treated between 1991 and 2016 in MD Anderson Cancer Center. Patients were divided into the following treatment groups: surgery alone, surgery with postoperative radiotherapy (PORT), surgery with postoperative chemoradiation (POCRT), and induction chemotherapy followed by surgery and PORT. Overall survival (OS), disease-specific survival, and relapse-free survival were compared. Survival between the groups was compared using univariate and multivariate analyses. Results The median follow-up was 28 months (range: 2–220 months). Five-year OS rates were 39, 42, 47, and 27% for the surgery only, PORT, POCRT, and neoadjuvant chemotherapy groups, respectively (log rank p = 0.73). Distant metastasis was the most common form of treatment failure and occurred in 59 (39%) patients. Five-year distant metastasis rates were 51, 45, and 58% for patients treated with surgery alone, PORT, and POCRT, respectively (log rank p = 0.21) but unable to be estimated in the neoadjuvant chemotherapy group due to low OS rates. Multivariate analysis demonstrated tumor site (hazard ratio [HR] = 2.32, 95% confidence interval [CI] = 1.24–4.15) and smoking status (HR = 1.77, 95% CI = 1.02–3.1) to be significant prognostic factors for survival. Conclusion Tumor site and smoking status were significant prognosticators in SNMM. A high rate of distant metastatic disease suggests that further investigation into novel, systemic therapies is required to improve outcomes in this disease entity.

Background: Sinonasal mucosal melanoma (SNMM) comprises

Background In this study, we evaluate our experience and the outcomes of patients with sinonasal cancer treated with endoscopic resection. Methods Retrospective review of patients with sinonasal cancer who had endoscopic resection was conducted. The outcomes of interest included survival outcomes and surgical complications. Results Overall, 239 patients were included. Median follow up time was 46.6 months. Of the 239 patients, 167 (70%) had a pure endonasal endoscopic approach, while 72 (30%) had an endoscopic-assisted approach. Postoperative cerebrospinal fluid (CSF) leakage occurred in 14 patients (5.9%). Negative margins were achieved in 209 patients (87.4%). There was no significant difference in the margin status between the pure endoscopic and endoscopic-assisted group (P = .682). There was no significant difference in the survival outcomes between both the groups. Conclusion Our data suggest that in properly selected patients, endoscopic approaches have acceptable morbidity with low complication rates and can provide an oncologically sound alterative to open approaches.

Background Sinonasal undifferentiated carcinoma (SNUC) is a rare, highly aggressive cancer. It is often difficult to determine whether SNUC is a distinct pathologic entity with poorly differentiated neuroendocrine features or it represents an undifferentiated tumor of squamous lineage. Also, reliable histopathologic markers that distinguish SNUC from poorly differentiated sinonasal squamous cell carcinoma (SNSCC) are lacking. Therefore, identification of new diagnostic molecular markers for SNUC is needed. Methods Treatment-naive tumor specimens obtained from 15 SNUC and 6 SNSCC patients were used. Gene expression analysis was performed using an oncology panel. Results An unsupervised cluster analysis divided the patients into the one with only SNUCs and the one with mainly SNSCCs. Of 132 differentially expressed genes, 7 genes completely distinguished SNUCs from SNSCCs. SNUCs were enriched in sets of genes related to DNA repair, synthesis/replication, and cell division. Conclusions Our study identified new diagnostic markers and potential therapeutic targets for SNUC.

To provide a comprehensive review of the literature highlighting the recent advances in the diagnosis and management of sinonasal undifferentiated carcinoma (SNUC) RECENT FINDINGS: SNUC usually presents at advanced stage and the prognosis is usually poor with high rates of locoregional recurrence and tendency to metastasize. Special attention should be made in differentiating SNUC from other sinonasal malignancies in order to guide the appropriate treatment accordingly. Multimodality treatment is usually recommended for treating SNUC. The use of neoadjuvant chemotherapy may be associated with improved outcome and can be used to guide the subsequent treatment selection. Despite the recent advances in chemotherapeutic agents, radiation techniques, and surgical approaches, the prognosis and survival outcomes of SNUC remain poor. The addition of induction chemotherapy to the treatment approach followed by definitive local therapy needs to be further studied as it might improve the outcome.

Background: Sinonasal undifferentiated carcinoma (SNUC) is a rare, highly aggressive cancer that arises in the nasal cavity and paranasal sinuses. Despite aggressive multimodal therapy the prognosis remains poor. Because of the locally advanced nature of SNUC, we have used cisplatin-based induction chemotherapy before definitive surgery or radiation therapy in our institution. Unfortunately, about 30% of SNUC patients do not respond to this treatment, and the lack of response is associated with poor survival. Therefore, developing strategies to overcome resistance to induction chemotherapy is crucial. Our current gene expression analysis of SNUC specimens indicated that the TGFβ signaling pathway might be activated in nonresponders. Using the MDA8788-6 SNUC cell line established from a nonresponder, we found that TGFβ signaling is upregulated in an autocrine manner in the SNUC cell line. Since inhibition of the TGFβ pathway overcame cisplatin resistance in this cell line, we decided to examine the effects of TGFβ inhibition in vivo. Materials and Methods: The MDA8788-6 SNUC cell line were cultured under serum-free condition overnight to induce TGFβ signaling. The cells were then resuspended in the serum-free conditioned medium collected from the same cell line to maintain activation of the pathway. Two million MDA8788-6 cells in the conditioned medium were inoculated into the flank of mice subcutaneously. On the same day of the inoculation, we started treatment with i) vehicle control, ii) cisplatin only (4 mg/kg, once per week, intravenously), iii) EW-7197 only (TGFβRI specific inhibitor, 40 mg/kg, five times per week, oral gavage), and iv) cisplatin plus EW-7197. After 5 courses of treatments, the mice were sacrificed. Average tumor volume of each treatment group 31 days after the cell inoculation was compared by Tukey’s multiple comparisons test. Area under the curve (AUC) was calculated according to the tumor growth curve of each mouse from 0 to 31 days after the cell inoculation. AUC of CDDP group and CDDP plus EW-7197 group was compared by unpaired, two-tailed t test with Welch’s correction. Results: The EW-7197 treated group itself did not show antitumor growth effect compared to the control group. Comparison of AUC of the tumor volume showed significant difference between the cisplatin alone and cisplatin plus EW-7197; the combination of cisplatin and EW-7197 had better antitumor growth effect compared to cisplatin alone. Conclusions: Our finding suggests that TGFβ inhibition may offer hope to SNUC patients struggling with chemoresistance. Citation Format: Yoko Takahashi, Hideaki Takahashi, Moran Amit, Frederico O. Gleber-Netto, Diana Bell, Tong-Xin Xie, Dianna Roberts, Ahmed S. Abdelmeguid, Curtis Pickering, Jeffrey N. Myers, Ehab Y. Hanna. Overcoming cisplatin resistance in sinonasal undifferentiated carcinoma by inhibiting the TGFβ signaling pathway in vivo [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr B08.

To provide a comprehensive review of the literature focusing on the recent advances in the diagnosis and management of olfactory neuroblastoma.Multimodality treatment is usually recommended for the majority of ONB cases. Recent advances in surgical approaches include the evolving role of endonasal endoscopic surgical resection and reconstruction. The introduction of new conformal radiation techniques has improved the outcomes and reduced treatment-related toxicity to important structures such as the eye and the brain. The role of neoadjuvant and adjuvant chemotherapy is yet to be defined. In the last two decades, there have been advances in surgical techniques with endoscopic approaches, either alone or in combination with craniotomy, gradually replacing the open traditional approaches. Prolonged surveillance is recommended for ONB due to late recurrences associated with that tumor. The role of chemotherapy and elective neck irradiation is still controversial and needs more studies to investigate their optimal role.

Mucosal melanomas in the head and neck region are most often located in the nasal cavity and paranasal sinuses. To the authors' knowledge, the prognostic effects of lymph node metastasis in patients with sinonasal mucosal melanoma (SNMM) have not been established. Therefore, the objective of the current study was to determine the effects of lymph node metastasis on survival.The current study included 198 patients with SNMM who had been treated between 1985 and 2016 at The University of Texas MD Anderson Cancer Center in Houston. Patients' clinical and pathologic lymph node statuses were evaluated and characterized. A multivariate analysis was used to assess the associations between regional spread and survival outcomes.Therapeutic neck dissection was performed in 23 patients with SNMM (11.6%). Regional disease recurrence occurred in 7 of the patients who had lymph node metastasis at the time of presentation (30.4%) and in 30 of those who had N0 disease at the time of presentation (17.1%) (P = .15). Metastasis to the contralateral lymph nodes was present in 7 patients (3.5%). The 5-year disease-specific survival rate was 66% in patients with lymph node spread compared with 45% in patients with N0 status (P = .04, log-rank test). A multivariate analysis demonstrated that distant metastasis was the only variable found to be independently associated with both overall survival (hazard ratio, 2.96; 95% confidence interval, 1.54-6.95 [P = .01]) and disease-specific survival (hazard ratio, 3.32; 95% confidence interval, 1.79-7.14 [P = 0.01]).The results of the current study demonstrated that lymph node status in patients with SNMM was not a significant predictor of outcome. This finding, together with the low incidence of lymph node metastases in patients with SNMM, suggests that elective treatment of the neck should be highly selective in this patient population. Cancer 2018;124:514-20. © 2017 American Cancer Society.

Background Optimal treatment and prognostic factors affecting long-term survival in patients with sinonasal adenoid cystic carcinoma (ACC) have yet to be clearly defined. Methods We conducted a retrospective review of patients treated with curative intent from 1980-2015 at MD Anderson Cancer Center. Results One hundred sixty patients met inclusion criteria, including 8 who were treated with radiotherapy alone. Median follow-up time was 55 months. The 5-year overall survival (OS) and disease-free survival (DFS) rates were 67.0% and 49.0%, respectively. The 10-year OS and DFS rates were 44.8% and 25.4%, respectively. Factors that portended for poor survival on multivariate analysis were recurrent disease, any solid type histology, epicenter in the sinus cavity, the presence of facial symptoms, or the original disease not treated with surgery. There was no association between surgical margin status or nodal status and survival. Conclusion In this large cohort of patients with sinonasal ACC with extended follow-up, long-term survival is better than reported in prior literature. Future research should target patients with adverse risk factors.