Induction chemotherapy with docetaxel and doxorubicin followed by proton beam radiation therapy for platinum-resistant unresectable sinonasal undifferentiated carcinoma

Sinonasal undifferentiated carcinoma is a rare and aggressive tumor with an extremely poor prognosis. In the vast majority of cases, this tumor can not be resected due to its rapid local growth. Correct morphological diagnosis is impossible without a thorough differential diagnosis between sinonasal undifferentiated carcinoma and a number of lowgrade tumors of the nasal cavity and paranasal sinuses. Very few case reports and retrospective studies on sinonasal undifferentiated carcinoma have been published so far. No unified widely accepted guidelines on sinonasal undifferentiated carcinoma treatment are currently available due to the lack of statistically significant data from randomized clinical trials. The optimal treatment strategy should be based on an aggressive multimodal approach involving radical surgery, precision radiation therapy, and intensive chemotherapy. The benefits of systemic targeted therapy for patients with sinonasal undifferentiated carcinoma are still unclear. The best results can be achieved by employing tailored treatment approaches preferably in multidisciplinary cancer centers, where healthcare professionals experienced in managing patients with head and neck tumors can be involved. In this article, we report a case of complete radiological response after induction chemotherapy with docetaxel and doxorubicin and proton radiation therapy for the primary tumor area in a 53‑year-old female patient with non-resectable platinum-resistant sinonasal undifferentiated carcinoma.

A Rare Malignancy of Head And Neck Region: Sinonasal Undifferentiated Carcinoma

Sinonasal undifferentiated carcinoma is a rare malignancy of the head and neck region. Its diagnosis and treatment are difficult due to its rare and aggressive tumor nature and the complex anatomy of its localization. A 70-year-old male who presented with symptoms caused by this rare tumor was reported. The patient presented with pain on the left side of the head and vision loss in the left eye for 1 month, and his endoscopic biopsy was reported as undifferentiated carcinoma. This case report aimed to discuss the diagnosis and treatment of sinonasal undifferentiated carcinoma.

Complete response to immunotherapy in sinonasal undifferentiated carcinoma

Sinonasal undifferentiated carcinoma (SNUC) is an uncommon aggressive tumor. Locally advanced disease is usually diagnosed at presentation. Multidisciplinary approach is essential and aims to ensure optimal trimodal strategy. Induction chemotherapy is preferred in order to select patients who will benefit from chemoradiotherapy or surgery. Immunotherapy is not indicated in patients with recurrent SNUC. We describe an impressive response in a young man previously treated with radiotherapy and chemotherapy and demolitive surgery who had metastatic bone and lung disease. We also report data on PD-L1, next-generation sequencing, and neutrophil/platelets ratio.

Genetic analysis of sinonasal undifferentiated carcinoma discovers recurrent SWI/SNF alterations and a novel PGAP3-SRPK1 fusion gene

Background Sinonasal Undifferentiated Carcinoma (SNUC) is a rare and aggressive skull base tumor with poor survival and limited treatment options. To date, targeted sequencing studies have identified IDH2 and SMARCB1 as potential driver alterations, but the molecular alterations found in SMARCB1 wild type tumors are unknown. Methods We evaluated survival outcomes in a cohort of 46 SNUC patients treated at an NCI designated cancer center and identify clinical and disease variables associated with survival on Kaplan-Meier and Cox multivariate survival analysis. We performed exome sequencing to characterize a series of SNUC tumors (n = 5) and cell line (MDA8788–6) to identify high confidence mutations, copy number alterations, microsatellite instability, and fusions. Knockdown studies using siRNA were utilized for validation of a novel PGAP3-SRPK1 gene fusion. Results Overall survival analysis revealed no significant difference in outcomes between patients treated with surgery +/− CRT and CRT alone. Tobacco use was the only significant predictor of survival. We also confirmed previously published findings on IDH and SMARC family mutations and identified novel recurrent aberrations in the JAK/STAT and PI3K pathways. We also validated a novel PGAP3-SRPK1 gene fusion in the SNUC cell line, and show that knockdown of the fusion is negatively associated with EGFR, E2F and MYC signaling. Conclusion Collectively, these data demonstrate recurrent alterations in the SWI/SNF family as well as IDH, JAK/STAT, and PI3K pathways and discover a novel fusion gene (PGAP3-SRPK1). These data aim to improve understanding of possible driver mutations and guide future therapeutic strategies for this disease.

Genetic Analysis of Sinonasal Undifferentiated Carcinoma Discovers Recurrent SWI/SNF Alterations and a novel PGAP3-SRPK1 Fusion Gene

Background: Sinonasal Undifferentiated Carcinoma (SNUC) is a rare and aggressive skull base tumor with poor survival and limited treatment options. To date, targeted sequencing studies have identified IDH2 and SMARCB1 as potential driver alterations, but the molecular alterations found in SMARCB1 wild type tumors are unknown.Methods: We evaluate survival outcomes in a cohort of 46 SNUC patients treated at an NCI designated cancer center and identify clinical and disease variables associated with survival on Kaplan-Meier and Cox multivariate survival analysis. We perform exome sequencing to characterize a series of SMARCB1 wild type tumors and cell line including identification of high confidence mutations, copy number alterations, microsatellite instability, and fusions. Knockdown studies using siRNA was utilized for validation of a novel PGAP3-SRPK1 gene fusion. Results: We discover recurrent aberrations to the SWI/SNF and FAT gene families. We also validate a novel PGAP3-SRPK1 gene fusion in the SNUC cell line, and show that knockdown of the fusion is negatively associated with EGFR, E2F and MYC signaling. Conclusion: Collectively, these data demonstrate recurrent alterations in the SWI/SNF and FAT gene families and discover a novel fusion gene (PGAP3-SRPK1). These data aim to improve understanding of possible driver mutations and guide future therapeutic strategies for this disease.