SMARCB1 (INI-1)-Deficient Sinonasal Carcinoma: A Systematic Review and Pooled Analysis of Treatment Outcomes

SIMPLE SUMMARY: SMARCB1 (INI-1)-deficient sinonasal carcinoma is a rare but locally aggressive malignancy which usually presents very late with invasion into the orbits and intracranium, and compression of adjacent cranial nerves and their branches at diagnosis, and has a poor survival outcome. So far, less than 200 cases have been reported. The optimal treatment strategy for this rare but intractable malignancy is yet to be determined. We performed a systematic review and included patients treated at our institution for treatment outcome and survival analysis. Multivariable analysis revealed that T4b disease at diagnosis was the only prognostic factor of overall survival. In view of the extreme challenge of managing this malignancy, we are initiating a phase II trial on tazemetostat, an EHZ2 inhibitor, as induction therapy with systemic chemotherapy followed by radical surgery or chemoradiation, and as maintenance therapy for previously untreated stage III to IVA SMARCB1 (INI-1)-deficient sinonasal carcinoma. ABSTRACT: (1) Background: SMARCB1 (INI-1)-deficient sinonasal carcinoma is a rare sinonasal malignancy; since its discovery and description in 2014, less than 200 cases have been identified. It is almost impossible to perform randomized-controlled trials on novel therapy to improve treatment outcomes in view of its rarity. We performed a systematic review of all the published case reports/series and included our patients for survival analysis. (2) Methods: In this systematic review, we searched from PubMed-MEDLINE, EMBASE, Scopus, Cochrane Library, CINAHL, and Google Scholar for individual patient data to identify and retrieve all reported SMARCB1-deficient sinonasal carcinoma. Clarification on treatment details and the most updated survival outcomes from all authors of the published case reports/series were attempted. Survival analysis for overall survival (OS) and identification of OS prognostic factors were performed. This systematic review was registered with PROSPERO (CRD42022306671). (3) Results: A total of 67 publications were identified from the systematic review and literature search. After excluding other ineligible and duplicated publications, 192 patients reported were considered appropriate for further review. After excluding duplicates and patients with incomplete pretreatment details and survival outcomes, 120 patients were identified to have a complete set of data including baseline demographics, treatment details, and survival outcomes. Together with 8 patients treated in our institution, 128 patients were included into survival analysis. After a median follow up of 17.5 months (range 0.3–149.0), 50 (46.3%) patients died. The 1-year, 2-year and 3-year OS rates were 84.3% (95% CI % 77.6–91.0), 62.9% (95% CI 53.1–72.7), and 51.8% (95% CI 40.8–62.8), respectively, and the median OS was 39.0 months (95% CI 28.5–49.5). Males (p = 0.029) and T4b disease (p = 0.013) were significant OS prognostic factors in univariable analysis, while only T4b disease (p = 0.017) remained significant in multivariable analysis. (4) Conclusions: SMARCB1-deficient sinonasal carcinoma is an extremely aggressive sinonasal malignancy with a dismal prognosis. Early diagnosis and a multimodality treatment strategy are essential for a better treatment and survival outcome.