Ferrari, Marco

Background: Sinonasal undifferentiated carcinoma (SNUC) is an extremely rare, high-grade, and aggressive tumor of the sinonasal tract. Due to the rarity of this malignancy, current treatment guidelines are based on small and often/mainly single-center retrospective datasets. In the absence of a universally accepted standard of care for SNUC, treatment approaches vary across countries and institutions, reflecting real-world clinical practice. The primary aim of this study was to describe real-world treatment and outcomes for patients with confirmed SNUC. Methods: This was an international, multi-center, retrospective, observational cohort study that pooled patients into the largest SNUC dataset to date. Fifteen centers were enrolled to contribute data, including seven from Europe, four from the United States, three from the United Kingdom, and one from Canada. In the absence of a universally accepted standard of care for SNUC, treatment approaches varied across countries and institutions, reflecting real-world clinical practice. Patients included were those with histologically confirmed SNUC who were treated between 1997 and 2021. Results: This study yielded 485 patients treated for SNUC. The median age at diagnosis was 55.6 years (IQR: 44.5–67.6), and 63.7% were male. Most cases presented at advanced stages, with 70.8% as T4a or T4b. Overall survival (OS) outcomes were available for 412 patients, with a median follow-up of 26.0 months. The 5- and 10-year OS were 47.2% (95% CI: 40.8–53.3%) and 39.6% (95% CI: 32.5–46.6%), respectively. Advanced age, dichotomized T-stage (T4a/b vs. T1–3), M-stage, and orbital involvement were significant poor prognostic factors on univariable analysis (p’s < 0.01). On multivariable analysis, orbital involvement (HR: 2.73, 95% CI: 1.42–5.27, p = 0.003) and distance metastasis stage (HR: 3.00, 95% CI: 1.25–7.21, p = 0.014) were both independently associated with worse OS. Conclusions: This observational study presents the largest multi-center cohort analysis of SNUC to date, providing new insights into prognostic factors for a rare cancer treated at global centers of excellence. Orbital involvement and the presence of metastases are candidate independent risk factors associated with poorer OS.

ABSTRACT Introduction Sinonasal sarcomas are exceedingly rare entities, constituting less than 7% of head and neck sarcomas. Their complex histology needs specialized treatment, which is often based on multimodal approaches including surgery, radiation therapy, and/or chemotherapy. This manuscript aims to gather expert opinions to establish common management principles for sinonasal sarcomas. Methods This international consensus followed a modified Delphi method in seven steps, including statements definition by the core group, expert panel recruitment, and a two‐round survey. Sixty‐two statements on sinonasal sarcoma management were developed. Experts from multiple continents participated, and results were anonymized and analyzed between March and May 2025. Results A total of 44 invited experts were recruited, 43.2% otorhinolaryngologists/head and neck surgeons, 31.8% medical oncologists, and 25% radiation oncologists. Participants varied in age and experience, representing Europe (70.5%), North America (18.2%), South America (6.8%), and Asia (4.5%). Among all histologies, biphenotypic sarcoma, chondrosarcoma, leiomyosarcoma, and myofibrosarcoma are principally treated with an upfront surgical management, differently from Ewing sarcoma and rhabdomyosarcoma in which chemotherapy, eventually associated with radiotherapy, is often chosen. In the remaining histologies (angiosarcoma, liposarcoma, malignant peripheral nerve sheath tumor [MPNST], osteosarcoma, and synovial sarcoma), a precise multimodal treatment is less standardized and needs to be discussed on a case‐by‐case basis. Conclusion Sinonasal sarcomas require a histology‐driven approach to determine upfront treatment, whether surgical, medical, or multimodal. Despite this structured strategy, prognosis remains highly variable across subtypes. Multidisciplinary evaluation and individualized management in referral centers are crucial to address the biological diversity and anatomical complexity of these rare malignancies.

ABSTRACT Objective There is limited consensus on endoscopic skull base surgery (ESBS) reconstruction principles. This study aims to generate comprehensive themes regarding ESBS reconstruction by pooling the experiences of ESBS experts, with comparison to a literature review of current published evidence. Methods Structured qualitative interviews of ESBS experts regarding postoperative management and reconstruction of various defect locations were conducted. Results A total of 68 experts comprising 40 academic teams across 13 countries with an average of 18 years of ESBS experience were included. We propose 10 stepwise algorithms for common skull base reconstruction scenarios based on these expert interviews. When available, the nasoseptal flap is used for all high_flow cerebrospinal leak defects. Multilayered reconstruction is favored at all anatomical subsites with increasing number of layers for increasing defect size and complexity. Heterogeneity exists in terms of inlay technique and materials, free grafting versus various pedicled flap options for low‐flow defects or in the absence of a nasal septum, nasal packing, tissue sealant, lumbar drain use, and postoperative management. Commonalities and discrepancies between experts were summarized. Conclusion Skull base reconstruction and post‐ESBS management is highly complex with a wide variety of practice patterns and expert strategies. Further research of higher quality evidence is warranted to identify optimal management patterns, though the current work aims to inform surgeons on these controversial areas by drawing from numerous experiences.

Abstract Background Sinonasal malignancies with orbital invasion have dismal prognosis even when treated with orbital exenteration (OE). Sugawara et al. developed a surgical strategy called “extended‐OE (EOE),” showing encouraging outcomes. We hypothesized that a similar resection is achievable under endoscopic guidance through the exenterated orbit (endoscopic‐EOE). Methods The study was conducted in three institutions: University of Vienna; Mayo Clinic; University of Insubria; 48 orbital dissections were performed. A questionnaire was developed to evaluate feasibility and safety of each step, scoring from 1 to 10, (“impossible” to “easy,” and “high risk” to “low risk,” respectively), most likely complication(s) were hypothesized. Results The step‐by‐step technique is thoroughly described. The questionnaire was answered by 25 anterior skull base surgeons from six countries. Mean, median, range, and interquartile range of both feasibility and safety scores are reported. Conclusions Endoscopic‐EOE is a challenging but feasible procedure. Clinical validation is required to assess real‐life outcomes.

Abstract Background Sinonasal neoplasms, whether benign and malignant, pose a significant challenge to clinicians and represent a model area for multidisciplinary collaboration in order to optimize patient care. The International Consensus Statement on Allergy and Rhinology: Sinonasal Tumors (ICSNT) aims to summarize the best available evidence and presents 48 thematic and histopathology‐based topics spanning the field. Methods In accordance with prior International Consensus Statement on Allergy and Rhinology documents, ICSNT assigned each topic as an Evidence‐Based Review with Recommendations, Evidence‐Based Review, and Literature Review based on the level of evidence. An international group of multidisciplinary author teams were assembled for the topic reviews using the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses format, and completed sections underwent a thorough and iterative consensus‐building process. The final document underwent rigorous synthesis and review prior to publication. Results The ICSNT document consists of four major sections: general principles, benign neoplasms and lesions, malignant neoplasms, and quality of life and surveillance. It covers 48 conceptual and/or histopathology‐based topics relevant to sinonasal neoplasms and masses. Topics with a high level of evidence provided specific recommendations, while other areas summarized the current state of evidence. A final section highlights research opportunities and future directions, contributing to advancing knowledge and community intervention. Conclusion As an embodiment of the multidisciplinary and collaborative model of care in sinonasal neoplasms and masses, ICSNT was designed as a comprehensive, international, and multidisciplinary collaborative endeavor. Its primary objective is to summarize the existing evidence in the field of sinonasal neoplasms and masses.