Teaching pack: Nasal cavity and paranasal sinus cancers (including esthesioneuroblastoma)

Sinonasal malignancies arise in the nasal cavity, maxillary and ethmoid sinuses and comprise squamous cell carcinoma (the majority, including HPV-related and inverted-papilloma-associated forms), intestinal-type adenocarcinoma (strongly linked to occupational wood and leather dust), esthesioneuroblastoma (olfactory neuroblastoma, graded by Hyams), sinonasal undifferentiated carcinoma (SNUC), neuroendocrine carcinoma, adenoid cystic carcinoma, mucosal melanoma, NUT carcinoma and SMARCB1- or SMARCA4-deficient carcinomas. Molecular reclassification has split SNUC: about half carry IDH2 R172 mutations, and others are SWI/SNF-deficient; DEK-AFF2 fusion defines a distinct carcinoma. Proximity to orbit, skull base and brain dictates both symptoms (late presentation with obstruction, epistaxis, proptosis) and treatment complexity.

Surgery is the mainstay for resectable tumours, and endoscopic endonasal and combined cranioendoscopic approaches have replaced craniofacial resection for most, with equivalent control and less morbidity. Post-operative IMRT or proton therapy is standard for advanced stage, close margins, high grade and esthesioneuroblastoma; protons reduce dose to optic pathways and brain. SNUC is treated with induction platinum-etoposide chemotherapy, and the response-adapted approach from MD Anderson (JAMA Oncol 2019) directs responders to definitive chemoradiotherapy and non-responders to surgery, with better outcomes than surgery-first. Esthesioneuroblastoma is managed by resection and radiotherapy, with chemotherapy for high Hyams grade or advanced disease.

• Endoscopic skull-base surgery has replaced open craniofacial resection for most tumours with equivalent oncological outcomes and far less morbidity.
• Response to induction chemotherapy is now used as a biomarker in SNUC to decide between organ-preserving chemoradiotherapy and surgery.
• Molecular splitting of SNUC into IDH2-mutant and SWI/SNF-deficient groups has given the first targetable alterations in a disease that had none.
• Proton therapy reduces dose to optic nerves and brain in tumours that sit against both.

1. 1924Esthesioneuroblastoma first described (Berger and Luc)
2. 1965Wood dust linked to sinonasal adenocarcinoma
3. 1986Frierson describes sinonasal undifferentiated carcinoma
4. 1988Hyams grading of esthesioneuroblastoma
5. 2000Endoscopic endonasal resection of sinonasal cancer established
6. 2017IDH2 mutations define a SNUC subset
7. 2019Response-adapted treatment of SNUC

• Proton therapy (technology)
• Enasidenib (treatment)
• Pembrolizumab (treatment)

• A Clinical Trial of Endoscopic Surgery Followed by Chemotherapy and Proton Radiation for the Treatment of Tumors in the Sinus and Nasal Passages (phase 2, n=3): result not yet recorded

• Late presentation: most tumours are locally advanced at diagnosis; awareness in ENT clinics and imaging AI are the response.
• No randomised trials exist for any sinonasal histology; international consortia are pooling cases.
• IDH2-mutant SNUC: prospective trials of IDH2 inhibitors.
• Visual and neurocognitive toxicity of radiotherapy: protons and reduced-margin planning.

1. What is the standard treatment for stage II-III triple-negative breast cancer today?
   Answer

   Neoadjuvant pembrolizumab with carboplatin/paclitaxel then anthracycline chemotherapy, surgery, and adjuvant pembrolizumab (KEYNOTE-522); adjuvant olaparib for germline BRCA carriers with residual disease (OlympiA); capecitabine for residual disease without BRCA.
2. What fraction of advanced melanoma patients on nivolumab plus ipilimumab are alive at ten years?
   Answer

   About 43% overall survival (CheckMate 067), with melanoma-specific survival around 52%.
3. Which cooperative group ran the trial that put nivolumab into first-line Hodgkin lymphoma?
   Answer

   SWOG (S1826, nivolumab-AVD vs BV-AVD), leading to FDA approval in March 2026 for ages 12 and over.

• NCI PDQ: paranasal sinus and nasal cavity cancer: https://www.cancer.gov/types/head-and-neck/patient/adult/paranasal-sinus-treatment-pdq
• NCCN Head and Neck Cancers: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1437
• Response-adapted SNUC treatment (JAMA Oncol 2019): https://doi.org/10.1001/jamaoncol.2018.5526
• Wikipedia: https://en.wikipedia.org/wiki/Esthesioneuroblastoma
• Guideline: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1437
• Guideline: https://doi.org/10.1001/jamaoncol.2018.5526