Proton Beam Therapy for Sinonasal Neuroendocrine Carcinoma: A Six-Case Series with Dosimetric Comparison and Literature Review.

Background: Sinonasal neuroendocrine carcinoma (SNEC) is an extremely rare malignancy, and, to date, no clinical reports have detailed the use of proton beam therapy (PBT) for this disease. The present study describes the clinical courses of patients with SNEC treated with PBT and highlights the advantages of PBT. Methods: In this retrospective study, we included patients with pathologically confirmed SNEC without distant metastasis who underwent PBT at our institution between 2006 and 2021. To evaluate the dosimetric advantages of PBT, comparative treatment plans using VMAT were created. Result: Six patients with pathologically diagnosed SNEC without distant metastasis were treated with PBT. Multimodal treatment was applied in five patients, including chemotherapy in four cases and surgery in two cases. The median follow-up period was 37.4 months (range: 6.9 to 108.9 months). At the end of the follow-up, three patients were alive without recurrence, while three had died due to the disease. Recurrence occurred in three cases: one local recurrence, one in cervical lymph nodes, and two distant metastases. A late adverse event of Grade 4 vision decrease was observed in one patient on the ipsilateral side. Compared with VMAT, PBT lowered the average brain dose (median 3.3 Gy (RBE) vs. 12.6 Gy), brainstem D2 cc (10.7 Gy (RBE) vs. 34.9 Gy) and contralateral optic nerve D0.1 cc (47.6 Gy (RBE) vs. 63.3 Gy), while doses to the ipsilateral optic pathway were comparable. Conclusions: PBT in multimodal treatment achieved feasible local control for SNEC. The dose-sparing effect of PBT was more evident in organs distant from the target, although careful consideration is required for adjacent structures.