The Evolving Role of Systemic Therapy in the Primary Treatment of Sinonasal Cancer

The inclusion of systemic therapy in the multimodal approach of locally advanced sinonasal cancers, at least in some selected histologies, may improve locoregional control and reduce the frequency of distant metastasis, allowing longer survival. Response to induction chemotherapy is a strong prognostic factor for a patient's outcome and it may improve disease control by surgery and radiation. Concurrent chemoradiation aims at increasing locoregional control in squamous cell cancer of the head and neck; this is particularly important in sinonasal cancers, with a risk of local relapse of about 30%. Selected histologies may benefit from specific drug combinations, according to varying chemosensitivity. Intestinal-type adenocarcinoma carrying a functional p53 protein may be treated with preoperative cisplatin, 5-fluorouracil, and leucovorin. Sinonasal undifferentiated carcinoma is a chemosensitive disease, where the multimodal approach is necessary to counterbalance the severe prognosis. Sinonasal neuroendocrine carcinoma and olfactory neuroblastoma may benefit from systemic treatments, but their added value has not been so clearly defined yet. Multimodality trials are ongoing to test the activity of induction chemotherapy followed by locoregional curative treatment. A deeper knowledge of the molecular deregulations of these diseases could help in identifying targeted therapies.