L03 - Role of induction chemotherapy in the multimodal management of locally advanced epithelial sinonasal cancer: a single center experience

Abstract

Background: outcomes of locally advanced epithelial sinonasal cancer remain unsatisfactory, despite the improvement in surgical approaches and advances in radiotherapy techniques. The incorporation of induction chemotherapy (IC) in the multimodal treatment strategy has shown promising results in few studies. Only limited and heterogeneous data exist on prognostic factors, due to the rarity of this disease. Materials and methods: we reviewed data of 63 consecutive patients (pts) with AJCC stage III-IV epithelial non glandular sinonasal cancer, treated at National Cancer Institute of Milan with IC followed by locoregional treatment between 1996 and 2013. Overall survival (OS) and progression free survival (PFS) were calculated with the Kaplan Meier method. Cox regression analysis was used to determine predictors of OS and PFS. Results: the following histotypes were represented: 25 sinonasal undifferentiated carcinoma (SNUC), 8 pure neuroendocrine cancer (SNEC), 24 keratinizing and not keratinizing squamous cell carcinoma (KSCC + NKSCC), 6 small cell cancer; neuroendocrine differentiation was present in 18 patients. Fifty patients had stage IV and 13 patients stage II-III. After IC, 27 pts were treated with surgery and (chemo)radiation, while 36 pts received chemoradiation. Overall, 53 patients showed a response to IC (PR= 45 CR= 8), 8 had stable disease and 2 had progression. Three-year OS and PFS rates were 73% and 53%, respectively. After stratification according to histological subtypes, 3-year OS rates were 86% for SNUC, 36% for SNEC, 74% for KSCC + NKSCC, and 50% for small cell tumors, respectively. When stratified according to response to IC, patients with a complete response showed a significantly better PFS compared to pts with partial response or stable disease (log-rank test; p 0.0325). Finally, in Cox regression models, patients with a tumoral neuroendocrine differentiation showed a significant worse PFS in respect to patients without neuroendocrine differentiation (HR: 2.8; p = 0.009). Conclusions: response to IC and neuroendocrine differentiation represent prognostic factors in locally advanced epithelial sinonasal cancer treated with a multimodality approach. Efforts are still needed to develop strategies overcoming tumor resistance in order to increase survival. Two phase II trials are ongoing to investigate the role of IC, surgery and photon/heavy ion radiation in these tumors (Clinicaltrials.gov identifier: NCT02099175 and NCT02099188).