Multidisciplinary approach for poor prognosis sinonasal tumors: Phase II studies of chemotherapy, surgery, photon and heavy ion radiotherapy integration for more effective and less toxic treatment–Trials in progress

Abstract

Background: Sinonasal tumors are rare diseases comprising several histological subtypes. Surgery followed by radiotherapy (RT) has been the usual approach for loco-regionally advanced disease. In poor-prognosis histological types, 5-year overall survival and disease free survival are less than 40%, with worst scenario for undifferentiated form and unresectable diseases. New therapeutic strategies are needed to obtain more efficient treatment with less morbidity. Some retrospective studies explored the role and feasibility of induction chemotherapy (CT). Histology and molecular pattern can guide the choice of administered CT. Proton/carbon ion beam therapy, compared to conventional photon therapy, provides a more accurate and intense dose to tumor area with less toxic side effects and potentially higher control of disease. Overall, multimodality treatment seems the best approach, although so far prospective data are missing.We started 2 prospective trials (SINTART 1 for operable and 2 for non-operable cancers) with integration of multiple modality of treatment modulated by histology, molecular profile and response to induction CT. Moreover, heavy ion RT combined with photon RT allows the use of latest technology with greater biological effectiveness and reduction of toxicities (Clinicaltrials.gov identifier: NCT02099175 and NCT02099188). Methods: SINTART 1 and 2 are two open-label, phase II, multicenter clinical trials, designed to assess the efficacy in term of progression-free survival of a multimodality treatment in the management of patients with poor prognosis sinonasal carcinomas (intestinal-type adenocarcinoma, sinonasal undifferentiated cancer, sinonasal neuroendocrine cancer, squamocellular cancer, Hyams grade 3-4 esthesioneuroblastoma) . Safety will also be evaluated, with specific focus on late toxicities. It is planned to recruit 40 patients over two years for SINTART 1 and 25 patients for SINTART 2. Conclusions: The trials are open to accrual and they will evaluate the effectiveness and safety of a multimodal approach in the treatment of sinonasal cancers.