Anti-Tumour Treatment The role of systemic therapy in the management of sinonasal cancer: A critical review Paolo Bossi a,⇑ , Nabil F. Saba b , Jan B. Vermorken c , Primoz Strojan d , Laura Pala a , Remco de Bree e , Juan Pablo Rodrigo f , Fernando Lopez f , Ehab Y. Hanna g , Missak Haigentz h , Robert P. Takes i , Piet J. Slootweg i , Carl E. Silver h , Alessandra Rinaldo j , Alfio Ferlito k a Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy b The Winship Cancer Institute of Emory University, Atlanta, GA, USA c Antwerp University Hospital, Edegem, Belgium d Institute of Oncology, Ljubljana, Slovenia e UMC Utrecht Cancer Center, Utrecht, The Netherlands f Hospital Universitario Central de Asturias, Oviedo, Spain g The University of Texas MD Anderson Cancer Center, Houston, USA h Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA i Radboud University Medical Center, Nijmegen, The Netherlands j University of Udine School of Medicine, Udine, Italy k International Head and Neck Scientific Group, Italy article info Article history: Received 20 May 2015 Received in revised form 23 July 2015 Accepted 26 July 2015 Available online xxxx Keywords: Sinonasal cancer Multimodality treatment Chemotherapy Targeted therapy abstract Purpose: Due to the rarity and the variety of histological types of sinonasal cancers, there is a paucity of data regarding strategy for their optimal treatment. Generally, outcomes of advanced and higher grade tumors remain unsatisfactory, despite the employment of sophisticated surgical approaches, technical advances in radiation techniques and the use of heavy ion particles. In this context, we critically evaluated the role of systemic therapy as part of a multidisciplinary approach to locally advanced disease. Results: Induction chemotherapy has shown encouraging activity and could have a role in the multi- modal treatment of patients with advanced sinonasal tumors. For epithelial tumors, the most frequently employed chemotherapy is cisplatin, in combination with either 5-fluorouracil, taxane, ifosfamide, or vincristine. Only limited experiences with concurrent chemoradiation exist with sinonasal cancer. The role of systemic treatment for each histological type (intestinal-type adenocarcinoma, sinonasal undifferentiated carcinoma, sinonasal neuroendocrine carcinoma, olfactory neuroblastoma, sinonasal primary mucosal melanoma, sarcoma) is discussed. Conclusions: The treatment of SNC requires a multimodal approach. Employment of systemic therapy for locally advanced disease could result in better outcomes, and optimize the therapeutic armamentarium. Further studies are needed to precisely define the role of systemic therapy and identify the optimal sequencing for its administration in relation to local therapies. Ó 2015 Elsevier Ltd. All rights reserved. Background Sinonasal cancer (SNC) is a rare disease, with an incidence of less than 1 case per 100,000 annually, representing 3% of all head and neck cancers [1]. Almost half of the tumors originate in the nasal cavity. The majority of other tumors originate in the maxillary or ethmoid sinuses, while tumors of the frontal and sphenoid sinuses are rare. Tumors arising in the sinonasal tract usually remain asymp- tomatic for a long period. Therefore, patients more often present with extensive tumors with significant invasion of neighboring organs and tissues such as the eyes, optic nerves and chiasm, lacri- mal glands, frontal and temporal lobes of the brain, brainstem, and pituitary gland. The usual clinical presentation of SNC includes symptoms that are indistinguishable from inflammatory sinus dis- ease such as (unilateral) nasal obstruction, discharge and epistaxis. Depending on the origin and further extension in surrounding http://dx.doi.org/10.1016/j.ctrv.2015.07.004 0305-7372/Ó 2015 Elsevier Ltd. All rights reserved. ⇑ Corresponding author at: Head and Neck Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy. Tel.: +39 0223902765; fax: +39 0223903769. E-mail address: paolo.bossi@istitutotumori.mi.it (P. Bossi). Cancer Treatment Reviews xxx (2015) xxx–xxx Contents lists available at ScienceDirect Cancer Treatment Reviews journal homepage: www.elsevierhealth.com/journals/ctrv Please cite this article in press as: Bossi P et al. The role of systemic therapy in the management of sinonasal cancer: A critical review. Cancer Treat Rev (2015), http://dx.doi.org/10.1016/j.ctrv.2015.07.004