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ICAR SINONASAL TUMORS

published in 2000 by Kim et al. In this matched-control study 34 patients with unresectable SCC of the maxil lary sinus were treated with neoadjuvant chemotherapy and RT and compared to 34 patients treated with RT alone. Despite a higher response rate to neoadjuvant chemotherapy, there was no OS or DFS benefit at 5 years posttreatment. 1074 However, since that time the application and treatment strategies have changed. Much of the more recent data regarding neoadjuvant systemic therapy in the treatment of SNSCC are from retrospective reviews from major cancer centers. In a 2014 review of 41 patients with unresectable maxillary SCC treated between 2008 and 2011 with neoadjuvant chemotherapy followed by either surgery (29.3%), defini tive CRT (58.5%), definitive RT (2.4%), or palliative RT (2.4%), the OS at 2 and 3 years was 41% and 35%, respec tively. Ultimately, the conclusion of this retrospective review was that IC has clinically significant benefit with acceptable toxicity. 1075 Hanna et al. performed a single-institution retrospective review of 46 patients with advanced-stage (T3–4) SNSCC published in 2011. They found that 67% of this cohort demonstrated at least a partial response to neoadjuvant chemotherapy and an additional 9% demonstrated stable disease; 24% of patients had progressive disease during IC. The patients who had stable disease or a partial response to neoadjuvant chemotherapy demonstrated an improved rate of 2-year OS compared to patients with progressive disease (77% vs. 36%, respectively). 1076 In an updated retro spective review of 127 patients with previously untreated, locoregionally advanced SNSCC treated with neoadju vant chemotherapy between 1988 and 2017 from the same group, Abdelmeguid et al. report similar findings. Most patients had at least partial response (52%), with com plete response in 5% and progression of disease in 17%. Recurrence occurred in 26.8% of patients at a median time of 8.3 months. Most recurrences were local (63.6%). The study showed better 2-year OS and DFS in patients who had at least partial response or stable disease compared to patients who had progression of disease after neoadjuvant chemotherapy ( p = 0.028and p = 0.021, respectively). The 2-year OS and DFS rates for the whole cohort were 61.4% and 67.9%, respectively. There was no statistically signif icant difference between survival outcomes between the locoregional treatment modalities. 1077 In all, a systematic review assessing the role of IC in advanced SNM by Khoury et al. from 2019 concludes that, while IC has similar OS out comes, it can be offered as an option to patients as part of multimodality therapy. 1078 This is particularly true in cases that would require deforming resections. While the goals of neoadjuvant systemic therapy for advanced-stage SNSCC are many— including decreasing the incidence of local recurrence

and distant metastasis in hopes of improving overall and disease-free survival—one major role of neoadjuvant sys temic therapy that has been advocated for is to improve tumor control, downstage the primary “T” stage, and offer orbital preservation. In a retrospective review of 21 patients, Ock et al. showed a 61.9% partial response to IC in their patient cohort. Their most common regimen was docetaxel, fluorouracil, and cisplatin. They concluded that patients with a partial response and a downgrade in “T” stage led to increased incidences of orbit preserva tion and improved OS. 1079 In a similar effort to preserve the orbit, some advocate for neoadjuvant CRT. In a study by Amsbaugh et al., 20 patients with SNM involving the orbit requiring orbital exenteration (eight of which were SNSCC) were studied. Fourteen patients underwent neoadjuvant CRT and orbit preserving surgery, while six patients received an exenteration with adjuvant CRT. They found that exenteration-free survival was 62% at 2 years after treatment for patients undergoing initial orbit preser vation treatment. Further, at 2 years posttreatment, there were no significant differences of PFS or OS. This is sug gestive that in select cases, neoadjuvant CRT may offer a lasting means of orbit preservation. 501 The role of neoadjuvant CRT is further supported by a large NCDB review by Robin et al. of 11,160 patients with sinonasal cancer, 3331 of whom had SNSCC. In a subset analysis of just SNSCC, compared to surgery alone, neoadjuvant chemotherapy followed by surgery, and neoadjuvant RT followed by surgery, only neoadjuvant CRT was found to increase the rate of negative margins. 159 However, in another NCDB study of 3835 patients pri marily designed to assess outcomes of SNSCC based on the volume of the treatment center, Teitelbaum et al. performed a multivariate regression analysis of different treatment regimens and found no statistically significant difference in outcomes for patients treated with surgery and neoadjuvant or adjuvant chemotherapy ( n = 34) and surgery with neoadjuvant chemotherapy and adjuvant RT ( n = 47). 1080 In an effort to increase cytotoxicity to tumor cells while decreasing systemic toxicity of chemotherapeutic agents, intra-arterial neoadjuvant chemotherapy has been described. Theoretically, this allows for a more direct delivery of high-dose cytotoxic agents to the tumor with potential to minimize side effects. However, because of small sample sizes and uncertainty about selection crite ria, as well as conflicting toxicity reports, generalizations regarding this approach are limited. 1081–1083 Neoadjuvant chemotherapy seems to have a role in treatment of locally advanced SNSCC. Response rates are variable, and responders seem to demonstrate an improved OS. Additionally, patients with locally advanced tumors treated with neoadjuvant chemotherapy seem to