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KUANetal.

TABLE XXIV.C.1 Evidence surrounding treatment of sinonasal neuroendocrine carcinoma.

Clinical endpoints

Study

Year LOE Study design Study groups

Conclusion

DSS

1. Surgery ± RT resulted in better DSS for all treatment groups than RT/CRT 2. No added benefit from adjuvant chemotherapy 3. Outcome improved over time, possibly due to improved surgical techniques 4. Study limited by mixed pathologies The incorporation of neoadjuvant chemotherapy resulted in better OS and DFS on both uni- and multivariate analysis 1. 5-year OS 74.6% 2. Primary surgery for low-grade SNEC and primary CRT for high-grade SNEC 3. Five of seven who completed CRT required salvage surgery 1. Response rate to neoadjuvant chemotherapy: 92.3% 2. No measurable correlation between response and PFS 3. 76% grade III–IV toxicities 4. Study limited by mixed pathologies Surgery ± RT resulted in better DSS thanRT Surgery ± RT resulted in better DFS thanCRT No significant differences in DSS between Surgery, Surgery + RT, andCRT 1. Neoadjuvant chemotherapy followed by RT resulted in good outcome (OS 74%, LRC 88%) 2. Study limited by mixed pathologies and no control group

701 SNEC patients

Van der Laan et al. 1404

2016 2

Systematic

including 115 ScNEC and459 SNUC/LcNEC

reviewand meta analysis

Turri-Zanoni et al. 1349

2017 3

Retrospective cohort

98 STND including 12 ScNEC and 10 LcNEC

1. OS 2. DFS

Keilin et al. 1474

2022 4

Retrospective case series

13 SNEC patients

OS

Patil et al. 1473

2016 4

Retrospective case series

25 STND including 13 SNEC

Response rate to neoadjuvant chemotherapy

Patel et al. 48

2015 4

Database study 201 SNEC including 52 ScNEC/LcNEC

DSS

Likhacheva et al. 1468

2011

4

Retrospective case series Retrospective case series Retrospective reviewof prospec tively enrolled case series

20 SNEC including 13 ScNEC/LcNEC

DFS

Mitchell

2011

4

28SNEC

DSS

et al. 1460

Fitzek et al. 540

2002 4

19 STND including 10 SNEC

1. OS 2. LRC

Abbreviations: CT, chemotherapy; DFS, disease-free survival; DSS, disease-specific survival; LcNEC, large-cell neuroendocrine carcinoma; LCR, local control rate; LRC, locoregional control; OS, overall survival; RT, radiation therapy; S, surgery; ScNEC, small-cell neuroendocrine carcinoma; SNEC, sinonasal neuroendocrine carcinoma; SNUC, sinonasal undifferentiated carcinoma; STND, sinonasal tumors with neuroendocrine differentiation.

and 66.9%. 48,1349,1464,1468 A distinction between ScNEC and LcNEC survival is only performed in a single case series. 1349 In this study, patients with LcNECs tended to fare better (5-year OS 52.5%) than those with an ScNEC (5-year OS 33.3%), but the difference did not prove to be significant. Unsurprisingly, Mitchell et al. and Patel et al. showed that survival for advanced-stage disease was signif icantly worse compared to early-stage disease. 1404,1460 Both studies also described a significantly better DSS for nasal

cavity primary site rather than in the ethmoid or maxil lary sinus, which might be attributable to the fact that nasal cavity tumors become symptomatic at an earlier stage.

D Sinonasal mucosal melanoma SNMM is an infrequently occurring sinonasal tumor, accounting for approximately 5% of sinonasal neoplasms