Table 1.

Table summarizing the goals of neoadjuvant chemotherapy (ChT) and chemoradiation (ChT-RT) alongside supporting evidence. A, adriamycin; C, cetuximab; CR, complete response; E, etoposide; F, 5-fluorouracile; I, ifosfamide; N.A., not available; P, cisplatin; T, taxane. * Concurrent to RT; ** Hirawaka et al. [58] used different evaluation criteria to measure response to treatment, other authors used RECIST (Response Evaluation Criteria In Solid Tumors).

Rationale	Supporting Evidence	Type of Neoadjuvant Treatment (Objective Response Rate)	ChT Regimens	Description	References
Orbit preservation	Yes	ChT (61.9–100%)	TPF	Neoadjuvant ChT is associated with a considerable chance of orbit preservation (range: 60.0–78.8%) in patients for whom orbital ablation would be indicated in case of upfront surgery.	Ock et al. [63] Hanna et al. [62] Chen et al. [64] Turri-Zanoni et al. [65] Ferrari et al. [49] Fernström et al. [66]
			TPI
			TP
			TF
			PF
		ChT-RT (57.1%; CR rate: 35.7–48.1%)	P *	Neoadjuvant ChT-RT reduces the rate of orbital ablation in patients with orbit-abutting SNSCC (range: 93–100%).	Amsbaugh et al. [67] Fernström et al. [66]
Stratification of prognosis	Yes	ChT (67.4–93.0% **)	TPF	A good response to neoadjuvant ChT is associated with a relatively favorable prognosis in terms of recurrence and survival.	Hanna et al. [62] Hirakawa et al. [68]
			TPI
			TF
			PF
Improvement of margin status	Yes	ChT-RT (N.A.)	N.A.	Neoadjuvant ChT-RT reduces the rate of involved margins in patients with orbit-abutting SNSCC.	Robin et al. [69]
Chemoselection	No	ChT (56.9%)	TPF	Effectiveness of locoregional treatment (surgery vs. (ChT)-RT) does not relate to response to neoadjuvant ChT.	Abdelmeguid et al. [70]
			TPI
			TP
			TP-C
Improvement of distant metastasis-free survival	No	ChT (56.9%)	TPF	Neoadjuvant ChT could reduce the risk of distant metastases; however, comparative evidence is lacking.	Bossi et al. [71] Abdelmeguid et al. [70]
			TPI
			TP
			TP-C