ICSNT Primer for the Skull Base Community: Navigating the Landscape of Sinonasal Tumors with Synthesized Literature Guidance

The growing recognition of the intricate challenges of skull base pathologies has spurred an unprecedented collaborative effort among multidisciplinary teams, both clinically and academically. A central concern within the skull base community revolves around the management of sinonasal tumors, given the predilection of these tumors to involve the anterior skull base. Despite intense interest, synthesis of the expanding evidence in sinonasal oncology is lacking. In response to this, the International Consensus Statement on Allergy and Rhinology: Sinonasal Tumors (ICSNT) was developed, serving as a comprehensive, up-to-date, and “one stop shop” compendium housing the best available evidence in sinonasal oncology.[1]

The ICSNT project was undertaken with several key missions in mind: to be (1) histopathology-driven; (2) international and diverse; (3) multidisciplinary; (4) comprehensive; (5) embody a collaborative spirit much like to model of care for oncologic and skull base patients; and (6) serve as a reference for the current state of the evidence but not as clinical guidelines. Much of the ICSNT content has built upon work from a prior consensus document, the International Consensus Statement on Endoscopic Skull-Base Surgery (ICSB),[2] and ICSNT was designed to be complementary and cross-referenced to the ICSB for areas of overlap. A total of 48 author “teams” (189 total authors spanning 20 countries) were invited to author the document and were selected based upon publication record and academic focus in sinonasal oncology; specifically, invited authors assembled a multidisciplinary team of collaborators and colleagues to co-write each section. The format is structured akin to a large-scale systematic review utilizing Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Authors were intentionally instructed to summarize the literature and avoid editorializing or interjecting individual preferences and biases. Each section underwent an iterative review process by four members of the editorial leadership, and consensus was achieved following a 1-month open review period. For those sections with the highest levels of evidence, the aggregate grade of evidence (AGE) and recommendations were reported based on American Academy of Pediatrics Steering Committee on Quality Improvement and Management guidelines.[3] Of note, ICSNT focuses primarily on those diseases which originate within the sinonasal tract, and does not cover intracranial neoplasms or surgical techniques; rather, it aims to bring clarity to diagnostic, management, and prognostic decisions.

ICSNT is divided into four sections—General Principles; Benign Lesions/Neoplasms; Malignant Neoplasms; and Morbidity, QOL, and Surveillance. The General Principles section covers critical concepts that are relevant to the skull base community when considering treatment of sinonasal tumors, including both surgical and nonsurgical (i.e., radiation) modalities ([Table 1]). The focus of the Benign Lesions/Neoplasms section is largely on the most predominant conditions, including inverted papillomas, juvenile nasopharyngeal angiofibroma, and intraconal orbital lesions ([Table 2]). The vast majority of the content is found in the Malignant Neoplasms section, which systematically analyzes each distinct histopathologic condition and examines the evidence surrounding evaluation, treatment, and outcomes ([Table 3]). The final section provides an overview of long-term care, such as tumor surveillance, treatment morbidity, assessment of quality of life, and complications.

Table 1 Summary of general principles in management of sinonasal tumors relevant to the skull base community, as derived from individual AGE tables within the ICSNT document[1]

Broad topic	Intervention	Recommendation	AGE
Principles of surgical treatment	The decision for en bloc versus piecemeal resection is based on tumor extension and sites of involvement	Option	C
	En bloc resection of the site of attachment should be attempted whenever possible	Recommendation	C
Workup of regional and distant disease	Combination of exam, endoscopy, and CT/MRI remains gold standard; PET is option	Recommendation	C
Surgical approach	For most tumors, recommend endoscopic approach first line for lower stage lesions Endoscopic approach is an option for higher stage lesions Depends on resectability and tumor biology	Recommendation for EEA for low-stage tumors Option for EEA for high-stage tumors	C
	For maxillary sinus lesions, recommend endoscopic approach first line for benign lesions Endoscopic approach is an option for malignant lesions Assess soft tissue involvement	Recommendation for EEA for IP and other benign lesions Option for EEA for malignant tumors based upon anatomical involvement and at the discretion and comfort of the surgeon	C
Margin analysis	If surgical treatment for curative intent is elected, the goal should be to obtain negative margins whenever feasible, not GTR Consider using frozen sections to guide resection Nuances based on tumor type (e.g., ACC where GTR may be consideration)	Recommendation for most malignancies Option for ACC with perineural invasion	C
Management of the orbit	Orbital preservation should be considered whenever possible but only if negative margins can be achieved Induction chemotherapy is an option for attempting orbital preservation For tumor involving the nasolacrimal system, assess for postoperative epiphora
Resectability	Orbital apex: consider nonsurgical treatment given low likelihood of obtaining negative margins Carotid artery: feasible, though no long-term data on survival benefits Skull base: brain parenchymal involvement portends worse prognosis; cavernous sinus resection may require ICA management but challenging to obtain negative margins PPF/ITF: no longer considered unresectable with extended approaches
Radiation modalities	IMRT is gold standard and associated with improved LRC, DFS, and OS in most cases Proton beam therapy considered whenever possible given sparing of critical structures at risk Heavy ion considered for salivary gland and radioresistant tumors	Recommendation	B (IMRT) C (other modalities)

Abbreviations: ACC, adenoid cystic carcinoma; AGE, aggregate grade of evidence; CT, computed tomography; DFS, disease-free survival; EEA, endoscopic endonasal approach; GTR, gross total resection; ICA, internal carotid artery; ICSNT, International Consensus Statement on Allergy and Rhinology: Sinonasal Tumors; IMRT, intensity-modulated radiation therapy; IP, inverted papilloma; ITF, infratemporal fossa; LRC, loco-regional control; MRI, magnetic resonance imaging; OS, overall survival; PET, positron emission tomography; PPF, pterygopalatine fossa.

Table 2 Histopathology-based management of benign sinonasal tumors

Broad topic	Intervention	Recommendation	AGE
IP	High-grade dysplasia cases at risk for malignant transformation Low-risk HPV (types 6 and 11) and EGFR mutations associated with IP and malignant transformation to IP-SCC	Recommendation	B
	Treatment of the hyperostotic site (even if involving skull base or orbit) with drilling, bony resection, or cauterization may decrease recurrence	Recommendation	C
	Consider RT only in unresectable disease, multiply recurrent lesions, or IP-SCC	Option	C
JNA	Endoscopic and combined approaches preferred over traditional open approaches	Recommendation	B
	Preoperative embolization of ECA feeders reduces perioperative bleeding, LOS, and need for transfusion	Recommendation	C
Orbital tumors	Endoscopic orbital surgical approaches may be offered in lieu of open surgery by trained multidisciplinary orbital teams following appropriate workup and candidacy determination	Option	C

Abbreviations: AGE, aggregate grade of evidence; ECA, external carotid artery; HPV, human papillomavirus; IP, inverted papilloma; IP-SCC, IP-transformed squamous cell carcinoma; JNA, juvenile nasopharyngeal angiofibroma; LOS, length of stay; RT, radiation therapy.

Table 3 Histopathology-based management of primary sinonasal malignancy (table partly derived from ICSNT Table 1.1[1])

Risk/grade category	Histopathology	Management strategy	Comments
Highest	Mucosal melanoma	Surgery ± RT + IT	Surgery (AGE C) primary modality RT, IT, elective neck treatment are options
High	Poorly differentiated SCC	IC → CRT vs. salvage surgery based on response	Locally advanced disease (orbit/skull base invasion)
	SNUC/subtypes		Primary IC for bioselection (AGE B)
	SNEC, large cell type		Biologically more similar to SNUC Primary IC for locally advanced disease and high-grade tumors (AGE C)
	Rhabdomyosarcoma		Pediatric cases: CRT (AGE B) primary modality Adult cases: derived from studies in pediatric patients (AGE C)
	SNEC, small cell type		IC for locally advanced disease and high-grade tumors (AGE C)
Moderate		Surgery + RT ± AC Note: IC for locally advanced
	Adenoid cystic carcinoma		Surgery (AGE C) followed by RT (AGE C) primary modality GTR acceptable if negative margins cannot be achieved
	Well/moderately differentiated SCC		Surgery (AGE C) followed by RT (AGE C) primary modality
Low	Olfactory neuroblastoma	Surgery + RT Note: IC for locally advanced	Surgery (AGE C) primary modality RT considered for Hyam's grades III/IV, Kadish stage C/D, and positive margins
	Adenocarcinoma		Surgery (AGE C) primary modality RT considered for advanced stage disease and high-grade tumors Non-ITAC: consider IC for functional p53 protein
	Biphenotypic sinonasal sarcoma		Surgery primary modality
	Nasopharyngeal carcinoma	RT ± C ± IC Note: surgery for select recurrent cases	RT (AGE A) for early stage disease, IC (AGE A; excluding T3N0) + CRT (AGE A; consider in stage II with bulky nodal disease) for advanced stage disease; IMRT standard of care Nasopharyngectomy (AGE C) option for early local recurrent NPC (rT1/T2 and select rT3 lesions)

Abbreviations: AC, adjuvant chemotherapy; AGE, aggregate grade of evidence; C, chemotherapy; CRT, chemoradiation therapy; GTR, gross total resection; IC, induction chemotherapy; ICSNT, International Consensus Statement on Allergy and Rhinology: Sinonasal Tumors; IMRT, intensity-modulated radiation therapy; IT, immunotherapy; ITAC, intestinal type adenocarcinoma; RT, radiation therapy; SCC, squamous cell carcinoma; SNEC, sinonasal neuroendocrine carcinoma; SNUC, sinonasal undifferentiated carcinoma.

Note: Surgical treatment is predicated on achievement of negative margins (not GTR).

One will notice that most of the recommendations are of low AGE—most commonly “C,” or derived from observational studies of case control and cohort design. In fact, most of the high-quality research has been driven by oncology colleagues in the form of clinical trials, especially for those tumor types which are treated nonsurgically (i.e., nasopharyngeal carcinoma, lymphoma), indicating that we have much to learn from each other. The ICSNT editorial team acknowledges the collaborative nature of the skull base community, urging all members to persist in research efforts, exchange ideas and experiences, and enhance the scientific rigor of skull base studies. It is hoped that the ICSNT proves valuable to the readership of the Journal of Neurological Surgery Part B: Skull Base, the membership of the North American Skull Base Society, and the broader skull base community, irrespective of expertise and training levels, and plays a role in fostering continuous improvement in patient care.

Publication History

Article published online:
23 May 2024

• References

• 1 Kuan EC, Wang EW, Adappa ND. et al. International Consensus Statement on Allergy and Rhinology: Sinonasal Tumors. Int Forum Allergy Rhinol 2024; 14 (02) 149-608
• 2 Wang EW, Zanation AM, Gardner PA. et al. ICAR: endoscopic skull-base surgery. Int Forum Allergy Rhinol 2019; 9 (S3): S145-S365
• 3 American Academy of Pediatrics Steering Committee on Quality Improvement and Management. Classifying recommendations for clinical practice guidelines. Pediatrics 2004; 114 (03) 874-877