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Okafor et al. Mini-invasive Surg 2024;8:28 https://dx.doi.org/10.20517/2574-1225.2023.128 Page 7 of 15

Locally invasive tumors can be resected with a combined approach involving both endoscopic endonasal
[69]
resection and a bifrontal craniotomy for the advanced intracranial component . The combined approach
has improved local control in advanced-stage olfactory neuroblastoma [59,65,69] . Studies comparing surgical
approaches have also supported the advantages of endonasal endoscopic approach, showing benefits in
terms of achieving gross total resections, negative margins, less local recurrence, and better disease-free
survival and overall survival rates [58,69] . Surgeons should aim to achieve negative margins, which remain a
crucial prognostic factor and have a greater impact on survival outcomes than the surgical approach .
[58]
Reconstruction is commonly performed via a multi-layered approach with grafts placed intradurally or
extradurally but intracranially, and flaps placed extracranially. The NSF, an intranasal vascularized flap
based on the pedicle of the posterior septal artery, a terminating branch of the sphenopalatine artery, is
commonly used if not involved by the tumor. During surgical resection, the surgeon must evaluate the
surrounding mucosa through both gross macroscopic assessment via direct visualization and microscopic
assessment via intraoperative frozen pathology. Any gross disease should be resected and margins should be
cleared prior to consideration of reconstruction. If clearing margins results in compromise of the NSF
vascular pedicle or surface area, then alternative reconstructive options such as a lateral nasal wall flap,
pericranial flap, free mucosal graft or free flaps may be employed [57,71,72] . Ultimately, reconstruction with a
NSF should be deferred given the risks of recurrence with close margins and the potential for delayed
recurrence [72-76] .

Nonetheless, endoscopic resection and reconstruction with a vascularized flap has been associated with
faster recovery, shorter hospital stay, improved neurological, visual, and functional outcomes as well as
lower chance of failure during adjuvant radiation therapy [77-81] .

ADJUVANT RADIATION AND CHEMOTHERAPY
While primary radiation therapy has been considered, multiple reports suggest better outcomes with
postoperative adjuvant radiation therapy, particularly in cases with high-grade tumors [4,82-86] . There is
conflicting evidence on the long-term survival benefits of adjuvant radiation therapy for early-stage tumors,
Kadish A [83,87] . However, there is greater consensus that advanced-stage (Kadish C and D), high-grade
tumors (Hyams III-IV), and tumors with close or positive resection margins require adjuvant radiation
therapy . Intensity-modulated radiation therapy (IMRT) is the most used method, as it safely delivers an
[88]
effective radiation dose and reduces treatment toxicity. Proton beam radiation has shown promise in terms
of long-term survival outcomes and reduced radiation-induced toxicity compared to conventional radiation
[89]
therapy .
The role of chemotherapy in olfactory neuroblastoma management lacks definitive evidence but has been
explored to improve management outcomes in advanced disease. Acceptable indications for chemotherapy
include high histological tumor grade (Hyams grade III or IV), positive or close resection margins,
unresectable tumors and metastatic or recurrent tumors [19,90] . Even in predominantly advanced-stage
tumors, neoadjuvant chemotherapy followed by radiation therapy for Kadish stage C lesions showed a
[91]
disease-free survival of 82.6% at 15 years. This regimen employed vincristine and cyclophosphamide .
Neoadjuvant chemotherapy is also used as an organ preservation strategy in the setting of significant orbital
[92]
involvement in order to preserve a functional eye with relatively good oncological outcomes . Adjuvant
chemoradiation using a combination of cisplatin and etoposide for Kadish stage C tumors improved the
median time of the tumor relapse without a significant effect on overall survival .
[93]

There are no official treatment guidelines for the pediatric population due to the relatively small cohort size
and limited trials documented. In the pediatric population, neoadjuvant chemotherapy followed by surgical