xRead - Nasal Obstruction (September 2024) Full Articles

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The pathological features are typically high grade with nests, sheets, or ribbons of undifferentiated cells with out glandular or squamous features. Testing for keratins, including pancytokeratin (AE1/AE3) and cytokeratins 7, 8, and 18, is often positive. 1393 S100 and Epstein–Barr virus tests are negative. 1397 IDH2 hotspot mutations are iden tified in a significant subset of SNUCs, and IDH2(R172S) is the most common. IDH-mutant SNUC demonstrates a hypermethylation phenotype, and DNA-based profiling studies show that IDH-mutant SNM constitutes a dis tinct group from IDH-wild-type tumors. 1398–1400 Presently, no morphologic or immunohistochemical differences between SNUC that are IDH-mutant or wild-type are rec ognized. Imaging differentiates SNUC from other SNM. SNUC has consistently been found to have a lower ADC ratio than ACC and a higher FDG avidity than ONB, metastatic tumors, or ACC on PET imaging. 200,223,1127,1401 Orbital and skull base invasions are frequent; 80% of tumors are T3 or T4 at diagnosis. 499,1394,1396 Surgery with adjuvant RT or CRT and definitive CRT both have demon strated survival benefit over surgery or RT alone. 1394,1402 Trimodality treatment has had variable superiority over bimodality treatment. 499,1394,1403 Some studies have sug gested better outcomes with surgery plus adjuvant therapy than with definitive CRT, but this is possibly related to selection bias based on resectability. 367,1404,1405 While the preponderance of studies show that patients treated with surgery with negative margins followed by RT or CRT have favorable survival, margin status has not been consistently reported as a prognostic indicator and resectable patients remain in the minority. 367,1406 Radiation doses greater than 60 Gy have been associated with improved survival. 499,1397 A growing body of evidence supports the potential bene fit of IC. Around half of patients will experience disease recurrence within 3 years of treatment. 497,1396 Five-year survival rates range from 35% to 81%. 499,1395,1403,1407 Numer ous mutations are being considered for novel targeted therepeutics. 1399,1408–1410 Several prospective studies are currently underway (e.g., NCT00707473, NCT02099175, and NCT02099188), but none have been published to date. Evidence surrounding surgical management of SNUC was discussed in ICSB 2019 and will not be addressed here. 5 XXIV.B.I.A. Elective management of the neck Regional metastases are found in approximately 15% of patients (range 5%–30%). Metastases are more common with advanced disease, particularly skull base invasion, and have been associated with poorer prognosis. 497,1394–1396,1405,1411,1412 A dozen studies have evaluated the evidence for elective neck treatment for SNUC, but all have been retrospective cohort studies or case series. These were systematically reviewed in a meta-analysis by Faisal et. al., which demonstrated an 80%

lower risk of regional recurrence for patients undergoing elective neck treatment (OR 0.20; 95% CI: 0.08–0.49; p = 0.0004). 1412 This has traditionally included lymph node levels I through III. Several caveats exist to the recommendation for neck treatment. It is worth noting that 83% of patients in the aforementioned meta-analysis had T4 disease, and 96% had T3 or higher, so there was not an adequate sam ple to demonstrate the benefit of elective neck treatment for nonadvanced SNUC. The question of unilateral ver sus bilateral neck treatment has also not been answered. Ahn et al. demonstrated that the incidence of nodal metas tases is greatest with nonethmoidal tumors, although the incidence of nodal metastases for nasal/ethmoid sinus tumors was also significant at 15%. 229 Consideration of bilateral elective neck treatment may be most warranted for advanced midline tumors or nonethmoidal tumors with significant contralateral involvement. Although the authors of the systematic review recommend END over ENI for staging accuracy and sequela mitigation, it is unknown whether one treatment is superior. 1412 It is also not known if adjuvant neck radiation should be with held if an END does not yield disease. 1413 Proponents of ENI point to the advantage of the ability of RT to treat retropharyngeal nodes, a common drainage basin for the posterior nasal cavity and the ethmoid sinus. The retropha ryngeal nodes are not easily accessible or salvageable after recurrence with surgery, and their inclusion in radio therapy fields is without significant additional morbidity and well tolerated. Regardless of the outcome of END, the retropharyngeal nodal basin needs to be treated dur ing postoperative RT to the primary tumor, particularly for locally advanced tumors and/or early-stage tumors involving posterior nasal cavity/ethmoid sinus. a Role of neoadjuvant/induction chemotherapy Several studies support the use of IC for SNUC; however, this is not universal. 497,1402,1403,1414,1415 In particular, neoad juvant therapy response appears to best serve as a guide for determining subsequent treatment—namely, surgery with adjuvant RT versus definitive CRT. 1403 Amit et al. found that patients who had a partial or complete response to IC had a 5-year DSS rate of 81% when treated with defini tive CRT, compared to 51% for those receiving surgery with adjuvant RT or CRT. In patients who did not respond to IC and were not treated with surgical resection, 5-year DSS was 0%. Still, DSS appears to be better for patients who received IC followed by surgery with adjuvant treatment than for other cohorts who underwent bi- and trimodal ity treatment without neoadjuvant therapy. 1395,1402 One study found preoperative radiation to be associated with a 78% greater likelihood of negative margins, although this analysis included numerous types of malignancies. 1416