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105

ICAR SINONASAL TUMORS

TABLE XII.1 (Continued)

Clinical endpoints

Study

Year LOE Study design Study groups

Conclusions

Janecka et al. 415

No evidence of disease status

The ability to achieve NM in SCC is directly related to no evidence of disease status LR was detected in 15 out of 20 patients with PM versus one out of 44 patients with NM

1994 4

Retrospective review

Patients with SCC treated with CBS with PM (33%) versus NM (77%) Patients with SCC or adenocarcinoma of the maxillary sinus withPM( n = 20) versusNM( n = 44)

Hordijk and Brons 389

1985 4

Retrospective review

LR

Abbreviations: AC, adenocarcinoma; bEEATC, bilateral endoscopic resection with transnasal craniectomy; CRT, chemoradiation therapy; DM, distant metastasis; DSS, disease-specific survival; IFSH, intraoperative frozen section histopathology; LR, local recurrence; LRC, locoregional control; macro-PM, macroscopic positive margins; micro-PM, microscopic positive margins; MS, margin status; NM, negative margins; NPV, negative predictive value; OR, open resection; OS, overall survival; PFS, progression-free survival; PM, positive margins; PPV, positive predictive value; RPFS, regional progression-free survival; RR, regional recurrence;

SCC, squamous cell carcinoma; SS, salvage surgery; uEEATC, unilateral endoscopic resection with transnasal craniectomy. a LOE downgraded as study most consistent with retrospective case series with secondary analysis of margin status. b LOE downgraded as study most consistent with retrospective case series with multiple subanalyses/comparison groups.

Preoperative planning and counseling of the patient are essential whenever there is suspicion of involvement of either the orbit or the skull base given the potential con sequences of clearing margins along either of these vital structures. With the orbit, if the lamina papyracea is invaded, periorbita should be sampled as a margin. 316,335 Should this be positive, orbital fat/orbital contents would need to be assessed. 316,335 If the bone of the skull base is invaded, dura would need to be sampled as a margin. 316,382 Any areas with positive margins should be re-resected until they are negative unless prohibited by proximity to crit ical neurovascular structures where biopsy may result in significant morbidity or mortality. B Frozen sections for margin analysis Frozen sections can play several roles in endoscopic tumor resection. Given sinonasal tumors often occur within close proximity to or involve the nasal septum, it is recom mended that frozen sections of septal mucosa be taken from along the course of the planned NSF to confirm no malignant cells are present prior to using the NSF for reconstructive purposes. 382 Several authors endorse continuous intraoperative assessment of surgical mar gins by way of frozen section analysis during tumor resection. 106,140,182,289,316,365 Given SNM can have submu cosal, subperiosteal, and perineural spread, relying on gross identification of tumor for defining the extent of resection is insufficient. 106 Continual assessment with frozen section allows the surgeon to enlarge the resec tion until margins are cleared (when possible), thereby achieving definitive resection. 106,130,182,289 One caveat to this is PNI. Surgery is considered inadequate for clear

ing PNI, especially given the frequency of “skip lesions.” Therefore, the use of intraoperative frozen analysis to clear PNI is not considered effective. This is particu larly salient in ACC, a tumor with a propensity for PNI. Indeed, several series on ACC have shown margin sta tus to not correlate with survival metrics. 247,377,389 When definitive resection is not feasible, frozen section analysis can be used during debulking surgeries to achieve nega tive margins near vital structures in an effort to reduce RT dose. 130 Few studies have evaluated the accuracy of frozen sec tion margins in sinonasal tumors. One study showed 100% accuracy of frozen sections for several histologic sub types including SCC, adenocarcinoma, ONB, ACC, and SNUC. 384 For the entire cohort, which included mucosal melanoma, the overall false-negative rate was 6.5% and both false negatives occurred in melanoma cases. 384 With an overall false-negative rate of 25% for melanoma, the authors concluded that intraoperative frozen sections are not reliable for this tumor type. 384 A second study focusing on the accuracy of frozen section in ONB found it to be an accurate tool for the assessment of intraoperative margins with a positive predictive value (PPV) of 86% and NPV of 97%. 385 The inadequacy of frozen section analysis for melanoma is well reported. 271,373,384,390 The reason is likely due to the variability of melanoma appearance on both gross and his tological evaluations. Up to 41% of tumors in one study were amelanotic, thereby increasing the difficulty of gross examination. 373 Histologically, tumor cells can appear in both different configurations and shapes. 391 Immunohis tochemical staining is required to differentiate tumor cells from normal tissue and currently, there are no frozen sec tion immunohistochemical stains that have been studied