Does Clearance of Positive Margins Improve Local Control in Oral Cavity Cancer? A Meta‐analysis

Abstract

Objectives To compare local recurrence-free survival (LRFS) in early oral cavity cancer (OCC) patients with positive/close frozen section (FS) cleared with further resection (R1 to R0) or positive FS not cleared (R1) to those with negative margins on initial FS analysis (R0). Data Sources PubMed, EMBASE, and Cochrane. Review Methods We followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) for reporting in our study. Only English-language articles that included patients with OCC and local recurrence (LR) comparisons between R0 and initially R1 to final R0 or final R1 groups were included. We requested the raw data from the corresponding authors of eligible studies and performed an individual participant data (IPD) meta-analysis of LRFS outcomes across groups. Results Pooled LRFS data from 8 studies showed that patients in the R1 to R0 group had worse LRFS compared to the R0 group (hazard ratio [HR] = 2.897, P < .001). Patients in the R1 group were also found to have worse LRFS compared to the R0 group (HR = 3.795, P < .001). When compared to final R1 group, the initially R1 to final R0 only showed a trend toward better LRFS. Conclusion Margin revision of initially positive margins to “clear” based on FS guidance does not equate to an initially negative margin and does not significantly improve local control. These findings call into question the effectiveness of the current methodology of intraoperative FS in OCC resections and call for a prospective study to determine what system of resected specimen analysis best predicts completeness of resection.

A Global Genome-wide Scan with Optimal Cutoff Mining for Emerging Biomarkers in Head and Neck Squamous Cell Carcinoma

“…The Brandwein-Gensler's risk model (lymphocytic host response, WPOI-5, and PNI) [48] [49] was suggested to be routinely performed on pathological examination. In previous reports of HN-SCC, the loco-regional failure will be high when the initial frozen section has a positive/close surgical margin, and even the final margin revision revealed negative [50]. According to Table 2 and Table 4 in our study, the positive surgical margin yielded a hazard ratio greater than 1.6 to influence on patient's OS.…”

A prospective study of intraoperative assessment of mucosal squamous cell carcinoma margins in the head and neck

“…Margin status is most relevant for smaller primary tumors whereby surgical excision without other treatments can offer cure, that is, pT1 and pT2 tumors 8 . The majority of our patients fell into either of these tumor stages.…”

“…It must also be considered that there is much evidence that margin revision after resection has negligible value for the patient 23‐26 . This is due to sampling error regarding where the original margins were actually positive and leads to a false sense of security when in actual fact the patient has residual disease and can actually be associated with worse local control 8 . If margins are in question, the ideal time to revise them is at the time of initial surgery.…”

“…While what constitutes an “involved” or “close” margin is highly contentious, it is clear that an “adequate” margin is desirable 4‐7 . Studies have shown that a close margin is an independent risk factor for local recurrence, but that values ranging from 1 to 7 mm have been reported as “clear.” 8,9 …”

“…[4][5][6][7] Studies have shown that a close margin is an independent risk factor for local recurrence, but that values ranging from 1 to 7 mm have been reported as "clear." 8,9 Determining the margin status relies on a close working relationship and good communication between surgeon and pathologist regarding specimen orientation and prosection. 10 Intraoperative assessment by frozen section of margins is commonly employed.…”