A Proposal to Redefine Close Surgical Margins in Squamous Cell Carcinoma of the Oral Tongue

Abstract

IMPORTANCE Resection of the primary tumor with negative margins is the gold standard treatment for squamous cell carcinoma of the oral tongue (SCCOT). A microscopically positive surgical margin is clearly associated with a higher risk for local recurrence, whereas a negative margin has traditionally been defined as greater than 5.0 mm clearance from the tumor, with lesser margins arbitrarily designated as close. The precise cutoff at which the risk for local recurrence with a close margin approximates that of a microscopically positive margin remains unclear. OBJECTIVE To determine whether the arbitrarily defined close margin (<5.0 mm) would portend as high a risk for local recurrence as a positive margin after resection of SCCOT. DESIGN, SETTING, AND PARTICIPANTS In this retrospective study, head and neck pathologists reviewed archived tumor specimens from 381 patients with SCCOT who underwent primary surgical resection at a tertiary care center from January 1, 2000, through December 31, 2012. Data were analyzed from November 15, 2015, to January 5, 2016. Time-dependent receiver operating characteristic curve analysis was used in patients who did not have a microscopically positive margin to determine an optimal margin cutoff for local recurrence-free survival (LRFS). Pathologic factors were assessed for LRFS in a multivariate Cox proportional hazards regression model. MAIN OUTCOMES AND MEASURES The primary end point was evaluation of the margin distance associated with LRFS. RESULTS Among the 381 patients included in the analysis (222 men [58.3%] and 159 women [41.7%]; mean [SD] age, 58 [14.7] years), the optimal cutoff associated with LRFS was determined to be 2.2 mm. This cutoff was compared with the traditionally accepted cutoff of 5.0 mm. Patients with a margin of 2.3 to 5.0 mm had similar LRFS as patients with a margin of greater than 5.0 mm (hazard ratio [HR], 1.31; 95% CI, 0.58–2.96), and all other comparisons were significantly different (HR for positive margin, 9.03; 95% CI, 3.45–23.67; HR for 0.01-to 2.2-mm margin, 2.83; 95% CI, 1.32–6.07). Based on this result, negative margins were redefined as those with a clearance of greater than 2.2 mm. In a multivariate model adjusting for pathologic factors, positive margins (adjusted HR, 5.73; 95% CI, 2.45–13.41) and margins of 0.01 to 2.2 mm (adjusted HR, 2.00; 95% CI, 1.13–3.55) were the variables most significantly associated with LRFS. CONCLUSIONS AND RELEVANCE In this study, local recurrence-free survival was significantly affected only with surgical margins of less than or equal to 2.2 mm in patients with SCCOT. This new definition of close margins stratifies the risk for local recurrence better than the arbitrary 5.0-mm cutoff that has been used.

The role of adjuvant treatment in early‐stage oral cavity squamous cell carcinoma: An international collaborative study

“…Although patients with T1‐2N0M0 OCSCC can be treated with surgery alone, those with positive and close margins may benefit from adjunctive treatment . It has been suggested that adequate resection of OCSCC requires at least 5‐mm margins, although smaller margins have also been suggested . Because of the complexity of these tumors, clear margins are achieved in only 50% to 80% of patients treated at cancer centers .…”

Role of Extracapsular Nodal Spread and Surgical Margin Status in defining High-risk Head and Neck Squamous Cell Carcinoma and its Treatment Intensity

“…Two recent studies provided a more objective definition of ECS and margin status, in order to improve identification of high-risk HNSCC. 8,29 Recent inclusion of one of the parameters into the TNM staging system may help to guide the intensification of treatment for high-risk HNSCC. …”

“…8,29 These studies empirically quantified ECS extent and margin status by two-dimensional metric measurements, before subjecting it to rigorous statistical analysis. Time-dependent receiver operator characteristic (ROC) analysis was chosen to identify a prognostic cut-off at which sensitivity and false-positive rate were balanced optimally for both individual parameters.…”

“…Although multiple previous studies had shown that the prognostic utility of macroscopic ECS was better than that of microscopic ECS, this study was the first to empirically define an exact prognostic cut-off between these entities in the context of well-defined prognostic factors. Zanoni et al 29 used the same approach to identify a cut-off of 2.2 mm margin distance that optimally balanced the sensitivity and false-positive rate in the same oral cavity cancer cohort. Prognostic analysis revealed that patients with a margin of 2.2 mm or greater experienced virtually identical outcome as patients with the classical 5 mm margin [90% 2-year local recurrence-free survival (LRFS)].…”

Tumor margin classification of head and neck cancer using hyperspectral imaging and convolutional neural networks

“…2 Recently, the definition of a negative margin was proposed to 2.2 mm, decreasing from the previous standard of 5 mm for the oral tongue. 3 Another study found cuts within 1 mm of oral cavity SCCa tumor margins are associated with significantly increased recurrence rates. 4 Additionally, the incidence rate for differentiated thyroid carcinomas in the United States is approximately 20 per 100,000 females and 6 per 100,000 males, predominantly papillary and follicular carcinoma.…”