Zanoni Daniella Karassawa, Migliacci Jocelyn C, Xu Bin, Katabi Nora, Montero Pablo H, Ganly Ian, Shah Jatin P, Wong Richard J, Ghossein Ronald A, Patel Snehal G
Head and Neck Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
JAMA Otolaryngol Head Neck Surg. 2017 Jun 1;143(6):555-560. doi: 10.1001/jamaoto.2016.4238.
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.
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.
The primary end point was evaluation of the margin distance associated with LRFS.
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.
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.
原发肿瘤切缘阴性是口腔舌鳞状细胞癌(SCCOT)的金标准治疗方法。显微镜下手术切缘阳性显然与局部复发风险较高相关,而传统上切缘阴性被定义为距肿瘤边缘有大于5.0 mm的切缘宽度,较小的切缘宽度则被随意定义为切缘接近。切缘接近时局部复发风险接近显微镜下切缘阳性的精确临界值仍不清楚。
确定在SCCOT切除术后,随意定义的切缘接近(<5.0 mm)是否预示着与切缘阳性一样高的局部复发风险。
设计、地点和参与者:在这项回顾性研究中,头颈病理学家回顾了2000年1月1日至2012年12月31日在一家三级医疗中心接受原发手术切除的381例SCCOT患者的存档肿瘤标本。于2015年11月15日至2016年1月5日进行数据分析。对显微镜下切缘无阳性的患者采用时间依赖性受试者工作特征曲线分析来确定无局部复发生存(LRFS)的最佳切缘临界值。在多变量Cox比例风险回归模型中评估病理因素对LRFS的影响。
主要终点是评估与LRFS相关的切缘宽度。
在纳入分析的381例患者中(222例男性[58.3%]和159例女性[41.7%];平均[标准差]年龄为58[14.7]岁),确定与LRFS相关的最佳临界值为2.2 mm。将此临界值与传统认可的5.0 mm临界值进行比较。切缘宽度为2.3至5.0 mm的患者与切缘宽度大于5.0 mm的患者具有相似的LRFS(风险比[HR],1.31;95%置信区间,0.58 - 2.96),所有其他比较均有显著差异(切缘阳性的HR为9.03;95%置信区间,3.45 - 23.67;切缘宽度为0.01至2.2 mm的HR为2.83;95%置信区间,1.32 - 6.07)。基于这一结果,切缘阴性被重新定义为切缘宽度大于2.2 mm。在对病理因素进行调整的多变量模型中,切缘阳性(调整后HR,5.73;95%置信区间,2.45 - 13.41)和切缘宽度为0.01至2.2 mm(调整后HR,2.00;95%置信区间,1.13 - 3.55)是与LRFS最显著相关的变量。
在本研究中,SCCOT患者中仅手术切缘宽度小于或等于2.2 mm时,无局部复发生存会受到显著影响。这种新的切缘接近定义比一直使用的随意的5.0 mm临界值能更好地对局部复发风险进行分层。