Sumi Misa, Sato Shuntaro, Nakamura Takashi
Department of Radiology and Cancer Biology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Clinical Research Center, Nagasaki University Hospital, Nagasaki, Japan.
PLoS One. 2017 Aug 24;12(8):e0183611. doi: 10.1371/journal.pone.0183611. eCollection 2017.
Extranodal spread (ENS) in patients with head and neck squamous cell carcinoma (HNSCC) can greatly influence the prognostic outcomes. However, the relative risks of ENS in the primary (1st) and secondary (2nd) metastatic nodes (mets) are not well documented. We retrospectively analyzed the hazard ratios (HRs) of ENS in the 1st and 2nd mets from 516 HNSCC patients who had undergone primary tumor excision. The impact of clinically and/or histologically confirmed ENS-positive mets on prognosis in terms of cancer-specific survival was analyzed. Cox proportional hazard regression analysis indicated that ENS-positive 1st met (adjusted HR = 3.15; 95% CI, 1.40-7.56; p = 0.006) and ENS-positive 2nd met (adjusted HR = 4.03; 95% CI, 1.41-16.96; p = 0.007) significantly and independently predicted poor prognosis; however, other variables including primary site, met size or numbers, and met location in the contralateral side of the primary lesion, did not. Cumulative incidence function and Cox analyses indicated that differences in ENS profiles of 1st and 2nd mets stratified HNSCC patients with varying risks of poor outcome; HRs relative to patients with ENS-positive 1st met (-)/ENS-positive 2nd met (-) were 4.02 (95% CI, 1.78-8.24; p = 0.002), 8.29 (95% CI, 4.58-14.76; p <0.001), and 25.80 (95% CI, 10.15-57.69; p <0.001) for patients with ENS-positive 1st met (+)/ENS-positive 2nd met (-), ENS-positive 1st met (-)/ENS-positive 2nd met (+), and ENS-positive 1st met (+)/ENS-positive 2nd met (+) patients, respectively. Kaplan-Meier analysis indicated that the 2nd met that appeared in the neck side with a history of 1st met and neck dissection had a higher risk of ENS than the 2nd met in the neck side without the history (p = 0.003). These results suggested that ENS is a dominant prognostic predictor of HNSCC patients, with double-positive ENS in the 1st and 2nd mets predicting the most devastating outcome.
头颈部鳞状细胞癌（HNSCC）患者的结外扩散（ENS）会极大地影响预后结果。然而，原发（第1站）和继发（第2站）转移淋巴结（mets）中ENS的相对风险尚无充分记录。我们回顾性分析了516例接受原发性肿瘤切除的HNSCC患者第1站和第2站转移灶中ENS的风险比（HRs）。分析了临床和/或组织学证实的ENS阳性转移灶对癌症特异性生存预后的影响。Cox比例风险回归分析表明，ENS阳性的第1站转移灶（调整后HR = 3.15；95%CI，1.40 - 7.56；p = 0.006）和ENS阳性的第2站转移灶（调整后HR = 4.03；95%CI，1.41 - 16.96；p = 0.007）显著且独立地预测预后不良；然而，包括原发部位、转移灶大小或数量以及转移灶位于原发灶对侧等其他变量则不然。累积发病率函数和Cox分析表明，第1站和第2站转移灶的ENS特征差异对预后不良风险不同的HNSCC患者进行了分层；相对于ENS阳性第1站转移灶（-）/ENS阳性第2站转移灶（-）的患者，ENS阳性第1站转移灶（+）/ENS阳性第2站转移灶（-）、ENS阳性第1站转移灶（-）/ENS阳性第2站转移灶（+）以及ENS阳性第1站转移灶（+）/ENS阳性第2站转移灶（+）患者的HR分别为4.02（95%CI，1.78 - 8.24；p = 0.002）、8.29（95%CI，4.58 - 14.76；p <0.001）和25.80（95%CI，10.15 - 57.69；p <0.001）。Kaplan - Meier分析表明，在有第1站转移灶和颈部清扫病史的颈部一侧出现的第2站转移灶比无该病史的颈部一侧的第2站转移灶具有更高的ENS风险（p = 0.003）。这些结果表明，ENS是HNSCC患者主要的预后预测指标，第1站和第2站转移灶均为ENS阳性预示着最严重的预后结果。
