Level V Metastases in Node-Positive Oral Squamous Cell Carcinoma: Beyond Level IIA and III.

Surgical management of level V in clinically node positive (cN+) oral squamous cell carcinomas (OSCCs) is controversial. The objectives of the study were to identify predictors of level V metastases in cN+ OSCC. This retrospective study is based on institutional data of operated cN+ OSCC between April 2018 and December 2022. Clinical and pathological parameters were subjected to univariate analysis. Significant parameters in univariate analysis were further subjected to multivariate analysis. A p value of less than 0.05 was considered statistically significant. None of cN1 or pN1 patients had a level V metastasis. No skip metastasis to level-V was noticed. Total number of positive lymph nodes, lymph node ratio (LNR), extranodal extension, pN classification, and the presence of level II and III metastases were found to be significant predictors for level V metastases. The post hoc analysis suggested that ≥5 positive nodes, LNR >0.1, and pN3 status were independent risk factors for level V metastases. Selective neck dissection for N+ OSCC is feasible in the N1 neck, preferably where nodal metastases is limited to level-I only. Patients with a bulky nodal disease, particularly those with N3 neck, ≥5 positive nodes, ENE, and metastatic lymph nodes in levels II and III should be offered comprehensive neck dissection. Surgical management of level V in clinically node positive (cN+) oral squamous cell carcinomas (OSCCs) is controversial. The objectives of the study were to identify predictors of level V metastases in cN+ OSCC. This retrospective study is based on institutional data of operated cN+ OSCC between April 2018 and December 2022. Clinical and pathological parameters were subjected to univariate analysis. Significant parameters in univariate analysis were further subjected to multivariate analysis. A p value of less than 0.05 was considered statistically significant. None of cN1 or pN1 patients had a level V metastasis. No skip metastasis to level-V was noticed. Total number of positive lymph nodes, lymph node ratio (LNR), extranodal extension, pN classification, and the presence of level II and III metastases were found to be significant predictors for level V metastases. The post hoc analysis suggested that ≥5 positive nodes, LNR >0.1, and pN3 status were independent risk factors for level V metastases. Selective neck dissection for N+ OSCC is feasible in the N1 neck, preferably where nodal metastases is limited to level-I only. Patients with a bulky nodal disease, particularly those with N3 neck, ≥5 positive nodes, ENE, and metastatic lymph nodes in levels II and III should be offered comprehensive neck dissection.

Majumdar KS ，Kailey VS ，Varshney A ，Abhinav T ，Panuganti A ，Usmani SA ，Kaul P ，Maharaj DD ，Singh A ，Moideen A ，Prasath R ，Ravichandran N ，Devi NS ，Bhardwaj A ，Priya M ，Malhotra M ... -  《-》

Oncological outcomes of pathological extranodal extension (pENE) in oral squamous cell carcinoma (OSCC): A proposal to refine the current staging.

Extranodal extension (ENE) is an important prognostic factor in oral squamous cell carcinoma (OSCC), often associated with poor survival outcomes. However, the current nodal (N) staging system may need to be revised to reflect the prognosis. Emerging evidence suggests that the number of positive lymph nodes may offer improved prognostic accuracy. This study evaluates the outcomes of OSCC patients with pathological ENE (pENE) and explores the prognostic significance of absolute positive lymph node count. This retrospective cohort study analyzed 640 OSCC patients with pENE who underwent curative-intent surgery and standard adjuvant therapies between May 2015 and December 2021. Receiver Operating Characteristic (ROC) curve analysis was performed to identify a cutoff for the number of positive lymph nodes predicting overall survival (OS). Survival analyses were conducted using Kaplan-Meier curves, and Cox proportional hazards regression was used to identify independent predictors of OS and disease-free survival (DFS). In the entire cohort, the median DFS was 16 months (95 % CI: 12-19), and the mean OS was 57 months (95 % CI: 52-62). ROC analysis identified four positive lymph nodes as the optimal cutoff for predicting OS (AUC = 0.562, p = 0.01), with a sensitivity of 46.3 % and specificity of 65.2 %. Patients with > 4 positive lymph nodes had significantly poorer outcomes compared to those with ≤ 4 nodes: median DFS was 9 months vs. 21 months (p < 0.001), and mean OS was 26 months vs. 61 months (p < 0.001). Multivariate Cox regression confirmed the number of positive lymph nodes as an independent predictor for OS (HR = 0.6, p < 0.001) and DFS (HR = 0.5, p < 0.001). Patients with pENE and > four positive lymph nodes have significantly worse survival outcomes despite standard adjuvant therapies. This highlights the need for improved risk stratification in the current nodal staging system. These findings suggest incorporating lymph node burden into staging frameworks could improve prognostic accuracy.

Nemade H ，Thaduri A ，Gondi JT ，Chava SK ，Kumar A ，Arya SS ，Sekara Rao S LMC ... -  《-》

Correlation of preoperative 18F-FDG-PET/CT tumor staging and maximum standardized uptake values with preoperative CT, postoperative tumor classification, and histopathological parameters of oral squamous cell carcinoma.

This study aimed to correlate preoperative 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT) tumor staging, and maximum standardized uptake values (SUVmax) with preoperative CT data, postoperative tumor classification, and histopathological parameters of oral squamous cell carcinoma (OSCC). Thirty-seven OSCC patients staged via full-body 18F-FDG-PET/CT, including contrast agent CT of the head and neck in 2020 and 2021, were enclosed. Patients received tumor resection and stage-dependent neck dissection. Preoperative clinical (c) 18F-FDG-PET/CT UICC tumor stages and TNM classifications were correlated to corresponding CT and to postoperative histopathological (p) UICC tumor stages and TNM classifications. SUVmax of the primary tumor was associated with pUICC and pTNM, including extranodal extension (ENE), perineural invasion (Pn), lymphatic spread (L), vascular invasion (V), tumor grading (G), and -thickness. Comparing 18F-FDG-PET/CT and CT, cUICC, cT, and cN differed in 32.3%, 16.7%, and 37.8% of the cases, respectively. For 18F-FDG-PET/CT, a moderate correlation was found between c- and pUICC (0.494; p = 0.0018) with a misestimation of c- compared to pUICC in 43.2% of the cases. Comparing c- and pTNM, misestimations concerning c- and pT were seen in 51.4% and concerning c- and pN in 37.8% of the cases. An increased SUVmax significantly correlated with increased pT- and pUICC (adjusted Odds ratio 1.103; p = 0.042 and 1.126; p = 0.021, respectively). The predictive quality of an SUVmax cutoff value for detecting cervical lymph node metastases and G was poor, as indicated by the low AUC values from the ROC analysis. No correlations were found between SUVmax and ENE, Pn-, L-, and V-status. A strong correlation was found between SUVmax and tumor thickness with an adjusted coefficient of 1.034 (p = 0.01). The predictive value of 18F-FDG-PET/CT and SUVmax on histopathological tumor classification and parameters appears limited. 18F-FDG-PET/CT can not unreservedly be recommended for primary OSCC staging. There is an urgent need to specify its indications in detail further.

Müller G ，Veit DA ，Becker P ，Thiem DGE ，Kämmerer PW ，Diekmeyer B ，Werkmeister R ，Heimes D ，Pabst A ... -  《-》

Frequency of lymph node metastases at different neck levels in patients with oral squamous cell carcinoma: a systematic review and meta-analysis.

Currently, neck dissection is a standard treatment for the majority of oral squamous cell carcinoma (OSCC) patients. However, the procedure can lead to a series of complications, significantly reducing patient quality of life and even affecting the antitumor immune response in patients undergoing immunotherapy. Therefore, in the era of precision surgery, gaining a deeper understanding of the patterns of lymph node metastasis (LNM) in OSCC is crucial. Literature searches were performed on PubMed, Embase, Web of Science, Cochrane Library, WANFANGDATA, and China National Knowledge Infrastructure (CNKI) (inception to 10 April 2024). In addition, a manual searching was conducted in Scopus, Google Scholar, and Education Resources Information Center (ERIC). The authors included observational studies that evaluated the frequency of LNM in OSCC patients. Systematic review and a random effects model meta-analysis were performed. The search identified 4694 articles, of which 17 studies included in our study. The authors calculated the frequency of LNM according to the data reported in the articles. Frequency of LNM=number of patients with positive lymph node / number of patients with OSCC. The frequency of LNM was 12% in level I (95% CI: 0.11-0.15, I2 =38.01%), 20% in level II (95% CI: 0.17-0.22, I2 =47.71%), 10% in level III (95% CI: 0.08-0.12, I2 =49.10%), 2% in level IV (95% CI: 0.01-0.03, I2 =27.58%), 1% in level V (95% CI: 0.00-0.01, I2 =11.37%). The frequency of LNM is consistent with the 'cascade theory' and appears to be no significant difference from different primary sites. The frequency of LNM were low in levels I-III and were very low in level IV-V, which implicated that more conservative treatments may be considered for OSCC in the future. This study will help clinicians better determine the extent of surgery and preserve lymph nodes during neck dissection.

Yu YF ，Cao LM ，Li ZZ ，Zhong NN ，Wang GR ，Xiao Y ，Wu QJ ，Liu B ，Bu LL ... -  《-》

Impact of different staging methods of lymph nodes metastases on prognosis in advanced hypopharyngeal squamous cell carcinoma.

Lymph node ratio (LNR), log odds of positive lymph nodes (LODDS), and the number of postoperative lymph node staging (pN) are prognostic indicators of various cancers. However, the prognostic values of these indicators remain unclear in hypopharyngeal squamous cell carcinoma (HPSCC). This study's primary objective was to investigate the predictive value of LNR, LODDS, and pN for advanced HPSCC, and the secondary objective was to compare which of the values had the best predictive value for advanced HPSCC. A retrospective study was conducted on 166 patients with stage Ⅲ-Ⅳ HPSCC. LNR and LODDS were divided into two groups according to the defined cut-off values. Univariate and multivariate analyses on the risk of overall survival (OS) and progression-free survival (PFS) were performed, respectively. The predictive value of LNR was compared with that of LODDS and pN using receiver operating characteristic (ROC) curves. According to the X-tile, the cut-off values are 0.11 for LNR and -0.91 for LODDS. LNR, LODDS, and pN were significantly correlated with PFS by univariate analysis (p < 0.05). Multivariate analysis demonstrated that LNR was an independent prognostic factor for PFS (p < 0.01). Multivariate analysis also revealed that postoperative tumor staging (pT) classification (p = 0.003), LNR (p = 0.029), and surgical margins (p = 0.001) were independent prognostic factors for OS. LNR was demonstrated as an independent prognostic factor for PFS, other than LODDS and pN. LNR was an independent predictor for OS and PFS for advanced HPSCC.

Wang T ，Zhang D ，Hsueh C ，Lau HC ，Tao L ，Wu C ... -  《-》