Prognostic value of lymph node density on cancer staging system for gastric cancer without distal metastasis: a population-based analysis of SEER database.

BACKGROUND: Accurate tumor staging is the cornerstone of tumor treatment. Current tumor staging system for gastric cancer (GC) is based on regional positive lymph nodes while ignoring the total number of examined lymph nodes. We aim to assess the prognostic value of lymph node density (LND), the ratio of positive nodes to the total number examined nodes, in GC without distal metastasis. METHODS: Clinical information of patients with histologically confirmed GC and without distal metastasis was identified from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015. The X-Tile software was used to identify the ideal prognosis-related cutoff point for LND. The prognostic value of LND on cancer-specific survival (CSS) and overall survival (OS) was assessed in Cox regression models. Subgroup analysis stratified by LND was performed on current lymph node staging system to further explore the interaction between LND and current lymph node staging system. RESULTS: A total of 4281 participants were identified from the SEER database for the final analysis. The optimal prognosis-related cutoff values of LND were calculated as 0.1 and 0.4, and LND was divided into three levels: LND1 (< 0.1), LND2 (> = 0.1, < 0.4), and LND3 (> = 0.4). LND3 was associated with worse CSS and OS in GC patients. Compared to patients with LND1, those with LND2 and LND3 had 2.43 (HR = 2.43, 95% CI 2.09-2.84, P < 0.001) and 4.69 (HR = 4.69, 95% CI 4.02-5.48, P < 0.001) folds increase in mortality in CSS, respectively. Similar results were found in the evaluation of OS in GC patients. Subgroup analysis stratified by LND also found that patients in the same current lymph node stage still had different prognosis due to the different LND levels after adjustment for other prognosis-related covariates (all P values < 0.001). CONCLUSION: LND is an independent prognostic factor for GC without distal metastasis. In the current lymph node staging system, LND has potential value in further accurately classifying GC patients without distal metastasis.

Lymph node ratio as a predictor for outcome in oral squamous cell carcinoma: a multicenter population-based cohort study.

OBJECTIVES: Recently, multiple studies addressed the importance of lymph node ratio (LNR) in specifying patients' risk of disease recurrence in various malignancies. The present study examines the prognostic significance of LNR in predicting outcome of oral squamous cell carcinoma (OSCC) patients after surgical treatment with curative intent. METHODS: Here, we describe a retrospective population-based cohort with 717 patients previously diagnosed with OSCC. Histopathologically verified lymph node metastasis was diagnosed in 290 patients. Among these patients, we evaluated the impact of LNR on overall survival (OAS) and recurrence-free survival (RFS) in uni- as well as multivariate analysis. RESULTS: A median cutoff (0.055) in LNR was found to significantly predict outcome in OSCC patients. Five-year OAS was 54.1% in patients with a low LNR, whereas a high LNR was associated with a 5-year OAS of 33.3% (p < 0.001). Similar results were detected for RFS with a 5-year survival rate of 49.8% (LNR low) and 30.3% (LNR high) (p = 0.002). Results were confirmed in multivariate Cox regression which substantiated the importance of LNR in predicting survival in OSCC patients. CONCLUSIONS: LNR was shown to be an independent prognostic factor for outcome of OSCC in a population-based cohort in uni- as well as multivariate analysis. Hereby, a LNR ≥ 0.055 predicted a shorter OAS and RFS in our cohort. CLINICAL RELEVANCE: Besides established histopathological factors, LNR can be used as a reliable predictor of outcome in OSCC and might therefore be further applied in evaluating adjuvant treatment after resection in curative intention.

Prognostic value of lymph node density for major salivary gland carcinoma without clinical lymph node metastasis.

BACKGROUND AND OBJECTIVE: This study aimed to investigate whether lymph node density (LND) was correlated with overall survival (OS) in major salivary gland carcinoma without clinical lymph node metastasis. METHODS: Sixty patients who were diagnosed with major salivary gland carcinoma without clinical lymph node metastasis were enrolled. Of these, 50 patients underwent neck dissection. LND was defined as the ratio of the number of positive lymph nodes to the total number of resected lymph nodes. RESULTS: An LND of ≥0.1 was significantly associated with a short OS (p < 0.05). Multivariate analysis with adjustment for pathological N classification and positive surgical margin showed that an LND of ≥0.1 is a predictor of OS. CONCLUSION: Results demonstrated that lymph node density functions as a predictor of outcomes for major salivary gland carcinoma without clinical lymph node metastasis.

Lymph node density as a predictive factor for worse outcomes in laryngeal cancer.

BACKGROUND: The lymph node density (LND) is the number of positive metastatic lymph nodes divided by the total number of dissected lymph nodes. The purpose of this study was to evaluate LND as a prognostic factor in patients with laryngeal squamous cell carcinoma (SCC). METHODS: The study included 186 patients with laryngeal SCC submitted to laryngeal surgical treatment with neck dissection between January 2009 and December 2016. Clinical-pathological variables were assessed, as well as the cut-off point for LND. RESULTS: LND value was calculated considering pN+ (LND = 0.060). The Kaplan-Meier curve (log-rank) related to cumulative survival demonstrated that patients with LND ≥ 0.060 had a higher mortality rate than those with LND < 0.060, presenting a more aggressive form of the disease, with earlier recurrence. However, only the LND ≥ 0.060 group had impact on both disease-free survival and overall survival. CONCLUSION: The LND proved to be an important index in the prognostic evaluation of larynx SCC patients having a direct relationship with disease recurrence. Patients with LND ≥ 0.060 should be considered for adjuvant therapy.

Long-Term Mortality in Patients with Positive Lymph Nodes at the Time of Radical Prostatectomy.

BACKGROUND: The aim of this study was to determine prognostic factors and to provide long-term mortality data in patients with positive lymph nodes at the time of radical prostatectomy in a sample with long-term follow-up. METHODS: A total of 527 patients with complete data sets treated in the years 1992-2014 were studied. The median follow-up was 7.2 years. The median number of removed lymph nodes was 15. Age, year of surgery, Gleason score, local tumor stage, prostate-specific antigen level, lymph node density, lymph node count and the number of positive lymph nodes were included in multivariable competing risk analyses with prostate cancer mortality as endpoint. RESULTS: After 20 years, 28% of patients (95% CI 20-36%) died from non-prostate cancer (competing) causes, whereas 29% (95% CI 23-36%) died from prostate cancer. Only lymph node density (stratified by the median of 11.1%; hazard ratio [HR] 1.66, 95% CI 1.04-2.64, p = 0.0340) and Gleason score (8-10 vs. <8: HR 5.97, 95% CI 3.18-11.23, p < 0.0001) were independent predictors of prostate cancer mortality. Patients with a Gleason score <8 and a lymph node density < median had a 20-year prostate cancer mortality of only 5% (95% CI 0-10%), whereas this rate in patients with Gleason score 8-10 and a lymph node density ≥ median was 44% (95% CI 32-56%), p < 0.0001. CONCLUSIONS: Mortality in patients with positive lymph nodes was determined by tumor aggressiveness and the relative extent of spread; neither the year of surgery nor the number of removed lymph nodes was associated with outcome. Patients with a lymph node density of <11.1% and a Gleason score <8 had an excellent long-term outcome.

Lymph node density as a prognostic predictor in patients with betel nut-related oral squamous cell carcinoma.

OBJECTIVES: Lymph node metastasis in oral squamous cell carcinoma (OSCC) is a poor prognostic factor. The histopathologic stage (e.g., pN) is used to evaluate the severity of lymph node metastasis; however, the current staging system insufficiently predicts survival and recurrence. We investigated clinical outcomes and lymph node density (LND) in betel nut-chewing individuals. MATERIAL AND METHODS: We retrospectively analyzed 389 betel nut-exposed patients with primary OSCC who underwent surgical resection in 2002-2015. The prognostic significance of LND was evaluated by overall survival (OS) and disease-free survival (DFS) using the Kaplan-Meier method. RESULTS: Kaplan-Meier analyses showed that the 5-year OS and DFS rates in all patients were 60.9 and 48.9%, respectively. Multivariate analysis showed that variables independently prognostic for OS were aged population (hazard ratio [HR] = 1.6, 95% confidence interval [95% CI] = 1.1-2.5; P = .025), and cell differentiation classification (HR = 2.4, 95% CI = 1.4-4.2; P = .002). In pathologic N-positive patients, a receiver operating characteristic (ROC) curve for OS was used and indicated the best cutoff of 0.05, and the multivariate analysis showed that LND was an independent predictor of OS (HR = 2.2, 95% CI = 1.3-3.7; P = .004). CONCLUSIONS: Lymph node density, at a cutoff of 0.05, was an independent predictor of OS and DFS. OS and DFS underwent multiple analyses, and LND remained significant. The pathologic N stage had no influence in the OS analysis. CLINICAL RELEVANCE: LND is a more reliable predictor of survival in betel nut-chewing patients for further post operation adjuvant treatment, such as reoperation or adjuvant radiotherapy.

The relevance of the lymph node ratio as predictor of prognosis is higher in HPV-negative than in HPV-positive oropharyngeal squamous cell carcinoma.

OBJECTIVES: Lymph node ratio (LNR) is an established predictor in different entities of carcinoma, including head and neck malignancies. In oropharyngeal squamous cell carcinoma (OPSCC), lymph node involvement differs between human papilloma virus (HPV)-positive and HPV-negative tumours. Herein, we evaluate the impact of HPV association on the concept of LNR. METHODS: 88 surgically treated patients were included in this retrospective chart review. HPV-positive and HPV-negative OPSCC were evaluated for prediction of outcome by LNR separately. The endpoints were 5-year overall survival (OS) and recurrence-free survival (RFS). RESULTS: The OS of all patients was 60.1%. In univariate analysis, LNR was a significant predictor of overall survival rate (P=.008) in OPSCC independently of the HPV status, as well as extracapsular spread (ECS). T-classification was only a significant predictor in the univariate analysis in HPV-positive OPSCC carcinoma. However, in the multivariate analysis LNR remained predictor of prognosis in all OPSCC and in HPV-negative OPSCC. In patients with HPV-positive OPSCC, only T-classification reached significance to predict OS. CONCLUSION: Prognosis of primarily operated HPV-positive patients might be more dependent on the extent of primary tumour site, whereas prognosis of HPV-negative patients is based more on cervical metastatic spread, represented by LNR.

Radical cystectomy with super-extended lymphadenectomy: impact of separate vs en bloc lymph node submission on analysis and outcomes.

OBJECTIVE: To update our previous analysis of the clinical and pathological impact of the change in the submission of lymphadenectomy specimens from en bloc to 13 separate anatomically defined packets, which took place at the University of Southern California in May 2002, and to determine whether lymph node (LN) packeting resulted in any change in oncological outcomes. PATIENTS AND METHODS: A total of 846 patients who underwent radical cystectomy (RC) with super-extended LN dissection for cTxN0M0 bladder cancer between January 1996 and December 2007 were identified. Specimens of 376 patients were sent en bloc (group 1), and specimens of 470 patients were sent in 13 separate anatomical packets (group 2). RESULTS: The pathological tumour stage distribution and the proportion of LN-positive patients (group 1: 82 patients [22%] versus group 2: 99 patients [21%]; P = 0.80) were similar between the two groups: the median [range] number of total LNs identified increased significantly (group 1: 32 [10-97] versus group 2: 65 [10-179]; P < 0.001). LN density decreased (group 1, 11% versus group 2, 4%; P = 0.005). The median [range] number of positive LNs removed was similar (group 1: 0 [0-30] versus group 2: 0 [0-97]; P = 0.87). No nodal stage shift was observed. The 5-year overall survival (group 1: 58% versus group 2: 59%; P = 0.65) and recurrence-free survival rates (group 1: 68% versus group 2: 70%; P = 0.57) were similar. CONCLUSIONS: The incidence of patients with positive LNs remained unchanged, regardless of how the LN specimen was submitted. Submitting 13 separate nodal packets significantly increased the total LN yield, but did not result in a significant increase in the number of positive LNs or a consecutive nodal stage shift and did not affect oncological outcomes. Based on these results LN density is not an accurate prognosticator.

Lymph node ratio predicts survival in hypopharyngeal cancer with positive lymph node metastasis.

The lymph node density (LND) has been reported to be a significant prognostic factor in various types of carcinoma. This study investigated whether the LND is associated with survival in patients with hypopharyngeal squamous cell carcinoma (HPSCC) who have positive lymph nodes without distant metastasis. Forty-six patients who were pathologically diagnosed with HPSCC with positive lymph nodes and without distant metastasis were enrolled in this study. The LND was defined as the ratio of positive lymph nodes to the total number of lymph nodes. An LND of ≥0.09 was found to be significantly correlated with a shorter overall (p = 0.044) and disease-specific (p = 0.019) survival according to a log-rank test. In a multivariate survival analysis using a Cox proportional hazards model adjusted for the pathological T category (pT3-4/pT1-2), pathological N category (pN2/pN1) and positive surgical margin and/or extracapsular spread (presence/absence), both an LND of ≥0.09 and pT3-4 category were associated with significantly shorter overall survival (p < 0.01) and disease-specific survival (p < 0.01). These results suggest that the LND functions as a prognostic factor for HPSCC patients with positive lymph nodes who do not have distant metastasis.

Multi-Center Assessment of Lymph-Node Density and Nodal-Stage to Predict Disease-Specific Survival in Patients with Bladder Cancer Treated by Radical Cystectomy.

BACKGROUND: Prognostic tools in pathological-node (pN) patients after radical cystectomy (RC) are needed. OBJECTIVES: To evaluate the prognostic impact of lymph node (LN)-density on disease-specific survival (DSS) in patients with bladder cancer (BC) undergoing RC with pelvic lymph node dissection. METHODS: We analyzed a multi-institutional cohort of 1169 patients treated with upfront RC for cT1-4aN0M0 urothelial BCat nine centers. LN-densitywas calculated as the ratio of the number of positive LNs×100% to the number of LNs removed. The optimal LN-density cut-off value was defined by creating a time-dependent receiver operating characteristic (ROC) curve in pN patients. Univariable and multivariable Cox' regression analyses were used to assess the effect of conventional Tumor Nodes Metastasis (TNM) nodal staging system, LN-density and other LN-related variables on DSS in the pN-positive cohort. RESULTS: Of the 1169 patients, 463 (39.6%) patients had LN-involvement. The area under the ROC curve was 0.60 and the cut-off for LN-density was set at 20%, 223 of the pN-positive patients (48.2%) had a LN-density ≥ 20%. In multivariable models, the number of LN-metastases (HR 1.03, p = 0.005) and LN-density, either as continuous (HR 1.01, p = 0.013) or as categorical variable (HR 1.37, p = 0.014), were independently associated with worse DSS, whereas pN-stage was not. CONCLUSIONS: LN-density ≥ 20% was an independent predictor of worse DSS in BC patients with LN-involvement at RC. The integration of LN-density and other LN-parameters rather than only conventional pN-stage may contribute to a more refined risk-stratification in BC patients with nodal involvement.

Prognostic Value of Lymph Node Density in Node-Positive Oral Squamous Cell Carcinoma.

Lymph node status is an important prognostic factor in head and neck cancer. The purpose of this study is to investigate the prognostic value of lymph node density (LND) in node-positive oral cavity cancer patients who received surgery plus adjuvant radiotherapy. From January 2008 to December 2013, a total of 61 oral cavity squamous cell cancer patients who had positive lymph node and received surgery and adjuvant radiotherapy were analysed. LND was calculated for each patient. The endpoints were 5-year overall survival (OS) and 5-year disease-free survival. All patients were followed for a period of 5 years. Mean 5-year overall survival for cases with LND of ≤ 0.05 was 56.1 ± 11.6 months, whereas mean 5-year overall survival for cases with LND > 0.05 was 40.0 ± 21.6 months. Log rank is 0.04 95% CI = 53.4-65. Mean 5-year disease-free survival for cases with LND of ≤ 0.05 was 50.5 ± 15.8 months, whereas mean disease-free survival for cases with LND > 0.05 was 15.8 ± 22.9 months. Log rank 0.03 95% CI = 43.3-57.6. Nodal status, disease stage and lymph node density were found to be significant predictors of prognosis in univariate analysis. In multivariate analysis, only lymph node density is found to be the predictor of prognosis. LND is an important prognosis factor for 5-year OS and 5-year DFS in oral cavity squamous cell carcinoma.

Prognostic Value of Lymph Node Yield, Lymph Node Density, and pN in Oral Cancer.

OBJECTIVES: To investigate thresholds for lymph node yield (LNY), lymph node density (LND), and pN in patients with oral squamous cell carcinoma in relation to previous findings in the literature. STUDY DESIGN: Retrospective register-based study. SETTING: Copenhagen Oral Cavity Squamous Cell Carcinoma database. METHODS: Appropriate thresholds for LNY, LND, and pN were determined by areas under the curve and subsequently subjected to multivariate analysis. Five-year overall survival and 3-year recurrence-free survival were determined by Kaplan-Meier survival curves. RESULTS: In total, 413 patients diagnosed with oral squamous cell carcinoma were included. In the pN0 cohort, no superior/prognostic LNY cutoff values were detected. In the pN+ cohort, areas under the curve determined thresholds of LNY, LND, and pN to be 21 nodes, 5%, and 3 metastases, respectively. The 5-year overall survival was 52% for patients with LNY ≥21 vs 38% for patients with LNY <21 (hazard ratio [HR], 1.49; 95% CI, 1.05-2.11; P < .05), 60% for patients with LND ≤5% vs 38% for patients with LND >6% (HR, 1.63; 95% CI, 1.03-2.57; P < .05), and 43% for patients with pN <3 vs 26% for patients with pN ≥3 (HR, 1.40; 95% CI, 1.04-2.15; P < .05). CONCLUSIONS: Increased nodal yield, decreased LND, and decreasing number of pN were associated with significantly improved survival outcomes. LNY might serve as a prognosticator of survival as well as a surgical quality indicator. LND may have implications as a tool in cancer staging and treatment planning.

The Value of Lymph Node Dissection in Patients With Node-Positive Upper Urinary Tract Urothelial Cancer: A Retrospective Cohort Study.

Purpose: The value of lymphadenectomy during radical nephroureterectomy (RNU) remains unclear. This study aimed to determine the effects of the removed lymph node (RLN) counts, positive lymph node (pLN) counts, and pLN density (pLND) on survival outcomes in patients with node-positive upper urinary tract urothelial cancer (UTUC). Methods: A total of 306 patients with node-positive UTUC in the Surveillance, Epidemiology, and End Results database between 2004 and 2016 were identified. Multivariable Cox regression analyses were used to evaluate the effect of RLN counts, pLN counts, and pLND on survival outcomes. The maximally selected rank statistics were used to determine the most informative cutoff value for pLND on survival outcomes. Results: The RLN counts or pLN counts were not associated with survival outcomes, whereas higher pLND was associated with lower cancer-specific survival (CSS) and overall survival (OS) [hazard ratio (HR) 1.75, P = 0.014 and HR 1.62, P = 0.036, respectively]. The most informative cutoff value for pLND in relation to survival was 27%. Patients with pLND ≥27% had worse 5-year survival rates than those with pLND <27% (52.9% vs. 75.9% for CSS and 18.7% vs. 34.2% for OS, each P < 0.05). Furthermore, the multivariable Cox regression model with pLND could predict 5-year CSS (AUC 0.732 vs. 0.647) or OS (AUC 0.704 vs. 0.621) more accurately than the model without pLND. Conclusions: For patients with node-positive UTUC, more lymph nodes removed do not offer a better therapeutic effect. However, pLND provides additional prognostic value.

Prognostic Value of Lymph Node Density Compared to Pre-operative Platelet-to-Lymphocyte Ratio and Neutrophil-to-Lymphocyte Ratio in Patients with Tongue Squamous Cell Carcinoma.

Background: We aimed to investigate the prognostic significance of lymph node density (LND), and pre-operative neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) for outcome measuring in tongue squamous cell carcinoma (TSCC)' patients. Methods: A total of 129 patients who underwent surgery for TSCC were enrolled in this retrospective study. LND and pre-operative NLR and PLR were used as outcome measures and their correlations with different clinicopathological features were examined. Results: The cutoff values for NLR, PLR, and LND were obtained 1.21, 97.81, and 0.02, respectively, by receiver operating characteristic (ROC) curve approach. Only LND was found to be significantly associated with decreased overall survival (HR = 4.24; 95% CI 1.49-12.10; P = 0.007) and disease-free survival (HR = 3.48; 95% CI 1.43-8.45; P = 0.006) both in univariate and multivariate analyzes. Conclusion: Based on the findings, the LND has superiority over pre-operative NLR and PLR in predicting outcomes for the patients with TSCC.

Lymph Node Ratio as a Prognostic Factor in Neck Dissection in Oral Cancer Patients: A Systematic Review and Meta-Analysis.

Many studies have evaluated the clinical implications of lymph node ratio (LNR) as a prognostic factor in patients with oral squamous cell carcinoma (OSCC). The main purpose of this systematic review and meta-analysis was to address LNR as a prognosticator in patients with OSCC. A systematic search was conducted in the following databases: PubMed, EMBASE, Google Scholar, OpenGrey, Cochrane library, and ClinicalTrials.gov, and studies between 2009 and 2020 were sought. The pooled relative risk was calculated along with 95% confidence intervals for the following endpoints: overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), distant metastasis-free survival (DMFS), locoregional disease-free survival (LRDFS), local recurrence-free survival (LRFS), and recurrence-free survival (RFS) according to the random-effects model (Der Simonian-Laird approach). Subgroup and meta-regression analyses were performed as well. Finally, 32 cohort studies were eligible, which included 20,994 patients with OSCC. Patients were subdivided into two categories, group YES (studies that included in their analysis only patients with positive lymph nodes) and group NO (studies that did not exclude LNR = 0 patients). In the group YES, patients with high LNR had shorter OS (RR = 1.68, 95% CI: 1.47-1.91), DFS (RR = 1.68, 95% CI: 1.42-1.99), DSS (RR = 1.94, 95% CI: 1.56-2.42), DMFS (RR = 1.83, 95% CI: 1.13-2.96), LRDFS (RR = 1.55, 95% CI: 1.10-2.20), and LRFS (RR = 1.73, 95% CI: 1.41-2.13) compared to patients with low LNR. In the group NO, patients with high LNR in comparison had shorter OS (RR = 2.38, 95% CI: 1.99-2.85), DFS (RR = 2.04, 95% CI: 1.48-2.81), and DSS (RR = 2.90, 95% CI: 2.35-3.57) compared to patients with low LNR. Based on those findings, LNR might be an independent prognostic factor for OS in patients with OSCC and could be incorporated into future classification systems for better risk stratification.

Impact of Examined Lymph Node Count and Lymph Node Density on Overall Survival of Penile Cancer.

BACKGROUND: Few studies have explored the optimal examined lymph node count and lymph node density cutoff values that could be used to predict the survival of patients with penile cancer. We further clarify the prognostic value of lymph node density and examined lymph node count in penile cancer. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was explored to recruit penile cancer patients from 2010 to 2015. A retrospective analysis of penile cancer patients' data from the First Affiliated Hospital of Anhui Medical University was performed for verification (2006-2016). The cutoff values of examined lymph node count and lymph node density were performed according to the ROC curve. Kaplan-Meier survival analysis was used to compare survival differences among different groups. Univariate and multivariate Cox proportional hazard regression analyses were used to determine the significant variables. On the basis of Cox proportional hazards regression model, a nomogram was established and validated by calibration plot diagrams and concordance index (C-index). RESULTS: A total of 528 patients in the Surveillance, Epidemiology, and End Results cohort and 156 patients in the Chinese cohort were included in this study. Using the ROC curve, we found that the recommended cutoff values of ELN and LND were 13 and 9.3%, respectively (P <0.001). Kaplan-Meier curves suggested the significant differences of overall survival among different examined lymph nodes and lymph node density. Multivariate analysis indicated ELN and LND were independent prognostic factor for OS of penile cancer patients. Nomogram showed the contribution of ELN and LND to predicting OS was large. The C-index at 3-, and 5-year were 0.744 for overall survival (95% CI 0.711-0.777). CONCLUSIONS: The more lymph nodes examined, the lower the density of lymph nodes, and the higher the long-term survival rate of penile cancer. We recommended 13 examined lymph nodes and lymph node density >9.3% as the cutoff value for evaluating the prognosis of penile cancer patients.

Comparison of different lymph node staging systems in patients with positive lymph nodes in oral squamous cell carcinoma.

OBJECTIVES: The evaluation of neck lymph node metastasis is critical for predicting survival after head and neck cancer treatment. However, traditional pathological N staging does not completely correlate with survival; the total number of lymph nodes resected during surgery affects staging, and a minimal number of nodes must be resected to achieve a superior outcome. Thus, the prognostic abilities of various lymph node staging systems for oral cavity squamous cell carcinoma (OSCC)-positive lymph nodes were compared. MATERIALS AND METHODS: Data for 639 patients with OSCC-positive nodes who were treated and monitored at the Changhua Christian Hospital were retrospectively analyzed. The different N staging systems were compared to evaluate their disease-free survival (DFS) predictability. RESULTS: The areas under the receiver operating characteristic curve were as follows: 0.551 for the traditional American Joint Committee on Cancer (AJCC) N staging, 0.60 for lymph node density (LND), 0.596 for log odds of positive lymph nodes (LODDS), and 0.597 for the number of metastatic lymph nodes (nmLN). The LND, LODDS, and nmLN systems could predict DFS better than AJCC N staging. Multivariable analysis for DFS revealed that extranodal spread, level IV or V positive nodes, and tumor invasion deeper than 13 mm were independent prognostic factors in these four models. LND and LODDS predicted DFS better than pathological N staging. CONCLUSION: LND and LODDS staging predicted DFS better than AJCC N staging for OSCC-positive nodes. In the future, the prognostic ability of AJCC staging may be strengthened by LND or LODDS staging.

Lymph Node Yield and Ratio in Selective and Modified Radical Neck Dissection in Head and Neck Cancer-Impact on Oncological Outcome.

Background: Lymph node metastases are associated with poor prognosis in head and neck squamous cell carcinoma (HNSCC). Neck dissection (ND) is often performed prior to or after (chemo)radiation (CRT) and is an integral part of HNSCC treatment strategies. The impact of CRT delivered prior to ND on lymph node yield (LNY) and lymph node ratio (LNR) has not been comprehensively investigated. Material and methods: A retrospective cohort study was conducted from January 2014 to 30 June 2019 at the University Hospital of Bern, Switzerland. We included 252 patients with primary HNSCC who underwent NDs either before or after CRT. LNY and LNR were compared in patients undergoing ND prior to or after CRT. A total of 137 and 115 patients underwent modified radical ND (levels I to V) and selective ND, respectively. The impact of several features on survival and disease control was assessed. Results: Of the included patients, 170 were male and 82 were females. There were 141 primaries from the oral cavity, 55 from the oropharynx, and 28 from the larynx. ND specimens showed a pN0 stage in 105 patients and pN+ in 147. LNY, but LNR was not significantly higher in patients undergoing upfront ND than in those after CRT (median: 38 vs. 22, p < 0.0001). Cox hazard ratio regression showed that an LNR ≥ 6.5% correlated with poor overall (HR 2.42, CI 1.12-4.89, p = 0.014) and disease-free survival (HR 3.416, CI 1.54-754, p = 0.003) in MRND. Conclusion: ND after CRT leads to significantly reduced LNY. An LNR ≥6.5% is an independent risk factor for decreased overall, disease-free, and distant metastasis-free survival for MRND.

Factors affecting lymph node sampling patterns and the impact on survival of lymph node density in patients with Wilms tumor: a Surveillance, Epidemiology, and End Result (SEER) database review.

BACKGROUND: Lymph node (LN) involvement is an important prognostic indicator for patients with Wilms tumor (WT), and there have been previous reports of utilizing LN density (LND = positive LN/LNs examined) as an advanced metric to risk-stratify patients with WT. OBJECTIVE: The purpose of this study was to describe patient characteristics that affect LN yield and assess the effect of LND on the overall survival (OS) in patients with WT, with the expectation that patients with LNDs above a critical cut-point would demonstrate lower OS. STUDY DESIGN: The Surveillance, Epidemiology, and End Result (SEER) database was queried for all patients diagnosed with unilateral WT from 2004 to 2015. Patient and disease characteristics were collected, and Poisson regression was used to identify characteristics correlated with LN yield. LND was calculated for LN-positive patients, and multivariable survival analysis was performed, including patient demographics and LND as variables. RESULTS: 1489 patients with unilateral WT were identified for analysis, 231 (15.51%) of whom were LN-positive. Median patient age at diagnosis was three years (IQR 1-5). On Poisson regression, the year of diagnosis, patient age, tumor size and laterality, and stage were found to impact LN yield. For patients with positive LNs, five-year OS of patients with LNDs above 0.4 was worse than those below 0.4 (76.1% vs 89.6%, p = 0.041). On multivariable analysis, tumor size and LND remained significant predictors of OS. DISCUSSION: Administrative databases such as SEER provide an excellent resource for studying conditions where large patient numbers for analysis are difficult to obtain. Unfortunately, the SEER database is unable to account for every factor that could affect LN sampling patterns. Additionally, favorable vs unfavorable histology is not available in SEER, and SEER utilizes its own staging system, which makes comparison to Children's Oncology Group staging difficult. Despite these limitations, the findings of this study are similar to those previously published using administrative databases analyzing LN sampling patterns and the effect of LND on OS in WT. CONCLUSIONS: Analysis of the SEER database confirms that there are several patient- and disease-specific factors that affect the number of LNs sampled during nephrectomy for WT, and that LND may be a predictor of OS. These findings highlight the need for standardization of LN sampling patterns for pediatric renal tumors and support the investigation of LND in future studies to further risk-stratify WT patients to tailor therapy intensity.

Prognostic capacity of the lymph node ratio in squamous cell carcinomas of the head and neck. / Capacidad pronóstica de la densidad ganglionar en los carcinomas escamosos de cabeza y cuello.

INTRODUCTION AND OBJECTIVES: Lymph node density or lymph node ratio (LNR), defined as the quotient between the total number of positive lymph nodes and the total number of dissected lymph nodes, has demonstrated a prognostic capacity in several tumour models, including patients with head and neck squamous cell carcinomas (HNSCC). The aim of the present study is to analyse the prognostic value of LNR in a wide cohort of patients with HNSCC. METHODS: We carried out a retrospective study of a cohort of 1,311 patients with HNSCC treated with unilateral or bilateral neck dissections. Of the patients included in the study, 55.0% had lymph node metastases (pN+). We proceeded to calculate the value of the LNR, and its categorization through a recursive partition analysis considering specific survival as the dependent variable. RESULTS: Three categories were defined according to the value of the LNR with a cut-off point at the values < of .025 and .118. The 5-year specific survival for patients with an LNR less than .025 (n=654, 49.8%) was 87.2%, for patients with a LNR .025-.118 (n=394, 30.1%) it was 51.6%, and for patients with a LNR greater than .188 (n=263, 20.1%) it was 27.3% (P=.0001). According to the results of a multivariate analysis, the LNR significantly related to specific survival. CONCLUSION: The LNR can be a prognostic variable to be considered in the pathological staging of the lymph nodes.