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AbstractBackgroundAims/objectivesMaterials and methodsResultsConclusions and significancePrognostic factors from neck dissection for regional recurrent or residual head and neck cancer remain undetermined.We studied whether continuous variables from pathologic lymph nodes of salvage neck dissection could estimate survival outcomes in patients with head and neck squamous cell carcinomas (HNSCC).Pathologic continuous variables from neck dissection without primary tumor resection in 184 patients with HNSCC were retrospectively evaluated. Cutoff values from both lymph node density (LND) and log odds of positive lymph nodes (LODDS) as the variables were applied to death estimation. Uni-/multivariate survival analyses adjusting for pathologic N classification and extranodal extension were evaluated by log-rank test or Cox’s proportional hazard model, respectively.LND ≥ 0.14 and LODDS ≥ −1.72 were significantly related to univariate shorter survival outcomes. Multivariate analysis indicated a significant association between LND ≥ 0.14 and shorter overall (hazard ratio [HR] = 2.16, 95% confidence interval [CI] = 1.30–3.58), local recurrence-free (HR = 2.34, 95% CI = 1.06–5.16), regional recurrence-free (HR = 2.32, 95% CI = 1.27–4.25), and distant metastasis-free survival (HR = 2.17, 95% CI = 1.31–3.61).Based on the obtained results, increased LND was a poor prognostic factor following salvage neck dissection. [ABSTRACT FROM AUTHOR]

Background: The Ministry of Health and Welfare has reported oral cancer to be one of the most prevalent malignant cancers; it has the third highest incidence rate of all cancers and is the fifth leading cause of death among men in Taiwan. Lymph node metastasis in oral cancer usually has a low survival rate, with no significant improvement in the past 30 years. Therefore, a more effective survival predictor is warranted. Many cancer studies have revealed that monitoring tumor thickness and lymph node density, in addition to tumor, node, and metastasis (TNM) stages, can provide more accurate predictions. Methods: This retrospective study analyzed data from 612 patients with oral cancer who had the habit of chewing betel nuts. The study focused on tumor thickness, lymph node density, and the regional distribution of lymph node metastasis to determine their effectiveness as predictors. Results: The results revealed that a tumor thickness of 6 mm indicated cervical lymph node metastasis and was the optimal cutoff point for overall survival. The optimal cutoff value for lymph node density was 0.04. Patients with a tumor thickness of >6 mm and a lymph node density of >0.04 had significantly lower overall survival rates. Additionally, patients with >1 lymph node metastasis level and lower cervical metastasis exhibited a relatively worse prognosis. Conclusions: Therefore, in addition to TNM staging, tumor thickness, lymph node density, and metastasis level are suitable as parameters for predictors that can be used as references for adjuvant therapies for better therapeutic effects. [ABSTRACT FROM AUTHOR]

Background: The Ministry of Health and Welfare has reported oral cancer to be one of the most prevalent malignant cancers; it has the third highest incidence rate of all cancers and is the fifth leading cause of death among men in Taiwan. Lymph node metastasis in oral cancer usually has a low survival rate, with no significant improvement in the past 30 years. Therefore, a more effective survival predictor is warranted. Many cancer studies have revealed that monitoring tumor thickness and lymph node density, in addition to tumor, node, and metastasis (TNM) stages, can provide more accurate predictions. Methods: This retrospective study analyzed data from 612 patients with oral cancer who had the habit of chewing betel nuts. The study focused on tumor thickness, lymph node density, and the regional distribution of lymph node metastasis to determine their effectiveness as predictors. Results: The results revealed that a tumor thickness of 6 mm indicated cervical lymph node metastasis and was the optimal cutoff point for overall survival. The optimal cutoff value for lymph node density was 0.04. Patients with a tumor thickness of >6 mm and a lymph node density of >0.04 had significantly lower overall survival rates. Additionally, patients with >1 lymph node metastasis level and lower cervical metastasis exhibited a relatively worse prognosis. Conclusions: Therefore, in addition to TNM staging, tumor thickness, lymph node density, and metastasis level are suitable as parameters for predictors that can be used as references for adjuvant therapies for better therapeutic effects.

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. [ABSTRACT FROM AUTHOR]

Lymph node density (LND)—the proportion of positive nodes among the total number of resected nodes—has emerged as a reliable prognostic factor in solid tumors. This study aims to assess the importance of LND in lingual squamous cell carcinoma (LSCC) and its prognostic involvement. A retrospective longitudinal study with 62 patients was performed. All patients were diagnosed with LSCC and submitted for tumor resection and neck dissection. Patients were stratified into low (<0.04) and high risk (≥0.04) based on LND. We analyzed the impact of LND on overall survival (OS) and disease-free survival (DFS), as well as the relationship between LND and the pathological staging, the involvement of positive margins, depth of invasion (DOI) and perineural infiltration. This study provides a substantial relationship between lymph node density (LND), overall survival (OS) and disease-free survival (DFS) in lingual squamous cell carcinoma (LSCC). A statistically significant distribution was found between LND, perineural infiltration and pathological staging, whereas no association was found with the rest of the prognostic variables analyzed. [ABSTRACT FROM AUTHOR]

Abstract 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.

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. [ABSTRACT FROM AUTHOR]

Lymph node density (LND)—the proportion of positive nodes among the total number of resected nodes—has emerged as a reliable prognostic factor in solid tumors. This study aims to assess the importance of LND in lingual squamous cell carcinoma (LSCC) and its prognostic involvement. A retrospective longitudinal study with 62 patients was performed. All patients were diagnosed with LSCC and submitted for tumor resection and neck dissection. Patients were stratified into low (

BackgroundFew 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.MethodsThe 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).ResultsA 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 9.3% as the cutoff value for evaluating the prognosis of penile cancer patients.

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. [ABSTRACT FROM AUTHOR]

Zhenyu Pan,1–3,* Qingting Bu,4,* Haisheng You,5 Jin Yang,1,2 Qingqing Liu,1,2 Jun Lyu1,2 1Clinical Research Center, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2School of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi, People’s Republic of China; 3Department of Pharmacy, The Affiliated Children Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 4Department of Genetics, Northwest Women’s and Children’s Hospital, Xi’an, Shaanxi, People’s Republic of China; 5Department of Pharmacy, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China *These authors contributed equally to this work Objective: Previous studies showed that the lymph node density (LND) was a predictor of survival in Wilms’ tumor (WT). However, the optimal LND cutoff point is controversial due to methodological shortcomings of previous studies, and no studies have shown the effect of LND on survival in children with WT. The purpose of this study was to remedy this situation.Methods: We identified 376 children with WT. LND cutoff point was determined using the median value, the X-tile program, the survival-tree algorithm, and the time-dependent ROC curve analysis. Survival functions were estimated by the Kaplan–Meier method. We used Cox regression analysis to determine the impact of LND on survival. Smooth curve fitting between relative mortality risk and LND was performed.Results: The LND cutoff point was 0.44, 0.65, 0.65, and 0.64 according to the median value, the X-tile program, the survival-tree algorithm, and the time-dependent ROC curve analysis, respectively. The 5-, 10-, and 20-year overall survival rates were 86.9%, 86.9%, and 84.7%, respectively, in the

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. [ABSTRACT FROM AUTHOR]

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., Competing Interests: BWGvR, SFS, ARZ, AH, TCMZ and YL are Editorial Board Members of this journal but were blinded and not involved in the peer-review process nor had access to any information regarding its peer-review. Peter J. Bostrom: Peter Bostrom reports research grant from Juselius Foundation and Cancer Foundation Finland. Additionally, consultation fees from Astellas and Janssen are reported. Shahrokh. F. Shariat: S.F. Shariat reports advisory board of/and or speaker for Astellas, Astra Zeneca, Bayer, BMS, Cepheid, Ferring, Ipsen, Janssen, Lissy, MSD, Olympus, Pfizer, Pierre Fabre, Roche, Sanochemia and Sanofi. Joost L. Boormans: JL Boormans received travel grants from Combat medical to attend scientific meetings and has received honoraria by MSD, Roche, BMS and Janssen Pharmaceuticals for consultancy work. Yair Lotan: Y Lotan reported consultancy for Nanorobotics, C2I genomics, Photocure, Astra-Zeneca, Merck, Fergene, Abbvie, Nucleix, Ambu, Seattle Genetics, Hitachi, Ferring Research, verity pharmaceutics, virtuoso surgical, Stimit, Urogen, Vessi medical, CAPs medical, Xcures, BMS, Nonagen, Aura Biosciences, Inc., Convergent Genomics, Pacific Edge, Pfizer, Phinomics Inc, CG oncology, Uroviu, On target lab. Bas WG van Rhijn: BWG van Rhijn reported Advisory board meetings: QED Therapeutics and Incyte International Biosciences. The remaining authors reported no further conflicts of interest., (© 2024 – The authors. Published by IOS Press.)

Lu-Lu Ye,1,2,* Jia Rao,2,3,* Xing-Wen Fan,1,2 Qing-Hai Ji,2,4 Chao-Su Hu,1,2 Hong-Mei Ying1,2 1Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China; 3Department of Pathology, 4Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China *These authors contributed equally to this work Purpose: To analyze the potential variables affecting the survival of patients undergoing primary surgery for hypopharyngeal squamous cell carcinoma.Patients and methods: Between August 2007 and December 2016, 93 patients with primary hypopharyngeal squamous cell carcinomas undergoing radical surgery at Fudan University Shanghai Cancer Center were reviewed. The clinicopathological features were analyzed retrospectively. The optimal cutoff values were determined based on the receiver operating characteristic curve analysis. Pearson correlation coefficients were used to assess the correlations between variables. The Kaplan–Meier and Cox proportional hazard methods were used to evaluate the impact of variables on overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS).Results: Cox multivariate analysis revealed that a depth of invasion (DOI) ≥ 4.3 mm was correlated with inferior OS (P=0.045), DSS (P=0.046), and DFS (P=0.046). A primary tumor volume (PTV) ≥0.36 mL was related to poor OS (P=0.018), DSS (P=0.026), and DFS (P=0.036). A lymph node density (LND) ≥0.07 was also associated with worse OS (P=0.014) and DSS (P=0.045). Moreover, additional prognostic value was observed in the combined use of PTV and LND.Conclusion: The DOI, PTV, and LND obtained from the surgical specimens could provide additional valuable information for prognostic stratification and allowed the more appropriate selection of suitable candidates for more aggressive adjuvant therapy. Keywords: hypopharynx, surgery, depth of invasion, primary tumor volume, lymph node density, survival

Haisheng You,1,* Jin Yang,2,3,* Qingqing Liu,2,3 Lina Tang,1 Qingting Bu,4 Zhenyu Pan,5 Jun Lyu2,3 1Department of Pharmacy, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2Clinical Research Center, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 3School of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi, People’s Republic of China; 4Department of Genetics, Northwest Women’s and Children’s Hospital, Xi’an, Shaanxi, People’s Republic of China; 5Department of Pharmacy, The Affiliated Children Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China *These authors contributed equally to this work Objective: The objective of this study was to determine the impact of the lymph node density (LND) on overall survival of patients with Wilms’ tumor (WT) using the Surveillance, Epidemiology, and End Results (SEER) database.Methods: Data from the SEER database were extracted from patients with WT in whom the LND could be obtained. Patients were divided into a low LND group and high LND group. Survival curves based on the LND stratification were plotted using the Kaplan–Meier method and compared with the log-rank test. The impact of prognostic factors on overall survival was analyzed using Cox regression models.Results: A total of 1,924 patients were identified from the database. Overall survival for the low LND group at 5, 10, and 20 years was significantly better than the high LND group (5-year survival: 94.1% vs 81.4%; 10-year survival: 92.6% vs 80.8%; 20-year survival: 90.6% vs 79.1%; P

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. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Lymph node ratio (LNR) has been shown to be an independent prognostic factor for oral squamous cell carcinoma (OSCC) in various centre-based studies recently. A range of cut-off values have been suggested. A meta-analysis was performed to evaluate the prognostic effects of LNR and to investigate the cut-off value. Electronic search on Pubmed, Embase and Cochrane library and manual search were performed for studies up to January 2018. The outcomes were overall survival (OS), disease specific survival (DSS), disease free survival (DFS), local recurrence free survival (LF), locoregional disease free survival (LRF), and distant metastasis disease free survival (DM). 19 studies between 2009 and 2017 were included. The total number of patients was 14,254 (range 19-3958). Data was grouped into Group A (with pathological nodal disease, pN+) and Group B (with and without pathological nodal disease, pN+ and pN-). In the meta-analysis, the high LNR was significantly related to short OS (A = HR 1.902; 95%CI: 1.453-2.488, B = HR 2.76; 95%CI: 2.13-3.59), DSS (A = HR 1.728; 95%CI: 1.159-2.579; B = HR 2.83; 95%CI: 1.8-4.44) and DFS (A = HR 2.27; 95%CI: 1.74-2.96; B = HR 2.01; 95%CI: 1.44-2.82) in both groups; and shorter LRF in Group B (HR 5.013; 95%CI: 3.584-7.011). In the analysis, all cut-off values were shown to be significant and there was no strong evidence to consider a possibility of a second significant value. Based on our results, LNR is an independent prognostic factor in OSCC and may be considered in future oncologic staging systems. [ABSTRACT FROM AUTHOR]

Background Pancreatic cancer has the worst prognosis of all gastrointestinal malignancies. Lymph node metastasis is a powerful determinant of prognosis. The ratio between the number of affected lymph nodes and the total number of examined lymph nodes is known as lymph node density (LND). LND has proved clinically important in other gastrointestinal malignancies. Our main objective was to identify the role of LND in the prognosis of patients after pancreatic cancer resection. Patients and methods Our study included 30 patients who underwent pancreatic cancer resection from 2010 to 2015. Pathological reports and medical records were retrieved retrospectively for tumor-specific data and patient-specific data (age, sex, and presence of diabetes mellitus). LND was calculated as the number of metastatic lymph nodes divided by the total number of lymph nodes examined. Survival time was calculated from the date of operation to the date of death. Results Patients with LND less than 0.2 have a probability of 1-year survival of 98% and 3-year survival of 62%, which is better than those with LND more than 0.2 (P=0.001). Conclusion LND was significantly related to survival outcome after pancreatic cancer resection, as patients with LND more than or equal to 0.2 displayed a poor prognosis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: The prognosis of bladder cancer patients with positive lymph node (LN) disease is affected by both the extent of lymphadenectomy and LN density retrieved during radical cystectomy. This study aimed at assessing the differences in LN metastasis between patients who presented primarily with muscle-invasive transitional cell carcinoma of the bladder "de novo disease" versus "progressive disease." The latter is defined as patients who progressed to muscle-invasive bladder cancer (MIBC) following prior conservative management of a non-muscle-invasive disease. Methods: Data were prospectively collected from consecutive 41 radical cystectomies that were divided into two groups: Group I included de novo MIBC cases and Group II included progressive MIBC cases. Results: The median age was 60 years (44-75). Thirty-four patients exhibited de novo disease versus 7 patients who presented as progressive MIBC with a median duration of 9 months between the resection of the first non-invasive tumor and the diagnosis of progressive MIBC (range: 6-56 months). The median number of retrieved LNs in both groups was 15 LNs (range: 4-36). Ten patients (24.39%) had positive pathological LN disease; distributed as 9 patients in Group I and 1 patient in Group II. The median LN density of LN-positive patients was 15.73% (6.46 % in Group I, 28.57% in Group II). Five patients had LN density >20%. Conclusion: Although non-muscle-invasive urothelial bladder tumor may progress to muscle-invasive disease, it still carries less aggressive course than de novo MIBC based on differences in LN metastasis and density. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: We investigated the value of lymph node density (LND) as a predictor of survival in patients with laryngeal squamous cell carcinoma (SCC) and positive neck node (pN+) after laryngectomy.Study Design: Case series with chart review.Setting: Katip Celebi University Ataturk Training and Research Hospital, Izmir, Turkey.Subjects and Methods: We reviewed the records of 289 patients with newly diagnosed primary laryngeal carcinomas who underwent partial or total laryngectomy and combined neck dissection at a tertiary referral center between June 2006 and December 2014. Patients with pN+ laryngeal SCC (n = 101) were included in the study. Overall survival (OS) and disease-free survival (DFS) were used to evaluate the prognostic significance of LND.Results: In 101 patients with pN+ laryngeal SCC, LND ≥0.09 and number of metastatic lymph nodes >4 were significantly associated with OS and DFS but not the overall tumor, node, and metastasis stage. Forward stepwise Cox regression analysis revealed that LND ≥0.09 was the only independent predictor of both DFS and OS. Furthermore, the odds ratio of LND ≥0.09 was 10 times higher in patients with regional recurrence when compared patients without regional recurrence.Conclusions: LND was the only independent prognostic predictor of OS and DFS in patients with pN+ laryngeal SCC. Moreover, patients with LND ≥0.09 were significantly associated with high risk of regional recurrence. Thus, patients with LND ≥0.09 are at high risk of regional recurrence and death and may be considered for adjuvant chemoradiation. [ABSTRACT FROM AUTHOR]

Background The purpose of this study was to evaluate the utility of lymph node density for predicting the survival of patients with tonsillar cancer and positive neck nodes. Methods We reviewed data for 64 patients diagnosed with tonsillar cancer with lymph node metastasis in a retrospective single center audit. Results Lymph node density (≥0.05), extracapsular spread (ECS), number of ECS (≥3), vascular invasion, perineural invasion, and N classification (N1/N2a vs N2b/N2c) were significant predictors of 5-year disease-free survival (DFS). Lymph node density (≥0.05), human papillomavirus (HPV) infection, and N classification (N1/N2a vs N2b/N2c) were significant predictors of 5-year overall survival (OS). In the multivariate analysis, categorical lymph node density remained a significant predictor of DFS ( p = .025 *; hazard ratio [HR] = 6.063) and no parameter was significantly predictive of OS. Conclusion Lymph node density might be useful as an independent predictor of survival in patients with tonsillar cancer and positive lymph nodes. © 2015 Wiley Periodicals, Inc. Head Neck 38: E705-E711, 2016 [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The association between lymph node density and survival free of lung metastases in oral squamous cell carcinoma (SCC), has not been investigated so far to our knowledge. Lymph node density ≧ 0.07 has been reported by a multicentre international study to be a significant predictor of shorter survival in patients with oral SCC who have invaded nodes. We investigated whether a lymph node density of ≧ 0.07 correlates with shorter overall survival, survival free of distant metastases, and survival free of lung metastases, in patients with oral SCC and invaded lymph nodes. Thirty-five patients with histologically-confirmed invaded lymph nodes werestudied. Their density was calculated as the ratio of the number of invaded lymph nodes:total number of nodes. A density of ≧ 0.07 correlated significantly with shorter overall survival (p < 0.02), survival free of distant metastases (p < 0.01), and survival free of lung metastases (p < 0.01) on log rank testing. On testing by Cox's proportional hazards model of multivariate survival analysis with adjustment for the pathological stage (pstage IV/pstage III), and invaded surgical margins or extracapsular spread, or both, we found that lymph node density ≧ 0.07 was associated with significantly shorter survival (p < 0.02). We conclude that lymph node density predicts lung metastases in patients with oral SCC. [ABSTRACT FROM AUTHOR]

Lymph node density (LND) has been reported to be a significant predictor of survival in patients with oral and other carcinomas exhibiting positive lymph nodes. The present study investigated whether the LND is associated with overall survival in subjects with major salivary gland carcinoma. A total of 78 patients newly diagnosed with major salivary gland carcinoma underwent primary tumor resection and neck dissection without preoperative treatment. Of these 78 patients, 32 with pathologically positive lymph nodes were enrolled in the present study. The LND was calculated as the ratio of the number of positive lymph nodes to the number of total lymph nodes. The survival rate was analyzed according to the Kaplan-Meier method. A univariate survival analysis was performed using the log-rank test, and a multivariate survival analysis was performed using the Cox proportional hazards model. An LND of =0.38 was found to significantly correlate with a shorter overall survival time in univariate analysis (P=0.017). In multivariate survival analysis, after adjusting for anatomical location (parotid gland/others), an LND of =0.38 was identified to be associated with a significantly shorter overall survival time. These results suggest that the LND functions as a prognostic factor in cases of major salivary gland carcinoma. [ABSTRACT FROM AUTHOR]

Background We examined the prognostic value of lymph node density in predicting cancer-specific mortality (CSM) for patients with lymph nodes positive (pN+) laryngeal squamous cell carcinoma (SCC) after laryngectomy. Methods The records of 156 patients with laryngeal SCC who initially underwent curative resection of the primary tumor combined with neck dissection were reviewed. Results The 5-year cumulative incidence of CSM was 20.4%. N classification and extralaryngeal spread (ELS) were independent variables for CSM in all patients. Univariate analyses in 71 pN+ patients showed that ELS, number of positive lymph nodes >4, and lymph node density >0.044 were significantly associated with increased CSM, whereas pN classification was not ( p = .218). On multivariate analysis, lymph node density ≥0.044 remained an independent predictor of CSM ( p = .001). Conclusion Among the pN+ patients with laryngeal SCC, no pN classification but lymph node density was noted to have an independent impact on CSM. © 2014 Wiley Periodicals, Inc. Head Neck 37: 1319-1325, 2015 [ABSTRACT FROM AUTHOR]

Background: Although lymph node (LN) status and the LN burden determine the outcome of bladder cancer patients treated with cystectomy, compelling arguments have been made for the incorporation of LN density into the current staging system. Here, we investigate the relationship between LN density and clinical outcome in patients with LN-positive disease, following radical cystectomy for bladder cancer. Methods: PubMed, SCOPUS, the Institute for Scientific Information Web of Science, and the Cochrane Library were searched to identify relevant published literature. Results: Fourteen studies were included in the meta-analysis, with a total number of 3311 patients. Of these 14 publications, 6 studies, (533 patients), 10 studies (2966 patients), and 5 studies (1108 patients) investigated the prognostic association of LN density with disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS), respectively. The pooled hazard ratio (HR) for DFS was 1.45 (95 % confidence interval [CI], 1.10-1.91) without heterogeneity (I2 = 0 %, p = 0.52). Higher LN density was significantly associated with poor DSS (pooled HR, 1.53; 95 % CI, 1.23-1.89). However, significant heterogeneity was found between studies (I2 = 66 %, p = 0.002). The pooled HR for OS was statistically significant (pooled HR, 1.45; 95 % CI, 1.11-1.90) without heterogeneity (I2 = 42 %, p = 0.14). The results of the Begg and Egger tests suggested that publication bias was not evident in this meta-analysis. Conclusions: The data from this meta-analysis indicate that LN density is an independent predictor of clinical outcome in LN-positive patients. LN density may be useful in future staging systems, thus allowing better prognostic classification of LN-positive bladder cancer. [ABSTRACT FROM AUTHOR]

Background The purpose of this study was to determine the prognostic value of lymph node density in head and neck cancer. Methods We utilized a prospective, multicenter database of 223 patients with head and neck cancer to identify patients who underwent lymph node dissection before chemoradiation to assess the prognostic significance of lymph node density. Results In 38 patients who met study criteria, lymph node density ≤0.20 predicted for improved overall survival (OS; 79% vs 50%; p = .04). Lymph node density was also associated with a trend toward improved 3-year locoregional control (96% vs 79%; p = .14) and distant metastasis-free survival (93% vs 78%; p = .13). In the patients with treatment failure distantly or locoregionally, that failure was earlier in patients with lymph node density >0.20 than in patients with lymph node density ≤0.20 (median, 12.7 months vs 5.2 months; p = .004). Conclusion Our data suggest that lymph node density predicts for OS in patients with head and neck cancer and that the difference in OS may be because of differences in time to failure. © 2013 Wiley Periodicals, Inc. Head Neck 36: 266-272, 2014 [ABSTRACT FROM AUTHOR]

The presence of lymphatic metastasis is associated with markedly worse prognosis in patients with bladder cancer, although surgical resection and chemotherapy can still provide long-term survival for selected patients. The prognostic stratification of patients with positive lymph nodes has been broadly discussed in the current literature and a more extensive pelvic lymph node dissection and thorough pathologic assessment has been advocated. It is clear that stratification using the tumor node metastasis staging system is insufficient to adequately discriminate prognosis between patients with different lymph node involvement. Lymph node density and extranodal extension have been extensively investigated and appear to influence the prognosis of these patients. Molecular markers have been developed to improve the diagnosis of micrometastatic disease, and new targeted therapies have shown promising preclinical results and are now being tested in different clinical scenarios. [ABSTRACT FROM AUTHOR]

Objective: To analyse whether the reported differences in nodal yield at pelvic lymph node dissection (PLND) for bladder cancer, between two hospitals, are reflected in the survival rates. Patients and methods: We assessed follow-up data of all 174 patients (mean age: 62.7, median follow-up: 3 years) who underwent PLND between 1 January 2007 and 31 December 2009 at two different hospitals. PLND was performed according to a standardized template by the same urologists for comparable bladder cancer patients. Mean number of reported lymph nodes was 16 at hospital A versus 28 at hospital B. We compared the overall survival (OS), disease-specific survival (DSS) and recurrence-free survival (RFS) between both cohorts and performed a multivariate analysis. Results: The cumulative probability for 2-year OS, DSS and RFS for hospital A are 61, 64 and 54 %, versus 58, 58 and 53 % for hospital B, respectively. Kaplan-Meier survival curves did not reveal statistically significant differences between both groups (OS: p log-rank = 0.75, DSS: p log-rank = 0.56, and RFS: p log-rank = 0.80). Also after adjustment for pT stage and neoadjuvant chemotherapy, survival was not significantly different between hospital A and hospital B. Conclusion: Despite differences in lymph node yield in PLND specimens, this study reveals no significant differences in survival outcomes between both hospitals. Standardized histopathological methods should be agreed upon by pathologists before integrating nodal yield and subsequent lymph node density as indicators of the quality of surgery and as prognostic factors. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To validate the prognostic relevance of lymph node density (LND) and identify its optimal cut-points in a large international multicenter series of patients treated with radical cystectomy (RC) for invasive bladder cancer. Methods: From 1993 to 2005, 4,430 bladder cancer patients who underwent RC without neoadjuvant chemotherapy were reviewed; of these, 1,038 were pN+M0 disease and form the basis of this report. Results: Median age of patients was 67 years with median follow-up in survivors of 33 months. Overall, 5-year DSS estimate was 36%. Median number of lymph nodes removed was 18 (IQR, 11–32), median number of positive lymph nodes was 2 (IQR, 1–5), and median LND was 14.3% (IQR, 6.67–33.3%). LND as continuous variable was a stronger prognostic factor for DSS in patients that underwent a more extensive PLND (P < 0.001). HR for inverse association of LND with DSS increased incrementally with increasing LND cut-points. Categorizing LND into quintiles revealed strong tertiary distribution of risk based on LND <6%, 6%–41%, or >41% with cumulative 5-year DSS of 47%, 36%, and 21%, respectively (P < 0.001). When patients were stratified by adjuvant chemotherapy, LND remains independently prognostic in patients who received adjuvant chemotherapy as well as those who did not. Conclusion: Lymph node density is prognostic in bladder cancer patients who undergo a more extensive PLND and remains prognostic even when adjuvant chemotherapy is used. Prognostic value of LND is best represented as a continuum of risk and LND <6% represents the best possible outcome in patients with nodal disease. [Copyright &y& Elsevier]

Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Patients with positive lymph nodes at radical cystectomy have a poor prognosis. The actual outcome of patients varies based on many factors, among which lymph node density has emerged as being more informative than nodal status of TNM staging. We combined clinical data from two major cancer centres in the USA and identified patients with an adequate lymphadenectomy and no perioperative chemotherapy to understand the natural history of the disease. Using this information, we created prognostic tools incorporating lymph node density that can be used for risk stratification, patient counselling and clinical trial design. OBJECTIVE To develop a clinical tool based on lymph node density (LND) for patient counselling after radical cystectomy and for design of clinical trials of adjuvant therapies after radical cystectomy., PATIENTS AND METHODS Using pooled data from two comprehensive cancer centres, we identified patients with lymph node metastases after radical cystectomy who received an adequate lymph node dissection according to existing literature (resection of eight or more nodes)., Only patients who had not received neoadjuvant or adjuvant chemotherapy were included to ensure that prediction models were based on the natural course of the disease., Thresholds for LND ranging from 5% to 35%, in 5% increments, were used to dichotomize the study population. Within each set of two groups, the Kaplan-Meier product-limit estimator was used to estimate disease-specific survival (DSS) for each group, and Cox proportional hazards regression was used to test the significance of differences in DSS between the group with higher LND and the group with lower LND., Tables and graphs showing the relationship between LND categories and 2-year and 5-year estimated DSS were created to aid in clinical decision-making., RESULTS LND was valuable as a tool for stratifying node-positive patients into different risk groups based on expected survival., At each LND threshold from 10% to 35%, patients with higher LND had significantly worse DSS than patients with lower LND ( P≤ 0.001)., As expected, DSS in the higher-LND group worsened with each 5% increase in LND threshold: patients with LND > 35% had a 5-year DSS rate of 4%., Using our data as a tool, multiple cut-offs can be employed to categorize patients into various risk groups with different risk. For example, patients with LND ≤ 10% have an estimated 5-year DSS rate of 61.9%, whereas patients with LND > 15% have an estimated 5-year DSS rate of 19.2%., CONCLUSIONS Patients with node-positive bladder cancer have poor outcomes, and survival varies widely according to LND., Categorical LND should be used to risk-stratify patients for counselling regarding prognosis., Furthermore, categorical LND should be used as a tool for designing and reporting on clinical trials of adjuvant therapies. [ABSTRACT FROM AUTHOR]

Objective: To identify lymph node density thresholds and their prognostic role in patients who underwent radical cystectomy and pelvic lymph node dissection, and to validate findings in an external series. Methods: Between May 2001 and September 2009, data from 750 radical cystectomies carried out at 'Regina Elena' National Cancer Institute (Rome, Italy) were collected in a prospectively-maintained database. Once patients who had undergone neoadjuvant treatments and those who had undergone salvage radical cystectomy were excluded from the 210 pN+ patients, 156 patients with urothelial carcinoma were selected for analysis. Optimal cut-off points for age, lymph node count and lymph node density were identified by considering these variables as continuous. External validation of findings was carried out by using data of 154 pN+ patients selected from two prospective series. Results: The optimal identified cut-off points were 11% and 30% for lymph node density, nine and 30 nodes for lymph node count, and 73 years for age. Median cancer-specific survival of patients were significantly different in patients with lymph node density <12%, between 12% and 30%, and >30% (71 months, 24 months and 11 months, respectively; P < 0.001). Cancer-specific survival was independently predicted by lymph node density cut-off points (12-30% vs <12%: hazard ratio 1.51, P = 0.047; >30% vs <12%: hazard ratio 2.89, P < 0.001). In the external series, the prognostic effect of lymph node density according to tertiary distribution of risk based on these lymph node density cut-off points was confirmed at Cox multivariable analysis (12-30% vs <12%: hazard ratio 1.5, P = 0.048; >30% vs <12%: hazard ratio 2.5, P = 0.004). Conclusions: Lymph node density is the strongest predictor of cancer-specific survival. Identified lymph node density thresholds have shown to be independent predictors of cancer-specific survival in the external validation series. [ABSTRACT FROM AUTHOR]

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Summary: Pathological lymph node metastases (pN+) are an established prognostic factor in oral cavity squamous cell carcinoma (OSCC). We retrospectively examined the prognostic significance of lymph node (LN) density in pN+ OSCC patients who underwent neck dissection (ND) and postoperative adjuvant therapy. We examined 309 pN+ patients who underwent levels I–III ND and 148 pN+ patients treated with levels I–V ND. The 5-year control and survival rates served as the main outcome measures. The 5-year rates for patients treated with levels I–III and I–V NDs were as follows: local control, 79%, 74% (p =0.0630); neck control, 81%, 68% (p =0.0014); distant metastasis, 21%, 36% (p =0.0003); disease-free survival (DFS), 59%, 43% (p =0.0001); disease-specific survival (DSS), 66%, 46% (p <0.0001); and overall survival (OS), 49%, 37% (p =0.0048), respectively. Multivariate analysis demonstrated that an LN density ⩾0.16 was an independent prognostic factor for 5-year neck control (all data presented as p, hazard ratio [95% confidence interval]) (0.003, 2.691 [1.412–5.128]), distant metastases (0.001, 2.831 [1.520–5.270]), DFS (<0.001, 2.464 [1.571–3.866]), and DSS (0.036, 1.781 [1.040–3.052]) in levels I–III ND patients. An LN density ⩾0.048 was an independent predictor of 5-year local control (0.004, 4.871 [1.654–14.344]), neck control (0.002, 24.738 [3.367–181.771]), DFS (<0.001, 4.151 [2.264–7.610]), DSS (<0.001, 3.791 [2.017–7.125]), and OS (<0.001, 2.806 [1.706–4.613]) in levels I–V ND patients. Our findings demonstrate the prognostic value of LN density for guiding treatment strategies in OSCC patients who are to receive adjuvant therapy. [Copyright &y& Elsevier]

Purpose: In this study, we aimed to validate the lymph node density (LND) as an independent prognostic factor of oral squamous cell carcinoma (OSCC) and identify a combined prognostic factor including LND, predicting better performance in risk stratification. Methods: We reviewed the clinical, pathological variables and biomarker of 95 OSCC patients who underwent surgery. LND was calculated as the ratio of positive lymph nodes to total lymph nodes removed. Principle component analysis was performed to identify a combined predictor. Results: Multivariate analysis showed that variables independently prognostic overall survival were IMP3 (hazard ratio [HR] = 3.01, 95% confidence interval [95% CI] = 1.17-7.75, P = 0.022) in a model without LND and were IMP3 (HR = 3.64, 95% CI = 1.38-9.58, P = 0.008) and LND (HR = 0.57, 95% CI = 0.57-1.75, P = 0.322; HR = 2.45, 95% CI = 1.20-4.97, P = 0.013) in a model with LND. The risk stratification using the combined prognostic factor was more significant ( P = 0.00117) than the conventional staging system and biomarker. Conclusions: The LND was shown to be an independent prognostic factor in OSCC, and a combined factor including LND may be used for risk stratification of OSCC patients, which displayed the best performance. [ABSTRACT FROM AUTHOR]

Background: To evaluate the prognostic role of lymph node density (LND) in patients affected by prostate cancer (PCa) and treated with radical prostatectomy (RP), pelvic lymph node dissection (PLND), and adjuvant hormonal blockade. Methods: A total of 124 consecutive patients with lymph node positive PCa formed the basis of this report. Clinical and pathological parameters were collected. All patients were stratified in two groups according to LND: Group A (LND ≤ 32%) and Group B (LND ≥ 33%). Time to the first biochemical recurrence (BCR) was the main measure of outcome. Results: Mean number of lymph nodes removed was 5.2 (range 1–17). The mean number of positive lymph nodes was 1.6 (range 1–5). At a mean follow-up of 84.3 mo, 22 patients in Group A (43.1%) and 40 in Group B (54.7%) had BCR. The mean overall BCR-free survival was 46.2 mo (range 8–90). No significant correlation was found between the number of positive lymph nodes and BCR-free survival (P = 0.68). In addition, the patients with LND ≥ 33% had a poor prognosis with significantly decreased disease-specific and BCR-free survival rates (hazard ratio: 0.48; 95% CI, 0.28–0.78; P = 0.0039). At multivariate and artificial neural network (ANN) analyses, LND, Gleason score, and stage were identified as independent prognostic factors of BCR-free survival (P = 0.002; P = 0.003; P = 0.003). Conclusions: The current study highlights the role of LND in predicting BCR-free survival in patients with lymph node positive PCa after prostatectomy. It also reinforces the need for a stratification of patients with nodal metastasis. [Copyright &y& Elsevier]

Abstract: Background: The prognosis for patients with lymph node (LN)–positive bladder cancer (BCa) is likely affected by the extent of lymphadenectomy in radical cystectomy (RC) cases. Specifically, the prognostic significance of the LN density (ratio of positive LNs to the total number removed) has been demonstrated. Objective: To evaluate the prognostic signature of lymphadenectomy variables, including the LN density, for a large, multicentre cohort of RC patients with LN-positive BCa. Design, setting, and participants: The clinical and histopathologic data from 477 patients with LN-positive urothelial BCa (pN1–2) were analysed. The median follow-up period for all living patients was 28 mo. Measurements: Multivariable Cox regression analysis was used to test the effect of various pelvic lymph node dissection (PLND) variables on cancer-specific survival (CSS) based on colinearity in various models. Results and limitations: The median number of LNs removed was 12 (range: 1–66), and the median number of positive LNs was 2 (range: 1–25). Two hundred ninety (60.8%) of the patients presented with stage pN2 disease. The median and mean LN density was 17.6% and 29% (range: 2.3–100), respectively, where 268 (56.2%) and 209 (43.8%) patients exhibited am LN density of ≤20% and >20%, respectively. In separate multivariable Cox regression models adjusted for age, sex, pTN stage, grade, associated Tis, and adjuvant chemotherapy, the interval-scaled LN density (hazard ratio [HR]: 1.01; p =0.002) and the LN density, ordinal-scaled by 20% (HR: 1.65; p <0.001) exhibit independent effects on CSS. In addition, an independent contribution appears from the pT but not the pN stage. Limitations include surgeon selection bias when determining the extent of lymphadenectomy. Conclusions: Our results support the prognostic relevance of LN density in patients with LN-positive BCa, where a threshold value of 20% stratifies the population into two prognostically distinct groups. Before LN density is integrated into the clinical decision-making process, these results should be validated by prospective studies with defined LN templates and standardised histopathologic methods. [Copyright &y& Elsevier]

BACKGROUND: Diagnostic and therapeutic importance of pelvic lymph node (LN) dissection (PLND) in radical cystectomy (RC) has gained recent attention. A method of pathological analysis of LN affects total number of LN removed, number of LN involved, and LN density. OBJECTIVE: To compare extended lymphadenectomy to standard lymphadenectomy in terms of LN yield, density, and effect on survival. MATERIALS AND METHODS: From Jan 2004 - July 2009, 78 patients underwent RC whose complete histopathological report was available for analysis. All were transitional cell carcinoma. From July 2007 onward extended LN dissection was started and LNs were sent in six packets. Twenty-eight patients of standard PLND kept in group I. Group II had 23 patients of standard PLND (LN sent in four packets), and group III had 23 patients of extended PLND (LN sent in six packets). SPSS 15 software used for statistical calculation. RESULTS: Distribution of T-stage among three groups is not statistically significant. Median number of LN harvested were 5 (range, 1-25) in group I, 9 (range, 3-28) in group II, and 16 (range, 1-25) in group III. Although this is significant, we did not find significant difference in number of positive LN harvested. We did not find any patient with skip metastasis to common iliac LN in group 3. CONCLUSIONS: Separate package LN evaluation significantly increased the total number of LN harvested without increasing the number of positive LN and survival. [ABSTRACT FROM AUTHOR]