The prognostic value of the lymph node ratio in patients with distal cholangiocarcinoma after curative intended surgery: A single-center retrospective study

What are the problems with the current staging of discontinuous tumour nodules (DTNs) in colorectal carcinoma? Is there a better way?

Re-appraising the role of lymph node status in predicting survival in resected distal cholangiocarcinoma – A meta-analysis and systematic review

Introduction/BackgroundThe aim of this study was to investigate the prognostic value of lymph node ratio (LNR) in patients with vulvar cancer (VC).MethodologyWe retrospectively included 192 patients treated for VC at...

The purpose of this study was to evaluate the prognostic value of lymph node ratio (LNR) in patients with gastric cancer liver metastasis (GCLM) who received combined surgical resection.A retrospective analysis of 46 patients from two hospitals was conducted. Patients were dichotomized into two groups (high LNR and low LNR) by the median value of LNR. The overall survival (OS) and recurrence-free survival (RFS) were analyzed by the Kaplan–Meier method with the log-rank test. The Cox proportional hazard model was used to carry out the subsequent multivariate analyses. And the relationship between LNR and clinicopathological characteristics was assessed.The cut-off value defining elevated LNR was 0.347. With a median follow-up of 67.5 months, the median OS and RFS of the patients were 17 and 9.5 months, respectively. Six patients survived for >5 years after surgery. Patients with higher LNR had significantly shorter OS and RFS than those with lower LNR. In the multivariate analyses, higher LNR and multiple liver metastatic tumors were identified as the independent prognostic factors for both OS and RFS. Elevated LNR was significantly associated with advanced pN stage (P <0.001), larger primary tumor size (P = 0.046), the presence of microvascular invasion (P = 0.008), and neoadjuvant chemotherapy (P = 0.004).LNR may be prognostic indicator for patients with GCLM treated by synchronous surgical resection. Patients with lower LNR and single liver metastasis may gain more survival benefits from the surgical resection. Further prospective studies with reasonable study design are warranted.

ObjectiveTo investigate the prognostic value of the lymph node ratio (LNR) in patients with small-cell carcinoma of the cervix (SCCC) after cancer-directed surgery using a population-based national registry (Surveillance Epidemiology and End Results [SEER]).MethodsWe retrospectively reviewed the data of SCCC patients in the SEER database from 1980 to 2012. The prognostic impact of LNR with respect to cause-specific survival (CSS) and overall survival (OS) was analyzed.ResultsA total of 118 patients with SCCC were identified. The median follow-up was 30.5 months. All these patients were treated with cancer-directed surgery and lymphadenectomy. Sixty (50.8%) patients had nodal metastases. The median LNR was 0.16 in patients with positive lymph nodes. Univariate analysis showed that prognostic factors such as International Federation of Gynecology and Obstetrics (FIGO) stage, nodal status, LNR, and local treatment modalities affected CSS and OS (P<0.05). Multivariate analysis showed that LNR was an independent prognostic factor for CSS and OS. Patients with a higher LNR had worse CSS (hazard ratio [HR]: 8.832; 95% confidence interval [CI]: 3.762–20.738; P<0.001) and OS (HR: 8.462; 95% CI: 3.613–19.821; P<0.001). LNR was associated with CSS and OS by stage, especially in FIGO stage I–II patients.ConclusionLNR is an independent prognostic factor in SCCC patients and it may help to individualize adjuvant therapy.

PurposePenile cancer is a rare male neoplasm with a wide variation in its global incidence. In this study, the prognostic value of lymph node ratio (LNR) was compared to that of positive lymph node count (PLNC) in penile squamous cell carcinoma.MethodsA total of 249 patients with penile squamous cell carcinoma were enrolled from The Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015. The X-tile program was used to calculate the optimal cut-off values of LNR and PLNC that discriminate survival. We used the χ2 or the Fisher exact probability test to assess the association between clinical-pathological characteristics and LNR or PLNC. Univariate and multivariate Cox regression analyses were performed to identify independent prognostic factors for survival. Spearman correlation analysis was used to determine the correlation between LNR and PLNC.ResultsWe found that patients with high LNR tended to have advanced N stage, the 7th AJCC stage, and higher pathological grade, while patients with high PLNC had advanced N stage and the 7th AJCC stage. Univariate Cox regression analysis revealed that the N stage, M stage, the 7th AJCC stage, lymph-vascular invasion, LNR, and PLNC were significantly associated with prognosis. Multivariate Cox regression analysis demonstrated that LNR rather than PLNC was an independent prognostic factor for cancer-specific survival. Subgroup analysis of node-positive patients showed that LNR was associated with CSS, while PLNC was not.ConclusionLNR was a better predictor for long-term prognosis than PLNC in patients with penile squamous cell carcinoma.

1115 Background: Breast cancer is currently staged according to the TNM (tumors, nodes, metastases) classification of the American Joint Committee on Cancer (AJCC) Staging System. Lymph node ratio (LNR, the ratio of positive axillary lymph nodes to the total number of nodes examined) may provide additional prognostic information to that provided by TNM scores. Furthermore, LNR may potentially identify subpopulations within the traditional AJCC stages that are at increased risk of adverse outcomes. Methods: We performed a single institution retrospective study of all patients diagnosed with early breast cancer between January 2000 and January 2011. Patients were divided into low- (≤0.14), intermediate- (0.15-0.39) and high-risk (≥0.4) LNR groups. We assessed the impact of LNR and conventional AJCC staging parameters on overall survival (OS) and disease-free survival (DFS). Results: 786 patients were included in the analsyis, 238 of whom were node positive. As expected nodal status according to pathologic nodal (pN) stage was prognostic for OS and DFS with OS decreasing from 88.3% in pN1 patients to 40.8% in those with pN3 disease (p&lt;0.001). LNR was also significantly associated with prognosis. OS decreased from 94% in the low-risk LNR group to 64% in the high-risk group, while DFS decreased from 92% in the low-risk LNR group to 50% in the high-risk (p&lt;0.001). When Stage III patients were divided into low- and high-risk LNR groups, OS decreased from 100% in the low LNR group to 63% in the high LNR group (p&lt;0.05). Similarly, DFS decreased from 96% in the low LNR group to 56% in the high LNR group (p&lt;0.05). A similar trend was not observed when Stage III patients were stratified according to pN status. LNR was also found to be prognostic when pN1 patients were divided into low- and high-risk LNR groups. Although both LNR and nodal status were significantly associated with OS and DFS on univariate analysis, LNR retained its significance on multivariate analysis, while nodal status did not. Conclusions: LNR can identify subpopulations within the traditional AJCC staging that are at higher risk of adverse outcomes. These findings should be examined in larger retrospective studies and, if validated, be considered as a stratification factor in future adjuvant trials.

Objective To investigate the application value of the anatomical location of positive nodes (N staging) from TNM staging systems published by American Joint Committee on Cancer (AJCC) (7th edition), number of metastatic lymph nodes(NMLN), lymph node ratio (LNR) and log odds of metastatic lymph nodes (LODDS) as prognostic predictors in advanced gallbladder carcinoma(GBC). Methods The retrospective cross-sectional study was conducted. The clinicopathological data of 176 patients who underwent radical resection of advanced GBC in the First Affiliated Hospital of Xi′an Jiaotong University between January 2008 and December 2014 were collected. According to preoperative assessment, intraoperative exploration and frozen section biopsy, staging and surgical procedure were confirmed. Observation indicators and evaluation criteria: (1)surgical and postoperative situations; (2) follow-up and survival situations; (3) N staging related indicators based on TNM staging systems of AJCC (7th edition): LNR=NMLN / total number of lymph node dissection, LODDS=Log (NMLN+0.5) / (total number of lymph node dissection - NMLN+0.5); (4) lymph node staging based on NMLN, LNR and LODDS: LODDS <-1.0 as LODDS 1 staging, -1.0 ≤ LODDS < 0 as LODDS 2 staging, LODDS ≥0 as LODDS 3 staging; (5) prognostic comparisons of patients with different lymph node staging; (6) accuracy of 4 different types of lymph node staging predicting the prognosis of patients. Follow-up using outpatient examination and telephone interview was performed to detect postoperative survival up to December 31, 2017. Measurement data with normal distribution were represented as ±s. Measurement data with skewed distribution were described as M(range), and comparisons were done using the nonparametric test.The survival rate was calculated by the Kaplan-Meier method, and the Log-rank test was used for survival comparison. Correlation analysis was done using the Spearman correlation analysis, r ≥ 0.800 as a high correlation, 0.500 ≤ r < 0.800 as a moderate correlation and 0.300 ≤ r < 0.500 as a low correlation. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were respectively drawn and calculated based on 4 kinds of binary logistic regression model. Akaike information criterion (AIC) and Harrell concordance index (Harrell c-index) were respectively calculated based on 4 kinds of COX proportional hazard regression model. The larger values of AUC and Harrell c-index caused a smaller value of AIC, but a lymph node staging standard correlated with greater prognostic accuracy. Harrell c-index < 0.50 was no prediction, and 0.50 ≤ Harrell c-index ≤ 1.00 was an obvious prediction. Results (1) Surgical and postoperative situations: 176 patients underwent successful radical resection of GBC, including 161 in R0 resection and 15 in R1 resection, 99 with D1 lymph node dissection and 77 with D2 lymph node dissection. Of 176 patients, 9 with postoperative complications were improved by symptomatic treatment, including 6 with bile leakage, 2 with hepatic dysfunction and 1 with intra-abdominal hemorrhage. Results of postoperative pathological examination: total number of lymph node dissection, NMLN and LNR were respectively 6.7±4.4, 0 (range, 0-12.0) and 0 (range, 0-1.00); high-differentiated, moderate-differentiated and low-differentiated tumors were respectively detected in 16, 81 and 79 patients; 162 and 14 patients were in T3 and T4 stages; 60 patients were combined with infiltration of the liver. (2) Follow-up and survival situations: 176 patients were followed up for 1-118 months, with a median time of 33 months. The 1-, 3- and 5-year overall survival rates were respectively 63.1%, 42.0% and 32.0%. (3) N staging related indicators based on TNM staging systems of AJCC (7th edition): 95, 45 and 36 patients were respectively detected in staging N0, N1 and N2. NMLN, LNR and LODDS were respectively 2.0 (range, 1.0-7.0), 0.40 (range, 0.08-1.00), -0.15 (range, -0.99-1.04)in staging N1 and 4.0 (range, 1.0-12.0), 0.57 (range, 0.13-1.00), 0.11 (range, -0.70-1.04) in staging N2, with a statistically significant difference in NMLN (Z=-3.888, P 0.05). (4) Lymph node staging based on NMLN, LNR and LODDS: NMLN and LNR as a cut-off point were respectively 4.0 and 0.70, NMLN 1 staging (NMLN=0) was detected in 95 patients, NMLN 2 staging (1.0 ≤ NMLN ≤ 4.0) in 61 patients and NMLN 3 staging (NMLN>4.0) in 20 patients; LNR 1 staging (LNR=0) was detected in 95 patients, LNR 2 staging (0 0.70) in 23 patients. LODDS 1, 2 and 3 stagings was detected in 61, 70 and 45 patients, respectively. The lymph node staging based on NMLN and LNR was significantly correlated with based on N staging of TNM staging systems of AJCC (7th edition) (r=0.949, 0.922, P<0.05); the lymph node staging based on LODDS was moderately correlated with based on N staging of TNM staging systems of AJCC (7th edition) (r=0.758, P<0.05). (5) Prognostic comparisons of patients with different lymph node staging: 1-, 3- and 5-year overall survival rates were respectively 86.3%, 65.3%, 52.2% in N0 staging patients and 44.4%, 22.2%, 13.3% in N1 staging patients and 25.0%, 5.6%, 2.8% in N2 staging patients, with a statistically significant difference (χ2=88.895, P<0.05). The 1-, 3- and 5-year overall survival rates were respectively 86.3%, 65.3%, 52.2% in NMLN 1 staging patients and 47.5%, 19.7%, 11.1% in NMLN 2 staging patients and 0, 0, 0 in NMLN 3 staging patients, with a statistically significant difference (χ2=121.086, P<0.05). The 1-, 3- and 5-year overall survival rates were respectively 86.3%, 65.3%, 52.2% in LNR 1 staging patients and 41.4%, 17.2%, 11.8% in LNR 2 staging patients and 17.4%, 8.7%, 0 in LNR 3 staging patients, with a statistically significant difference (χ2=86.503, P<0.05). The 1-, 3- and 5-year overall survival rates were respectively 85.2%, 65.5%, 51.8% in LODDS 1 staging patients and 65.7%, 40.0%, 31.3% in LODDS 2 staging patients and 28.9%, 13.3%, 5.9% in LODDS 3 staging patients, with a statistically significant difference (χ2=59.195, P<0.05). (6) Accuracy of 4 different types of lymph node staging predicting the prognosis of patients: according to N staging of TNM staging systems of AJCC (7th edition), NMLN, LNR and LODDS, AUC, AIC and Harrell c-index of lymph node staging were respectively 0.878, 0.881, 0.870, 0.864 and 1 047.5, 1 026.4, 1 044.2, 1 063.6 and 0.77, 0.78, 0.77, 0.76. AIC value was smaller with increased values of AUC and Harrell c-index based on NMLN, showing a greatest accuracy predicting the prognosis of patients. Conclusion Among N staging of TNM staging system of AJCC (7 edition), NMLN, LNR and LODDS as prognostic predictors, NMLN can more precisely predict radical resection of advanced GBC. Key words: Gallbladder neoplasms, advanced; Radical resection; N staging; Number of positive lymph nodes; Positive lymph node ratio; Log odds of metastatic lymph node; Prognosis

ObjectiveLung cancer is the leading cause of cancer-related mortality. Lymph node involvement remains a crucial prognostic factor in non-small cell lung cancer (NSCLC), and the TNM system is the current standard for staging. However, it mainly considers the anatomical location of lymph nodes, neglecting the significance of node count. Metrics like metastatic lymph node count and lymph node ratio (LNR) have been proposed as more accurate predictors.MethodsWe used data from the SEER 17 Registry Database (2010–2019), including 52,790 NSCLC patients who underwent lobectomy or pneumonectomy, with at least one lymph node examined. Primary outcomes were overall survival (OS) and cancer-specific survival (CSS). Cox regression models assessed the prognostic value of negative lymph node (NLN) count, number of positive lymph node (NPLN), and LNR, with cut-points determined using X-tile software. Model performance was evaluated by the Akaike information criterion (AIC).ResultsThe Cox proportional hazards model analysis revealed that NLN, NPLN, and LNR are independent prognostic factors for OS and LCSS (P < 0.0001). Higher NLN counts were associated with better survival (HR = 0.79, 95% CI = 0.76–0.83, P < 0.0001), while higher NPLN (HR = 2.19, 95% CI = 1.79–2.67, P < 0.0001) and LNR (HR = 1.64, 95% CI = 1.79–2.67, P < 0.0001) values indicated worse outcomes. Kaplan-Meier curves for all three groups (NLN, NPLN, LNR) demonstrated clear stratification (P < 0.0001). The NLN-based model (60,066.5502) exhibited the strongest predictive performance, followed by the NPLN (60,508.8957) and LNR models (60,349.4583), although the differences in AIC were minimal.ConclusionsNLN count, NPLN, and LNR were all identified as independent prognostic indicators in patients with NSCLC. Among these, the predictive model based on NLN demonstrated a marginally superior prognostic value compared to NPLN, with NPLN outperforming the LNR model. Notably, higher NLN counts, along with lower NPLN and LNR values, were consistently associated with improved survival outcomes. The relationship between these prognostic markers and NSCLC survival warrants further validation through prospective studies.

Objective: The presence of metastatic cervical lymph nodes (MCNs) is an unfavorable prognostic factor in head and neck cancer. The total volume of MCNs (MNV) and the lymph node ratio (LNR) may be superior to conventional nodal staging in cervical metastasis from an unknown primary tumor (CUP). We evaluated the prognostic value of MNV and LNR in CUP patients. Methods: Thirty-nine patients with CUP who underwent surgery plus postoperative radiotherapy were reviewed. MNV was measured by preoperative computed tomography and LNR was determined using neck dissection samples. The association of clinicopathologic factors, MNV, and LNR with disease-free survival (DFS) and overall survival (OS) was analyzed. Results: Five-year DFS and OS were 68.4 and 70.8%, respectively, for a median follow-up of 49 months. In multivariate analysis, MNV (>30 ml) was an independent prognostic factor for both DFS and OS (p = 0.004 and p < 0.001, respectively). LNR (>0.14) was identified as an independent predictive factor for DFS (p = 0.041). Conclusion: MNV and LNR are independent prognostic factors in patients with CUP and could facilitate the identification of high-risk patients requiring intensive treatment and surveillance.

The 8th American Joint Committee on Cancer (AJCC) staging system for distal cholangiocarcinoma (DCC) included a positive lymph node count (PLNC), but a comparison of the prognostic predictive power of PLNC and lymph node ratio (LNR) is still under debate. This study aimed to compare various staging models made by combining the abovementioned factors, identify the model with the best predictive power, and propose a modified staging system. We retrospectively reviewed 251 patients who underwent surgery for DCC at four centers. To determine the superiority of various staging models for predicting overall OSR, Akaike information criterion (AIC), Bayesian information criterion (BIC), AIC correction (AICc), and Harrell’s C-statistic were calculated. In multivariate analysis, age (p = 0.003), total lymph node count (p = 0.033), and revised T(LNR)M staging (p < 0.001) were identified as independent factors for overall survival rate. The predictive performance of revised T (LNR) M staging (AIC: 1288.925, BIC: 1303.377, AICc: 1291.52, and Harrell’s C statics: 0.667) was superior to other staging system. A modified staging system consisting of revised T category and LNR predicted better overall survival of DCC than AJCC 7th and AJCC 8th editions. In the future, external validation of the proposed new system using a larger cohort will be required.

We evaluated the prognostic value of lymph node ratio (LNR) in patients with advanced laryngeal and hypopharyngeal squamous cell carcinoma. Retrospective chart review. Between 1994 and 2018, 79 patients underwent total laryngopharyngectomy and adjuvant therapy. LNR was determined and statistically compared to patients' overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), locoregional and distant failure. The 5-year OS, DSS and DFS rates were 45.6%, 73.4% and 56.9%, respectively. 24.1% and 25.3% developed loco- regional failure or distant metastatic disease, respectively. Univariate analyses showed that high LNR (cut-off >0.07) was significantly associated with distant and locoregional failure. On multivariate analysis, LNR remained an independent predictor for OS (P=.004), DSS (P=.009) and DFS (P=.044). Increased LNR in patients with advanced laryngeal or hypopharyngeal carcinoma is significantly linked to shortened OS, DSS, DFS and higher locoregional and distant metastatic disease.

Prognostic Significance of the Lymph Node Ratio in Surgical Patients With Distal Cholangiocarcinoma

Lymph node ratio (LNR) is increasingly accepted as a useful prognostic indicator in colorectal cancer. However, variations in methodology, statistical stringency and cohort composition has led to inconsistency in respect of the optimally prognostic LNR. The aim was to apply a robust regression-based analysis to generate and appraise LNRs optimally prognostic for colon and rectal cancer, both separately and in combination. LNR was established for all patients undergoing either a colonic (n = 379) or rectal (n = 160) cancer resection with curative intent. The optimal LNR associated with disease-free and overall survival were established using a classification and regression tree technique. This process was repeated separately for patients who underwent either colonic or rectal resection and for the combined cohort. Survival associated with differing LNR was estimated using the Kaplan-Meier method and compared using a log-rank test. Relationships between LNR, disease-free survival (DFS) and overall survival (OS) were further characterised using Cox regression analysis. All statistical analyses were conducted in the R programming environment, with statistical significance was taken at a level of p < 0.05. Optimal LNRs differed between each cohort, when either overall or disease-free survival was considered. LNRs generated from combined cohorts also differed from those generated by individual cohorts. In relation to DFS, LNR values were obtained and included 0.18 for the colon cancer cohort and 0.19 for the rectal and combined colorectal cancer cohorts. In relation to OS, multiple LNR values were obtained for colon and combined cohorts; however, an optimal LNR was not evident in the rectal cancer cohort. Survival patterns according to LNR closely resembled those associated with standard nodal staging. Application of a data-driven approach based on recursive partitioning generates differing lymph node ratios for colon, rectal and combined colorectal cohorts. In each cohort, LNR was similarly prognostic to standard nodal staging in respect to overall and disease-free survival. Overall survival was associated with a multiplicity of LNR values, whilst disease-free survival was associated with a single LNR only. The paper demonstrates the merits of utilising a data-driven approach to determining lymph node ratios from specific patient cohorts. Utilising such an approach enabled the generation of those LNRs that were most associated with particular survival trends in relation to overall and disease-free survival. These differed markedly for colon cancer, rectal cancer and combined cohorts. In general, the survival patterns associated with LNRs generated were similar to those observed with standard nodal staging.

The lymph node (LN) ratio (LNR) has been proposed as a sensitive prognosticator in patients with esophageal squamous cell carcinoma (ESCC), especially when the number of LNs harvested is insufficient. We investigated the association between the LNR and survival in patients with locally advanced ESCC who received neoadjuvant chemotherapy (NAC) and explored whether the LNR is a prognosticator in these patients when stratified by their response to NAC. We retrospectively reviewed 199 locally advanced ESCC patients who received curative resection after NAC between January 2011 and December 2019. The predictive accuracy of the adjusted X-tile cut-off values for LNR of 0 and 0.13 was compared with that in the Union for International Cancer Control pathological N (UICC pN) categories. The association between survival rate and clinicopathological features was examined. Multivariate analysis identified that the LNR was an independent risk factor for recurrence-free survival [RFS; hazard ratio (HR) 6.917, p<0.001] and overall survival (OS) (HR 4.998, p<0.001). Moreover, even when stratified by response to NAC, the LNR was a significant independent risk factor for RFS and OS (p<0.001). The receiver operating characteristic curves identified that the prognostic accuracy of the LNR tended to be better than that of the UICC pN factor in all cases and responders. The LNR had a significant prognostic value in patients with locally advanced ESCC, including in those who received NAC.