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Background: The AJCC pN-staging system is the current risk stratification strategy for axillary nodal staging in most cancer centers. Recently, another staging system named "Lymph Node Ratio" or LNR has been developed and also postulated to have prognostic value. Precise prognostication of breast cancer by these two systems has multiple methodological dilemmas which are overlooked in the literature and still remain matters of debate. Methods: These two issues are categorized into seven queries, including: the number of nodes considered adequate for proper axillary staging; attitude toward Z-0011 trial; impacts of neo-adjuvant therapies; the origin and evolution of stratification cutoffs; the position where patients without axillary involvement should be placed; role of diverse endpoints in survival definition, outcome analyses and prognosis prediction; and ultimately the current opinion regarding the superiority between the two systems. This review sought to explore these topics through analysis of 58 recently published articles found by MEDLINE search. Results: The analysis revealed that precise prognostication by pN-staging system requires at least 10 excised-nodes, but LNR system minimally depends on the quantity of excised-nodes. Adhering to Z-0011 trial findings obstructs the provision of sufficient nodes for pN-staging. Neo-adjuvant chemotherapy alters the axillary nodal climate and therefore disrupts proper axillary staging. Cutoffs of LNR system have a more clear history of formation than the pN-staging's. Breast cancer-specific survival is the type of survival better portraying cancer-related events. Conclusions: LNR system seems at least as accurate as pN-staging in prognostication of breast cancer patients.

Objective: The pathologic staging of rectal cancer is an important prognostic factor. A sufficient number of harvested lymph nodes is necessary for accurate staging. In patients with an insufficient number of dissected lymph nodes, the lymph node ratio (LNR) can be used as a prognostic factor. The aim of this study was to determine the effect of the LNR on the prognosis of patients with rectal cancer. Materials and Methods: A total of 130 patients who had rectal adenocarcinoma and who underwent surgery between 1996 and 2011 were included in this study. Age, gender, serum carcinoembryonic antigen, type of surgery, and pathological features were retrieved retrospectively. Cut-off values for LNR were 1/12, 1/4, and 1/2; patients were stratified into four groups according to this ratio. The relationship between disease-free survival (DFS) and overall survival (OS) and LNR was investigated. Cumulative survival curves were calculated by the Kaplan Meier method, and survival differences between groups were calculated by the log-rank test. Results: The mean number of lymph nodes examined was 11.5+/-8. In 75 of all patients (57.7%), fewer than 12 lymph nodes were harvested. Seventy-six patients (58.5%) were evaluated as N0, 35 (26.9%) were N1, and 19 (14.6%) were N2. The number of patients in these LNR groups was 87 (66.9%), 13 (10%), 17 (13.1%), and 13 (10%), respectively. The 5-year survival rate was found to be 72.3% in the LNR1 group, 55.6% in the LNR2 group, 44.4% in the LNR3 group, and 22.2% in the LNR4 group. The difference in OS and DFS rates was significant (p

Background: Breast cancer in Egypt is the most common cancer among women and is the leading cause of cancer mortality. Traditionally, axillary lymph node involvement is considered among the most important prognostic factors in breast cancer. Nonetheless, accumulating evidence suggests that axillary lymph node ratio should be considered as an alternative to classical pN classification. Materials and methods: We performed a retrospective analysis of patients with operable node-positive breast cancer, to investigate the prognostic significance of axillary lymph node ratio. Results: Five-hundred patients were considered eligible for the analysis. Median follow-up was 35 months (95% CI 32–37 months), the median disease-free survival (DFS) was 49 months (95% CI, 46.4–52.2 months). The classification of patients based on pN staging system failed to prognosticate DFS in the multivariate analysis. Conversely, grade 3 tumors, and the intermediate (>0.20 to ⩽0.65) and high (>0.65) LNR were the only variables that were independently associated with adverse DFS. The overall survival (OS) in this series was 69 months (95% CI 60–77). Conclusion: The analysis of outcome of patients with early breast cancer in Egypt identified the adverse prognostic effects of high tumor grade, ER negativity and intermediate and high LNR on DFS. If the utility of the LNR is validated in other studies, it may replace the use of absolute number of axillary lymph nodes.

Background Surgical resection is the mainstay of pancreatic cancer treatment; however, the ideal lymphadenectomy remains unsettled. This study sought to determine whether number of examined lymph nodes (eLNs) and lymph node ratio (LNR) impact survival. Methods The U.S. National Cancer Data Base (2003-2011) was reviewed for patients who underwent initial resection for clinical stage I and II pancreatic adenocarcinoma. Univariate and multivariate survival analyses were performed. Results Of 14,007 patients, 15.6% had 0-6 eLN, 27.1% 7-12, 13.4% 13-15, and 38.6% > 15 eLN. Median eLN was 11 for pancreaticoduodenectomy, and 14 for distal, total pancreatectomy, or other procedure. ELN >15 was associated with significantly improved survival in both node negative and positive disease ( P < 0.001, both). In multivariable analysis, 7-12, 13-15, and >15 eLN had improved survival relative to 0-6 eLN (HR 0.87, P < 0.001, HR 0.89, P = 0.002, HR 0.82, P < 0.001, respectively). A total of 34.5% of patients had an LNR of 0, 31.5% ≤ 0.2, 20.3% 0.2-0.4, 11.7% 0.4-0.8, and 2.0% had an LNR >0.8. Patients with LNR 0 had improved survival in T1-T3 disease ( P < 0.01). In multivariable analysis, higher LNR was negatively associated with survival (LNR 0-0.2: HR 1.44, P < 0.001, LNR 0.2-0.4: HR 1.82, P < 0.001, LNR 0.4-0.8: 2.03, P < 0.001, LNR >0.8, P < 0.001). Even with suboptimal eLN (eLN ≤6 or ≤12), higher LNR remained an independent predictor of mortality. Conclusions Greater lymph node retrieval in stage I & II pancreatic adenocarcinoma may have prognostic value, even in node-negative disease. Lymph node ratio is inversely related to survival and may be useful with suboptimal eLN. [ABSTRACT FROM AUTHOR]

Background There is no published study on the influence of lymph node ratio on locoregional recurrence of squamous cell carcinoma (SCC) of the buccal mucosa. Therefore, we focused in our study on this specific anatomic subsite. Methods We conducted a retrospective chart review of 95 patients from 2003-2013 with treatment-naive SCC of the buccal mucosa. Exclusion criteria were neoadjuvant chemoradiotherapy, perioperative death, N3 disease, unresectable disease, synchronous malignancy, and follow-up <3 months. Statistical analysis was performed using univariate and multivariate analysis. Results Significant correlations were found between locoregional recurrence and pathologic N classification ( P < .001), grading ( P = .001), and lymph node ratio ( P < .001). Multivariate analysis indicated lymph node ratio as an independent risk factor for locoregional recurrence ( P = .002). A cutoff value under 7% led to a 10.383-fold higher risk of incurring a locoregional recurrence. Conclusion Lymph node ratio is a useful parameter to stratify the risk of locoregional recurrence in patients with SCC of the buccal mucosa. [ABSTRACT FROM AUTHOR]

Objective To estimate the prognostic significance of lymph node ratio and number of positive nodes in vulvar cancer patients. Methods This international multicenter retrospective study included patients diagnosed with vulvar cancer treated with inguinal lymphadenectomy. Lymph node ratio (LNR) is the ratio of the number of positive lymph nodes (LN) to the number of removed LN. Patients were stratified into risk groups according to LNR. LNR was correlated with clinical-pathological parameters. Survival analyses were performed. Results This analysis included 745 patients. In total, 292 (39.2%) patients had positive inguinal LN. The mean (SD) number of resected and positive LN was 14.1 (7.6) and 3.0 (2.9), respectively. High LNR was associated with larger tumor size and higher tumor grade. Patients with LNRs 0% (N0), > 0 < 20%, and > 20% had 5-year overall survival (OS) rates of 90.9%, 70.7%, and 61.8%, respectively ( P < 0.001). LNR was associated with both local and distant recurrence-free survival ( P < 0.001). Patients with 0, 1, 2, 3 or > 3 positive lymph nodes had 5-year OS rates of 90.9%, 70.8%, 67.8%, 70.8% and 63.4% respectively ( P < 0.001). In multivariate analysis, LNR ( P = 0.01) and FIGO stage ( P < 0.001), were associated with OS, whereas the number of positive nodes ( P = 0.8), age ( P = 0.2), and tumor grade ( P = 0.7), were not. In high-risk patients, adjuvant radiotherapy was associated with improved survival. Conclusions LNR provides useful prognostic information in vulvar cancer patients with inguinal LN resection in vulvar cancer. LNR allows for more accurate prognostic stratification of patients than number of positive nodes. LNR seems useful to select appropriate candidates for adjuvant radiation. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to evaluate the prognostic value of the lymph node ratio (LNR), which was defined as the proportion of involved nodes of all dissected nodes, in pN1 breast cancer. Materials and Methods: We retrospectively analyzed the clinical data of patients with pN1 breast cancer (n = 144) treated at Keimyung University Dongsan Medical Center, Daegu, Korea between 2001 and 2010. The median age was 46 years (range, 27 to 66 years). The LNR was 0.01-0.15 (low LNR) in 130 patients and >0.15 (high LNR) in 14 patients. Sixty-five patients (45.1%) had T1 tumors, 74 (51.4%) had T2 tumors, and 5 (3.5%) had T3 tumors. Eighty-eight patients (61.1%) underwent total mastectomy and 56 (38.9%) underwent partial mastectomy. Fifty-nine patients (41.0%) underwent radiotherapy and 12 (8.3%) underwent regional radiotherapy. The median follow-up period was 65 months. Results: The 5- and 10-year disease-free survival (DFS) rates were 92.7% and 82.4%, respectively. Univariate analyses revealed that high LNR (p = 0.004), total mastectomy (p = 0.006), no local radiotherapy (p = 0.036), and stage T2 or T3 (p = 0.010) were associated with worse DFS. In multivariable analysis, only high LNR (p = 0.015) was associated with worse DFS. Conclusion: High LNR is an independent prognostic factor in pN1 breast cancer and could be an indication for adjuvant radiotherapy in these patients. [ABSTRACT FROM AUTHOR]

Purpose Attempts have been made to revise the nodal stage due to simplicity of current N staging system in ampullary adenocarcinoma. However, because of the disease rarity, there have only been a few studies assessing the prognostic impact of lymph node (LN) parameters. Methods We retrospectively analyzed 120 patients who underwent radical resection followed by adjuvant chemoradiotherapy for ampullary adenocarcinoma. The effect of LN parameters (number of total harvest LNs, number of metastatic LN (MLN), lymph node ratio (LNR), and log odds of positive LNs (LODDS)) on overall survival (OS), locoregional relapse-free survival (LRFS) and distant metastasis-free survival were evaluated. Cutoff points of MLN, LNR and LODDs were determined using maximal χ 2 method. Results Fifty-seven patients (48%) were staged as pN1 and their survival was not significantly decreased compared with pN0 patients. There was also no significant difference between patients with MLN 0 vs. 1. In univariate analyses, MLN (0–1 vs. ≥2), LNR (≤17% vs. >17%) and perineural invasion were common prognosticators for OS and LRFS. Distant metastasis-free survival was not influenced by LN status. In addition, multivariate analysis revealed that among the LN parameters, LNR was able to independently predict both OS and LRFS. Conclusions LNR performs better than other LN related parameters for predicting survival. After radical resection followed by adjuvant treatment, survival of patients with one positive LN does not seem to differ from patients without LN metastasis. [ABSTRACT FROM AUTHOR]

Background We aimed to investigate the impact of lymph node ratio (LNR, number of positive nodes/total number of excised nodes) on regional-only-failure, distant-only-failure and overall survival (OS) in oral squamous cell carcinoma (OSCC). Methods Retrospective review of pN0-2 OSCC-patients (1994–2012) treated with curative-surgery with neck dissection ± postoperative radiotherapy (PORT) ± concurrent chemotherapy. LNR was subjected to multivariable analysis (MVA) of regional-only-failure, distant-only-failure and OS. Results Overall 914 patients were identified; median follow-up: 51 months (1–189); pN0: 482 (52.7%), pN1: 128 (14%), pN2a: 6 (0.7%); pN2b: 225 (24.6%); pN2c: 73 (8%); median number of dissected nodes: 36 (6–125); median number of pN+: 2 (1–49); median LNR for pN+ patients: 6%; extranodal extension: 187 (20.5%). Bilateral neck dissection: 368 (40.3%); PORT: 452 (49.5%); and concurrent chemotherapy: 80 (8.8%). High grade, lymphovascular invasion perineural invasion and pT3–4 were associated with high LNR. On MVA, LNR was associated with regional-only-failure (HR = 1.06; 95%CI: 1.04–1.08; p < 0.001), distant-only-failure (HR = 1.03; 95%CI: 1.02–1.05; p = 0.004) and lower OS (HR = 1.03; 95%CI: 1.02–1.05; p < 0.001). Similarly, in pN2-subgroup: LNR was associated with regional-only-failure (HR = 1.04; 95%CI: 1.02–1.06; p < 0.001), distant-only-failure (HR = 1.03; 95%CI: 1.01–1.06; p = 0.045) and lower OS (HR = 1.03; 95%CI: 1.02–1.04; p < 0.001). Conclusion High LNR is associated with higher regional-only-failure/distant-only-failure and lower OS. LNR should be assessed in future prospective trials for selection of adjuvant therapy. [ABSTRACT FROM AUTHOR]

Survival after pancreatic cancer surgery is extremely unfavorable even after curative resection. Prognostic factors have been explored but remain largely undefined. The present study was to identify the role of clinical and laboratory variables in the prognostic significance of resectable pancreatic adenocarcinoma. A total of 96 patients who underwent curative resection for pancreatic cancer were included. Survival was evaluated based on complete follow-up visits and was associated with potential prognostic factors using the Kaplan-Meier method and Cox proportional hazard model survival analyses. The results showed that prognostic variables significantly reduced survival, including old age, poorly differentiated tumors, elevated tumor markers and positive lymph node metastasis (LNM). Age of older than 60 years (HR=1.83, P=0.04), LNM (HR=2.22, P=0.01), lymph node ratio (00.2, HR=1.92, P=0.017), initial CA199 (HR=4.80, P=0.004), and CEA level (HR=2.59, P=0.019) were identified as independent prognostic factors by multivariate analysis. It was concluded that LNR may be potent predictor of survival and suggests that surgeons and the pathologists should thoroughly assess lymph nodes prior to surgery. [ABSTRACT FROM AUTHOR]

Introduction Locoregional recurrence plays a key role in treatment failure of patients with squamous cell carcinoma of the tongue. In a large amount of studies lymph node ratio could be demonstrated as a promising parameter to stratify risk of patients with oral cavity cancer. However data on the influence of lymph node ratio on locoregional recurrence of tongue squamous cell carcinoma is very rare. Material and methods Retrospective chart review of 130 patients with treatment naive squamous cell carcinoma of the tongue. Exclusion criteria were neoadjuvant chemoradiotherapy, perioperative death, N3 disease, unresectable disease, synchronous malignancy, follow up <3 months. Contingency tables and χ 2 -test were performed to analyze associations between clinicopathological features and recurrence. All statistic were 2-sided and a p -value <0.05 was considered as significant. Multivariate analysis was performed using binary logistic regression analysis. A cut off value of 6% for lymph node ratio was applied. Results Significant correlations were found between locoregional recurrence and pathologic N-Classification (<0.001), UICC stage (<0.001), perineural invasion ( p = 0.025), grading ( p = 0.001), number of resected lymph nodes ( p = 0.007) and lymph node ratio ( p < 0.001). Multivariate analysis indicated lymph node ratio as solely independent risk factor for locoregional recurrence. Conclusions Lymph node ratio may be an useful parameter to stratify risk of locoregional recurrence of patients with squamous cell carcinoma of the tongue. Thus lymph node ratio might help to improve diagnosis and therapy of affected patients. [ABSTRACT FROM AUTHOR]

Background: Although several markers, including the lymph node ratio (LNR), have been proposed as a clinically prognostic tool for colorectal cancer (CRC), it remains unclear which markers have the most relevance in determining recurrence following adjuvant chemotherapy for stage III CRC. Methods: Independent risk factors for recurrence-free survival (RFS) were retrospectively determined using the Cox proportional hazard model in 360 stage III CRC patients and validated using an independent cohort comprising 172 stage III CRC patients. Results: The LNR was independently associated with RFS (HR, 1.96; 95% CI, 1.11 to 3.28; P = 0.020). A higher LNR value was significantly associated with recurrence, microsatellite stable, and shorter time to recurrence. A combination of the LNR with pre-chemotherapy CEA and CA19-9, other independent risk factors, provided accurate risk stratification of RFS and conferred additional information on recurrence within each stage III CRC subgroup, which was then validated in an independent cohort. A beneficial effect in patients at risk of recurrence, and a reduced effect in patients at low risk, was exhibited by the addition of oxaliplatin to 5-fluorouracil-based adjuvant chemotherapy. Conclusion: A higher LNR is one of the most aggressive phenotypes with recurrence risk following adjuvant chemotherapy for stage III CRC. [ABSTRACT FROM AUTHOR]

The metastatic lymph node status (N classification) is an important prognostic factor for patients with colorectal cancer (CRC). The aim of the present study was to evaluate and compare the prognostic assessment of three different lymph node staging methods, namely standard lymph node (pN) staging, metastatic lymph node ratio (LNR) and log odds of positive lymph nodes (LODDS) in CRC patients who undergo curative resection (R0). Data were retrospectively collected from 192 patients who had undergone R0 resection. Kaplan-Meier survival curves, Cox proportional hazards model and accuracy of the three methods (pN, LNR and LODDS) were compared to evaluate the prognostic effect. Univariate analysis demonstrated that pN, LNR and LODDS were all significantly correlated with survival (P=0.001, P<0.001 and P<0.001, respectively). The final result of the 3-step multivariate analysis demonstrated that LODDS was superior to the other two N categories. Patients in the same pN or LNR classifications may be classified into different LODDS stages with different prognoses. Thus, LODDS may be a meaningful prognostic indicator and superior to the pN and LNR classifications in CRC patients who undergo curative (R0) resection. [ABSTRACT FROM AUTHOR]

ABSTRACT Background The minority of head and neck cutaneous squamous cell carcinomas (SCC) metastasize to regional lymph nodes. The purpose of this study was to describe the clinical outcomes and prognostic factors for patients with node-positive head and neck cutaneous SCC who underwent lymphadenectomy. Methods We conducted a retrospective single center study using the Kaplan-Meier method for the investigation of the overall survival (OS) and locoregional control rates. The Cox proportional hazards model was evaluated to identify prognostic factors. Results The median number of positive lymph nodes from 149 lymphadenectomies was 2 in the neck and 1 in the parotid gland. The 5-year OS and locoregional control rates were 50% and 77%, respectively. OS was worse among older patients (hazard ratio [HR], 1.04; p = .015), immunosuppressed patients (HR, 2.06; p = .034), and patients with a high total lymph node ratio (calculated from the number of positive lymph nodes divided by the total number of nodes; multivariate analysis [MVA]; HR, 1.13; p = .019). Conclusion Low total lymph node ratio is associated with improved outcomes in node-positive head and neck cutaneous SCC. © 2017 Wiley Periodicals, Inc. Head Neck 39: 772-778, 2017 [ABSTRACT FROM AUTHOR]

Objectives: The paper aimed to compare the efficacy of log odds (LODDS) compared to a classification based on the distribution of involved lymph nodes (pN) and lymph node ratio (LNR). Methods: Material was collected retrospectively from an online survey-based database of the Polish Lung Cancer Group and included a group of 17,369 patients who received radical surgical treatment (R0) due to lung cancer. Results: In the whole group the median survival for N0, N1 and N2 was 76.1, 41.7 and 24.2 months, respectively. The median survival for individual LODDS categories (-6,-4], (-4,-3], (-3,-2], (-2,-1], (-1,0], (0,1] and (1,2] was 76.5, 76.3, 71.7, 45.4, 25.0, 19.1 and 17.7 months, respectively. The median survival for LNR in individual categories (0), (0,0.25], (0.25,05], (0.5075] and (0.75,1.0] was 75.6, 40.3, 24.1, 18.8 and 16.4 months, respectively. A multi-variant analysis demonstrated that each LODDS category is an independent prognostic factor: (-4,-3] (HR = 0.982; 95% CI 0.867e1.112; P = 0.775), (-3,-2] (HR = 1.114; 95% CI 0.984e1.262; P = 0.089), (-2,-1] (HR = 1.241; 95% CI 1.080e1.425; P = 0.002), (-1,0] (HR = 1.617; 95% CI 1.385e1.887; P < 0.0001), (0,1] (HR = 1.918; 95% CI 1.579e2.329; P < 0.0001) and (1,2] (HR = 2.016; 95% CI 1.579e2.573; P < 0.0001). Conclusions: Based on LODDS it is possible to discriminate patients with regard to lung cancer stage more effectively compared to pN and LNR classification, and it is also a better classification system. [ABSTRACT FROM AUTHOR]

Aim The ratio of positive nodes to total nodes, the lymph node ratio ( LNR), is a proposed alternative to the current N1/N2 classification of nodal disease. The true clinical benefit of adopting the LNR, however, has not been definitively demonstrated. This study compared the LNR with the current N1/N2 classification of Stage III colon cancer. Method Patients with Stage III colon cancer were identified from a prospectively maintained database (1996-2012). The specificity and sensitivity of the N1/N2 classification in the prediction of overall survival were determined using R. A cut-off point for the LNR was determined by setting the specificity the same as for the N1/N2 classification. The sensitivity of the two methods was then compared, and bootstrapping 1000-fold was performed. This was then repeated for disease-specific survival. Results The specificity and sensitivity of the N1/N2 classification in predicting 3-year overall survival in this cohort ( n = 402) was 62.2% and 52.1%, respectively. The cut-off point for the LNR was determined to be 0.27 for these data. On comparing LNR with the N1/N2 classification showed that for a given specificity, the LNR did not provide a statistically significant improvement in sensitivity (52.8% vs 52.1%, P = 0.31). For disease-specific death at 3 years, the specificity and sensitivity were 60.8% and 54.6%, respectively. The LNR did not provide a statistically significant improvement (55.4% vs 54.6%, P = 0.44). Conclusion Both the N1/N2 system and the LNR predict survival in colon cancer, but both have low specificity and sensitivity. The LNR does not provide additional prognostic value to current staging for overall or disease-specific survival for a given cut-off point. [ABSTRACT FROM AUTHOR]

Purpose We aimed to identify a combined prognostic factor for predicting better performance in risk stratification. Materials and Methods We reviewed the clinical and pathological variables of 316 patients with oral squamous cell carcinoma ( OSCC) who underwent surgery. To identify a combined predictor, principal component analysis ( PCA) was performed. Results Univariate analysis showed that the independent prognostic variables for overall survival ( OS) were pathologic T stage (T1 vs T4, HR = 1.99, 95% CI: = 1.083-3.675, P = 0.026) and pathologic N stage (N0 vs N2, HR=1.90, 95% CI: = 1.17-3.08, P = 0.008). In the multivariate analysis, only pathologic T stage was significant ( P = 0.006 and P = 0.007); however, the multivariate model was not significant ( P = 0.191). The multivariate model became significant by including lymph node ratio ( LNR) instead of pathologic N stage ( P = 0.0025 in numeric LNR, P = 0.0007 in categorized LNR). Also, the performance of prediction model was improved by a combined prognostic factor ( P = 0.0002). Conclusions The newly identified combined prognostic factor included resection margin, differentiation, and LNR, and they were insignificant factors independently except for LNR. This combined prognostic factor showed a good performance although it did not include molecular markers; therefore, it may be used conveniently for risk stratification of patients with OSCC by combining only clinical information. [ABSTRACT FROM AUTHOR]

Background: The metastatic lymph node (LN) ratio (LNR) has shown to be an important prognostic factor in various gastrointestinal malignancies. Nevertheless, the prognostic significance of LNR in gallbladder carcinoma (GBC) remains to be determined., Methods: From January 2007 to January 2018, 144 advanced GBC patients (T2-4 stages) who underwent curative surgery with at least 6 LNs retrieved were enrolled. Receiver operating characteristic (ROC) curve was performed to identify the optimal cut-off value for LNR. The clinicopathological features stratified by LNR level were analyzed. Meanwhile, univariate and multivariate Cox regression proportional hazard models were performed to identify risk factors for overall survival (OS)., Results: The optimal cut-off point for LNR was 0.28 according to the ROC curve. LNR>0.28 was associated with higher rate of D2 LN dissection (P=0.004) and higher tumor stages (P<0.001). Extent of liver resection, extrahepatic bile duct resection, tumor stage, LNR, margin status, tumor differentiation, and perineural invasion were associated with OS in univariate analysis (all P<0.05). GBC patients with LNR≤0.28 had a significantly longer median OS compared to those with LNR>0.28 (27.5 vs 18 months, P=0.004). Multivariate analysis indicated that tumor stage (T2 vs T3/T4; hazard ratio (HR) 1.596; 95% confidence interval (CI) 1.195-2.132), LNR (≤0.28 vs >0.28; HR 0.666; 95% CI 0.463-0.958), margin status (R0 vs R1; HR 1.828; 95% CI 1.148-2.910), and tumor differentiation (poorly vs well/moderately; HR 0.670; 95% CI 0.589-0.892) were independent prognostic factors for GBC (all P<0.05)., Conclusions: LNR is correlated to advanced GBC prognosis and is a potential prognostic factor for advanced GBC with at least 6 LNs retrieved., (© 2023. The Author(s).)

Background: The prognostic nutritional index (PNI), alkaline phosphatase (ALP), and lymph node ratio (LNR) are reportedly related to prognosis. The aim of this study was to elucidate the clinical importance of the LNR and hematological parameters in patients with high grade rectal neuroendocrine neoplasms (HG-RNENs) who were undergoing radical resection., Methods: We reviewed the medical records of patients with HG-RNENs from 17 large-scale medical centers in China (January 1, 2010-April 30, 2022). A nomogram was constructed by using a proportional hazard model. Bootstrap method was used to draw calibration plots to validate the reproducibility of the model. Concordance index (C-Index), decision curve analysis (DCA), and time-dependent area under the receiver operating characteristic curve (TD-AUC) analysis were used to compare the prognostic predictive power of the new model with American Joint Committee on Cancer (AJCC) TNM staging and European Neuroendocrine Tumor Society (ENETS) TNM staging., Results: A total of 85 patients with HG-RNENs were enrolled in this study. In the 45 patients with HG-RNENs who underwent radical resection, PNI ≤ 49.13 (HR: 3.997, 95% CI: 1.379-11.581, P = 0.011), ALP > 100.0 U/L (HR: 3.051, 95% CI: 1.011-9.205, P = 0.048), and LNR > 0.40 (HR: 6.639, 95% CI: 2.224-19.817, P = 0.0007) were independent predictors of relapse-free survival. The calibration plots suggested that the nomogram constructed based on the three aforementioned factors had good reproducibility. The novel nomogram revealed a C-index superior to AJCC TNM staging (0.782 vs 0.712) and ENETS TNM staging (0.782 vs 0.657). Also, the new model performed better compared to AJCC TNM staging and ENETS TNM staging in DCA and TD-AUC analyses., Conclusions: LNR, ALP, and PNI were independent prognostic factors in patients with HG-RNENs after radical resection, and the combined indicator had better predictive efficacy compared with AJCC TNM staging and ENETS TNM staging., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Introduction: Lymph node metastasis in patients with papillary thyroid carcinoma (PTC) is associated with postoperative recurrence. Recently, most studies have focused on the evaluation of recurrence in patients with late-stage PTC, with limited data on those with early-stage PTC. We aimed to assess the relationship between lymph node ratio (LNR) and recurrence in low-to-intermediate-risk patients and validate its diagnostic efficiency in both structural (STR) and biochemical recurrence (BIR)., Methods: Clinical data of patients with PTC diagnosed at the Affiliated Hospital of Jining Medical University were retrospectively collected. The optimal LNR cut-off values for disease-free survival (DFS) were determined using X-tile software. Predictors were validated using univariate and multivariate Cox regression analyses., Results: LNR had a higher diagnostic effectiveness than metastatic lymph nodes in patients with low-to-intermediate recurrence risk N1a PTC. The optimal LNR cutoff values for STR and BIR were 0.75 and 0.80, respectively. Multivariate Cox regression analysis showed that LNR≥0.75 and LNR≥0.80 were independent factors for STR and BIR, respectively. The 5-year DFS was 90.5% in the high LNR (≥0.75) and 96.8% in low LNR (<0.75) groups for STR. Regarding BIR, the 5-year DFS was 75.7% in the high LNR (≥0.80) and 86.9% in low LNR (<0.80) groups. The high and low LNR survival curves exhibited significant differences on the log-rank test., Conclusion: LNR was associated with recurrence in patients with low-to-intermediate recurrence risk N1a PTC. We recommend those with LNR≥0.75 require a comprehensive evaluation of lateral neck lymphadenopathy and consideration for lateral neck dissection and RAI treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ma, Cui, Shi, Liang, Song, Zhang, Wang and Shi.)

Background: The matter of postoperative radiotherapy (PORT) in esophageal cancer (ESCA) was far from conclusive. Some evidence indicated that lymph node status could affect treatment. We evaluated lymph node ratio (LNR) as an indicator that could be applied to predict PORT benefit., Methods: Retrospective cohort study collected the data of N1, N2, N3 stage ESCA patients from the Surveillance, Epidemiology, and End Results database (SEER) to analyze the association between LNR and prognosis from 2004 to 2015. Patients were categorized into two subsets based on the LNR cut-off value of 0.23 using receiver operating characteristic curve (ROC). Kaplan-Meier analysis was utilized to estimate the proportion of overall survival (OS) and esophagus cancer-specific survival (CSS) in two LNR groups. Cox regression analysis and competitive risk model was adopted to investigate the impacts of LNR on prognosis., Results: Of 2,165 ESCA patients identified, 1,165 (53.8%) had LNR>0.23. The LNR was an independent prognostic factor and associated with better OS and CSS of LNR≤0.23 (P < 0.001). In competitive risk model, a worse CSS was analyzed of LNR>0.23 (HR = 1.71; 95% CI 1.53-1.91). Subgroup analyses indicated that PORT was associated with favorable OS and CSS. Furthermore, when stratified by Node stage, PORT was associated with a survival benefit only in N1 stage with higher LNR (LNR>0.23) after adjusting for other covariates., Conclusions: LNR exceeding 0.23 was negatively associated with prognosis in ESCA. The survival benefit from PORT in ESCA seems to be limited to LNR of 23% or more only in N1 stage. This study highlights the biomarker meaning of LNR on identifying PORT beneficiary in N1 stage., Competing Interests: Declaration of competing interest All authors have completed the ICMJE uniform disclosure form. The authors have no conflicts of interest to declare., (Copyright © 2023 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)

Introduction: The aim of this study is to assess the impact of lymph node ratio (LNR) and number of positive lymph nodes (NPLN) on mortality and recurrence rates in patients with laryngeal squamous cell carcinoma., Materials and Methods: We conducted a retrospective multicenter international study involving 24 Otorhinolaryngology-Head and Neck Surgery divisions. Disease-specific survival (DSS) and disease-free survival (DFS) were evaluated as the main outcomes. The curves for DSS and DFS according to NPLN and LNR were analyzed to identify significant variations and establish specific cut-off values., Results: 2507 patients met the inclusion criteria. DSS and DFS were significantly different in the groups of patients stratified according to LNR and NPLN. The 5-year DSS and DFS based on LNR and NPLN demonstrated an improved ability to stratify patients when compared to pN staging., Conclusion: Our data demonstrate the potential prognostic value of NPLN and LNR in laryngeal squamous cell carcinoma., (© 2023 Wiley Periodicals LLC.)

Introduction: Lymph node (LN) metastases in papillary thyroid microcarcinomas (microPTCs) are common. The lymph node ratio (LNR) has been proposed as a risk factor for recurrence in papillary thyroid cancer. However, its relevance in microPTC is undetermined., Methods: Patients who underwent resection of their microPTC with concomitant LN clearance between 2005 and 2018 were identified. The LNR was calculated as the ratio of positive LNs to the total number of LNs., Results: Data on 50 patients (36 female [72%]; median age 47 years [range: 19-84]) who underwent LN clearance (28 central [56%] vs 22 central + lateral [44%]) were analysed. Positive LNs were found in over two-thirds of the patients ( n = 34; 68%). After a median follow-up of 61 months, 14 patients (28%) had developed recurrence. Positive LNs were not found to impact recurrence-free survival; extranodal extension and an LNR ≥ 0.26 were found to significantly increase the risk of recurrence on unadjusted analyses ( p < 0.05)., Conclusions: LN metastases are frequent among patients with microPTC. A higher LNR seems to be associated with recurrence. Additional studies are needed to further clarify these findings and to assess the possible role of LNR in treatment and surveillance.

Background Oral squamous cell carcinoma (OSCC) incidence and its mortality have increased recently. The oral part of the tongue is one of the commonest sites for OSCC. Apart from Tumour-Node-Metastasis (TNM) staging, lymph node ratio (LNR) has been implicated as one of the useful predictors for the better clinical outcome of the disease. The aim of the present study was to assess the LNR as a prognostic factor for patients having oral tongue squamous cell carcinoma (OTSCC). Materials and methods It is a retrospective study of 122 patients with OTSCC who were managed primarily by surgery with curative intent from January 2014 to December 2016. The mean lymph node ratio was measured and compared with various parameters of clinical outcome such as five-year overall survival (OS), five-year disease-free survival (DFS), locoregional failure (LRF) within three years, and distant metastasis (DM) within five years using Kruskal-Wallis Test followed by Mann-Whitney Post Hoc Test. The association of LNR with other tumor characteristic features like perineural invasion, extra-nodal extension (ENE), and histopathological grading was also elicited. Results The study population's mean age was 50.5 ± 11.77 years. Among them, 85 were males and 37 were females. On comparing the mean LNR value with patient status after primary treatment, the patients with minimal LNR value had statistically significant five-year OS and five-year DFS (p< 0.001). High mean LNR values were associated with other adverse features like perineural invasion and ENE, which were statistically significant (p<0.001). Receiver operator characteristics (ROC) curve analysis for the LNR parameter for determining the cut-off (0.02) between OS and DFS had 86% sensitivity and 40% specificity. Conclusion The LNR could be an important prognosis factor for OTSCC that helps in determining better clinical outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Sundaram et al.)

Background and Objectives : Small bowel adenocarcinomas (SBAs) are rare tumors of the gastrointestinal system. Lymph node metastasis in patients with curatively resected SBAs is associated with poor prognosis. In this study, we determined the prognostic utility of the number of removed lymph nodes and the metastatic lymph node ratio (the N ratio). Materials and Methods : The data of 97 patients who underwent curative SBA resection in nine hospitals of Turkey were retrospectively evaluated. Univariate and multivariate analyses of potentially prognostic factors including the N ratio and the numbers of regional lymph nodes removed were evaluated. Results : Univariate analysis showed that perineural and vascular invasion, metastatic lymph nodes, advanced TNM stage, and a high N ratio were significant predictors of poor survival. Multivariate analysis revealed that the N ratio was a significant independent predictor of disease-specific survival (DSS). The group with the lowest N ratio exhibited the longest disease-free survival (DFS) and DSS; these decreased significantly as the N ratio increased (both, p < 0.001). There was no significant difference in either DFS or DSS between groups with low and high numbers of dissected lymph nodes (i.e., <13 and ≥13) (both, p = 0.075). Conclusions : We found that the N ratio was independently prognostic of DSS in patients with radically resected SBAs. The N ratio is a convenient and accurate measure of the severity of lymph node metastasis.

Background: The prognostic significance of lymph node ratio (LNR) in N1b papillary thyroid cancer is unclear. Therefore, the impact of LNR on disease-specific mortality (DSM) and overall survival (OS) in patients with N1b papillary thyroid cancer (PTC) needs to be defined., Methods: We used the Surveillance, Epidemiology, and End Results (SEER) database of patients who had undergone thyroidectomy and lymph node dissection. Factors associated with DSM and OS were analyzed and identified using univariate and multivariate Cox proportional risk models. X-tile software was used to find the best cutoff value of LNR. Kaplan-Meier estimates for DSM were plotted for LNR and were compared with the log-rank test. The ROC curve evaluated the validity of the model., Results: A total of 3223 patients with N1b PTC were identified in the SEER database between 1975 and 2019. The best cutoff value for LNR was 0.6. The multivariate Cox proportional risk model showed that age, race, T3/T4 classification, distant metastasis, extent of surgery, number of metastatic lymph nodes, and LNR > 0.6 were independent risk factors for DSM (all p < 0.05). Age, sex, T4 classification, distant metastasis, extent of surgery, and LNR > 0.6 were independent risk factors for OS (all p < 0.05). The Kaplan-Meier method plotted a cumulative risk curve and showed that patients with LNR > 0.6 had a significantly higher risk of DSM than patients with LNR ≤ 0.6 (p = 0.002)., Conclusion: LNR was a powerful predictor of DSM and OS in N1b PTC patients. LNR could be a useful tool for the stratification of PTC patients with lateral neck metastases., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Tumor-node-metastasis (TNM) staging is the central gastric cancer (GC) staging system, but it has some disadvantages. However, the lymph node ratio (LNR) can be used regardless of the type of lymphadenectomy and is considered an important prognostic factor. This study aimed to evaluate the relationship between LNR and survival in patients who underwent curative GC surgery., Methods: All patients who underwent radical gastric surgery between January 2014 and June 2022 were retrospectively evaluated. Clinicopathological features of tumors, TNM stage, and survival rates were analyzed. LNR was defined as the ratio between metastatic lymph nodes and total lymph nodes removed. The LNR groups were classified as follows: LNR0 = 0, 0.01 < LNR1 ≤ 0.1, 0.1 < LNR2 ≤ 0.25 and LNR3 > 0.25. Tumor characteristics and overall survival (OS) of the patients were compared between LNR groups., Results: After exclusion, 333 patients were analyzed. The mean age was 62 ± 14 years. According to the LNR classification, no difference was found between groups regarding age and sex. However, TNM stage III disease was significantly more common in LNR3 patients. Most patients (43.2%, n = 144) were in the LNR3 group. In terms of tumor characteristics (lymphatic, vascular, and perineural invasion), the LNR3 group had significantly poorer prognostic factors. The Cox regression model defined LNR3, TNM stage II-III disease, and advanced age as independent risk factors for survival. Patients with LNR3 demonstrated the lowest 5-year OS rate (35.7%) (estimated mean survival was 30 ± 1.9 months) compared to LNR 0-1-2., Conclusion: Our study showed that a high LNR was significantly associated with poor OS in patients who underwent curative gastrectomy. LNR can be used as an independent prognostic predictor in GC patients., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: The study investigates the prognostic significance of lymph node ratio (LNR) on patients with head and neck squamous cell carcinoma (HNSCC) with coexistence of multiple adverse pathological features., Methods: In total, 100 patients with coexistence of perineural invasion, lymphovascular invasion, and extranodal extension of first primary HNSCC treated with radical surgery followed by adjuvant chemoradiotherapy were enrolled., Results: The optimal LNR cut-off value for predicting overall survival (OS) and cancer specific survival (CSS) was 7%. In Cox model, we observed that LNR ≥7% was a statistically significant unfavorable predictor of OS (HR: 2.689; 95% CI: 1.228-5.889; p = 0.013) and CSS (HR: 3.162; 95% CI: 1.234-8.102; p = 0.016)., Conclusion: For HNSCC patients with coexistence of multiple adverse pathological features, LNR is an independent survival predictor. Novel intensified treatments are needed for the subgroup of patients with a high LNR., (© 2023 Wiley Periodicals LLC.)

Background: Most of previous studies on predictive models for patients with small cell lung cancer (SCLC) were single institutional studies or showed relatively low Harrell concordance index (C-index) values. To build an optimal nomogram, we collected clinicopathological characteristics of SCLC patients from Surveillance, Epidemiology, and End Results (SEER) database., Methods: 24,055 samples with SCLC from 2010 to 2016 in the SEER database were analyzed. The samples were grouped into derivation cohort (n=20,075) and external validation cohort (n=3,980) based on America's different geographic regions. Cox regression analyses were used to construct nomograms predicting cancer-specific survival (CSS) and overall survival (OS) using derivation cohort. The nomograms were internally validated by bootstrapping technique and externally validated by calibration plots. C-index was computed to compare the accuracy and discrimination power of our nomograms with the 8th of version AJCC TNM staging system and nomograms built in previous studies. Decision curve analysis (DCA) was applied to explore whether the nomograms had better clinical efficiency than the 8th version of AJCC TNM staging system., Results: Age, sex, race, marital status, primary site, differentiation, T classification, N classification, M classification, surgical type, lymph node ratio, radiotherapy, and chemotherapy were chosen as predictors of CSS and OS for SCLC by stepwise multivariable regression and were put into the nomograms. Internal and external validations confirmed the nomograms were accurate in prediction. C-indexes of the nomograms were relatively satisfactory in derivation cohort (CSS: 0.761, OS: 0.761) and external validation cohort (CSS: 0.764, OS: 0.764). The accuracy of the nomograms was superior to that of nomograms built in previous studies. DCA showed the nomograms conferred better clinical efficiency than 8th version of TNM staging system., Conclusions: We developed practical nomograms for CSS (https://guowei2020.shinyapps.io/DynNom-CSS-SCLC/) and OS (https://drboidedwater.shinyapps.io/DynNom-OS-SCLC/) prediction of SCLC patients which may facilitate clinicians in individualized therapeutics., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liu, Zhang, Wang, Guo and Guo.)

Purpose: The Ki67 index and lymph node ratio (LNR) have been proposed as components of alternative pathological classification schemes, but the most appropriate classification for patients with medullary thyroid cancer (MTC) remains unknown. The aim of the present study was to examine the usefulness of a new grading system combining the Ki67 index and LNR as a predictor of prognostic and disease-free survival (DFS) in MTC., Methods: We conducted a retrospective study of patients with MTC who were registered at Sun Yat-sen University Cancer Center, Guangzhou, P. R. China from June 2003 to October 2021. The DFS rates were assessed using risk-adjusted Cox proportional hazard regression modeling to explore the relationship among pathological features, nutritional status and DFS. The Ki67 index (cutoff value: 5% and 10%) and LNR (cutoff value: 0.2 and 0.3) were combined to create a new grading system., Results: In total, 101 matched patients were assessed. The integrated grading system showed better separation of Kaplan Meier (KM) curves for DFS. As the grading stage progressed, there was a significant stepwise decrease in DFS, which was better than Ki67, LNR and N staging alone. According to the grading system, the high-risk group had a worse prognosis., Conclusion: The proposed grading scheme demonstrated a better prognostic performance in MTC patients than the Ki67, LNR and N staging alone. However, larger scale studies are needed to further verify our findings., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: To investigate the value of lymph node ratio (LNR) for postoperative major salivary duct carcinoma (MSDC) and to establish a model for prognosis assessment and treatment optimization., Methods: Data of MSDC were retrieved in public database, and prognostic factors were identified by univariate and multivariate analyses. A nomogram and risk stratification system were constructed., Results: Four hundred and eleven eligible patients were included (training cohort vs. validation cohort: 287: 124). LNR ≥0.09 was associated with worse overall survival (OS). Age at diagnosis, sex, T stage, and LNR were identified as prognostic factors and integrated into nomogram. Low-risk patients were found to have better OS than high-risk patients. Furthermore, postoperative radiotherapy (PORT) significantly improved OS in the high-risk subgroup, but chemotherapy did not confer a long-term survival benefit., Conclusions: A nomogram model integrating LNR could better assess postoperative prognosis and risk stratification in MSDC, and identify patients who might benefit from PORT to avoid overtreatment., (© 2023 Wiley Periodicals LLC.)