• endometrial cancer
• lymph node ratio
• meta‐analysis
• survival
• uterine cancer

• cadaver dissection
• lymph node dissection
• subpancreatic transverse colon vessel
• surgical anatomy
• transverse mesocolon

Background: Colorectal cancer (CRC) is one of the most prevalent malignant diseases worldwide. Risk prediction for tumor recurrence is important for making effective treatment decisions and for the survival outcomes of patients with CRC after surgery. Herein, we aimed to explore a prediction algorithm and the risk factors for postoperative tumor recurrence using a machine learning (ML) approach with standardized pathology reports for patients with stage II and III CRC. Methods: Pertinent clinicopathological features were compiled from medical records and standardized pathology reports of patients with stage II and III CRC. Four ML models based on logistic regression (LR), random forest (RF), classification and regression decision trees (CARTs), and support vector machine (SVM) were applied for the development of the prediction algorithm. The area under the curve (AUC) of the ML models was determined in order to compare the prediction accuracy. Genomic studies were performed using a panel-targeted next-generation sequencing approach. Results: A total of 1073 patients who received curative intent surgery at the National Cheng Kung University Hospital between January 2004 and January 2019 were included. Based on conventional statistical methods, chemotherapy (p = 0.003), endophytic tumor configuration (p = 0.008), TNM stage III disease (p < 0.001), pT4 (p < 0.001), pN2 (p < 0.001), increased numbers of lymph node metastases (p < 0.001), higher lymph node ratios (LNR) (p < 0.001), lymphovascular invasion (p < 0.001), perineural invasion (p < 0.001), tumor budding (p = 0.004), and neoadjuvant chemoradiotherapy (p = 0.025) were found to be correlated with the tumor recurrence of patients with stage II–III CRC. While comparing the performance of different ML models for predicting cancer recurrence, the AUCs for LR, RF, CART, and SVM were found to be 0.678, 0.639, 0.593, and 0.581, respectively. The LR model had a better accuracy value of 0.87 and a specificity value of 1 in the testing set. Two prognostic factors, age and LNR, were selected by multivariable analysis and the four ML models. In terms of age, older patients received fewer cycles of chemotherapy and radiotherapy (p < 0.001). Right-sided colon tumors (p = 0.002), larger tumor sizes (p = 0.008) and tumor volumes (p = 0.049), TNM stage II disease (p < 0.001), and advanced pT3–4 stage diseases (p = 0.04) were found to be correlated with the older age of patients. However, pN2 diseases (p = 0.005), lymph node metastasis number (p = 0.001), LNR (p = 0.004), perineural invasion (p = 0.018), and overall survival rate (p < 0.001) were found to be decreased in older patients. Furthermore, PIK3CA and DNMT3A mutations (p = 0.032 and 0.039, respectively) were more frequently found in older patients with stage II–III CRC compared to their younger counterparts. Conclusions: This study demonstrated that ML models have a comparable predictive power for determining cancer recurrence in patients with stage II–III CRC after surgery. Advanced age and high LNR were significant risk factors for cancer recurrence, as determined by ML algorithms and multivariable analyses. Distinctive genomic profiles may contribute to discrete clinical behaviors and survival outcomes between patients of different age groups. Studies incorporating complete molecular and genomic profiles in cancer prediction models are beneficial for patients with stage II–III CRC.

• colorectal cancer
• lymph-node ratio
• prognostic value
• resection length

Introduction: Lymph node status has become part of the new staging system for cervical cancer (CC). It has been shown that patients staged as IIIC1 had heterogeneous prognoses and, in some cases, experienced better outcomes than patients with lower stages. We evaluated the impact of the number of metastatic pelvic lymph nodes (MPLNs) among patients with stage IIIC1 cervical cancer. Methods: Survival analyses were conducted in order to identify the best cut-off prognostic value relative to the number of MPLNs. Disease free survival (DFS) was considered the main outcome. Results: 541 patients were included in the study. Eighty-nine patients were of stage IIIC1. The best prognostic cut-off value of the number of MPLNs was 2. Patients with >2 MPLNs (n > 2 group) had worse DFS compared with those having <2 (N1-2 group) (5 yr DFS: 54.7% vs. 78.1%, p value = 0.006). Multivariate analyses demonstrated that the extent of MPLNs had little impact on DFS and that replacement of IIIC1 staging with N1-2 and n > 2 grouping provided a better, statistically significant model (p value = 0.006). Discussion: Using a cut-off value of 2, the number of MPLNs could better predict prognostic outcomes within stage IIIC1 cervical cancer and have potential implications for therapeutic decision-making in the treatment of patients with stage IIIC1 CC.

• FIGO
• IIIC
• cervical cancer
• cut-off
• lymph node
• number of lymph nodes
• number of metastatic lymph nodes
• staging system

Background: The proportion of the number of involved lymph nodes (LNs) to the number of examined LNs—defined as metastatic LN ratio (mLNR)—has been considered as a prognostic parameter. This study aims to elucidate the prognostic implication of the mLNR in colorectal cancer (CRC) according to the tumor location. Methods: We evaluated the correlation between prognoses and the involved and examined LNs as well as mLNR according to the tumor location in 266 surgically resected human CRCs. Besides, to evaluate the optimal cutoff for high and low mLNRs, we investigated the correlation between mLNR and survival according to the various cutoffs. Results: LN metastasis was found in 146 cases (54.9%), and colon and rectal cancers were found in 116 (79.5%) and 30 (20.5%) of the cases, respectively. The mean mLNRs were significantly higher in rectal cancer than in colon cancer (0.38 ± 0.28 vs. 0.21 ± 0.24, P = 0.003). Besides this, the number of involved LNs in rectal cancer was significantly high compared to colon cancer (11.83 ± 10.92 vs. 6.37 ± 7.78, P = 0.014). However, there was no significant difference in the examined LNs between the rectal and colon cancers (31.90 ± 12.28 vs. 36.60 ± 18.11, P = 0.181). In colon cancer, a high mLNR was significantly correlated with worse survival for all cutoffs (0.1, 0.2, 0.3, and 0.4). However, rectal cancer only showed a significant correlation between high mLNR and worse survival in the subgroup with a cutoff of 0.2. Conclusions: Our results showed that high mLNR was significantly correlated with worse survival. The number of involved LNs and mLNRs were significantly higher in rectal cancer than in colon cancer. The cutoff of 0.2 can be useful for the differentiation of prognostic groups, regardless of tumor location.

• LN metastasis
• colorectal cancer
• metastatic lymph node ratio
• survival

• colorectal cancer
• meta-analysis
• metastatic lymph node ratio
• prognostic factor

• Colorectal Neoplasms/diagnosis
• Colorectal Neoplasms/physiopathology
• Disease-Free Survival
• Humans
• Lymph Node Ratio/methods
• Lymph Node Ratio/standards
• Lymph Nodes/abnormalities
• Lymphatic Metastasis/physiopathology
• Prognosis

• NRF-2017R1C1B5018063 National Research Foundation of Korea (NRF)

To analyze the survival trends in colorectal cancer (CRC) based on the different classifications recommended by the seventh and eighth editions of the American Joint Committee on Cancer staging system (AJCC-7^th and AJCC-8^th).

The database from our institution was queried to identify patients with pathologically confirmed stage 0-IV CRC diagnosed between 2006 and 2012. Data from 2080 cases were collected and 1090 cases were evaluated through standardized inclusion and exclusion criteria. CRC was staged by AJCC-7^th and then restaged by AJCC-8^th. Five-year disease-free survival (DFS) and overall survival (OS) were compared. SPSS 21.0 software was used for all data. DFS and OS were compared and analyzed by Kaplan-Meier and Log-rank test.

Linear regression and automatic linear regression showed lymph node positive functional equations by tumor-node-metastasis staging from AJCC-7^th and tumor-node-metastasis staging from AJCC-8^th. Neurological invasion, venous infiltration, lymphatic infiltration, and tumor deposition put forward stricter requirements for pathological examination in AJCC-8^th compared to AJCC-7^th. After re-analyzing our cohort with AJCC-8^th, the percentage of stage IVB cases decreased from 2.8% to 0.8%. As a result 2% of the cases were classified under the new IVC staging. DFS and OS was significantly shorter (P = 0.012) in stage IVC patients compared to stage IVB patients.

The addition of stage IVC in AJCC-8^th has shown that peritoneal metastasis has a worse prognosis than distant organ metastasis in our institution’s CRC cohort. Additional datasets should be analyzed to confirm these findings.

• Colorectal cancer
• Tumor-node-metastasis staging
• Prognosis
• Peritoneal metastasis
• Disease-free survival

• CRC
• LncRNA CHRF
• TWIST1/EMT
• metastasis
• miR-489

The lymph node ratio (LNR) (i.e. the number of metastatic lymph nodes divided by the number of totally resected lymph nodes) has recently emerged as an important prognostic factor in colorectal cancer (CRC). However, the tumor node metastasis (TNM) staging system for colorectal cancer does not consider it as a prognostic parameter. Therefore, we conducted a meta-analysis to evaluate the prognostic role of the LNR in node positive CRC. A systematic search was performed in PubMed, Embase and the Cochrane Library for relevant studies up to November 2015. As a result, a total of 75,838 node positive patients in 33 studies were included in this meta-analysis. Higher LNR was significantly associated with shorter overall survival (OS) (HR = 1.91; 95% CI 1.71–2.14; P = 0.0000) and disease free survival (DFS) (HR = 2.75; 95% CI: 2.14–3.53; P = 0.0000). Subgroup analysis showed similar results. Based on these results, LNR was an independent predictor of survival in colorectal cancer patients and should be considered as a parameter in future oncologic staging systems.

• colorectal cancer
• lymph node
• lymph node ratio
• meta-analysis
• prognostic role

Negative lymph node counts has recently attracted attention as a prognostic indicator in colorectal cancer (CRC). But little is known about prognostic significance of negative to positive lymph node ratio (NPR) in CRC. Our aim was to determine impact of NPR on oncological outcomes in patients with stage III CRC. This retrospective study included 2,256 patients with stage III CRC under curative resection at Fudan university Shanghai cancer center. Kaplan-Meier methods and multivariable Cox regression models were built for the analysis of survival outcomes and risk factors. Accuracy of the NPR was assessed with the Harrell's concordance-index(C-index).X-tile program identified 2.38 or 0.55/2.38 as the optimal cutoff value for NPR to divide the cohort into high/low risk or high/middle/low risk subsets in terms of CRC cause specific survival (CCSS). In a multivariate analysis, NPR was significant independent prognostic factors for CCSS (P<0.05), notably, N classification was not an independently prognostic factor (P>0.05). Further analysis found NPR could give detailed prognostic classification for both N1 and N2 stage (P<0.05). Interestingly, patients in N2+ NPR >2.38 stage have similar survival outcome with N1+ NPR >2.38 stage (χ2=0.030, P=0.863), and better than those at N1+ NPR ≤2.38 and N2+ NPR ≤2.38 stage (P<0.001). The TN_NPRM stage was more accurate for predicting CCSS (C-index = 0.659) than current TNM stage system(C-index = 0.628) (P<0.001). Collectively, NPR was an independent prognostic factor for stage III CRC patients, it could provide more accurate prognostic information than the current node stage system.

• colorectal cancer
• lymph node ratio
• prognosis analysis
• surgical resection

• colorectal cancer
• log odds of positive lymph nodes
• lymph node
• lymph node ratio
• survival

• Colonic neoplasms
• disease-free survival
• liver resection
• lymph nodes
• metastasis
• survival analysis

• Adult
• Aged
• Aged, 80 and over
• Colonic Neoplasms/pathology
• Female
• Hepatectomy
• Humans
• Liver/pathology
• Liver/surgery
• Liver Neoplasms/secondary
• Liver Neoplasms/surgery
• Lymph Node Excision
• Lymph Nodes/pathology
• Lymphatic Metastasis/pathology
• Male
• Middle Aged
• Multivariate Analysis
• Neoplasm Staging
• Prognosis
• Survival Analysis
• Sweden
• Treatment Outcome

Lymph node (LN) status after surgery for rectal cancer is affected by preoperative radiotherapy. The purpose of this study was to perform a population-based evaluation of the impact of pathologic LN status after neoadjuvant radiotherapy on survival. A total of 1,650 patients receiving neoadjuvant chemotherapy in Surveillance, Epidemiology, and End Results Program (SEER)-registered ypIII stage rectal cancer was analyzed. We identified the optimal cutoff for retrieved LNs as 10 (χ2 = 14.006, P < 0.001), which was validated as an independent prognosis factors in a Cox regression model. Further analysis showed that the LN count was only a prognosis factor with the number from 8 to 16(except for 13).After the number 16, the 5-year survival rate decreased gradually. Collectively, our results confirmed that the number of LNs in yp III stage rectal patients was a prognosis factor only with the numbers from 8 to 16(except for 13). Using the total mesorectal excision technique with an adequate pathologic examination, a large number of LNs retrieved (≥17) might indicate worse tumor response grade and poorer survival.

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Chemotherapy, Adjuvant
• Combined Modality Therapy
• Endometrial Neoplasms/mortality
• Endometrial Neoplasms/pathology
• Endometrial Neoplasms/therapy
• Female
• Follow-Up Studies
• Humans
• Lymph Node Excision
• Lymph Nodes/pathology
• Lymphatic Metastasis
• Middle Aged
• Neoplasm Grading
• Neoplasm Recurrence, Local/diagnosis
• Neoplasm Staging
• Prognosis
• Radiotherapy, Adjuvant/mortality
• Retrospective Studies
• Survival Rate

• K12 CA088084 NCI NIH HHS
• P30 CA016672 NCI NIH HHS
• CA016672 NCI NIH HHS

To examine the prognostic value of lymph node ratio (LNR) for patients with node-positive breast cancer with varying numbers of minimum nodes removed (>5, > 10 and > 15 total node count).

This study examined the original histopathological reports of 332 node-positive patients treated in the state of New South Wales (NSW), Australia between 1 April 1995 and 30 September 1995. The LNR was defined as the number of positive lymph nodes (LNs) over the total number of LNs removed. The LNR cutoffs were defined as low-risk, 0.01–0.20; intermediate-risk, 0.21– 0.65; and high-risk, LNR >0.65.

The median follow-up was 10.3 years. In multivariate analysis, LNR was an independent predictor of 10-year breast cancer specific survival when > 5 nodes were removed. However, LNR was not an independent predictor when > 15 nodes were removed. In a multivariate analysis the relative risk of death (RR) decreased from 2.20 to 1.05 for intermediate-risk LNR and from 3.07 to 2.64 for high-risk while P values increased from 0.027 to 0.957 for intermediate-risk LNR and 0.018 to 0.322 for high-risk with the number of nodes removed increasing from > 5 to > 15.

Although LNR is important for patients with low node denominators, for patients with macroscopic nodal metastases in several nodes following an axillary dissection who have more than 15 nodes dissected, the oncologist can be satisfied that prognosis, selection of adjuvant chemotherapy and radiotherapy fields can be based on the numerator of the positive nodes.

The online version of this article (doi:10.1186/s40064-015-0865-2) contains supplementary material, which is available to authorized users.

• Breast cancer specific survival
• Lymph node ratio
• Number of nodes removed
• pN stage

• LODDS
• colorectal cancer
• prognosis

• colon cancer
• prognosis
• rectal cancer

• Cervical cancer
• Lymph node ratio

• Adult
• Aged
• Analysis of Variance
• Disease-Free Survival
• Female
• Humans
• Hysterectomy
• Lymph Node Excision
• Lymph Nodes/pathology
• Lymph Nodes/surgery
• Lymphatic Metastasis
• Middle Aged
• Multivariate Analysis
• Neoplasm Staging
• Retrospective Studies
• Risk
• Survival Rate
• Uterine Cervical Neoplasms/pathology
• Uterine Cervical Neoplasms/surgery
• Young Adult

• K12 CA088084 NCI NIH HHS
• P30 CA016672 NCI NIH HHS
• CA016672 NCI NIH HHS

Colon cancer with lymph node metastases has been considered as advanced stage and to have poor survival. We postulated that patients with solitary lymph node metastasis are a distinct subset with better colon cancer-specific survival than those with multiple lymph node metastases.

In this retrospective study, we searched Surveillance, Epidemiology, and End-Results (SEER) population-based data and identified 86,674 patients who had been diagnosed with colon cancer without distant metastases and with less than three metastatic nodes between 1991 and 2005. We divided lymph node status into three subgroups: pN0, pN1a, and pN1b and obtained 5-year colon cancer-specific survival for each pT stage. We used Kaplan–Meier and multivariate Cox regression models to assess correlations between risk factors and survival outcomes.

Analysis of SEER data confirmed that patients with solitary lymph node metastases had better 5-year cancer-specific survival than pN1b according to both univariate and multivariate analysis. This finding was confirmed by further analyses in five pT subgroups. Cancer-specific survival of patients with pT1-2N1a was comparable to that of those with pIIA but higher than those with pIIB. In addition, survival of patients with pT3-4aN1a was better than those with pIIC.

Colon cancer patients with solitary lymph node metastasis are a distinct subset with a favorable prognosis; full consideration should be given to this in clinical practice.

KRAS gene mutations play an important role in the carcinogenesis of colorectal tumors. However, studies that have assessed the association between KRAS gene mutation status and disease characteristics report conflicting results. To assess KRAS gene status (mutated or wild-type) and its association with the clinical, epidemiological, and histopathological features of metastatic colorectal adenocarcinoma as well its association with clinical outcomes.

Cross-sectional descriptive study in which clinical and histopathological data were collected from the medical records of 65 patients diagnosed with metastatic colorectal adenocarcinoma at the Clinical Oncology Service of the Teaching Hospital of the School of Medicine of Ribeirao Preto, University of Sao Paulo (Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto, Universidade de Sao Paulo -HCFMRP-USP) between 2005 and 2012 and analyzed based on their KRAS gene status.

KRAS gene mutations were found in 49.2% of the tumors, and G/A (25.5%) and Gly12Asp (34.37%) were the most frequent mutations. Among the investigated clinical features (gender, ECOG (Eastern Cooperative Oncology Group), histology, degree of cell differentiation, lymph node ratio, primary tumor site, staging, presence of synchronous metastasis, lung metastasis, and liver metastasis), the association between age less than 65 years with KRAS mutation was statistically significant (P = 0.046). KRAS mutation status did not exhibit a significant correlation with the overall survival of the patients (P = 0.078); however, the cases with KRAS mutation exhibited shorter survival. In the multivariate analysis, synchronous metastasis (P = 0.03) and liver metastasis (P = 0.008) behaved as independent factors of poor prognosis relative to the overall survival of the patients.

The KRAS mutation status did not exhibit prognostic value in the investigated sample. Among the older patients (> 65 years old), wild-type KRAS was more frequently observed compared to mutated KRAS.

• Colon neoplasms
• Epidermal growth factor receptor
• Pronto-oncogene proteins p21 (ras)
• Survival analysis
• Tumor biological markers

• AIC
• AJCC
• AJCC Cancer Staging Manual, 6(th) edition
• AJCC Cancer Staging Manual, 7(th) edition
• AJCC-6
• AJCC-7
• Akaike information criterion
• American Joint Committee on Cancer
• CC
• DSS
• LN
• OS
• SEER
• Surveillance, Epidemiology and End Results
• colon cancer
• disease-specific survival
• lymph node
• overall survival

• Adult
• Aged
• Aged, 80 and over
• Colonic Neoplasms/mortality
• Colonic Neoplasms/pathology
• Female
• Humans
• Lymphatic Metastasis
• Male
• Middle Aged
• Neoplasm Staging
• Practice Guidelines as Topic
• Prognosis
• SEER Program
• Survival Analysis

• R01 CA090848 NCI NIH HHS

AIM: To develop a prognostic model to predict survival of patients with colorectal cancer (CRC).

METHODS: Survival data of 837 CRC patients undergoing surgery between 1996 and 2006 were collected and analyzed by univariate analysis and Cox proportional hazard regression model to reveal the prognostic factors for CRC. All data were recorded using a standard data form and analyzed using SPSS version 18.0 (SPSS, Chicago, IL, United States). Survival curves were calculated by the Kaplan-Meier method. The log rank test was used to assess differences in survival. Univariate hazard ratios and significant and independent predictors of disease-specific survival and were identified by Cox proportional hazard analysis. The stepwise procedure was set to a threshold of 0.05. Statistical significance was defined as P < 0.05.

RESULTS: The survival rate was 74% at 3 years and 68% at 5 years. The results of univariate analysis suggested age, preoperative obstruction, serum carcinoembryonic antigen level at diagnosis, status of resection, tumor size, histological grade, pathological type, lymphovascular invasion, invasion of adjacent organs, and tumor node metastasis (TNM) staging were positive prognostic factors (P < 0.05). Lymph node ratio (LNR) was also a strong prognostic factor in stage III CRC (P < 0.0001). We divided 341 stage III patients into three groups according to LNR values (LNR1, LNR ≤ 0.33, n = 211; LNR2, LNR 0.34-0.66, n = 76; and LNR3, LNR ≥ 0.67, n = 54). Univariate analysis showed a significant statistical difference in 3-year survival among these groups: LNR1, 73%; LNR2, 55%; and LNR3, 42% (P < 0.0001). The multivariate analysis results showed that histological grade, depth of bowel wall invasion, and number of metastatic lymph nodes were the most important prognostic factors for CRC if we did not consider the interaction of the TNM staging system (P < 0.05). When the TNM staging was taken into account, histological grade lost its statistical significance, while the specific TNM staging system showed a statistically significant difference (P < 0.0001).

CONCLUSION: The overall survival of CRC patients has improved between 1996 and 2006. LNR is a powerful factor for estimating the survival of stage III CRC patients.

• Colorectal cancer
• Prognostic factors
• Cox proportional hazard regression
• Lymph node ratio

• Adult
• Aged
• Aged, 80 and over
• Asian People
• China/epidemiology
• Colorectal Neoplasms/diagnosis
• Colorectal Neoplasms/ethnology
• Colorectal Neoplasms/mortality
• Colorectal Neoplasms/pathology
• Female
• Humans
• Kaplan-Meier Estimate
• Lymphatic Metastasis
• Male
• Middle Aged
• Multivariate Analysis
• Neoplasm Grading
• Neoplasm Invasiveness
• Neoplasm Staging
• Prognosis
• Proportional Hazards Models
• Risk Factors
• Survival Rate
• Time Factors
• Young Adult

• Aged
• Esophageal Neoplasms/mortality
• Esophageal Neoplasms/pathology
• Esophageal Neoplasms/surgery
• Female
• Humans
• Lymph Nodes/pathology
• Male
• Middle Aged
• Prognosis
• Retrospective Studies
• Survival Rate

• Adult
• Aged
• Aged, 80 and over
• Colonic Neoplasms/mortality
• Colonic Neoplasms/pathology
• Female
• Humans
• Lymph Nodes/pathology
• Lymphatic Metastasis
• Male
• Middle Aged
• Neoplasm Staging
• Prognosis
• SEER Program

The nodal stage of colorectal cancer is based on the number of positive nodes. It is inevitably affected by the number of removed lymph nodes, but lymph node ratio can be unaffected. We investigated the value of lymph node ratio in stage III colorectal cancer in this study. The clinicopathologic factors and follow-up data of 145 cases of stage III colorectal cancer between January 1998 and December 2008 were analyzed retrospectively. The Pearson and Spearman correlation analyses were used to determine the correlation coefficient, the Kaplan-Meier method was used to analyze survival, and the Cox proportional hazard regression model was used for multivariate analysis in forward stepwise regression. We found that lymph node ratio was not correlated with the number of removed lymph nodes (r = -0.154, P = 0.065), but it was positively correlated with the number of positive lymph nodes (r = 0.739, P < 0.001) and N stage (r = 0.695, P < 0.001). Kaplan-Meier survival analysis revealed that tumor configuration, intestinal obstruction, serum carcinoembryonic antigen (CEA) concentration, T stage, N stage, and lymph node ratio were associated with disease-free survival of patients with stage III colorectal cancer (P < 0.05). Multivariate analysis showed that serum CEA concentration, T stage, and lymph node ratio were prognostic factors for disease-free survival (P < 0.05), whereas N stage failed to achieve significance (P = 0.664). We confirmed that lymph node ratio was a prognostic factor in stage III colorectal cancer and had a better prognostic value than did N stage.