Screening for oncogenic AF1q expression predicts disease recurrence in gastric cancer patients.

AF1q associates with tumor progression and metastases upon WNT signaling. The downstream WNT target CD44 has demonstrated prognostic significance in gastric cancer (GC). This study evaluates the impact of AF1q on tumor stage and survival in GC patients. Immunohistochemical marker expression was analyzed and data were processed to correlation and survival analysis. Out of 182 GC samples, 178 (97.8%) showed moderate to high AF1q expression (p < 0.001), these samples correlated with positive lymph node stage (p = 0.036). In a subgroup analysis of patients with nodal-positive GC (n = 129, 70.9%), enhanced tumoral AF1q expression resulted in impaired recurrence-free survival (RFS, p = 0.030). Enhanced tumoral CD44 expression resulted in impaired disease-specific survival (DSS) in the subgroup of patients with nodal-positive GC (p = 0.031) as well as in the overall GC group (p = 0.005). AF1q demonstrated as an independent prognostic marker for RFS (p = 0.035) and CD44 for DSS (p = 0.036). AF1q has shown potential for prognostication of RFS in GC patients and is predominantly expressed in nodal-positive GC. Testing AF1q provides a possibility of identifying patients with locoregional (and advanced) disease, particularly at risk for disease recurrence. Implementing AF1q into the diagnostic process may facilitate screening, prognosis estimation as well as consideration of preoperative multimodal treatment in patients qualifying for elective upfront surgery.

Comparison of the predictive performance of three lymph node staging systems for late-onset gastric cancer patients after surgery.

Introduction: Lymph node (LN) status is a vital prognostic factor for patients. However, there has been limited focus on predicting the prognosis of patients with late-onset gastric cancer (LOGC). This study aimed to investigate the predictive potential of the log odds of positive lymph nodes (LODDS), lymph node ratio (LNR), and pN stage in assessing the prognosis of patients diagnosed with LOGC. Methods: The LOGC data were obtained from the Surveillance, Epidemiology, and End Results database. This study evaluated and compared the predictive performance of three LN staging systems. Univariate and multivariate Cox regression analyses were carried out to identify prognostic factors for overall survival (OS). Three machine learning methods, namely, LASSO, XGBoost, and RF analyses, were subsequently used to identify the optimal LN staging system. A nomogram was built to predict the prognosis of patients with LOGC. The efficacy of the model was demonstrated through receiver operating characteristic (ROC) curve analysis and decision curve analysis. Results: A total of 4,743 patients with >16 removed lymph nodes were ultimately included in this investigation. Three LN staging systems demonstrated significant performance in predicting survival outcomes (P < 0.001). The LNR exhibited the most important prognostic ability, as evidenced by the use of three machine learning methods. Utilizing independent factors derived from multivariate Cox regression analysis, a nomogram for OS was constructed. Discussion: The calibration, C-index, and AUC revealed their excellent predictive performance. The LNR demonstrated a more powerful performance than other LN staging methods in LOGC patients after surgery. Our novel nomogram exhibited superior clinical feasibility and may assist in patient clinical decision-making.

A novel log odds of positive lymph nodes-based nomogram for predicting overall survival in patients with colorectal signet ring cell carcinoma: a SEER population-based study.

PURPOSE: Considering the poor prognosis and high lymph node (LN) involvement rate of colorectal signet ring cell carcinoma (SRCC), this study aimed to construct a prognostic nomogram to predict overall survival (OS) with satisfactory accuracy and utility, based on LN status indicators with superior predictability. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database, we obtained cases of colorectal SRCC patients and employed univariate and multivariate Cox analyses to determine independent prognostic factors. Kaplan-Meier curves were utilized to visualize survival differences among these factors. Receiver operating characteristic curves were generated to assess predictive performances of models incorporating various LN status indicators. A novel nomogram, containing optimal LN status indicators and other prognostic factors, was developed to predict OS, whose discriminatory ability and accuracy were evaluated using calibration curves and decision curve analysis. RESULTS: A total of 1663 SRCC patients were screened from SEER database. Older patients and those with grades III-IV, tumor sizes > 39 mm, T3/T4 stage, N1/N2 stage, M1 stage, and higher log odds of positive lymph nodes (LODDS) values exhibited poorer prognoses. Age, grade, tumor size, TNM stage, and LODDS were independent prognostic factors. The model containing N stage and LODDS outperformed the one relying solely on N stage as LN status indicator, resulting in a validated nomogram for accurately predicting OS in SRCC patients. CONCLUSION: The integration of LODDS, N stage, and other risk factors into a nomogram offered precise OS predictions, enhancing therapeutic decision-making and tailored follow-up management for colorectal SRCC patients.

Construction and validation of a nomogram based on the log odds of positive lymph nodes to predict cancer-specific survival in patients with small cell lung cancer after surgery.

Background: The lymph node ratio (LNR) is useful for predicting survival in patients with small cell lung cancer (SCLC). The present study compared the effectiveness of the N stage, number of positive LNs (NPLNs), LNR, and log odds of positive LNs (LODDS) to predict cancer-specific survival (CSS) in patients with SCLC. Materials and methods: 674 patients were screened using the Surveillance Epidemiology and End Results database. The Kaplan-Meier survival and receiver operating characteristic (ROC) curves were performed to address optimal estimation of the N stage, NPLNs, LNR, and LODDS to predict CSS. The optimal LN status group was incorporated into a nomogram to estimate CSS in SCLC patients. The ROC curve, decision curve analysis, and calibration plots were utilized to test the discriminatory ability and accuracy of this nomogram. Results: The LODDS model showed the highest accuracy compared to the N stage, NPLNs, and LNR in predicting CSS for SCLC patients. LODDS, age, sex, tumor size, and radiotherapy status were included in the nomogram. The results of calibration plots provided evidences of nice consistency. The ROC and DCA plots suggested a better discriminatory ability and clinical applicability of this nomogram than the 8th TNM and SEER staging systems. Conclusions: LODDS demonstrated a better predictive power than other LN schemes in SCLC patients after surgery. A novel LODDS-incorporating nomogram was built to predict CSS in SCLC patients after surgery, proving to be more precise than the 8th TNM and SEER staging.

Evaluation of the prognostic value of negative to positive lymph node ratio in gastric cancer: results from multi-institutional cohorts from western and eastern datasets - Cohort study.

Lymph node (LN) stage is important for prognosis evaluation of gastric cancer (GC) patients. This study aimed to evaluate the prognostic value of the ratio of negative to positive LNs (Rnp) in GC. Methods: The authors evaluated the clinical significance of the Rnp stage in 7660 GC patients from three high-volume institutions in China. Meanwhile, the authors verified the value of the Rnp stage in 11 234 GC patients from the Surveillance, Epidemiology, and End Results (SEER) database. Results: The patients were stratified into different subgroups based on the N stage of the eighth edition of the TNM staging system, the ratio of positive to detected LNs (Rpd) and Rnp. The survival analysis showed clear differences between the three LN stages in both the China and Surveillance, Epidemiology, and End Results cohorts. In univariate and multivariate analyses, the Rnp stage provided smaller Akaike information criterion or Bayesian information criterion values and a larger likelihood ratio χ2 than the N or Rpd stages in both two cohorts. For patients with inadequate examined LNs (<16), the Rnp stage showed better prognostic evaluation performance than the other two stages. In addition, the 5-year disease-specific survival of GC patients showed a slight variation with increasing LNs in the same subgroup classified by the Rnp or Rpd stages compared to the N stage. Conclusions: Along with the higher prognostic value, the Rnp stage has excellent universality with GC patients compared to the N or Rpd stages. Studies with larger sample sizes are needed to predict the prognosis and provide more precise treatment for GC patients.

Comparing the predictive performance of different lymph node staging systems for postoperative overall survival in patients with ampullary carcinoma.

Aim: This study was to analyze and compare the predictive performance of the 7th and the 8th edition American Joint Committee on Cancer (AJCC) N staging system, lymph nodes ratio (LNR) and log odds of positive lymph node (LODDS) for the survival of patients with ampullary carcinomas (ACs). Method: This retrospective cohort study included patients with primary ACs after surgery from the Surveillance, Epidemiology, and End Results (SEER) 2004-2015. Univariate and multivariate Cox proportional hazard models were used. The study population was divided into a training set and a testing set in a ratio of 7-3. The C-index and area under the curve (AUC) were used to compare the predictive performance of the four staging on overall survival (OS) in the training set and the testing set. Results: A total of 7,480 patients with primary ACs (1,178 survived and 1,128 dead) were in this study. The average follow-up time was 41.1 months. N1 stage and N2 stage of the 8th edition AJCC N staging system, LNR staging (0-0.3), LNR (>0.3), LODDS (-2.4 to -0.8) and LODDS (>-0.8) were associated with OS in AC patients after adjusting for age, race, pT stage, tumor size, grade, radiation, and insurance. The C-index of the 7th AJCC N staging was significantly lower than the C-index of the 8th AJCC N staging in the training set [0.608 vs. 0.629, P < 0.001] and testing set [0.635 vs. 0.658, P < 0.001]. The C-index of the LODDS staging was significantly higher than the C-index of the 8th AJCC N staging in the training set [0.641 vs. 0.629, P = 0.034] and testing set [0.671 vs. 0.658, P = 0.034]. LODDS staging may be a potential predictor of OS at 6 months [AUC = 0.687], 12 months (AUC = 0.692), and 48 months (AUC = 0.709), and LNR staging (AUC = 0.655) may be a potential predictor of OS at 24 months in AC patients. The predictive ability of LNR staging and LODDS staging were also found in different subgroups. Conclusion: The LNR and LODDS staging systems' predictive performance for OS of AC patients were superior to the 8th edition AJCC N staging system, especially in patients ages ≥65 or with higher tumor grade (grade II and III). The LNR staging and the LODDS staging were potential predictors for 24-month OS, and 6, 12, 24 and 48-month OS, respectively.

Lymph node ratio is superior to AJCC N stage for predicting recurrence in papillary thyroid carcinoma.

OBJECTIVE: Recently, lymph node ratio (LNR) has emerged as an alternative to American Joint Committee on Cancer (AJCC) N stage, with superior prognostic value. The utility of LNR in Middle Eastern papillary thyroid carcinoma (PTC) remains unknown. Therefore, we retrospectively analyzed a large cohort of 1407 PTC patients for clinicopathological associations of LNR. METHODS: Receiver operating characteristics (ROC) curve was used to determine the cut-off for LNR. We also performed multivariate logistic regression analysis to determine whether LNR or AJCC N stage was superior in predicting recurrence in PTC. RESULTS: Based on ROC curve analysis, a cut-off of 0.15 was chosen for LNR. High LNR was significantly associated with adverse clinicopathological characteristics such as male sex, extrathyroidal extension, lymphovascular invasion, multifocality, bilateral tumors, T4 tumors, lateral lymph node (N1b) involvement, distant metastasis, advanced tumor stage, American Thyroid Association (ATA) high-risk category and tumor recurrence. On multivariate analysis, we found that LNR was a better predictor of tumor recurrence than AJCC N stage (odds ratio: 1.96 vs 1.30; P value: 0.0184 vs 0.3831). We also found that LNR combined with TNM stage and ATA risk category improved the prediction of recurrence-free survival, compared to TNM stage or ATA risk category alone. CONCLUSIONS: The present study suggests LNR is an independent predictor of recurrence in Middle Eastern PTC. Integration of LNR with 8th edition AJCC TNM staging system and ATA risk stratification will improve the accuracy to predict recurrence in Middle Eastern PTC and help in tailoring treatment and surveillance strategies in these patients.

Comparison of Four Lymph Node Stage Methods for Predicting the Prognosis of Distal Cholangiocarcinoma Patients After Surgery.

BACKGROUND: The metastatic status of regional lymph nodes is an effective risk factor for the prognosis of distal cholangiocarcinoma (dCCA). But existing lymph node staging is not accurate enough and is susceptible to interference. This study aims to explore the predictive ability of the log odds of positive lymph nodes (LODDS) staging system of dCCA compared with existing lymph node staging systems. METHODS: A total of 928 dCCA patients were selected from the Surveillance, Epidemiology, and End Results (SEER) database as the training cohort, and 207 dCCA patients from West China Hospital who underwent surgery were reviewed as the validation cohort. The least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression were conducted to identify the most meaningful factors relevant to prognosis. The performance of four lymph node stage systems was compared by a model-based approach. RESULT: Age at diagnosis, pathological grade, American Joint Committee on Cancer (AJCC) tumor 7th T stage, tumor size, radiotherapy, chemotherapy, and lymph node stage system were independent prognostic factors. The model with the LODDS system had a better model fit with the highest C-index (0.679) and 1-/3-/5- area under the receiver operating characteristic curve (AUC) (0.739/0.671/0.658) as well as the lowest Akaike information criterion (AIC) (5,020.52). External validation results from 207 dCCA patients showed a C-index of 0.647 and 1-/3-/5-AUC of 0.740/0.683/0.589. Compared with the lymph node ratio (LNR), AJCC 8th N system, and 7th N system, the 5-year net reclassification improvement (NRI) of the LODDS system was 0.030 (95% CI: -0.079 to 0.147), 0.042 (95% CI: -0.062 to 0.139), and 0.040 (95% CI: -0.057 to 0.146), respectively. The integrated discrimination improvement (IDI) of LODDS improved compared with the LNR model (0.016; 95% CI: -0.001 to 0.036), AJCC 8th N system (0.020; 95% CI: 0.003-0.037), and AJCC 7th N system (0.019; 95% CI: 0.002-0.036). Decision curve analysis (DCA) also shows a greater net benefit of LODDS. In lymph node-negative patients, LODDS reveals a positive linear relationship with the hazard ratio (HR). The stage capacity of LODDS in a subgroup analysis stratified by examined lymph node number (ELNN) was consistent. CONCLUSIONS: The LODDS lymph node stage system has superior predictive performance as compared with the LNR, AJCC 7th, and 8th lymph node stage systems. Meanwhile, LODDS has a more detailed staging ability and good stability.

Combination of GP88 Expression in Tumor Cells and Tumor-Infiltrating Immune Cells Is an Independent Prognostic Factor for Bladder Cancer Patients.

Urothelial bladder cancer (BCa) is the ninth most commonly diagnosed cancer worldwide and accounts for approximately 3% of global cancer diagnoses. We are interested in prognostic markers that may characterize tumor cells (TCs) and immune cells (ICs) and their relationship in BCa. A potential candidate marker that meets these criteria is progranulin (GP88), which is expressed separately in TCs and ICs. We analyzed GP88 expression by immunohistochemistry (IHC) in 196 muscle-invasive BCa samples using a tissue microarray. The immunoreactive score for GP88 staining in TCs and the percentage of GP88-positive ICs was determined. An easy cutoff for the staining status of TCs (positive vs. negative) and ICs (0% vs. >0%) and, more generally, negative vs. positive GP88 staining could be applied. We detected 93 patients (47.4%) and 92 patients (46.9%) with GP88-positive TCs or ICs, respectively. The IHC results were correlated with clinicopathological and survival data. Positive GP88 staining in TCs appeared to be an independent poor prognostic factor for disease-specific survival (DSS) (RR (relative risk) = 1.74; p = 0.009) and recurrence-free survival (RFS) (RR = 1.92; p = 0.002). In contrast, negative GP88 staining in ICs was an independent negative predictor for overall survival (OS) (RR = 2.18; p < 0.001), DSS (RR = 2.84; p < 0.001) and RFS (RR = 2.91; p < 0.001) in multivariate Cox's regression analysis. When combining GP88 staining in TCs and ICs, a specific combination of GP88-positive TCs and GP88-negative ICs was associated with a 2.54-fold increased risk of death, a 4.21-fold increased risk of disease-specific death and a 4.81-fold increased risk of recurrence compared to GP88-negative TCs and GP88-positive ICs. In summary, GP88 positivity in TCs is a negative prognostic factor for DSS and RFS. In addition, GP88 positivity can mark ICs that are associated with a good prognosis (OS, DSS and RFS). The combination of GP88 staining in TCs and ICs appears to be a significant independent prognostic biomarker in muscle-invasive BCa.

Superiority of log odds of positive lymph nodes (LODDS) for prognostic prediction after gastric cancer surgery: a multi-institutional analysis of 7620 patients in China.

PURPOSE: To compare the 8th pN system with ratio-based and Log odds of positive lymph nodes (LODDS) staging systems for predicting the overall survival (OS) of gastric cancer (GC) patients after curative gastric resection. METHODS: We analyzed, retrospectively, clinicopathologic and prognostic data from three Chinese medical centers, on 7620 patients who underwent curative surgery for GC. We established a hypothetical tumor-LODDS-metastasis (TLM) and tumor-ratio-metastasis (TRM) staging system. The relative discriminative abilities of the different staging systems were assessed using Akaike's Information Criterion (AIC), a linear trend chi-square test, and a likelihood ratio chi-square test. RESULTS: The cut-off points of the LODDS were set as: ≤ - 1.5, - 1.5 to - 1.0, - 1.0 to - 0.5, - 0.5 to 0, and > 0. There were significant differences in the survival of patients in different LODDS classifications for each pN or LNR group. When stratified by the LODDS classification, the prognosis was more homologous according to the pN or lymph-node ratio (LNR) classifications. The modified TLM staging system had better discriminatory ability and better optimistic prognostic stratification than the 8th TNM or the TRM staging systems for predicting the prognosis of patients with GC. CONCLUSIONS: The LODDS staging system was superior to other lymph-node classifications for predicting the prognosis of patients undergoing gastrectomy GC. LODDS may be incorporated into a GC staging system if these results are confirmed by other studies.

Comparative study on metastatic lymph node radio and pathological lymph node stage in prognosis evaluation of patients with gastric cancer after radical resection / 中华内分泌外科杂志

Objective:To study the value of metastatic lymph node radio (rN) and pathological lymph node stage (pN) in evaluating the prognosis of patients after radical gastric cancer.Methods:The clinicopathological data of 491 patients who underwent radical gastrectomy in Tantai Yantaishan Hospital from Jan. 2013 to Dec. 2017 were retrospectively analyzed. X-tile software was used to group the metastatic lymph node radio by rN. According to the number of lymph node metastasis, pN stage was performed. The correlation between metastatic lymph node radio and other clinicopathological factors was assessed. The metastatic lymph node radio and the pathological lymph node stage in evaluating the prognosis of patients after radical gastric cancer were compared.Results:(1) X-tile analysis showed that the best cut-off values for the metastatic lymph node radio in this study were 0.14 (14%) and 0.63 (63%) . (2) According to the cut-off value, the 491 patients included in the study were divided into rN1 (256 cases) , rN2 (160 cases) , and rN3 (75 cases) three subgroups. The results of the analysis of differences showed that there were significant differencesbetween the groups in terms of tumor diameter, tumor location, surgical resection range, stage, lauren classification, degree of differentiation, pT, pN, vascular cancer emboulus, nerve invasion, and pathological TNM staging groups. (3) Comparison of rN and pN staging in evaluation of the prognosis of patients after radical gastric cancer: ①Kaplan-Meier survival analysis results showed that rN was better than pN. ② Both single factor and multivariate cox analysis showed that rN was an independent risk factor for the prognosis of gastric cancer. In univariate analysis, rN group HR=3.18 (95% CI 2.63-3.84, P<0.001) , pN stage HR=1.88 (95% CI 1.66-2.15, P<0.001) ; rN group HR=2.21 in multivariate analysis (95% CI 1.73-2.82, P<0.001) , pN staging HR=1.31 (95% CI 0.95-1.79, P=0.095) . ③The time-dependent ROC analysis showed that the prognostic ability of rN was better than pN staging before 52 months of postoperative follow-up, and pN staging was more advantageous after 52 months. ④The Lauren classification was used as a stratification factor for stratified analysis. The Kaplan-Meier survival curve indicated that rN was better than pN staging in intestinal, mixed and diffuse gastric cancer, and the AUC curve showed the prediction of rN in patients with mixed and diffuse gastric cancer was better than pN staging, while pN staging performance was slightly better in patients with intestinal gastric cancer. Conclusions:rN is an independent factor affecting the prognosis of patients after radical gastric cancer surgery. When judging the prognosis of patients within 52 months after radical gastric cancer, rN has a better prognostic value than pN. In patients with mixed and diffuse gastric cancer in the Lauren classification, rN shows better prognostic value.

The taxane-based chemotherapy triplet is superior to the doublet in one to nine node-positive but not node-negative triple-negative breast cancer: results from a retrospective analysis.

Background: Taxane-based regimens that are frequently used in adjuvant chemotherapy in early triple-negative breast cancer (TNBC) include a three-drug regimen (TAC and AC-T) and a two-drug regimen (TA and TC). Whether pathological lymph node stage guides taxane-based de-escalating chemotherapies in TNBC in adjuvant setting is still unclear. Methods: We retrospectively examined 381 patients with early TNBC over a median follow-up period of 75.9 months and compared the disease-free survival (DFS) and overall survival (OS) of patients who received adjuvant taxane-based three-drug chemotherapy and two-drug chemotherapy according to pathological lymph node stage (negative, pN0; 1-3 positive, pN1; 4-9 positive, pN2). Results: In 222 pN0 patients, the taxane-based three-drug regimen was not superior to the two-drug regimen. In 159 pN1-2 patients, the taxane-based three-drug regimen significantly improved DFS (5-year DFS rate, 78.2% vs. 46.9%; log-rank p=0.0002) and OS (5-year OS rate, 90.7% vs. 64.3%; log-rank p=0.0001) compared with the two-drug regimen. In a multivariable Cox regression analysis of pN1-2 patients, after adjustment for clinical characteristics, the taxane-based three-drug regimen significantly decreased the risk of recurrence (adjusted HR, 0.37; 95% CI, 0.22 to 0.64; p=0.0004) and death (adjusted HR, 0.22; 95% CI, 0.10 to 0.48; p=0.0001) compared with the two-drug regimen. Conclusions: The taxane-based chemotherapy triplet is superior to the chemotherapy doublet in patients with one to nine positive lymph nodes but not node-negative TNBC in adjuvant setting. These data suggest that pathological lymph node stage leads to de-escalating chemotherapy strategies in operable TNBC patients.

CCL2 Expression in Tumor Cells and Tumor-Infiltrating Immune Cells Shows Divergent Prognostic Potential for Bladder Cancer Patients Depending on Lymph Node Stage.

Bladder cancer (BCa) is the ninth most commonly diagnosed cancer worldwide. Although there are several well-established molecular and immunological classifications, markers for tumor cells and immune cells that are associated with prognosis are still needed. The chemokine CC motif ligand 2 (CCL2) could be such a marker. We analyzed the expression of CCL2 by immunohistochemistry (IHC) in 168 muscle invasive BCa samples using a tissue microarray. Application of a single cut-off for the staining status of tumor cells (TCs; positive vs. negative) and immune cells (ICs; ≤6% of ICs vs. >6% of ICs) revealed 57 cases (33.9%) and 70 cases (41.7%) with CCL2-positive TCs or ICs, respectively. IHC results were correlated with clinicopathological and survival data. Positive CCL2 staining in TCs was associated with shorter overall survival (OS), disease-specific survival (DSS), and relapse-free survival (RFS) (p = 0.004, p = 0.036, and p = 0.047; log rank test) and appeared to be an independent prognostic factor for OS (RR = 1.70; p = 0.007; multivariate Cox's regression analysis). In contrast, positive CCL2 staining in the ICs was associated with longer OS, DSS, and RFS (p = 0.032, p = 0.001, and p = 0.001; log rank test) and appeared to be an independent prognostic factor for DSS (RR = 1.77; p = 0.031; multivariate Cox's regression analysis). Most interestingly, after separating the patients according to their lymph node status (N0 vs. N1+2), CCL2 staining in the ICs was differentially associated with prognosis. In the N0 group, CCL2 positivity in the ICs was a positive independent prognostic factor for OS (RR = 1.99; p = 0.014), DSS (RR = 3.17; p = 0.002), and RFS (RR = 3.10; p = 0.002), whereas in the N1+2 group, CCL2 positivity was a negative independent factor for OS (RR = 3.44; p = 0.019)) and RFS (RR = 4.47; p = 0.010; all multivariate Cox's regression analyses). In summary, CCL2 positivity in TCs is a negative prognostic factor for OS, and CCL2 can mark ICs that are differentially associated with prognosis depending on the nodal stage of BCa patients. Therefore, CCL2 staining of TCs and ICs is suggested as a prognostic biomarker for BCa patients.

Benefits of postoperative thoracic radiotherapy for small cell lung cancer subdivided by lymph node stage: a systematic review and meta-analysis.

BACKGROUND: Whether postoperative thoracic radiotherapy (PORT) is beneficial for small cell lung cancer (SCLC) of different lymph node stages remains uncertain; therefore, the purpose of this meta-analysis was to explore the clinical significance of PORT for SCLC patients subdivided by lymph node status. METHODS: The PubMed, OVID, Web of SCI, EMBASE, Google Scholar, Cochrane Library, Chinese National Knowledge Infrastructure and Wanfang databases were systematically searched to identify eligible studies where SCLC patients received PORT based on lymph node stage. The main outcome measures were 1-, 3- and 5-year overall survival (OS) rates, as well as 1-, 2- and 3-year local regional recurrence (LRR) rates. All data were analyzed using STATA 12.0 and expressed as risk ratios (RR) with their corresponding 95% confidence intervals (95% CI). RESULTS: Five cohort studies, including 3,497 SCLC patients (578 receiving PORT and 2,919 not) were included in this study. PORT significantly decreased the 1-, 2- and 3-year LRR rates (RR =0.14, 0.28 and 0.27, respectively; Pall<0.05), but did not improve the 1-, 3- or 5-year OS rates when all patients were analyzed together. However, subgroup analysis showed that in the pN0 group PORT did not improve the 1-, 3- or 5-year OS rates or decrease the 1-, 2- or 3-year LRR rates; in the pN1 group PORT reduced the 1-, 2- and 3-year LRR rates (RR =0.11, 0.16 and 0.17, respectively; Pall<0.05) and improved the 1-year OS rate (RR =0.40; P<0.001), but not the 3- or 5-year OS rates; in the pN2 group PORT significantly reduced the 1-, 2- and 3-year LRR rates (RR =0.14, 0.15 and 0.15 respectively; Pall<0.05) and improved the 1-, 3- and 5-year OS rates (RR =0.46, 0.72 and 0.85, respectively; Pall<0.05). CONCLUSIONS: This is the first meta-analysis of the benefits of PORT for SCLC patients. Although derived from retrospective cohort studies, the data showed that PORT significantly reduced the risk of recurrence and improved survival for patients with pN2-SCLC; however, patients with pN0-SCLC did not benefit from PORT, whereas for patients with pN1-SCLC, PORT reduced the LRR rates and improved the 1-year survival rate. The long-term survival benefits of PORT remain unclear and will require further prospective studies.

Distinct features of distant metastasis and lymph node stage in lung adenocarcinoma patients with epidermal growth factor receptor gene mutations.

BACKGROUND: The influence of epidermal growth factor receptor (EGFR) mutation status on distant and lymph node metastasis is not fully understood. METHODS: Ninety-five consecutive patients with stage IV lung adenocarcinoma, who had been examined for the EGFR mutation status, were retrospectively analyzed with regard to numbers of distant metastasis and clinical stage of lymph node metastasis at the time of diagnosis. RESULTS: While EGFR mutation status did not influence the presence or absence of distant metastasis in the lung, brain, or liver, patients with EGFR mutations demonstrated a significantly greater number of metastatic lesions in the lung (median: 85 vs. 4, P=0.01) and the brain (11 vs. 3.5, P=0.04). On the other hand, patients with EGFR mutations showed a significantly lower lymph node staging (P<0.01). CONCLUSION: The presence of EGFR mutations in patients with lung adenocarcinoma correlates with lower lymph node stage and a greater number of metastatic lesions in the lung and brain.

Prognostic Factors for Serosal Invasive Gastric Cancer: Clinical Significance of Metastatic Lymph Node Ratio

PURPOSE: The important prognostic factors for gastric cancer are the depth of invasion by the primary tumor and the lymph node metastasis. The 5th edition of the Union Internationale Contrala Cancrums (UICC) TNM classification, which is based on the number of metastatic lymph nodes, has proved to be a reliable and objective method for predicting the prognosis of patients suffering with gastric cancer. However, its value for the prognosis of treating patients with serosal invasive (T3) gastric cancer, it is still being debated. So, we retrospectively studied the prognostic factors for T3 gastric cancer patients and we also evaluated the staging method according to the number of metastatic lymph nodes and the metastatic lymph node ratio. METHODS: This retrospective study was based on the medical records of 369 patients who underwent curative resection for serosal invasive (pT3) gastric cancer from 1992 to 2000. The patients were divided into four groups according to the number of metastatic lymph nodes and the clinicopathologic factors were evaluated by comparative study and the patients were then, classified into 4 groups by the metastatic lymph node ratio (0.5). We evaluated the prognostic factors and performed a survival analysis by using the Kaplan-Meier method and the Cox proportional hazard model. RESULTS: Among the four groups, the significant different factors were tumor size, the Borrmann type, the type of gastrectomy, the histologic type, and lymph node dissection. According to the univariate survival analysis, the tumor size, Borrmann type, lymph node stage, and the metastatic lymph node ratio significantly affected the prognosis. Yet, when comparing each survival rate, there was not significant difference between the pT3pN0 and pT3pN1 calassification. When we classified the metastatic lymph node ratio into 4 categories, each group then showed a significantly different survival rate. By conducting a multivariate analysis, only the metastatic lymph node ratio was an independent prognostic factor for serosal invasive gastric cancer (P=0.028). CONCLUSION: For evaluating patients with serosal invasive gastric cancer, there have been some problems with using the lymph node staging, so the metastatic lymph node ratio is a more reliable prognostic factor as it provides information about the extent of lymph node dissection and the degree of lymph node metastasis.