Tiehua Rong

Three Immunomarker Support Vector Machines-Based Prognostic Classifiers for Stage IB Non-Small-Cell Lung Cancer

PURPOSE Approximately 30% of patients with stage IB non-small-cell lung cancer (NSCLC) die within 5 years after surgery. Current staging methods are inadequate for predicting the prognosis of this particular subgroup. This study identifies prognostic markers for NSCLC. PATIENTS AND METHODS We used computer-generated random numbers to study 148 paraffin-embedded specimens for immunohistochemical analysis. We studied gene expression in paraffin-embedded specimens of lung cancer tissue from 73 randomly selected patients with stage IB NSCLC who had undergone radical surgical resection and evaluated the association between the level of expression and survival. We used support vector machines (SVM)-based methods to develop three immunomarker-SVM-based prognostic classifiers for stage IB NSCLC. For validation, we used randomly assigned specimens from 75 other patients. RESULTS We devised three immunomarker-SVM-based prognostic classifiers, including SVM1, SVM2, and SVM3, to refine prognosis of stage IB NSCLC successfully. The SVM1 model integrates age, cancer cell type, and five markers, including CD34MVD, EMA, p21ras, p21WAF1, and tissue inhibitors of metalloproteinases (TIMP) -2. The SVM2 model integrates age, cancer cell type, and 19 markers, including BCL2, caspase-9, CD34MVD, low-molecular-weight cytokeratin, high-molecular-weight cytokeratin, cyclo-oxygenase-2, EMA, HER2, matrix metalloproteinases (MMP) -2, MMP-9, p16, p21ras, p21WAF1, p27kip1, p53, TIMP-1, TIMP-2, vascular endothelial growth factor (VEGF), and beta-catenin. The SVM3 model consists of SVM1 and SVM2. The three models were independent predictors of overall survival. We validated the classifiers with data from an independent cohort of 75 patients with stage IB NSCLC. CONCLUSION The three immunomarker-SVM-based prognostic characteristics are closely associated with overall survival among patients with stage IB NSCLC.

Primary pulmonary lymphoepithelioma-like carcinoma: fifty-two patients with long-term follow-up.

Pulmonary lymphoepithelioma‐like carcinoma (LELC) is a rare kind of cancer.

Overexpression of cyclooxygenase-2 is associated with chemoradiotherapy resistance and prognosis in esophageal squamous cell carcinoma patients

Our objective was to investigate whether cyclooxygenase-2 (COX-2) expression can predict the patients response to chemoradiotherapy (CRT) and ensuing prognosis in esophageal squamous cell carcinoma (ESCC). The clinicopathological and follow-up data of 112 patients with ESCC who underwent CRT from January 2001 to June 2006 were analyzed retrospectively. The immunohistochemical expression level of COX-2 was examined for all biopsy specimens of primary tumors, and the correlation of COX-2 expression with the patients response to CRT and prognosis was examined. COX-2 positive immunostaining was detected in 111 (99.1%) of the patients, including overexpression in 54 (48.2%) patients and low expression in 58 (51.8%) of the patients. The response of tumors with a low level expression of COX-2 (70.7%, 41/58) was significantly higher than that of tumors with COX-2 overexpression (42.6%, 23/54; P = 0.003). Patients with a low level of COX-2 expression had a higher downstaged rate than those with a high level of COX-2 expression (9/13 vs 2/8), but the difference was not statistically significant (P = 0.08). In the definitive CRT group (91 cases), COX-2 overexpression was significantly associated with poor 3-year overall survival (P = 0.028). Multivariate analysis showed that only metastatic stage (nonregional node metastasis) was an independent prognosis factor. The assessment of COX-2 status may provide additional information to identify ESCC patients with poor chances of response to CRT and potential candidates for more individualized treatment.

Outcome of elderly patients with oesophageal squamous cell carcinoma after surgery

Oesophagectomy may have morbidity and mortality rates that severely compromise long‐term survival in elderly patients. The aim of this study was to compare clinical outcomes in elderly patients with oesophageal squamous cell carcinoma (SCC) with those of younger controls.

Characteristics and Prognostic Analysis of 69 Patients With Pulmonary Sarcomatoid Carcinoma.

Background:Pulmonary sarcomatoid carcinoma (PSC) is a rare malignancy. Methods:A total of 69 patients with PSC treated at a single institution in southern China with long-term follow-up were evaluated in this study. We analyzed the clinical characteristics, immunohistochemical profiles, epidermal growth factor receptor mutation status, K-RAS mutation status, treatments, and prognosis. Results:PSC mainly occurred in young male patients with a history of smoking. Most patients received multimodality treatments and the majority had early-stage disease. The median survival time was 19.1 months, and the 5-year survival rate was 17.4%. The patients without distant metastasis, with normal or higher body mass index (≥18.5), with normal hemoglobin, with smaller tumor size (⩽4 cm), and those who received complete resection had significantly better overall survival (P<0.05). The patients with pleomorphic carcinoma had much worse prognosis. In a Cox regression model, M stage, pathology, and having received a complete resection were independent prognostic factors (P<0.05). Conclusions:PSC is a unique lung malignancy with poor prognosis. Patients receiving complete resection had better prognosis, likely a reflection of early-stage disease. Neither neoadjuvant nor adjuvant chemotherapy improved patient survival for those with early-stage disease. The retrospective design and small sample size limited the generalizability. Future multicenter collaborations may be necessary to determine the optimal treatment.

Can Lymph Node Ratio Replace pN Categories in the Tumor-Node-Metastasis Classification System for Esophageal Cancer?

Background: We evaluated the prognostic value of lymph node ratio (LNR) in esophageal squamous cell carcinoma (ESCC) patients after tri-incisional esophagectomy by making comparisons with pN categories in the UICC/AJCC (International Union Against Cancer/American Joint Committee on Cancer) classification system (seventh edition). Methods: Seven hundred ESCC patients underwent tri-incisional esophagectomy at our center (1988–2008) without neoadjuvant therapy. The adjusted X-tile cutoff values for LNR of 0 and 0.25 were compared with those in UICC/AJCC pN categories. Results: Univariate and multivariate analyses identified LNR as a significant prognostic factor regardless of the number of retrieved LNs. Spearman’s correlation analysis showed close linear correlations between the number of examined and metastatic LNs (r = 0.205, p < 0.001), but not between the number of examined LNs and LNR (r = 0.058, p = 0.123). Significant prognostic differences were seen among LNR categories in all pT categories (p < 0.05), but not in pN categories stratified by tumor status (except T3: p < 0.001). Significant prognostic difference was seen among LNR categories in all pN categories (p < 0.05), but not between pN categories in all LNR categories (p > 0.05). Significant differences in 5-year cancer-specific survival rates were found among retrieved-node groups in the same pN category (except N2+3: p = 0.733), but not within the same LNR category (except N0: p < 0.001). Conclusions: LNR is an independent prognostic factor after tri-incisional esophagectomy, regardless of the number of retrieved LNs. In ESCC, LNR might reduce stage migration, have more potential for predicting patient outcomes, and compensate for deficiencies in UICC/AJCC pN categories.

Identification and Validation of Lymphovascular Invasion as a Prognostic and Staging Factor in Node-Negative Esophageal Squamous Cell Carcinoma

Introduction: Lymphovascular invasion (LVI) is a histopathological feature that is associated with an increased risk for micrometastasis. The aim of this study was to determine the prognostic and staging value of LVI among patients with esophageal squamous cell carcinoma (ESCC) undergoing esophagectomy. Methods: A prospective database of patients with ESCC was used to retrospectively analyze 666 cases to identify the relationship between LVI and survival, and to evaluate predictive accuracy of prognosis after combining LVI and the tumor, node, and metastasis (TNM) system. Pathological slides were reassessed by gastrointestinal pathologists according to the strict criteria; 1000‐bootstrap resampling was used for internal validation, and 222 cases from an independent multicenter database were used for external validation. Results: LVI was present in 33.8% of patients, and the proportion increased with advancing T and N classification. LVI was an independent predictor of unfavorable disease‐specific survival (DSS) (hazard ratio = 1.59, 95% confidence interval: 1.30–1.94) and disease‐free survival (DFS) (hazard ratio = 1.62, 95% confidence interval: 1.32–1.98) after T classification. Among node‐negative patients, LVI and T classification were two independent predictors of DSS and DFS (p < 0.001). The risk score model combing LVI and T classification improved the predictive accuracy of the TNM system for DSS and DFS by 3.5% and 4.8%, respectively (p < 0.001). The external validation showed congruent results. The DSS of TxN0MO disease with LVI was similar to the DSS of TxN1M0 (both p > 0.05). In contrast, LVI was not associated with DSS or DFS among node‐positive patients. Conclusions: The independent prognostic significance of LVI existed only in node‐negative patients with ESCC, and the combination of LVI and the TNM system enhanced the predictive accuracy of prognosis. After confirmation, node‐negative patients with LVI might be considered for upstaging in pathological staging.

Stage migration and therapy modification after thoracoscopic internal mammary lymph node dissection in breast cancer patients

Although internal mammary lymph node (IMN) status is a major prognostic factor in breast cancer, it is not routinely assessed. To evaluate the impact of IMN status on staging and treatment of breast cancer, we enrolled 50 consecutive patients with inner or central tumors who received IMN dissection by video-assisted thoracoscopic surgery (VATS) after breast surgery. Of the 50 patients, 20 (40%) had IMN metastases. Of the 20 patients, 6 (12%) were upstaged from N0 to N2b and 5 (10%), 3 (6%) and 6 patients (12%) were upstaged from N1a, N2a, and N3a, respectively, to N3b. Because of the upstaging, 6 patients (12%) with only IMN metastases received more aggressive adjuvant chemotherapy. Because the whole IMN chain was removed in all patients, radiotherapy on IMN field was not required in our cohort independent of IMN status. In conclusion, VATS IMN dissection might lead to stage migration and therapy modification.

Do tumor location and grade affect survival in pT2N0M0 esophageal squamous cell carcinoma

BACKGROUND The TNM staging system for esophageal cancer in the seventh edition of the AJCC Cancer Staging Manual incorporates tumor grade and location for staging pT2-3N0M0 esophageal squamous cell carcinoma. Patients with pT2N0M0, classified as stage IIA according to the sixth edition of the AJCC Cancer Staging Manual, can now be classified as stage IB, IIA, or IIB. We discuss whether these changes lead to a better prediction of the prognosis of these patients and aimed to find out other factors to forecast patient prognosis. METHODS We retrospectively analyzed 317 patients with postoperative pathologic stage T2N0M0 who underwent esophagectomy between 1990 and 2005 at Sun Yat-sen University Cancer Center. We performed univariate and multivariate analyses to identify prognostic factors for survival and used the Kaplan-Meier method to demonstrate the prognostic efficacy of each prognostic factor, including tumor grade and location. RESULTS The 5-year overall survival was 57%, with a median survival of 84.5 months (6.94 years). Univariate analysis indicated that age, alcohol consumption, and tumor grade were associated with survival. Multivariate Cox proportional hazard regression analysis revealed that alcohol consumption and tumor grade were independent prognostic factors. Survival analysis using the Kaplan-Meier method demonstrated age, cigarette smoking, alcohol consumption, tumor grade, and location as prognostic factors. CONCLUSIONS For pT2N0M0 esophageal squamous cell carcinoma, the seventh edition of the AJCC Cancer Staging Manual does not provide a more distinguishable prediction of prognosis compared with the sixth edition. Tumor grade is an independent prognostic factor in patients with pT2N0M0 esophageal squamous cell carcinoma, whereas tumor location is not. Furthermore, alcohol consumption is an independent prognostic factor that may imply a worse prognosis.

Mediastinal Lymph Node Dissection Affects Survival in Patients with Stage I Non-Small Cell Lung Cancer

BACKGROUND The therapeutic value of mediastinal lymph node dissection (LND) for early-stage non-small cell lung cancer (NSCLC) remains controversial. We conducted a retrospective study to investigate the impact of mediastinal LND on survival in patients with stage I NSCLC. METHODS Clinical data of patients with stage I NSCLC who were treated with surgical resection during a period of ten years were reviewed. The patients were categorized into lobectomy (or pneumonectomy) combined with mediastinal LND or lymph node sampling (LNS) according to the record of their operative procedures. The Kaplan-Meier method was used for survival analysis. Cox proportional hazards model was used for multivariate analysis. RESULTS Of the 319 patients who were included in the study, 139 patients received mediastinal LND, while 180 underwent LNS. There was a significant difference in overall survival (OS) between the group with LND and the group with LNS (5-year survival rate: 76.4 % vs. 65.9 %, P = 0.015 by log rank test). Multivariate analysis showed that lymph node dissection (RR = 0.548, 95 %CI: 0.350 - 0.858, P = 0.009), together with the stage, significantly influenced overall survival. CONCLUSIONS Lobectomy combined with mediastinal LND can improve survival in patients with stage I NSCLC. It should be performed in all patients with clinical stage I NSCLC.