Zefen Xiao

Primary small cell carcinoma of the esophagus.

Introduction: Primary small cell esophageal carcinoma (SCEC) is a rare and aggressive disease for which there is no recommended standard treatment at this time. Methods: A total of 126 patients with SCEC, diagnosed histologically between May 1985 and June 2005 at our institution, were analyzed retrospectively. All were staged according to the Veterans’ Administration Lung Study Group staging system. The TNM system for esophageal carcinoma (6th edition, American Joint Committee on Cancer) was also used for those who underwent esophagectomies. SPSS (10.0) software was used for statistical analysis. Cox’s hazard regression model was performed to identify prognostic factors. The Kaplan-Meier and log-rank methods were used to estimate and compare survival rates. The &khgr;2 test was performed to examine frequencies between different groups. Results: Through a median follow-up of 13 months, 108 patients died, 10 were alive, and 8 were lost to follow-up. Of the entire study population, the overall median survival time (MST) and 1-, 3-, and 5-year overall survival rates were 12.5 months and 52.2%, 15.9%, and 12.2%, respectively. For limited disease, the MST and 1-, 2-, and 3-year overall survival rates were 14.0 months and 62.1%, 30.8%, and 22.4%, respectively; for extensive disease, the respective values were 7.0 months and 29.3%, 13.6%, and 2.7% (p = 0.0001). The MST of 14.5 months for cases who received chemotherapy was superior to that of 5.2 months for cases who did not (p = 0.0001). Tumor stage, length of the primary lesion, and chemotherapy, but not surgery were independent prognostic factors in a multivariate analysis. Conclusions: SCEC is systemic disease. Tumor stage and chemotherapy were independent prognostic factors. Systemic therapy, based on chemotherapy with radiotherapy, is recommended.

Postoperative Radiotherapy for Resected Pathological Stage IIIA–N2 Non-Small Cell Lung Cancer: A Retrospective Study of 221 Cases from a Single Institution

BACKGROUND For patients with resected pathological stage IIIA-N2 non-small cell lung cancer (NSCLC), the role of postoperative radiotherapy (PORT) is not well defined. In this single-institutional study, we re-evaluated the effect of PORT on overall survival (OS) as well as tumor control in this subgroup of patients. METHODS In 2003-2005, 221 consecutive patients with resected pathological stage IIIA-N2 NSCLC at our institution were retrospectively analyzed in an institutional review board-approved study. The effect of PORT on OS, cancer-specific survival (CSS), and disease-free survival (DFS) was evaluated using the Kaplan-Meier method and log-rank tests. The impact of PORT on locoregional control and distant metastasis was also analyzed. Results. Compared with the control, patients treated with PORT had a significantly longer OS time (χ2, 3.966; p = .046) and DFS interval (χ2, 6.891; p = .009), as well as a trend toward a longer CSS duration (χ2, 3.486; p = .062). Patients treated with PORT also had a significantly higher locoregional recurrence-free survival rate (χ2, 5.048; p = .025) as well as distant metastasis-free survival rate (χ2, 11.248; p = .001). Multivariate analyses showed that PORT was significantly associated with a longer OS duration (p = .000). CONCLUSIONS PORT can significantly improve the survival of patients with resected pathological stage IIIA-N2 NSCLC. A prospective randomized multicenter clinical trial is ongoing.

PTTG Overexpression Promotes Lymph Node Metastasis in Human Esophageal Squamous Cell Carcinoma

Human pituitary tumor transforming gene (PTTG) overexpression correlates with metastasis in multiple tumors, and yet its molecular mechanisms of action remain elusive. We detected PTTG overexpression in 66% (111 of 169) of primary esophageal squamous cell carcinoma (ESCC) tumor tissues by in situ hybridization. PTTG overexpression correlated with lymph node metastasis (P < 0.05). Ectopic PTTG overexpression in a representative ESCC cell line, EC9706, increased in vitro cell migration and invasion and promoted in vivo lymph node metastasis. Suppressing PTTG expression by siRNA decreased cell motility in both PTTG-HA/EC9706 and KYSE150 cells. By using mass spectrometric analysis, we identified that PTTG up-regulated S100A4 and galectin-1 secretion and down-regulated tissue inhibitor of metalloproteinase-2 secretion to the culture media. PTTG induced S100A4 and galectin-1 mRNA and protein expression as assessed by Western blot and reverse transcription-PCR. Attenuating galectin-1 expression by siRNA constrained PTTG-HA/EC9706 cell motility (P < 0.05). PTTG activated E-box transcription and induced c-Myc protein expression in EC9706 cells, which in turn may act on an E-box motif within the galectin-1 promoter. Chromatin immunoprecipitation assays further confirmed specific c-Myc binding to galectin-1 promoter. PTTG-induced galectin-1 transactivation and expression were mediated by c-Myc, and both inductions were suppressed by c-Myc RNAi cotranfection. These findings elucidate the molecular mechanisms of PTTG overexpression in promoting tumor metastasis, whereby up-regulated PTTG modulates expression and secretion of metastasis-related factors to facilitate cell motility.

Role of Adjuvant Radiotherapy for Stage II Thymoma After Complete Tumor Resection

PURPOSE To determine whether patients with Masaoka stage II thymoma benefit from adjuvant radiation therapy after complete tumor resection. METHODS AND MATERIALS A total of 107 patients with stage II thymoma who underwent complete resection of their tumors between September 1964 and October 2006 were retrospectively analyzed. Sixty-six patients were treated with adjuvant radiotherapy, and 41 patients received surgery alone. RESULTS Eight patients (7.5%) had a relapse of their disease, including two patients (4.5%) who had surgery alone, and 6 patients (9.5%) who had adjuvant radiation therapy. Disease-free survival rates at 5 and 10 years were 92.3% and 82.6%, respectively, for the surgery-plus-radiation group, and 97.6% and 93.1%, respectively, for the group that underwent surgery alone (p = 0.265). Disease-specific survival rates at 5 and 10 years were 96.4% and 89.3%, respectively, for the surgery-plus-radiation group and 97.5% and 97.5% for the surgery group (p = 0.973). On univariate analysis, patients with type B3 thymomas had the lowest disease-free survival rates among all subtypes (p = 0.001), and patients with large thymomas (>7 cm) had lower disease-specific survival rates than those with small tumors (<7 cm) (p = 0.017). On multivariate analysis, histological type (type B3) thymoma was a significant independent prognostic factor. CONCLUSIONS Adjuvant radiotherapy after complete tumor resection for patients with stage II thymoma did not significantly reduce recurrence rates or improve survival rates. Histological type (type B3) thymoma was a significant independent prognostic factor. Further investigation should be carried out using a multicenter randomized or controlled study.

Epidermal Growth Factor Receptor Is a Prognosis Predictor in Patients With Esophageal Squamous Cell Carcinoma

BACKGROUND Our previous study indicated the survival rate for esophageal squamous cell cancer (ESCC) patients in stage III and positive lymph node groups with postoperative radiation therapy was significantly increased compared with surgery alone. But a predictive biomarker was needed to identify the patients who would benefit from postoperative radiotherapy. This study aims to evaluate epidermal growth factor receptor (EGFR) as an indicator to predict the prognosis of ESCC and to identify the patients who would benefit from postoperative radiotherapy. METHODS Tissue samples were collected from our previous randomized study: 243 in the surgery alone group and 198 in the surgery plus radiotherapy group. Expression of EGFR was analyzed by immunohistochemical staining. RESULTS The expression of EGFR is correlated with depth of tumor invasion (p=0.005), lymph node metastasis (p<0.001), and pathologic stage (p<0.001). The survival rate of patients with high EGFR expression is significantly lower than that of patients with low EGFR expression (p=0.000). Notably, in stage IIA cases, the 5-year survival rate is 57.6% in the low EGFR expression group and 36.6% in the high expression group (p=0.020). EGFR is one of the independent variants that influence the prognosis. Moreover, for high EGFR expression patients the survival rate of the surgery plus radiotherapy group is higher than that of the surgery alone group (p=0.034). CONCLUSIONS Expression of EGFR can be a prognostic predictor for ESCC. Patients with high expression of EGFR may benefit from postoperative radiation therapy.

Etoposide and cisplatin versus paclitaxel and carboplatin with concurrent thoracic radiotherapy in unresectable stage III non-small cell lung cancer: a multicenter randomized phase III trial

Background The optimal chemotherapy regimen administered currently with radiation in patients with stage III non-small cell lung cancer (NSCLC) remains unclear. A multicenter phase III trial was conducted to compare the efficacy of concurrent thoracic radiation therapy with either etoposide/cisplatin (EP) or carboplatin/paclitaxel (PC) in patients with stage III NSCLC. Patients and methods Patients were randomly received 60–66 Gy of thoracic radiation therapy concurrent with either etoposide 50 mg/m2 on days 1–5 and cisplatin 50 mg/m2 on days 1 and 8 every 4 weeks for two cycles (EP arm), or paclitaxel 45 mg/m2 and carboplatin (AUC 2) on day 1 weekly (PC arm). The primary end point was overall survival (OS). The study was designed with 80% power to detect a 17% superiority in 3-year OS with a type I error rate of 0.05. Results A total of 200 patients were randomized and 191 patients were treated (95 in the EP arm and 96 in the PC arm). With a median follow-up time of 73 months, the 3-year OS was significantly higher in the EP arm than that of the PC arm. The estimated difference was 15.0% (95% CI 2.0%–28.0%) and P value of 0.024. Median survival times were 23.3 months in the EP arm and 20.7 months in the PC arm (log-rank test P = 0.095, HR 0.76, 95%CI 0.55–1.05). The incidence of Grade ≥2 radiation pneumonitis was higher in the PC arm (33.3% versus 18.9%, P = 0.036), while the incidence of Grade ≥3 esophagitis was higher in the EP arm (20.0% versus 6.3%, P = 0.009). Conclusion EP might be superior to weekly PC in terms of OS in the setting of concurrent chemoradiation for unresectable stage III NSCLC. Trial registration ID NCT01494558.

Expression of epidermal growth factor receptor is an independent prognostic factor for esophageal squamous cell carcinoma

BackgroundThe overall survival of patients with esophageal squamous cell carcinoma (ESCC) remains poor. Prognostic predictions in ESCC are usually based on histological assessment of tumor invasion and lymph node metastasis, but a biomarker with better predictive accuracy could be more useful. Because overexpression of epidermal growth factor receptor (EGFR) has been associated with poor prognosis, this study investigated whether EGFR is an independent prognostic factor for overall survival and disease-free survival of ESCC patients.MethodsESCC tissue specimens from 243 patients obtained during surgical resection between 1980 and 1997 were retrieved for immunohistochemical analysis of EGFR expression.ResultsThe data showed that EGFR protein was overexpressed in 187 of 243 (77%) ESCC tissues. Elevated expression was associated with higher pathologic tumor stages (P = 0.001), lymph node metastasis (P = 0.002), and higher Union for International Cancer Control (UICC) stage (P <0.0001), as well as poorer disease-free survival and overall survival of ESCC patients (P <0.0001). A multivariate analysis showed that overexpression of EGFR protein was an independent factor for disease-free survival (P = 0.003) and overall survival (P = 0.001) of these patients. Subgroup analysis of patients with stage IIA (UICC 2002) showed that EGFR overexpression was associated with poorer disease-free survival (P = 0.007) and overall survival (P = 0.010) of the patients in univariate analyses.ConclusionsThe current study demonstrated that EGFR overexpression was an independent prognostic factor for overall survival and disease-free survival of ESCC patients. However, targeting of EGFR activity using gefitinib or erlotinib could be useful for clinical treatment of ESCC patients.

Risk Factors for Brain Metastases in Locally Advanced Non-Small Cell Lung Cancer With Definitive Chest Radiation

PURPOSE We intended to identify risk factors that affect brain metastases (BM) in patients with locally advanced non-small cell lung cancer (LA-NSCLC) receiving definitive radiation therapy, which may guide the choice of selective prevention strategies. METHODS AND MATERIALS The characteristics of 346 patients with stage III NSCLC treated with thoracic radiation therapy from January 2008 to December 2010 in our institution were retrospectively reviewed. BM rates were analyzed by the Kaplan-Meier method. Multivariate Cox regression analysis was performed to determine independent risk factors for BM. RESULTS The median follow-up time was 48.3 months in surviving patients. A total of 74 patients (21.4%) experienced BM at the time of analysis, and for 40 (11.7%) of them, the brain was the first site of failure. The 1-year and 3-year brain metastasis rates were 15% and 28.1%, respectively. In univariate analysis, female sex, age ≤60 years, non-squamous cell carcinoma, T3-4, N3, >3 areas of lymph node metastasis, high lactate dehydrogenase and serum levels of tumor markers (CEA, NSE, CA125) before treatment were significantly associated with BM (P<.05). In multivariate analysis, age ≤60 years (P=.004, hazard ratio [HR] = 0.491), non-squamous cell carcinoma (P=.000, HR=3.726), NSE >18 ng/mL (P=.008, HR=1.968) and CA125 ≥ 35 U/mL (P=.002, HR=2.129) were independent risk factors for BM. For patients with 0, 1, 2, and 3 to 4 risk factors, the 3-year BM rates were 7.3%, 18.9%, 35.8%, and 70.3%, respectively (P<.001). CONCLUSIONS Age ≤60 years, non-squamous cell carcinoma, serum NSE >18 ng/mL, and CA125 ≥ 35 U/mL were independent risk factors for brain metastasis. The possibilities of selectively using prophylactic cranial irradiation in higher-risk patients with LA-NSCLC should be further explored in the future.

Selection of proper candidates with resected pathological stage IIIA-N2 non-small cell lung cancer for postoperative radiotherapy

To establish a prediction model in selecting fit patients with resected pIIIA‐N2 non‐small cell lung cancer (NSCLC) for postoperative radiotherapy (PORT), and evaluate the model in clinical practice.

Patterns and predictors of recurrence after radical resection of thymoma

BACKGROUND Recurrence of thymomas even after complete resection is common, but the relapse patterns remain controversial. This study aimed to define the patterns and predictors of relapse after complete resection of thymoma. METHODS A single-institution retrospective study was performed with 331 patients who underwent radical resection of thymoma between 1991 and 2012. RESULTS After a median follow-up of 59 months, the recurrence rate was 6.9% (23/331). Relapse occurred in 23 patients with the pleura (14) and tumor bed (6) as the most common sites of recurrence. According to the definitions of the International Thymic Malignancy Interest Group, 10 (43.5%) patients had local relapse, 15 (65.2%) had regional relapse, 10 (43.5%) had distant relapse. The difference in survival following relapse between lung and regional relapse was statistically significant (P=0.027) but that between lung and distant relapse was not (P=0.808). The recurrence rates correlated with the initial Masaoka stage. Further, recurrence also correlated with World Health Organization (WHO) tumor type. The recurrence-free survival rates in patients with tumor size ⩾8 cm were worse than those of patients with tumor size <8 cm (P=0.007). Tumor size was also correlated with stage (r=0.110). As tumor becomes larger, the stage is more advanced (P=0.023). Multivariate analysis showed that Masaoka stage (P=0.005), tumor size (P=0.033), and WHO histological type (P=0.046) were predictive factors of relapse. CONCLUSION Regional recurrence is the most common relapse pattern but local and distant relapse are also common. Advanced Masaoka stage, larger tumor size, and type B3 are risk factors of recurrence. Lung relapse should be considered distant relapse. Further, tumor size was correlated with Masaoka stage and therefore should be considered in the staging system.