Clinical response of large cell neuroendocrine carcinoma of the lung to perioperative adjuvant chemotherapy.

Patients with large cell neuroendocrine carcinoma (LCNEC) of the lung are considered to have poor prognosis. However, the benefit of adjuvant chemotherapy for these patients has not been established. In this study, we retrospectively evaluated the efficacy of perioperative chemotherapy for patients with completely resected LCNEC in a single-center setting. From 1999 through 2007, 45 patients with surgically resected LCNEC or mixed LCNEC containing at least one portion of the neuroendocrine differentiation or morphology in non-small cell lung carcinoma were enrolled as participants of this study. Survival rates were calculated by the Kaplan-Meier method. Differences between survival curves were computed with the log-rank test. For multivariate analysis, the Cox's proportional hazards regression model was used to evaluate variables that were significant predictors of survival. Of 1397 patients undergoing surgical resection for primary lung cancer from 1999 to 2007, 45 (3.2%) were classified as LCNEC. Thirty-six (80%) patients were men, and nine (20%) were women. Twenty-four (92%) of 26 patients were present or past smokers. Twenty-three (41%) of 45 patients received perioperative chemotherapy, including seven induction chemotherapies and 16 adjuvant chemotherapies. Survival of patients who underwent perioperative adjuvant chemotherapy was significantly higher than that of those who received surgery alone (P = 0.04). The 5-year survival rate of patients who underwent perioperative adjuvant chemotherapy was 87.5%, whereas that of patients who underwent surgery alone was 58.5%. Even in stage I cases, perioperative adjuvant chemotherapy still favors survival compared with surgery alone. In the Cox proportional hazard multivariate analysis, surgery with or without chemotherapy showed an independent prognostic influence on overall survival (P = 0.0457). Patients who received surgery alone were 9.5 times more likely to die than patients who underwent surgery plus chemotherapy. In conclusion, perioperative chemotherapy will be needed to improve survival in patients with LCNEC. As the population of LCNEC is small, it has been difficult to conduct randomized controlled trials to show the survival benefit of adjuvant chemotherapy. This should be, therefore, evaluated further in prospective multi-institutional phase II trials.

Significance of expression of TGF-beta in pulmonary metastasis in non-small cell lung cancer tissues.

Recent studies have evaluated the cytokine network involved in the local immune response to tumors. In addition to infiltrating inflammatory cells, tumors also produce cytokines and growth factors that may alter tumor growth and tumor immunogenicity. Ninety-one samples of NSCLC were used in this study. We measured the expression of VEGF, TNF-alpha, TGF-beta, IL-6, IL-8, IL-12, INF-gamma, and MCP-1 in NSCLC tissues, by ELISA. The expression of IL-6 and IL-8 were significantly higher in squamous cell carcinoma than in adenocarcinoma (p=0.016 and p<0.001, respectively). The expression of TGF-beta, MCP-1 and IL-8 were significantly higher in pulmonary metastasis positive than negative cases (p=0.002, p=0.001, and p=0.008, respectively). In multivariate logistic regression analysis, the expression of TGF-beta was an independent risk factor for the occurrence of pulmonary metastasis (p=0.008, 95% CI=1.002-1.011). We confirmed that tumor infiltrating stromal cells were major sources of TGF-beta by immunohistochemical analysis. The expression of VEGF and IL-8 were significantly higher in cases with central necrosis (p=0.006 and p=0.011, respectively). We speculated that TGF-beta expression in tumor infiltrating stromal cells may regulate the occurrence of spontaneous pulmonary metastasis in NSCLC. (Ann Thorac Cardiovasc Surg 2003; 9: 295-300)