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Prognostic impact of histology on early-stage non-small cell lung cancer.

The purpose of this study is to evaluate the significance of histology as a predictor of recurrence after resection in early-stage non-small cell lung cancer patients.

METHODS: A total of 1870 consecutive stage I and II patients with adenocarcinoma or squamous cell carcinoma (SCC) who underwent complete tumor resection with systematic lymph node dissection between August 1992 and December 2007 were included.

RESULTS: In SCC, significantly more tumors exhibited stage IB or higher. Ever smokers were more common in patients with SCC, and more patients with SCC died from other diseases. In stage IA, a statistically significant difference in the 5-year recurrence-free probability was observed between adenocarcinoma and SCC (91.4% and 82.6%, respectively; p < 0.001), whereas no such difference was observed in stage IB (74.4% and 73.6%, respectively; p = 0.934). In stage II, the 5-year recurrence-free probability for adenocarcinoma was significantly lower than that for SCC (47% and 73%, respectively, p < 0.001). In stage IA, patients with predominantly bronchioloalveolar carcinoma subtype were more common compared to stage IB or higher in adenocarcinoma patients.

CONCLUSION: It is important to offset the prognostic impact of comorbidities associated with cigarette smoking because more patients with SCC died from other diseases. When evaluating its significance as a predictor of recurrence stratified by stage, histology showed different impact on postoperative recurrence within different substages. Histologic subtype distribution was different among substages in adenocarcinoma patients. Disease stages should be considered while evaluating histology as a predictor of recurrence.

Oral Vinorelbine and Cisplatin with Concurrent Radiotherapy After Induction Chemotherapy with Cisplatin and Docetaxel for Patients with Locally Advanced Non-small Cell Lung Cancer: The GFPC 05-03 Study.

The aim of this multicenter phase II trial was to evaluate the combination of oral vinorelbine and cisplatin with radiotherapy (RT) after cisplatin-docetaxel induction chemotherapy (CT) in patients with locally advanced non-small cell lung cancer (NSCLC).

PATIENTS AND METHODS:: Patients with previously untreated, inoperable, histologically or cytologically confirmed stage IIIA or IIIB NSCLC, with performance status ≤1 and weight loss ≤10% received two cycles of induction CT with cisplatin (75 mg/m) and docetaxel (75 mg/m) every 3 weeks. Patients with a tumor response or stabilization continued to receive cisplatin (80 mg/m) and oral vinorelbine (40 mg/m) on days 1 and 8 for two cycles, with concomitant thoracic RT (2 Gy/d, 5 d/wk, and total dose 66 Gy).

RESULTS:: Fifty-six patients were enrolled. All patients (n = 38) who received CT-RT were assessable for the tumor response. There were no complete responses. In the intent-to-treat analysis, the response rates were 32.1% after induction CT and 41.1% after CT-RT. The median progression-free and overall survival times were 9.2 months (95% confidence interval: 7-14) and 20.8 months (95% confidence interval: 13.7-24.1), respectively. Adverse effects of RT-CT were grades 3 to 4 neutropenia (four patients) and grade 3 esophageal toxicity (one patient). No treatment-related deaths occurred.

CONCLUSION:: The oral vinorelbine-cisplatin combination with concurrent RT is feasible and has a favorable risk-benefit ratio in stage IIIA/IIIB NSCLC.

The Role of Tumor-Infiltrating Immune Cells and Chronic Inflammation at the Tumor Site on Cancer Development, Progression, and Prognosis: Emphasis on Non-small Cell Lung Cancer.

In addition to malignant neoplastic cells, cancer tissues also include immune cells, fibroblasts, and endothelial cells, including an abundant collection of growth factors, proangiogenic mediators, cytokines, chemokines, and components of the extracellular matrix.

The main physiological function of the immune cells is to monitor tissue homeostasis, to protect against invading pathogens, and to eliminate transformed or damaged cells. Between immune cells and malignant cells in the tumor stroma, there is in fact a complex interaction which has significant prognostic relevance as the immune system has both tumor-promoting and -inhibiting roles. In non-small cell lung cancer (NSCLC), there is a marked infiltration of different types of immune cells, and the distribution, tissue localization, and cell types are significantly associated with progression and survival.

Cancer immunotherapy has seen a significant progress during the last decade. An increased understanding of the mechanisms by which lung cancer cells escape the immune system, and the recognition of the key tumor antigens and immune system components in tumor ignorance have led to the development of several lung cancer vaccines. As the NSCLC prognosis in general is dismal, one may hope that future immunotherapy may be an effective adjunct to standard therapy, reversing immunologic tolerance in the tumor microenvironment.

This review reports on the tumor stroma and in particular tumor-suppressing and -promoting roles of the immune system. Furthermore, it presents recent literature on relevant immune cell-related research in NSCLC.

Predictors and Impact of Second-Line Chemotherapy for Advanced Non-small Cell Lung Cancer in the United States: Real-World Considerations for Maintenance Therapy.

Recent clinical trials incorporating maintenance chemotherapy into the initial treatment of advanced non-small cell lung cancer (NSCLC) have highlighted the benefits of exposing patients to second-line therapies. We, therefore, determined the predictors and impact of second-line chemotherapy administration in a contemporary, diverse NSCLC population.

METHODS:: We performed a retrospective analysis of consecutive patients diagnosed with stage IV NSCLC from 2000 to 2007 at clinical facilities associated with the University of Texas Southwestern Medical Center. Demographic, disease, treatment, and outcome data were obtained from hospital tumor registries. The association between these variables was assessed using univariate analysis and multivariate logistic regression.

RESULTS:: A total of 406 patients in this cohort received first-line chemotherapy and were included in the analysis. Mean age was 59 years, 28% were women, and 59% were white. Among these patients, 197 (49%) received second-line chemotherapy. Among those patients who had not progressed after four to six cycles of first-line chemotherapy, 67% received second-line chemotherapy. Receipt of second-line chemotherapy was significantly associated with patient insurance type (p = 0.007), number of cycles of first-line chemotherapy (p < 0.001), and receipt of prechemotherapy palliative radiation therapy (p = 0.005) but was not associated with patient age, gender, race, histology, or year of diagnosis. In a multivariate model, second-line chemotherapy administration remained associated with insurance type (p = 0.003), number of cycles of first-line chemotherapy (p < 0.001), and receipt of prechemotherapy palliative radiation therapy (p = 0.008). The number of cycles of first-line chemotherapy and administration of second-line chemotherapy were associated with overall survival in both univariate and multivariate analyses.

CONCLUSIONS:: In this unselected, contemporary, and diverse cohort of patients with advanced NSCLC, 67% of individuals whose disease had not progressed after four to six cycles of first-line chemotherapy eventually received second-line chemotherapy. Markers of socioeconomic status, symptom burden, and response to and tolerance of first-line chemotherapy were associated with receipt of second-line chemotherapy. These factors may assist in the selection of patients most likely to benefit from maintenance chemotherapy.

Chemoradiation therapy in nonsmall cell lung cancer.

The majority of patients with nonsmall cell lung cancer (NSCLC) present with locally advanced mediastinal disease. Radiation therapy is the backbone, and nowadays a combination with chemotherapy is considered standard treatment. In this review we present a short history of the developments in this field with an update of all new developments. We address the questions how to optimally combine chemotherapy, targeted agents and radiation therapy.

RECENT FINDINGS: The results from recently published papers dealing with combined chemoradiotherapy (CRT) and the data of two meta-analyses are reviewed. Some drugs are very suitable candidates for CRT such as cisplatin, pemetrexed and etoposide, whereas others should be avoided or used with caution (adriamycin, gemcitabine).

SUMMARY: Our evaluation indicates that there are quite a number of positive developments in the treatment of locally advanced NSCLC but there is still much to improve. Variables such as patient condition, tumor biology, dose of radiation therapy, method of application (intensity modulated radiation therapy, four-dimensional planning) and dose of chemotherapy all influence treatment outcome and should be taken into account in designing the best treatment. Well-defined studies should be undertaken balancing the possible positive effect of therapy and toxicity.

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