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For patients with early (stage I/II) non-small cell lung cancer (NSCLC) surgery is considered as the standard treatment of choice, although recent data on additional chemotherapy (CHT) showed that it may be beneficial in this setting. There is, however, a subset of patients that never undergo surgery. These patients are considered technically operable, but medically inoperable, due to existing comorbidities. In addition, frequently elderly patients with early NSCLC are denied surgery due to expected peri- and/or postoperative complications. Finally, in recent years there has been an increase in the incidence of patients refusing surgery. For all these patients, radiation therapy (RT) was traditionally considered as the standard treatment option. Data accumulated over the last 5 decades showed that RT alone can produce median survival times of up to > 30 months and 5-year survival of up to 30%. When cancer-unrelated deaths were taken into account, cause-specific survival rates were usually higher for some 10-15%. Accumulated experience seems to suggest that doses of at least 65 Gy with standard fractionation or its equivalent when altered fractionation is used are necessary for control of the disease. Smaller tumors seem to have favorable prognosis, while the issue of elective nodal RT continues to be controversial. Patterns of failure have clearly identified local failure as the predominant one. Although a number of potential pretreatment patient- and tumor-related prognostic factors have been examined, none has been shown to clearly influenced survival. Toxicity was usually low., (Copyright 2010 S. Karger AG, Basel.)

Patients with extensive disease small cell lung cancer (ED-SCLC) represent approximately one-third of all SCLC patients. For these patients, chemotherapy (CHT) is the standard treatment of choice. With CHT given alone, however, there is not a high risk of distant progression, but also progression within the thorax and brain frequently occurs, even in patients achieving a response to CHT. To improve poor figures obtained with CHT alone and address important issue of intrathoracic tumor control and it relationship to overall survival, thoracic radiation therapy (TRT) was introduced with a curative intent in a prospective randomized trial by Jeremic et al (1988-1993). In that trial CHT alone was compared with CHT followed by TRT, and in both groups by a prophylactic cranial irradiation. This trial showed that TRT can offer an improvement on local control that leads to an improvement in overall survival. Toxicity was acceptable, while multivariate analysis identified number of metastasis as an independent prognosticator of outcome. Based on the data of this trial, researchers in the USA and Europe will undergo two prospective trials addressing the issue of TRT in ED-SCLC., (Copyright 2010 S. Karger AG, Basel.)

Purpose: To test whether radiation-induced elevations of transforming growth factor-beta1 (TGF-beta1) during radiation therapy (RT) correlate with radiation-induced lung toxicity (RILT) in patients with non-small-cell lung cancer (NSCLC) and to evaluate the ability of mean lung dose (MLD) to improve the predictive power., Methods and Materials: Eligible patients included those with Stage I-III NSCLC treated with RT with or without chemotherapy. Platelet-poor plasma was obtained pre-RT and at 4-5 weeks (40-50 Gy) during RT. TGF-beta1 was measured using an enzyme-linked immunosorbent assay. The primary endpoint was > or = Grade 2 RILT. Mann-Whitney U test, logistic regression, and chi-square were used for statistical analysis., Results: A total of 165 patients were enrolled in this study. The median radiation dose was 60 Gy, and the median MLD was 15.3 Gy. Twenty-nine patients (17.6%) experienced RILT. The incidence of RILT was 46.2% in patients with a TGF-beta1 ratio > 1 vs. 7.9% in patients with a TGF-beta1 ratio < or = 1 (p < 0.001), and it was 42.9% if MLD > 20 Gy vs. 17.4% if MLD < or = 20 Gy (p = 0.024). The incidence was 4.3% in patients with a TGF-beta1 ratio < or = 1 and MLD < or = 20 Gy, 47.4% in those with a TGF-beta1 ratio >1 or MLD > 20 Gy, and 66.7% in those with a TGF-beta1 ratio >1 and MLD > 20 Gy (p < 0.001)., Conclusions: Radiation-induced elevation of plasma TGF-beta1 level during RT is predictive of RILT. The combination of TGF- beta1 and MLD may help stratify the patients for their risk of RILT.

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 chi2 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.

Angiotensin-converting enzyme (ACE) plays an important role in pulmonary fibrosis and may be involved in the development of radiation-induced lung damage. The objective of this study was to evaluate the predictive value of plasma ACE in radiation pneumonitis (RP). Patients with stage I-III lung cancer were treated with radiotherapy with or without chemotherapy. ACE levels were measured using enzyme-linked immunosorbent assay before radiotherapy (pre-RT) and when a median dose of 45 Gy (Range: 40-48 Gy) was reached (during-RT). The primary end point was > or = grade 2 RP. Statistic significances were evaluated with independent T-test and chi-square. Thirty-nine patients were enrolled in this study, among which 33.3% experienced > or = grade 2 RP. ACE levels, either pre-RT or during-RT, were significantly lower in the RP group than in the non-RP group (P=0.02 and 0.03, respectively). Nine out of the 19 patients (47.4%) with pre-RT ACE levels < or = 462 ng/mL experienced RP, versus 3 of 19 (15.8%) patients with ACE levels > 462 ng/mL (P=0.04). This study suggested that plasma ACE as a predictive factor for radiation pneumonitis deserves further study.

Background: Cells derived from lung cancer are biological heterogeneous and have different intrinsic radiosensitivity, it is a key question for us to investigate radiosensitive parameters for an individualized radiotherapy plan. The comet assay is a sensitive and facilitated method to detect single-cell DNA damage and repair, and the results from it have been proven to be so highly coincident with those from clonogenic assay by cell-line investigations that it has been considered as a promising method in predicting radiosensitivity. The study is designed to evaluate preliminarily the correlation between initial DNA damage detected by alkaline comet assay and the clinical endpoints., Methods: Biopsy samples from 31 lung cancer patients by fibrous bronchial endoscopy were detected by alkaline comet assay from April, 2002 to November, 2002. The adjusted tail moment (R TM) was measured and thoracic local-region lesions were measured by computer tomography scan. Response rate (RR) and time to progression (TTP) for the local-region lesions were as clinical endpoints. SPSS 10.0 software was used to compare median R TM of different RR and TTP groups by Mann-Whitney U and Kruskal-Wallis H rank test, the correlations between R TM with RR and TTP were estimated by Spearman's rank test., Results: There were no statistic differences of median R TM among different pathological types with a median R TM of 0.98, 1.27 and 1.05 in squamous cell carcinoma group, adenocarcinoma group and small cell lung cancer group, respectively (Chi-square=0.347, P=0.84). Through a median follow-up of 10 months, a median R TM of 1.08 and 1.21 for squamous cell carcinoma group and small cell lung cancer group in RR≥50% group was greater than 0.88 and 0.91 in RR < 50% group; median R TM in TTP > 9-monthgroups stratified according to pathological type was greater than that in TTP≤9-month groups (1.26, 1.38 and 1.39 versus 0.71, 0.48 and 1.03 for squamous cell carcinoma group, adenocarcinoma group and small cell lung cancer group respectively), but the differences of R TM classified by RR or TTP were not statistically significant (U=63.5, P=0.58; U=71, P=0.057); the Spearman's coefficients of R TM with RR and TTP were -0.105 (P=0.57) and 0.38 (P=0.035). The coefficients of R TM with TTP was 0.47 for non-small cell lung cancer indicating a modest correlation (P=0.048) and 0.043 for small cell lung cancer (P=0.89)., Conclusions: Although the results are confounded due to sampling and the greater background tail moments, Spearman's coefficient of R TM with TTP for non-small cell lung cancer indicates a modest positive correlation. The comet assay might be a promising method in predicting intrinsic radiosensitivity of lung cancer cells and techniques for sampling and assaying need to be further improved.