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Objective:To obtain stable radioresistant non-small-cell lung cancer (NSCLC) cell lines and identify the genetic pattern of conventional fractioned and hypofractionated radiotherapy. Methods:A549 NSCLC cells were treated with 6 MV of x-rays through conventional fractionated (2 Gy, 17 f) and hypofractionated irradiation (4 Gy, 7 f) to establish a radiation resistance cell model. Tumor cell radioresistance was determined using a clonogenic assay andγ-H2AX immunofluorescence staining combined with confocal microscopy. After extracting total mRNA from the cells, a whole genome expression microarray was applied to detect differential gene expression. The genes with at least a twofold increase in expression (P<0.05) were analyzed, and the pathway (Q<0.05) methods were used to further analyze the chip results. Results:After irradiating the A549 cells, two radioresistant cell lines were obtained, namely, the A549R2Gy-R and the A549R4Gy-R cell lines. The A549R2Gy-R cell line was radioresistant to the conventional fractionated irradiation, whereas the A549R4Gy-R cell line was ra-dioresistant to hypofractionated irradiation. Microarray analysis showed that the A549R2Gy-R cells exhibited 1 701 differentially expressed genes (357 upregulated, 1 344 downregulated) compared with the parental A549 cell. By contrast, the hypofractionated irradiation-resistant A549R4Gy-R cells had 944 upregulated genes and 2 602 downregulated genes compared with the A549 cells. The A549R2Gy-R cells exhibited 318 upregulated genes and 699 downregulated genes compared with the A549R4Gy-R cells. Several signaling pathways were implicated in radioresistance when conventional fractionated radiotherapy was compared with hypofractionated irradiation radiotherapy using path way-significant enrichment analysis, especially the PI3K and Erb B channel signaling pathway kinase. Conclusion:Multiple genes and signaling pathways are involved in the development of radiation resistance in NSCLC. The underlined radioresistance mechanisms under conventional and hypofractionated radiotherapy need further study and elucidation to provide new targets for drug development.
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ObjectiveTo investigate the effectiveness and toxicity of CyberKnife in the treatment of lung metastases.MethodsTreatment details and outcomes were reviewed for 93 targets of 48 histologically verified patients treated by CyberKnife at the CyberKnife Center of Tianjin between September 2006 and June 2010.The median tumor volume was 6.0(0.2 - 135.2) cm3,the median biological equivalent dose was 140.8(53 - 180) cGy (α/β =10),the median fraction was 3(1-7) times and the median isodose line was 81％ (71％-91％ ).ResultsThe rate of follow-up is 96％.33 cases were followed up for more than 2years.The effective rate was 90.3％.Two targets of 2 patients locally progressed.The 1-and 2-year local control rates,overall survival (OS) rates and progression-free survival (PFS) rates were 98％ and 98％,83％ and 63％,and 64％ and 37％,respectively.Univariate analyses showed that age older than 60 versus ≤60 years tended to be predictor for PFS ( x2 =3.45,P =0.063 ) ;The PFS of patients who had single lesion was better than patients with multiple lesions ( x2 =4.49,P =0.034 ) ; patients with disease-free interval longer than 18 months had better OS ( x2 =6.50,P =0.011 ).Five patients were reported to experience treatment-related grade 1 radiation pulmonary injury,and one each for subcutaneous fibrosis with pigmentation,grade 2 and grade 3 adverse event.ConclusionsFor patients with lung metastatic lesion,CyberKnife is an effective option with high local control rate and little acute reaction.The long-term outcome and toxicity need further study.
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Objective To evaluate clinical risk factors that can predict brain metastasis after complete resection of small cell lung cancer (SCLC) and to assess the role of prophylactic cranial irradiation (PCI) in such kind of patients.Methods Eighty-eight patients with completely resected stage Ⅰ - Ⅲ SCLC from Jan.2000 to Dec.2009 in our hospital were retrospectively analyzed.Kaplan-Meier was used to compare the differences in the incidence of metastasis free survival in different groups.Logistic model was used to assess the independent risk factors for brain metastasis.Results The follow-up rate is 100％,and 37 patients were followed up for more than three years.None of the 3 patients who received PCI developed brain metastasis,while for patients without receiving PCI,24％ developed brain metastases.The incidence of brain metastasis for stage Ⅰ,Ⅱ and Ⅲ SCLC after surgery were 4％,26％ and 29％ ( x2 =7.57,P =0.023),respectively.The median survival time and the 3-year survival rate were 18 months and 25％ for patients who developed brain metastasis,and 48 months and 59％ for those without brain metastasis ( x2 =10.63,P =0.001 ).Both univariate and multivariate analyses showed that pre-treatment disease stage wasindependent risk factor for brain metastasis ( x2 =7.57,8.52 ; P =0.023,0.004 ).Age,sex,tumor location,pathological type,induction chemotherapy,and postoperative chemotherapy/radiotherapy were not significantly correlated with the incidence of brain metastasis ( x2 =0.03,0.00,0.00,2.58,0.01,1.23,0.84;P =0.869,0.998,0.992,0.109,0.936,0.266,0.361,respectively).Conclusions Pre-treatment disease stage was independent risk factor for brain metastasis in SCLC.PCI may be important for stage Ⅱ -Ⅲ SCLC but not for stage Ⅰ disease.=Carcinoma,small cell lung/surgery; Neoplasm metastasis,brain/prophylactic irradiation; Factors analysis