Association Study Between Single Nucleotide Polymorphism And Effect As Well As Prognosis For Small Cell Lung Cancer Treated With Carboplatin Based Regimen

Partâ… Objective: To evaluate the clinical outcomes of small cell lung cancer (SCLC) treated with carboplatin plus etoposide (CE) regimen combined with radiotherapy.Method: Retrospectively, we collected and analyzed the symptoms, diagnosis, clinical characteristics and survival of 136 cases of SCLC patients, who were treated in our hospital without surgery from OCT 1999 to NOV 2007.Result: Median age and sex ratio of the population were 56 year old and 3. 1:1. There were 98 smokers in all cases, and 94 smokers in male patients. Limited Disease (LD) - and Extensive Disease (ED) - SCLC accounted for 36. 1% and 63.9%, respectively. The response rate of CE regimen was 80. 1% in all cases, and the rate was 91.8% and 73.6% in LD- and ED-SCLC, respectively. Radiotherapy was given to 71. 3% ED-SCLC patients. After a median follow up of 13 months, the median survival time was 19 months for all cases and was 30 and 16 months for LD- and ED-SCLC, respectively; survival rate of 1, 2, 3 years was 71%,37. 3%, 23. 3% for all cases, 82.1%,56.8%, 41.1% for LD-SCLC, and 64.3%,24.1%, 10.7% for ED-SCLC, respectively. There was only 6 cases received prophylactic cranial radiotherapy (PCI). Brain metastasis rate of 1 and 2 years was 27.9% and 45.5%, respectively.Conclusion: The most SCLC patients are old males with a close relationship with smoking; CE regimen combined with radiotherapy is a feasible treatment model; Palliative radiotherapy with higher doses may improve treatment effect of ED-SCLC whose disease is relative limited and with better performance status. PCI should be given for SCLC in an active manner. Further follow up is needed to evaluate the treatment effect in this study. Partâ…¡Objective: To analyze clinical prognostic factors for SCLC treated with CE regimen combined with radiotherapy.Method: Retrospectively, we collected the symptoms, clinical characteristics and survival of 136 cases of SCLC patients, who were treated in our hospital without surgery from OCT 1999 to NOV 2007, and then analyzed factors related with prognosis.Result: In log rank test, disease staging was one of the most prognostic factors, the median survival time for LD- and ED-SCLC was 30 and 16 months, respectively; and survival rate of 3 years was 41.1% and 10.7%, respectively. Patients with Syndrome of inappropriate antidiuretic hormone secretion (SIADH), increased serologic tumor marker level and increased lactate dehydrogenase (LDH) had a poor prognosis; the prognosis, however, was better for patients less than 60 years old compared with those more than 60 years old. Patients responsed to chemotherapy and received radiotherapy had better prognosis than those without response and who did not received radiotherapy; receiving radiotherapy was still a better prognostic factor for ED-SCLC. TTP (time to progression) more or less than 6 months was another important prognostic factor. In COX hazard proportional model analysis, SIADH, radiotherapy and TTP were all independent prognostic factors.Conclusion: Clinical characteristics have preliminary effect for prognosis; treatment effect of chemo and radiotherapy was important factors for prognosis, radiotherapy was also important factor for ED-SCLC. TTP that has relationship with biologic characteristics of SCLC was a better prognostic factor. Further investigation is needed for some molecular mechanisms to evaluate prognosis. Partâ…¢Objective: To find out molecular factors associated with prognosis and effect for SCLC treated with CE regimen combined with radiotherapy by association study between single nucleotide polymorphisms (SNPs) and effect as well as prognosis of SCLC.Method: Genome-wide DNA was extracted from blood drawn from 136 cases of SCLC patients and than digested by 2 restriction enzymes. A subset of fragments were ligated with adaptors and PCR amplified, amplified DNA was then fragmented, end labeled and hybridized to the Affymetrix genome-wide human SNP array 5.0. After washing, incubating and staining, the hybridized DNA was scaned and analyzed. All SCLC patients were classified into 3 groups according to chemotherapeutic effect, TTP and overall survival time. Fisher's exact test was used to analyze different genotyping among patients in 3 groups aiming at finding out SNPs associated closely with chemotherapeutic effect, TTP and overall survival time.Result: There were 262, 243 and 278 SNPs associated closely with chemotherapeutic effect, TTP and overall survival time when P<0.001 was defined. Among all the SNPs, rs1465405 (in 5-hydroxytryptamine receptor 4) was associated with chemotherapeutic effect and TTP simultaneously; rs573161(in RAB38, which is one of members of RAS oncogene family),rs10054090 (in cytoplasmic polyadenylation element binding protein 4),rs6677798,rs11007707 (in supervillin),rs16835577,rs11709369 and rs12125740 were associated with TTP and overall survival time simultaneously.Conclusion: Genome-wide association study identified thousands of SNPs associated with chemotherapeutic effect, TTP and overall survival time, and especially several SNPs associated simultaneously with those factors. These findings indicate that there really exist genes had relationship with effect and prognosis, and further study of the function of these genes product may find moleculars factors for predictting and prognosis.