Thoracic Radiation Therapy (TRT) Improved The Prognosis For Patients With Small Cell Lung Cancer

PartⅠ:Treatment modality selection and prognosis of early stagesmall cell lung cancer Background:The retrospective study was to evaluate the role of surgery followed bychemotherapy versus sequential chemoradiotherapy in the multimodality management in patients with stageⅠandⅡsmall cell lung cancer(SCLC).Methods:Between January 1996 and December 2006, the records of 145 patients diagnosed with clinical stageⅠandⅡdisease SCLC (T1-3N0-1) were included in this study. Ninety-Six patients received surgery followed by chemotherapy(GroupⅠ) and 49 patients were treated with sequential chemoradiotherapy(GroupⅡ). Surgical procedures included wedge excision, segmentectomy, lobectomy or pneumonectomy and with ipsilateral hilar and mediastinal lymphadenectomy. The ChT regimens consisted of either carboplatin and etoposide (CE) or cisplatin and etoposide (PE). The total dose of TRT was 50-60 Gy, with 1.8-2.0 Gy per fraction. Kaplan-Meier and Cox regression analyses were used to compare overall survival (OS) for all patients.Results:For the whole group, The median survival time (MST) was 54.0 months, and the 2-year and 5-year OS rates were 72.9% and 48.0% for the whole group of patients. The MST and 2-year and 5-year OS rates of the groupⅠwere 91.0 months and 74.7%, 57.0%, respectively, and those of the groupⅡwere 34.6 months,69.4% and 31.4%, respectively (p=0.004). The subset analysis showed that surgery followed by chemotherapy was superior to sequential chemoradiotherapy in patients with stageⅠdisease(p=0.050), but not in stageⅡSCLC(p=0.192). The 2-year and 5-year PFS rates were 50.6% and 44.4% for the whole group of patients. The 2-year and 5-year PFS rates in groupⅠand groupⅡwere 60.8%,53.5% and 30.6%,26.2%, respectively (p=0.0026). The local recurrence-free survival (LRFS) at 5-year was 69.0% in group I and 47.1% in groupⅡ(p=0.018). The distant metastasis-free survival (DMFS) in groupⅠand group II was 72.1% and 41.5%, respectively (p=0.001). Multivariate analysis revealed that KPS score≥80(p=0.015) and surgery (p=0.004) were independent favorable prognostic factors for OS. Conclusions:The use of surgery followed by chemotherapy in patients with early stage SCLC was associated with improved survival outcomes, especially to stageⅠdisease. Further, Surgery and KPS score were independent favorable prognostic factors for OS. Part II:Chemoradiotherapy in local disease small cell lung cancerBackground:The retrospective study was to evaluate the role of chemoradiotherapy in local disease small cell lung cancer(SCLC).Methods:Between January 2003 and December 2006, the records of 177 patients diagnosed with local disease SCLC were included in this study and were given chemoradiotherapy. The chemotherapy (ChT) regimens consisted of either carboplatin and etoposide (CE) or cisplatin and etoposide (PE). The dose of thoracic radiation therapy (TRT) was 1.8-2.0 Gy per fraction. Kaplan-Meier and Cox regression analyses were used to compare overall survival (OS) for all patients.Results:For the whole group, one hundred and seventy-four(98.3%) were given sequential chemoradiotherapy. The total dose of TRT was 36Gy-66Gy and the median dose was 56Gy, only 8 patients was given TRT with dose less than 50Gy. The median survival time (MST) was 23.0 months, and the 2-year and 5-year OS rates were 45.2% and 17.9% for the whole group of patients. Multivariate analysis revealed that the cycle of ChT(p=0.000), KPS score≥80(p=0.055) and age (p=0.060) were independent favorable prognostic factors for OS.Conclusions:Chemoradiotherapy is the standard treatment for local disease small cell lung cancer. Further, the cycle of ChT, KPS score≥80 and age were favorable prognostic factors for OS. PartⅢ:Thoracic radiation therapy (TRT) improved the prognosis for patients with extensive stage small cell lung cancerObjective:To evaluate the effect of thoracic radiation therapy (TRT) in patients with extensive stage small cell lung cancer(SCLC).Methods:Between January 2003 and December 2006,154 patients diagnosed with extensive stage SCLC were enrolled in this study. Eighty nine patients received chemotherapy and thoracic radiation therapy (ChT/TRT), and 65 patients were treated with chemotherapy alone (ChT/without TRT). The chemotherapy regiments were CE (carboplatin and etoposide),PE (cisplatin and etoposide) or CAO (CTX,ADM and VCR) regimens. The total dose of thoracic irradiation was 40Gy～60Gy with 1.8Gy-2.0Gy per fraction. Prognostic factors such as gender,age,performance status (PS),smoking history,weight loss,distant metastasis,the number of matastasis,brain metastasis,the cycle of chemotherapy and thoracic radiation therapy (TRT) for ED-SCLC patients were evaluated by univariate and multivariate analysis.Results:For the whole group, the median survival time (MST) was 13.7 months, the 2-year and 5-year overall survival rates were 27.9% and 8.1% respectively. The MST,overall survival rates at 2-year and 5-year in ChT/TRT group and ChT/without TRT group were 17.2 months,36.0%,10.1% and 9.3 months,16.9%,4.6% respectively (p=0.001). The median progression-free survival (PFS) for all patients was 7.3 months, the 2-year and 5-year PFS were 11.7% and 5.1% respectively. The median PFS,2-year and 5-year PFS in ChT/TRT group and ChT/without TRT group were 9.6 months,14.6%,5.4% and 6.0 months,7.7%,4.6% respectively (p=0.0001). The incidences of local failure in thoracic were 29.6% in ChT/TRT group, and 70.0% in ChT/without TRT group (P= 0.000). By multivariate analysis, smoking history was a statistically significant poor factor for OS in ED-SCLC patients (versus no-smoking, hazard ratio (HR)=1.462,P=0.036). In addition,≥4 cycles of chemotherapy and TRT were favorable prognostic factors (≥4 cycles versus<4 cycles, HR=0.420,P=0.000; ChT/TRT versus ChT, HR=0.634, P=0.013). Conclusions:Patients with extensive stage SCLC received ChT/TRT can improve overall survival, progress free survival, and reduce local regional failure rate comparing to patients received ChT/ without TRT. Smoking is independent unfavorable prognostic factors and≥4 cycles of chemotherapy, TRT are independent favorable prognostic factors for OS in ED-SCLC by multivariate analysis. PartⅣ:The relevant of COX-2 proteins and COX-2 -1195G/A polymorphism in inoperable locally advanced non-small cell lung cancer.Purpose:Elevated COX-2 expression and COX-2 -1195G/A polymorphism have been reported to be correlated with reduced survival after radiotherapy. This study examined whether genetic variations in the COX-2 gene are associated with COX-2 proteins in inoperable locally advanced non-small cell lung cancer (NSCLC).Methods:Fifty patients with inoperable stageⅢA-B NSCLC receiving thoracic irradiation between 2004 and 2007 were recruited in this study. COX-2 -1195G/A polymorphisms were genotyped using DNA from blood lymphocytes by polymerase chain reaction andresriction fragment length polymorphism analysis (PCR-RFLP) method. Immunohistochemical (IHC) technique. Immunohistochemical (IHC) staining was used to detect the level of COX-2 proteins.Results:In 50 patients, only 44 patients were tested the level of COX-2 proteins by immunohistochemical staining. According to the IHC index, they were divided into two groups, moderate-high level(IHC≥4) and low level (IHC<4). In 35 patients with COX-2 -1195GA and GG genotypes,IHC<4 was affirmed in 20 patients and IHC≥4 in 15 patients, In 9 patients with COX-2 -1195AA genotypes, IHC<4 was affirmed in 4 patients and IHC≥4 in 5 patients, the difference of IHC level in the two genotypes was not significantly, with p value=0.495. In 22 patients with squamous cell carcinoma, IHC<4 was affirmed in 16 patients and IHC≥4 in 6 patients; In 17 patients with adenocarcinoma, IHC<4 was affirmed in 6 patients and IHC≥4 in 11 patients, the difference of IHC level in the two types was significantly, with p value= 0.019.Conclusion:COX-2 -1195G/A polymorphism is not associated with the level of COX-2 proteins in in inoperable locally advanced non-small cell lung cancer (NSCLC).