Objective To investigate the mechanism of an antifibrotic drug, pirfenidone, in preventing radiation-induced pulmonary fibrosis. Methods Male BALB/C mice were randomized into 4 groups:control group (C), radiation alone group (R), pirfenidone alone group (P), and pirfenidone plus radiation group (P + R). Irradiation was administrated to the whole pulmonary with a single fraction of 12 Gy. The pirfenidone was given 0. 3 ml/kg/d from 3 days prior to irradiation to 12 weeks after.Bronchoalveolar lavage fluid (BALF) from right lung was collected for macrophages counting every monthmonthly until 6 months after irradiation, and left lungs were collected and fixed for. The pulmonary fibrosis was assessed by Masson trichrome staining. The plasma transforming growth factor β(TGF-β) was measured by ELISA. The lung hydroxyproline was evaluated by alkaline solution. Results Compared to group R, the counts of macrophages in BALF in group P + R were reduced by 76% and 62%, and hydroxyproline levels were reduced by 21% and 24% at the 4th and 5th months, respectively. The plasma TGF-β decreased from the 3rd month to 5th month. Pirfenidone markedly ameliorated the severity of lung fibrosis at the 4 - 6th month after radiation. Conclusions Pirfenidone can prevent radiation-induced pulmonary fibrosis, the mechanism of which may be the reduced of inflammation and collagen deposition by decreasing macrophages and hydroxyproline.

Objective To study if the dose verification technique for three dimensional conformal radiation therapy ( 3 DCRT) can be applied for simplified intensity modulation radiation therapy ( sIM RT). Methods From 1988 patients treated by sIMRT in our department,12 were chosen randomly for the study. For each case,3 differert plans of 3DCRT,sIMRT,and IMRT were worked out with Pinnacle TPS,and the dose verification for each plan was carried out with Elekta Precise LA by using 2D diode-matrix of MapCHECK Model 1175. Results For slMRT,the overall average percentages of pass points for DD(DTA) 2% (2 mm) ,3% (3 mm)and 4% (4 mm) were 90.5% ,94.8% and 98.2% reapectively,which were slightly worse when comparing with those of 3DCRT with deterioration of 1.9% (t=2.19,P=0.040) ,1.0% (t= 1.52,P=0.144) and 0.2% (t=0.05,P=0.623), but slightly better comparing with those of IMRT with increment of 2.1% (t=2.17,P=0.041) ,1.5% (t=2.62,P=0.016) and 1.5% (t=3.68,P=0.001) for 2% (2 mm) ,3% (3 mm) and 4% (4 mm) ,respectively. Conclusions The sIMRT technique simplifies the complicated dose verification procedure of I MRT. When the sIMRT technique is formally used, the procedure of dose distribution verification for 3DCRT can be used directly for slMRT.

ObjectiveTo evaluate whether oral administration of Chinese tradiational medicine,Qing-Xue granula,can prevent mouse lung injury caused by thoracic radiation.Methods128 BalB/C mice were divided into 4 groups:control (C) group; radiation (R) group; radiation plus high dose Qing-Xue granula (H) group and radiation plus median dose Qing-Xue granula ( M ) group.The H and M groups were fed 0.64 g and 0.32 g of Qing-Xue granula dissolved in 0.5 nl anline once daily for two months,which were 4 and 2 times of human dosage,respectively.Whole thorax radiation of 12 Gy was delivered with a single ventral-dorsal field with 6 MV X-ray.Group C and group R received 21 days of 0.5 ml saline feeding.Mice were sacrificed at 1,2,4 or 6 months after radiation. Macrophage cell count of lung lavage fluid and hydroxyproline content of left lung were assayed,and the lung fibrosis was scorred according to the Ashcroft's criteria.The plasma interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) concentration were assayed with ELISA method.The One-way ANOVA was used to test the significance of any differences between groups at each time point. Results The macrophage cell number of lung lavage fluid was significantly lower in the 1st month in group M than in group R (2∶4,q =3.92,P ＜ 0.05 ),but had no significant difference between group M and C ( 1 ∶ 4,q =2.13,P＞0.05 ).The hydroxyproline content of group H was significantly lower than group R in the 1st and 6th months (q =3.62,3.54,all P ＜ 0.05 ),but still higher than group C ( q =4.09,3.72,all P ＜ 0.05 ).The fibrosis score of group H was significantly lower than group R in the 2nd,4th and 6th months (q=3.38 -4.16,all P＜0.05).The IL-6 concentration of group H was significantly lower than group R in the 1st month ( q=3.53,P＜0.05 ),but not significantly higher than group C (q =1.41,P＞0.05).The VEGF concentration was significantly higher in group R than group C since the 2nd month ( q =3.12 - 3.78,P ＜ 0.05 ).The VEGF concentration was significantly higher in group H and M than group R in the 2nd and 6th months ( q =3.08 - 3.92,all P ＜ 0.0 5 ).Conclusions Oral Chinese traditional medicine,Qing-Xue granula,could prevent radiation induced lung fibrosis in mice,especially at high dosage.The degree of elevation of VEGF in plasma was not parallel with that of lung fibrosis.

ObjectiveTo evaluate the effect on lung injury of gefitinib or/and radiation.Methods Totally 160 mice were divided into five groups:control (C) ;gefitinib (G) ;radiation (R) ;gefitinib followed by irradiation ( G + R) ;and R + G.12 Gy irradiation was delivered.Geiitinib fed by 200 mg/kg once daily for 3 weeks.Mice were sacrificed on 1,2,4 or 6 months after radiation.Macrophage count of lung lavage fluid and hydroxyproline assessed,lung fibrosis scored.and plasma TGF-β1 concentration assayed.One-way ANOVA was used to test the significance. Results The lung lavage macrophage cell number were significantly higher in group R,R + G and G + R than group C ( q =2.95 - 8.61,all P ＜ 0.05 ) on 4 and 6months,yet no significant difference between the three groups ( q =0.37 -3.49,all P ＜ 0.05 ) ; The macrophage was significantly lower in month 1,4 and 6 in group G than R,R + G and G + R ( q =3.37- 6.25,all P ＜ 0.05 ).The hydroxyproline content and the fibrosis score of G,R,R + G and G + R were significantly higher than C ( q =3.14 - 4.76,all P ＜ 0.05 ),but no significant difference between the four groups ( q =0.70 - 4.19,all P ＞ 0.05 ).The TGF-β1 concentration of R,G + R,R + G at all time points and TGF-β1 concentration of G at 1 st and 2nd months were significantly higher than C ( q =3.76 -8.09,all P ＜ 0.05).ConclusionsGefitinib could cause lung fibrosis in vivo in BalB/C mouse.The combination of gefitinib and radiation did not significantly exacerbate lung injury caused byeither alone.The mechanism of lung fibrosis caused by gefitinib might be different from that by radiation which needs further research.

Objective This study was to assess the three-dimensional gross tumor volume(GTV)motion of lung cancer caused by respiration using four-dimensional computed tomography(4DCT),and to analyze the influenee factors.Methotis Four-DCT scans of 22 lung focuses in 21 patients with lung cancer were analyzed.The gross tumor volume was contoured in all 10 respiration phases of 4DCT scans.The changes in volume of GTV,the 3D motion of the centroid,boundary of GTV and the 3D spatial motion vectors were calculated and the irdluenee factors were analyzed.Results The average change in volume of GTV was+14.3%(0.2%.42.5%)/-8.4%(0.4%-38.6%),the average movement amplitude of GTV centroid and GTV boundary were(0.18±0.12)cm,(0.20±0.16)cm,(0.53±0.59)cm and(0.42±0.23)cm,(0.41±0.22)cm,(0.57±0.70)cm in medio-lateral,vertro-dorsal,cranio-caudal(CC) direction,respectively.The CC movement was larger than other directions(Z=-2.12,P=0.034;Z:-2.10,P=0.035),and no significant difference was observed in 3D motion of GTV boundary(Z=-0.81.P=0.417;Z=-0.86,0.391).The CC motion of GTV eentroid in lower lobe was larger than that in upper lobe[(0.87±0.64)and(0.35±0.49)cm,(t=-2.12,P=0.047)],and no significant difference was found in other directions[(0.23±0.10)and(0.19±0.18)em(t=-0.49,P=0.629),(0.21±0.13)and(0.17±0.11)cm(t=0.76,P=0.460)].There was no correlation of the 3D movement and 3D spatial motion vector of GTV to the volume of GTV(r=-0.306,-0.062,-0.279,-0.300;P=0.189,0.796.0.234,0.199).Conclusions GTV motion of patients with lung cancer is individual,the CC movement is the moat obvious,using 4DCT to assess is comparatively accurate.The motion amplitude of lower lobe focuses is larger.No significant correlation of the GTV motion to the volume was observed.Larger sample study is needed to analyze the influence of adjacency to the GTV motion.

Objective To investigate the correlation between apolipoprotein E (ApoE)polymorphisms and cerebral infarction in Dali Bai populations in Yunnan province.Methods A total of 40 Dali Bai patients with cerebral infarction (female.23,male 17) and 43 Dali Bai normal controls (female 18,male 25) were included in the study.Polymerase chain reactionrestriction fragment length polymorphism (PCR-RFLP) analysis was used to detect APoE genotype,meanwhile the lipid levels were detected,and finally,ApoE gene sequencing was conducted.The correlation between the APoE gene polymorphism and the types of cerebral infarction were further studied.Results The frequencies of genotype ε3/ε4 (22.5% vs.4.7%,P ＜0.05) and ε4 (12.5% vs.3.5%,P ＜0.05) in the Dali Bai cerebral infarction group were significantly higher than those in Dali Bai normal control group,and the frequencies of genotype

Objective To investigate independent prognostic factors for overall survival (OS) in extensive disease small cell lung cancer (EDSCLC). Methods Between January 2003 and December 2006, 154 patients diagnosed with extensive stage small cell lung cancer were enrolled in this study.Prognostic factors such as gender, age, performance status, smoking history, weight loss, distant metastasis, the number of matastasis, brain metastasis, the cycle of chemotherapy and thoracic radiation therapy (TRT) for EDSCLC patients were evaluated by univariate and multivariate analysis. Results The median following-up time was 40. 5 months. The rate of follow-up was 92. 2%. The MST and overall survival rates at 3-year in smoking group and no-smoking group were 13 months, 11.8% and 17 months,22. 8%,respectively (χ2=3.40,P =0. 064);in ChT/TRT group and ChT group, they were 17. 2 months, 17.9%and 9.3 months,13.9%, respectively(χ2=10.47,P=0.001);and in the cycle of chemotherapy ≥4 group and ＜ 4 group, they were 16 months, 20. 1% and 9.3 months, 2. 9%, respectively (χ2=17.79,P=0. 000). By multivariate analysis, smoking history was a statistically significant unfavorable factor for OS in EDSCLC patients (versus no-smoking, hazard ratio (HR)=1.462, χ2=4.40, P=0.036). In addition, ≥4 cycles of chemotherapy and TRT were favorable prognostic factors ( ≥4 cycles vs ＜4 cycles, HR =0. 420,χ2 = 17. 17, P = 0. 000; ChT/TRT vs ChT, HR = 0. 634, χ2 = 6. 20, P = 0. 013). Conclusions Smoking is a independent unfavorable prognostic factor and ≥ 4 cycles of chemotherapy And TRT are independent favorable prognostic factors for OS in EDSCLC.

ObjectiveTo evaluate the value of the international union against cancer (UICC)stage,pathologic complete response (pCR),and the estimated treatment response as various means for prognostic stratifying patients after surgery in patients with squamous cell carcinoma of the esophagus who received preoperative radiotherapy (RT).MethodsA retrospective review was performed on 311 patients with esophageal squamous cell carcinoma who received RT before the esophagectomy. Data collected included the demographics,the RT details,the pathologic findings,and the survival.Prognostic survival was analyzed by Kaplan-Meier method and Logrank test.ResultsThe follow-up rate was 96.5％,89 and 43 patients,respectively were followed up more than 5 and 10 years.In univariate analysis,residual disease and the number of positive lymph node were predictors of the overall survival ( T-pCR,x2 =11.53,P =0.001 ;0,1 -3,≥4,x2=42.13,P=0.000,respectively).Further study found the 7th stage system of UICC cannot (can or cannot) entirely predict the prognosis of this group of patients.If categorizing the stages of their lymph nodes into three groups:N0(0),N1 (1-3) and N2(≥4)),and the modified UICC system can accurately distinguish ypStage Ⅰ with ypStage Ⅱ ( T0.3 N 1 M0 + T3 N0 M0 ) ( x2 =11.15,P =0.001 ) and ypStage Ⅱ with ypStage Ⅲ ( T4 N0-1 M0 and T0-3 N2 M0 ) ( x2 =23.39,P =0.000 ).ConclusionsThe pathologic post-radiotherapy T stage and the number of positive lymph node are predictors for esophageal squamous cell carcinoma receiving preoperative radiotherapy.The modified UICC stage system can be a better survival predictor than the 7th UICC stage system.

Objective To analyze the influencing factors of cone-beam CT (CBCT) imagine registration in lung cancer. Methods From Mar. 2007 to Dec. 2007, 20 patients with lung cancer were treated with IGRT. The imagines of CBCT were collected from 6 to 19 fractions during the patients' radiotherapy. To compare the difference of set-up errors between the two groups according to the distance from the lesion in lung to the centrum. At the same time, CBCT imagines from the first, middle and the last fraction of these patients' radiotherapy were registrated in bone and grey methods by four doctors. The difference of set-up errors between different doctors and registrated methods were compared. Results The mean values of set-up errors were ＜2 mm in the two groups without significant difference (x:-1.31mm vs 0. 10 mm (t=0. 07,P=0.554);y:1.24 mm vs 1.37 mm (t=0. 05,P=0. 652);z: - 1.88mm vs -1.26mm (t= -0. 12,P=0.321)). The mean values of set-up errors were ＜ 1.3 mm in four doctors and registrated methods without significant difference, for bone registration,x: -0. 05 mm, -0. 01 mm,0. 05 mm, -0.12 mm and -1.31 mm ( F=-0.01,P=0.887) ;y:0.56 mm,0.35 mm,0.51 mm and 0.43 mm (F= -0.01,P=0.880);z: -1.16 mm, -1.20 mm, -0.88 mm and -1.03 mm (F= -0.04,P=0. 555 ), for grey registration ,x: -0.32 mm, -0.341 mm, -0.395 mm and - 0.37 mm(F=-0.01, P=0.874);y:0.34 mm,0.54 mm, -0.04 mm and 0.27 mm (F= -0.03,P=0.622);x:-1.12 mm,- 1.15 mm, - 1.13 mm and - 1.04 mm (F=0. 00,P=0. 812). Conclusions With the same registrated box and imagine quality, the location of the lesions in lung, registred methods and different doctors are not the influencing factors for CBCT imagine registration.

Objective To compare postoperative three-dimensional conformal radiotherapy (3DCRT) and conventional radiotherapy (CR) in patients with non-small-cell lung cancer (NSCLC). Methods From Nov. 2002 to Mar. 2006,162 patients with stage ⅠB～ⅢB NSCLC receiving postoperative radiotherapy in our department were restrospetcively analyzed. Among them,86 received 3DCRT and 76 re-ceived CR. The survival outcome, pattern of failure and treatment-related side effects in both groups were an-alyzed. Results The median follow-up was 29.4 months in the 3DCRT group and 24 months in the CR group. The 1-,2- and 3-year local-regional free survival was 97.5% ,83.2% and 83.2% in 3DCRT group, and 84.3% ,76.0% and 65.6% in CR group(χ2= 5.46, P = 0.019), respectively. No statistically signifi-cant difference was found in the overall survival, disease-free survival or distant metastasis-free survival be-tween the two groups. The local-regional failure rate was statistically different between the two groups (14.5% vs 33.3% ,χ2 =7.70,P =0.006). The incidence of distant metastasis in the two groups was simi-lar. Radiation pneumonitis of NCI CTC grade 2-3 occurred in 10 patients(11.6%)in 3DCRT group and 18 (23.7%) in CR group,which was statistically different(χ2 =4.10,P=0.043). Conclusions Postopera-tive 3DCRT for NSCLC provides a better local-regional control and lower incidence of radiation pneumonitis compared with CR.