| Part ? Clinical research on stereotactic body radiotherapy for early small hepatocellular carcinomaObjective:To investigate the efficacy and adverse reactions of stereotactic bodyradiotherapy with?-ray and X-ray (?- knife and X- knife) for early small hepatocellular carcinoma.Methods:Between June 2008 and Novermber 2011,70 patients with early small hepatocellular carcinoma who were unable to tolerate surgery were randomized divided into two groups, one group using ?- knife treatment,70% isodose coverage GTV,50% isodose surrounding PTV, Prescription dose ofGTV was70Gy/10F, PTV was 50Gy/ 10F; another using X-knife treatment,90% isodose volume surrounding GTV, Prescription dose of GTV was 70Gy/10F, PTV was 63Gy/10F.Results:All patients were successfully completed treatment.The V5, V10, V20, V30, V40 and MDTNL in ?- knife group was lower than those of X-knife group(P<0.05). The total effective rate (CR+PR) of ?- knife group and X-knife group respectively was 94.7% and 96.9%, which had no statistically significant differences (P=1.000). The median survival time of the two groups was 38.7 months and 37.9 months, respectively(P>0.05).The over all 1 year,2 years and 3 years survival rates of the two groups were 97.4% and 96.9%(P=1.000),92.1% and 90.6%(P=1.000),73.7% and 78.1%(P=0.666), respectively.The incidence of grade ?-? gastrointestinal reactions was 23.7%(9/38) and 46.9% (15/32) (P=0.042), respectively. The incidence of grade ?-? myelosuppression rates were 31.6%(12/38) and 31.3%(10/38) (P=0.976), respectively. The occurrence of radiation-induced liver disease in ?- knife group was 26.3%(10/38), X-knife group was 50.0%(16/32).Compared with ?- knife group, the incidence of radiation-induced liver diseasein patients who treated with X-knife is higher (P=0.041).Conclusion:Stereotactic body radiotherapy is an effective and non-invasive treatment of early small hepatocellular carcinoma. The efficacy of X-knife and ?- knife for early small hepatocellular carcinoma was quite, with better local control rate, improved the quality of life of patients and prolonged survival, and ?- knife had certain advantages in the protection of surrounding normal tissue, reducing the incidenceof radioactive liver injury.Part II Clinical research on y-Knife Combined with TACE and Intensity-modulated Radiation Therapy Combined with TACE for Patients with Large Primary Liver CarcinomaObjective:To evaluate the therapeutic effect and adverse reaction ofy-knife and intensity-modulated radiation therapy combined with TACE for patients with large liver carcinoma.Methods:69 patients with large liver carcinoma were randomly divided into A group and B group.A group were treated with TACE plus ?-knife, A group were treated with TACE plus intensity-modulated radiation therapy.All the patients were treated with TACE firstly, y-knife or intensity-modulated radiation therapy was performed according to the group condition after two times TACE was given.Results:All patients were successfully completed treatment.The V5, V10, V20, V30, V40 and MDTNL in ?-knife group was lower than those of IMRTgroup (P<0.05).CR was of A group and B group 5.7% and 0 respectively and PR was 57.1% and 55.9% respectively,SD was 22.9% and 23.5% respectively,PD was 14.3% and 20.6% respectively,RR was 62.8% and 55.9% respectively.The survival rate was 82.9%(29/35) in 1 year and 60.0%(21/35) in 2 years in group A,79.4%(27/34) and 58.8%(20/34) in group B respectively (P1 year=0.714, P2 years=0.921). The adverse reactionswere gastrointestinal effects, radioactive liver disease, myelosuppres sion. The I-IV degree ofradioactive liver disease and gastrointestinal effects of group B is higher than that of group A (P=0.041, P=0.040).The I-IV degree ofmyelosuppression of the two groups were equal (P=0.229)Conclusion:y-knife combined with TACE and intensity-modulated radiation therapy combined with TACE for treatment of large primary liver cancer is safe,effective method. ?-knife combined with TACE on bone marrow suppression effect less.Part? Clinical research on alternating hyperfraction intensity modulated radiotherapy for massive hepatocellular carcinomaObjective:To observe the efficacy and adverse reactions onalternating hyperfractionr-adiotherapy of massive hepatocellular carcinoma.Methods:Seventy-two cases of massive hepatocellular carcinoma(tumor sizes were 15-35cm) were random-lydivided into two groups,group A and group B. The liver sub lesions of group A were treated by alternating hyperfraction intensity modulated radiotherapy.The interval of the radiotherapy to the sub lesionswas at least six hours. The average radiotherapy dose of thesub lesions were 2Gy/fraction, once a day,5 times per week, the gross tumor volume (GTV) with a total dose of 40 to50Gy, and the clinicaltarget volume(CTV) with a total dose of 30 to 40Gy. The lesions of group B were treated by IMRT,2Gy/fraction, once a day,5 times per week, the gross tumor volume (GTV) with a total dose of 40 to50Gy, and the clinicaltarget volume(CTV) with a total dose of 30 to 40Gy.Results:One patientin group A was not finished with radiotherapy because of upper gastrointestinal hemorrhage. Four patients in groupBwere not finished with radiotherapy because ofthe severeadverse reaction. The overall response rate of the two groups was 82.9% and 81.3%, respectively(P=0.864). The alternating hyperfractionra-diotherapy offered better survival (P=0.002). The median survival time of thetwo groups was9.7 months and 6.5 months, respectively.The overall 6 months, lyear,2 years and 3 years survival ratesof the two groups were62.9% and 59.4%(P=0.770), 48.6% and 21.9%(P=0.040),17.1% and 0%(P=0.025),2.9% and 0%(P=1.000), respectively.The adverse reactionswere gastrointestinal effects, abnormal liver function, myelosuppre-ssion (mainly for I-II degree) and radiation-induced liver disease. The I-II degree ofgastrointestinal effects and myelosuppression of the two groups were equal (P value was 0.864 and 0.587, respectively). The I-II degree of abnormal liver function and radiation-induced liver disease of group B is higher than that of group A(P value was 0.021 and 0.046, respectively).Conclusion:Compared with intensity modulated radiotherapy, the incidence rate of radiation-induced liver injury is less to the alternating hyperfraction intensity modulated radiotherapy for massive hepatocellular carcinoma.The alternating hyperfraction intensity modulated radiotherapy can improve the quality of life and prolong the survival time, suggesting that it is an effective radiation pattern.Part? Clinical research on semi-liver alternating and Intensity Modulated Radiation Therapy combined with Traditional Chinese Medicine for advanced diffused hepatocellular carcinomaObjective:To observe the recent effects and side effects of Semi-liver alternating and Intensity Modulated Radiation Therapy combined with Traditional Chinese Medicine for advanced diffused hepatocellular carcinoma.Methods:66 cases of advanced diffused hepatocellular carcinoma patients were randomly divided into two groups, group A and group B. Group A were treated by Semi-liver alternating radiotherapy (IMRT, intensity modulated radiotherapy)and Traditional Chinese Medicine. Group B were treated by Semi-liver alternating radiotherapy only.The liver targets were divided into left and right semi-liver, with a total dose of 30 Gy,2 Gy/fraction, once a day,5 times per week.The more side of liver lesions were irradiated first.Results:The number of the two groups completing the treatment were 32 and 31, respectively. The ratio of KPS score rised more than 10 points of the two groups after treatment were 90.6% and 71.0%, respectively (P=0.047).Compared with before the treatment, the levels of CD3+,CD4+ and CD4+/CD8+ of the two groups were higher after the treatment (P value for group A were 0.000,0.000 and 0.000, respectively. P value for group B were 0.029,0.047 and 0.001, respectively), the level of CD8+ was lower (P value for the two groups were 0.009 and 0.044, respectively). After the treatment, the levels of CD3+,CD4+and CD4+/CD8+ of group A were also higher than group B (P value were 0.047,0.035 and 0.045, respectively), and the level of CD8+ of the two groups were equal (P=0.490).The disease control rate of the two groups were 78.1%(25/32) and 77.4%(24/31), respectively (P=0.946). The median survival time of the two groups was 5.2 months and 5.1 months, respectively(P>0.05).The three months, six months and one year survival rates of the two groups were 90.6%(29/32) and 87.1%(27/31)(P=0.708),40.6%(13/32) and 32.3%(10/31)(P=0.490),18.6%(6/32) and 0%(0/31)(P=0.024).The toxic reactions were gastrointestinal reaction, radioactive liver damage and myelosuppression(mainly for I-II degree).The I-II degree of gastrointestinal reactions of the two groups were equal(P=0.535).The I-II degree of radioactive liver damages and myelosuppression of group A were lower than that of group B(P value was 0.039 and 0.048, respectively).Conclusion:Semi-liver alternating and Intensity Modulated Radiation Therapy combined with Traditional Chinese Medicine can improve the quality of life, enhance immune function, prolong the survival time, reduce the incidence of radioactive liver damages and myelosuppression, suggesting that it is worth popularization and application in clinic.Part V The role of TGF-? signaling pathway on hepatocellular carcinoma radiotherapy and its mechanismObjective:To determine changes of TGF-? signaling in human hepatocellular cancer cells HepG2 cells by irradiation.Methods:Human hepatocellular cancer cells HepG2 were treated with or without TGF-? ahead of being irradiated. Clonogenic survival, apoptosis and changes of important molecular in TGF-? signals following graded radiation doses were detected.Results:Consistent with increased clonogenic cell death, radiation-induced Smad3 overexpression, and phosphorylation of Smad3 was significantly increased in HepG2 cells after irradiation. Extrinsic TGF-?1 made this phenomenon more obviously. At the same time, Smad7 expression was down-regulated by irradiation individually. The results suggested X-Ray induced Bax expression on HepG2 cells, and this phenomenon was more obviously when TGF-?1 was presented ahead of irradiation. On the contrary, there was not an apparent changes of Bcl-2 expression no matter X-ray and TGF-?1 was performed on cells, separately.Conclusion:These results showed that radiation could reduce HepG2 cancer cells proliferation,meanwhile could promote HepG2 cell apoptosis by up-regulation of Smad3, p-Smad3 expression.And rate of proliferation reduction and rate of apoptosis seemed have a positive correlation with graded irradiation from 2Gy to 8Gy. And Smad7 expression was down-regulated. We found this new phenomenon in HCC cells when exposed to radiation. More mechanisms should be explored in future. We used siRNA-Samd3 to knock down Smad3 suppressed the apoptosis and attenuated the proliferational effects and apoptosis induced by radiation. |
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