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Application of risk category system to evaluate the treatment outcome of locoregionally advanced nasopharyngeal carcinoma treated by intensity-modulated radiation therapy alone

Guanzhu SHEN ; Xiaowu DENG ; Shaoxiong WU ; Weiwei XIAO ; Fei HAN ; Anchuan LI ; Chong ZHAO

Chinese Journal of Radiological Medicine and Protection.2015;35(7):518-521. doi:10.3760/cma.j.issn.0254-5098.2015.07.009

Objective To explore the feasibility of employing a risk category system in evaluating the treatment outcome of locoregionally advanced nasopharyngeal carcinoma (NPC) treated by intensitymodulated radiation therapy (IMRT) alone,and offering evidence for relevant perspective studies.Methods Totally 185 locoregionally advanced NPC patients were divided into high-risk and low-risk groups for evaluation and comparison.The patients who met at least one of the following criteria were defined as high-risk group and others as low-risk group:GTVnx ＞ 30 cm3;Clinical stage T4N2M0;multiple neck node metastases with 1 node size ＞4 cm,and N3 with any T stage.Results With a median follow up of 110.9 months (6.7-152.4 months),the 5-year overall survival,locoregional relapse-free survival,distant metastasis-free survival for the high-risk group vs.the low-risk group were 61.0％ vs.90.5％ (x2 =30.298,P＜0.05),78.3％ vs.91.5％ (x2 =6.352,P＜0.05)and 71.6％ vs.92.0％ (x2 =16.346,P ＜0.05).Conclusions As a simple and practicable method,the risk category system is helpful for discriminating locoregionally advanced nasopharyngeal carcinoma with different risk-group of treatment failure and in further perspective clinical research.

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Clinical analysis of intensity modulated radiation therapy in cervical cancer patients with para-aortic lymph node metastasis after initial treatment

Xiaofan LI ; Yongheng LI ; Xing SU

Chinese Journal of Radiological Medicine and Protection.2015;35(7):522-527. doi:10.3760/cma.j.issn.0254-5098.2015.07.010

Objective To evaluate the efficacy and toxicities of intensity modulated radiation therapy (IMRT) with or without concurrent chemotherapy in the treatment of cervical cancer patients with para-aortic lymph node (PALN) metastases after initial treatment.Methods From Oct 2008 to Aug 2013,56 cervical cancer patients with PALN metastases after initial treatment,including radical resection or pelvic radiotherapy/chemoradiotherapy,were selected for analysis.The delivered radiation dose to PALN was 55-60 Gy for GTV and 45-50 Gy for CTV respectively with 25-30 fractions during 5-6 weeks.36 patients received concurrent paclitaxel (135 mg/m2) and cisplatin (60 mg/m2) chemoradiotherapy (CRT group) and 20 patients received RT alone (RT group).Results The median follow-up time after treatment was 22.7 months (2.7 to 74.4 months).98.2％ (55/56) of patients completed RT.In CRT group,38.9％ underwent concurrent TP regimen 2-3 cycles and the rest completed one cycle.The rates of CR plus PR in CRT and RT groups were 91.7％ (33/36) and 85％ (17/20),respectively (x2 =0.516,P ＞0.05).The 3-year overall survival rate in CRT group and RT group were 57.5％ and 32.7％ (x2 =4.059,P ＜ 0.05),and 3-year progression-free survival rates were 50.4％ and 29.2％ (x2 =4.184,P ＜ 0.05),respectively.TP regimen concurrent chemoradiotherapy was more effective than radiotherapy alone.The 3-year overall survival rate was 53％ and 39.5％ in patients with isolated PALN and nonisolated PALN,respectively (x2 =4.265,P ＜ 0.05).Grade 3 or 4 acute leukopenia was found in 10 (27.8％,CRT group) and 6 (30％,RT group) patients (x2 =0.693,P ＞ 0.05).Grade 3 gastrointestinal toxicity occurred in 1 patient each group (x2 =0.847,P ＞ 0.05).Conclusions TP regimen concurrent CRT is associated with better survival than RT alone,and the treatment toxicities could be tolerant.

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Correlation occurrence of radiation induced encephaledema with target dose and volume in stereotactic radiosurgery of epilepsy

Yuefei FAN ; Mingying GENG

Chinese Journal of Radiological Medicine and Protection.2015;35(7):528-531. doi:10.3760/cma.j.issn.0254-5098.2015.07.011

Objective To study the correlation between the occurrence of encephaledema and the target dose-volume after the low dose stereotactic radiosurgery of epilepsy.Methods Totally 136 epilepsy patients treated by low dose stereotactic radiosurgery with Novalis System were analysed retrospectively.The target doses and volumes of the patients were analysed by drawing out the scatterplot and conducting the binary Logistic regression to all of the data.An equation was obtained to predict the occurrence of radiation induced encephaledema in certain range of target volume and dose.Results Among all of 136 patients,different degree of local encephaledema occurred in 19 cases after the radiosurgery.Higher occurrence of radiation induced encephaledema was observed when the target central dose (i.e.90％ isodose circling the target)was more than 18 Gy or the target volume more than 30 cm3.Moreover,in patients with multitargets the doses of different targets devoted to each other,which could lead to the occurrence of local encephaledema.The equation to predict the occurrence probability was obtained by regression analysis.By testing this equation in all of 136 patients the coincidence percentage was 94.7％.Conclusions The target dose and volume could be effective parameters in certain range to predict the occurrence probability of radiation induced encephaledema.This equation would help to establish and optimize the therapeutic planning system.So it could finally reduce the side-effect of low dose stereotactic radiosurgey in epilepsy patients.The equation has some clinical value.

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Performance comparison of four common LINAC daily QA instruments

Qiaoqiao HU ; Yibao ZHANG ; Zhuolun LIU ; Jian ZHANG ; Haizhen YUE ; Hao WU

Chinese Journal of Radiological Medicine and Protection.2015;35(7):532-535. doi:10.3760/cma.j.issn.0254-5098.2015.07.012

Objective To compare the performances of four commercially available LINAC daily QA instruments.Methods The dosimetric stability of a LINAC including central axis output,flatness and symmetry were verified and fine-tuned using a 3-dimensional water phantom,dosimeters and ionization chambers.The baseline of the four instruments including LINA-C,QUICK-C,BEAM-C and QA3 were set thereafter.Daily measurements of LINAC were conducted with these instruments respectively and the results were compared.Arbitrary errors (CAX and SYM) beyond TG-142 tolerances were introduced to the LINAC to test the sensibilities of each instrument in detecting these changes.Results Relative to the baseline that were measured by the 3-dimensional water phantom and dosimeters,the results monitored by the four instruments were comparable.The maximum disparities of the CAX,FLAT,and SYM were 0.5％ (LINA-C),-0.45％ (QUICK-C),and 0.5％ (BEAM-C),respectively.All checkers detected the known errors successfully.Conclusions The stabilities of all the four evaluated instruments met the requirements of daily QA for LINAC.LINA-C verifies CAX only.QUICKE-C,BEAM-C and QA3 can be used to perform all the daily QA protocols as suggested by AAPM TG 142 report.They also provide unique additional functions.The setup of baseline determines if the morning checkers could measure the LINAC dosimetric parameters correctly.When an error is alarmed by the morning checker,it is recommended to verify the performance of the instrument first rather than recalibrating the LINAC immediately.

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Monitoring of radiation dose to medical staff during 125I seeds loading

Yao YUE ; Haisheng LIU ; Junjie WANG ; Chengxiang GUO ; Yuliang JIANG ; Haitao SUN

Chinese Journal of Radiological Medicine and Protection.2015;35(7):536-538. doi:10.3760/cma.j.issn.0254-5098.2015.07.013

Objective To analyze the dose of radiation to medical staff during 125I seeds loading Methods The radiation dose at different distances was measured by using thermoluminescence dosimeters (TLD),and the safe range for medical person was calculated.The doses and annual accumualive doses to the medical staff were estimated.Results The dose attenuation rates were 77.61％,98.04％,98.79％,99.30％,99.71％ and 100％ at distance of 10,20,30,40,50 and 100 cm from seeds tank,respectively.The dose to fingertips,chest,lens and thyroid of doctor were 51.08,35.50,34.73 and 33.78 μGy,and the annual dose reached 12.77,8.88,8.68 and 8.45 mGy when the number of annual operations was 250.The attenuation rate was 79.60％ and 28.36％ of inside and outside lead glass,respectively.Conclusions The radiation is undetectable at 100 cm away from seeds tank in the process of loading of 125I seeds,and lead glass is necessary for radiation protection.

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The effects of γ-ray radiation on hematopoiesis and T lymphocyte subset function

Wenxiu HAN ; Zhiyin ZHENG ; Liming YIN ; Ruilan GAO

Chinese Journal of Radiological Medicine and Protection.2014;34(3):172-175,187. doi:10.3760/cma.j.issn.0254-5098.2014.03.004

Objective To observe the effects of whole body γ-ray radiation on hematopoiesis and cytokines related to T cell subsets in mouse,to detect the expression of transcription factors of splenic T cell subsets,and to investigate the correlation between hematopoiesis injury and abnormal immune function.Methods Totally 50 BALB/c mice were divided into radiation group and blank control group with the random number table method.The former group were given 5.5 Gy 60Co γ-ray radiation on whole body and another received sham radiation.The numbers of white blood cells and platelets of radiation group were counted at 4,8,12 and 20 d after radiation,and these numbers of blank control mice were counted only at 20 d.Hematopoietic tissue proliferation was evaluated by biopsy sections of mice femur.The contents of Th1,Th2,and Th17 in peripheral blood were detected with cytometric bead array (CBA).The expressions of T-bet/GATA-3 and RORγt/Foxp3 proteins related to the differentiation of T cell subsets in spleen tissue were measured by Western blot.Results The numbers of white blood cells and platelets of radiation group mice were reduced obviously (t WBC =18.48,15.72,9.79,3.30; t PLT =22.52,19.74,11.78,4.70,P ＜ 0.05) compared with blank control group.Biopsy sections showed that bone marrow hematopoietic cells of the radiated mice were less than those of blank group,and adipocytes became more.At 8 d,the marrow suppressions were more obvious than those at 20 d.Serum contents of Th1 cytokines IFN-γ,TNF-α and Th2 cytokines IL-4,IL-6 in the radiation group were higher than those in the blank control group at 8 and 12 d(t IFN-γ =2.93,3.36,t TNF-α =6.09,8.11,6.43,4.49,tIL-4 =4.49,3.18,t IL-6=5.11,8.67,6.67,8.55,P＜0.05).IL-17A secreted mainly by Th17 cells was also higher than the blank (t =3.68,6.24,5.32,4.06,P ＜ 0.05).Compared with the blank control group,the expression of T-bet protein increased significantly (t =5.64,2.75,3.56,4.65,P ＜ 0.05),and the expressions of GATA-3,RORγt,and Foxp3 proteins decreased at 4,8 and 12 d except the RORγt at 20 d (tRORγt =6.79,4.31,4.47,tGATA-3 =3.88,8.06,2.84,3.23,tFoxp3 =10.00,8.06,2.89,5.93,P＜ 0.05).Conclusions 5.5 Gy whole body γ-ray radiation inhibits bone marrow hematopoiesis of BALB/c mice and makes the differentiation and function of T cells to be abnormal,which may be associated with bone marrow hematopoiesis obstacle.

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Role of replication protein A in the radioresistance of esophageal cancer cell line and its mechanism

Dahai YU ; Chong ZHOU ; Ye TIAN

Chinese Journal of Radiological Medicine and Protection.2012;32(4):347-349,368. doi:10.3760/cma.j.issn.0254-5098.2012.04.003

Objective To evaluate the effect of replication protein A (RPA) gene suppression on the radiosensitivity of esophageal cancer cells (TE-1R ) and underlying mechanism. Methods A radioresistant human esophageal cancer cell line TE-1 R was screened out by fractionated irradiation to TE-1 cells,then siRPA1 or siRPa2 was transfected to TE-1R cells.The untransfected (Con) group and nonsense siRNA transfected (NC) group were set as control groups.The survival was measured with colony-forming assay and the cell cycle distribution was measured with flow eytometry.Results Compared with the Con and NC groups,the protein expression of RPA1 and RPA2 decreased significantly 48 h after siRPA1 and siRPA2 transfection.The D0,Dq,and SF2 values reduced from 2.09,1.70,0.85 in NC group to 1.67,0.71,0.44 and 1.82,0.89,0.51 in siRPAl and siRPA2 transfection groups,respectively.Accordingly,the sensitization enhancement ratios of Dq were 2.39 and 1.91,respectively.The G2/M arrest in siRPA1 and siRPA2 transfection groups increased from (18.701 3.14)％ of NC group to (26.95 ± 3.96)％ and (25.28 ± 2.74) ％ (t =2.827,2.853,P ＜0.05),respectively.Conclusions Knocking down of RPA1 or RPA2 genes can enhance the raidosensitivity of human esophageal cancer cells TE-1R,where the inhibition of radiation-induced sublethal damage repair may be involved.Accordingly,RPA may become a new target of radiosensitization in esophageal cancer.

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Effect of sanguinarine on the growth and radiosensitivity of human ovarian cancer cells

Jiaying XU ; Junmin JI ; Yang HAO ; Li WU ; Saijun FAN

Chinese Journal of Radiological Medicine and Protection.2012;32(1):6-10,14. doi:10.3760/cma.j.issn.0254-5098.2012.01.002

Objective To study the effect of sanguinarine on the growth and radiosensitivity of ovarian cancer SK-OV-3 cells.Methods Cell growth was determined by MTT and clonogenic assay.Cell cycle analysis was performed by flow cytometry assay.The cell apoptosis was analyzed by Annexin V/PI assay.Results Sanguinarine inhibited SK-OV-3 cell growth in a dose-and time-dependent fashion and its IC50 values were 3.02 and 1.11 μmol/L at 24 and 48 h,respectively. Sanguinarine also significantly triggered a sub-G1 peak,an indicator of apoptosis,and caused a G0/G1 arrest.Furthermore,the cell apoptosis induced by X-irradiation was significantly increased at 6 Gy when the cells were pre-treated with sanguinarine,in which the early apoptotic population increased from 10.28％ to 43.28％ (t =19.41,P ＜0.01 ) and the late apoptotic population increased from 20.26％ to 30.80％ ( t =8.78,P ＜ 0.01 ).The multi-target click model was used to fit survival curves and the SER of sanguinarine treatment approached to 1.625 at the dose of D0. Conclusions Sanguinarine could inhibit SK-OV-3 cell growth by inducing apoptosis and cell cycle arrest and enhance cell radiosensitivity at low doses.

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Simultaneous silence of bcl-2 and XIAP increases radiosensitivity of UMSCC12 head and neck cancer cells

Wenyan LI ; Wei LIU ; Xiaojie MENG

Chinese Journal of Radiological Medicine and Protection.2012;32(1):40-43,59. doi:10.3760/cma.j.issn.0254-5098.2012.01.009

Objective To investigate the radiosensitization effect of the simultaneous silence of bcl-2 and XIAP on human head and neck cancer cell line in vitro.Methods Four groups of UMSCC12 cells were transfected with siRNA-bcl-2,siRNA-XIAP,siRNA-bcl-2 plus siRNA XIAP,and siRNA control,respectively.The silence efficiency was tested by Western blot assay. Apoptosis was evaluated with the activities of caspase-3 and caspase-9,and radiosensitization effect was evaluated with clonogenic assay.Results Bcl-2 and XIAP protein expressions were effectively eliminated in the cells simultaneously transfected with siRNA-bcl-2 and siRNA-XIAP.Transfection of cells with bcl-2 siRNA increased radiationinduced apoptosis ( t =5.32,6.27 ; P ＜ 0.05 ),but transfection with XIAP siRNA did not impact cell apoptosis.Since the simultaneous transfection of the above two siRNAs,the activities of caspase-3 and caspase-9 were increased by 1.36 and 1.34 times ( t =11.47,6.22 ; P ＜ 0.05 ) in nonirradiated cells and increased by 1.72 and 1.98 times ( t =12.02,20.14; P ＜ 0.05 ) in irradiated cells,respectively.The colonic assay showed that the SERs were 1.06,1.15 and 1.41 for the cells transfected with XIAP siRNA,bcl-2 siRNA and both siRNAs,respectively.Conclusions Compared to single silence of XIAP or bcl-2,simultaneous silence of XIAP and bcl-2 offers a potential approach to improving the radiosensitivity of the head and neck cancer cells,and apoptosis might contribute to the enhancement of radiosensitization.

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Deficiency of DNA double-strand break repair and enhanced radiosensitivity in Tip60 silenced cells

Rong FAN ; Shimeng ZHANG ; Xiaodan LIU ; Yu WANG ; Qinzhi XU ; Pingkun ZHOU

Chinese Journal of Radiological Medicine and Protection.2011;31(5):511-514. doi:10.3760/cma.j.issn.0254-5098.2011.05.001

Objective To investigate the effect of Tip60 on the cellular radiosensitivity,and to explore the related mechanism.Methods siRNA and anacardic acid (AA,an inhibitor of Tip60 acetyltransferase) were used to inhibit Tip60 expression and its acetyltransferase activity,respectively.Radiosensitivity was analyzed by colony-forming ability assay.γ-H2AX foci were detected to analyze the DNA double-strand break (DSB).Immunoprecipitation was used to determine the interaction of proteins.Results siRNA-mediated silencing of Tip60 led to enhanced sensitivity of U2OS cells at 1,2 Gy after γ-ray irradiation,but had no significant effect at 4 Gy post-irradiation ( t =3.364,3.979,P ＜ 0.05 ).γ-H2AX foci detection indicated that Tip60 silencing resulted in a decreased capability of DNA doublestrand break repair at 1,4 and 8 h after irradiation( t =3.875,3.183 and 3.175,respectively,P ＜ 0.05 ).The interaction of Tip60 and DNA-PKcs was prompted by ionizing radiation.Anacardic acid largely abrogated the phosphorylation of DNA-PKcs at T2609 site induced by irradiation.Conclusions Tip60plays a role in the cellular response to ionizing radiation-induced DNA damage through,at least in part,interacting with DNA-PKcs and regulating its phosphorylation.

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