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A study of radiosensitizing effect of PKM2 silencing in lung adenocarcinoma cells and xenografts

Huanhuan WANG ; Xianliang ZENG ; Maobin MENG ; Dong QIAN ; Guoguang YING ; Lujun ZHAO ; Zhiyong YUAN ; Ping WANG

Chinese Journal of Radiation Oncology.2015;(4):466-470. doi:10.3760/cma.j.issn.1004-4221.2015.04??028

Objective To investigate the impacts of pyruvate kinase M2 isoform (PKM2) silencing on the radiosensitivity of lung adenocarcinoma cell line (A549 cells) and the radiation synergy of xenografts, and to explore their mechanisms. Methods Plasmid pshRNA?PKM2 for interference with PKM2 expression was transfected into A549 cells, and empty vector?transfected cells and untransfected cells were set as con?trols. The silencing efficiency of pshRNA?PKM2 and the expression level of microtubule?associated protein 1 light chain 3(LC3) were measured by Western blot assay. The radiosensitizing effects in A549 cells and xen?ografts after PKM2 silencing were determined by colony?forming assay and xenografts growth curves. Autoph?agy formation in A549 cells and xenografts was analyzed by transmission electron microscopy, and the ex?pression level of PKM2 in xenografts was measured by immunohistochemistry. Comparison between groups was made by Student′s t?test, and the body weights of nude mice and xenograft volumes were subjected to a?nalysis of variance for continuous variables. Results Stable A549 cell lines transfected with pshRNA?PKM2 were successfully produced. Transfection with pshRNA?PKM2 significantly down?regulated PKM2 expression in A549 cells and xenografts (P= 0?? 001;P= 0?? 000). The sensitizer enhancement ratios for A549 cells and xenografts were 1?? 47 and 2?? 00, respectively. Interference with PKM2 expression enhanced radiation?in duced autophagy formation and significantly increased the ratio of LC 3 ? II / I ( P= 0.000 1 ) . Conclusions Silencing of PKM2 expression may enhance the radiosensitivity of A549 cells and xenografts by regulation of autophagy, which holds promise for becoming an effective radiosensitizing target for non?small cell lung canc?er, but still needs to be confirmed by further studies.

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Preliminary efficacy of bevacizumab for cerebral radiation necrosis

Mianshun PAN ; Yong LI ; Shujun QIU ; Lei CHEN ; Xianjun SHAO ; Li ZHANG ; Guoyu ZHANG ; Fenghua ZHUGE

Chinese Journal of Radiation Oncology.2015;(4):434-437. doi:10.3760/cma.j.issn.1004-4221.2015.04??020

Objective To evaluate the preliminary clinical efficacy of bevacizumab for cerebral radiation necrosis (CRN). Methods Nineteen patients with CRN for whom the treatment with steroids and mannitol failed were retrospectively analyzed with a total of 22 lesions. Except for 5 lesions confirmed by pathological evidence, all lesions were confirmed by the following imaging evidence:1. computed tomography (CT)?or magnetic resonance imaging (MRI)?enhanced lesions showed loss of tension and were accompanied by substantial edema;2. CT?or MRI?enhanced lesions had a low perfusion pressure;3. magnetic resonance spectroscopy indicated that the enhanced areas had a decreased choline peak; 4. positron emission tomography showed that the fluorodeoxyglucose uptake was substantially reduced in the enhanced areas. All patients were given 5 mg/ kg bevacizumab at an interval of 14 days for 2?6 cycles. MRI examination was performed in each cycle before treatment, and the enhanced lesions on T1?weighted images ( T1 WI) and edema on T2?weighted images (T2 WI) were compared before and after treatment. The clinical symptoms, Karnofsky Performance Status ( KPS), and adverse reactions in all patients were evaluated. Comparison before and after treatment was performed by paired t test. Results All 19 patients completed the treatment successfully and there were no severe adverse reactions. The clinical symptoms of patients were substantially improved after the second cycle of treatment, and the KPS score increased by 26?? 8 on average. The visible volume of enhanced lesions on MRI T1 WI was significantly reduced by 54?? 8% after treatment (P= 0?? 000), while the visible volume of edema on MRI T2 WI was reduced by 80?? 7% after treatment (P= 0?? 000). The follow?up time ranged from 3 to 12 months with a mean value of 5?? 6 months. Eleven patients kept clinical improvement in CRN, four patients had recurrence, and four patients died from tumor progression. Conclusions Bevacizumab is preliminarily confirmed to substantially improve the clinical symptoms and quality of life in patients with CRN.

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Safety analysis of Intensity-modulated radiation therapy of glioblastoma with simultaneous integrated boost technique

Zheng WANG ; Wei JIANG ; Qingsong PANG ; Ping WANG

Chinese Journal of Radiation Oncology.2015;(4):431-433. doi:10.3760/cma.j.issn.1004-4221.2015.04??019

Objective To investigate clinical efficacy of simultaneous integrate boost for glioblastoma with intensity?modulated radiotherapy ( SIB?IMRT). Methods A total of 46 patients with glioblastoma who underwents SIB?IMRT from January 2013 to August 2014,were retrospectively analyzed. Toxicity after completion of SIB?IMRT were assessed. Kaplan?Meier method was used to analyze survival and progression?free survival. Multivariate analyses were performed to determine significant prognostic factors. Results There was no patients delayed by more than grade 3 radiation toxicity. The median overall survival and 1?year survival rates was 69 weeks and 73%,respectively. The progression free survival and 1?year progression?free survival rate were 43 weeks and 39%,respectively. The pattern of failure was identical (9 Local, 7 distant and 0 marginal recurrence). Multivariate analyses show that temozolomide concurrent chemoradiotherapy were independent factors correlated to prognosis. Conclusions The preliminary results demonstrate that SIB?IMRT for glioblastoma appear to be effective and safe. With the limted number of patients in this group,SIB?IMRT could be used for treating glioblastoma with caution,which deserves further study.

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Paired observation of californium-252 neutron intraluminal brachytherapy combined with external-beam radiotherapy with and without lead shielding for cervical cancer

Zhuojie DAI ; Xin LEI ; Yonghong CHEN ; Jia LIU

Chinese Journal of Radiation Oncology.2015;(4):400-403. doi:10.3760/cma.j.issn.1004-4221.2015.04??012

Objective To compare the efficacy between californium?252 ( 252 Cf ) neutron intraluminal brachytherapy combined with external?beam radiotherapy with lead?shielding pelvic parallel opposing field technique and non?lead?shielding four?field box technique for cervical cancer. Methods A total of 52 patients with stage Ⅱa?Ⅲb cervical squamous cell carcinoma who were admitted to our hospital from 2004 to 2007 were enrolled as subjects and paired by clinical stage, age, tumor size, and degree of anemia. The 26 pairs of patients were divided into lead?shielding pelvic parallel opposing field group (lead?shielding group) and non?lead?shielding four?field box group (non?lead?shielding group). For all patients in both groups, 252 Cf neutron brachytherapy was added in external?beam radiotherapy. The local control (LC), overall survival (OS), and disease?free survival (DFS) rates were calculated using the Kaplan?Meier method and analyzed using the log?rank test. The difference in the incidence of late complications was analyzed using the McNemar method. Results There were significant differences in 5?year LC, OS, and DFS rates between the lead?shielding group and the non?lead?shielding group (85% vs. 81%, P= 0?? 014;89% vs. 73%, P=0?? 013; 89% vs. 73%, P= 0?? 013 ). There was also significant difference in the incidence of late complications between the lead?shielding group and the non?lead?shielding group ( 12% vs. 23%, P=0?? 008). Conclusions When intraluminal brachytherapy combined with external?beam radiotherapy is used to treat cervical cancer, the centers of the front and back fields should be shielded by lead, regardless of whether the parallel opposing field technique or the four?field box technique is used.

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A study of changes in volume and location of target areas and organs at risk in intensity-modulated radiotherapy for cervical cancer

Jianwu CHEN ; Ping LIU ; Wenjuan CHEN ; Penggang BAI ; Jiangshan LI ; Xiaolei NI ; Kaiqiang CHEN ; Qixin LI

Chinese Journal of Radiation Oncology.2015;(4):395-399. doi:10.3760/cma.j.issn.1004-4221.2015.04??010

Objective To investigate the changes in volume and spatial location of target areas and normal tissues before and during intensity?modulated radiotherapy (IMRT) for cervical cancer by quantitative means. Methods Forty patients with cervical cancer who were treated with IMRT were enrolled as subjects. Computed tomography ( CT) was performed before IMRT and during IMRT when a dose of 27 Gy ( 15 fractions) was reached. Clinicians delineated the target areas and organs at risk in the two groups of CT images. The target areas and organs at risk in one group of images were mapped to the other group of CT image by image registration using the Pinnacle treatment planning system. Volume changes in target areas and organs at risk were analyzed, and changes in the spatial location were evaluated by volume difference method and Dice similarity method. Comparison was made by paired t?test. Results There were significant differences in gross target volumes of primary tumor lesions ( GTV?T) and pelvic metastatic lymph nodes (GTV?N) before and during IMRT ( P= 0?? 000; P= 0?? 000). According to the evaluation by volume difference method, the average rate of change in GTV?T was (38.64±19?? 50)% with a range between 3?? 16%and 86?? 49%, while the average rate of change in GTV?N was (42.49± 25?? 68)% with a range between 2?? 79% and 87?? 42%. In the organs at risk, the bladder had the maximum rate of volume change, the average of which was (55.13±33?? 40)% with a range between 3?? 25% and 116?? 01%. According to the evaluation by Dice similarity method, the average Dice similarity coefficient for GTV?T was 0.50± 0?? 18 with a range between 0?? 10 and 0?? 85, while the average Dice similarity coefficient for GTV?N was 0.31±0?? 20 with a range between 0?? 00 and 0?? 71. The rectum had the minimum Dice coefficient in the organs at risk, the average of which was 0.57± 0?? 14 with a range between 0?? 18 and 0?? 76 . Conclusions For patients with cervical cancer to receive IMRT, since there are substantial changes in volume and spatial location of target areas and normal tissues before and during treatment, it is quite necessary to modify the treatment regimen in time in order to provide adequate doses for target areas and avoid overdose for organs at risk.

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Real-time patient transit dose verification of volumetric modulated arc therapy by a 2D ionization chamber array

Xiao LIU ; Yunlai WANG ; Zhongjian JU ; Wei XU ; Liyuan JIN

Chinese Journal of Radiation Oncology.2015;(4):462-465. doi:10.3760/cma.j.issn.1004-4221.2015.04??027

Objective To study the real?time dose verification with 2D array ion chamber array in volumetric modulated arc therapy ( VMAT) with a 2D array ion chamber array. Methods The 2D ion chamber array was fixed on the panel of electronic portal imaging device (EPID). Source?detector distance (SDD) was 140 cm. 8 mm RW3 solid water was added to the 2D array to improve the signal noise ratio. Patient plans for esophageal, prostate and liver cancers were selected to be delivered on the cylindrical Cheese phantom 5 times in order to validate the reproducibility of doses. Real?time patient transit dose measurements were performed at each fraction. Dose distributions were evaluated using gamma index criteria of 3 mm DTA and 3% dose difference referred to the first time result. Results The gamma index pass rate in the Cheese phantom were about 98%;the gamma index pass rate for esophageal, prostate and liver cancer patient were about 92%, 92% and 94%, respectively. Gamma pass rate for all single fraction were more than 90%. Conclusions The 2D array is capable of monitoring the real time transit doses during VMAT delivery. It is helpful to improve the treatment accuracy.

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Investigation of CT numbers correction of kilo-voltage cone-beam CT images for accurate dose calculation

Xuetao WANG ; Sen BAI ; Guangjun LI ; Xiaoqin JIANG ; Chen SU ; Yanlong LI ; Zhihui ZHU

Chinese Journal of Radiation Oncology.2015;(4):457-461. doi:10.3760/cma.j.issn.1004-4221.2015.04??026

Objective To study CT numbers correction of kilo?voltage cone?beam CT (KV?CBCT) images for dose calculation. Method Aligning the CBCT images with plan CT images, then obtain the background scatter by subtracting CT images from CBCT images. The background scatter is then processed by low?pass filter. The final CBCT images are acquired by subtracting the background scatter from the raw CBCT. KV?CBCT images of Catphan600 phantom and four patients with pelvic tumors were obtained with the linac?integrated CBCT system. The CBCT images were modified to correct the CT numbers. Finally, compare HU numbers between corrected CBCT and planning CT by paired T test. Evaluate the image quality and accuracy of dose calculation of the modified CBCT images. Results The proposed method reduces the artifacts of CBCT images significantly. The differences of CT numbers were 232 HU, 89 HU, 29 HU and 66 HU for air, fat, muscle and femoral head between CT and CBCT respectively (P= 0?? 39,0?? 66,0?? 59,1).The differences of CT numbers between CT and CBCT was reduced to within 5 HU. And the error of dose calculation with corrected CBCT images was within 2%. Conclusions The CT numbers of corrected CBCT are similar with plan CT images and dose calculations based on the modified CBCT show good agreement with plan CT.

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The effect of the shrinkage of thermoplastic mask on patient positioning

Yin ZHANG ; Jianrong DAI ; Minghui LI ; Guishan FU

Chinese Journal of Radiation Oncology.2015;(4):454-456. doi:10.3760/cma.j.issn.1004-4221.2015.04.025

Objective This study analyzes the effect of the shrinkage of thermoplastic mask on patient positioning. Methods Design of the two test. Test 1:thermoplastic film shrinkage test. Get some thermoplastic film by the size of 10 cm×5 cm, extrude it at a certain rate after heated. Measure the length of thermoplastic film on different time, and calculate the contraction. Test 2:phantom test. Take advantage of head and neck phantom, and simulate the procedure that from making mask for patients to radiation therapy. Measure the off set of isocenter which caused by the contraction of thermoplastic mask. Results The largest shrinkage of thermoplastic had happened in 20 minutes. Different tensile ratio had little effect on the shrinkage. The offset of isocenter which caused by the shrinkage of thermoplastic mask were:LR ( -0?? 1± 0?? 3) mm,SI (-0?? 2±0?? 2) mm, AP (0.6±0?? 4) mm,respectively. There was little change in the course of six weeks ( P= 0.185?0?? 961). Conclusions The cooling time should be more than 20 minutes, when making a mask for the patient. The setup errors which caused by the shrinkage of thermoplastic mask is at an acceptable level on this premise.

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The technique and development of total skin electron irradiation-Taiwan experiences

Jiaming WU ; Shian YE ; Yimin REN

Chinese Journal of Radiation Oncology.2015;(4):449-453. doi:10.3760/cma.j.issn.1004-4221.2015.04??024

Objective The aim of this study is to present two novel technique?Lying on position and rotational board TSEI in which uniform dose to the whole body as well as the soles and vertex of scalp can be achieved in one electron beam treatment fraction. Methods Patients are treated with two groups in prone and supine position by leaning on inner rotational board in prone and supine position, each group can further be separated into two subgroup with tilting and rotation positions for treatment. By incorporating all these setting on the aswirl board with the optimal gantry angle, the patient will final accumulate compensated dosages on whole body surface. Results The dose uniformity for the rotational board?TSET or Lying on position could be control within ±10%. Conclusions The two TSEItechnique?Lying on and Rotational board TSEI techniques presented in this study is able to deliver a uniform dose to the patient’s skin surface as well as to the vertex and the soles all in one time, eliminating the troubles of having to further boost fields for these two regions when using the Stanford Six Field Technique.

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Comparing different image registration methods in kilovolt cone-beam computed tomography image-guided radiotherapy for liver cancer

Jianting WANG ; Ming LIU ; Fushan ZHAI ; Anfeng WANG ; Xiaohui CAO ; Chaoen BAO

Chinese Journal of Radiation Oncology.2015;(4):444-448. doi:10.3760/cma.j.issn.1004-4221.2015.04??023

Objective To study the methods of matching kilovolt CBCT image with planning CT scan. Methods A total of 121 CBCT scans were matched with planning CT scan using a manual and four automatic match methods by four observers in the offline. In the manual match, the live contour was used as a surrogate for image registration. Four automatic match methods, including routine soft?tissue match, routine bone match, automatic liver match and vertebral body match, were performed using image registration sofeware. First, the stability of the sofeware was tested. Then, the reproducibility of the same automatic match method was evaluated by comparing different observers’ match results. After the manual match by four observers, the mean of the match results was used as a standard to compare with others. The differerces was test by McNemar method. Results In the uniform match factors, automatic match result would not change. The reproducibility of routine soft?tissue and bone match are best, automatic vertebral body match is better than automatic liver match. Howerver, the automatic liver match result is the most similar to manual match, the percentages of match result have an absolute error no more than 3 mm in left?right, superior?inferior and anterior?posterior directions are 84?? 3%, 77?? 7% and 92?? 6%. Conclusions Automatic liver match can be used in image?guided radiotherapy for liver cancer, however, it should be performed by experienced oncologist and technologist together in each fraction, after that, the matching result should be adjusted carefully according to live contour.

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