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Recent advances in DNA damage repair mechanism

Chinese Journal of Radiation Oncology.2017;26(9):1103-1108. doi:10.3760/cma.j.issn.1004-4221.2017.09.025

The stability of cell genetic material is influenced by a variety of factors, both internal and external, which can cause various types of DNA damage, such as DNA alkylation, oxidation, mismatching, loop structure, atypical DNA structure, single-strand break, and double-strand break.These DNA damages disrupt cellular homeostasis and dynamic equilibrium, which cause gene mutations, chromosomal abnormalities, and even degradation, aging, and death at different biological levels.By searching and identifying DNA damage sites, the cell activates a series of biochemical pathways, coordinates the progress of DNA replication and transcription, and then repairs the DNA damage.In this way, the cell maintains its independence and stability.While radiotherapy plays a role in eliminating tumors by DNA damages, it also initiates DNA damage responses.Among the responses, base excision repair, nucleotide excision repair, mismatch repair, double-strand break repair, and post-translesion synthesis repair play a key role in repairing the damages.The dysfunction of these repair pathways will cause differences in tumor radiation sensitivity.This paper summarizes recent research results in DNA damage repair, and focuses on the types of DNA damage and their repair mechanisms, so as to promote the understanding of the great significance of this field and to provide a theoretical basis for exploring the application of DNA damage repair pathways in tumor therapy.

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Research progress in internal mammary lymph node irradiation for breast cancer

Binbin CONG ; Jinming YU ; Yongsheng WANG

Chinese Journal of Radiation Oncology.2017;26(9):1094-1098. doi:10.3760/cma.j.issn.1004-4221.2017.09.023

Internal mammary lymph node irradiation (IMLNI) could reduce local recurrence and distant recurrence and improve survival.The NCCN Guidelines have updated the recommends in IMLNI.However, the relative toxicities of IMLNI to the heart and lungs should be carefully considered by clinicians, so individualized indications for IMLNI are needed.Internal mammary sentinel lymph node biopsy (IM-SLNB) could be an accurate technique to guide IMLNI with minimally invasive staging, and provide more survival benefits to patients.This article reviews the benefits of IMLNI, controls of the side effect, and discussion of IMLNI guided by IM-SLNB.

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Recent advances in delineation of clinical target volume in radiotherapy for rectal cancer

Yongqiang YANG ; Yaqun ZHU ; Ye TIAN

Chinese Journal of Radiation Oncology.2017;26(9):1089-1093. doi:10.3760/cma.j.issn.1004-4221.2017.09.022

The delineation of clinical target volume (CTV) is a critical step in planning conformal radiotherapy for rectal cancer.Several guidelines suggest different subvolumes and anatomical boundaries in radiotherapy for rectal cancer, potentially leading to a misunderstanding of CTV definition.This article reviews recent advances in the delineation of CTV in radiotherapy for rectal cancer.

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Liver kinase B1 gene enhances radiosensitivity of lung cancer H460 cells:an in vivo study

Hao LI ; Wei ZHANG ; Haoying HUANG ; Xiangnan QIU ; Shaodong TONG ; Xinjun ZHANG ; Hui WANG ; Ruilin XIE ; Zhaohui QIN ; Yuanhu YAO

Chinese Journal of Radiation Oncology.2017;26(9):1084-1088. doi:10.3760/cma.j.issn.1004-4221.2017.09.021

Objective To investigate the effect of liver kinase B1(LKB1) on the radiosensitivity of subcutaneous xenograft tumor of lung cancer H460 cells in nude mice.Methods Human lung cancer H460 cells were implanted into female nude mice (BALB/c-nu) to establish a subcutaneous xenograft tumor model of lung cancer.A total of 24 female nude mice in which the model was successfully established were equally and randomly divided into four groups:pEGFP-Ctrl plasmid (empty vector plasmid) group, irradiation (IR)+pEGFP-Ctrl plasmid group, pEGFP-LKB1 plasmid (overexpressing LKB1) group, and IR+pEGFP-LKB1 plasmid group.The growth of xenograft tumors was observed and the tumor inhibition rate and enhancement factor (EF) were calculated.The expression of LKB1 in each group was measured by immunohistochemistry and Western blot to analyze the relationship between LKB1 and radiosensitivity.Results Compared with the pEGFP-Ctrl plasmid group, the IR+pEGFP-Ctrl plasmid group, pEGFP-LKB1 plasmid group, and IR+pEGFP-LKB1 plasmid group showed varying degrees of inhibition of tumor growth, particularly in the IR+pEGFP-LKB1 plasmid group, and the tumor inhibition rates were 31.30%, 14.78%, and 43.48%, respectively.The EF of LKB1 in the IR+pEGFP-LKB1 plasmid group was 1.18.The immunohistochemistry and Western blot showed that LKB1 could be effectively expressed in the pEGFP-LKB1 plasmid group and IR+pEGFP-LKB1 plasmid group, but not in the other two groups.Conclusions The subcutaneous xenograft tumor model of human lung cancer H460 cells has been successfully established in nude mice.LKB1 has a radiosensitizing effect on the subcutaneous xenograft tumor of lung cancer H460 cells in nude mice.

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Setup error of Orfit versus vacuum bag in radiotherapy for cervical cancer

Lijuan GAO ; Jiamin HUANG ; Jun HUANG ; Jianxin SU ; Yuqi WU ; Chengguang LIN

Chinese Journal of Radiation Oncology.2017;26(9):1080-1083. doi:10.3760/cma.j.issn.1004-4221.2017.09.020

Objective To compare the setup errors of the negative pressure vacuum air cushion (vacuum bag) and the Orfit body foam fixator (Orfit frame) in radiotherapy for cervical cancer.Methods A total of 40 patients receiving three-dimensional radiotherapy for cervical cancer were enrolled in this study and equally and randomly divided into vacuum bag group and Orfit frame group.And the two groups were divided into Orfit-1 group, Orfit-2 group, vacuum-1 group, and vacuum-2 group according to the treatment course.The Orfit-1 group and vacuum-1 group were the data in the first 12 treatments, while the Orfit-2 group and vacuum-2 group were the data in the following 13 treatments.A cone-beam computed tomography scan was performed before each treatment to analyze setup error and then the body position was corrected to start the treatment.Comparison of continuous data between groups was made by paired t-test, while comparison of categorical data was made by chi-square test.Results There was a significant difference in the setup error in y-axis direction between the Orfit-1 group and the Orfit-2 group (P=0.003) and the setup error in r-axis direction between the vacuum-1 group and the vacuum-2 group (P=0.013).There were no significant differences in the setup errors in four directions (x-axis, y-axis, z-axis, and r-axis) between the Orfit-1 group and the vacuum-1 group (P>0.05).There were significant differences in the setup errors in y-axis and z-axis directions between the Orfit-2 group and the vacuum-2 group (P=0.007;P=0.001).Conclusions The Orfit frame and the vacuum bag have their own advantages and disadvantages in the fixation of body position in radiotherapy for cervical cancer.The setup error can be improved by long vacuum bags, ultrasound bladder capacity scanner, image-guided radiotherapy, or sectional radiotherapy plan.

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A comparative study of measurement of small field data and calculation based on Monte Carlo method

Ning CHEN ; Jianliang ZHOU ; Jie QIU ; Bo YANG ; Tingtian PANG ; Nan LIU ; Xia LIU ; Lang YU ; Wenbo LI ; Tingting DONG ; Fuquan ZHANG

Chinese Journal of Radiation Oncology.2017;26(9):1077-1079. doi:10.3760/cma.j.issn.1004-4221.2017.09.019

Objective To compare the relative dose of small fields measured by clinically common detectors and those obtained from Monte Carlo simulation in order to obtain the accurate measurement method, and to modify the inappropriate detectors.Methods The percentage depth-dose distribution curve and profile (flatness and symmetry) curves were collected at 2 cm×2 cm, 3 cm×3 cm, and 4 cm×4 cm under 6-MV X-ray of Trilogy linear accelerator by CC13, PFD, SFD, and blue phantom.The results were compared with the stimulation results from Monte Carlo method (the current gold standard).The correction factors for the detectors with large error were calculated to provide reference data for clinical practice.Results The results measured by SFD detector were most close to the results from Monte Carlo simulation.The measurement errors of CC13 and PFD detectors were large.The correction factor in the penumbra for CC13 and PFD detector was 0.664-1.499.Conclusions SFD detector is better than CC13 and PFD detector in the measurement of small fields, but CC13 and PFD detector can provide reference data for clinical practice after the corresponding correction.

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Influence of CT value division on dose calculation in treatment planning

Jun ZHANG ; Dingyi ZHOU ; Conghua XIE ; Hui LIU ; Fuxiang ZHOU ; Yahua ZHONG ; Jing DAI ; Yunfeng ZHOU

Chinese Journal of Radiation Oncology.2017;26(9):1067-1071. doi:10.3760/cma.j.issn.1004-4221.2017.09.017

Objective To divide computed tomography (CT) values into different ranges and investigate the influence of CT value division on dose calculation, and to propose a method to combine magnetic resonance imaging (MRI) with assigned CT values.Methods Ten CT images each were collected from patients with head and neck, chest, and pelvic tumors.Random sampling was performed for the CT values of main tissues or organs at the three parts, and then the mean CT value of each tissue or organ was calculated to divide the CT values into different ranges.A virtual phantom was built in the Varian Eclipse treatment planning system, and for the prescribed dose of 100 cGy, the machine output was recorded at different CT values.The influence of different CT value ranges on dose calculation was analyzed.The treatment plans of intensity-modulated radiotherapy were selected from 5 cervical cancer patients, and new CT values were assigned to the planning target volume (PTV) and organs at risk to obtain new CT images.The plans were transferred to the new CT images and compared with the results on the original CT images in terms of dosimetric parameters.Results After dividing the CT values into different ranges and verifying the results in dose calculation, the CT values corresponding to different human tissues or organs were-100 to 100 HU.The influence of CT value variation on dose calculation was within 3%.In the same treatment plan, there were small differences in dosimetric parameters between new CT images and original CT images.Dmax, Dmean, D98%, D95%, D5%, and D2% of PTV were all below 3%, and Dmax and Dmean of the bladder, rectum, small intestine, femoral head, and bone marrow were below 2%.Conclusions The influence of CT value division on dose calculation in the treatment planning for pelvic tumors is acceptable, so it can be used in combination with MRI.

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Dosimetric analysis of 3D-printed coplanar template-assisted and CT-guided 125I seed implantation for the treatment of malignant tumors

Ran PENG ; Yuliang JIANG ; Zhe JI ; Fuxin GUO ; Haitao SUN ; Jinghong FAN ; Xu LI ; Junjie WANG

Chinese Journal of Radiation Oncology.2017;26(9):1062-1066. doi:10.3760/cma.j.issn.1004-4221.2017.09.016

Objective To compare the pre-and post-operative tumor target volume and to examine the consistency in physical dosimetric parameters of organs at risk (OAR) following 3D-printed coplanar template (3D-PCT)-assisted and CT-guided radioactive seed implantation.Methods The 3D-printed coplanar template was designed using a computer software, and the coordinate system was established where the center was used as the basis for setting the x axis and y axis.Crosses defining the center of treatment were drawn on the patient''s body and matched with the corresponding central point, x axis, and y axis of the coplanar template.3D-PCT-assisted and CT-guided radioactive seed implantation was performed based on the pre-operative plan, and the pre-operative, operative, and post-operative plans were designed to evaluate the target tumor volume and the normal dose received by the tissues.In addition, dosimetric parameters, including D90(minimum dose received by 90% of the gross target volume), V100, V150, V200(percentage of GTV that received 100%, 150%, and 200% of the prescribed dose, respectively), minimum peripheral dose (MPD), conformal index (CI), external index (EI), and homogeneity index (HI) in the pre-operative and post-operative plans were also assessed and compared using the Wilcoxon test. Results Fourteen patients treated in our institution from August to October, 2016 were included in this study. The median age of the patients was 61.5 years, and the median Karnofsky Performance Scale score was 80. A total of 14 lesions from the 14 patients were treated by seed implantation in the neck (n=4), chest (n=3), abdomen (n=5), and pelvis (n=2). Of the 14 patients that underwent implantation, 8 had previously received radiation therapy, and 6 had not received radiation therapy. Dosage optimization was performed for all patients during the operation. The median activity of the implanted seeds was 0.625 mCi (0.55-0.75 mCi,1 Ci=3.7×1010 Bq), and the preoperatively planned median number of needling and implanted seeds were 9(4-34) and 45.5(10-162), respectively. However, the actual median number of needling and implanted seeds were 9.5(4-34) and 45.5(10-162), respectively. Dosimetric analysis showed that there were no significant changes in tumor volume (P=0.135), D90(P=0.208), MPD (P=0.104), V100(P=0.542), V150(P=0.754), V200(P=0.583), CI (P=0.426), EI (P=0.326), and HI (P=0.952) after implantation. Conclusions 3D-PCT guidance and dosage optimization can result in good consistency between pre-and post-operative plans for radioactive seed implantation. 3D-PCT is a convenient and cheap technique suitable for large-scale clinical application.

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Dosimetric comparison between volumetric-modulated arc therapy and intensity-modulated radiotherapy for esophageal cancer:a meta-analysis

Han GAO ; Pengfei JIA ; Bingsen CHEN ; Lemin TANG

Chinese Journal of Radiation Oncology.2017;26(9):1055-1061. doi:10.3760/cma.j.issn.1004-4221.2017.09.015

Objective To investigate the dosimetric comparison of target volumes and organs at risk (OAR) between volumetric-modulated arc therapy (VMAT) and intensity-modulated radiotherapy (IMRT) for esophageal cancer by a meta-analysis.Methods A literature search was performed to collect the clinical studies on dosimetric comparison between VMAT and IMRT.The primary endpoints of interest were dosimetric parameters of target volumes and OAR, number of monitor units (MUs), and treatment time (TT).Results A total of 17 studies involving 323 patients were included in this meta-analysis.When the total dose was>50.4 Gy, VMAT showed significantly lower mean dose (Dmean) of gross tumor volume (GTV) and maximum dose (Dmax) of planning target volume (PTV) than IMRT (P=0.009;P=0.039).There were no significant differences in Dmean, V30, and V40 of the heart, Dmax of the spinal cord, and V5, V10, and Dmean of the lung between VMAT and IMRT (P>0.05).VMAT showed significantly lower V15, V20, and V30 of the lung than IMRT (P=0.001;P=0.000;P=0.023).When the single dose was 1.8 Gy and 2.0 Gy, VMAT showed significantly lower TT (reduced by 323.5 s and 193.7 s) and number of MUs (reduced by 275.4 MU and 134.2 MU) than IMRT (P=0.000 and 0.009;P=0.000 and 0.022).Conclusions VMAT can significantly reduce TT, MUs, irradiation dose to the lung, and the risk of radiation pneumonitis, and improve the utilization rate of equipment.Compared with IMRT, VMAT has no significant advantages in protection of the spinal cord and the heart and dosimetric parameters of target volumes except Dmean of PTV and Dmean and Dmax of GTV when the total dose was ≤50.4 Gy.

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Interfractional dosimetric study of target volume and organs at risk following intracavitary brachytherapy for cervical cancer

Junfang YAN ; Lang YU ; Ke HU ; Xiaorong HOU ; Jie SHEN ; Xin LIAN ; Zhikai LIU ; Fuquan ZHANG

Chinese Journal of Radiation Oncology.2017;26(9):1045-1049. doi:10.3760/cma.j.issn.1004-4221.2017.09.013

Objective To examine the interfractional dosimetric variations among inverse three-dimensional (3D) plan, forward 3D plan, and two-dimensional (2D) plan of intracavitary brachytherapy for cervical cancer, and to discuss the risk of implementing the interval plan on different implantation applicators at short time intervals.Methods Twenty-five groups of CT-guided intracavitary brachytherapy (two consecutive radiations at ≤4 d apart) plans from 11 cervical cancer patients who received radical radiation therapy in our hospital were reviewed and compared.The dwelling location and time of the first intracavitary brachytherapy plan (Plan-1) were simulated on the CT image of the second intracavitary brachytherapy to form Plan-1-S.The target coverage indices and D 2 cc of organs at risk (OARs) of Plan-1-S and Plan 2(actual plan of the second intracavitary brachytherapy) under the three planning modes were recorded and compared using the paired t-test, Wilcoxon signed rank test, and ANOVA.Results The D90, D100, and V100 of high-risk CTV were significantly lower in Plan-1-S created under the inverse mode in the actual plan (-9.11±13.46%,-13.16±18.79%, and-7.80±13.34%, P=0.002, 0.002, and 0.005, respectively).D90, D100, and V100 of the interval plan had the greatest reduction under the inverse mode (76%, 80%, and 76%, respectively).The maximum reductions in D90, D100, and V100 were 332.14 cGy (2D), 244.12 cGy (forward), and 41.76%(inverse).OAR overdose occurred most frequently under the forward mode;the rates of D90, D100, and V100 reductions accompanied by one OAR overdose were 29.41%, 37.50%, and 25.00%, and the rates of D90, D100, and V100 reductions by two OAR overdoses were 5.88%, 12.50%, and 6.25%,respectively.Overdose occurred most frequently in the small intestine (36%).Comparison of the three planning modes showed that the inverse plan had a greater reduction in each target coverage index than the 2D plan.Conclusions The simulated interval plan can significantly reduce target coverage and increase the risk of OAR overdose regardless of the planning mode and the short time intervals, and is therefore not recommended for clinical application.

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