Neoadjuvant immunotherapy combined with stereotactic body radiation therapy for stage Ⅲ/N2 non-small cell lung cancer: Three cases reports / 中国胸心血管外科临床杂志

@#We reported three cases of stageⅢ/N2 non-small cell lung cancer (NSCLC) treated with neoadjuvant immunotherapy and stereotactic body radiation therapy (SBRT) in our hospital, including 2 males and 1 female with a mean age of 65.7 years. The patients received two doses of the programmed cell death protein-1 inhibitor toripalimab after 1 week of SBRT. Thereafter, surgery was planned 4-6 weeks after the second dose. One patient achieved pathologic complete response, one achieved major pathologic response (MPR), and one did not achieve MPR with 20% residual tumor. There were few side effects of toripalimab combined with SBRT as a neoadjuvant treatment, and the treatment did not cause a delay of surgery.

Asiatic acid inhibits lung cancer cell growthandby destroying mitochondria

Asiatic acid (AA), a pentacyclic triterpene found in, displays significant anti-proliferative effects on cancer cellsalthough the underlying mechanism of this effect remains unknown. This study investigated the efficacy and mechanism of action of AA against lung cancer bothand. Using the MTT assay, AA was found to induce apoptosis in a dose- and time-dependent manner, an effect enhanced by pretreatment with an autophagy inhibitor. It also elevated expression of microtubule-associated protein 1 light chain 3 (LC3) and decreased the expression of p62. Furthermore, exposure to AA resulted in collapse of the mitochondrial membrane potential and generation of reactive oxygen species (ROS), suggesting mitochondria are the target of AA. In the mouse lung cancer xenograft model, oral administration of AA significantly inhibited tumor volume and weight accompanied by significant apoptosis of lung cancer cells. In addition, it led to a significant decrease in the expression of proliferating cell nuclear antigen (PCNA). In summary, the results show that AA significantly reduces lung cancer cell growth bothandand that the associated apoptosis is mediated through mitochondrial damage.

Study on the application of personalization customized oral positioning stent in head and neck cancer patients with intensity modulated radiation therapy / 医学研究生学报

Objective Head and neck cancer radiotherapy patients often appear a series of oral complications including mucositis, xerostomia, pain, dysphagia.The purpose of this study was to investigate whether personalization customized positioning oral stent was able to push normal tissue off the high dose target area and maintain accurate repeatable stable positions, thus protecting the normal tissue during radiotherapy of the nasopharyngeal carcinoma patients.Methods 15 newly diagnosed nasopharyngeal carcinoma patients were collected from March to August 2016 in Department of Radiation Oncology, Nanjing General Hospital of Nanjing Military Region and randomly divided into trial group and control group.Two groups of patients were treated with intensity modulated radiation therapy (IMRT).Trial group patients wear personalization customized oral positioning stents during radiotherapy while the control group did not wear.After radiotherapy, we compared the exposure doses of clinical target area(CTV) and normal oral tissue in two groups.ResultsThe left parotid gland radiotherapy doses of the trail group and the control group were 2223.557±294.549 cGy and 2900.563±374.660 cGy, the difference was statistically significant(t=3.847, P=0.002);the right parotid gland radiotherapy doses of the trail group and control group were 2284.957±256.673 cGy and 2994.670±339.264 cGy, the difference was statistically significant(t=4.512, P=0.001).The mean exposure doses of CTV in two groups were no statistically significant difference (6142.829±135.986 cGy vs 173.306±6221.825 cGy, t=0.971, P=0.349.Conclusion During the intensity modulated radiation therapy, patients with personalization customized oral positioning stents can keep the mandible in a precise repeatable stable position.And it can reduce the exposure dose of bilateral parotid without affect the radiotherapy effect of the clinical target area.

Advantages of tracking no less than three gold markers in radiotherapy with CyberKnife / 中华放射肿瘤学杂志

Objective To analyze the differences between CyberKnife radiotherapy with different numbers of gold markers.Methods A total of 424 patients undergoing CyberKnife with gold markers from 2013 to 2014 were enrolled and analyzed.In these patients,330 patients with no less than 3 gold markers were assigned to observation group and 94 patients with less than 3 gold markers were assigned to control group.The setup error and treatment error were recorded and analyzed for each patient.Results The mean setup error and mean treatment error were 0.031 mm and 0.314 mm in the observation group and 0.057 mm and 1.122 mm in the control group,respectively.Conclusion Tracking no less than 3 gold markers can substantially improve the accuracy and quality of treatment.

Clinical effect of temozolomid combined with concurrent radiotherapy on high grade intracranial glioma / 肿瘤研究与临床

Objective To evaluate the survival and adverse effects of adjuvant concurrent temozolomid (TMZ) combined with radiochemotherapy in postoperative patients with high grade intracranial glioma.Methods 84 postoperative patients with high grade intracranial glioma were randomly divided into the observation group (42 cases including 25 grade Ⅲ cases and 17 grade Ⅳ cases) and the control group (42 cases including 23 grade Ⅲ cases and 19 grade Ⅳ cases).All patients were treated with concurrent radiochemotherapy after surgical operations,the total radiation dose was 60-66 Gy.The patients in observation group were given daily oral TMZ 75 mg/m2 during radiotherapy.4 weeks after radiotherapy,all of the patients received 6 cycles of TMZ,each cycle lasted 5 days with 28 days interval between each cycles.150 mg/m2 of TMZ was given for the first cycle for 5 days,followed by 200 mg/m2 of drug for the rest of the cycles if no significant drug related toxicities were observed.Results The overall response rates (CR+ PR) were 71.7 ％ (33/46) in the observation group,and 32.6 ％ (15/46) in the control group,and with significant difference between the two groups (P ＜ 0.001).The 1,2 and 3 year survival rates of patients in the observation group were 71.7 ％,47.8 ％,36.9 ％,and 56.5 ％,26.1％,15.2 ％ in the control group.The significant differences were found in 2-year and 3-year survival rates between the two groups (P =0.031,0.018).The median recurrent period in the observation group were 22 and 12 months in the control group,and with singnificant difference (P =0.015).The main side effects were limited to grade Ⅰ or Ⅱ.Conclusions Concurrent TMZ combined with radiotherapy in the treatment of high grade gliomas has better clinical efficacy,and can improve the 2-year and 3-year survival rates.Patients tolerate the strategy well and no severe toxicities are observed.

Effect of EGFR mutation on radiation-induced DNA repair in pulmonary adenocarcinoma cells / 中华放射医学与防护杂志

Objective To observe the effect of EGFR mutation on radiation induced DNA repair in pulmonary adenocarcinoma ceils.Methods A549 cells with wild-type EGFR and H1975 cells with mutated-type of EGFR were irradiated by 4 Gy of 6 MV X-rays.After irradiation,the formation of nuclear γ-H2AX foci was assayed with immunostaining method,the level of DNA-PKcs-EGFR interaction was detected with coimmunoprecipitation,and nuclear RAD51 expression and EGFR nuclear translocation were detected using Western blot.Results DNA repair in the H1975 cells was significantly lower than that in A549 cells.In the irradiated H1975 cells,there was no EGFR translocation with further nuclear DNA-PKcs binding,and the expression of nucleus RAD51 was not altered.But in the irradiated A549 cells,EGFRDNA-PKcs interaction and nucleus RAD51 were increased.Conclusions Lung adenocarcinoma cell line with mutations in the tyrosine kinase domain (TKD) of EGFR exhibits a high radiosensitivity due to the reduction of the non-homologous end-joining (NHEJ) and homologous recombination (HR) DNA DSB repair kinetics.

Clinical observation on compound matrine combined with intensity modulation radiotherapy in the treatment of local advanced nasopharyngeal carcinoma / 肿瘤研究与临床

ObjectiveTo detect the efficacy of compound matrine combined with intensity modulated radiotherapy (IMRT) for patients with locally advanced nasopharyngeal carcinoma (NPC). MethodsA total of 96 patients with locally advanced NPC were randomized into compound matrine combined with IMRT group (the therapeutic group) (n =48) and IMRT group (control group) (n =48). The nasopharyngeal DT and lymph nodes Dr were 66-78 Gy/(33-39 f)in 6-8 weeks,60-70 Gy/(30-35 f)in 6-8 weeks, respectively.The prophylactic dose of neck was 50-54 Gy.ResultsThe NPC efficacy of the therapeutic group was 93.8 ％(45/48)and control group was 79.2 ％(38/48).There was significant difference between the two groups in curative effect (P ＜0.05). The lymph nodes efficacy of the therapeutic group was 87.5 ％ (44/48) and control group was 75.0 ％ (30/48). There was significant difference between the two groups in curative effect (P ＜0.05). The side effects of mucosa were fewer in therapeutic group while the infection rate of pharynx oralis was higher in control group (P ＜0.01). ConclusionCompound matrine combined injection can improve shortterm curative effect of IMRT of locally advanced NPC and significantly decreased side effect of radiotherapy.

Percutaneous gold seed fiducials implantation in CT-guided for 132 solid tumors before cyberknife radiosurgery treatment / 肿瘤研究与临床

Objective To evaluate the technical points and security of CT-guided in percutaneous gold seed fiducials implantation for 132 solid tumors before cyberknife radiosurgery treatment. Methods 132 solid tumors were implanted with gold seed fiducials guided by CT before cyberknife radiosurgery treatment.The complications were analyzed. The methods for the prevention and treatment of the complications were suggested. Results Of 132 cases, the achievement rate of puncture was 99.2%(131/132), including 16 (12.1%) cases of pain in the location of puncture, 10(7.6%) cases of tachycardia, and 6 (4.5%) cases of hypertension. Among the 68 cases of lung cancer, there were 3(4.4%) cases of slight pneumothorax, 3(4.4%)cases of generous pneumothorax. Among the 50 cases of liver cancer, there were 1 (2.0%) case of gold seed fiducials transmigration, 2 (4.0%) cases of small amount bleeding from needle channel. Conclusion Percutaneous gold seed fiducials implantation in CT-guided for solid tumors before cyberknife radiosurgery treatment is a slight trauma and safe method.

Characteristics of multivoxel proton MR spectroscopy in brain tumors: comparison of histological pathology / 医学研究生学报

Objective: To investigate the multivoxel proton MR spectroscopy findings of brain tumors and the clinical value in differential diagnosis. Methods:Sixty patients with brain tumors underwent multivoxel proton MR spectroscopic examination with PRESS sequence. Distribution of the 60 final diagnoses of neoplasms was as follow: meningioma (n=22), glioma (n=21), lymphoma (n=3), metastasis (n=5), acoustic neuroma, pituitary tumor, PNET (n=2, respectively), vascularblastoma, arachnoid cyst, neurofibromatosis (n=1,respectively). The concentrations of NAA, Cho, Cr, Lac-Lip were obtained in the tumors and the contralateral normal brain region. The ratios of NAA/Cr, Cho/Cr, NAA/Cho, tumor NAA/normal NAA, tumor Cho/normal Cho, tumor Cr/normal Cr were calculated. Results: 1H MRS showed decreased NAA, Cr and elevated Cho. NAA concentrations in meningioma, glioma, lymphoma decreased significantly to acoustic neuroma, metastasis, but Cho in tumors changed without significance. NAA/Cr ratio was significantly lower in glioma than in acoustic neuroma and metastasis, and p value was 0.014, 0.027, respectively. No significance was found in tumor Cho/Cr data. Conclusion:Multivoxel proton MR spectroscopy is available for study of tumor metabolites. The tumor NAA/normal NAA, NAA/Cr were helpful for the diagnosis and differential diagnosis of intracranial tumors.

Set-up errors in radiation therapy for pelvic tumor patients of different somatotypes / 医学研究生学报

Objective: The purpose of this study was to quantitatively assess the systematic and random errors in radiation therapy for pelvic tumor patients of different somatotypes and seek an individualized mathematic basis for defining the planning target volume(PTV) and planning organ at risk volume(PRV) in 3 dimensional space.Methods: Thirty patients with pelvic tumor were immobilized by thermoplastic body mask in a spine position and divided into four somatotypes according to their body mass indexes(BMI).CT simulations were performed and digitally reconstructed radiographs(DRR) were generated as the reference image.To define the appropriate PTV-and PRV-margins for intensity modulation radiated therapy(IMRT),inter-fractional set-up errors and intra-fractional organ motions were quantitatively evaluated in the right-left(R-L),anterior-posterior(A-P) and cranial-caudal(C-C) directions.And the frequency of shift in the three directions were observed.Results: For the pelvic tumor patients with different BMIs,the inter-fractional set-up errors of the emaciated,moderate,overweight and obese somatotypes were 1.8,1.8,2.2 and 2.7 mm in the R-L direction,2.2,1.8,3.6 and 2.8 mm in the A-P direction,and 2.4,2.1,2.7 and 2.6 mm in the C-C direction.The intra-fractional organ motions of the four somatotypes were 1.9,1.9,2.3 and 2.5 mm in the R-L,2.1,2.2,2.9 and 3.0 mm in the A-P,and 1.8,1.9,2.2 and 2.5 mm in the C-C direction.Conclusion: In the pelvic irradiation,the definition of PTV and PRV should be individualized.

Analysis of MRI-CT image registration accuracy by Tris-Axes Landmark / 医学研究生学报

Objective: To study the accuracy of MRI-CT image registration in order to find a more effective method of image fusion and a standard for the evaluation of post-operative intra-cranial tumor radiotherapy.Methods: Twenty-four patients with intra-cranial tumor underwent MR T1-weighed sequence and post-operative location CT scan under the same location condition.The trans-axial MR T1-weighed sequence and CT image were registered and the correlation between registration scores and errors was analyzed by the method of Tris-Axes Landmark.The linear registration errors were observed in the three-dimensional space of every patient.Results: An improved linear correlation was found between registration scores and errors(r=-0.985,y=-0.551 3x+5.351 4).The registration met the clinical standard when the scores exceeded 6.61.Conclusion: Tris-Axes Landmark is a preferable registration method to be used in clinical radiotherapy for rapid and precise evaluation of MRI-CT image registration accuracy.

Differentially expressed gene in rat hippocampus irradiated by 6MV X-rays / 医学研究生学报

Objective: To observe differentially expressed genes in rat hippocampus irradiated by 6 MV X-rays during radiotherapy.Methods:After whole brain irradiation of 50 Gy in 25 fractions with 2 Gy per fraction,the capability of learning and memory was investigated in a shuttle box model,then rats were killed and the hippocampus were taken,mRNA from sham irradiation group and irradiation group were reversely transcribed to cDNA with incorporation of fluorescence dUTP(Cy5 and Cy3 dUTP) to prepare for hybridization probes.The mixed probes were hybridized to the cDNA microarray.Axon Genechix 4000 BandGenePix Pro3.0 software was used to scan and analyze the fluorescent signals. Results:①The active avoidance response of irradiated rats were lowered significantly.②Compared with the sham group,significant changes took place in 43 genes,among which 28 genes were upregulated and 15 down regulated,other genes did not change significantly.③Among the 43 malexpressed genes,16 were reported previously,others were newly found genes. Conclusion: The influence of ionizing radiation on learning and memory was a complex course,including many transduction factors and might be related to mitochondrial dysfunction.

Technical progresses of three-dimensional conformal radiotherapy for carcinomas / 医学研究生学报

Radiotherapy is one of the three main therapies for carcinomas. The techniques of three dimensional conformal radiotherapy and intensity modulated radiotherapy signify a new age of precise localization, planning and treatment. The author reviewed the development of three dimensional conformal radiotherapy and its related new techniques nowadays.

Clinical applicatios of ~1H-MRS in brain tumors / 医学研究生学报

Proton magnetic resonance spectroscopy is a new technique that can determine the concentrations of a few detectable metabolites altered in diseases.Proton magnetic resonance spectroscopy and spectroscopic imaging are of noninvasive and accuracy.This article focus on the role of proton MRS in preoperative diagnosis and differentiation,tumor grading,evaluation of the efficacy of brain tumor therapies and radiotherapy induced changes.

The research of different MRI-CT image registration for the stability of radiotherapeutic target delineation on gliomas after surgery / 中国癌症杂志

Background and purpose:Accurate target delineation in IMRT setting has been a challenge for post-operative gliomas.The fusion technology with MR+CT image registration could improve the accuracy of target delineation,but there are no reports as to whether this technique could increase the stability of target delineation.This study was to investigate the accuracy of different fusion technologies with MRI+CT image registration so it could improve stability of target delineation of clinical target volume in patients with post-operative gliomas.Methods:The post-operative and pre-operative MRI+CT were registrated in nine patients with post-operative gliomas.Clinical target volume in the two registration images and localized CT images were delineated at 5 different times.The image registration accuracy and stability of target delineation were also quantitatively assessed.Results:The registration accuracy in 3D space was always less than 1.5 mm.The concordance index in CT+MRI(pre-matched),CT+MRI(post-matched)and CT(conv)were(68?9)%,(61?7)% and(41?12)% respectively.The same volumes delineated with three sets of images were(82?7)% for CT+MRI(pre-matched),(78?5)% for CT+MRI(post-matched)and(65?8)% CT(conv),respectively.Conclusions:The volume delineated according to pre-operative MRI registered with CT image have the largest volume and the best stability(P

Radiation-inducible expression of human perforin N-terminal in lung cancer cells / 中国免疫学杂志

Objective:To construct an eukaryotic radiation-inducible expressing vector of the human perforin N-terminal(hPFN-N),and to investigate the distribution and the killing effect of human perforin N-terminal truncated 118 amino acid polypeptide (rhPFN-N,22-139aa) on tumor cells.Methods:The gene hPFN-N was amplified by PCR from the plasmid pcDNA3.1(+)/hPFN and an enkaryotic radiation-inducible expression vector pcDNA3.1(+)/ Egr-hPFN-N was constructed after DNA recombination.After transfecting SPC-A1 cells with this recombination vector via liposome mediation,the expression of the hPFN-N protein was detected by RT-PCR and Immunocytochemical method and the killing effect of hPFN-N protein was assessed by standard MTT chromatometry.Results:DNA sequencing and restriction endonuclease digestion analysis indicated that the eukaryotic radiation-inducible expressing vector pcDNA3.1(+)/ Egr-hPFN-N had been constructed successfully.After the recombinant plasmid being transfected into SPC-A1 cells and being irradiated by X ray,RT-PCR verified the expression of hPFN-N mRNA.The result of Immunocytochemical assay was positive and in MTT assay the killing activity of rhPFN-N on target cells was 29.2%.Conclusion:After being irradiated the hPFN-N gene is expressed on the cell membrane and the killing activity of rhPFN-N on target cells is 29.2%.