A Case of Off-Pump Coronary Artery Bypass Grafting Following High-Dose Dexamethasone Therapy in a Patient with Idiopathic Thrombocytopenic Purpura / 日本心臓血管外科学会雑誌

Man in his 70s, who had suffered from idiopathic thrombocytopenic purpura (ITP), was admitted to our hospital with chest pain at rest. Coronary angiography revealed obstruction of the right coronary artery and triple vessel disease. Because a bleeding tendency was expected during coronary artery bypass grafting, we performed percutaneous coronary intervention to the culprit lesion first, and then intravenous immunoglobulin and high dose dexamethasone were tried. His platelet count rose from 49,000 to 103,000/mm3, so we performed coronary artery bypass grafting. The patient had no postoperative hemorrhagic complications. We believe that high dose dexamethasone therapy is useful for patients with ITP who need surgery immediately.

Analysis of influential factors for blood concentrations and adverse drug reaction in the treatment of lymphoma with high-dose methotrexate / 中国药房

OBJECTIVE To discuss the factors affecting the blood concentration of high-dose methotrexate （HD-MTX） and the occurrence of adverse drug reactions （ADR） when treating lymphoma with HD-MTX. METHODS From July 2020 to November 2021， the information of HD-MTX patients who had been monitored for HD-MTX blood drug concentration in the First Affiliated Hospital of Guangdong Pharmaceutical University was collected by retrospective analysis， such as medical record number， age， sex， height， body mass， chemotherapy plan， dosage； test indexes such as alanine transaminase， aspartate transaminase， total bilirubin， creatinine clearance （CrCl）， albumin （ALB） and other indexes were also collected before and after administration. The blood concentrations （c6 h， c24 h， c48 h） of HD-MTX were recorded， drug information of proton pump inhibitors （PPIs） was extracted and used， and ADR occurring within 48 h after administration were all evaluated. Single factor analysis， multiple linear regression and χ2 test were used to analyze the influential factors. RESULTS A total of 133 patients were included in this paper. The results of the single factor analysis of HD-MTX blood drug concentration showed that age， CrCl had an effect on c 6 h （P＜0.05）； age， CrCl and ALB had an effect on c24 h （P＜0.05）； age， body mass index （BMI）， CrCl， combined use of PPIs and ALB had an effect on c48 h （P＜0.05）. The results of multiple linear regression analysis showed that age and CrCl had no effect on c 6 h （P＞0.05）， age was the main influential factor of c 24 h （P＜0.05）， and CrCl and combined use of PPIs were the main influential factors of c48 h （P＜0.05）； the coefficient of variance expansion was between 1 and 3.5， indicating that the analysis results were acceptable. The overall incidence of adverse reactions was 51.13%， of which the blood and lymphatic system reactions were the most common. The results of the influential factors of ADR showed that age， BMI， liver function and CrCl had effect on the incidence of ADR （P＜0.05）. CONCLUSIONS During the process of HD-MTX in the treatment of lymphoma， the patient’s age， CrCl and combined use of PPIs should be considered， and the patient’s blood concentration should be monitored； at the same time， the age of patients， BMI， liver function and CrCl have an impact on the incidence of ADR.

Transform routine medical accelerators to achieve Flash-RT and physical performance measurements / 中华放射肿瘤学杂志

Objective:To investigate the feasibility of transforming conventional medical accelerator to achieve ultra-high dose rate required to achieve Flash radiotherapy (Flash-RT), and to understand the physical properties of the Flash-RT beam.Methods:By transforming the Varian 23CX medical accelerator, the radiation average dose rate at the isocenter was not less than 40 Gy/s. The relevant physical measurement scheme was designed to accurately measure the actual radiation dose rate of different source skin distance (SSD) conditions, the percent depth dose (PDD) curve and the off-axis dose distribution of the beam.Results:The average dose rate of 9 MeV electron beam after the transformation was measured using the HD-V2 type film, the average dose rate of 3 s was 97.9 Gy/s, and the average dose rate of 6 s was 99.27 Gy/s. When the SSD was 100 cm, 80 cm and 60 cm, the average dose rate of 9 MeV electron beam after the transformation was 99.3 Gy/s, 168 Gy/s and 297.5 Gy/s, respectively. After the transformation, the R100 of the 9 MeV beam was 2.2 cm underwater, R50 was 3.87 cm underwater, the electron range Rp was 4.58 cm, and the maximum possible energy Ep,0 on the phantom surface was 9.28 MeV. These parameters were slightly higher than those of the conventional 9 MeV beam, manifested with slight increase in the surface dose and widening high dose flat area. The overall deposit dose distribution exhibited the highest central axis and the increase in dose declines from the axis distance. Under the condition that the field size was 20 cm×20 cm and the SSD was 100 cm, the FWHM of the vertical and horizontal off-axis dose distribution curves were 16.6 cm and 16.4 cm, respectively. Conclusion:By transforming conventional medical accelerator, the average dose rate of the beam at the isocycle meets the requirement of Flash-RT, and the average dose rate under the condition of 60 cm SSD is much higher than the requirement of at least 40 Gy/s for Flash-RT.

Screening of Hub genes contributing to acute T lymphoblastic leukemia induced by ultra-high dose rate radiotherapy based on GEO database / 中华放射医学与防护杂志

Objective:To analyze the data of ultra-high dose rate (FLASH) radiotherapy in GEO (Gene Expression Omnibus) database by bioinformatics method, in order to find the hub genes involved in flash radiotherapy induced acute T-lymphoblastic leukemia.Methods:The gene expression profiles of malignant tumors receiving FLASH radiotherapy were downloaded from GEO database. The R software was used to screen the differential expressed genes (DEGs) and analyze their biological functions and signal pathways. The protein-protein interaction (PPI) network of DEGs was analyzed by online tool of STRING, and Hub genes were screened by Cytoscape plug-in. The expressions of screened Hub genes in acute T lymphoblastic leukemia were identified with TCGA (The Cancer Genome Atlas) and GTEx (Genotype-Tissue Expression) database.Results:Based on the analysis of GSE100718 microarray dataset of GEO database, a total of 12 800 genes were found to be associated with radiosensitivity of acute T lymphoblastic leukemia, of which 61 significantly altered DEGs were selected for further analysis. It was found that these genes were involved in the biological processes of metabolism, stress response, and immune response through the pathways of oxidative phosphorylation, unfolded protein response, fatty acid metabolism, and so on. PPI analysis indicated that HSPA5 and SCD belonged to the Hub genes involved in the regulation of FLASH radiosensitivity, and they were significantly highly expressed in acute T lymphoblastic leukemia combined with TRD/LMO2-fusion gene.Conclusions:Through bioinformatics analysis, the Hub genes involved in regulating the sensitivity of FLASH radiotherapy and conventional radiotherapy can be effectively screened, and thus the gene expression profiles can be used to guide the stratification of cancer patients to achieve a precise radiotherapy.

Effect of vitamin E on retinal pigment epithelial cells injured by high dose blue light / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM:To study the effect of vitamin E on the injury of human retinal pigment epithelial(hRPE)cells induced by high-dose blue light, and provide experimental evidence for intercepting blue light damaged hRPE cells. <p>METHODS: The hRPE cell injury model was established with 3000±150Lx blue light. The apoptosis rate and reactive oxygen species(ROS)of the six groups of hRPE cells were detected by flow cytometry at 0, 3, 6, 9, 12 and 24h respectively. Apoptosis and ROS in hRPE cells were detected by cytometry in 0h-irradiation group, 6h-irradiation group, and vitamin E added groups(vitamin E concentration 10, 50, 100μmol/L)before or after 6h-irradiation. The fluorescence intensity of hRPE cells was observed under a fluorescence microscope using Hoechst 33258 staining reagent.<p>RESULTS: Compared with the 0h-irradiation group, the relative amount of reactive oxygen species increased significantly in 3, 6, 9, 12 and 24h groups(all <i>P</i><0.01), the apoptosis rate of hRPE cells increased significantly in 6, 9, 12 and 24h groups(all <i>P</i><0.01), the apoptosis rate of the 3h-irradiation group was not statistically significantly increased(<i>P</i>=0.46). Compared with the 6h-irradiation group, the relative amounts of ROS and apoptotic rate of the six groups of hRPE cells added vitamin E were significantly decreased, and the blue fluorescence of Hoechst 33258 released in the cells gradually decreased, which was concentration dependent(all <i>P</i><0.01),except for apoptosis rate of hRPE cells in the 10 μmol/L vitamin E group before irradiation(<i>P</i>=0.66). Compared with the 0h-irradiation group, the difference in the relative amount of ROS and apoptosis rate of hRPE cells in added groups were statistically significant(all <i>P</i><0.01). At the same concentration of vitamin E, the relative amount of ROS and apoptosis rate of hRPE cells added vitamin E after irradiation were significantly lower than those added vitamin E before irradiation(all <i>P</i><0.01), except for apoptosis rate of hRPE cells in the 10 μmol/L vitamin E group, which had no difference between added before and after irradiation(<i>P</i>=0.08).<p>CONCLUSION: After hRPE cells had been irradiated by blue light, the increase in the relative amount of intracellular ROS was earlier than that of apoptosis. Elimination of intracellular ROS is the idea of intercepting high doses of blue light induced hRPE cell injury. Vitamin E protects RPE cell against damage induced by high doses of blue light, and the effect becomes stronger as the concentration of vitamin E increases, which is better when added after irradiating. However, it doesn't take effect until the concentration reaches a certain level. And the damage can't be completely repaired.

Research progress on high-dose-rate brachytherapy of localized prostate cancer / 中华放射肿瘤学杂志

Brachytherapy has played an important role in localized prostate cancer. High-dose-rate brachytherapy has evolved over the decades, as either monotherapy or in combination with external beam, it offers many advantages over other treatment alternatives. Precise control over dose delivery allows for focal dose escalation while sculpting dose around organs at risk to maintain excellent tolerance. The high dose per fraction exploits the low α/β ratio of prostate cancer and triggers transcriptional changes in the tumor genome, thereby enhancing radiation sensitivity. In this article, the development, patient selection, application of techniques, clinical efficacy and adverse events for high-dose-rate brachytherapy were summarized.

Interpretation for Evidence-based Practice Guideline of Medication Therapy of High-dose Methotrexate in China / 中国药房

Evidence-based Practice Guideline of Medication Therapy of High-dose Methotrexate in China was published in the British Journal of Clinical Pharmacology in February 2022. The guideline followed the latest definition of clinical practice guideline and the methodology specification for the guideline development of WHO. The Grading of Recommendations Assessment ， Development，and Evaluation （GRADE）approach was applied to rate the quality of evidence and determine the strength of recommendations. Finally ，this guideline presents 28 recommendations covering the whole process of clinical medication of high-dose methotrexate ，involving evaluation prior to administration （liver and renal function ，pleural effusion and ascites ， comedication，genetic testing ），pre-treatment and routine dosing regimen （pretreatment of hydration and alkalization ，urine alkalization，routine dosing regimen ），therapeutic drug monitoring （necessity，method，timing，target concentration ），leucovorin rescue（rescue timing ，rescue regimen ，rescue dose optimization ），and management of toxicities （liver and kidney function monitoring，supportive treatment ，blood purification treatment ）. This article aims to summarize and interpret the recommendations of this guideline ，so as to promote the better promotion and implementation of this guideline and provide comprehensive technical support and suggestions for whole-course individualized administration of high-dose methotrexate in China.

Evaluation of clinical efficacy and safety of single-channel intracavitary applicator for uterine cervical cancer: 3-year long-term results of a prospective randomized phase Ⅱ clinical trial / 中华放射肿瘤学杂志

Objective:To evaluate the 3-year survival outcomes and late injury between the self-designed patent single-channel applicator, which was modified from the traditional tandem applicator and wrapped with a oval-shield alloy around the source channel and standard Fletcher-type applicator in the high-dose-rate brachytherapy for cervical cancer.Methods:Patients initially diagnosed with cervical cancer in the Affiliated Hospital of Southwest Medical University from December 2011 to April 2017 were enrolled and randomly assigned into the external beam radiotherapy (EBRT)+ single-channel intracavitary applicator group (the patent single-channel group) and EBRT+ the Fletcher applicator group. The whole pelvis irradiation was delivered with 6-MV photons via a four-field box variant or anterior and posterior parallel fields. Five to six fractions of intracavitary brachytherapy were performed at a dose of 7 Gy at point A once a week after 30 Gy (Equivalent Dose in 2 Gy at point A: 80-90 Gy). Chemotherapy was given with intravenous injection of cisplatin at a dose of 40 mg/m 2 once weekly during EBRT. Clinical efficacy and safety were evaluated after corresponding treatment. Results:In total, 150 eligible cases were assigned into the Fletcher applicator group and 149 cases into the patent single-channel group. Up to December 2020, all patients had been followed up for 3 years, and the median duration of follow-up was 61 months. In the Fletcher group, the 3-year overall survival, progression-free survival and locoregional failure-free survival was 76.3%, 78.1% and 75.4%, and 83.8%, 80.3% and 85.5% in the single-channel group, respectively. In the Fletcher group, the cumulative rate of grade 3-4 late rectal complications was 3.3% and 6.7% in the single-channel group ( P=0.122). The cumulative rate of grade 3-4 bladder complications was 1.3% in the Fletcher group and 0.7% in the single-channel group ( P=1.000). Conclusion:The self-designed patent single-channel intracavitary applicator yields equivalent long-term clinical efficacy and safety to the standard Fletcher-type three-channel applicator in the HDR brachytherapy for uterine cervical cancer.

Application of FLASH radiotherapy with an ultra-high dose rate in malignant tumor / 中华放射医学与防护杂志

As a method for local treatment, radiotherapy plays a key role in the management of tumors. In the past few decades, great progress has been made in radiotherapy technology, with improvements in conformity, homogeneity, and radiotherapy efficiency, and the results are encouraging. Nevertheless, the maximum tolerated dose of normal tissue has limited the further increase in radiotherapy dose in the tumor area. If radiation-induced toxicities can be reduced, a higher radiotherapy dose can be delivered to tumor tissue, so as to achieve a better treatment response. In recent years, the unique FLASH effect of ultra-high-dose-rate radiotherapy (FLASH-RT) is capable of maintaining a consistent tumor response whilst reducing radiation-induced toxicities in normal tissue, and therefore, FLASH-RT has become a research hotspot in the field of radiotherapy across the world. At present, some scholars tend to explain the FLASH effect using the theory of acute oxygen depletion, but the protective effect of FLASH-RT on normal tissue remains to be clarified. In addition, preliminary clinical studies have been conducted for FLASH-RT, and the results are promising. Based on existing evidence, this article elaborates on the research advances in FLASH-RT in the treatment of malignant tumor, so as to provide a reference for the translation and application of this new technique.

Experimental study on measurement of short pulsed and high-dose-rate X-ray by therapeutic grade ionization chamber / 中华放射医学与防护杂志

Objective:To investigate the application of therapeutic grade ionization chamber to rapid measurement of short pulsed and high-dose-rate X-ray.Methods:The half-value layer of pulsed X-ray caused by an electron accelerator was measured by interpolation method and its equivalent energy was estimated. The cumulative doses from a certain amount of pulsed radiation at different distances in the same direction around the equipment were compared using the therapeutic grade ionization chamber and thermoluminescence measurement method . The relationship between the measurement result by using ionization chamber dosimeter and the distances away from source was analyzed. The cumulative doses from a certain amount of pulsed radiation at the same location at different frequencies were compared.Results:In working condition, 100 pulses of radiation were received accumulatively at 1 to 12 meters away from the outer wall of the equipment. The range of air Kerma was 0.08-9.65 mGy measured by using thermoluminescence dometers and 0.08 - 9.85 mGy using the ionization chamber dosimeters, respectively. The difference between both is within 10%. At different frequencies (1-10 Hz), there was no significant difference in X-ray air Kerma from 100 pulses measured by ionization chamber dosimeter at 2 m away from the front of the equipment ( P>0.05). Conclusions:The therapeutic grade ionization chamber dosimeter can be used for the rapid measurement of short pulsed X-ray radiation dose in the range of dose rates and pulse frequencies involved in the experimental accelerator device.

Progress on the effect of high-dose fluid resuscitation on the prognosis of children with septic shock / 中国小儿急救医学

Septic shock refers to sepsis combined with severe circulatory disorders and cell metabolism disorders, with high incidence, high fatality rate, and dangerous condition.It is one of the leading cause of death in children in pediatric intensive care units.Therefore, early diagnosis and effective treatment of septic shock are very important.Among them, fluid resuscitation is an important part of treatment.However, the research in recent years has a lot of controversy about subsequent fluid balance management issues.This review summarized fluid balance therapy, focusing on the large dose of fluid resuscitation on the prognosis of children with septic shock, aiming to provide a reference for the future improvement of fluid therapy for children with sepsis.

Evaluation of high-dose vitamin A treatment in postmolar patients with low and plateauing serum human chorionic gonadotropin levels / Avaliação de alta dose de vitamina A em pacientes pósmola hidatiforme, com valores baixos e em platô de gonadotrofina coriônica humana

Abstract Objective To compare the effect of high-dose vitamin A (HD Vit-A) use during postmolar follow-up of patients with low and plateauing (L&P) serum human chorionic gonadotropin (hCG) levels, from the moment serum hCG plateaued (P-hCG) to the first normal serum hCG value (< 5IU/L). Methods The present retrospective series case study compared two nonconcurrent cohorts of patients. Control group (CG): 34 patients with L&P serum hCG levels who underwent expectant management for 6 months after uterine evacuation, from 1992 to 2010; study group (SG): 32 patients in similar conditions who received 200,000 IU of Vit-A daily, from the identification of a P-hCG level to the first normal hCG value or the diagnosis of progression to gestational trophoblastic neoplasia (GTN), from 2011 to 2017. The present study was approved by the Ethics Committee of the institution where it was conducted. Results In both groups, the prevalence of persistent L&P serum hCG levels was < 5%. In the SG, hCG levels at plateau were higher (CG = 85.5 versus SG = 195 IU/L; p = 0.028), the rate of postmolar GTN was lower (CG = 29.4% versus SG = 6.3%, p = 0.034) and follow-up was shorter (CG = 14 versus SG = 10 months, p < 0.001). During GTN follow-up, there were no differences in GTN staging or treatment aggressiveness in both groups. High-dose Vit-A use did not have any relevant toxic effect. There were no GTN relapses or deaths. Conclusion The limited use of HD Vit-A seems to have a safe and significant effect on the treatment of postmolar patients with L&P serum hCG levels and may decrease the development of postmolar GTN in this population.

Resumo Objetivo Comparar o efeito de alta dose de vitamina A (VitA) no seguimento pósmolar de pacientes com gonadotrofina coriônica humana (hCG) sérica apresentando valoresbaixoseem platô(L&P). Métodos Estudo retrospectivo de série de casos comparando duas coortes não simultâneas. Grupo controle (CG): 34 pacientes com títulos de hCG sérico L&P submetidos a manejo expectante por 6 meses após o esvaziamento uterino, de 1992 a 2010; Grupo de Estudo (SG): de 2011 a 2017, 32 pacientes em condições semelhantes de hCG receberam Vit-A na dose de 200.000 IU por dia, do momento da identificação dohCG em platôate o primeirohCG normaloudiagnóstico de progressão para neoplasia trofoblástica gestacional (NTG). O presente estudo foi aprovado pelo Comitê de Ética da Instituição na qual foi desenvolvido. Resultados Em ambososgrupos, aprevalência de hCGL&P foi < 5%. No SG, os níveis de hCGemplatô forammaiores (CG = 85.5 versus SG = 195 IU/L; p = 0,028), e foram significantemente menores tanto a prevalência de NTG pós-molar (CG = 29.4% versus SG = 6.3%, p = 0,034) como o tempo de seguimento (CG = 14 versus SG = 10 meses, p < 0.001). Na evolução para NTG não houve diferença no estadiamento da Interna tional Federation of Gynecology and Obstetrics (FIGO, na sigla em inglês) ou na agressividade do tratamento. Com altas doses de Vit-A não houve qualquer efeito tóxico relevante. Não houve casos de recidiva de NTG ou de óbito. Conclusão O uso limitado de altas doses de Vit-A parace ser seguro e apresenta efeitos significativos na evolução de pacientes em controle pós-molar com títulos de hCG sérico L&P, e pode diminuir o desenvolvimento de NTG pós-molar nessa população.

Evolution of the treatment of primary central nervous system lymphoma in a Regional Cancer Center of South India: Impact of high-dose methotrexate on treatment outcome

Objective: Primary central nervous system lymphoma (PCNSL) is a rare form of aggressive extranodal non-Hodgkin lymphoma. This study attempts to delineate the clinicopathological and radiological profile of PCNSL cases at our center. Materials and Methods: All the pathologically confirmed PCNSL cases between January 2007 and July 2016 were analyzed retrospectively. The influence of potential prognostic parameters and therapeutic strategies on survival was investigated by log-rank test and Cox regression analysis. Results: Of the 53 PCNSL patients, 34 (64%) patients were males. Median age at diagnosis was 44 years (range 22–65 years). The most common location in the brain was the cerebral hemispheres in 32 patients (60%), and 16 patients (30%) had multiple intracranial lesions. Histologically, all patients were diffuse large B-cell lymphomas, except one case of anaplastic large-cell lymphoma. The median survival of the patients received whole-brain radiation alone ( n = 6), standard CHOP chemotherapy + radiation ( n = 14), and DeAngelis protocol ( n = 31) was 8 months, 13 months, and 23 months, respectively. Among the 31 patients treated with DeAngelis protocol, Memorial Sloan Kettering Cancer Center Class 1 ( n = 23) and Class 2 ( n = 8) patients had a median overall survival (OS) of 25 months and 13 months, respectively. The incidence of treatment-related neurotoxicity was significantly higher with DeAngelis protocol, in comparison to CHOP + whole-brain radiation therapy (26% vs. 14%, P < 0.05). Conclusion: None of the potential prognostic factors had a statistically significant influence on OS in our patients. High-dose methotrexate-based chemotherapy combined with radiation was the only factor, which had a significant impact on survival (log-rank P = 0.000) but at the cost of increased neurotoxicity

Retrospective evaluation and prediction of clearance and toxicity of high dose methotrexate in childhood acute lymphoblastic leukemia patients

To find the predictors of High Dose Methotrexate toxicities in childhood Acute Lymphoblastic Leukemia Patients. This study included 198 Childhood Acute Lymphoblastic Leukemia patients (303 infusions) who were treated with High Dose Methotrexate. Methotrexate levels at different time point were measured by modified enzyme multiplied immunoassay technique assay. The correlation between Methotrexate levels and toxicity was evaluated by Receiver Operating Characteristic curve. When the Methotrexate level at 42 h was lower than 0.76 µmol/L, the sensitivity for predicting thorough clearance at 66 h was 90.78%. When the Methotrexate level at 42 h was higher than1.5 µmol/L, the sensitivity for predicting delayed clearance was 82.17%. When the Methotrexate level at 66 h was higher than 0.5 µmol/L, the sensitivity for predicting Methotrexate toxicity was 89.09%. When the Methotrexate level at 66 h was lower than 0.1 µmol/L, the sensitivity for predicting Methotrexate nontoxicity was 92.73%. The Methotrexate level at 42 h could be predictor for delayed clearance. The Methotrexate level at 66 h could be predictor for toxicity.

Strive to Improve the Eradication Rate of Helicobacter pylori / 胃肠病学

As the awareness of the harmfulness of Helicobacter pylori (Hp) infection increases, the indications for Hp eradication continue to expand. "Kyoto Global Consensus Report on Helicobacter pylori Gastritis" puts forward "Hp infected individuals should be offered eradication therapy, unless there are competing considerations" and the statement has been accepted by more and more scholars. In our country, "the confirmed Hp infection" has been listed as an indication for eradication. However, as the antibiotic resistance rate of Hp increases, the eradication rate of Hp is gradually decreasing, and the proportion of people who has failed multiple treatments is increasing. This article was specially written for helping the clinicians to improve the eradication rate of Hp infection.

A New Generation of Radiotherapy Technology-Flash Radiotherapy / 中国医疗器械杂志

Flash radiotherapy is a kind of radiotherapy method using ultra-high dose rate radiation. Compared with the traditional dose rate radiotherapy, it has unique radiobiological advantages. In this paper, the principle of flash radiotherapy, the process and results of biological experiments are summarized. At the same time, the advantages and challenges of flash radiotherapy are analyzed, and the future clinical application is prospected.

Hematotoxicity Correlation of MTHFR Gene Polymorphism with High-dose of Methotrexate in Hematological Neoplasm Patients ：A Meta-analysis / 中国药房

OBJECTIVE：To systematically evaluate the c orrelation of methylenetetra hydrofolate reductase （MTHFR）C677T and A 1298C gene polymorphisms with blood system adverse events induced by high-dose of methotrexate （HDMTX）. METHODS ： Retrieved from Medline ，Embase，Clinical Trials.gov ，CNKI，Wanfang database ，CBM，cohort studies about MTHFR gene polymorphism in hematological neoplasm treated by HDMTX were collected from inceptions to March 2018. After data extraction of included literatures ，quality evaluation with Newcastle Ottawa scale ，Meta-analysis was performed for adverse events of blood system induced by HDMTX in different genetic models with Rev Man 5.3 software. RESULTS ：Totally 25 cohort studies were included，23 studies of which were related to MTHFR C677T site （including 1 858 patients）and 16 studies related to MTHFR A1298C site （including 1 088 patients）. Results of Meta-analysis showed that MTHFR C677T mutation type significantly increased the risk of hematotoxicity [TT/CT vs. CC ：OR＝1.57，95％CI（1.12，2.20），P＝0.009；TT vs. CT/CC ：OR＝2.19，95％CI（1.49， 3.23），P＜0.001；T vs. C ：OR＝1.34，95％CI（1.03，1.74）， P＝0.03] and severe hematotoxicity [TT/CT vs. CC ：OR＝m 2.33，95％CI（1.43，3.81），P＜0.001]，including leukopenia [TT/CT vs. CC ：OR＝1.37，95％CI（1.02，1.82），P＝0.03]， severe leukopenia [TT/CT vs. CC ：OR＝1.63，95％CI（1.03， 010-82265810。E-mail：zhao_rongsheng@163.com 2.56），P＝0.04]，severe gra nulopenia [TT/CT vs. CC ：OR＝ ·2.26，95％CI（1.50，3.39），P＜0.001]. The mutation genotypes of MTHFR A1298C significantly decreased the risk of severe hematotoxicity [CC/AC vs. AA ：OR＝0.17，95％CI（0.04，0.76），P＝0.02]，including leukopenia [CC/AC vs. AA ：OR＝0.68， 95％CI（0.48，0.97），P＝0.03；CC vs. AC/AA ：OR＝0.28，95％CI（0.14，0.59），P＜0.001] and severe leukopenia [CC/AC vs. AA：OR＝0.43，95％CI（0.19，0.97），P＝0.04]. CONCLUSIONS ：Among patients with hematological neoplasms ，MTHFR C677T mutation may significantly increase the risk of hematotoxicity by HDMTX including the risk of leukopenia and granulopenia ；while MTHFR A1298C may reduce the risk of hematotoxicity by HDMTX ，including the risk of leukopenia.

Effect of different definitions of prescription point “A” in high dose rate brachytherapy for cervical cancer

Aim: This study intended to compare the dosimetric parameters using different definitions of prescription point A in high dose rate (HDR) brachytherapy of cervical cancer patients. Background: Manchester point A has been widely used for prescribing dose in brachytherapy. However, due to certain limitations of this point, a new definition of point A has been recommended by the American Brachytherapy Society (ABS). Materials and Methods: We retrospectively investigated 55 computed tomography-based plans of 20 cervical cancer patients treated with Ir-192-based intracavitary HDR brachytherapy. The dose of 7 Gy in 3 fractions each was prescribed to point A using revised Manchester definition of point A (AMAN) and ABS guideline definition (AABS). The effect of both definitions on various parameters including dose to point A and 90% of tumor volume (D90), dose received by 2cc volume of bladder, rectum and small bowel and treatment volume receiving 100% of prescription dose (V100) was analyzed. Results: Mean percentage difference of point AMAN dose and AABS dose with respect to prescription dose was 1.25% ± 1.43% and 1.21% ± 1.01%, respectively. Mean V100 was 80.4 ± 20.45cc and 88.47 ± 16.78cc for AMAN and AABS plans, respectively, while mean percentage difference between prescribed dose and D90 was found to be –37.90% ± 25.06% and –30.47% ± 25.50% respectively for both the definitions. Conclusion: Doses to both Manchester point A and ABS point A may be recorded during the transition period. However, ABS point A can be preferred over the Manchester point A as it conforms better with the desired dosimetric outcome and is found to be more static.

Interfraction physical dose variations in high-dose-rate brachytherapy for carcinoma cervix based on computed tomography image dataset to find the compatibility of the first fraction plan to treat successive fractions

Context: Due to limited resources and/or affordability by majority of the patients, many centers in low- and middle-income countries are still not able to adapt three-dimensional image-based brachytherapy planning in their routine practice. Aim: The aim of the study was to see the feasibility of using computed tomography (CT)-based plan of the first fraction to treat successive fractions of intracavitary brachytherapy based on the estimation of the physical dosimetric differences between successive applications. Materials and Methods: CT image-based brachytherapy plans of 38 patients who received three insertions of intracavitary application with high-dose-rate brachytherapy have been analyzed. Revised plans for the second and third insertions were generated by adapting dwell time and dwell position of the first insertion plan. The dose to point “A” and maximum doses to 2, 1, and 0.1 cc volumes of the rectum and bladder have been used for dosimetric comparison. Results: The statistical differences of mean point “A” doses were observed insignificant except between original and revised plans for the second insertions. The dosimetric differences between consecutive original and revised plans for the bladder and rectum have not shown any significance except minimum dose to 0.1 cc volume of the rectum for the third insertions. Conclusions: Dosimetric deviation for tumor and organs at risk is within acceptable limit while using CT image-based brachytherapy plan of the first fraction for treating successive fractions

Interdigitated versus sequential high-dose-rate intracavitary brachytherapy with external beam radiotherapy in locally advanced carcinoma cervix

Aims: To decrease overall treatment time (OTT) and to compare the clinical outcome of interdigitated high-dose-rate intracavitary brachytherapy (HDRICBT) versus sequential HDRICBT with external beam radiotherapy (EBRT) in the treatment of locally advanced carcinoma cervix. Methods: Eighty-two patients with histologically confirmed carcinoma of the cervix, untreated International Federation of Gynecology and Obstetrics Stage IIB–IIIB, were included and randomized into two groups. The study group received EBRT 50 Gy/25 fractions with interdigitated HDRICBT 8 Gy/fraction weekly a total of three fractions. Patients in the control group received EBRT 50 Gy/25 fractions with sequential HDRICBT 8 Gy/fraction weekly a total of three fractions. At the end of the study, results of both groups compared in terms of OTT, acute and late toxicities, and response to therapy clinically. Results: A total of 82 patients were enrolled 41 in each arm. Seventy-two patients completed treatment and were analyzed. Mean OTT in study group and control group was 40 and 60 days, respectively. The median follow-up duration was 10 months (3–18). Most of the acute and late toxicities were of Grade 1 and 2 type and comparable in both study and control groups. Treatment interruption due to treatment-related toxicity was slightly higher in the study group than the control group, but it was statistically insignificant. Os negotiability was not found to be a limiting factor for interdigitated HDRICBT. Conclusion: Interdigitated HDRICBT has equivalent response and toxicities as sequential HDRICBT with the advantage of significant reduction in OTT