LUNG DOSE DETERMINATION IN TOTAL BODY IRRADIATION PRIOR TO BONE MARROW TRANSPLANTATION

Total body irradiation (TBI) combined with chemotherapy prior to bone marrow transplantation (BMT) is used successfully for treatment leukemias. It need a high and homogeneous radiation dose to all target cells, dispersed In the whole body. The lung is the most sensitive vital organ at risk in TBI. The lung dose must be within it' s tolerable level. So, the determination of the lung dose is most Important for TBI. The determination of the lung dose is dependent on at least 8 parameters. In order to determine the effect of 8 parameters on the lung dose, using a system of phantom of Essen University hospital in F. R. Germany, a lot of measurements and a systematical investigation was made by varying 8 parameters, under the Essen translation TBI conditions. A analysis and discussion of results was made.

A Clinical Dosimetry Analysis of Total Body Irradiation for Leukemia Patients

Background and Purpose: To perform a retrospective in vivo dosimetry study of 129 total body irradiation (TBI) on leukemia and bone marrow transplant patients treated in our clinic from 2008 to 2011 and to find out if there is any indication of the necessity of developing a new efficient TBI approach. Materials and Methods: The in vivo dosimetry data of 129 patients treated with TBI between 2008 and 2011 were retrieved from the database and analyzed. These patients were mostly treated with the regime of a single fraction or 6 fractions with some exceptions of 8-fraction or 2-fraction treatments depending on the protocols that were applied. For every fraction of treatment, 10 pairs of diode dosimeters were used to monitor the doses to the midline of head, neck, arms, mediastinum, left lung, right lung, umbilicus, thigh, knee, and ankle for both AP and PA fields. The doses to the midline of the above body parts were considered to be the average of the AP and PA readings of each diode pair. Dose deviation from the prescribed value for each body part was studied by plotting the histogram of the frequency versus deviation and comparing this with the dose delivered to the midline of the umbilicus to where the dose was prescribed. The correlation of dose deviation to body part thickness was also studied. By studying the dose deviations, we can find the uniformity of general dose distributions for conventional TBI treatments. Results: The retrospective dosimetry study of the 129 TBI patient treatments indicates that for most of the patients treated in our clinic, the doses received by different body parts monitored with in vivo dosimetry were within the window of 10% difference from the prescribed dose. The inhomogeneity of dose on different body parts could be manually improved by using compensators, but the method is cumbersome and time consuming. The dose deviation in many histograms ranging from about ?10% to 10% indicates some incongruity of dose distribution. This could be due to the method of using lead compensators for a manual dose adjustment which could not ideally compensate for different body thicknesses everywhere. Conclusions: The conventional TBI could give uniform dose to the major body parts under the online in vivo dosimetry monitoring at the level of 10%, but the treatment procedure is cumbersome and time consuming. This implies the importance of developing a new and efficient TBI method by adopting modern radiation therapy technique.

Comparison of Mathematical Equations Applicable to Tolerance of Total Body Irradiation in Humans and Decay of Isotopes, Uranium and Thorium: Differences and Similarity

A clear and exact quantitative relationship between dose of total body irradiation and mortality in humans is still not known because of lack of human data that would enable us to determine LD50 for humans in total body irradiation. Analysis of human data has been primarily from radiation accidents, radiotherapy and the atomic bomb victims. The author published the general mathematical equations of LD50 constructed on the basis of data presented by Cerveny, MacVittie and Young, employing the probacent formula model. In this study, the author compared the equations of tolerance of total body irradiation and decay of isotopes, uranium and thorium. Differences and similarity in these equations of the two groups are presented. The significance of similarity is specially described.

Low Dose Total Body Irradiation for Relapsed Low Grade Non-Hodgkin’s Lymphoma: Experience of National Cancer Institute, Cairo

Background and Purpose: The relapsed low grade non-Hodgkin’s lymphoma (LG-NHL) is currently?incurable disease and the optimal treatment regimen has not determined yet. Low dose total body irradiation (LTBI) provides an alternative mechanism of action against cancer cells rather than direct cell kill. The mode of action of LTBI is immune-modulatory effect, induction of apoptosis and?hypersensitivity to low radiation doses. The aim of our study is to evaluate the effect of LTBI on relapsed?LG-NHL and reporting our experience at National Cancer Institute, Cairo (NCI, Cairo). Material and Methods: Fifty eight patients with relapsed LG-NHL and received LTBI studied retrospectively.?LTBI dose was 1.6 Gy/8 fractions divided on 2 courses;each course 4 fractions treated over 4 days with 2 weeks rest between the 2 courses. Results: The median age is 54 years;65% of the patients are men. Forty (69%) patients had performance status of 2 or more. Twenty seven patients were stage II/III and 31 patients (53%) had stage IV disease. Twenty six (45%) patients had bulky disease more than 10 cm and 22 (38%) patients had B symptoms at the time of relapse. The?extranodal disease was present in 17 patients (29%) and 78% of the patients received?>3 regimens of chemotherapy before referral to LTBI. Twenty three patients received IFRT (mean dose 32 ± 4 Gy) to initially bulky sites after LTBI. Fourteen patients (24%) achieved complete remission (CR) while 45%, 21% and 10% had partial remission (PR), stable disease (SD) and progressive disease (PD) respectively. The median PFS duration was 14 months and the median OS duration?was 39 months. Stage VI,?>3 regimen of chemotherapy and bad response to LTBI (SD) affected?progression duration adversely (0.03, 0.05 and 0.01 respectively). The response to LTBI is the only factor affected the OS duration significantly. The 3-year PFS was 19% ± 9%, and 3-year OS was 45% ± 8%. Stage IV was the only factor affected the 3-year PFS significantly with p value 0.03. The hematological toxicity was the main side effect of LTBI. Eleven patients developed G3/4 anemia while 8 patients only developed G3/4 thrombocytopenia and 13 patients developed G3/4 leucopenia. Conclusion: The use of LTBI in patients with relapsed low grade NHL is a feasible, effective and tolerable treatment that is worthy of testing in a future with chemotherapy and Rituximab maintenance.

Predictive formulas expressing relationship among dose rate, duration of exposure and mortality probability in total body irradiation in humans

A clear and exact quantitative relationship between dose of radiation and mortality in humans is still not known because of lack of human data that would enable to determine LD50 for humans in total body irradiation. Analysis of human data has been primarily from radiation accidents, radiotherapy and the atomic bomb victims.The death rate equation derived from the 'probacent'-probability model of survival probability is employed in this study to construct the general formula of mortality probability as a function of dose rate and duration of exposure in total body irradiation in humans. There is a remarkable agreement between formula-predicted and published estimated LD50 and also between both mortality probabilities. The formulas of LD50 ans mortality probability in lethal radiation exposure for humans might be helpful in preventing radiation hazard and injury, and further for safety in radiotherapy.

Predictive formulas expressing relationship between dose rate and survival time in total body irradiation in mice

The Gompertz model is the long-time well-known mathematical model of exponential expression among mortality models in the literature that are used to describe mortality and survival data of a population. The death rate of the “probacent” model developed by the author based on animal experiments, clinical applications and mathematical reasoning was applied to predict age-specific death rates in the US elderly population, 2001, and to express a relationship among dose rate, duration of exposure and mortality probability in total body irradiation in humans. The results of both studies revealed a remarkable agreement between “probacent”-formula-predicted and published-reported values of death rates in the US elderly population or mortality probabilities in total body irradiation in humans (p - value > 0.995 in χ2 test in each study). In this study, both the Gompertz and “probacent” models are applied to the Sacher’s comprehensive experimental data on survival times of mice daily exposed to various doses of total body irradiation until death occurs with an assumption that each of both models is applicable to the data. The purpose of this study is to construct general formulas expressing relationship between dose rate and survival time in total body irradiation in mice. In addition, it is attempted to test which model better fits the reported data. The results of the comparative study revealed that the “probacent” model not only fit the Sacher’s reported data but also remarkably better fit the reported data than the Gompertz model. The “probacent” model might be hopefully helpful in research in human tolerance to low dose rates for long durations of exposure in total body irradiation, and further in research in a variety of biomedical phenomena.

A SIMPLIFIED IN VIVO DOSIMETRY FOR TOTAL BODY IRRADIATION PRIOR TO BONE MARROW TRANSPLANTATION

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Low Dose Total Body Irradiation (600 cGy) as a Conditioning Regimen in Allogenic Hematopoietic Stem Cell Transplant in Children with Acute Lymphoblastic Leukemia

Total body irradiation (TBI) is conditioning regimen in children with acute lymphoblastic leukemia (ALL) with a very high risk of relapse or in those who have not achieved remission and have relapsed and subsequently received allogenic hematopoietic stem cell transplantation (HSCT). A retrospective evaluation of 33 ALL patients in full remission with an indication of HSCT was performed to evaluate overall survival (OS) and event-free survival (EFS). The inclusion criteria included a myeloablative conditioning regimen of TBI at a dose of 600 cGy. The observed OS at 5 years was 50%, and the EFS of 32% we observed difference in the EFS stem cell origin;the peripheral blood (PB) 60%, and the umbilical cord blood (UC) accounted for 40%. Overall, 45% had a documented chimerism. The OS at 5 years from patients with chimeras was 75%, while those without chimeras had an OS at 5 years of 25%. The mortality in the first 100 days was 24%. A total of 24.2% of children presented with acute graft versus-host disease (GVHD), while 33% had chronic GVHD. Currently, there is no general agreement among all international centers regarding the optimum TBI dose. Our study reports an acceptable range of adverse events with a relatively low dose of 600 cGy.

Study on Fractionated Total Body Irradiation before Hematopoietic Stem Cell Transplantation

OBJECTIVE To observe the dose and the complicationsfrom total body irradiation before hematopoietic stem celltransplantation.METHODS This study involved 312 patients with total bodyirradiation before hematopoietic stem cell transplantation. Theywere entered into the treated research from May 1999 to October2005. All patients had received the irradiation from ^(60)Co of anabsorbed dose rate of (5.2 ± 1.13) cGy/min. The total dose of TBIwas 7～12 Gy, 1 f/d × 2 d. A high-dose rate group (≥10 Gy) included139 cases and a low-dose rate group (< 10 Gy) included 173 cases.RESULTS The probability of acute gastrointestinal reactionsin the high-dose rate group was more compared with that in thelow-dose rate group. The differences for other reactions, such ashematopoietic reconstitution and graft survival rate, between thetwo groups were insignificant.CONCLUSION Using fractional total body irradiation at a doserate of 5 cGy/min, with a total dose of 7～12 Gy, 1 f/d × 2 d , withthe lung receiving under 7.5 Gy is a safe and effective pretreatmentfor hematopoietic stem cell transplantation.

The protective effects of Xuebijing injection on intestinal injuries of mice exposed to irradiation

Background:Gastrointestinal(GI)injury is one of the most common side effects of radiotherapy.However,there is no ideal therapy method except for symptomatic treatment in the clinic.Xuebijing(XBJ)is a traditional Chinese medicine,used to treat sepsis by injection.In this study,the protective effects of XBJ on radiation-i nduced intestinal injury(RⅢ)and its mechanism were explored.Methods:The effect of XBJ on survival of irradiated C57BL/6 mice was monitored.Histological changes including the number of crypts and the length of villi were evaluated by H&E.The expression of Lgr5^(+)intestinal stem cells(ISCs),Ki67^(+)cells,villin and lysozymes were examined by immunohistochemistry.The expression of cytokines in the intestinal crypt was detected by RT-PCR.DNA damage and apoptosis rates in the small intestine were also evaluated by immunofluorescence.Results:In the present study,XBJ improved the survival rate of the mice after 8.0and 9.0 Gy total body irradiation(TBI).XBJ attenuated structural damage of the small intestine,maintained regenerative ability and promoted proliferation and differentiation of crypt cells,decreased apoptosis rate and reduced DNA damage in the intestine.Elevation of IL-6 and TNF-α was limited,but IL-1,TNF-β and IL-10 levels were increased in XBJ-treated group after irradiation.The expression of Bax and p53 were decreased after XBJ treatment.Conclusions:Taken together,XBJ provides a protective effect on RⅢby inhibiting inflammation and blocking p53-related apoptosis pathway.

Allogeneic compact bone-derived mesenchymal stem cell transplantation increases survival of mice exposed to lethal total body irradiation： a potential immunological mechanism

Background Radiation-induced injury after accidental or therapeutic total body exposure to ionizing radiation has serious pathophysiological consequences,and currently no effective therapy exists.This study was designed to investigate whether transplantation of allogeneic murine compact bone derived-mesenchymal stem cells （CB-MSCs） could improve the survival of mice exposed to lethal dosage total body irradiation （TBI）,and to explore the potential immunoprotective role of MSCs.Methods BALB/c mice were treated with 8 Gy TBI,and then some were administered CB-MSCs isolated from C57BL/6 mice.Survival rates and body weight were analyzed for 14 days post-irradiation.At three days post-irradiation,we evaluated IFN-Y and IL-4 concentrations; CD4＋CD25＋Foxp3＋ regulatory T cell （Treg） percentage; CXCR3,CCR5,and CCR7 expressions on CD3＋T cells; and splenocyte T-bet and GATA-3 mRNA levels.CB-MSC effects on bone marrow hemopoiesis were assessed via colony-forming unit granulocyte/macrophage （CFU-GM） assay.Results After lethal TBI,compared to non-transplanted mice,CB-MSC-transplanted mice exhibited significantly increased survival,body weight,and CFU-GM counts of bone marrow cells （P＜0.05）,as well as higher Treg percentages,reduced IFN-Y,CXCR3 and CCR5 down-regulation,and CCR7 up-regulation.CB-MSC transplantation suppressed Th1 immunity.Irradiated splenocytes directly suppressed CFU-GM formation from bone marrow cells,and CB-MSC co-culture reversed this inhibition.Conclusion Allogeneic CB-MSC transplantation attenuated radiation-induced hematopoietic toxicity,and provided immunoprotection by alleviating lymphocyte-mediated CFU-GM inhibition,expanding Tregs,regulating T cell chemokine receptor expressions,and skewing the Th1/Th2 balance toward anti-inflammatory Th2 polarization.

Enhancement of antitumor immunity by low-dose total body irradiation is associated with selectively decreasing the proportion and number of T regulatory cells

Low-dose total body irradiation （LTBI） is used in the treatment of some cancers mainly for immune enhancement rather than cell killing. However, the mechanism underlying LTBI remains unknown. In this study, by analyzing the immune patterns of lymphocytes, we found that the percentage and absolute number of CD4^＋CD25^＋Foxp3^＋ regulatory T cells are markedly decreased in naive mice following treatment with LTBI. On the contrary, the CD4^＋CD44^＋/CD8^＋CD44^＋ effector-memory T cells are greatly increased. Importantly, naive mice treated with dendritic cell-gp100 tumor vaccines under LTBI induced an enhancement of antigen-specific proliferation and cytotoxicity as well as interferon-γ, （IFN-γ） secretion against FIO melanoma tumor challenge, compared to treatment with either the tumor vaccine or LTBI alone. Consequently, the treatment resulted in a reduced tumor burden and prolonged mouse survival. Our data demonstrate that LTBI＇s enhancement of antitumor immunity was mainly associated with selectively decreasing the proportion and number of T regulatory cells, implying the potential application of the combination of LTBI and a tumor vaccine in antitumor therapy.

全身照射小鼠模型肠道通透性HPLC-ELSD检测方法的建立

目的:建立评价全身照射(total body irradiation,TBI)实验小鼠模型肠黏膜通透性双糖吸收试验的高效液相色谱(high-performance liquid chromatography,HPLC)检测方法。方法:TBI实验小鼠模型和正常小鼠各8只,采用高效液相色谱-蒸发光散射检测器分析(HPLC-ELSD)检测尿液标本中乳果糖(lactulose,L)和甘露醇(mannitol,M)的排出率比值,评价两组小鼠的肠道黏膜通透性。结果:尿液中甘露醇和乳果糖浓度分别在0.5～6 mg/mL和0.25～3 mg/mL范围内线性关系良好,本方法测定甘露醇和乳果糖的最低检测极限分别为500 ng和为250 ng。甘露醇和乳果糖的加样回收率分别为86.5%～109.2%和86.3%～114.4%。甘露醇和乳果糖排出量的平均日内变异系数分别为0.86%和1.13%(n=6);平均日间变异系数分别为1.11%和1.39%(n=6)。TBI组小鼠肠道通透性(乳果糖/甘露醇比值:0.5108±0.03266)显著高于正常组小鼠(0.2908±0.05332)。结论:HPLC-ELSD检测肠道通透性具有简便、专一灵敏、重复性好、准确可靠等特点,可用于TBI小鼠肠道黏膜通透性的测定和监测。

MOSFET探测器在全身放疗质量控制中的应用

目的探讨MOSFET探测器在全身放疗质量控制中的价值。方法在源轴距360 cm处使用电离室对MOSFET探测器进行标定,同时根据体模入射面、出射面与中间层面的剂量换算关系,利用标定后的MOSFET探测器检测行全身放疗患者的辐射剂量,控制并减少相应误差。结果 10个MOSFET探测器中,有7个最大偏差均<3%,另3个经再次重新标定后,最大偏差亦<3%,均可用于临床测量。结论在全身放疗中应用MOSFET探测器能够起到监测治疗剂量、控制误差的作用。

一种抗总剂量辐照的新型PD SOI器件

提出了一种具有叠层埋氧层的新栅型绝缘体上硅(SOI)器件。针对SOI器件的抗总电离剂量(TID)加固方案,对绝缘埋氧层(BOX)采用了叠层埋氧方案,对浅沟槽隔离(STI)层采用了特殊S栅方案。利用Sentaurus TCAD软件,采用Insulator Fixed Charge模型设置固定电荷密度,基于0.18μm CMOS工艺对部分耗尽(PD)SOI NMOS进行了TID效应仿真,建立了条栅、H栅、S栅三种PD SOI NMOS器件的仿真模型。对比三种器件辐照前后的转移特性曲线、阈值电压漂移量、跨导退化量,验证了该器件的抗TID辐照性能。仿真结果表明,有S栅的器件可以抗kink效应,该PD SOI NMOS器件的抗TID辐照剂量能力可达5 kGy。

Computational and Experimental Approaches for Evaluating Dose under a Block in TBI Geometry

Total Body Irradiation (TBI) patients are often treated at extended distances of several meters, with blocking made from high-Z materials placed close to the patients’ skin. Evaluating the dose under a block (e.g., for implanted medical device shielding purposes) in such a geometry is challenging. We compare the performance of two commonly used dose calculation algorithms, Anisotropic Analytical Algorithm (AAA) and Acuros XB, with Optically Stimulated Lumine- scence (OSLD) and ion chamber measurements in phantoms. The calculations and phantom measurements are also compared with in-vivo OSLD measure- ments. We find that OSLD and ion chamber measurements in phantom are good predictors of in-vivo measurements, while both AAA and Acuros XB sys- tematically overestimate the block transmission. We found Acuros XB to be accurate enough for a rough upper estimate (dose under block overestimated by 7% - 22%), while for AAA the overestimate was more severe (90% - 110%);the reason is that AAA does not account for the increase in pair production cro- ss-section in high-Z materials.

TBI Technique Improvements for Anesthetized Pediatric Patients Based on Near-Miss Incident Reporting

Purpose: To share our clinical experience of an optimized and comprehensive pediatric TBI technique. Methods and Materials: Through the use of incident learning, safety-critical areas were identified in our procedure for total body irradiation (TBI) for pediatric patients under anesthesia for bone-marrow transplant. The previous procedure lacked flexibility to accommodate various requests from the anesthesia team due to the wide range of patient sizes. To address this issue and to improve the process overall, we updated our procedure for TBI simulation, dosimetry planning, patient setup during treatment, and in vivo dosimetry. A simulation form was redesigned with additional detailed instructions and documentation requirements. The dose calculation procedure was reformulated to remove dependence on setup variations. Tissue compensation determination and therefore dose uniformity were improved by introducing rigorous calculation methods. Calculations were performed on 28 previously-treated patients to compare the dose uniformity using the new versus previous methods. Results: The new procedures improve interdepartmental communication, simplify the workflow, decrease the risk of treating patients in a setup that differs from that used during the simulation, and reduce dose heterogeneity. The new compensator design significantly improved patient dose uniformity: 0.8% ± 0.4% (new method) vs. 4.2% ± 2.3% (previous method) (p Conclusion: A near-miss incident reporting system was used to improve the safety and quality of pediatric TBI procedures under anesthesia.

智能控制自移行全身放射治疗床的研制

目的:研制一种智能控制自移行全身放射治疗床,使患者能以舒适、松弛的卧姿安全、精准地接受既定处方剂量的放射治疗。方法:该治疗床由床架、行走机构和智能控制部分组成。其中床架由铝合金框架和聚碳酸酯板制作,并设置有射野补偿板和肺挡铅。行走机构由驱动轮组和方向舵轮组成。智能控制部分由AT89S51单片机、液晶屏、键盘、激光束探测电路(2个)、超声波测距电路(2个)和脉冲宽度调制(pulse width modulation,PWM)功率模块组成。结果:该治疗床能使患者全程以卧姿接受各种处方剂量的精准治疗,而且显著提升了对肺的保护。结论:采用该治疗床可改善患者在治疗中的舒适性以及对长时间治疗的耐受性,同时可获得更加精准、安全的治疗。

一种用于全身照射技术的全身模拟定位CT扫描与图像重建方法

目的:探索一种适用于全身照射(TBI)的CT重建方法,可同体位连续扫描后获得一套完整的全身模拟定位CT。方法:使用TBI CT重建方法对患者进行CT模拟定位,完成后于Eclipse v15.5计划系统中生成一套全身模拟定位CT,将其运用到TBI计划设计与评估。在应用过程中,基于Python系统开发出相应的图像重建软件,与手动图像重建结果进行对比。结果:该全身模拟定位扫描方案可在Eclipse v15.5中实现两套CT的重建。在工作效率上,手工重建方法生成全身模拟定位CT平均需要10 min,软件重建方法只需要5 s。两种CT重建方法在图像质量上无差异,重建CT与真实值相比误差小于1 mm。使用重建的全身模拟定位进行TBI计划设计与评估,靶区适形度指数(CI)=0.854,剂量均匀性指数(HI)=0.199。结论:本文介绍的TBI全身模拟定位CT扫描与图像重建的方法可以简单、快速地获得完整的全身模拟定位CT图像,适用于后期的TBI计划设计、优化和评估过程。

基于多种免疫细胞的细胞免疫治疗联合含硼替佐米的化疗方案治疗多发性骨髓瘤的临床观察

目的:观察分析基于多种免疫细胞的细胞免疫疗法联合含硼替佐米的化疗方案治疗多发性骨髓瘤患者的临床效果。方法:选取2012年10月-2013年10月在我院住院治疗的76例多发性骨髓瘤患者,随机将他们分为2组,1组(38例)采用细胞免疫疗法联合含硼替佐米化疗方案(复合治疗组),另1组(38例)采用含硼替佐米的单纯化疗方案(单纯化疗组),比较2组患者治疗缓解率、免疫表型表达水平变化、无进展生存期(PFS)及不良反应发生情况。结果:复合化疗组总缓解率明显高于单纯化疗组(P<0.05);治疗后复合治疗组患者CD38^+、CD56^+、CD138^+和MRD^+表达率均明显低于单纯化疗组,CD19^+表达率均明显高于单纯化疗组(P<0.05);复合治疗组1、2、3年PFS均明显长于单纯化疗组(P<0.05);复合治疗组乏力、皮疹、周围神经病变、贫血、粒细胞缺乏等方面不良反应发生率均明显低于单纯化疗组(P<0.05)。结论:细胞免疫治疗联合含硼替佐米的化疗方案可显著增加多发性骨髓瘤患者的临床治疗疗效,明显提高缓解率的同时显著延长这类患者的生存期,而且可降低部分患者的不良反应的发生率,增加患者的化疗耐受。