Total body irradiation: Significant dose sparing of lung tissue achievable by helical tomotherapy

PurposeTotal body irradiation (TBI) is an important procedure in the conditioning for bone marrow and hematopoietic stem cell transplantation. Doses up to 12 Gy are delivered in hyperfractionated regimes. TBI performed with helical Tomotherapy® (Accuray, Madison, Wisconsin, USA) is an alternative to conventional techniques to deliver dose in extended target volumes with the possibility of simultaneous dose sparing to organs at risk. In this study we focused on maximum dose reduction to the lungs in TBI using helical Tomotherapy®.Material and methodsForty treatment plans of patients who received TBI were calculated with TomoH® (Accuray, Madison, Wisconsin, USA, Version 2.0.4) with a dose of 12 Gy delivered in six equal fractions (2 × 2 Gy/day). Planning iterations necessary to accomplish ICRU 83 report should be less than 250. Treatment time should be practicable in daily routine (<60 min.). Besides the usual contouring of organs at risk special contouring was required for optimization processes which focused on maximum dose sparing in the central lung tissue. Dose constraints (D2, D98, D99) were predefined for target volumes (i.e. PTV TBI D99: 90% of prescribed dose). Homogeneity index <0.15 was defined for acceptability of the treatment plan.ResultsFor all patients acceptable treatment plan fulfilling the predefined constraints were achievable. An average time of 46 min is required for treatment. Thirty-four of forty patients fulfilled D2 in the PTV TBI. Four patients failed D2 due to a high BMI >28 (maximum dose 13.76 Gy = 114.7%). The D98 in the PTV TBI was not reached by 2/40 patients due to BMI > 31 (minimum dose 11.31 Gy = dose coverage of 94.2%). Also these two patients failed the homogeneity index <0.15. The mean lung dose over all patients of the right lung was 7.18 Gy (range 6.4–9.5 Gy). The left lung showed a median (D50) dose of 7.9 Gy (range 6.7–9.3 Gy). Central lung dose showed a mean dose (D50) of 5.16 Gy (range 4.02–7.29 Gy). The D80 of the central lung showed an average dose of 3.87 Gy.ConclusionsTotal body irradiation using helical Tomotherapy® can be delivered with maximum lung tissue sparing (<6 Gy) but without compromise in adjacent PTV TBI structures (i.e. ribs, heart). High conformity and homogeneity in extended radiation volumes can be reached with this technique in an acceptable planning and treatment time. Limitations may occurred in patients with high body mass index.     

Automated Detection and Quantification of Brain Lesions in Acute Traumatic Brain Injury Using MRI

The purpose of this study is to develop a reproducible method for quantifying brain lesions in traumatic brain injury (TBI). Quantifying the effects of neuropathology is an important goal in the study of brain injury and disease, yet examiners have encountered significant difficulty quantifying brain lesions in neurotrauma where there may exist multiple, overlapping forms of injury including large focal lesions and more subtle, diffuse hemorrhage and/or shear injury. In the current study, we used conventional MRI to quantify brain lesion volume at separate time points in individuals with severe TBI. We present an automated method (ISODATA) for quantifying brain lesions that is compared against a standard semi-automated volumetric approach. The ISODATA method makes no assumptions about the location or extent of brain lesions, instead identifying areas of neuropathology via voxelwise comparisons of MRI signal intensity. The data reveal that ISODATA overlaps significantly with a semi-automated approach, is reliable across multiple observations, and is sensitive to change in lesion size during recovery from TBI. This study validates a reproducible, automated lesion quantification method used here to determine the location and extent of brain pathology following TBI. This approach may be used in conjunction with advanced imaging techniques to characterize the relationship between brain lesions and neurometabolism and function.     

Unrelated-Donor Bone Marrow Transplantation with a Conditioning Regimen Including Fludarabine, Busulfan, and 4 Gy Total Body Irradiation

We investigated the feasibility of reduced-intensity conditioning with 4 Gy total body irradiation, fludarabine (30 mg/m2 for 6 days), and busulfan (4 mg/kg for 2 days) for bone marrow transplantation from a serologically HLA-matched unrelated donor. Seventeen adult patients (median age, 55 years; range, 27-67 years) with various hematologic malignancies (6 in remission, 11 not in remission) were treated. Successful engraftment was achieved in all patients at a median of day 18 (range, day 14-35) after transplantation, although subsequent secondary graft failure was observed in 2 patients. The cumulative incidence of acute graft-versus-host disease (GVHD) of grades II to IV at day 100 was 48%. With a median follow-up of 286 days (range, 56-687 days), the rates of 1-year overall survival, 100-day nonrelapse mortality, and 1-year nonrelapse mortality were 41%, 14%, and 46%, respectively. Eleven patients died, and the causes of death were relapse (n = 4), pulmonary complications (n = 4), acute GVHD (n = 2), and sepsis (n = 1). The remaining 6 patients (at transplantation, 2 were in remission, and 4 were not in remission) are currently still in remission. These results suggest that this regimen reduces the risk of graft failure, but further studies are needed to ameliorate transplantation-related toxicities, primarily GVHD and/or pulmonary complications.     

Hippocampus, amygdala and global brain changes 10 years after childhood traumatic brain injury

Traumatic brain injury (TBI) in children results in damage to the developing brain, particularly in severely injured individuals. Little is known, however, of the long-term structural aspects of the brain following childhood TBI. This study investigated the integrity of the brain 10 years post-TBI using magnetic resonance imaging volumetrics in a sample of 49 participants with mild, moderate and severe TBI, evaluated against a normative sample of 20 individuals from a pediatric database with comparable age and gender distribution. Structural integrity was investigated in gray and white matter, and by manually segmenting two regions of interest (hippocampus, amygdala), potentially vulnerable to the effects of childhood TBI. The results indicate that more severe injuries caused a reduction in gray and white brain matter, while all TBI severity levels resulted in increased volumes of cerebrospinal fluid and smaller hippocampal volumes. In addition, enlarged amygdala volumes were detected in severely injured patients compared to their mild and moderate counterparts, suggesting that childhood TBI may disrupt the development of certain brain regions through diffuse pathological changes. The findings highlight the lasting impact of childhood TBI on the brain and the importance of monitoring brain structure in the long-term after early injury.     

TQ-2000多通道剂量仪在TBI体内相对剂量测量中的应用

全身照射（TBI）前，各放射治疗部门将针对本单位的设备、机房环境等实际情况，拟定相应的物理照射技术，进行必要的物理参数的测量。CDP仿真人体模型与TQ-2000多通道剂量仪的配合使用，可以快速、准确地测量TBI中体内相对剂量有关数据，为临床治疗提供质量保证。     

深圳市1994～2003年颅脑损伤住院病例流行病学特征分析

目的了解深圳市颅脑损伤住院病人流行病学特征及其规律,探讨防治措施。方法回顾性抽样调查深圳市1994～2003年颅脑损伤住院病例资料。结果等概率抽取39家医院创伤住院病历35万份中的7万份,60026份有效,颅脑损伤占10607份。主要年龄段20～40岁(63.56%);男女比2.79∶1.00;生产工人占(74.64%)。伤因车祸和打击伤各占(53.39%)、(18.67%),车祸时的交通工具主要为步行和摩托车。损伤地点为普通公路和公共场所。颅脑损伤病死率为4.26%。结论住院患者主要是40岁以下的男性工人,死亡率高,伤因主要为车祸和打击伤,多发生在普通公路和公共场所。加强交通安全教育和提高人员素质以降低颅脑损伤发病率和死亡率,减少对家庭和社会的危害。     

Dose-effect relationship for cataract induction after single-dose total body irradiation and bone marrow transplantation for acute leukemia

PURPOSE: To determine a dose-effect relationship for cataract induction, the tissue-specific parameter, alpha/beta, and the rate of repair of sublethal damage, mu value, in the linear-quadratic formula have to be known. To obtain these parameters for the human eye lens, a large series of patients treated with different doses and dose rates is required. The data of patients with acute leukemia treated with single-dose total body irradiation (STBI) and bone marrow transplantation (BMT) collected by the European Group for Blood and Marrow Transplantation were analyzed. METHODS AND MATERIALS: The data of 495 patients who underwent BMT for acute leukemia, who had STBI as part of their conditioning regimen, were analyzed using the linear-quadratic concept. The end point was the incidence of cataract formation after BMT. Of the analyzed patients, 175 were registered as having cataracts. Biologic effective doses (BEDs) for different sets of values for alpha/beta and mu were calculated for each patient. With Cox regression analysis, using the overall chi-square test as the parameter evaluating the goodness of fit, alpha/beta and mu values were found. Risk factors for cataract induction were the BED of the applied TBI regimen, allogeneic BMT, steroid therapy for >14 weeks, and heparin administration. To avoid the influence of steroid therapy and heparin on cataract induction, patients who received steroid or heparin treatment were excluded, leaving only the BED as a risk factor. Next, the most likely set of alpha/beta and mu values was obtained. With this set, the cataract-free survival rates were calculated for specific BED intervals, according to the Kaplan-Meier method. From these calculations, cataract incidences were obtained as function of the BED at 120 months after STBI. RESULTS: The use of BED instead of the TBI dose enabled the incidence of cataract formation to be predicted in a reasonably consistent way. With Cox regression analysis for all STBI data, a maximal chi-square value was obtained for alpha/beta = 1.75 Gy and mu = 0.75 h(-1). When Cox regression analysis was applied for patients who had no steroid treatment after BMT, a maximal chi-square value was obtained for alpha/beta = 1 Gy and mu = 0.6 h(-1). Cox regression analysis was repeated using the data of patients who had not received posttransplant steroid treatment and also no heparin administration; we found alpha/beta = 0.75 Gy and mu= 0.65 h(-1). An increased cataract incidence was observed after steroid treatment of >14 weeks and heparin administration. CONCLUSION: The alpha/beta value of 0.75 Gy and mu value of 0.65 h(-1) found for the eye lens are characteristic for late-responding tissues. The incidence of cataract formation can now be quantified, taking into account the values calculated for alpha/beta and mu, TBI dose, and dose rate. Also, the reduction in cataract incidence as a result of lens dose reduction by eye shielding can be estimated.     

全身照射的前期准备及在造血干细胞移植预处理中的应用

目的 探讨医用直线加速器高能X线全身照射(TBI)在造血干细胞移植预处理中的应用及治疗前的必要准备。方法 利用仿真人体体模和热释光测量设备，在高能X线全身照射条件下，对远距离大照射野的射线剂量均匀性进行测量和调整并测量了人体各重要组织和器官的吸收剂量。对已完成的12例TBI病例进行初步分析，观察临床应用效果。结果 经调整后的大照射野完全符合治疗要求，获得了人体内在全身照射条件下各器官的实际吸收剂量，为全身照射时照射剂量的评估和监测提供了可靠数据。完成的12例TBI治疗均成功。结论 经过仔细测量和调整后的医用直线加速器，完全可以胜任造血干细胞预处理全身照射的各项要求，临床应用可靠。