Fundamental and clinical study of three-dimensional compensating filters and direct dose monitoring system for total body irradiation

We devised 3D-compensating filters to improve dose distribution during total body irradiation (TBI). This study investigated the effect of these 3D-compensating filters and related complications in patients who had undergone bone marrow transplantation (BMT) followed by TBI. The 3D-compensating filters were fabricated by CT measurement of body thickness. The effectiveness of the 3D-compensating filters in producing a homogeneous dose distribution was checked by a thermoluminescent dosimeter (TLD) and semiconductor detectors in all patients. At the pelvis, the dose was measured simultaneously with an ionization chamber. The average dose distribution to each site when the 3D-compensating filter was used was 93% to the head, 97% to the neck, 99% to the thorax, and 98% to the pelvis in TLD when the scheduled dose was taken as 100%. There was no significant difference between the TBI and non-TBI groups with regard to the frequency of lung toxicity. Clinical interstitial pneumonitis occurred in 22.7% of the patients, interstitial pneumonitis with CMV in 13.6%, and idiopathic pneumonitis in 6.1% without any virus infection. Only one patient was regarded as having radiation-induced pneumonitis. 3D-compensating filters can be conveniently produced within a short time following CT measurement, and they seem to be safe and useful for dose flattening during TBI.     

Basic and clinical studies of total body irradiation for bone marrow transplantation

Basic and clinical studies of total body irradiation (TBI) with respect to the dose distribution are described. TBI was performed with 10 MV X-rays at the Department of Radiology of Hyogo College of Medicine Hospital. Two opposed bilateral fields were used, the source-axis distance was 400 cm, and the dose rate was 10 cGy/min. At 55 cm from the rear concrete wall, the back-scattered radiation from the wall was 0.91% of the radiation dose. The beam flatness was +/- 2.9% within 130 cm of the diagonal by using a beam flattening filter improved. The surface dose was 93.5% of the peak dose by the acrylic bolus (1.5 cm thickness) placed on the source side 45 cm from the center of the body axis. We devised compensating filters using lead plates to improve dose distribution of the head, neck and thorax. The effectiveness of the compensating filters in producing a homogeneous dose distribution was checked by the thermoluminescent dosimeters (TLDs) in a Rando phantom. The average dose distribution to each site when the compensators used was 94% for the head, 104% for the neck, and 99% for the thorax when the scheduled dose was taken as 100%. TBI was performed 4 to 1 days before bone marrow transplantation, and 10 Gy was given in equal daily fractions of 2.5 Gy over 4 days. During TBI, the patients were placed in the supine position with the knees bent. The body surface dose was measured with pairs of TLDs at the head, neck, thorax, and pelvis in 32 patients. At the pelvis, the dose was measured simultaneously with an ionization chamber. The average doses were 91% for the head, 95% for the neck, 93% for the thorax, and 106% for the pelvis.     

20 Years of Experience in Static Intensity-Modulated Total-Body Irradiation and Lung Toxicity

PURPOSE: To analyze lung complications after allogeneic or autologous transplantation following total-body irradiation (TBI) with compensators, so-called sIMRT (static intensity-modulated radiotherapy). PATIENTS AND METHODS: Between 1983 and 1998, 257 patients with different hematologic malignancies underwent TBI in six fractions to a total dose of 12 Gy within 3 consecutive days (212 with 11 Gy lung dose) prior to allogeneic (n=174) or autologous (n=83) transplantation. 40 patients were <16 years of age. Minimum follow-up time was 5 years. Median follow-up period was 110 months (13-231 months). RESULTS: 5-year survival rate was 47.9%, 5-year tumor-related mortality 23%, 5-year treatment-related mortality 29.2% (12 Gy lung dose: 53.3%+/-14.6%, 11 Gy: 24.1%+/-5.7%). Interstitial pneumonitis (IP) developed in 28 of 257 patients (10.9% +/- 3.8%). IP incidences in the allogeneic and autologous groups were 14.4% (+/-5.6%) and 3.6% (0-7.6%), respectively. IP incidences with 12/11 Gy lung dose were 22% (+/-12%)/8.5% (+/-3.7%). IP mortality was 9.3% (+/-3.6%). 13 of 28 patients with IP had a cytomegalovirus infection, five an acute graft-versus-host disease grade IV of the lungs. IP incidences with 12/11 Gy lung dose were 25% (9-50%)/4.2% (0.2-19.1%) in patients <16 years, and 20.7% (9.4-37.4%) and 13.3% (+/-6.5%) in older patients after allogeneic transplantation. CONCLUSION: Compensator-generated static intensity-modulated TBI with a total dose of 12 Gy and a lung dose of 11 Gy is a modern and comfortable treatment with moderate lung toxicity, small dose inhomogeneities and little setup failure before transplantation. Especially patients <16 years of age benefit from lung dose reduction.     

Biopsy of lung nodules with use of I-I device under intermittent CT fluoroscopic guidance: preliminary clinical study

PURPOSE: To investigate the efficacy of computed tomography (CT) fluoroscopy and a new needle holder (the I-I device) in lung nodule biopsy. MATERIALS AND METHODS: The I-I device is made of acrylate resin and was used to keep the entire needle in the tomographic plane. This study consisted of biopsies of 79 lung nodules in 77 patients. The final diagnoses were malignant in 54 patients, benign in 23, and unconfirmed in two. The biopsy procedure time from the beginning of the CT fluoroscopy procedure to the removal of the needle was measured for 24 needle passes. The radiation dose on the physician's hand was measured in five cases with use of a thermoluminescence ring. RESULTS: Fifty-one malignant and 20 benign lesions were correctly diagnosed with histologic specimens (90%). In 58 of 77 patients (75%), the biopsy procedures were completed within a single breath-hold. Pneumothorax occurred in 20 of 77 patients (26%) and chest tube insertion was required in five. The incidence of pneumothorax was significantly lower in patients who held their breath during biopsy procedures compared with those who did not (P < .0001; chi2 test). The biopsy procedure time ranged from 15 to 39 seconds (mean: 28.2 sec). The mean radiation dose on the physician's hand was 2 mSv/case. CONCLUSION: The diagnostic accuracy of biopsy with use of the I-I device under CT fluoroscopic guidance is comparable with that of the conventional method; however, a combination of CT fluoroscopy and the I-I device enables rapid biopsy procedures.     

Evaluation of the accuracy of a compensating filter based on compact NC-Mill for radiation therapy

The present report describes the fabrication technique and dosimetry aspects of a desktop numerically controlled milling machine (NC-Mill) based a compensator system that uses lead clay (Shield cray, Reactor Experiments, Inc., U.S.A.). Effective path lengths of patients were determined for CT image sets using the ray-tracing technique and converted to compensator thickness with the equivalent TMR method. Rigid urethane foam was processed with the NC-Mill to produce a mold for filters, and the lead clay was adopted as the compensating material. The dose distribution was measured on the compensating plane of an anthropomorphic phantom and a stair-step PMMA phantom. It was found that the radiation field with inhomogeneous dose was as high as 30%+/-3% with the compensating filters. In addition, when the absorbed dose at the central axis of 52 compensating filters that were used clinically was measured, 75.0% showed an error of less than +/-3%, and 3.8% showed the maximum dose error: >+/-5%. Overall, the present system was capable of producing dose uniformity to within +/-5% for a stair-step phantom, an anthropomorphic phantom, and clinical situations.     

Interstitial pneumonitis following allogeneic bone marrow transplantation in the treatment of leukemia based on BMT survey in Japan

Data from 208 patients with leukemia who were treated with allogeneic bone marrow transplantation between 1975 and 1985 were reported to the Japanese Bone Marrow Transplant Registry and were available for this analysis. These patients were classified into 82 of acute lymphocytic leukemia, 91 of acute non-lymphocytic leukemia, and 35 of chronic myelocytic leukemia. The incidence of interstitial pneumonitis (IP) was 39% (81/208) and fatality rate was 60% (49/81). Cytomegalovirus was the most frequent causative organism (54%). Using Cox's proportional hazard regression model, age of recipient (P = 0.0068), status of disease (P = 0.0191), and number of platelet transfusion (P = 0.0425) were found to be significant risk factors associated with IP. Probabilities of developing IP at three years were 65% and 42% in single dose and fractionated total body irradiation (TBI), respectively. In single dose TBI group, dose-rate affected the incidence of IP. On the contrary, in fractionated TBI group, number of fractions as well as dose-rate had no impact on the incidence of IP.     

计算机辅助检测在结肠低剂量多层螺旋CT成像中的应用

目的 评估计算机辅助检测系统(CAD)设置不同的检测过滤器数值(SFV)时,在低剂量MSCT成像中对结肠病变的检测能力.方法 56例结肠癌和(或)结肠息肉患者行MSCT结肠成像扫描,依据结肠镜和外科手术结果,将病变分为4组:结肠癌、最长径≥10.0mm息肉、最长径5.1～9.9 mm息肉和最长径≤5.0 mm息肉,之后确定病变在CT图像上的部位及大小,作为评估结肠CAD系统检测病变的金标准.将CAD系统的SFV设为0.25、0.50、0.75和1.00共4个等级,分别检测CT结肠成像图像,记录CAD标注出的病灶的部位和大小,根据上述金标准评估CAD系统对结肠病变的检出率,采用x2检验比较不同SFV设置时CAD对各组病变的检出率.结果 56例患者共有159个阳性病灶,其中结肠癌为44个,最长径≥10.0mm息肉45个,最长径5.1～9.9 mm息肉32个,最长径≤5.0 mm息肉38个.将结肠CAD系统SFV分别设置为0.25、0.50、0.75和1.00时,病灶的检出率分别85.5%(136/159)、85.5%(136/159)、79.2%(126/159)和56.0%(89/159).SFV为0.25和0.50时,与SFV为1.00时,CAD对病灶检出率的差异有统计学意义(P＜0.05).随着SFV数值的减低,病灶的检出率增高,假阳性数增加,但91.4%(138/151)～93.9%(31/33)的假阳性病灶很容易识别,仅有6.1%(2/33)～8.6%(13/151)的假阳性病灶,需借助MPR和3D仿真内镜识别.结论 在低剂量MSCT结肠成像中,结肠CAD系统可获得满意的病灶检出率,可调节CAD系统SFV数值,以便满足不同经验阅片者的需求.     

Interstitial pneumonitis after allogeneic bone marrow transplantation following total body irradiation.

The records of 40 patients who received allogeneic bone marrow transplantation (BMT) at Hyogo College of Medicine under the same conditioning regimen using cyclophosphamide and total body irradiation (TBI) from January 1984 to August 1989 were analyzed. The dose rate of TBI was 10 cGy per minute, and the total dose was 10 Gy (2.5 Gy daily for 4 days). Interstitial pneumonitis (IP) occurred in 13 of 40 patients, and was fatal in five patients. The probability of developing IP during the first year was 31%. We performed univariate analysis on the following factors but did not find any significant risk factors for IP: age and sex of patient, sex mismatch, ABO mismatch, grade of acute graft-versus-host disease, post immunosuppression regimen, and number of marrow cells transfused.     

Lung dose rate and interstitial pneumonitis in total body irradiation for bone marrow transplantation.

The effect of dose rate to the lungs and development of interstitial pneumonitis (IP) was evaluated in 114 bone marrow transplant patients receiving fractionated total body irradiation (TBI) (1200 rads TD in 6 fractions twice daily over 3 days) as part of their pre-conditioning regimen. The tumour dose (TD) was calculated as the mean lung dose as previously described (1). A 6MV linear accelerator at a mid-line dose rate of 7.5 rads/minute was used between March 1981 and June 1985 and a Co-60 source at 5 rads/minute thereafter. This resulted in a range of dose rates to the lung of between 6.9 and 8.9 rads/minute and 2.9 and 6.5 rads/minute respectively. In the majority of patients the aetiology of IP was investigated by lung biopsy with histology and culture. There was no statistically significant difference in the incidence of IP over the two sets of dose rates. Our study suggest that the incidence of IP using fractionated TBI is not influenced by dose rates below 8.9 rads per minute.     

A state-of-the-art pipeline for postmortem CT and MRI visualization: from data acquisition to interactive image interpretation at autopsy

The importance of autopsy procedures leading to the establishment of the cause of death is well-known. A recent addition to the autopsy work flow is the possibility of conducting postmortem imaging, in its 3D version also called virtual autopsy (VA), using multidetector computed tomography (MDCT) or magnetic resonance imagining (MRI) data from scans of cadavers displayed with direct volume rendering (DVR) 3D techniques. The use of the data and their workflow are presented. Data acquisition was performed and high quality data-sets with submillimeter precision were acquired. New data acquisition techniques such as dual-energy CT (DECT) and quantitative MRI, then were implemented and provided additional information. Particular findings hardly visualized in conventional autopsy can rather easy be seen at the full body CT, such as air distribution, e.g. pneumothorax, pneumopericardium, air embolism, and wound channels. MRI shows natural deaths such as myocardial infarctions. Interactive visualization of these 3D data-sets can provide valuable insight into the corpses and enables non-invasive diagnostic procedures. In postmortem CT imaging, not being limited by a patient depending radiation dose limit the data-sets can, however, be generated with such a high resolution that they become difficult to handle in today's archive retrieval and interactive visualization systems, specifically in the case of full body scans. To take full advantage of these new technologies the postmortem workflow needs to be tailored to the demands and opportunities that the new technologies allow.     

Calculating effective dose on a cone beam computed tomography device: 3D Accuitomo and 3D Accuitomo FPD

OBJECTIVES: This study evaluates two methods for calculating effective dose, CT dose index (CTDI) and dose-area product (DAP) for a cone beam CT (CBCT) device: 3D Accuitomo at field size 30x40 mm and 3D Accuitomo FPD at field sizes 40x40 mm and 60x60 mm. Furthermore, the effective dose of three commonly used examinations in dental radiology was determined. METHODS: CTDI(100) measurements were performed in a CT head dose phantom with a pencil ionization chamber connected to an electrometer. The rotation centre was placed in the centre of the phantom and also, to simulate a patient examination, in the upper left cuspid region. The DAP value was determined with a plane-parallel transmission ionization chamber connected to an electrometer. A conversion factor of 0.08 mSv per Gy cm(2) was used to determine the effective dose from DAP values. Based on data from 90 patient examinations, DAP and effective dose were determined. RESULTS: CTDI(100) measurements showed an asymmetric dose distribution in the phantom when simulating a patient examination. Hence a correct value of CTDI(w) could not be calculated. The DAP value increased with higher tube current and tube voltage values. The DAP value was also proportional to the field size. The effective dose was found to be 11-77 microSv for the specific examinations. CONCLUSIONS: DAP measurement was found to be the best method for determining effective dose for the Accuitomo. Determination of specific conversion factors in dental radiology must, however, be further developed.     

螺旋CT三维成像在诊断气管、支气管疾病中作用的评价

目的 评价综合运用三维成像技术在诊断气管、支气管疾病中的作用。材料与方法 选择５３直支气管以上气道疾病患者行高档螺旋ＣＴ扫描,将容积扫描数据预处理后传至计算机工作站,分别用ＣＴ仿真支气管内镜（ＣＴＶＢ）,表面遮盖显示法（ＳＳＤ）,最大强度投影（ＭＩＰ）,最小强度投影（Ｍｉｎ ＩＰ）,多平面重构（ＭＰＲ）进行重建,分析影像学表现,４例与手术标本进行对照。结果 在轴位图像基础上,气管肿瘤在ＭＰＲ、ＣＴ     

Value of three-dimensional US for optimizing guidance for ablating focal liver tumors

PURPOSE: To determine if three-dimensional ultrasound (3D US), by nature of its ability to simultaneously evaluate structures in three orthogonal planes and to study relationships of devices to tumor(s) and surrounding anatomic structures from any desired orientation, adds significant additional information to real-time 2D US used for placement of devices for ablation of focal liver tumors. MATERIALS AND METHODS: Sixteen patients underwent focal ablation of 23 liver tumors during two intraoperative cryoablation (CA) procedures, three intraoperative radiofrequency ablation (RFA) procedures, 11 percutaneous ethanol injections (PEI) procedures, and six percutaneous RFA procedures. After satisfactory placement of the ablative device(s) with 2D US guidance, 3D US was used to reevaluate adequacy to device position. Information added by 3D US and resultant alterations in device deployment were tabulated. RESULTS: 3D US added information in 20 of 22 (91%) procedures and caused the operator to readjust the number or position of ablative devices in 10 of 22 (45%) of procedures. Specifically, 3D US improved visualization and confident localization of devices in 13 of 22 (59%) procedures, detected unacceptable device placement in 10 of 22 (45%), and determined that 2D US had incorrectly predicted device orientation to a tumor in three of 22 (14%). CONCLUSIONS: Compared to conventional 2D US, 3D US provides additional relationship information for improved placement and optimal distribution of ablative agents for treatment of focal liver malignancy.     

Impact of treatment planning with deformable image registration on dose distribution for carbon-ion beam lung treatment using a fixed irradiation port and rotating couch

Objective:

When using a fixed irradiation port, treatment couch rotation is necessary to increase beam angle selection. We evaluated dose variations associated with positional morphological changes to organs.

Methods:

We retrospectively chose the data sets of ten patients with lung cancer who underwent respiratory-gated CT at three different couch rotation angles (0°, 20° and −20°). The respective CT data sets are referred to as CT₀, CT₂₀ and CT₋₂₀. Three treatment plans were generated as follows: in Plan 1, all compensating bolus designs and dose distributions were calculated using CT₀. To evaluate the rotation effect without considering morphology changes, in Plan 2, the compensating boli designed using CT₀ were applied to the CT_±20 images. Plan 3 involved compensating boli designed using the CT_±20 images. The accumulated dose distributions were calculated using deformable image registration (DIR).

Results:

A sufficient prescribed dose was calculated for the planning target volume (PTV) in Plan 1 [minimum dose received by a volume ≥95% (D₉₅) > 95.8%]. By contrast, Plan 2 showed degraded dose conformation to the PTV (D₉₅ > 90%) owing to mismatch of the bolus design to the morphological positional changes in the respective CT. The dose assessment results of Plan 3 were very close to those of Plan 1.

Conclusion:

Dose distribution is significantly affected by whether or not positional organ morphology changes are factored into dose planning.

Advances in knowledge:

In treatment planning using multiple CT scans with different couch positions, it is mandatory to calculate the accumulated dose using DIR.The use of particle beam therapy is rapidly growing worldwide.¹ Some particle beam systems use a rotational gantry to allow irradiation from multiple directions. However, as the gantry for carbon-ion beam therapy is larger and heavier than that for proton beam therapy,² many carbon-ion beam treatment systems feature a fixed gantry with one or two beam ports placed at the sides of the treatment couch. The treatment couch is rotated around its long axis to allow beam entrance at oblique angles, eliminating the need for gantry rotation. It is necessary to consider changes in organ morphology when treating a patient with a fixed irradiation port and rotating couch. Usually, two or three treatment planning CT data sets are acquired at different couch rotation angles. Treatment planning parameters and patient accessories (patient collimators and compensating boli) are designed at each beam angle using the respective CT images acquired in the planned rotation positions. Deformable image registration (DIR)^3,4 is used to calculate the accumulated dose distribution from multiple beam directions using more than two CT data sets to factor in morphological changes of organs with treatment couch rotation. Compared with single planning CT, multiple planning CTs require extra time for clinical workflow both for CT acquisition and deformation planning. To date, however, patient and target dose variations owing to position-dependent morphological changes with treatment couch rotation have not been evaluated.Here, we evaluated patient and target dose variations owing to position-dependent morphological changes with treatment couch rotation.     

Exposed dose comparison between coronary computed tomographic angiography and coronary angiography: basic examination by phantom

The new type of coronary angiography(CAG)that uses 40 mm volumetric computed tomography(VCT)has great potential for cardiac disease. However, it is still necessary to be cognizant of exposure dose. We measured doses of CAG by both VCT and cardiovascular X-ray using a body phantom within 170 glass dosimeters. VCT protocols were 120 kV, 570 mA, and 0.35 sec/rot with and without the dose-reduction features(small cardiac X-ray beam filter and ECG mA modulation). The cardiovascular X-ray protocol was Auto(65 - 77 kV)kV, Auto(41 - 46 mA)mA, 5 secx11 shots+11 min fluoroscopy(minimum protocol for screening). VCT with and without the dose-reduction features has the same dose distribution, however, the dose-reduction features reduced the amount of dose by about 40-50%. For VCT with those features, measured dose was about 70 mGy in the cardiac area and 60 mGy at the skin of the back, whereas those of cardiovascular X-ray were 10 mGy and 30 mGy. We measured detailed dose distributions and variations in the phantom, and we also demonstrated the possibility of VCT's dose-reduction features. The CT dose was still higher than that of cardiovascular X-ray, however, there were advantages of CT scanning, for instance, information about calcification, soft plaque, and 3D visualization. We think it is important to use both systems with an understanding of their advantages and limitations.     

The radiation protective devices for interventional procedures using computed tomography

A scattered dose and a surface dose from phantom measurements during interventional procedures with computed tomography (IVR-CT) were evaluated. To reduce the personnel exposure in IVR-CT, the new protective devices were developed and its effect evaluated. Two radiation protection devices were experimentally made using a lead vinyl sheet with lead equivalent 0.125mmPb. The first device is a lead curtain which shields the space of CT-gantry and phantom for the CT examination. The second device is a lead drape which shields on the phantom surface adjacent to the scanning plane for the CT-fluoroscopy. Scattered dose and phantom surface dose were measured with an abdominal phantom during Cine-CT (130 kV, 150 mA, 5 seconds, 10 mm section thickness). They were measured by using ionization chamber dosimeter. They were measured with and without a lead curtain and a lead drape. Scattered dose rate was measured at distance of 50-150 cm from the scanning plane. And, surface dose was measured at distance of 4-21 cm from the scanning plane on the phantom. On operator's standing position, scattered dose rates were from 8.4 to 11.6 micro Gy/sec at CT examination. The lead curtain and the lead drape reduced scattered dose rate at distance of 50 cm from the scanning plane by 66% and 58.3% respectively. Surface dose rate were 118 micro Gy/sec at distance of 5 cm from the scanning plane at CT-fluoroscopy. The lead drape reduced the surface dose by 60.5%. High scattered exposure to personnel may occur during interventional procedures using CT. They were considerably reduced during CT-arteriography by attaching the lead curtain in CT equipment. And they were substantially reduced during CT-fluoroscopy by placing the lead drape adjacent to the scanning plane, in addition, operator's hand would be protected from unnecessary radiation scattered by phantom. It was suggested that the scattered exposure to personnel could be sufficiently reduced by using radiation protection devices in IVR-CT. The radiation protection devices and the CT equipment should be improved or developed based on the radiation protection.     

Cerebral ischemia after filter-protected carotid artery stenting is common and cannot be predicted by the presence of substantial amount of debris captured by the filter device

PURPOSE: Protected carotid artery stent placement is currently under clinical evaluation as a potential alternative to carotid endarterectomy. The current study was undertaken to determine the incidence of new ischemic lesions found on diffusion-weighted MR imaging (DWI) in nonselected patients after protected carotid artery stent placement using a filter device and to determine the potential relationship between these new ischemic lesions and the presence or absence of a clear amount of debris captured by the neuroprotection filter device. MATERIALS AND METHODS: A nonrandomized cohort of 52 patients (40 men, 12 women) presenting with carotid occlusive disease underwent protected carotid artery stent placement using a filter device. DWI obtained 1 day before stent placement was compared with that obtained 1 day after stent placement. In addition, the macroscopic and microscopic analysis of debris captured by the filter device during the carotid stent placement procedure was assessed. RESULTS: Neuroprotected carotid stent placement was technically successful in all 53 procedures but was complicated by a transient ischemic attack in 3 patients (5.6%). In 22 patients (41.5%), new ischemic lesions were found on DWI, and in 21 filter devices (39.6%), a substantial amount of atheromatous plaque and/or fibrin was found. No clear relationship between the presence of debris captured by the filter device and new lesions detected by DWI was found (P = .087; odds ratio 3.067). CONCLUSION: Neuroprotected carotid artery stent placement will not avoid silent cerebral ischemia. Systematic microscopic analysis of debris captured by the filter device has no predictive value for potential cerebral ischemia after carotid artery stent placement.     

Total-body irradiation before bone marrow transplantation for acute leukemia in first or second complete remission

Aim

In order to assess the influence of total-body irradiation (TBI) on the outcome and incidence of complication after bone marrow transplantation (BMT), we retrospectively analyzed our patients treated for acute leukemia and conditioned with TBI prior to BMT.

Patients and Methods

Between 1980 and 1993, 326 patients referred to our department with acute non-lymphoblastic leukemia (ANLL, n=182) and acute lymphoblastic leukemia (ALL, n=144) in complete remission underwent TBI either in single dose (190 patients: 10 Gy administered to the midplane, and 8 Gy to the lungs [STBI]) or in 6 fractions (136 patients: 12 Gy on 3 consecutive days, and 9 Gy to the lungs [FTBI]) before BMT. The male-to-female ratio was 204/122 (1.67), and the median age was 30 years (mean: 30 ± 11, range: 3 to 63). The patients were analyzed according to 3 instantaneous dose rate groups: 118 patients in the LOW group (≤0.048 Gy/min), 188 in the MEDIUM group (> 0.048 and ≤ 0.09 Gy/min), and 20 in the HIGH group (> 0.09 cGy/min). Conditioning chemotherapy consisted of cyclophosphamide (CY) alone in 250 patients, CY and other drugs in 54, and 22 patients were conditioned using combinations without CY. Following TBI, allogeneic and autologous BMT were realized respectively in 118 and 208 patients. Median follow-up period was 68 months (mean: 67 ± 29, range: 24 to 130 months).

Results

Five-year survival, LFS, RI and TRM rates were 42%, 40%, 47%, and 24%, respectively. Five-year LFS was 36% in the STBI and 45% in the FTBI group (p = 0.17). It was 36% in the LOW group, 42% in the MEDIUM group, and 30% in the HIGH group (p > 0.05). Five-year RI was 50% in STBI, 43% in FTBI, 55% in LOW, 41% in MEDIUM, and 44% in HIGH groups (STBI vs. FTBI, p = 0.48; LOW vs. MEDIUM, p = 0.03: MEDIUM vs. HIGH, p = 0.68). TRM was not influenced significantly by the different TBI techniques. When analyzing separately the influence of fractionation and the instantaneous dose rate either in ANLL or ALL patients, no difference in terms of survival and LFS was observed. Fractionation did not influence the 5-year RI both in ANLL and ALL patients. However, among the patients with ANLL, 5-year RI was significantly higher (58%) in the LOW group than the MEDIUM group (31%, p = 0.001), whereas instantaneous dose rate did not significantly influence the RI in ALL patients. The 5-year TRM rate was significantly higher in allogeneic BMT group both in ANLL (37%) and ALL (37%) patients than those treated by autologous BMT (ANLL: 15%, ALL: 18%: p = 0.002 and 0.02, respectively). The 5-year estimated interstitial pneumonitis (IP) and cataract incidence rates were 22% and 19%, respectively, in all patients. IP incidence seemed to be higher in the HIGH group (46%) than the MEDIUM (19%, p = 0.05) or LOW (25%, p = 0.15) groups. Furthermore, cataract incidence was significantly influenced by fractionation (STBI vs. FTBI, 29% vs. 9%; p = 0.003) and instantaneous dose rate (LOW vs. MEDIUM vs. HIGH, 0% vs. 27% vs. 33%; p < 0.0001). Multivariate analyses revealed that the best factors influencing the survival were 1st CR (p = 0.0007), age ≤ 40 years (p = 0.003), and BMT after 1985 (p = 0.008). The RI was influenced independently only by the remission status (p = 0.0002). On the other hand, the TRM rate was lower in patients who did not experience graft-vs.-host disease (GvHD, p < 0.0001), and in those treated after 1985 (p = 0.0005). GvHD was the only independent factor involved in the development of IP (p = 0.01). When considering the cataract incidence, the only independent factor was the instantaneous dose rate (p = 0.0008).

Conclusion

The outcome of BMT patients conditioned with TBI for acute leukemia was not significantly influenced by the TBI technique, and TRM seemed to be lower in patients treated after 1985. On the other hand, cataract incidence was significantly influenced by the instantaneous dose rate.