Physical problems of total body irradiation

In the concept of combined treatment of acute leukemias the whole body has to be irradiated as precisely and homogeneously as reasonably achieveable. In fulfillment of these radiobiological requirements, total body irradiation (TBI) means a very special challenge to medical physicists. Very large, uniform high energy photon beams have to be realized and applied. The dose at any relevant reference point has to be determined, regarding all influences of the TBI treatment situation. The dose distribution has to be modified - if necessary - verified and recorded. The lungs - the vital organs at risk in TBI - have to be shielded to tolerable doses. Optimization of TBI demands to understand all physical limitations and to utilize all technical possibilities. These physical problems encountered with TBI dosimetry, treatment planning and treatment performance are discussed.     

Physical aspects of total body irradiation in Basel

Total body irradiations have been performed on 112 patients at the University Hospital in Basel since 1979. Total body irradiations are effected in order to prepare patients with leukemia for bone marrow transplantation. The irradiation technique with 4 MV X-rays is described. The patients are treated without lung-shieldings. The dose-measurements show an acceptable homogeneity. The applied technique is very easy in comparison with other centers. A main point is making the patient's position as comfortable as possible. The accuracy of dose-application and dose-distribution is considered clinically acceptable.     

Appropriate treatment planning method for field joint dose in total body irradiation using helical tomotherapy

Total body irradiation (TBI) using helical tomotherapy (HT) has advantages over the standard linear accelerator-based approach to the conditioning regimen for hematopoietic cell transplantation. However, the radiation field has to be divided into two independent irradiation plans to deliver a homogeneous dose to the whole body. A clinical target volume near the skin increases the skin surface dose; therefore, high- or low-dose regions arise depending on the set-up position accuracy because the two radiation fields are somewhat overlapped or separated. We aimed to determine an adequate treatment planning method robust to the set-up accuracy for the field joint dose distribution using HT-TBI. We calculated treatment plans reducing target volumes at the interface between the upper and lower body irradiations and evaluated these joint dose distributions via simulation and experimental studies. Target volumes used for the optimization calculation were reduced by 0, 0.5, 1.0, 2.0, 2.5, and 3.0 cm from the boundary surface on the upper and lower sides. Combined dose distributions with set-up error simulated by modifying coordinate positions were investigated to find the optimal planning method. In the ideal set-up position, the target volume without a gap area caused field junctional doses of up to approximately 200%; therefore, target volumes reduced by 2.0–3.0 cm could suppress the maximum dose to within 150%. However, with set-up error, high-dose areas exceeding 150% and low-dose areas below 100% were found with 2.0 and 3.0 cm target volume reduction. Using the dynamic jaw (DJ) system, dose deviations caused by set-up error reached approximately 20%, which is not suitable for HT-TBI. Moreover, these dose distributions can be easily adjusted when combined with the intensity modulation technique for field boundary regions. The results of a simulation and experimental study using a film dosimetry were almost identical, which indicated that reducing the target volume at the field boundary surface by 2.5 cm produces the most appropriate target definition.     

Total body irradiation in Essen--dosimetry and physical treatment planning

Since 1975, in Essen 109 patients received total body irradiation (TBI) prior to bone marrow transplantation. About 80 patients were treated by bilateral 5.7 MeV photon beams. Three new TBI techniques were developed providing precise, homogeneous, reliable and reasonable a. p./p. a. TBI for adults and children. Systematic TBI dosimetry and the beam-zone method enable for individual treatment planning.     

Modelling hematological parameters after total body irradiation

Abstract

Purpose: The time- and dose-dependent reconstitution of hematopoiesis after radiation exposure is strongly related to the stem cell population and can be used to predict hematological parameters. These parameters allow further insight into the hematopoietic system and might lead to the development of novel stem cell transplantation models.

Materials and methods: CD4-/- C57Bl/6 mice, transgenic for human CD4 and HLA-DR3, were irradiated in a single (3, 6, 8 and 12 Gy) and fractionated (6 × 1 Gy, 6 × 1.5 Gy, 6 × 2 Gy; twice daily) dose regimen. Blood was analyzed weekly for red blood cells (RBC), hemoglobin concentration (Hb), hematocrit (HCT) and white blood cells (WBC). Organ and tissue damage after irradiation were examined by histopathology.

Results: The recovery curves for RBC, Hb, HCT and WBC showed the same velocity (< 1 week) for all radiation doses (3–12 Gy) starting at different, dose-dependent times. The only dose-dependent parameter was defined by the beginning of the recovery process (dose-dependent shift) and higher doses were related to a later recovery of the hematopoietic system. The RBC, Hb and HCT recovery was followed by a saturation curve reaching a final concentration independent of the radiation dose. Histological analysis of the bone marrow in the single dose cohort showed a dose-dependent reduction of the cellularity in the bone marrow cavities. The fractioned radiation dose cohort resulted in a regeneration of all bone marrow cavities.

Conclusion: Specific functions were developed to describe the reconstitution of hematological parameters after total body irradiation.     

Dosimetric problems associated with total body irradiation

Total body irradiation (TBI), which is carried out with high energy photons at large source distances and with large fixed fields, involves special dosimetric requirements. The dose measurements published thus far on anthropomorphic phantoms have shown that deviations from the dose values calculated with "normal" dose functions occur as a result of completely different scatter radiation distributions. The higher the photon energy selected, the more slight these deviations become.     

全身照射的剂量学方法

全身照射是治疗白血病和晚期实体瘤的一个重要组成部分,然而由于各放疗中心的设备状况、射线的能量、射野大小及治疗室的大小各不相同,从而使各放疗中心所采用的物理照射技术也不相同。因此,对比各种不同物理照射技术及临床结果,对于确定最佳放射治疗计划就显得非常重要。本文从照射体位及射野均匀性、剂量计算、处方计算及分次照射、肺铅挡等四个方面讲述全身照射的剂量学方法,这个问题也是放疗医生、特别是放射物理人员在实施全身照射以前必须解决的问题。     

Problems of dose modification in total body irradiation

Physical treatment planning of total body irradiation (TBI) has the goal to optimize the spatial distribution of dose, taking radiobiological requirements and technical possibilities into account. In order to improve the dose homogeneity in the target volume or to reduce dose and dose rate in organs at risk dose modifications are needed to raise or to lower the local dose. Treatment optimization demands to know possible techniques, the methods of individual planning and calculation as well as the limitations of beam modifying aids.     

Secondary radiation dose during high-energy total body irradiation

Aim

The goal of this work was to assess the additional dose from secondary neutrons and γ-rays generated during total body irradiation (TBI) using a medical linac X-ray beam.

Background

Nuclear reactions that occur in the accelerator construction during emission of high-energy beams in teleradiotherapy are the source of secondary radiation. Induced activity is dependent on the half-lives of the generated radionuclides, whereas neutron flux accompanies the treatment process only.

Materials and methods

The TBI procedure using a 18 MV beam (Clinac 2100) was considered. Lateral and anterior–posterior/posterior–anterior fractions were investigated during delivery of 2 Gy of therapeutic dose. Neutron and photon flux densities were measured using neutron activation analysis (NAA) and semiconductor spectrometry. The secondary dose was estimated applying the fluence-to-dose conversion coefficients.

Results

The main contribution to the secondary dose is associated with fast neutrons. The main sources of γ-radiation are the following: ⁵⁶Mn in the stainless steel and ¹⁸⁷W of the collimation system as well as positron emitters, activated via (n,γ) and (γ,n) processes, respectively. In addition to 12 Gy of therapeutic dose, the patient could receive 57.43 mSv in the studied conditions, including 4.63 μSv from activated radionuclides.

Conclusion

Neutron dose is mainly influenced by the time of beam emission. However, it is moderated by long source–surface distances (SSD) and application of plexiglass plates covering the patient body during treatment. Secondary radiation gives the whole body a dose, which should be taken into consideration especially when one fraction of irradiation does not cover the whole body at once.     

An isocentrically mounted stand for total body irradiation

The purpose of this study was to construct a stand to support a patient for total body photon irradiation and to expedite the set-up and treatment by rotating the stand. As in other isocentric treatments, the midline dose is impacted less by source-to-skin distance variations. The method of immobilizing the patient is described. A 10 mm lucite plate is supported in front of the patient to increase skin dose. A matrix of holes in this plate serves to index the location of blocks used to shield the lungs. The dosimetry of the set-up is described, as is the production of tissue deficit compensators. The results of phantom studies and in vivo thermoluminescent dosimetry measurements are presented.     

In vivo ESR dosimetry in total body irradiation

Total body irradiation (TBI) using high doses (about 10 Gy) with photons in the range between 1 and 10 MV combined with intensive chemotherapy has been used successfully in treatment of acute and chronic leukemia before bone marrow transplantation. One of the principal international guidelines in TBI is to use in vivo dosimetry in order to compare the prescribed dose with that absorbed. The use of in vivo dosimetry is also useful as a retrospective evaluation of any deviation from the prescribed dose greater than +/- 5% for relevant parts of the body, especially in the lung and in other organs at risk. In this paper, Electron Spin Resonance (ESR), using alanine dosimeters, is demonstrated to be a powerful tool for absorbed dose evaluation in TBI by detection of free radicals produced in alanine by ionizing radiation. In this study, we present the results obtained using ESR dosimetry in eleven patients undergoing TBI. The major advantages appear to be: 1. the ESR signal in alanine dosimetry is stable for years without fading: 2. the detection of the ESR signal does not destroy the information and so enables a retrospective judgment of the TBI plan adopted.     

Treatment of neuroblastoma: role of total body irradiation

Advanced neuroblastoma, scarcely responsive to conventional therapies, can take advantage of high dose chemio-radiotherapic treatment followed by bone marrow transplant. Nineteen young patients underwent an ablative chemotherapy with high dose Vincristine and Melphalan plus Total Body Irradiation in Genoa, Italy; all of them underwent autologous bone marrow transplantation. Fourteen children were in complete remission (CR), 5 had residual disease. Thirteen are alive after a median of 7 months following transplant; 9 are in CR; 4 have disease; 1 died for toxicity; 5 for relapse. The results seem to suggest that ablative therapy should be given to patients in CR. Toxicity was not remarkable mainly as far as TBI is concerned.     

Dose compensation of the total body irradiation therapy.

The aim of the study is to improve dose uniformity in the body by the compensator-rice and to decrease the dose to the lung by the partial lung block. Rando phantom supine was set up to treat bilateral fields with a 15 MV linear accelerator at 415cm treatment distance. The experimental procedure included three parts. The first part was the bilateral irradiation without rice compensator, and the second part was with rice compensator. In the third part, rice compensator and partial lung block were both used. The results of thermoluminescent dosimeters measurements indicated that without rice compensator the dose was non-uniform. Contrarily, the average dose homogeneity with rice compensator was measured within +/- 5%, except for the thorax region. Partial lung block can reduce the dose which the lung received. This is a simple method to improve the dose homogeneity and to reduce the lung dose received. The compensator-rice is cheap, and acrylic boxes are easy to obtain. Therefore, this technique is suitable for more studies.     

The accuracy of dose determination during total body irradiation

AIM: The aim of this work was to estimate the error in dose calculations, to check the agreement between the measured and calculated doses and to analyse dose discrepancies in the group of patients undergoing total body irradiation. PATIENTS AND METHODS: A combination of lateral and anterior-posterior fields was used in 8 fractions and on 4 consecutive days. Doses were preliminarily calculated and then measured in vivo by thermoluminescent, semiconductor and ionization dosimeters attached to the body in 10 representative transverse cross-sections. Calculations and measurements were carried out for the beam at the body entry and exit. The error in dose calculations was estimated for each reference point. Dose deviations between calculations and measurements were analysed using the Student's t-test. RESULTS: The error in preliminary dose calculations ranged from 3% to 15% (Table 1). Standard deviations of the measurements and percent deviations from the calculations exceeded 10% only for the lung and neck exits (Table 3). Average thermoluminescent readings were 6% higher than the corresponding semiconductor readings. The measured doses fitted the calculated values within the limit of error, except for the lung, head and neck exits for the whole group, depending on the type of fields used (Table 4).     

Optimization of a dosimetric procedure in total body irradiation

The experimental dosimetry of 2 radiotherapy beams produced by a 60Co Picker unit and by a Siemens 4 MV unit, respectively, was analyzed to verify the use of tissue air ratio (TAR) and tissue maximum ratio (TMR) in the computerized planning of total body irradiation (TBI). The use of a small ionization chamber PRO5P Capintec in anthropometric phantoms allowed us to test a computed calculation procedure adopted to reduce both experimental uncertainties and time consumption. The experimental test on the computed procedure was also useful to identify the equivalent fields the patient's body had to be divided into for dosimetric planning. Such dosimetric specifications as average dose to the patient and degree of dose inhomogeneity are calculated when the thickness of compensator filters in perspex is optimized. Following the guidelines reported in ICRU 29, a dosimetric record is presented. In page 1 the target volume is described, in page 2 the provisional treatment planning, and in page 3 the actual treatment planning, checked with in vivo TLD measurements, and the dose specifications for TBI.