Examination of fragment dose contribution in heavy ion radiotherapy

Heavy-ion radiotherapy is an efficient method for the treatment of deep-seated tumors, because the stopping of ions in a tissue delivers the maximal absorbed dose to the tumor-affected areas with minimal damage to the healthy tissues. However, heavy ions can undergo nuclear reactions, giving products with lower Z-values and hence a longer range in the tissue. This causes a dose increase beyond the mean range of the primary beam. The contribution of such reaction products was examined in an experiment where a stack of tissue-like targets interleaved with CR-39 etched track detectors (ETD) was irradiated with heavy ions. The analysis was performed using a recently developed technique of trajectory tracing, which enables the spectroscopy of fragments with different Z-values.     

Biological verification of heavy ion treatment planning

Chinese hamster ovary (CHO) cells and thermoluminescent detectors (TLD-700) were used for physical and biological verification of heavy ion treatment planning. Experiments were performed in a cylindrical water phantom, in some cases with lung and bone equivalent material in front of the target volume. The results confirm the possibility of using thermoluminescent detectors for a quantitative verification of dose distributions. CHO cells can be used at least for qualitative dose verification. Received: 15 December 1997 / Accepted in revised form: 6 February 1998     

Microdosimetric structure of heavy ion tracks in tissue

Summary Energy dissipation in tracks of high energy heavy ions in tissue shows a lateral spread of several to many microns depending on the energy of the primary particle. Complete dosimetric characterization, therefore, requires in addition to the Linear Energy Transfer (LET) information on the radial energy distribution. The theory of track structure distinguishes two regions: core and penumbra. The core is a narrow central zone with a radius in tissue far below 1 micron where energy deposition occurs mainly in processes of excitation and electron plasma oscillation. According to the Equipartition Principle, half of the total energy dissipation accrues in this manner. The penumbra is a peripheral zone enveloping the core where energy deposition occurs mainly in ionization events by energetic secondary electrons released by the primary particle in the center of the core traveling at rather high speed thus spreading laterally. The extension of the penumbra depends in a complex manner on the maximum transferable energy to electrons which in turn depends on the speed of the primary particle. Local energy density in the penumbra decreases with the square of increasing radius. It therefore amounts only to a very small fraction of the core density already a few microns away from the center. In general terms, track structure can be described as exhibiting a core of enormous energy density with lateral dimensions remaining entirely on the submicroscopic level surrounded by a penumbra where energy density drops precipitously to very small levels. The relationships are illustrated with micrographs of different sections of a heavy particle track in nuclear emulsion and their counterpart graphical plots.     

Thymoma: Results of treatment and role of radiotherapy

Purpose

The aim of this study is to assess results of treatment, factors influencing prognosis with regard to causes of failure and treatment tolerance in patients with thymoma.

Material and methods

Between 1966 and 2006, 63 patients with thymoma had been treated at the Centre of Oncology in Krakow. Patients were treated by means of different treatment modalities: surgery followed by radiotherapy (52%), radiotherapy alone (13%), chemoradiotherapy alone (15%), surgery followed by chemoradiotherapy (5%), surgery alone (5%) and others.

Results

The 10-year locoregional recurrence-free survival (LRRFS) was 79%, disease free survival (DFS) was 57% and overall survival (OS) was 57%. Masaoka stage was the only independent prognostic factor for LRRFS. Masaoka stage and method of radiotherapy delivery (higher photon energies), were independent prognostic factors for OS. For DFS, the independent prognostic factors were age, type of treatment (favoured surgery followed by radiotherapy or chemoradiotherapy), Masaoka stage and year of start of treatment. Most common reactions were lung fibrosis in 36% of patients (mainly asymptomatic in most patients), pneumonitis (9%) and oesophagitis (4%).

Conclusions

Surgery combined with radiotherapy and chemoradiotherapy and modern radiotherapy techniques are correlated with improvement of survival in patients with early stage thymoma.     

Metallic nanoparticle radiosensitisation of ion radiotherapy: A review

The use of gold nanoparticle (GNP) and other metal nanoparticle (MNP) radiosensitisers to enhance radiotherapy offers the potential of improved treatment outcomes. Originally intended for use with X-ray therapy, the possibility of enhanced hadron therapy is desirable due to the superior sparing of healthy tissue in hadron therapy compared to conventional X-ray therapy. While MNPs were not expected to be effective radiosensitisers for hadron therapy due to the limited Z dependence of interactions, recent experimental measurements have contradicted this expectation. Key experimental measurements and Monte Carlo simulations of MNP radiosensitisation for hadron irradiation are reviewed in the current work. Numerous experimental measurements have found a large radiosensitisation effect due to MNPs for proton and carbon ion irradiation. Experiments have also indicated that the radiosensitisation is due in large part to enhanced reactive oxygen species (ROS) production. Simulations have found a large radial dose and ROS enhancement on the nanoscale around a single MNP. However, the short range of the dose enhancement is insufficient for a large macroscale dose enhancement or enhanced biological effect in a cell model considering dose to the nucleus from GNPs in the cytoplasm (a distribution observed in most experiments).     

A Green's function method for heavy ion beam transport

Abtract The use of Green's function has played a fundamental role in transport calculations for high-charge high-energy (HZE) ions. Two recent developments have greatly advanced the practical aspects of implementation of these methods. The first was the formulation of a closedform solution as a multiple fragmentation perturbation series. The second was the effective summation of the closedform solution through nonperturbative techniques. The nonperturbative methods have been recently extended to an inhomogeneous, two-layer transport media to simulate the lead scattering foil present in the Lawrence Berkeley Laboratories (LBL) biomedical beam line used for cancer therapy. Such inhomogeneous codes are necessary for astronaut shielding in space. The transport codes utilize the Langley Research Center atomic and nuclear database. Transport code and database evaluation are performed by comparison with experiments performed at the LBL Bevalac facility using 670A MeV²⁰Ne and 600A MeV⁵⁶Fe ion beams. The comparison with a time-of-flight and E detector measurement for the²⁰Ne beam and the plastic nuclear track detectors for⁵⁶Fe show agreement up to 35%–40% in water and aluminium targets, respectively.Submitted paper presented at the International Symposium on Heavy Ion Research: Space, Radiation Protection and Therapy, Sophia-Antipolis, France 21–24 March 1994     

Clustered DNA damage induced by heavy ion particles.

Clustered DNA damage (locally multiply damaged site) is thought to be a critical lesion caused by ionizing radiation, and high LET radiation such as heavy ion particles is believed to produce high yields of such damage. Since heavy ion particles are major components of ionizing radiation in a space environment, it is important to clarify the chemical nature and biological consequences of clustered DNA damage and its relationship to the health effects of exposure to high LET particles in humans. The concept of clustered DNA damage emerged around 1980, but only recently has become the subject of experimental studies. In this article, we review methods used to detect clustered DNA damage, and the current status of our understanding of the chemical nature and repair of clustered DNA damage.     

Computation of cell survival in heavy ion beams for therapy

A simplified method for the calculation of mammalian cell survival after charged particle irradiation is presented that is based on the track structure model of Scholz and Kraft [1, 2]. Utilizing a modified linear-quadratic relation for the x-ray survival curve, one finds that the model yields linear-quadratic relations also for heavy ion irradiation. If survival is calculated as a function of specific energy, z, in the cell nucleus – thus reducing the stochastic fluctuations of energy deposition – the increase in slope of the survival curve and therefore the coefficient β _z can be estimated with sufficient accuracy from the initial slope, α _z . This permits the tabulation of the coefficients α _z for the particle types and energies of interest, and subsequent fast calculations of survival levels at any point in a mixed particle beam. The complexity of the calculations can thereby be reduced in a wide range of applications, which permits the rapid calculations that are required for treatment planning in heavy ion therapy. The validity of the modified computations is assessed by the comparison with explicit calculations in terms of the original model and with experimental results for track-segment conditions. The model is then used to analyze the influence of beam fragmentation on the biological effect of charged particle beams penetrating to different depths in tissue. In addition, cell-survival rates after neutron irradiation are computed from the slowing-down spectra of secondary charged particles and are compared to experimental observations. Received: 10 August 1996 / Accepted in revised form: 16 December 1996     

Focusing of heavy ion beams by a high-current plasma lens

Results are presented from studies of the focusing of wide-aperture low-energy (100–400 eV) and moderate-energy (5–25 keV) beams of heavy-metal ions by a high-current electrostatic plasma lens. It is found experimentally that, because of the significant electron losses, the efficient focusing of such beams can be achieved only if the external potentials at the plasma-lens electrodes are maintained constant. Static and dynamic characteristics of the lens are studied under these conditions. It is shown that, as the beam current and the electrode voltage increase, the maximum electrostatic field in the lens tends to a certain limiting value because of the increase in the spatial potential near the lens axis. The role of spherical and moment aberrations in the focusing of wide-aperture low-divergence ion beams is revealed. It is shown that, even when spherical aberrations are minimized, unremovable moment aberrations decrease the maximum compression ratio of a low-energy heavy-ion beam because of the charge separation of multiply charged ions in the focal region. At the same time, as the ion energy increases, the role of the moment aberrations decreases and the focusing of high-current heavy-ion beams by a plasma lens becomes more efficient than the focusing of light-ion (hydrogen) beams. This opens up the possibility of using electrostatic plasma lenses to control ion beams in high-dose ion implanters and high-current accelerators of heavy ions.     

Molecular and cell models of biological effects of heavy ion radiation

Many quantitative models have been developed for the biological effectiveness of radiation of different quality. They differ substantially in their assumptions, and a lack of firm knowledge remains as to the detailed nature of the critical early molecular damage. Analyses of microscopic features of the stochastic structures of radiation tracks have led to hypotheses on the importance of clustered damage in DNA and associated molecules. Clustered damage of greater complexity or severity is suggested to be less repairable and therefore to dominate the biological consequences.Invited paper presented at the International Symposium on Heavy Ion Research: Space, Radiation Protection and Therapy, Sophia-Antipolis, France, 21–24 March 1994     

Novel synthetic phytochelatin-based capacitive biosensor for heavy metal ion detection

A novel capacitance biosensor based on synthetic phytochelatins for sensitive detection of heavy metals is described. Synthetic phytochelatin (Glu-Cys)(20)Gly (EC20) fused to the maltose binding domain protein was expressed in Escherichia coli and purified for construction of the biosensor. The new biosensor was able to detect Hg(2+), Cd(2+), Pb(2+), Cu(2+) and Zn(2+) ions in concentration range of 100 fM-10 mM, and the order of sensitivity was S(Zn)>S(Cu)>S(Hg)>S(Cd) congruent with S(Pb). The biological sensing element of the sensor could be regenerated using EDTA and the storage stability of the biosensor was 15 days.     

黏土矿物中重金属离子的吸附规律及竞争吸附

采用等温吸附法,研究了重金属铜、铅、镉、镍在膨润土中的吸附特征,发现膨润土对铜、铅的吸附明显强于镉、镍,吸附强度大小顺序为Pb2 >Cu2 >Ni2 >Cd2 。Langmuir和Freundlich方程对这4种金属离子等温吸附的拟合均呈极显著关系。Pb2 、Cd2 、Ni2 分别与Cu2 的双组分竞争吸附表明,黏土矿物对4种离子具有"选择性吸附"。在Pb2 、Ni2 、Cd2 的存在条件下,黏土矿物对Cu2 的吸附产生不同程度的下降;100mg/LCu2 对Pb2 的影响不大,但可完全抑制Ni2 、Cd2 的吸附。建立了IAS和LCA模型来预测Pb2 与Cu2 的双组分竞争吸附,并对LCA模型进行修正,提出了更符合实际情况的竞争吸附模型。文章最后用LCA修正模型对Pb2 与Cu2 的双组分竞争吸附进行了模拟。     

Investigation of lipid peroxidation in liposomes induced by heavy ion irradiation

Lipid peroxidation induced by heavy ion irradiation was investigated in 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLPC) liposomes. Lipid peroxidation was induced using accelerated heavy ions that exhibit linear energy transfer (LET) values between 30 and 15 000 keV/μm and doses up to 100 kGy. With increasing LET, the formation of lipid peroxidation products such as conjugated dienes, lipid hydroperoxides, and thiobarbituric acid-reactive substances decreased. When comparing differential absorption spectra and membrane fluidity following irradiation with heavy ions and x-rays (3 Gy/min), respectively, it is obvious that there are significant differences between the influences of densely and sparsely ionizing radiation on liposomal membranes. Indications for lipid fragmentation could be detected after heavy ion irradiation. Received: 6 March 1997 / Accepted in revised form: 31 March 1998