Stanley B. Curtis

Fluence-based relative biological effectiveness for charged particle carcinogenesis in mouse Harderian gland

Neoplasia in the rodent Harderian gland has been used to determine the carcinogenic potential of irradiation by HZE particles. Ions from protons to lanthanum at energies up to 670 MeV/a have been used to irradiate mice, and prevalence of Harderian gland tumors has been measured 16 months after irradiation. The RBE for tumor induction has been expressed as the RBEmax, which is the ratio of the initial slopes of the dose vs prevalence curve. The RBEmax has been found to be approximately 30 for ions with LET values in excess of 100 keV/micrometer. Analysis on the basis of fluence as a substitute for dose has shown that on a per particle basis all of the ions with LET values in excess of 100 keV/micrometer have equal effectiveness. An analysis of the probabilities of ion traversals of the nucleus has shown that for these high stopping powers that a single hit is effective in producing neoplastic transformation.

Treatment of cancer with heavy charged particles

A clinical radiotherapeutic trial using heavy charged particles in the treatment of human cancers has accrued over 400 patients since 1975, 378 of whom were treated with particles and 28 with low LET photons as control patients. Heavy charged particle radiotherapy offers the potential advantages of improved dose localization and/or enhanced biologic effect, depending on particle selected for treatment. Target sites have included selected head and neck tumors, ocular melanomata, malignant gliomata of the brain, carcinoma of the esophagus, carcinoma of the stomach, carcinoma of the pancreas, selected juxtaspinal tumors and other locally advanced, unresectable tumors. A Phase III prospective clinical trial has been started in carcinoma of the pancreas using helium ions. Phase I-II studies are underway with heavier particles such as carbon, neon and argon ions in order to prepare for prospective Phase III trials. Silicon ions are also under consideration for clinical trial. These studies are supported by the United States Department of Energy and National Institutes of Health.

A Calculation of the Physical Characteristics of Negative Pion Beams: Energy-Loss Distribution and Bragg Curves

Calculations have been made of the dE/dx distribution (LET spectrum) and central-axis depth-dose curves (Bragg curves) of stopping negative pion beams in water. Such beams are of interest because of the large deposition of energy at depth in the stopping pion region relative to that deposited at the surface. Nuclear interactions occurring when the pions come to rest cause low-energy highly ionizing particles to be emitted as the capturing nucleus breaks up, thus increasing the dose deposited in the stopping pion region. The calculations show that, for beams similar to those presently available experimentally, peak depth-to-entrance ratios of 3.4 and 2.9 can be expected in the absorbed dose in water for pure and contaminated beams, respectively, with a width of around 3.5 cm. The contaminated beam was assumed to contain 65% pions, 10% muons, and 25% electrons. The pions in these beams have a range of 25 cm of water. Comparison with experimental results taken with a lithium-drifted silicon detector shows th...

Fluence-related risk coefficients using the Harderian gland data as an example

The risk of radiation-induced cancer to space travelers outside the earths magnetosphere will be of concern on missions to the Moon and beyond to Mars. High energy galactic cosmic rays with high charge (HZE particles) will penetrate the spacecraft and the bodies of the astronauts, sometimes fragmenting into nuclear secondary species of lower charge but always ionizing densely, thus causing cellular damage which may lead to malignant transformation. To quantitate this risk, the concept of dose equivalent (in which a quality factor Q as a function of LET is assumed) may not be adequate, since different particles of the same LET may have different efficiencies for tumor induction. Also, RBE values on which quality factors are based depend on response to low-LET radiation at low doses, a very difficult region for which to obtain reliable experimental data. Thus, we introduce a new concept, a fluence-related risk coefficient (F), which is the risk of a cancer per unit particle fluence and which we call the risk cross section. The total risk is the sum of the risk from each particle type: sigma i integral Fi(Li) phi i(Li) dLi, where Li is the LET and phi i(Li) is the fluence-LET spectrum of the ith particle type. As an example, tumor prevalence data in mice are used to estimate the probability of mouse Harderian gland tumor induction per year on an extra-magnetospheric mission inside an idealized shielding configuration of a spherical aluminum shell 1 g/cm2 thick. The combined shielding code BRYNTRN/GCR is used to generate the LET spectra at the center of the sphere. Results indicate a yearly prevalence at solar minimum conditions of 0.06, with 60% of this arising from charge components with Z between 10 and 28, and two-thirds of the contribution arising from LET components between 10 and 200 keV/micrometers.

The OER of Mixed High- and Low-LET Radiation

The general validity of the phenomenon of a relatively large decrease in OER below the x-ray value with only modest admixture of high-LET radiation is pointed out. For example, a 40 percent admixture of radiation with OER = 1.15 will decrease OER from 2.6 to 1.3. It is also pointed out that the OER is not strictly dose modifying for a mixed high- and low-LET environment, even though it may be so for the two components separately. From these considerations, it is suggested that a low-LET, high-energy photon beam could be combined with a high-LET, heavy-ion beam to take advantage both of the increased skin-sparing characteristic of the photon depth--dose curve and of decreased OER in the tumor region due to the high-LET, heavy-ion admixture. (auth)

Human exposure to large solar particle events in space

Whenever energetic solar protons produced by solar particle events traverse bulk matter, they undergo various nuclear and atomic collision processes which significantly alter the physical characteristics and biologically important properties of their transported radiation fields. These physical interactions and their effect on the resulting radiation field within matter are described within the context of a recently developed deterministic, coupled neutron-proton space radiation transport computer code (BRYNTRN). Using this computer code, estimates of human exposure in interplanetary space, behind nominal (2 g/cm2) and storm shelter (20 g/cm2) thicknesses of aluminum shielding, are made for the large solar proton event of August 1972. Included in these calculations are estimates of cumulative exposures to the skin, ocular lens, and bone marrow as a function of time during the event. Risk assessment in terms of absorbed dose and dose equivalent is discussed for these organs. Also presented are estimates of organ exposures for hypothetical, worst-case flare scenarios. The rate of dose equivalent accumulation places this situation in an interesting region of dose rate between the very low values of usual concern in terrestrial radiation environments and the high dose rate values prevalent in radiation therapy.

RBE values for radiation-induced growth delay in rat rhabdomyosarcoma tumors exposed to plateau and peak carbon, neon and argon ions

Abstract Volume regression and regrowth characteristics of rat rhabdomyosarcoma tumors were monitored following exposure to plateau (high-energy) and peak (low-energy) charged-particle beams accelerated at the Berkeley BEVALAC facility. Values of the relative biological effectiveness (RBE) for radiation-induced growth delay were obtained for plateau and extended-peak radiation from carbon, neon and argon ions. The RBE values for tumor irradiation in the distal position of a 4 cm peak region of these three ion beams were similar; they ranged from 2.3 to 2.6 for the endpoint of a 50-day delay in growth to twice the volume measured on the day of irradiation. In contrast, RBE values for plateau carbon, neon and argon ions were 1.3, 1.8 and 2.9, respectively, for the 50-day growth delay end point. A therapeutically advantageous peak to plateau RBE ratio was thus obtained only with the carbon ion and neon-ion beams. These in vivo results are consistent with in vitro measurements of RBE in different regions of the Bragg cures of the charged-particle beams used in the present study.

Risk cross sections and their application to risk estimation in the galactic cosmic-ray environment

Radiation risk cross sections (i.e. risks per particle fluence) are discussed in the context of estimating the risk of radiation-induced cancer on long-term space flights from the galactic cosmic radiation outside the confines of the earths magnetic field. Such quantities are useful for handling effects not seen after low-LET radiation. Since appropriate cross-section functions for cancer induction for each particle species are not yet available, the conventional quality factor is used as an approximation to obtain numerical results for risks of excess cancer mortality. Risks are obtained for seven of the most radiosensitive organs as determined by the ICRP [stomach, colon, lung, bone marrow (BFO), bladder, esophagus and breast], beneath 10 g/cm2 aluminum shielding at solar minimum. Spectra are obtained for excess relative risk for each cancer per LET interval by calculating the average fluence-LET spectrum for the organ and converting to risk by multiplying by a factor proportional to R gamma L Q(L) before integrating over L, the unrestricted LET. Here R gamma is the risk coefficient for low-LET radiation (excess relative mortality per Sv) for the particular organ in question. The total risks of excess cancer mortality obtained are 1.3 and 1.1% to female and male crew, respectively, for a 1-year exposure at solar minimum. Uncertainties in these values are estimated to range between factors of 4 and 15 and are dominated by the biological uncertainties in the risk coefficients for low-LET radiation and in the LET (or energy) dependence of the risk cross sections (as approximated by the quality factor). The direct substitution of appropriate risk cross sections will eventually circumvent entirely the need to calculate, measure or use absorbed dose, equivalent dose and quality factor for such a high-energy charged-particle environment.

The multiple Coulomb scattering of very heavy charged particles

An experiment was performed at the Lawrence Berkeley Laboratory BEVALAC to measure the multiple Coulomb scattering of 650-MeV/A uranium nuclei in 0.19 radiation lengths of a Cu target. Differential distributions in the projected multiple scattering angle were measured in the vertical and horizontal planes using silicon position-sensitive detectors to determine particle trajectories before and after target scattering. The results were compared with the multiple Coulomb scattering theories of Fermi and Molière, and with a modification of the Fermi theory, using a Monte Carlo simulation. These theories were in excellent agreement with experiment at the 2 sigma level. The best quantitative agreement is obtained with the Gaussian distribution predicted by the modified Fermi theory.

TUMOR BIOLOGY OF HELIUM AND HEAVY IONS

Abstract Using three different in vivo tumor systems, i.e. the EMT6 tumor, R1 rhabdomyosarcoma, and 9L gifosarcoma, significant increases in biologic effectiveness were noted in the Bragg peak portion of heavy ion beams as compared to the entrance or plateau region of these beams. The biological advantages of the carbon and neon beams, at least in the distal portions of the spread out Bragg peak, were similar to those seen previously for 15 MeV neutrons and reflected a marked reduction in OER compared to low LET irradiations. There was close agreement in the results of RBE and OER determinations for the different heavy ion beams for the three tumor systems using various assay methods.