Extended Bragg Peak Research Articles

СРАВНИТЕЛЬНАЯ ОЦЕНКА ВЛИЯНИЯ ЛОКАЛЬНОГО ПРОТОННОГО ИЗЛУЧЕНИЯ В ДОЗЕ 30 ГР НА МЫШЕЙ ЛИНИЙ BALB/с И С57BL/6

Purpose: To evaluate the effect of local proton irradiation at a dose of 30 Gy on Balb/c and C57BL/6 mice in terms of the degree and dynamics of radiation-induced skin damage formation, changes in body weight and peripheral blood elements count. Material and methods: Experiments were performed on non-depilated male mice aged 7‒8 weeks from two strains: Balb/c and C57BL/6 (n=15). Local irradiation of the skin was carried out on the dorsal side of the animals using a scanning proton beam at an extended Bragg peak in the proton therapy complex «Prometheus» of the LPI Physico-technical Centre (Protvino) at a dose of 30 Gy with a proton energy of 87.8 MeV. During the irradiation session, animals were subjected to intraperitoneal anesthesia using a combination of Zoletil 100 (Virbac, France) and Xyla (Interchemie, Netherlands) in a previously determined ratio 1:3 (20‒40 mg/kg). Photographic documentation of radiation-induced skin damage was performed weekly for 70 days. Animals were examined daily for clinical manifestations of radiation-induced skin damage formation according to the RTOG international scale for 21 days following irradiation. The body weight dynamics of mice were evaluated one day before irradiation and then weekly for 70 days. Blood samples were collected from the tail vein by cutting the tip of the tail and analyzed using a DH36 Vet hematology analyzer (Dymind, China) one day before irradiation, one day and three days after irradiation, and weekly thereafter for 70 days. Experimental data were presented as mean ± standard deviation (M ± SD). Results: In this study, the impact of a single local exposure to proton radiation at a dose of 30 Gy on the degree and dynamics of radiation-induced skin damage formation was evaluated. It was demonstrated that Balb/c mice exhibited a higher frequency and degree of radiation-induced skin damage formation compared to the C57BL/6 mice. Analysis of body weight in mice after radiation exposure revealed no significant decrease in either mouse strain. A comparative analysis of the number of platelets, erythrocytes and hemoglobin concentration in both mouse strains did not reveal any changes, while a tendency towards a decrease in the number of leukocytes, lymphocytes, and granulocytes was observed in the irradiated Balb/c mice group compared to the control group. Conversely, in irradiated C57BL/6 mice, the number of lymphocytes was higher compared to control animals. Conclusion: In this study, Balb/c mice exhibited higher radiosensitivity compared to C57BL mice in response to a single local proton irradiation at a dose of 30 Gy.

Физика планирования протонной лучевой терапии

The most important stage of radiation therapy of oncological diseases is the planning of radiation treatment. In this work, this complex process in relation to proton therapy is proposed to be divided into medical and physical planning. In conventional therapy with photons and electrons, the latter is usually called dosimetric planning, however, when applied to proton radiation therapy, this stage involves a significantly wider range of tasks related to the modification and scanning of the proton beam, spreading and compensation of ranges, taking into account when planning for uncertainties and finiteness of proton ranges, a decrease in the contribution to the dose of secondary neutrons, the creation of error-tolerant optimization algorithms for dosimetric plans, and, finally, a precision calculation of dose distributions. The paper discusses the main stages and problems of physical planning of proton radiation therapy. Particular attention is paid to the formation of an extended high-dose region (extended Bragg peak) using the beam scattering method and scanning method, and to the algorithms for calculating the dose distributions created by protons in the scattering and beam scanning systems. The most detailed consideration is given to different versions of the proton pencil beam method, which allows to increase the dose calculation accuracy and take into account the transverse scattering and fluctuations in proton energy losses, especially at the end of the path (halo effect), analytical and numerical methods. Scanning are divided into three main technologies: homogeneous scanning, single field uniform dose (SFUD), multi-field uniform dose (MFUD), often called intensity modulated proton therapy (IMPT). Actual accounting problems are considered when planning the irradiation of the movement of organs, and uncertainties in determining path lengths and optimization of irradiation plans. In particular features, problems and modern approaches to the optimization of dosimetry plans of proton radiation therapy are discussed. It is noted that one of the most promising practical solutions for the uncertainty management in determining the path lengths of protons in optimization is to include possible errors in the objective function of the optimization algorithm. This technique ensures that an optimized irradiation plan will more reliably protect normal tissues and critical organs adjacent to the irradiation target from overexposure.

In vitro evaluation of photon and raster-scanned carbon ion radiotherapy in combination with gemcitabine in pancreatic cancer cell lines

Background: Pancreatic cancer is the fourth leading cause of cancer deaths, being responsible for 6% of all cancer-related deaths. Conventional radiotherapy with or without additional chemotherapy has been applied in the past in the context of neoadjuvant or adjuvant therapy concepts with only modest results, however new radiation modalities, such as particle therapy with promising physical and biological characteristics, present an alternative treatment option for patients with pancreatic cancer. Up until now the raster scanning technique employed at our institution for the application of carbon ions has been unique, and no radiobiological data using pancreatic cancer cells has been available yet. The aim of this study was to evaluate cytotoxic effects that can be achieved by treating pancreatic cancer cell lines with combinations of X-rays and gemcitabine, or alternatively with carbon ion irradiation and gemcitabine, respectively. Materials and Methods: Human pancreatic cancer cell lines AsPC-1, BxPC-3 and Panc-1 were irradiated with photons and carbon ions at various doses and treated with gemcitabine. Photon irradiation was applied with a biological cabin X-ray irradiator, and carbon ion irradiation was applied with an extended Bragg peak (linear energy transfer (LET) 103 keV/μm) using the raster scanning technique at the Heidelberg Ion Therapy Center (HIT). Responsiveness of pancreatic cancer cells to the treatment was measured by clonogenic survival. Clonogenic survival curves were then compared to predicted curves that were calculated employing the local effect model (LEM). Results: Cell survival curves were calculated from the surviving fractions of each combination experiment and compared to a drug control that was only irradiated with X-rays or carbon ions, without application of gemcitabine. In terms of cytotoxicity, additive effects were achieved for the cell lines Panc-1 and BxPC-3, and a slight radiosensitizing effect was observed for AsPC-1. Relative biological effectiveness (RBE) of carbon ion irradiation ranged from 1.5–4.5 depending on survival level and dose. Sensitizer enhancement ratio (SER) values calculated at 10% cell survival ranged from 1.24–1.66, depending on cell line, gemcitabine dose and irradiation modality. Experimentally ascertained survival curves matched those predicted by LEM-calculation. Conclusion: Our experiments have shown a combined treatment of irradiation and chemotherapy with gemcitabine to be a good means of achieving additive cytotoxic effects on pancreatic cancer cell lines. The data generated in this study will serve as radiobiological basis for further preclinical and clinical studies.

SU‐FF‐T‐487: Saturation of Repair Model for Cell Survival Applied to X‐Ray and Carbon‐Ion Irradiation

Purpose: To develop and test a model for cell survival after irradiation which ascribes differences in effect of x‐ray and Carbon‐ion beams to dependence on LET of effective available repair units. Methods and Materials: A model by Goodhead of the saturation of the mechanism for cellular repair of radiation damage is shown to behave as a log survival linear‐quadratic (LQ) function of dose at levels which do not saturate the repair and linearly for doses that do. This model is applied to published data for both X‐ray and C+6‐ion beam survival data extending to ∼ 4 × 10−3 survival for stationary phase Chinese hamster lung (V‐79) cells irradiated in the plateau and in the extended Bragg peak of a 400 MeV per amu heavy‐ion beam at LBL by Chapman et al. The same parameters of the model that fit the X‐ray survival data are used to fit the C+6‐ion beam data, except that the parameter defining the available cellular effective repair is allowed to vary according to the location of the irradiation in the extended Bragg peak. The model is also fitted to recently published data, including irradiated cultured cells of human lung cancer origin extending to a single dose 16 Gy and a survival fraction < 2 × 10−7. Results: The saturation of repair model provides an excellent fit to both the x‐ray and C+6‐ion beam data for the V‐79 cells, with a systematic decrease of the parameter of effective available repair with increase of LET. The model also provides excellent representations of recently‐published survival data for NSCLC and other cell lines with parameters that are comparable to those for the CH V‐79 cells. Conclusion: The Saturation of Repair model provides a viable mechanistic modeling of survival for Carbon‐ion and X‐irradiation, and may be tested in further experiments.

Radiobiological evaluation and correlation with the local effect model (LEM) of carbon ion radiation therapy and temozolomide in glioblastoma cell lines

Purpose: To investigate the cytotoxic effect of high linear-energy transfer (LET) carbon irradiation on glioblastoma cells lines in combination with temozolomide (TMZ).Methods and materials: The cell lines U87-MG expressing wild-type p53 and LN229 expressing both mutant and wild-type p53 were irradiated with monoenergetic carbon ion beams (LET 172 keV/μm) or an extended Bragg peak (LET 103 keV/μm) after treatment with 10 μM or 20 μM TMZ. Cytotoxicity was measured by a clonogenic survival assay, and cell growth as well as cell cycle progression, were examined.Results: The p53 mutant was more sensitive to X-ray irradiation than the p53 wild type cell line, which was also expressed in a shorter G2 block. High LET carbon ions show an increased biological effectiveness in both cell lines, which is consistent with the predictive calculations by the Local Effect Model (LEM) introduced by Scholz et al. The cell line LN229 was more sensitive to TMZ treatment than the U87MG cell line expressing wild-type p53 only. The combination of TMZ and irradiation showed an additive effect in both cell lines.Conclusion: High LET carbon ion irradiation is significantly more effective for glioblastoma cell lines compared to photon irradiation. An additional treatment with TMZ may offer a great chance especially for several tumor types.

Radiobiological Characterization of Human Tumor Cell Multilayers after Conventional and Particle Irradiation

The goal of this study was to establish planar multilayers from human tumor cells (WiDr and SiHa) as a model for irradiation of solid tumors. In addition to using conventional X rays (250 kV) as a reference standard, multilayers were tested for their suitability in cell survival studies with heavy-ion irradiation ((12)C(6+)) in the plateau and the extended Bragg peak with a scanned ion beam. Multilayers of both cell lines showed decreased survival compared to the corresponding monolayers after both X and heavy-ion irradiation. This multicellular sensitization effect is in contrast to the multicellular resistance or contact effect commonly described in the literature. Flow cytometry measurements showed an arrest of irradiated SiHa cells in G(2)/M phase. In contrast to the transient arrest of the monolayers, the multilayers stayed in a prolonged arrest. After Bragg-peak irradiation of monolayers, the arrest time was increased by 12-24 h, and more cells were arrested than with X rays. For multilayers, there were no differences between G(2) arrest after X rays and heavy ions for the entire observation period.

Chromosome aberrations induced by high-LET carbon ions in radiosensitive and radioresistant tumour cells

Chromosome aberration formation was analysed in two human tumour cell lines displaying different radiosensitivity. Aberrations involving chromosomes 2, 4, and 5 were studied in one radioresistant cell line (WiDr) and in one radiosensitive cell line (MCF-7). Chromosome aberrations were studied by application of single-colour FISH. We studied the effects of monoenergetic 100 MeV/u carbon ions and carbon ions from extended Bragg peak. Chromosome aberrations induced by carbon ions were compared with aberrations induced by standard 200 kV X-rays. In both tumour cell lines, carbon ions induced aberrations more effectively than X-rays. The radioresistance and radiosensitivity of the corresponding cell lines, as observed for X-rays, were also found after carbon ion irradiation. In both cell lines, the typical effects of ion irradiation were an increased proportion of cells containing complex aberrations, and an increased complexity of these complex exchanges. However, comparable effects were induced in MCF-7 cells by a much lower dose than in WiDr cells. Insertions were also induced more efficiently in MCF-7 cells than in WiDr cells.

Cytogenetic effects of densely ionising radiation in human lymphocytes: impact of cell cycle delays

The classical cytogenetic assay to estimate the dose to which an individual has been exposed relies on the measurement of chromosome aberrations in lymphocytes at the first post-irradiation mitosis 48 h after in vitro stimulation. However, evidence is accumulating that this protocol results in an underestimation of the cytogenetic effects of high LET radiation due to a selective delay of damaged cells. To address this issue, human lymphocytes were irradiated with C-ions (25-mm extended Bragg peak, LET: 60–85 keV/µm) and aberrations were measured in cells reaching the first mitosis after 48, 60, 72 and 84 h and in G₂-phase cells collected after 48 h by calyculin A induced premature chromosome condensation (PCC). The results were compared with recently published data on the effects of X-rays and 200 MeV/u Fe-ions (LET: 440 keV/µm) on lymphocytes of the same donor (Ritter et al., 2002a). The experiments show clearly that the aberration yield rises in first-generation metaphase (M1) with culture time and that this effect increases with LET. Obviously, severely damaged cells suffer a prolonged arrest in G₂. The mitotic delay has a profound effect on the RBE: RBE values estimated from the PCC data were about two times higher than those obtained by conventional metaphase analysis at 48 h. Altogether, these observations argue against the use of single sampling times to quantify high LET induced chromosomal damage in metaphase cells.

Dose-response curves for late functional changes in the normal rat brain after single carbon-on doses evaluated by magnetic resonance imaging: influence of follow-up time and calculation of relative biological effectiveness.

This study investigated late effects in the brain after irradiation with carbon ions using a rat model. Thirty-six animals were irradiated stereotactically at the right frontal lobe using an extended Bragg peak with maximum doses between 15.2 and 29.2 Gy. Dose-response curves for late changes in the normal brain were measured using T1- and T2-weighted magnetic resonance imaging (MRI). Tolerance doses were calculated at several effect probability levels and times after irradiation. The MRI changes were progressive in time up to 17 months and remained stationary after that time. At 20 months the tolerance doses at the 50% effect probability level were 20.3 +/- 2.0 Gy and 22.6 +/- 2.0 Gy for changes in T1- and T2-weighted MRI, respectively. The relative biological effectiveness (RBE) was calculated on the basis of a previous animal study with photons. Using tolerance doses at the 50% effect probability level, RBE values of 1.95 +/- 0.20 and 1.88 +/- 0.18 were obtained for T1- and T2-weighted MRI. A comparison with data in the literature for the spinal cord yielded good agreement, indicating that the RBE values for single-dose irradiations of the brain and the spinal cord are the same within the experimental uncertainty.

Design and construction of a ripple filter for a smoothed depth dose distribution in conformal particle therapy

The ripple filter was designed to broaden the Bragg maximum of carbon beams for the raster-scan technique, a special type of tumour-conformal ion beam treatment. In this technique the target volume is divided into individual layers that are treated sequentially by varying the energy from the accelerator stepwise. Because the unmodified Bragg maximum has a small half-width, below 1 mm for small energies (<160 MeV u-1), homogeneous irradiation at small penetration depths of 2-6 cm can only be obtained by using a large number of energy steps. If the energy step is too large, ripples are produced in the superimposed depth dose distribution. The ripple filter widens a Bragg peak to a Gaussian peak with a half-width of more than 2 mm. This helps to smooth the extended Bragg peak and to reduce the number of energy steps required by a factor of two to three, leading to significantly shorter overall irradiation times and a higher particle fluence per layer. The ripple filter consists of a 2 mm thick Plexiglass (PMMA) plate with a periodic structure of fine grooves. It can be mounted 60 cm upstream of the patient as a stationary device, because the fine structure of the grooves is completely washed out by the lateral scattering of the beam.

A Semi-Empirical Approach to the Evaluation of the Relative Biological Effectiveness of Therapeutic Proton Beams: The Methodological Framework

We address the problem of the evaluation of the relative biological effectiveness (RBE) of therapeutic proton beams for cell inactivation. We consider a general approach to the evaluation of the lethal effect of protons which is applicable to different situations, including those in which an extended Bragg peak is obtained via a modulated beam. Our approach combines two kinds of information: (1) the experimental results available in the literature for the response of Chinese hamster V79 cells to monoenergetic beams and (2) the energy spectrum of the beam in the target volume, computed through a Monte Carlo algorithm. We have applied this method to a simple Bragg peak produced by a broad-field proton beam of about 70 MeV initial energy, such as those that, after attenuation, are typically used for treatment of ocular tumors. We have found that the RBE increases with depth, even beyond the Bragg peak, up to a value close to 2, when evaluated at the same surviving fraction as that resulting after exposure to 2 Gy of X rays.

Dosimetry of 40 and 70 MeV/n 16O beams

Using CR-39 plastic track detectors the range values of 16O ions at two different energies (initially in the beam line, 39.97 MeV/n and 69.98 MeV/n) were measured after escaping the beam pipe and found to be (3050 ± 40) μm and (8210 ± 90) μm, respectively. The longitudinal and projected angular spread of oxygen ions of an initial energy of 69.98 MeV/n in the region of the Bragg peak was derived from the measured geometrical parameters of tracks. Based on a calibration curve (etch rate ratio vs total linear energy transfer in CR-39) and the measured track length distribution at the range end of oxygen ions, the complete depth dose profile of a 67.7 MeV/n 16O beam in CR-39 (plateau, extended Bragg peak and residual ionization caused by projectile like fragments) was obtained.

Relative biological effectiveness of intermediate energy protons. Comparisons with 60Co gamma-radiation using two cell lines

Range modulated proton beams are used for radiotherapy of malignant tumours at several accelerator laboratories with the aim of introducing proton therapy as a clinical hospital-based therapy modality. Due to the finite range and the sharpness of the dose gradients, the dose to well defined target volumes can be raised without excessive irradiation of non-target tissue. The prescribed proton doses are determined in part on the basis of the relative biological effectiveness (RBE) of the particular radiation quality. In this study, RBE values were determined for a proton beam with a maximal range of 33 mm, which corresponds to an energy of ∼67 MeV. The range modulated depth-dose distribution, with a 20 mm extended Bragg peak, was mainly designed for high precision treatment of small targets such as uveal melanomas. The tested cell lines, LS-174T and V79-379A, were chosen because of their suitability for clonogenic assays. The cells were irradiated with single doses in the range 2–10 Gy at different depths in the extended peak region of the range modulated proton beam. RBE values were determined by comparing the doses needed to obtain the same reduction in colony formation (0.5, 0.1 and 0.01) as with the reference 60Co gamma source. The mean RBE value was1.22 with a standard deviation of 0.08. The variations depended on both cell type and on the survival levels considered. The clonogenic cell survival showed only a very small decrease with depth when cells were placed in different positions, along the central axis of the range modulated depth-dose distribution, indicating only a small increase in RBE with depth. The RBE of the proton beam was greater than unity indicating that proton doses should be somewhat reduced in comparison with conventional radiation when irradiation of critical normal tissues is unavoidable.

Radiosensitization produced by iododeoxyuridine with high linear energy transfer heavy ion beams

Little is known about radiosensitization produced by iododeoxyuridine (IUDR) with high linear energy transfer radiation. Likewise, the effect of IUDR on repair of sublethal or potentially lethal damage is unclear. A series of in vitro experiments was performed examining these aspects of IUDR radiosensitization. Human T1 cells were grown in the presence of 3.0 micromolar IUDR for 72 hours (approximately three doubling times), an exposure which resulted in minimal cytotoxicity to unirradiated cells. As the cells entered plateau phase they were exposed to X rays and a variety of heavy ion beams. Sensitization was found to decrease as linear energy transfer (LET) increased. No sensitization took place in an extremely high LET Lanthanum ion beam (1000 keV/micrometer). However, IUDR produced significant sensitization in the Neon ion beam currently used to treat cancer patients at Lawrence Berkeley Laboratory. Sensitization enhancement ratios at the 40% cell survival level were found to be 1.8 for X rays, 1.5 for the proximal Bragg peak of the clinical Neon beam, and 1.3 for the distal peak of the clinical Neon beam. Cell survival curves fitted to the linear-quadratic model showed IUDR significantly increased the value of the linear component (alpha) in beams with LETS below 40 keV/micron. The value of the quadratic component (beta) was unaffected by IUDR, regardless of LET. Split-dose experiments with both X rays and proximal peak Neon ions revealed IUDR did not affect sublethal damage repair. Similarly, delayed-plating experiments showed IUDR did not affect repair of potentially lethal damage. In contrast to cells unexposed to IUDR, IUDR-treated cells showed near-equal levels of cell killing throughout the extended Bragg peak of the clinical Neon beam. These findings suggest that the addition of IUDR to Neon ion radiotherapy could enhance the therapeutic ratio of the clinical Neon beam.

Heavy charged-particle induced lesions in rabbit cerebral cortex

Fourteen male rabbits received single doses of 20, 40, and 80 Gy of neon irradiation with an extended Bragg peak. They were sacrificed at 1 day, 1 week, and 6 months post-irradiation. The tissue changes which showed a significant time-dose relationship were leakage of carbon particles from blood vessels, focal arachnoiditis, hemorrhage, cystic necrosis, and a total histopathologic score using a point system of grading. The focal nature of the lesion wasclearly demonstrated with 2 mm thick macrotome sections. The transition zone between damaged brain and microscopically normal appearing brain was less than 1 mm and the tissue damage induced was morphologically similar to that of other radiation modalities. These findings may have important therapeutic implications for patients. The sharply demarcated boundaries of heavy charged-particle induced lesions suggest these beams will be useful for obliterating tissue in areas where it is critical that a transition from undamaged to severely damaged tissue must occur over a short distance, such as in the central nervous system.

Morphometric studies of heavy ion damage in the brains of rodents

As an approach to determining the relative biological effectiveness (RBE) of each of five different heavy ions for the mammalian brain, histological preparations of brains from mice exposed to various HZE particles at different doses and primary LET ∞ values were examined by means of semi-automated image analysis for volume changes in specific regions of the olfactory bulb. The mice were irradiated at 100 days of age and euthanatized about 500 days (16 months) later. Exposures were: 60Co gamma photons (LET ∞ = 1–2 keV/ μm), 4He (LET ∞ = 6 keV/ μm, 12C (LET ∞ = 80 keV/ μm), 20Ne (LET ∞ = 150 keV/ μm, 56Fe (LET ∞ = 180 keV/ μm, and 40Ar (LET ∞ = 650 keV/ μm). Animals receiving particle radiation were exposed in an extended Bragg peak region except for iron where the plateau region was used. The zones measured in the olfactory bulb were 1) the external plexiform layer (zone) and 2) an internal region consisting of the granule cells, internal plexiform layer, and layer of mitral cells. These studies indicated that volume changes did indeed occur, not only in absolute terms but alos when expressed as the ratio of the structures to each other and to the bulb as a whole. Although this study is exploratory in character, the data obtained may nevertheless contribute to a determination of risk factors due to late effects from HZE particles.

Survival and Kinetic Response of V79-spheroids after Exposure to Heavy Ion Beams

Multicellular V79-spheroids and V79-monolayer cultures were irradiated with charged particle beams. The beams studied and their initial extraction energies were carbon (400 MeV/amu), neon (425 MeV/amu) and argon (570 MeV/amu). Survival was measured at a position in the plateau, and at a position in the middle of a 4 cm extended Bragg peak. Relative biological efficiency (r.b.e.) values for survival of spheroid cells at peak positions were high (4.1--4.2) in comparison to those obtained with monolayer cultures (1.8--2.4) of the same cell line. This finding is explained by the fact that three dimensional cell contact, which benefits survival after low LET radiation, does not influence survival after heavy ion irradiations in the Bragg peak. The peak-plateau r.b.e.-ratio was most advantageous for the carbon-ion beam (= 4.2). Whereas non-cycling inner spheroid cells showed hardly any kinetic changes up to 24 hours after heavy ion irradiation, outer cycling spheroid cells were arrested in G2 + M within a few hours after exposure.

Radiation Biophysical Studies with Mammalian Cells and a Modulated Carbon Ion Beam

CHAPMAN, J. D., BLAKELY, E. A., SMITH, K. C., URTASUN, R. C., LYMAN, J. T., AND TOBIAS, C. A. Radiation Biophysical Studies with Mammalian Cells and a Modulated Carbon Ion Beam. Radiat. Res. 74, 101-111 (1978). Chinese hamster (V-79) and human kidney (T-l) cells were irradiated in stirred suspensions placed at various positions in the plateau and extended Bragg peak of a 400-MeV/amu carbon ion beam. The range of the ions was modulated by a lead (translational) ridge filter and a brass (spiral) ridge filter designed to produce extended peaks of -4 and 10 cm, respectively. Stationary-phase and Gi-phase populations of Chinese hamster cells were found to have different absolute radiosensitivities which, in turn, were different from that of asynchronous human kidney cells. The increase in relative biological effectiveness (RBE) observed as carbon ions were slowed down and stopped in water was similar for the three cell populations at doses greater than 400 rad. At lower doses the RBE was greater for the hamster cell populations than for the human kidney cells. The gain in RBE (at the 50% survival level) between the plateaus and the middle region of the extended peaks was -2.0 and 1.7 for the 4- and 10-cm extended peaks, respectively. Oxygen enhancement ratios (OER) were determined at the 10% survival levels with stationary-phase populations of hamster cells. Values of 2.8, 2.65, and 1.65 were obtained for the OER of 220-kV X rays, plateau carbon, and the middle region of the 4-cm carbon peak, respectively. Across the 10-cm carbon peak the OER was found to vary between values of 2.4 to 1.55 from the proximal to distal positions.

Introduction to the use of protons and heavy ions in radiation therapy: Historical perspective

For over 20 years, medical irradiation using proton and subsequently helium ion beams has been utilized, principally for ablative therapy of the pituitary and most often with the plateau portion of the beam rather than the extended Bragg peak. More recently, cancer radiotherapy using proton beams has seen limited clinical trial in Sweden and more extensive ongoing trials in the Soviet Union.. Pilot studies of extended Bragg peak therapy of neoplastic disease using protons (Harvard cyclotron) and helium ions (184 in. Berkeley synchrocy-clotron) have been underway in this country for about one year. For ions heavier than helium, sufficiently penetrating beams for cancer radiotherapy became available August of 1974 with successful activation of the Bevalac at Berkeley. Extensive preclinical evaluation of the dosimetry and biological properties of these heavier ion beams are being directed toward an evaluation of their suitability for beginning clinical trials, with the latter planned for mid-1977 if results are favorable. Potential therapeutic advantages and the extent to which they are supported by present knowledge of the physical and biological characteristics of heavy charged particle beams will be discussed.

Repair of sublethal and potentially lethal radiation damage by rat embryos exposed to gamma rays or helium lons.

Embryonic survival was examined in rats exposed to a 24-hour split-dose regimen of gamma rays or extended-Bragg-peak (EBP) helium ions on the fifth and sixth days of gestation. The data indicate that EBP helium ions, which are known to have a single-dose relative biological effectiveness (RBE) of 1.0, exhibit a split-dose RBE of 1.5 with respect to embryo killing. Using an experimental rat embryo system, delayed implantation, it was also noted that the embryocidal damage induced by EBP helium ions contains a smaller potentially lethal component than that induced by gamma rays.