Conventional Radiations Research Articles

Conjunctive use of synchrotron X-ray diffraction and Rietveld refinement in Fe-oxide clays for forensic applications.

Soils have distinctive chemical, physical, mineralogical and biological properties, which make it possible to differentiate them in different environments and also to test for an association of a particular questioned item with a crime scene. Mineral compositions and structures in the soil clay fraction can reflect a distinct characteristic when analyzed by powerful techniques. In this way, the aim of this study was to compare the discriminative power of Fe-oxides concentrated clay samples from the same soil class with and without differences in parent material when analyzed using the Rietveld method and two sources of X-ray diffraction: conventional and high-resolution synchrotron radiations. Clay samples were Fe concentrated (kaolinite and gibbsite removal) to clarify mineralogical composition of 12 samples from three simulated crime scenes, developed under claystone and granite. By Rietveld refinement, detailed crystallographic data were obtained to discriminate samples according their provenance. By synchrotron radiation, mineral data demonstrated the power of quantitative (crystallite size and minerals contents) and qualitative (identification of majoritarian and accessory minerals) analysis by Rietveld refinement, which provides well-resolved data able to discriminate samples from different and same geology. The techniques can be applied in other criminal investigations given their potential of discrimination.

Inhibiting autophagy with chloroquine enhances the anti-tumor effect of high-LET carbon ions via ER stress-related apoptosis.

Energetic carbon ions (CI) offer great advantages over conventional radiations such as X- or γ-rays in cancer radiotherapy. High linear energy transfer (LET) CI can induce both endoplasmic reticulum (ER) stress and autophagy in tumor cells under certain circumstances. The molecular connection between ER stress and autophagy in tumor exposed to high-LET radiation and how these two pathways influence the therapeutic effect against tumor remain poorly understood. In this work, we studied the impact of autophagy and apoptosis induced by ER stress following high-LET CI radiation on the radiosensitivity of S180 cells both in vitro and in vivo. In the in vitro experiment, X-rays were also used as a reference radiation. Our results documented that the combination of CI radiation with chloroquine (CQ), a special autophagy inhibitor, produced more pronounced proliferation suppression in S180 cells and xenograft tumors. Co-treatment with CI radiation and CQ could block autophagy through the IRE1/JNK/Beclin-1 axis and enhance apoptotic cell death via the activation of C/EBP homologous protein (CHOP) by the IRE1 pathway rather than PERK in vitro and in vivo. Thus, our study indicates that inhibiting autophagy might be a promising therapeutic strategy in CI radiotherapy via aggravating the ER stress-related apoptosis.

Spatial and depth-resolved studies of air plasma-sprayed hydroxyapatite coatings by means of diffraction techniques: Part I

Abstract Hydroxyapatite coatings (HAp, Ca 10 (PO 4 ) 6 OH 2 ) were deposited by air plasma spraying onto Ti6Al4V substrates and investigated to determine the depth-dependent behaviour of phase composition, crystallinity, and residual stress using diffractometric techniques. Through-thickness characterisation was carried out by conventional X-ray and synchrotron radiations in reflection and transmission geometries. Results showed HAp together with its thermal decomposition products, tetracalcium phosphate (TTCP), tricalcium phosphate (TCP) and calcium oxide to be present throughout the coating thickness. Quantitative phase identification employing Rietveld refinement showed HAp and TTCP to be the two major phases, with the former decreasing with depth whilst the latter increases. The largest changes were observed adjacent to the coating-substrate interface region. Crystallinity investigation showed a similar trend, revealing a more crystalline near-surface region and increasing amorphisation toward the coating-substrate interface. Residual stress investigation revealed the normal components σ 11 and σ 33 to be tensile and compressive, respectively. The stresses relax and increase to respective minimum and maximum within the first 145 μm. With further penetration depth, both normal stress components became tensile.

The Radiation Enhancement of 15 nm Citrate-Capped Gold Nanoparticles Exposed to 70 keV/μm Carbon Ions.

Radiotherapy is an important modality for tumor treatment. The central goal of radiotherapy is to deliver a therapeutic dose to the tumor as much as possible whilst sparing the surrounding normal tissues. On one hand, heavy ion radiation induces maximum damage at the end of the track (called the Bragg Peak). Hadron therapy based on heavy ions is considered superior to conventional X-rays and γ-rays radiations for tumors sited in sensitive tissues, childhood cases and radioresistant cancers. On the other hand, radiation sensitizers enhanced the radiation effects in tumors by increasing the dose specifically to the tumor cells. Recently, the use of gold nanoparticles as potential tumor selective radio-sensitizers has been proposed as a breakthrough in radiotherapy with conventional radiations. The enhanced radiation effect of heavy ions in tumor by using gold nanoparticles as radio-sensitizer may provide alternative in hadron therapy. In this study, we investigated the radiosensitizing effects of carbon ions with a linear energy transfer of 70 keV/μm in the presence of 15 nm citrate-capped AuNPs. The existing of AuNPs resulted in 5.5-fold enhancement in hydroxyl radical production and 24.5% increment in relative biological effectiveness (RBE) values for carbon-ion-irradiated HeLa cells. The study indicated gold nanoparticles can be used as potential radio-sensitizer in carbon ions therapy.

The Histomorphological Changes in the Proximal Tubules of Metanephros of Developing Kidney of Chick Embryo Induced by Electromagnetic Radiations from Conventional and Advanced Mobile

Objective: The study was conducted to observe the histomorphogical effects of radiations from conventional and advanced mobile phone, on the developing kidney of chick embryo. Study Design: Randomized Control Trial Duration of Study conducted at Army Medical College, NUST, Rawalpindi, 3months from May 2012 till July 2012. Material and Methods: Fifty fertilized eggs of Fayoumi breed were selected and divided into five groups. Group I being control. Two groups II and IV were exposed to conventional mobile phone radiations and two groups III and V were exposed to advanced mobile phone radiations, for 15 and 30 minutes respectively. Results: Statistically significant change in the tubular diameters was observed after advanced cellular radiations whereas conventional cellular radiations decreased the epithelial height significantly. Conclusion: The changes induced by electromagnetic radiations from the advanced mobile phones affected the tubular diameters more by decreasing them while conventional decreased the epithelial height of the proximal tubule cells.

Cancer stem cells in head and neck tumors: evidence for metastatic spread and treatment resistance

The major challenge in the management of patients with oral squamous cell carcinomas (OSCC) is the development of resistance to therapy leading to disseminated disease. Since cancer stem cells (CSC) have emerged as important players in OSCC metastasis, our objectives were to explore the implications of CSC in OSCC tumor progression, invasion and response to conventional therapies. Methods: A panel of well-characterized cell lines originated from the most common sites in the head and neck area was used. Cells were cultured as floating spheres or under normal adherent conditions and analyzed for CD44, ALDH, CD24, CD29, CD56 by flow cytometry, PCR arrays for genes related to stemness, metastasis and EMT . We also investigated sLeX expression, known to play a key-role in many cancers metastasis by promoting tumor cells binding to endothelial E-selectin. We analyzed the tumorigenic potential of OSCC cells by invasion assays and in vivo OSCC experimental models comparatively to CSC cells. Moreover resistance to cisplatin and radiation was assessed by annexin V/PI assay and by colony forming assay. Results: The highest levels of sLeX expression were found in cell lines originated from oral cavity (9%-47%) compared to other head and neck locations (0.1%-7%). Cells grown as spheres were 95-100% positive for sLeX compared to 10-40% of adherent counterpart. Although sLeX+ and sLeX- cells were both able to form spheres, sLeX+ spheres were predominant and larger. Flow cytometry and PCR arrays indicated that the spheres were highly enriched in CSC and metastatic markers. Consistently, the spheres showed increased invasive and tumorigenic potential, and resistance to conventional chemotherapy and radiations. Conclusion: these studies are the first to unveil a novel link between sLeX expression, stem cell formation and metastatic spread in OSCC, and provide supportive evidence for CSC resistance to treatment. Understanding the mechanisms of tumor invasion and metastasis will improve patient outcome and survival.

Absorption Characteristics of Protons and Photons in Tissue

This presentation reviews the radiation quality of protons and other energetic ion beams, where radiation quality refers to those relevant physical properties other than the dose of the different types of radiations that can contribute to differences in the absorption characteristics in various tissues and the corresponding clinical outcomes. Prior to initiation of clinical trials with protons, neutrons, pions, and heavy ions, it was generally believed that such particles might have a therapeutic advantage resulting from their greater relative biological effectiveness (RBE). Potential clinical advantages resulting from a greater biological effectiveness, however, have generally been overshadowed during the last three decades by improved controls or reduced complications resulting primarily from the better dose delivery and localization that was possible with these heavier particles in conjunction with improved imaging. The successes both in delivery and in the clinical responses with protons and other light ions resulting from improved dose localization have arguably led the way in stereotactic radiosurgery, intensity modulated radiation therapy, and tomotherapy, stimulating improved methods with conventional radiations as well. Protons or light ions differ significantly in comparison with photon or electron beams in how they interact with the tissue atoms and molecules, and in how they transfer energy to those tissues. Microscopically, the heavier particles tend to travel in straight lines and produce long tracks with the energy concentrated closer to the track of the primary particle, while photons or electrons tend to scatter more easily and produce a more uniform distribution of energy transfers. Because they are hadrons, i.e., nuclear particles, protons and ions are more likely to produce long-range nuclear secondaries with higher masses. This higher concentration of energy associated with the heavier particle beams and the more massive secondaries results in differences in dose localization, clinically and microscopically, and therefore potential differences in short-term and long-term chemical and biological processes. Protons tend to have the least differences in clinical response in comparison with photons and electrons, the radiations used conventionally in therapy, but biological differences have been observed for these particles; it behooves us, therefore, to understand these different mechanisms if we are to take full advantage of their benefits. This article reviews the physical properties of these different particles in terms of microdosimetric distributions of energy deposition in order to compare protons with photons and heavy ions.

A review of ground-based heavy-ion radiobiology relevant to space radiation risk assessment. Part II: Cardiovascular and immunological effects

The future of manned space flight depends on an analysis of the numerous potential risks of travel into deep space. Currently no radiation dose limits have been established for these exploratory missions. To set these standards more information is needed about potential acute and late effects on human physiology from appropriate radiation exposure scenarios, including pertinent radiation types and dose rates. Cancer risks have long been considered the most serious late effect from chronic daily relatively low-dose exposures to the complex space radiation environment. However, other late effects from space radiation exposure scenarios are under study in ground-based accelerator facilities and have revealed some unique particle radiation effects not observed with conventional radiations. A comprehensive review of pertinent literature that considers tissue effects of radiation leading to functional detriments in specific organ systems has recently been published (NCRP National Council on Radiation Protection and Measurements. Information Needed to Make Radiation Protection Recommendations for Space Missions Beyond Low-Earth Orbit. Report #153, Bethesda, MD, 2006). This paper highlights the review of two non-cancer concerns from this report: cardiovascular and immunological effects.

A review of ground-based heavy ion radiobiology relevant to space radiation risk assessment: Cataracts and CNS effects

Analysis of the numerous potential risks of travel into deep space is critical to future manned missions. Despite the availability of significant new information on heavy-ion radiobiology at high doses and high dose-rates, radiation effects on human physiology during space travel, and later in the career of the space traveler, remain high on the list of what still needs to be known under space radiation scenarios. Cancer risks have long been considered the most serious late effect from chronic daily relatively low-dose exposures to the complex space radiation environment. However, other late radiation effects from space radiation scenarios are under study in ground-based accelerator facilities and have revealed some unique particle radiation effects not observed with conventional radiations. A comprehensive review of pertinent literature that considers functional degradation of specific body organs and systems at risk has recently been published (NCRP Report #153, 2006). This paper highlights the review of two noncancer concerns from this report: cataracts and effects on the central nervous system.

Design of a centre for biologically optimised light ion therapy in Stockholm

Radiation therapy is today in a state of very rapid development with new intensity-modulated treatment techniques continuously being developed. This has made intensity modulated electron and photon beams almost as powerful as conventional uniform beam proton therapy. To be able to cure also the most advanced hypoxic and radiation resistant tumours of complex local spread, intensity modulated light ion beams are really the ultimate tool and only slightly more expensive than proton therapy. The aim of the new centre for ion therapy and tumour diagnostics in Stockholm is to develop radiobiologically optimised three-dimensional (3D)-pencil beam scanning techniques. Beside the `classical' approaches using low ionisation density hydrogen ions (protons, but also deuterons and tritium nuclei) and high ionisation density carbon ions, two new approaches will be developed. In the first one lithium or beryllium ions, that induce the least detrimental biological effect to normal tissues for a given biological effect in a small volume of the tumour, will be key particles. In the second approach, referred patients will be given a high-dose high-precision `boost' treatment with carbon or oxygen ions during one week preceding the final treatment with conventional radiations in the referring hospital. The rationale behind these approaches is to reduce the high ionisation density dose to the normal tissue stroma inside the tumour and to ensure a microscopically uniform dose delivery. The principal idea of the centre is to closely integrate ion therapy into the clinical routine and research of a large radiotherapy department. The light ion therapy centre will therefore be combined with advanced tumour diagnostics including MR and PET-CT imaging to facilitate efficient high-precision high-dose boost treatment of remitted patients. The possibility to do 3D tumour diagnostics and 3D dose delivery verification with the same PET camera will be the ultimate step in high quality adaptive radiation therapy where alterations in the delivered dose can be performed by subsequent treatments. The increased knowledge in tumour and molecular biology will hopefully further improve the efficiency of this very unique new treatment modality that will be planned and delivered by radiobiologically optimised 3D-pencil beam scanning techniques to maximise the complication-free tumour cure and minimise normal tissue side effects. Finally, the design, cost, time scale and treatment capacity of the centre are reviewed. After a few years of running, the centre will be capable of treating 1000 patients/year with light ions and almost 3000 patients/year with the high-precision boost techniques.

Oxygen tension in transplanted mouse osteosarcomas during fractionated high-LET- and low-LET radiotherapy--predictive aspects for choosing beam quality?

The lower OER of high-LET radiations, compared to conventional (low-LET) radiations, has often been put forward as an argument for using high-LET radiotherapy in the management of hypoxic tumours. Among the different neutron beams used in therapy, the reactor fission neutrons have the lowest OER. The aim of the present study is to follow the variations of tumour oxygenation status during fractionated irradiation with different radiation qualities. Little information is available so far after fractionated high-LET irradiation. In addition, the RBE of reactor fission neutrons for effects on tumours and on normal tissues are compared. Murine OTS 64-osteosarcomas were transplanted in 102 balb-C mice and irradiated by 36 Gy of photons in fractions of 3 Gy five times a week (group P-36/3) or by 12 Gy of reactor fission neutrons in fractions of 2 Gy two times a week (group N-12/2). Irradiations started at a tumor volume of 500 to 600 mm3. A third group received no radiotherapy, but all investigations (group CG). Tumor volume and tumor oxygenation were measured once a week under therapy and during three weeks after therapy. For in vivo-evaluation of oxygen status a computerized polarographic needle electrode system (KIMOC pO2 histograph, Eppendorf) was used. The median pO2 and the hypoxic fraction (pO2 values < 5 mm Hg) of single tumors and of total groups were calculated from pooled histograms and from row data as well. In correlation with the increase of tumor volume, from day 1 to day 42 of follow-up the median pO2 decreased from 20 mm to 8 mm Hg and the hypoxic fraction increased from 7% to 31%. After fractionated photon therapy a growth delay of three weeks was observed. Six weeks after beginning of the irradiation the median tumor volume had been doubled again. After fission neutron therapy growth delay continued until the end of the follow-up period. In both of the irradiated groups a significant decrease of median pO2 values and an increase of the hypoxic fraction were observed under radiotherapy. Hypoxia was more intensive after neutrons with a decrease of the median pO2 from 20 mm Hg to 1 mm Hg vs. 10 mm Hg after photon therapy and with an increase of the hypoxic fraction from 7% to 78% vs. 36% respectively. Two weeks after the end of therapy the median pO2 and the hypoxic fraction of both treated groups reached the levels prior to irradiation indicating a complete reoxygenation. During fractionated irradiation of murine osteosarcomas with photons and reactor fission neutrons, a marked hypoxia was observed for both radiation qualities, but hypoxia was more intense during fractionated neutron irradiation. After irradiation, a complete reoxygenation occurred in both groups independently of the degree of hypoxia observed during the treatment. The RBE of reactor fission neutrons, after fractionated irradiation, was much higher for effects on murine osteosarcomas compared to their RBE observed for normal tissues in previous experiments. Present data are in agreement with our clinical observations on more than 300 patients treated with reactor fission neutrons for advanced and hypoxic tumours with various histologies.

Proton radiobiology, radiosurgery and radiotherapy.

This review briefly traces the historical developments of proton radiobiology, radiosurgery and radiotherapy for the benefit of young researchers and clinicians entering into this field. In preparing to use protons in radiosurgery and radiotherapy, radiobiological effects of protons were studied extensively by various groups, including the University of California at Berkeley, the University of Uppsala, Massachusetts General Hospital, and the Harvard Cyclotron Laboratory. Considerable work on proton radiobiology was also done because protons are a major component of the radiation environment in space. The biological effects of proton beams were found to be quantitatively and qualitatively similar to conventional radiations used in radiotherapy. The relative biological effectiveness (RBE) of protons suitable for large-field radiotherapy, compared with 60Co gamma-rays, is generally in the range 1.0-1.25, and remains the same with depth of penetration, except for the descending portion of the depth-dose curve. Also, unlike other heavier charged particles and neutrons, the RBE of high-energy protons, which are suitable for large-field radiotherapy, compared with 60Co gamma-rays, is generally found to be independent of the fraction size in in vivo experiments. The oxygen enhancement ratio for high-energy protons is not significantly different from that of X-rays. An RBE = 1.1, compared with 60Co gamma-rays, is generally used in the clinical application of protons; however, the radiobiological data on mouse, rat, rabbit and primate suggest that the gastrointestinal tissues may be relatively more sensitive to protons. About 13,000 patients have been treated with protons at about 15 facilities around the world. Nearly half of these patients were neurosurgical patients treated with stereotactic radiosurgery. The pioneering efforts at the Harvard Cyclotron in collaboration with the Massachusetts General Hospital and the Massachusetts Eye and Ear Infirmary were responsible for the development of proton treatment for choroidal melanoma and for the tumours of the skull base and spine. There has been extensive confirmation of these results by other groups, especially the groups at Lawrence Berkeley Laboratory and Paul Scherrer Institute. The first medically dedicated proton facility is in operation at Loma Linda University in California. The construction in the USA of another proton treatment facility at Massachusetts General Hospital has been decided upon, and there are plans for many more worldwide.

Neutron Radiobiology Revisited

The present paper reviews the experimental results of normal tissue and tumour studies in animals. The dose per fraction dependence of the RBE in normal tissues has been long recognised, together with the steeper increase of RBE at low doses for late responding tissues compared with acute reactions. The dose dependence for tumours is more complex, because of hypoxia and reoxygenation, as well as differences in repair capability after high LET damage. A comparison of tumour and normal tissue RBE values shows that there is little experimental evidence for a therapeutic advantage at clinically relevant doses. In particular, the RBE for slow growing tumours is even lower than that for the faster growing mouse tumours. The reasons for the loss of expected neutron benefits in clinically relevant experiments are discussed. The disappointing prospects for neutrons are contrasted with the current multifactorial approaches to overcoming resistance to more conventional low LET radiations, including acceleration, hyperfractionation and several types of hypoxic cell radiosensitizers.

Hydrogenated carbon layers produced by ion beam irradiation of PMMA and polystyrene films

The dissociation of the polymeric structure, which results from ion beam irradiation, leads to the formation of hydrogenated carbon layers exhibiting new optical and conducting properties at high fluence. The properties of these hydrogenated carbon layers have been compared to the properties of diamond-like carbon films prepared by plasma techniques: we discuss the modifications induced by ion beams in PMMA, which is known to be dominated by degradation, and in polystyrene, which gives rise to reticulation when exposed to conventional radiations. High energy ion beams tend to favour the formation of graphite-like phases (sp 2 hybridization of carbon) in contrast to deposition techniques assisted by low energy beams which produce mostly diamond-like phases (sp 3 hybridization of carbon).

On the use of effective dose in the treatment planning of high linear‐energy‐transfer radiation

Treatment planning for conventional radiations is based on the assumption that the effect of a combination of doses at any location in the treatment field in a multibeam plan will be equivalent to that of a single dose made up of the total sum of the doses delivered to that location. This is obviously valid for conventional low linear-energy-transfer (LET) radiations when the dose contributions from various beam components are associated with the same relative biological effectiveness (RBE) value of unity. However, this is not the case for the new generation of charged particle beams whose RBEs have been shown to vary significantly with depth. A concept of effective dose, defined as the mathematical product of physical dose and RBE value evaluated for an effect level, is developed for the treatment planning of these high-LET particle radiations. Based on radiobiological results in mixed radiation experiments, it is shown that these effective doses are linearly additive like physical doses and hence, can be used directly for general treatment planning using linear algorithms already developed for the use of physical doses. This is illustrated using examples of simplified one-dimensional plans for the TRIUMF pion beam.

Radiobiological Background for Negative Pion and Heavy Ion Therapy on Cancers

Recent advances in radiotherapy have been remarkable. However, there are some tumors which are incurable with conventional radiation therapy because of their histological features, localization and the like. In addition, conventional radiations such as photons, gamma rays or electrons show several disadvantages to bring tumors to cure. Hence more and more attention is being paid to new modalities such as fast neutrons, protons, negative pions and heavy ions, which are expected to overcome some of the defects of the conventional radiations. Except for fast neutrons, these particle radiations show excellent physical dose localization in tissue. Moreover, in terms of biological effects, they demonstrate several features compared to conventional radiations, namely low oxygen enhancement ratio ( OER), high value of relative biological effectiveness (RBE), smaller cellular recovery, larger therapeutic gain factor (TGF) and less cell cycle dependency in radiation sensitivity. In the present paper the biological effects of pions on murine tumor cells are shown comparing to the effects of conventional radiation, or heavy ions (Ne or Ar ions).

Heavy Ion Radiotherapy at the Lawrence Berkeley Laboratory

Heavy ion radiotherapy potentially offers both dose localization and biologic advantages over conventional radiations in the treatment of cancer. Approximately 400 patients have been treated with either helium , carbon, neon, argon or silicon beams. Aspects of particle therapy are reviewed. Experience with these beams have defined parameters required of a hospital based heavy ion machine. A design study of such a machine is now underway at LBL.

Calculated let distributions of heavy ion beams

The distribution of LET (energy losses) produced by heavy ion beams will to a great extent determine: (1) the relative probability of killing oxygenated and hypoxic tumor cells, (2) the relative effectiveness of charged particle beams over more conventional radiations in killing tumor and normal cells. It is known that, for cell-killing, highly ionizing heavy charged particles are more efficient per unit energy deposited than more sparsely ionizing radiation. Calculated distributions will be presented for various beams at different depths in a water phantom. Of particular interest are beams whose depth-dose distributions have been spread out by means of a variable depth absorber. Results for such beams will be presented and discussed. It can be concluded, for instance, that for a neon beam, median LET's in the 100–200 keV/μm region can be obtained throughout the “spread-out” peak region. Because of the broad distribution of LET found in the peak regions of the beams, however, the median LET may not be an adequate measure of beam quality. This problem will also be discussed.

Biological effects of negative pions

Most pion radiobiological work in the past was done at low dose rates using biological systems sensitive to small doses. Biological effects at the beam entrance were found to be nearly the same as conventional radiations, although some reports have indicated a higher RBE. LET distribution at the peak of a nearly monoenergetic pion beam is not much different from fast neutrons; therefore, one would expect similar biological responses, and the results are consistent with this hypothesis. The RBE at the peak for a nearly monoenergetic pion beam is significantly higher than at the entrance. The RBE peak/RBE plateau ratio is decreased with increasing width of the peak. The OER (∼1.6) at the peak for a nearly monoenergetic pion beam is also similar to fast neutrons and is expected to increase with increasing width of the peak. No OER data for broad peaks relevant to therapy are available. Preliminary measurements on radiosensitivity variation as a function of cell cycle indicate that there is a slight reduction in variation at the plateau, compared to X-rays, and a significant reduction at the narrow peak. With the availability of increasing intensity of pion beams, more radiobiological work relevant to radiotherapy is in progress at Los Alamos, Vancouver and Zurich.

Fast-neutron radiobiology and radiotherapy.

The application of fast neutrons, negative pions or heavy ions will only provide an advantage for the radiotherapy of cancer if, in comparison with conventional radiations, e.g., X-rays, gamma rays and electrons, better depth-dose and collimation characteristics or specific radiobiological dose response relationships result in greater local control probabilities for tumours without increased frequencies of severe noraml tissue damage. Differences in intrinsic radiosensitivity and the presence of hypoxic cells are considered to be the main factors which can cause values of the relative biological effectiveness (RBE) for responses of tumours to be larger than RBE values for normal tissue tolerance. Clinical studies on lung metastases irradiated with single dose of 15 MeV neutrons indicate that RBE values for tumour growth delay can vary between 1.2 and 4.0, while RBE values for damage to several normal tissues are estimated from corresponding animal data to be approximately 2.5.