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The use of positron emission tomography in pion radiotherapy.

The radioactive debris produced by pion radiotherapy can be imaged by the technique of Positron Emission Tomography (PET) as a method of non-invasive in situ verification of the pion treatment. This paper presents the first visualization of the pion stopping distribution within a tumor in a human brain using PET. Together with the tissue functional information provided by the standard PET scans using radiopharmaceuticals, the combination of pion with PET technique can provide a much better form of radiotherapy than the use of conventional radiation in both treatment planning and verification.

Brain Neoplasms↗

The response of mouse epidermis to fractionated doses of pi mesons.

An extensive series of preclinical experiments are described in which the relative biological effectiveness (RBE) of pions from TRIUMF has been determined for mouse skin. To measure the RBE at both high and low doses per fraction, a range of fractionation schedules was used, with 1, 2, 4, 10, and 20 fractions. Because the pion dose rate is much lower than the dose rate of X or gamma-rays used in radiotherapy, two sets of reference X ray data were obtained: one at the same dose rate as the pions (15 cGy min-1), and another at the more conventional 150 cGy min-1. This allowed a "biophysical" RBE for equivalent dose rates and a "practical" RBE for preclinical evaluation to be calculated. The pion RBE was significantly higher for 20 small fractions than for fewer large doses. The absolute value of RBE depends upon the dose rate of the reference X ray treatments. The "practical" RBE increased from 1.05 at high doses to 1.45 at the smallest dose per fraction tested. The "biophysical" RBE for equivalent dose rates ranged from 1.20 at high doses to 1.5 for 20 fractions.

Animals↗

Long-term results of pion therapy at Los Alamos.

Two hundred twenty-eight patients were treated at the Los Alamos Meson Physics Facility (LAMPF) with negative pi-mesons (pions) between 1974 and 1981. Of these, 19 patients with metastatic disease were treated in pilot studies. Following the clinical determination of relative biological effectiveness (RBE) of pions, 209 patients were treated in site and dose searching studies beginning in 1977. Advanced but regionally localized cancers that were considered poorly responsive to conventional therapy were selected for treatment. A wide range of treatment fractions (22 to 45) and of total dose (1800 to 4200 cGy at the 80% isodose level) to the prescribed target volumes was explored. A follow-up observation period of between 4.5 and 9 years has been completed. The analysis focuses on 129 patients receiving pion therapy alone. Thirty-six (28%) had persisting local tumor control of which 12 (9%) suffered complications of treatment. The results varied among treatment sites, for example: prostate cancer, 18/21 (86%) locally controlled, 6/21 (29%) complications; head and neck, 8/31 (26%) locally controlled, 1/31 (3%) complications; and pancreas, none controlled and no complications. Analysis of dose-fraction response suggests a steep rising curve of complications beyond the dose level of 3750 cGy minimum, 4700 cGy maximum, in 38 fractions. The tumor control response has a broader and ill-defined curve possibly due to the heterogeneity of tumor types. The RBE for late effects in normal tissues appeared to be higher than that for acute effects although the mixture of tumor types, sites, dose, and fractionation made this estimate highly uncertain. No late secondary neoplastic changes in pion irradiated tissues were seen. It is concluded that pions can locally ablate some advanced cancers, often without significant sequelae, but that the optimum therapeutic range is critical. The Los Alamos data may be of use to ongoing pion studies in Canada and Switzerland.

Elementary Particles↗

An intercomparison of two dynamic treatment techniques, ring scan and spot scan, for head and neck tumors with the Piotron.

An evaluation of the ring scan and the spot scan was made for the pion irradiation of head and neck tumors with the Piotron. For the geometry of the Piotron, with its 60 radially converging beams, two scanning techniques have been developed, ring scan and spot scan. They have different characteristics concerning achievable dose distributions and sensitivity to tissue inhomogenities. The optimized 3-dimensional dose distributions for the treatment with ring scan and spot scan techniques were calculated for two examples of the target volume. The comparison of the dose distributions has shown that the ring scan is better in sparing normal tissues than the spot scan for a simple shape target volume but not for an irregular shape target volume with the present status of the technique. The irradiation time needed for the ring scan is longer, for the present examples three times, than for the spot scan. From the practical view point the spot scan is preferable to the ring scan for the treatment of head and neck tumors with the Piotron.

Elementary Particles↗

Late effects of fractionated pi-mesons compared to X rays on mouse lung.

Early and late delayed effects of up to 20 fractions of pions and X rays were investigated in the mouse lung. The whole thorax of female CD-1 mice was irradiated under Ethrane/O2 anesthesia. Respiration rate was measured by whole body plethysmography at biweekly to monthly intervals. With signs of irreversible respiratory distress, animals were sacrificed and their lungs evaluated histologically. In addition to the effect of fractionation, the influence of dose-rate and anesthesia was studied as well. The degree of injury for the most predominant lesions (macrophage accumulation, fibrosis, vascular congestion) was scored, and the correlation with the relative change in respiratory rate and survival was analyzed. This analysis showed the primary lesion to be radiation pneumonitis at a median survival time of approximately 100 days. Focal fibrosis was observed to occur soon thereafter, and no evidence was obtained for an independent second wave of fibrotic injury. Fibrosis seemed primarily the result of pathological organization in areas with heavy concentration of macrophages. It was observed that the mice were unusually sensitive, with a single dose X ray ED50/180 of 8.8 Gy. A similar value was found for unanesthetized mice. This might have been the result of performing these studies at an altitude of 2100 m. The fractionation effect also seemed more pronounced, with alpha/beta values of 0.6 Gy for X rays and 4 Gy for pions, which is significantly lower compared to reported values. At the pion dose-rate of 0.25 Gy.min-1, RBE values for single doses were 0.9 when compared to high dose-rate X rays, and 1.36 at equivalent dose rates. This clearly shows that significant repair occurs during the relatively low dose-rate pion irradiations. With smaller doses per fraction, the dose-rate effect became less dominant, and for 20 fractions of pions the RBE was 1.4 compared to fractionated high dose-rate X rays. These RBE's are similar to values reported for acute effects in skin.

Acute Disease↗

Dynamic pion irradiation of unresectable soft tissue sarcomas.

Since November 1981, when pion irradiation was introduced for deep seated tumors at the Swiss Institute for Nuclear Research (SIN, now Paul Scherrer Institute, PSI) a dynamic, 3-dimensional spot scan treatment technique has been in use. To exploit this technique a special optimization treatment planning system has been designed. Of a total of 331 patients treated with pions from November 1981-December 1987, 35 were irradiated for unresectable soft tissue sarcomas. In 32/35 patients, tumor sites were retroperitoneal, pelvic or in the groin or thigh. Twenty-nine tumors had a maximum diameter of greater than 10 cm, 18 tumors of greater than 15 cm; 30 tumors had grade 2/3 and 32 Stage III B/IV A/IV B. Eight of 35 patients received a low pion total dose, 7-27 Gy. Twenty-seven patients received a total dose of 30-36 Gy, fraction size 150-170 cGy (90%-isodose), 20 fractions, 4 times per week. Of these 27 patients, severe late reactions appeared in five: 2/8 patients with extremity/groin sarcomas (1/2 caused by biopsy) and 3/19 patients with retroperitoneal/pelvic sarcomas (one a skin reaction after Actinomycin-D, one a small bowel reaction after 36 Gy, a dose no longer used). Seven of 27 patients had metastases at the beginning of irradiation. Three of 27 were treated with excisional biopsy, 9 with incisional biopsy or partial resection and in 15 patients biopsies were performed for histology only. The median follow-up of these 27 patients was 17 months (5-66). There was no progression in eight extremity/groin tumors but in 4 of 19 retroperitoneal/pelvic tumors. Three of these were marginal progressions. The actuarial 5-year rate of local tumor control is 64%; the actuarial 5-year survival rate of patients without metastases at the beginning of treatment is 58%. Dynamic spot scan pion irradiation proves to be a successful treatment technique for unresectable sarcomas with a high rate of tumor control and a very low rate of severe late reactions.

Adult↗

Spallation processes and nuclear interaction products of cosmic rays.

Most cosmic-ray nuclei heavier than helium have suffered nuclear collisions in the interstellar gas, with transformation of nuclear composition. The isotopic and elemental composition at the sources has to be inferred from the observed composition near the Earth. The source composition permits tests of current ideas on sites of origin, nucleosynthesis in stars, evolution of stars, the mixing and composition of the interstellar medium and injection processes prior to acceleration. The effects of nuclear spallation, production of radioactive nuclides and the time dependence of their decay provide valuable information on the acceleration and propagation of cosmic rays, their nuclear transformations, and their confinement time in the Galaxy. The formation of spallation products that only decay by electron capture and are relatively long-lived permits an investigation of the nature and density fluctuations (like clouds) of the interstellar medium. Since nuclear collisions yield positrons, antiprotons, gamma rays and neutrinos, we shall discuss these topics briefly.

Astronomical Phenomena↗

Proton-proton correlations at small relative momentum in neon-nucleus collisions at E/A=400 and 800 MeV.

Proton-proton small angle correlations have been measured in neon-nucleus collisions, using the 4 pi detector Diogene, at 400 and 800 MeV per nucleon incident energies. Values of the size of the emitting region are obtained by comparison with the Koonin formula, taking into account the biases of the apparatus. The dependence of the density on target mass and incident energy is also analysed.

Carbon↗

Theoretical contributions to coherent pion production in subthreshold and relativistic heavy-ion collisions.

The analytic results from a microscopic calculation for pion production in heavy-ion collisions at intermediate to relativistic energies both above and below pion threshold are presented and the most important terms that contribute to the pion spectrum are determined. The energy dependence and the effects on the pion spectrum due to the various parameters in the theory are examined. The model is applied to coherent pion-production in 16O + 12C collisions.

Carbon↗

Exclusive measurements of light fragment production at forward angles in Ne-Pb and Ne-NaF collisions at E/A=400 MeV and 800 MeV.

Emission of light fragments at small angles is studied in relativistic heavy ion collisions using the Diogene plastic wall for both symmetrical and non-symmetrical target-projectile systems with 400 MeV per nucleon and 800 MeV per nucleon incident neon nuclei. Efficiency of multiplicity measurements in the small angle range for the selection of central or peripheral collisions is confirmed for asymmetric systems. Differential production cross sections of Z = 1 fragments show evidence for the existence of two emitting sources. The apparent temperature of each source is obtained from comparison with a thermodynamical model.

Elementary Particles↗

Multiplicities of secondaries in interactions of 1.8 GeV/nucleon 56Fe nuclei with photoemulsion and the cascade evaporation model.

A nuclear photographic emulsion method was used to study the charge-state, ionization, and angular characteristics of secondaries produced in inelastic interactions of 56Fe nuclei at 1.8 GeV/nucleon with H, CNO, and AgBr nuclei. The data obtained are compared with the results of calculations made in terms of the Dubna version of the cascade evaporation model (DCM). The DCM has been shown to satisfactorily describe most of the interaction characteristics for two nuclei in the studied reactions. At the same time, quantitative differences are observed in some cases.

Bromides↗

Multiplicities of secondaries in nuclear interactions, induced by 20Ne, 40Ar and 56Fe nuclei at 0.1-0.5 GeV/nucleon.

Multiplicities of various species of charged secondaries produced in inelastic interactions of 20Ne, 40Ar and 56Fe nuclei with emulsion nuclei at 0.1-0.5 GeV/nucleon have been measured. The data obtained are compared with the results for interactions of higher energy nuclei with emulsion nuclei. The dependences of the nucleus-nucleus interaction parameters on masses and energies of colliding nuclei are examined.

Argon↗

A complex T-matrix derivation of a resonance amplitude.

A resonant transition amplitude, valid to arbitrary order, is derived through the use of a complex energy T-matrix. A feature of this amplitude is its generality and simplicity making it useful for widespread applications in resonance theory.

Elementary Particle Interactions↗

Bone loss during oestriol therapy in postmenopausal women.

In contrast to all other oestrogens examined thus far oestriol hemisuccinate (12 mg/day) did not prevent bone loss in 28 postmenopausal women. The average bone loss, however, was somewhat less than expected from placebo studies, while the bone loss achieved by a group taking 4-6 mg/day was equal to that achieved by previous placebo groups. To be an effective agent for prevention of post-menopausal osteoporosis oestriol would have to be prescribed in daily doses considerably in excess of 12 mg.

Adult↗

Tissue characterization of brain tumors during and after pion radiation therapy.

Negative Pi-mesons (pions) are applied at the Paul Scherrer Institute in the radiotherapy of highly malignant gliomas using a dose escalation program. The therapy effects of 7 randomly selected patients were followed up by 62 MRI examinations. The quantification of the effects is based on the relaxation times T1 and T2, which are acquired by a new designed multi-echo multiple saturation recovery imaging technique. As a summary of the results, roughly two reaction types are observed. For both types the relaxation times increase up to two to three months after the radiation therapy. Then in one type (two patients) the T1 and T2 values of the tumors, and of the edemas surrounding the tumors, further increase, indicating an unfavorable prognosis. In the other type (five patients) the relaxation times drop down towards, or even below, their initial values, reflecting the onset of the reparation processes in the tissue. This later behaviour reflects an at least temporary control of the disease; that is, the short term prognosis for these patients is more favorable. It further can be concluded, with respect to our MR parameters, that the radiotolerance of healthy brain tissue is much higher than that of malignant glioma tissue, despite the fact that these tumors are very seldom definitively radiosensible.

Astrocytoma↗

Galactic cosmic ray transport methods and radiation quality issues.

An overview of galactic cosmic ray (GCR) interaction and transport methods, as implemented in the Langley Research Center GCR transport code, is presented. Representative results for solar minimum, exo-magnetospheric GCR dose equivalents in water are presented on a component by component basis for various thicknesses of aluminum shielding. The impact of proposed changes to the currently used quality factors on exposure estimates and shielding requirements are quantified. Using the cellular track model of Katz, estimates of relative biological effectiveness (RBE) for the mixed GCR radiation fields are also made.

Animals↗

IAEA Nuclear Data Section: provision of atomic and nuclear databases for user applications.

The Nuclear Data Section (NDS) of the International Atomic Energy Agency (IAEA) provides a wide range of atomic and nuclear data services to scientists worldwide, with particular emphasis placed on the needs of developing countries. Highly focused Co-ordinated Research Projects and multinational data networks are sponsored under the auspices of the IAEA for the development and assembly of databases through the organised participation of specialists from Member States. More than 100 data libraries are readily available cost-free through the Internet, CD-ROM and other media. These databases are used in a wide range of applications, including fission- and fusion-energy, non-energy applications and basic research studies. Further information concerning the various services can be found through the web address of the IAEA Nuclear Data Section: and a mirror site at IPEN, Brazil that is maintained by NDS staff:.

Databases, Factual↗

Nuclear fragmentation cross-sections of 400 A MeV 36Ar and 40Ar in collisions with light and heavy target nuclei.

We have measured fragmentation cross-sections of Ar projectile nuclei at beam energy of 400 A MeV using experimental set-ups with plastic nuclear track detectors and different targets. In this paper total charge changing cross-sections and elemental fragmentation cross-sections for the production of fragments with charges ZF > or = 7 in interactions with H, C, Al, Cu, Ag and Pb target nuclei are presented. The dependence of the cross-sections on the fragment charge number and target charge number are discussed. The experimental results are compared to predictions of semi empirical cross-section models.

Algorithms↗