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PubMedDate not supplied

[Lethal action of accelerated heavy ions on mammalian cells as affected by inhibitors of DNA synthesis. Results of experimental research].

Radiosensitivity of Chinese hamster cells exposed to 137Cs-gamma-radiation and accelerated heavy ions of 4He (L = 22 and 60 keV/micron), 12C (L = 231 keV/micron), and 20Ne (L = 690 keV/micron) was studied in standard conditions and in the presence of arabinosylcytosine and hydroxyurea. These agents were shown to exert a radiosensitizing effect in the case of gamma-radiation. The effect was less pronounced with 4He ion-radiation and was absent upon irradiation with 12C and 20Ne ions. The radiosensitivity was maximum upon irradiation with 4He ions at L = 60 keV/micron. The RBE coefficients of heavy ions under study decreased in the presence of DNA synthesis inhibitors.

Animals↗
PubMedDate not supplied

[Lethal action of accelerated heavy ions on mammalian cells as affected by inhibitors of DNA synthesis. A theoretical analysis].

Günter-Schulz's model and the authors' own model were used to study the dependence of radiosensitivity (D0(-1)) of Chinese hamster cells on linear energy transfer (LET) upon irradiation in standard conditions and in the presence of DNA synthesis inhibitors, arabinosylcytosine and hydroxyurea. A better agreement of the experimental and theoretical results was obtained using Kozubek-Krasavin's model than the model of Günter and Schulz.

Animals↗
PubMed1987

Variations of pion RBE in a volume with an asymmetric beam configuration.

The relative biological effectiveness for the radiation response of mouse jejunum for pions was determined in a clinically relevant asymmetric treatment geometry. A cylindrical volume of 570 ccm, with mouse holders in proximal and distal positions, was irradiated by spot scan technique with a sector of 31 concentric pion beams. The physical dose distribution within the treatment field was homogeneous and the average dose rate was 8.5 cGy/min. The aim was to determine RBE differences between the proximal and distal edge of the field and to compare it with the predictions. The RBE, relative to 200 kVp X-rays, was 1.3 for proximal position and 1.4 for the distal one. The results are in agreement with the calculations of the therapy planning computer program and with the microdosimetric characteristics at the two positions. The variation of the RBE is smaller than for the same field irradiated by a single pion beam.

Animals↗
PubMed1979

The design of clinical trials comparing pi-meson therapy with conventional radiotherapy.

Comparative clinical trials of pi-meson therapy for several tumor sites will be performed in Vancouver using the TRIUMF facility. The design of these trials poses some particular problems related to the limited numbers of patients available. In this paper, some principles of study design are set forth and applied to the issue of randomised and non-randomised designs in general, and to the pi-meson trials in particular.

Clinical Trials as Topic↗
PubMed1985

Cell-cycle-dependent recovery from heavy-ion damage in G1-phase cells.

The cell-cycle-dependent capacity of synchronized G1-phase human T-1 cells to repair damage from either 425 MeV/u Bragg peak neon ions or 225 kVp X rays has been compared. The dose-survival response to each radiation was measured at early (1.5 h), mid (3.0 h), and late (4.5 h) times after mitotic selection. In addition the age response was characterized by irradiating cell populations at seven ages between 1.5 and 6.0 h after mitosis with single doses of either radiation. Repair of potentially lethal damage (PLDR) was evaluated in both the dose-survival and age-response experiments by holding irradiated cultures at 37 degrees C for 6 h in PBS or PBS containing 60 microM of the DNA polymerase inhibitor 1-beta-D-arabinofuranosyladenine (beta-araA) before trypsinization and plating. Delayed plating showed significant PLDR at all ages irradiated with X rays, with up to 10-fold increases of survival depending on the dose and the cell age at irradiation. There was negligible PLDR after neon-ion exposures to early and mid G1-phase cells; only late G1-phase cells repaired neon damage. The beta-araA treatment after X rays reduced the shoulder of the survival curves at all G1 ages studied, and in early and mid G1 reduced survival below the immediately plated control. beta-araA similarly reduced repair of PLD where it was measurable after neon ions. Differences between low- and high-LET radiation damage and repair are discussed.

Cell Cycle↗
PubMed1985

Proportional counter dosimetry and microdosimetry for radiotherapy with multiple pion beams.

At the Swiss Institute for Nuclear Research (SIN) cancer patients are irradiated with negatively charged pi mesons using a 60-beam medical pion generator, the Piotron. A low-pressure tissue-equivalent proportional counter was used to measure absorbed dose and microdosimetric spectra. A method was developed to allow discrimination of events from different beam components, i.e., beam contamination (electrons and muons), pions in flight, and stopping pions. Measurements were performed along the axis and at lateral distances off one of these identical pion beams. The marked changes of total microdosimetric spectra with depth in phantom detected in earlier measurements are mainly due to large variations in the dose contributions of the beam components and much less to changes in the shapes of the individual microdosimetric spectra. The single beam measurements were used to calculate three-dimensional distributions of absorbed dose and of dose mean lineal energy, yD, for dynamic patient irradiations. Within the whole target volume yD remains nearly constant when irradiated with all 60 beams, whereas considerable changes were found for irradiations with 31 beams coming from a semicircle. Both size and shape of target volumes influence yD, the maximum values ranging from 30 to 45 keV/micron.

Elementary Particles↗
PubMed1985

In vitro and in vivo studies of the TRIUMF pion therapy beam.

Patient treatments at TRIUMF (Tri-University Meson Facility, Vancouver, B. C.) use a moving spot raster scan technique where the pion range is modulated in depth for each position of the moving spot. The spot scans in a stepwise fashion and can produce any desired field shape. This approach provides very good dose uniformity across the treatment field and allows maximum flexibility in shaping the treatment volume. Survival of cultured cells has been used as a biological dosimeter to test the isoeffectiveness of the pion dose distributions, which must be shaped in depth to compensate for the depth-dependent LET distribution. Isoeffectiveness across the treatment field has also been verified using this system, which involves irradiating cells supported in a gelatin matrix. The response of pig skin to pion irradiation at TRIUMF has provided a check on the in vivo RBE for acute effects derived from our earlier studies with mouse foot. In addition, the pig skin reactions have been followed for several months to assess the later dermal response. The RBE of our pion beam relative to 270 kVp X rays is approximately 1.5 for both the acute epidermal and the later dermal responses.

Animals↗
PubMed1985

Possible damage of repair systems by Pi-mesons of different LET spectra.

Pi-meson experiments with repair-deficient spermatides and oocytes of Drosophila melanogaster have permitted a study of the LET dependence of the repair of different types of chromosomal lesions. The data show a distinction between primary events connected with fusion modalities (repair or misrepair) and those associated with no fusion. Repair deficiency increases the induction of chromosomal loss and dominant lethality (early damage) and decreases the induction of translocations (misrepair), perhaps responsible for late effects. The induction of nonfusion events is higher for pions compared to X rays and increases with mean lineal energy spectra, whereas the production of translocations is maximal at intermediate ionization density. The direct damage of repair systems by high-LET pions is postulated to explain these observations.

Animals↗
PubMed1985

Review of the SIN and Los Alamos Pion Trials.

Negative pi mesons (pions) were used to treat 227 patients at the Los Alamos Meson Production Facility (LAMPF) between 1974 and 1981. Persisting local control values for 129 patients treated with pions alone in the following tumor sites were recorded at a minimum post-treatment observation interval of 2.5 years in the following tumor sites: cerebral gliomas 3/29; head and neck, 8/31; lung, 1/7; pancreas, 0/17; large bowel, 3/13; cervix, 2/45; bladder, 3/4; prostate, 18/20; miscellaneous sites, 0/4. Late severe sequelae ranged from none to 30% for major sites. A dose-response relationship was seen for late severe sequelae with a high probability following dose levels of 4750 cGy (max) in approximately 38 fractions. RBE values for pions appeared to lie in the range of 1.4-1.6 for both acute normal tissue reactions and late sequelae. At the Swiss Institute for Nuclear Research (SIN), 126 patients were treated in Phase I-II protocol studies between 1982 and 1984 with a new technique of scanning with a focused spot of pions. With minimum observation intervals of only 6 months, the local complete response values in 67 evaluable patients treated with pions alone to selected sites are gliomas 1/15 (9 months); pancreas, 3/11; cervix, 4/8; bladder, 18/26 (at 1 year, 9/22); sarcomas, 4/5; biliary tract, 3/4. Late severe sequelae ranged from none to 50% for major sites. A steep dose-response relationship is seen for late severe sequelae with high probability following doses exceeding 3800 cGy (max) in 20 fractions and very low probability with doses below 3500 cGy (max).

Brain Neoplasms↗
PubMed1985

Results of curative pion therapy at SIN.

The experiences of the treatment of bladder carcinoma indicated the direction in which the dose optimization program of intraabdominal tumours can be carried out. Small intraabdominal target volumes seem to tolerate doses from 31 to 33 Gy applied in 20 fractions. The best results with local tumour control and low complication rates have so far been reached in carcinoma of the cervix. It has not so far been organizationally possible at SIN to treat with pions on more than four days per week. This restricts changes to the fractionation scheme in the treatment of highly malignant gliomas. An improvement of results could be possible on the basis of experience to date. The significance of a postbiopsy preoperative radiotherapy, of the increase of target volume and the increase of the total dose will be tested in a study by the SAKK (Swiss Group for Clinical Cancer Research).

Elementary Particles↗