Pion treatment of prostate carcinoma at Paul Scherrer Institute (formerly Swiss Institute for Nuclear Research (SIN)) from 1983 to 1992.

BACKGROUND: - Between 1983 and 1992 a total of 55 patients suffering from prostate cancer were treated with pions (pi-mesons) at the Paul Scherrer Institute in Villigen, Switzerland. This form of therapy was used at only three centers world wide on 245 patients with this diagnosis. Since the last project in Vancouver, Canada, was closed in 1994, this form of therapy has been relegated to the realm of history. METHODS: - In a retrospective analysis, the data of 49 of the 55 patients, that was qualified for evaluation was brought up-to-date and evaluated. Median and mean age at the time of therapy was 65 years. Advanced stage tumors were overly represented, in respect to T-stages (35/49 stage T3 and T4) and differentiation (11/49 G1). The treatment volumes were between 67 and 1330 cm(3), and the mean delivered dose was 32.2 pion-Gray. Survival probability, the probability of metastases and the local control rate were calculated according to Kaplan-Meier. RESULTS: - Seven of the 49 patients had already been diagnosed with metastatic disease before treatment began, 16 developed metastases during the follow-up observation period. Local control after 2 years was 89%, and after 5 years 83%. The survival rate after 2 years was 87%, and 66% after 5 years, excluding non-tumor related deaths. The rate of late toxicity was acceptable. CONCLUSIONS: - Seen in retrospect, pion treatment of prostate carcinoma proved to be an effective form of therapy with a low rate of late toxicity. But, in comparison to the possibilities offered by modern conventional radiation therapy, this method would certainly not be today's first choice.

Intensity modulated proton therapy: a clinical example.

In this paper, we report on the clinical application of fully automated three-dimensional intensity modulated proton therapy, as applied to a 34-year-old patient presenting with a thoracic chordoma. Due to the anatomically challenging position of the lesion, a three-field technique was adopted in which fields incident through the lungs and heart, as well as beams directed directly at the spinal cord, could be avoided. A homogeneous target dose and sparing of the spinal cord was achieved through field patching and computer optimization of the 3D fluence of each field. Sensitivity of the resultant plan to delivery and calculational errors was determined through both the assessment of the potential effects of range and patient setup errors, and by the application of Monte Carlo dose calculation methods. Ionization chamber profile measurements and 2D dosimetry using a scintillator/CCD camera arrangement were performed to verify the calculated fields in water. Modeling of a 10% overshoot of proton range showed that the maximum dose to the spinal cord remained unchanged, but setup error analysis showed that dose homogeneity in the target volume could be sensitive to offsets in the AP direction. No significant difference between the MC and analytic dose calculations was found and the measured dosimetry for all fields was accurate to 3% for all measured points. Over the course of the treatment, a setup accuracy of +/-4 mm (2 s.d.) could be achieved, with a mean offset in the AP direction of 0.1 mm. Inhalation/exhalation CT scans indicated that organ motion in the region of the target volume was negligible. We conclude that 3D IMPT plans can be applied clinically and safely without modification to our existing delivery system. However, analysis of the calculated intensity matrices should be performed to assess the practicality, or otherwise, of the plan.

Sources of variation in patient response to radiation treatment.

PURPOSE: To investigate sources of variation in radiosensitivity displayed by cancer patients and blood donors using the leukocyte apoptosis assay. METHODS AND MATERIALS: Probes were obtained from 105 healthy blood donors, 48 cancer patients displaying normal sensitivity to radiotherapy, 12 cancer patients displaying hypersensitivity to radiotherapy, 12 Ataxia telangiectasia blood donors, and 4 additional individuals with genetic diseases of potentially modified radiosensitivity; 2 neurofibromatosis (NF) donors, a Nijmegen breakage syndrome (NBS) donor, and an Immunodeficiency, Chromosome fragility, Facial anomaly syndrome (ICF) donor. Heparinized blood was diluted in medium, irradiated, and left to incubate for 48 h. CD4 and CD8 T-lymphocyte DNA was stained with propidium iodide and the cells were analyzed by flow cytometry. RESULTS: Radiation-induced apoptosis depended on age and cell type. Cohorts of hypersensitive cancer patients, NBS and AT donors displayed compromised apoptotic response. An asymmetric apoptotic response of T-lymphocytes was observed in an ICF donor and a cryptic hypersensitivity donor. Two NF donors displayed no abnormal sensitivity to radiotherapy but compromised apoptotic T-cell response to X-rays. CONCLUSION: Our studies reveal 4 physiologic sources of variation in radiation response-2 are genetic: cryptic hypersensitivity and hereditary disease, and 2 are epigenetic: cell type and donor age. They emphasize the important role of proteins involved in the recognition and repair of DNA double-strand breaks in determining the response of individuals to radiotherapy.

[Percutaneous radiotherapy of bone metastases]. / Perkutane Strahlentherapie von Knochenmetastasen.

Bone metastases causing pain syndromes and imminent pathologic fractures are among the main reasons for radiotherapy in patients suffering from malignant tumors. The indication is much influenced by the radiologic findings. Surgical methods are to be chosen in the first place in cases of pathologic fractures or patients with a high risk of such fractures. Different authors recommend various therapeutic regimens. Effective pain control can be achieved with one single dose of radiation. Doses of 6 to 40 Gy applied in one to 19 days are also efficient. Side effects, especially nausea and vomiting occur in 25% of cases; this number rises to 50% in cases of half body irradiation. Visible changes of bone mineral density may be noticed about 6 weeks after termination of radiotherapy. About 70% of osteolytic metastases show progressive sclerosis whereas osteosclerotic lesions may show both increase or decline of bone mass. In spite many years of experience the optimal strategy for radiation therapy of bone metastasis has not been defined; further studies are needed.

Review of the allergic contact dermatitis hazard posed by chromium-contaminated soil: identifying a "safe" concentration.

At least 200 sites in the United States contain soil with elevated levels of trivalent and hexavalent chromium [Cr(III) and Cr(VI)]. Although the potential cancer hazard posed by airborne Cr(VI) has been the primary concern for these sites, a soil cleanup standard based on the potential elicitation of allergic contact dermatitis has been proposed for sites in Hudson County, N.J. This paper describes the rationale for identifying a soil concentration of Cr(VI) that should not pose an allergic contact dermatitis hazard-even in sensitized persons. A literature review of eight published patch test studies that evaluated the allergic response to potassium dichromate was conducted. These studies were evaluated for clinical and statistical relevance in establishing a threshold dose of Cr(VI) to which no more than 10% of the subpopulation sensitized to chromium would respond, and that would protect at least 99.84% of the general population. Although each of the studies had certain methodological limitations when evaluated against current test methods, the data set proved useful for deriving an estimated threshold. Using computer data-fitting techniques based on truncated lognormal distributions, a weighted mean 10% threshold of approximately 150 ppm potassium dichromate or 54 ppm Cr(VI) was identified for the eight studies. Due to the types of limitations noted for these studies, this threshold is likely to be somewhat conservative. Test results have shown that between 5 and 10% of the Cr(VI) at concentrations less than about 500 ppm are released from a soil matrix into an isotonic saline solution simulating sweat. Using human sweat as the extractant, it has been shown that only 0.1% of the CR(VI) at concentrations of approximately 1,000 ppm are released from a soil matrix into sweat. Based on 10% solubilization of soil-bound Cr(VI) and the results of our statistical analysis of previous threshold studies, a concentration of approximately 350 to 500 ppm Cr(VI) in soil should be sufficiently low to protect virtually all exposed people, including children, from chromium-induced allergic contact dermatitis.

Effect of aluminum on performance and mineral metabolism in young chicks and laying hens.

This study was performed to determine the long-term effects of dietary aluminum on egg production and reproductive parameters in the mature laying hen and on growth rate and feed efficiency in young chicks. The diets used in these studies were adequate in phosphorus and other essential nutrients. Aluminum added to constitute 0.30% of the diet severely depressed growth and reduced feed efficiency, bone ash and plasma phosphorus in male Ross x Leghorn chicks. At the same time, 0.15% added aluminum mildly depressed growth, feed efficiency and bone ash but had no effect on plasma phosphorus levels. The reduction in bone ash was relatively mild, and no clinical signs of rickets were observed. In laying hens, diets containing 0.15% added aluminum did not affect egg production, but 0.30% added aluminum reduced production significantly. Long-term exposure to aluminum increased percent shell in both groups receiving aluminum, whereas egg weight remained similar to that in controls. There were no changes in hatchability or bone ash associated with dietary aluminum. Although dietary aluminum influenced bone aluminum content, egg aluminum content was not affected. These studies indicate that dietary aluminum interferes with systems in addition to phosphorus metabolism.