Radiation therapy is currently the most utilized technique for the treatment of tumors by means of ionizing radiation, such as electrons, protons and x/gamma rays, depending on the type, size and ...depth of the cancer mass. Radiation therapy has in general fulfilled the main requirement of targeting thus damaging the malignant cells and sparing the healthy tissues as best as possible. In this scenario, electron linear accelerators have been operated as viable tools for the delivery of both high-energetic electrons and x-ray beams, which are obtained via the bremsstrahlung process of the electrons hitting on a high-Z material. Recently, it has been experimentally demonstrated that ultrahigh dose-rate bursts of electrons and x-ray beams increase the differential response between healthy and tumor tissues. This beneficial response is referred to as the FLASH effect. For this purpose, we have developed the first dedicated compactS-band linear accelerator for FLASH radiotherapy. This linac is optimized for a nominal energy of 7 MeV and a pulsed electron beam current of 100 mA and above. The accelerator is mounted on a remote-controlled system for preclinical research studies in the FLASH regime. We will show the rf and beam dynamics design of theS-band linac as well as the commissioning and high-power rf tests. Furthermore, the results of the dosimetric measurements will be illustrated.
Purpose: Intraoperative electron radiotherapy (IOeRT) is considered the first clinical translation of FLASH with electrons. A crucial aspect is represented by the precise dose monitoring and ...measurement; to this aim, we propose a method fully based on Monte Carlo (MC) simulation that uses as input the beam current measurement and the beam optics simulation. To validate this approach, we chose the NOVAC11 (produced by Sordina IORT Technologies SpA) accelerator, which provides a well-studied model. Methods: We used FLUKA and FRED MC software to simulate in detail the geometry of the NOVAC11 and the coupled applicator usually adopted in clinical practice to deliver the dose in the surgical bed. The simulation results of the longitudinal and off-axis profiles and dose per pulse obtained in a water phantom with different applicators are compared to the experimental data. Results: A very good agreement not only for the relative dosimetry in both the longitudinal and off-axis profiles, with a gamma index pass rate of 100% with 3%/3 mm acceptance criteria, but also for the absolute dosimetry was obtained. Conclusion: The results completely validate the MC description of the system and provide a reliable evaluation of the dose per pulse and output factor with an accuracy of the order of few % for different sets of applicator diameters and lengths.
Tartrate-resistant acid phosphatase (TRAP) activity is regarded as an important cytochemical marker of osteoclasts; its concentration in serum is utilized as a biochemical marker of osteoclast ...function and degree of bone resorption. This study was carried out to assess the sensitivity of TRAP activity both as a cytochemical marker in histological sections and as a biochemical marker in serum in comparison with the standardized histomorphometric variables of osteoclasts. To this end we investigated 24 patients (21 women, 3 men; 60 +/- 17 years of age) affected with various metabolic bone diseases. Osteoclast surface (OcS/BS) and osteoclast number (OcN/BS) were evaluated by standardized histomorphometry in iliac crest biopsies. On the basis of TRAP cytochemical activity, TRAP-positive osteoclast surface (TRAP + OcS/BS) and number (TRAP + OcN/BS) were measured. TRAP-positive cells adjacent to bone and showing one nucleus or no nuclei at all in the plane of section were included in the counts as osteoclasts. Serum TRAP activity was determined by spectrophotometric assay. Values of OcS/BS and OcN/BS were much lower than those of TRAP + OcS/BS (-50%) and TRAP + OcN/BS (-60%), respectively. Correlations between OcS/BS and TRAP + OcS/BS, and between OcN/BS and TRAP + OcN/BS, were highly significant. Serum TRAP was significantly correlated with OcS/BS, OcN/BS, and TRAP + OcN/BS. These correlations, however, were rather low. Moreover, serum TRAP did not correlate with TRAP + OcS/BS. From these results, the conclusion can be drawn that while TRAP activity is confirmed as a valid cytochemical marker for identification of osteoclasts, serum TRAP activity is an osteoclastic marker of weak sensitivity. This may be due to known factors, such as synthesis of the enzyme not being unique to osteoclasts, enzyme instability, and the presence of inhibitors in serum. Mononucleated osteoclasts do not significantly influence the serum enzyme levels.
The aim of this study was to establish the duration and annual rate of menopause-related bone loss and to investigate the relationship between bone turnover and bone loss in early healthy ...postmenopausal women. The rate of change in bone mineral density (BMD) at the lumbar spine and in bone turnover was measured twice at the exact interval of 12 months by dual-energy X-ray absorptiometry (DXA) and by the determination of plasma alkaline phosphatase levels (ALP) and fasting urinary hydroxyproline/creatinine ratio (OHPr/Cr), respectively, in 123 healthy premenopausal and postmenopausal women 45-60 years of age. The subjects were divided into nine groups according to their menstrual status and years since menopause (YSM). Annual bone loss at the lumbar spine of women who were menopausal for 1, 2, 3, 4, and 5 years was -2.62 +/- 0.37 (95% confidence interval -3.66, -1.58), -3.87 +/- 0.96 (-6.02, -1.73), -2.50 +/- 0. 37 (-3.29, -1.70), -2.86 +/- 0.73 (-4.44, -1.27), and -1.54 +/- 0.41 (-2.42, -0.66), respectively, and was significantly less than zero. But, the annual bone loss of women who were premenopausal or menopausal for 6, 7, and 8 years was -0.76 +/- 0.60 (-2.04, +0.53), -1.16 +/- 0.68 (-2.61, +0.29), 0.24 +/- 0.48 (-0.78, +1.26), and 0. 16 +/- 0.63 (-1.18, -1.49), respectively, and was not significantly different from zero. These results demonstrate that the early hormone-dependent bone loss commences in the first year after menopause and is arrested within 6 years after the onset of menopause. The overall bone loss for this phase is estimated to be approximately 15%. Annual change in ALP and OHPr/Cr seems to indicate that bone resorption prevails on bone formation in the first 2 YSM, whereas osteoblastic activity relatively prevails from YSM 3 to YSM 5, which explains the progressive repairing of the imbalance between bone resorption and formation.
To assess how two different serum markers of bone resorption may reflect changes in bone turnover, we compared age- and sex-related changes in serum C-terminal telopeptide of type I collagen ...(betaCTx) and tartrate-resistant acid phosphatase activity (TRAP) in 136 healthy men and 184 normal women. Serum levels of the two markers were also assessed in several groups of patients of both sexes presenting with the most common metabolic and endocrine bone diseases: established osteoporosis (n = 77), primary hyperparathyroidism (n = 44), glucocorticoid excess (n = 17), chronic renal failure (n = 39), active Paget's disease of bone (n = 5), humoral hypercalcemia of malignancy (n = 3), osteomalacia (n = 3), hyperthyroidism (n = 10), post-surgical hypoparathyroidism (n = 10), acromegaly (active disease, n = 8) and Cushing's syndrome (n = 10). In men the regression of betaCTx with age showed an initial decrease in bone resorption followed by an increase thereafter, starting from the sixth decade of life. No age-related change in serum TRAP activity was observed. In women, by contrast, a slight but significant linear correlation of both serum betaCTx and TRAP with age (r = 0.223, p<0.003 and r = 0.333, p<0.0001, respectively) was found, the two markers being positively correlated (r = 0.238, p<0.002). In each class of patients the mean Z-scores of betaCTx were significantly higher than those of TRAP activity. Moreover, compared with normal subjects, serum betaCTx seems to be characterized by a superior sensitivity relative to TRAP measurement, at least in the disorders studied.
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