IORT Novac7: a new linear accelerator for electron beam therapy.
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Combined Modality Therapy↗
Biomedical subjects
M Benassi
Publications and source records attributed to M Benassi.
Dosimetric protocols in radiotherapy: a computer program.
A computer program to evaluate the dose to water in a specified point for low, medium and high energy photon and electron radiotherapeutic beams using different ionization chambers, phantom materials and new dosimetric standard protocols has been developed. The absorbed dose to air cavity calibration factors of the ionization chambers at the radiation quality, the updated physical quantities and dosimetric parameters are part of the data base, which is extendable to individual users' needs. Moreover, the management software permits comparison of different dosimetric protocols and reduction of errors on the dose delivered to patients.
Humans↗
Effect of cisplatin and c-myb antisense phosphorothioate oligodeoxynucleotides combination on a human colon carcinoma cell line in vitro and in vivo.
We investigated the effect of c-myb antisense phosphorothioate oligodeoxynucleotides [(S)ODNs] and cisplatin (CDDP) combination on the human colon carcinoma cell line LoVo Dx both in vitro and in nude mice bearing LoVo Dx solid tumour. We show that antisense (S)ODN treatment decreases c-myb mRNA and protein expression, induces growth arrest in the G1 phase of the cell cycle, and inhibits cell proliferation. In vivo treatment with c-myb antisense (S)ODNs results in a reduction in tumour growth. A greater inhibition of cell proliferation in vitro and a higher increase of tumour growth inhibition and growth delay in vivo were obtained with the combination of (S)ODNs and CDDP than when the two agents were administered separately. This comparative study, using the same tumour cell line in vitro and in vivo, suggests that c-myb antisense (S)ODNs might be useful in the therapy of colon cancer in combination with antineoplastic drugs.
Animals↗
Rhein enhances the effect of adriamycin on mitochondrial respiration by increasing antibiotic-membrane interaction.
The effect of the combination of Adriamycin (ADM) with rhein (RH), an anti-inflammatory drug, on the electron flow through site III and IV of the respiratory chain of rat liver mitochondria was investigated. RH, even at high concentrations, does not inhibit either duroquinol (DHQ) oxidation or cytochrome oxidase activity both of which are decreased by ADM in a dose-dependent manner. The analysis of interaction, performed with the isobolar method, shows a strong synergistic effect that cannot be ascribed to increased permeability of the mitochondrial membranes brought about by RH. The mechanism by which RH potentiates the effect of ADM on DHQ oxidation and cytochrome oxidase activity is most likely to be changes induced in the physical status of the inner mitochondrial membrane such as to permit low ADM concentrations to bind and segregate enough cardiolipin to inhibit electron transport through complex III and IV.
Animals↗
Study on the reference dose level in radiotherapy treatment planning.
PURPOSE: The reference dose level of the dose distribution in the tumor volume is studied. METHODS AND MATERIALS: The study is performed using a formula based on the Linear Quadratic (LQ) model. The calculated reference dose level to which the prescribed dose must be referred, for the eradication of a homogeneous tumor, is investigated by varying the dose distribution, that is, the dose volume histogram shape, its range, the prescribed total dose, the fraction size and the linear quadratic model parameters, alpha and beta. RESULTS: For all the simulated dose volume histograms the calculated reference dose level is lower than the mean dose level, depending on the range of dose variation and the considered tumor sensitivity. When the dose nonuniformity is not too great the reference dose level is very near to the mean dose level; when the inhomogeneity of dose distribution is high the reference level is clearly lower than the mean level but not necessarily equal to the minimum level in the tumor. For the dose volume histograms derived from the actual dose distributions obtained from a two tangential beams technique, a four beams technique and a moving beam technique, the reference levels are calculated and compared with the ICRU 29 reference point dose level. In two cases the reference levels are lower than the level at the ICRU 29 reference point. In the case of the four beams technique, the two levels are equal. CONCLUSION: These theoretical results show the possibility of administering the prescribed dose to a dose level higher than the minimum in the tumor, with the same value of Tumor Control Probability (TCP) as the one corresponding to a uniform tumor irradiation. The application of the proposed study can offer a general support to the choice of the reference dose level, based on the actual dose distribution in the tumor volume.
Humans↗
Magnetic resonance guided radiosurgery in children: tridimensional extrapolation from isodose neuroimaging superimposition.
In stereotactic radiosurgery, thin external beams of ionizing radiation concentrated in a single dose onto a sharply defined target are employed to treat lesions within the brain, avoiding doses which may produce unwanted damage to the surrounding healthy tissue. The dynamic irradiation technique used with the linear accelerator employs variable arcs of irradiation rotating around the isocenter of the target. The technique of stereotactic magnetic resonance (MR) guided radiosurgery is supported by a dedicated computerized system for treatment planning simulation. The system, based on a personal computer, allows the acquisition, reconstruction, and visualization of the target volume from MR images, and permits calculation and visualization of a three-dimensional dose distribution directly superimposed upon MR images of the lesion. The desired goal of destroying neoplastic tissue without damaging cerebral parenchyma is of particular importance in children. Consequently, adapting the three-dimensional isodose profiles to the morphology of the lesion to be treated is crucial. From this, the importance of the computer simulation is evident, as it permits one to go deeply into the study of isodose distribution, changing beam collimation, and the number and amplitude of arcs of irradiation.
Brain Neoplasms↗
A simple method to calculate the influence of dose inhomogeneity and fractionation in normal tissue complication probability evaluation.
PURPOSE: Since volumetric dose distributions are available with 3-dimensional radiotherapy treatment planning they can be used in statistical evaluation of response to radiation. This report presents a method to calculate the influence of dose inhomogeneity and fractionation in normal tissue complication probability evaluation. METHODS: The mathematical expression for the calculation of normal tissue complication probability has been derived combining the Lyman model with the histogram reduction method of Kutcher et al. [14] and using the normalized total dose (NTD) instead of the total dose. RESULTS: The fitting of published tolerance data, in case of homogeneous or partial brain irradiation, has been considered. For the same total or partial volume homogeneous irradiation of the brain, curves of normal tissue complication probability have been calculated with fraction size of 1.5 Gy and of 3 Gy instead of 2 Gy, to show the influence of fraction size. The influence of dose distribution inhomogeneity and alpha/beta value has also been simulated: considering alpha/beta = 1.6 Gy or alpha/beta = 4.1 Gy for kidney clinical nephritis, the calculated curves of normal tissue complication probability are shown. CONCLUSION: Combining NTD calculations and histogram reduction techniques, normal tissue complication probability can be estimated taking into account the most relevant contributing factors, including the volume effect.
Brain↗
Estimate of normal tissue damage in treatment planning for stereotactic radiotherapy.
A personal computer (PC) system was developed to perform treatment planning for radiosurgery and stereotactic radiotherapy. These techniques of irradiation of the brain may be accomplished with a linear accelerator by performing several non-coplanar arcs of a highly collimated beam focused at a fixed point. The PC system allows the acquisition, reconstruction and the visualization of the target volume from CT or MR images, and then it permits to calculate a three-dimensional (3-D) dose distribution due to small photon beams and to visualize it. The software calculates not only total dose distribution, administered fractionated or in single fraction, but also the NTD2 (normalized total dose) predicted to have a biological effect equivalent to the single irradiation. The choice of the best technique is supported by the dose volume histograms (DVH) calculation and by an estimate of complication probability to the brain normal tissue (NTCP). The algorithm for NTCP calculation is based on two models: the linear quadratic and the logistic. A comparison of three different dose calculations for a typical cerebral target volume is presented to demonstrate the system performances.
Algorithms↗
Thermal behavior of a human glioma cell line and its response to combinations of hyperthermia and lonidamine.
The effect of hyperthermia and lonidamine, alone and in combination, on the clonogenic activity of a human glioma cell line was investigated. The time-temperature relationship of asynchronous, exponentially growing cells was defined in the range of 40-45 degrees C. All survival curves were exponential and an Arrhenius plot for heat killing was linear over the temperature range tested, with an activation energy of 192 Kcal/mol. The survival curve of lonidamine-treated cells was also exponential after an initial shoulder. The analysis of the interaction between lonidamine and hyperthermia, performed by the isobolar method, demonstrated an additivity of response so that the effectiveness of the combined treatment was the result of two independent effects. Lonidamine inhibits the neoplastic growth mainly through an ATP depletion, but the thermal killing was not mediated by the drug-induced changes in the energy status of the cell. The effectiveness of the combined treatment was strongly influenced by the schedule of administration. In fact, the sequence lonidamine-->hyperthermia made the cells less sensitive to heat so that the pre-established end-point, i.e. 30% survival, was never achieved whichever combination was used. This "drug-induced heat resistance" was not associated with the induction of heat shock proteins, but rather with modification of cell cycle. On the contrary, showing a purely additive effect, the sequence hyperthermia-->lonidamine allowed achievement of the pre-established cell killing (70%), with exposure times (1-2 hr) and with a temperature (42 degrees C) generally accepted as clinically achievable. Therefore, also considering its low systemic toxicity, lonidamine may be useful in reducing the side effects of hyperthermia.
Antineoplastic Agents↗
Thermosensitization, heat shock protein synthesis and development of thermotolerance in M-14 human tumor cells subjected to step-down heating.
M-14 human tumor cells have been subjected to two regimens of step-down heating (SDH) consisting of a conditioning treatment at 42 degrees C for 1 h or at 44.5 degrees C for 20 min, immediately followed by heating at 40 degrees C. Both conditioning treatments thermosensitize the cells towards the subsequent heating at 40 degrees C; the thermosensitization ratio is 6.4 for cells conditioned at 42 degrees C for 1 h and 32.3 for cells conditioned at 44.5 degrees C for 20 min. The overall protein synthetic activity is reduced to 32.7% or 18.4% of control values following 1 h at 42 degrees C and 20 min at 44.5 degrees C, respectively; this inhibition is followed by a full recovery of the synthetic activity during the subsequent exposure at 40 degrees C. SDH-treated cells synthetize four heat shock proteins, with approximate molecular weights of 28, 64, 70 and 90 kDa. The pattern of HSPs induction observed in SDH-treated cells is similar to that found in cells subjected to single hyperthermic exposures. Cells subjected to the SDH sequence 42 degrees C/1 h-->40 degrees C/4 h develop thermotolerance, as indicated by a reduced sensitivity to further hyperthermic challenges.
Animals↗
Survival response of a human glioma cell line to hyperthermia associated with rhein.
The effect of association of hyperthermia with the anti-inflammatory drug rhein (RH), 4,5-dihydroxyanthraquinone-2-carboxylic acid, on the clonogenic activity of human glioma cells has been examined. RH inhibits neoplastic growth mainly through an ATP depletion, but thermal cell killing is not mediated by the drug-induced changes in the energy status of the cell. The analysis of the interaction between RH and hyperthermia, performed with the isobolar method, demonstrates an additivity of the response so that the effectiveness of the combined treatment is the result of two independent effects. Although the effect of this combination is purely additive, RH allows us to achieve a pre-established cell killing with exposure times at 42 degrees C, which is generally accepted to be clinically achievable. RH might, therefore, be employed to reduce the side effects of hyperthermia without impairing its therapeutic effectiveness.
Anthraquinones↗
Inhibition of membrane redox activity by rhein and adriamycin in human glioma cells.
The effect of the combination of adriamycin (ADM) with the anti-inflammatory drug rhein (RH) on the membrane redox activity in human glioma cells was investigated. RH, although less effective than ADM, inhibits ferricyanide reduction by human glioma cells in a dose-dependent manner as well as ferricyanide-induced proton release. The inhibition of the plasma membrane redox system might represent a further mechanism by which RH, other than ATP depletion, affects cell survival. The analysis of the interaction between ADM and RH, performed with the isobolar method, demonstrates a strong synergic response, probably due to an effect on different sites of action. The synergism of the ADM-RH association allows us to achieve a pre-established extent of inhibition with ADM concentrations much lower than with ADM alone. RH might, therefore, represent a very useful tool to improve the therapeutic index of ADM and to lower its general toxicity.
Anthraquinones↗
Ideal dose level in treatment planning optimization.
The biological response of the tumor is expressed in terms of tumor control probability (TCP) and its dependence on the inhomogeneous dose distribution throughout the tumor volume is studied. The ideal dose level to which the prescribed dose must be referred is derived, by employing a formula based on the linear quadratic model. To administer the prescribed dose to the ideal dose level renders the tumor control probability equal to that one corresponding to a uniform irradiation of the tumor. For the normal tissue irradiated a normal tissue complication probability index (NTCPI) is also defined and calculated. The comparison between NTCPIs of competing plans supports the optimization. In general the resulting ideal dose level is lower than the mean dose level, but not necessarily equal to the minimum in the tumor. This result shows the possibility of administering the prescribed dose to a dose level higher than the minimum, maintaining the tumor control probability at a good level and consequently lowering the complications to the normal tissue. The method offers a general support for the choice of the reference dose level and of the better technique. An example of application of the method is shown.
Humans↗
Effects of lonidamine on the membrane electrical properties of Ehrlich ascites tumor cells.
The effects of lonidamine on membrane electrical properties of Ehrlich ascites tumor cells are investigated. Using a dielectric relaxation technique based on the Maxwell-Wagner effect and elaborated by a 'single-shell' fitting procedure, the data indicate that both membrane conductivity and membrane permittivity increase after treatment of these cells with lonidamine while the conductivity of the cytosol remains unchanged. Changes in membrane proteins and/or lipids are suggested which lead to altered membrane structure and/or function.
Animals↗
Definitive radiation therapy for localized prostatic adenocarcinoma.
From 1974 to 1987, a total of 199 patients with prostatic carcinoma localized to the pelvis were treated with definitive external beam radiation therapy at the Istituto Medico e di Ricerca Scientifica. The median follow-up for all 126 surviving patients was 60 months. Actuarial 5-(and 10-) year overall survival rates for U.I.C.C. clinical Stage T1-2, T3 and T4 disease were 76.1% (58.5), 66% (42.5), and 27.6%, respectively. The corresponding 5- and 10-) year disease-specific survival rates were 81.7% (73), 72.5% (57.4), and 36.2%. The corresponding values of disease-free survival were 81.3% (76.8), 59.2% (57), and 17%, respectively. In 120 patients with more than 5 years of follow-up, local failure was seen alone in eight patients (6.6%) and associated with distant metastases in 19 patients (15.8%). In 28 patient (23.3%), distant metastases were observed alone. The median survival from the first evidence of metastases was 20 months, with no patient surviving beyond 5 years. The incidence of complications was acceptable. Serious complications, consisting of stenosis of both ureters and sigmoid colon requiring both urinary and intestinal diversion, occurred in two patients (1.3%). This study reveals that external radiotherapy is an efficacious and safe modality for locoregional control of prostate cancer.
Aged↗
One versus four heat treatments in combination with radiotherapy in metastatic mammary carcinoma.
To optimize the total and the weekly number of heat treatments to be combined with a conventional radiotherapy course, a study was designed on a 75-year-old woman with 40 cutaneous nodules of metastatic mammary carcinoma. All nodules were individually irradiated by means of orthovoltage radiation to doses of 36 to 44 Gy, given in 20 equal fractions in 4 weeks. The nodules were randomly assigned to receive radiotherapy alone or radiotherapy combined with one or four heat treatments. Eight lesions were left untreated as a control arm of the systemic therapy (endocrine manipulation). Hyperthermia at a minimum temperature of 43 degrees C was applied for 45 min once per week for four times or only once, during a course of radiotherapy. Percent mean diameter of the treated lesions continuously decreased, reaching a minimum of 25-30% of the initial value after 4 months from the beginning of treatment with no difference between the three arms. After this period, tumors treated with radiotherapy alone or radiotherapy plus one heat treatment started to regrow, whereas those treated with radiotherapy plus four heat treatments continued to decrease slowly. The actuarial analysis of freedom from local progression showed a trend of improvement of response duration with four hyperthermic treatments with respect to radiotherapy alone or combined with one hyperthermic treatment.
Aged↗
Practical experience in electromagnetic hyperthermia quality control procedures within the context of international guidelines.
Recent international guidelines on hyperthermia (HT) quality assurance have pointed out the necessity of defining standard operative procedures and technical checks to guarantee an accurate performance of HT treatments. In the present paper, experience is described of quality control procedures that are performed in agreement with the more general guidelines concerning thermometry, sensor positioning, phantoms, applicator characterisation, and electromagnetic (EM) radiation leakage. This practical experience comes from the use of equipment for superficial and loco-regional HT working in the range 13.56-915 MHz.
Evaluation Studies as Topic↗
[Intraoperative radiotherapy using electrons. Applicable software].
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Electrons↗