Step-and-Shoot IMRT by Siemens Beams: An EPID Dosimetry Verification During Treatment.

PURPOSE: This work reports the extension of a semiempirical method based on the correlation ratios to convert electronic portal imaging devices transit signals into in vivo doses for the step-and-shoot intensity-modulated radiotherapy Siemens beams. The dose reconstructed at the isocenter point Diso, compared to the planned dose, Diso,TPS, and a γ-analysis between 2-dimensional electronic portal imaging device images obtained day to day, seems to supply a practical method to verify the beam delivery reproducibility. METHOD: The electronic portal imaging device images were obtained by the superposition of many segment fields, and the algorithm for the Diso reconstruction for intensity-modulated radiotherapy step and shoot was formulated using a set of simulated intensity-modulated radiotherapy beams. Moreover, the in vivo dose-dedicated software was integrated with the record and verify system of the centers. RESULTS: Three radiotherapy centers applied the in vivo dose procedure at 30 clinical intensity-modulated radiotherapy treatments, each one obtained with 5 or 7 beams, and planned for patients undergoing radiotherapy for prostatic tumors. Each treatment beam was checked 5 times, obtaining 900 tests of the ratios R = Diso/Diso,TPS. The average R value was equal to 1.002 ± 0.056 (2 standard deviation), while the mean R value for each patient was well within 5%, once the causes of errors were removed. The γ-analysis of the electronic portal imaging device images, with 3% 3 mm acceptance criteria, showed 90% of the tests with Pγ < 1 ≥ 95% and γmean ≤ 0.5. The off-tolerance tests were found due to incorrect setup or presence of morphological changes. This preliminary experience shows the great utility of obtaining the in vivo dose results in quasi real time and close to the linac, where the radiotherapy staff may immediately spot possible causes of errors. The in vivo dose procedure presented here is one of the objectives of a project, for the development of practical in vivo dose procedures, financially supported by the Istituto Nazionale di Fisica Nucleare.

Film-densitometric verification of the Hogstrom algorithm used in "PLATO" treatment planning system (TPS).

We consider dose distributions in suitable homogeneous and inhomogeneous phantoms irradiated with electron beams at a fixed energy (11MeV). Dose distributions were obtained by film densitometry on Kodak X-Omat V film, and compared to corresponding distributions computed by means of the Hogstrom algorithm, included in PLATO TPS by Nucletron. Principal critical points found when checking the algorithm, which could be significant in clinical practice, are briefly discussed.

A treatment planning system for stereotactic radiotherapy.

Stereotactic radiotherapy to treat neoplastic lesions or artero-venus malformations in the brain may be accomplished with a linear accelerator by performing several non-coplanar arcs of irradiation with a highly collimated beam focused on a fixed point. This paper introduces a system to perform treatment planning. It is based on a Personal Computer and allows the acquisition, reconstruction and visualization of the target volume, within the brain, from CT (Computerized Tomography) or MR (Magnetic Resonance) images, and then it permits calculation and visualization of a 3-D (three-dimensional) dose distribution due to small photon beams. The performances of the system and its use in a practical case are described.

Clinical modulation of epirubicin resistance by lonidamine in patients with advanced soft-tissue sarcomas.

To determine if lonidamine (LND) could reverse anthracycline resistance In patients with advanced, soft-tissue sarcomas, thirty-six patients were treated with epirubicin (EPI) 120 mg/m(2) i.v. every 3 weeks. Progressive patients were given the same chemotherapy regimen on day 4 in combination with oral LND, 150 mg on day 1, 300 mg on day 2, and 450 mg on days 3 to 5. Among 35 evaluable patients there were 2 complete responses and 3 partial responses (PR) for an overall response rate of 14%. In the group treated with EPI+LND (24 evaluable patients) 2 PR were observed, lasting 3 and 10 months respectively. The overall survivall was 11.5 months. The most common side-effects were myelotoxicity, nausea and vomiting. Clinical cardiotoxicity was. not observed. Only in one patient a >20% decrease in LVEF from baseline was recorded. LND related toxicities were mild to moderate myalgia and photophobia. In a pharmacokinetic study performed parallel to the clinical study, no difference was observed between the parameters derived from EPI and EPI+LND curves except for Vapp. This study indicates that LND may circumvent clinical resistance in some cases without altering chemotherapy related toxicity.

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.

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.

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.

Invivo control of tumor-growth with the association of ionidamine with radiation and or hyperthermia.

The effect of lonidamine (LND) in association with fractionated doses of radiation and/or hyperthermia on tumor growth has been evaluated. The results may be summarized as follows: (i) the fractionation of the radiation dose, in spite of the higher dose delivered (20 Gy) does not increase tumor growth delay when compared to that obtained with a single irradiation treatment. A similar behaviour was also found when the fractionated irradiation was associated with LND. (ii) Hyperthermia is less effective than radiation in controlling tumor growth, but its effect is potentiated by LND although to a lesser extent that with radiation. (iii) LND delivered together with hyperthermia and radiation arrests tumor growth, and leads to the disappearance of the tumor in 75% of mice. The possible mechanisms underlying these effects are discussed.

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.

Interaction of cytotoxic agents: a rule-based system for computer-assisted cell survival analysis.

The actual effectiveness of environmental noxious agents or anticancer drugs can be fully determined only by knowing if the effects (in the present case, the cytotoxic effects) induced by a given agent are enhanced by exposure to another (or other) agent(s). Given a certain combination of agents, it is possible to distinguish three types of interaction: (a) zero interaction or additivity; (b) positive interaction or synergism; and (c) negative interaction or antagonism. In this work, the methodological problems involved in evaluating the type and level of interaction between biologically active agents are discussed and an "intelligent" approach to the problem is proposed. In particular, a prototype of a computer-assisted rule based system, named CISA (Cytotoxic Interaction and Survival Analysis), designed in a KES environment (Knowledge Engineering System) and implemented on a personal computer, is described. By constructing isoboles based on experimental cell survival data and taking into account the relative confidence intervals, the system can indicate the appropriate combinations of dosages to be tested and finally determine the type and level of interaction. The system, which represents an attempt to administer "intelligently" the experimental data, is therefore able to identify the best strategy of analysis, to carry out the data processing and to offer suggestions to the investigator about the usefulness of the data and the planning of further experiments.

A simulation model for tumor growth controlled by therapeutic agents.

Results obtained in a controlled tumor growth depend on the experimental model used, the agent employed (drugs, ionizing radiations, heat), aw well as the administration scheduling and the host environment. Empirical search and treatment optimization are related to a discrete number of agent combinations and fractioning, and system parameters and dependencies are strictly connected to biological assumptions. A simplified model for the evaluation of the rate of change of tumor volume at the time of cytotoxic agent administration is proposed here, as well as a computer program to perform the simulation of tumor growth controlled by therapeutic agents.