Per Engström

Acceptance tests and quality control (QC) procedures for the clinical implementation of intensity modulated radiotherapy (IMRT) using inverse planning and the sliding window technique: experience from five radiotherapy departments

BACKGROUND AND PURPOSE An increasing number of radiotherapy centres is now aiming for clinical implementation of intensity modulated radiotherapy (IMRT), but--in contrast to conventional treatment--no national or international guidelines for commissioning of the treatment planning system (TPS) and acceptance tests of treatment equipment have yet been developed. This paper bundles the experience of five radiotherapy departments that have introduced IMRT into their clinical routine. METHODS AND MATERIALS The five radiotherapy departments are using similar configurations since they adopted the commercially available Varian solution for IMRT, regarding treatment planning as well as treatment delivery. All are using the sliding window technique. Different approaches towards the derivation of the multileaf collimator (MLC) parameters required for the configuration of the TPS are described. A description of the quality control procedures for the dynamic MLC, including their respective frequencies, is given. For the acceptance of the TPS for IMRT multiple quality control plans were developed on a variety of phantoms, testing the flexibility of the inverse planning modules to produce the desired dose pattern as well as assessing the accuracy of the dose calculation. Regarding patient treatment verification, all five centres perform dosimetric pre-treatment verification of the treatment fields, be it on a single field or on a total plan procedure. During the actual treatment, the primary focus is on patient positioning rather than dosimetry. Intracavitary in vivo measurements were performed in special cases. RESULT AND CONCLUSION The configurational MLC parameters obtained through different methods are not identical for all centres, but the observed variations have shown to be of no significant clinical relevance. The quality control (QC) procedures for the dMLC have not detected any discrepancies since their initiation, demonstrating the reliability of the MLC controller. The development of geometrically simple QC plans to test the inverse planning, the dynamic MLC modules and the final dose calculation has proven to be useful in pointing out the need to remodel the single pencil beam scatter kernels in some centres. The final correspondence between calculated and measured dose was found to be satisfactory by all centres, for QC test plans as well as for pre-treatment verification of clinical IMRT fields. An intercomparison of the man hours needed per patient plan verification reveals a substantial variation depending on the type of measurements performed.

MAGIC-type polymer gel for three-dimensional dosimetry: Intensity-modulated radiation therapy verification

A new type of polymer gel dosimeter, which responds well to absorbed dose even when manufactured in the presence of normal levels of oxygen, was recently described by Fong et al. [Phys. Med. Biol. 46, 3105-3113 (2001)] and referred to by the acronym MAGIC. The aim of this study was to investigate the feasibility of using this new type of gel for intensity-modulated radiation therapy (IMRT) verification. Gel manufacturing was carried out in room atmosphere under normal levels of oxygen. IMRT inverse treatment planning was performed using the Helios software. The gel was irradiated using a linear accelerator equipped with a dynamic multileaf collimator, and intensity modulation was achieved using sliding window technique. The response to absorbed dose was evaluated using magnetic resonance imaging. Measured and calculated dose distributions were compared with regard to in-plane isodoses and dose volume histograms. In addition, the spatial and dosimetric accuracy was evaluated using the gamma formalism. Good agreement between calculated and measured data was obtained. In the isocenter plane, the 70% and 90% isodoses acquired using the different methods are mostly within 2 mm, with up to 3 mm disagreement at isolated points. For the planning target volume (PTV), the calculated mean relative dose was 96.8 +/- 2.5% (1 SD) and the measured relative mean dose was 98.6 +/- 2.2%. Corresponding data for an organ at risk was 34.4 +/- 0.9% and 32.7 +/- 0.7%, respectively. The gamma criterion (3 mm spatial/3% dose deviation) was fulfilled for 94% of the pixels in the target region. Discrepancies were found in hot spots the upper and lower parts of the PTV, where the measured dose was up to 11% higher than calculated. This was attributed to sub optimal scatter kernels used in the treatment planning system dose calculations. Our results indicate great potential for IMRT verification using MAGIC-type polymer gel.

The feasibility of using Pareto fronts for comparison of treatment planning systems and delivery techniques

Pareto optimality is a concept that formalises the trade-off between a given set of mutually contradicting objectives. A solution is said to be Pareto optimal when it is not possible to improve one objective without deteriorating at least one of the other. A set of Pareto optimal solutions constitute the Pareto front. The Pareto concept applies well to the inverse planning process, which involves inherently contradictory objectives, high and uniform target dose on one hand, and sparing of surrounding tissue and nearby organs at risk (OAR) on the other. Due to the specific characteristics of a treatment planning system (TPS), treatment strategy or delivery technique, Pareto fronts for a given case are likely to differ. The aim of this study was to investigate the feasibility of using Pareto fronts as a comparative tool for TPSs, treatment strategies and delivery techniques. In order to sample Pareto fronts, multiple treatment plans with varying target conformity and dose sparing of OAR were created for a number of prostate and head & neck IMRT cases. The DVHs of each plan were evaluated with respect to target coverage and dose to relevant OAR. Pareto fronts were successfully created for all studied cases. The results did indeed follow the definition of the Pareto concept, i.e. dose sparing of the OAR could not be improved without target coverage being impaired or vice versa. Furthermore, various treatment techniques resulted in distinguished and well separated Pareto fronts. Pareto fronts may be used to evaluate a number of parameters within radiotherapy. Examples are TPS optimization algorithms, the variation between accelerators or delivery techniques and the degradation of a plan during the treatment planning process. The issue of designing a model for unbiased comparison of parameters with such large inherent discrepancies, e.g. different TPSs, is problematic and should be carefully considered. fc

Studies of in vivo electropermeabilization by gamma camera measurements of (99m)Tc-DTPA

A protocol was developed to study the drug uptake from in vivo electropermeabilization at different settings of parameters influencing the uptake efficiency. Radiolabelled diethylenetriaminepentaacetic acid (DTPA) was used to trace the distribution and internalization of a hydrophilic drug after in vivo electropermeabilization. Skeletal muscle tissue in rat was treated with permeabilizing electric pulses before or after intravenous administration of (99m)Tc-DTPA. The drug accumulation in the treated volume was subsequently evaluated with a scintillation camera. The dependence of uptake on field strength and duration of the applied electric pulses was investigated for exponentially decaying pulses and square wave pulses. Further, the uptake dependence on time interval between injection and pulsation was studied as well as the uptake dependence on the number of pulses applied in a single electropermeabilization treatment. Dynamic gamma camera studies were performed to quantify the time scale of the drug uptake in electropermeabilized tissue.

In vivo dose verification of IMRT treated head and neck cancer patients

An independent in vivo dose verification procedure for IMRT treatments of head and neck cancers was developed. Results of 177 intracavitary TLD measurements from 10 patients are presented. The study includes data from 10 patients with cancer of the rhinopharynx or the thyroid treated with dynamic IMRT. Dose verification was performed by insertion of a flexible naso-oesophageal tube containing TLD rods and markers for EPID and simulator image detection. Part of the study focussed on investigating the accuracy of the TPS calculations in the presence of inhomogeneities. Phantom measurements and Monte Carlo simulations were performed for a number of geometries involving lateral electronic disequilibrium and steep density shifts. The in vivo TLD measurements correlated well with the predictions of the treatment planning system with a measured/calculated dose ratio of 1.002±0.051 (1 SD, N = 177). The measurements were easily performed and well tolerated by the patients. We conclude that in vivo intracavitary dosimetry with TLD is suitable and accurate for dose determination in intensity-modulated beams.

Dynamic gamma camera studies of 111In–bleomycin complex in normal and glioma bearing rats after in vivo electropermeabilization using exponential high-voltage pulses

Abstract This study reports a non-invasive technique to continuously study the uptake and retention of radiopharmaceuticals after in vivo electropermeabilization in tumour bearing rats. A gamma camera was used for a dynamic visualisation of 111 In -labelled bleomycin in tumour and normal tissue in rats treated with electrochemotherapy (ECT). The advantages of a continuous in vivo monitoring of radiolabelled drugs are the possibilities to give a non-invasive, relative quantification of the electropermeabilization effect and to optimise parameters influencing the electropermeabilization treatment efficiency. Fischer-344 rats with N32 glioma tumours implanted subcutaneously on the thigh were used. 111 In –bleomycin complex ( 111 In–BLMC ) was given intravenously as a bolus injection and internalised by local electropermeabilization. ECT using exponential pulses was performed on the 4th and the 7th min after drug administration using external rectangular electrodes covering the tumour on the leg. From a series of whole-body gamma camera measurements, the drug uptake and clearance of the tumour and selected regions of the body were followed over a period up to 10 days. The gamma camera study showed that among the tumour bearing animals, the group treated with 111 In–BLMC followed by electropermeabilization resulted in a very high drug retention in the tumour area and a six to 10 fold increase in tumour uptake compared to those given 111 In–BLMC only. The in vivo stability of the 111 In–BLMC was also proven when compared with gamma camera studies of 111 InCl 3 .

Conversion of helical tomotherapy plans to step-and-shoot IMRT plans--Pareto front evaluation of plans from a new treatment planning system.

PURPOSE The resulting plans from a new type of treatment planning system called SharePlan have been studied. This software allows for the conversion of treatment plans generated in a TomoTherapy system for helical delivery, into plans deliverable on C-arm linear accelerators (linacs), which is of particular interest for clinics with a single TomoTherapy unit. The purpose of this work was to evaluate and compare the plans generated in the SharePlan system with the original TomoTherapy plans and with plans produced in our clinical treatment planning system for intensity-modulated radiation therapy (IMRT) on C-arm linacs. In addition, we have analyzed how the agreement between SharePlan and TomoTherapy plans depends on the number of beams and the total number of segments used in the optimization. METHODS Optimized plans were generated for three prostate and three head-and-neck (H&N) cases in the TomoTherapy system, and in our clinical treatment planning systems (TPS) used for IMRT planning with step-and-shoot delivery. The TomoTherapy plans were converted into step-and-shoot IMRT plans in SharePlan. For each case, a large number of Pareto optimal plans were created to compare plans generated in SharePlan with plans generated in the Tomotherapy system and in the clinical TPS. In addition, plans were generated in SharePlan for the three head-and-neck cases to evaluate how the plan quality varied with the number of beams used. Plans were also generated with different number of beams and segments for other patient cases. This allowed for an evaluation of how to minimize the number of required segments in the converted IMRT plans without compromising the agreement between them and the original TomoTherapy plans. RESULTS The plans made in SharePlan were as good as or better than plans from our clinical system, but they were not as good as the original TomoTherapy plans. This was true for both the head-and-neck and the prostate cases, although the differences between the plans for the latter were small. The evaluation of the head-and-neck cases also showed that the plans generated in SharePlan were improved when more beams were used. The SharePlan Pareto front came close to the front for the TomoTherapy system when a sufficient number of beams were added. The results for plans generated with varied number of beams and segments demonstrated that the number of segments could be minimized with maintained agreement between SharePlan and TomoTherapy plans when 10-19 beams were used. CONCLUSIONS This study showed (using Pareto front evaluation) that the plans generated in Share-Plan are comparable to plans generated in other TPSs. The evaluation also showed that the plans generated in SharePlan could be improved with the use of more beams. To minimize the number of segments needed in a plan with maintained agreement between the converted IMRT plans and the original TomoTherapy plans, 10-19 beams should be used, depending on target complexity. SharePlan has proved to be useful and should thereby be a time-saving complement as a backup system for clinics with a single TomoTherapy system installed alongside conventional C-arm linacs.

EFFECT OF HIGH VOLTAGE PULSES ON SURVIVAL OF CHINESE HAMSTER V79 LUNG FIBROBLAST CELLS

The objective is to study the effect of high voltage pulses on living cells to find the most effective combination of physical parameters to be used in tumour therapy. Four parameters that affect the cell survival are the pulse shape, electric field strength, pulse length and the number of pulses and their cell killing effect were investigated in this work. High voltage square wave or exponentially decaying pulses was applied to V79 lung fibroblast cells in suspension with 106 cells per ml at room temperature after 5 min of acclimatisation in a vial with electrodes. For eight exponential decaying pulses with a pulse length of 1 ms, 50% reduction in cell survival is achieved around 850 V/cm. For eight square wave pulses generated by the BTX820, the corresponding electric field strength is 820 V/cm. Using square wave pulses generated by the Dialog device, the largest reduction in cell survival was achieved at electric field strength of 2400 V/cm resulting in 60% cell survival. At low electric field strengths of about 600 V/cm, very long pulses of several ms are required to kill the cells. However, at high field strengths of about 1200 V/cm short pulses of 0.1 ms kill 50% of the cells. Treatment performed with different number of pulses at field strength show an effective killing at about 8 pulses. Copyright (C) 1998 Elsevier Science S.A. (Less)

Haematological toxicity in adult patients receiving craniospinal irradiation – Indication of a dose-bath effect

BACKGROUND AND PURPOSE The purpose of this study was to investigate the correlation between the haematological toxicity observed in patients treated with craniospinal irradiation, and the dose distribution in normal tissue, specifically the occurrence of large volumes exposed to low dose. MATERIALS AND METHODS Twenty adult male patients were included in this study; eight treated with helical tomotherapy (HT), and twelve with three-dimensional conformal radiation therapy. The relative volume of red bone marrow and body that was exposed to low dose (i.e. the so-called dose bath) was evaluated and correlated with nadir blood values during treatment, i.e. the severity of anaemia, leukopaenia, and thrombocytopaenia. The correlation was tested for different dose levels representing the dose bath using the Pearson product-moment correlation method. RESULTS We found a significant correlation between the volume of red bone marrow exposed to low dose and the severity of thrombocytopaenia during treatment. Furthermore, for the HT patients, a significant correlation was found between the relative volume of the body exposed to low dose and the severity of anaemia and leukopenia. CONCLUSIONS The severity of haematological toxicity correlated with the fraction of red bone marrow or body that was exposed to low dose.

Monte Carlo study of TLD measurements in air cavities

Thermoluminescent dosimeters (TLDs) are used for verification of the delivered dose during IMRT treatment of head and neck carcinomas. The TLDs are put into a plastic tube, which is placed in the nasal cavities through the treated volume. In this study, the dose distribution to a phantom having a cylindrical air cavity containing a tube was calculated by Monte Carlo methods and the results were compared with data from a treatment planning system (TPS) to evaluate the accuracy of the TLD measurements. The phantom was defined in the DOSXYZnrc Monte Carlo code and calculations were performed with 6 MV fields, with the TLD tube placed at different positions within the cylindrical air cavity. A similar phantom was defined in the pencil beam based TPS. Differences between the Monte Carlo and the TPS calculations of the absorbed dose to the TLD tube were found to be small for an open symmetrical field. For a half-beam field through the air cavity, there was a larger discrepancy. Furthermore, dose profiles through the cylindrical air cavity show, as expected, that the treatment planning system overestimates the absorbed dose in the air cavity. This study shows that when using an open symmetrical field, Monte Carlo calculations of absorbed doses to a TLD tube in a cylindrical air cavity give results comparable to a pencil beam based treatment planning system.