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Biomedical subjects

A G Visser

Publications and source records attributed to A G Visser.

At least 19 recordsLinked to original sources

An analysis of anatomic landmark mobility and setup deviations in radiotherapy for lung cancer.

PURPOSE: To identify thoracic structures that exhibit little internal motion during irradiation and to determine setup variations in patients with lung cancer. METHODS AND MATERIALS: Intrafractional images were generated with an electronic portal-imaging device from the AP fields of 10 patients, during several fractions. To determine the intrafractional mobility of thoracic structures, visible structures were contoured in every image and matched with a reference image by means of a cross-correlation algorithm. Setup variations were determined by comparing portal images with the digitized simulator films using the stable structures as landmarks. RESULTS: Mobility was limited in the lateral direction for the trachea, thoracic wall, paraspinal line, and aortic notch, and in the craniocaudal direction for the clavicle, aortic notch, and thoracic.wall. Analysis of patient setup revealed random deviations of 2.0 mm (1 SD) in the lateral direction and 2.8 mm in the craniocaudal direction, while the systematic deviations were 2.5 and 2.0 mm (1 SD) respectively. CONCLUSIONS: We have identified thoracic structures that exhibit little internal motion in the frontal plane, and recommend that these structures be used for verifying patient setup during radiotherapy. The daily variation in the setup of lung cancer patients at our center appears to be acceptable.

Humans

Inclusion of geometrical uncertainties in radiotherapy treatment planning by means of coverage probability.

PURPOSE: Following the ICRU-50 recommendations, geometrical uncertainties in tumor position during radiotherapy treatments are generally included in the treatment planning by adding a margin to the clinical target volume (CTV) to yield the planning target volume (PTV). We have developed a method for automatic calculation of this margin. METHODS AND MATERIALS: Geometrical uncertainties of a specific patient group can normally be characterized by the standard deviation of the distribution of systematic deviations in the patient group (Sigma) and by the average standard deviation of the distribution of random deviations (sigma). The CTV of a patient to be planned can be represented in a 3D matrix in the treatment room coordinate system with voxel values one inside and zero outside the CTV. Convolution of this matrix with the appropriate probability distributions for translations and rotations yields a matrix with coverage probabilities (CPs) which is defined as the probability for each point to be covered by the CTV. The PTV can then be chosen as a volume corresponding to a certain iso-probability level. Separate calculations are performed for systematic and random deviations. Iso-probability volumes are selected in such a way that a high percentage of the CTV volume (on average > 99%) receives a high dose (> 95%). The consequences of systematic deviations on the dose distribution in the CTV can be estimated by calculation of dose histograms of the CP matrix for systematic deviations, resulting in a so-called dose probability histogram (DPH). A DPH represents the average dose volume histogram (DVH) for all systematic deviations in the patient group. The consequences of random deviations can be calculated by convolution of the dose distribution with the probability distributions for random deviations. Using the convolved dose matrix in the DPH calculation yields full information about the influence of geometrical uncertainties on the dose in the CTV. RESULTS: The model is demonstrated to be fast and accurate for a prostate, cervix, and lung cancer case. A CTV-to-PTV margin size which ensures at least 95% dose to (on average) 99% of the CTV, appears to be equal to about 2Sigma + 0.7sigma for three all cases. Because rotational deviations are included, the resulting margins can be anisotropic, as shown for the prostate cancer case. CONCLUSION: A method has been developed for calculation of CTV-to-PTV margins based on the assumption that the CTV should be adequately irradiated with a high probability.

Female

Multiple two-dimensional versus three-dimensional PTV definition in treatment planning for conformal radiotherapy.

PURPOSE: To demonstrate the need for a fully three-dimensional (3D) computerized expansion of the gross tumour volume (GTV) or clinical target volume (CTV), as delineated by the radiation oncologist on CT slices, to obtain the proper planning target volume (PTV) for treatment planning according to the ICRU-50 recommendations. MATERIALS AND METHODS: For 10 prostate cancer patients two PTVs have been determined by expansion of the GTV with a 1.5 cm margin, i.e. a 3D PTV and a multiple 2D PTV. The former was obtained by automatically adding the margin while accounting in 3D for GTV contour differences in neighbouring slices. The latter was generated by automatically adding the 1.5 cm margin to the GTV in each CT slice separately; the resulting PTV is a computer simulation of the PTV that a radiation oncologist would obtain with (the still common) manual contouring in CT slices. For each patient the two PTVs were compared to assess the deviations of the multiple 2D PTV from the 3D PTV. For both PTVs conformal plans were designed using a three-field technique with fixed block margins. For each patient dose-volume histograms and tumour control probabilities (TCPs) of the (correct) 3D PTV were calculated, both for the plan designed for this PTV and for the treatment plan based on the (deviating) 2D PTV. RESULTS: Depending on the shape of the GTV, multiple 2D PTV generation could locally result in a 1 cm underestimation of the GTV-to-PTV margin. The deviations occurred predominantly in the cranio-caudal direction at locations where the GTV contour shape varies significantly from slice to slice. This could lead to serious underdosage and to a TCP decrease of up to 15%. CONCLUSIONS: A full 3D GTV-to-PTV expansion should be applied in conformal radiotherapy to avoid underdosage.

Humans

In vivo dosimetry for prostate cancer patients using an electronic portal imaging device (EPID); demonstration of internal organ motion.

PURPOSE: To investigate the use of a commercially available video-based EPID for in vivo dosimetry during treatment of prostate cancer patients. METHODS: For 10 prostate cancer patients, the inter-fraction variation within measured portal dose images (PDIs) was assessed and measured PDIs were compared with corresponding predicted PDIs based on the planning CT scan of the patient. RESULTS: For the lateral fields, the average standard deviation in the measured on-axis portal doses during the course of a treatment was 0.9%; for the anterior fields this standard deviation was 2.2%. The difference between the average on-axis measured portal dose and the predicted portal dose was 0.3+/-2.1% (1 SD) for the lateral fields and 0.7+/-3.4% (1 SD) for the anterior fields. Off-axis differences between measured and predicted portal doses were regularly much larger (up to 15%) and were caused by frequently occurring gas pockets inside the rectum of the patients during treatment or during acquisition of the planning CT scan. The detected gas pockets did sometimes extend into the gross tumour volume (GTV) area as outlined in the planning CT scans, implying a shift of the anterior rectum wall and prostate in the anterior direction (internal organ motion). CONCLUSIONS: The developed procedures for measurement and prediction of PDIs allow accurate dosimetric quality control of the treatment of prostate cancer patients. Comparing measured PDIs with predicted PDIs can reveal internal organ motion.

Follow-Up Studies

Accurate portal dose measurement with a fluoroscopic electronic portal imaging device (EPID) for open and wedged beams and dynamic multileaf collimation.

Measuring portal dose with an electronic portal imaging device (EPID) in external beam radiotherapy can be used to perform routine dosimetric quality control checks on linear accelerators and to verify treatments (in vivo dosimetry). An accurate method to measure portal dose images (PDIs) with a commercially available fluoroscopic EPID has been developed. The method accounts for (i) the optical 'cross talk' within the EPID structure, (ii) the spatially nonuniform EPID response and (iii) the nonlinearity of the EPID response. The method is based on a deconvolution algorithm. Measurement of the required input data is straightforward. The observed nonlinearity of the EPID response was largely due to the somewhat outdated EPID electronics. Nonlinearity corrections for more modern systems are expected to be smaller. The accuracy of the method was assessed by comparing PDIs measured with the EPID with PDIs measured with a scanning ionization chamber in a miniphantom, located at the same position as the fluorescent screen. For irradiations in open, wedged and intensity modulated 25 MV photon beams (produced with dynamic multileaf collimation) EPID and ionization chamber measurements agreed to within 1% (1 SD).

Fluoroscopy

Portal dose image (PDI) prediction for dosimetric treatment verification in radiotherapy. I. An algorithm for open beams.

A method is presented for calculation of transmission functions for high energy photon beams through patients. These functions are being used in our clinic for prediction of portal dose images (PDIs) which are compared with PDIs measured with an electronic portal imaging device (EPID). The calculations are based on the planning CT-scan of the patient and on the irradiation geometry as determined in the treatment planning process. For each beam quality, the required input data for the algorithm for transmission prediction are derived from a limited number of measured beam data. The method has been tested for a PDI-plane at 160 cm from the focus, in agreement with the fixed focus-to-detector distance of our fluoroscopic EPIDs. For 6, 23 and 25 MV photon beams good agreement (approximately 1%) has been found between calculated and measured transmissions through anthropomorphic phantoms.

Algorithms

Fractionated high-dose-rate brachytherapy in primary carcinoma of the nasopharynx.

PURPOSE: A growing body of data suggests that local control in nasopharyngeal cancer (NPC) is related to the radiation dose administered. We conducted a single-institution study of high-dose radiotherapy (RT), which incorporated high-dose-rate (HDR) brachytherapy (BT). These results were analyzed together with data obtained from controls who did not receive BT. PATIENTS AND METHODS: The BT group comprised 42 consecutive patients of whom 29 patients were staged according to the tumor, node, metastasis system as T1 through 3, 13 patients were T4, and 34 patients were N+ disease. BT was administered on an outpatient basis by means of a specially designed flexible nasopharyngeal applicator, and the dose distributions were optimized. Treatment for T1 through 3 tumors comprised 60 Gy of external-beam radiotherapy (ERT) followed by six fractions of 3 Gy BT (two fractions per day). Patients with parapharyngeal tumor extension and/or T4 tumors received 70 Gy ERT and four fractions of 3 Gy BT. The no-BT group consisted of all patients treated from 1965 to 1991 (n = 109), of whom 82 patients had stages T1 through 3, 27 patients had T4, and 80 patients had N+ disease. Multivariate Cox proportional hazards analyses were performed by using the end points time to local failure (TTLF), time to distant failure (TTDF), disease-free survival (DFS), cause-specific survival (CSS), and the prognostic factors age, tumor stage, node stage, and grade. Because the overall treatment time varied substantially in the no-BT group, the dependence of local failure (LF) on the physical dose as well as the biologic effective dose (BED) corrected for the overall treatment time (OTT) (BEDcor10) was studied. RESULTS: The BT group had a superior 3-year local relapse-free rate (86% v 60%; univariate analysis, P = .004). Multivariate analysis showed hazards ratios for BT versus no-BT of 0.24 for TTLF (P = .003), 0.35 for TTDF (P = .038), 0.31 for DFS (P < .001), and 0.44 for CSS (P = .01). The best prognostic group consisted of patients with T1 through 3, N0 through 2b tumors treated with BT who attained a 5-year TTLF of 94% and CSS of 91%. In contrast, the worst prognostic group, i.e., 5-year TTLF of 47% and CSS of 24%, was composed of patients with T4 and/or N2c through 3 tumors who did not receive BT. CONCLUSION: High doses of radiation (73 to 95 Gy) can be administered to patients with NPC with minimal morbidity by means of optimized HDR-BT. The use of a BT boost proved to be of significant benefit, particularly in patients with T1 through 3, N0 through 2b disease. The steep dose-effect relationship seen for the physical dose and the BEDcor10 indicates that the results are dose related. The analysis has identified a poor prognostic group in whom treatment intensification with chemotherapy (CHT) is indicated.

Adult

Fractionated high-dose-rate and pulsed-dose-rate brachytherapy: first clinical experience in squamous cell carcinoma of the tonsillar fossa and soft palate.

PURPOSE: Fractionated high-dose-rate (fr.HDR) and pulsed-dose-rate (PDR) brachytherapy (BT) regimens, which simulate classical continuous low-dose-rate (LDR) interstitial radiation therapy (IRT) schedules, have been developed for clinical use. This article reports the initial results using these novel schedules in squamous cell carcinoma (SCC) of the tonsillar fossa (TF) and/or soft palate (SP). METHODS AND MATERIALS: Between 1990 and 1994, 38 patients with TF and SP tumors (5 T1, 22 T2, 10 T3, and 1 T4) were treated by fr.HDR or PDR brachytherapy, either alone or in combination with external irradiation (ERT). Half of the patients were treated with fr.HDR, which entailed twice-daily fractions of > or = 3 Gy. The other 19 patients were administered PDR, which consisted of pulses of < or = 2 Gy delivered 4-8 times/day. The median cumulative dose of IRT +/- ERT series was 66 Gy (range 55-73). The results in these patients treated by brachytherapy were compared to 72 patients with similar tumors treated in our institute with curative intent, using ERT alone. The median cumulative dose of ERT-only series was 70 Gy (range 40-77). RESULTS: Excellent locoregional control was achieved with the use of IRT +/- ERT, with only 13% (5 of 38) developing local failure, and salvage surgery being possible in three of the latter (60%). Neither BT scheme (fr.HDR vs. PDR) nor tumor site (TF vs. SP) significantly influenced local control rates. The type and severity of the side effects observed are comparable to those reported in the literature for LDR-IRT. These results contrast sharply with our ERT-only series, in which 39% of patients (28 of 72) developed local failure, with surgical salvage being possible only in three patients (11%). Taking the data set of 110 patients, in a univariate analysis IRT, T stage, N stage, overall treatment time (OTT), and BEDcor10 (biological effective dose with a correction for the OTT) were significant prognostic factors for local relapse-free survival (LRFS) and overall survival (OS) at 3 years. Using Cox proportional hazard analysis, only T stage and BEDcor10 remained significant for LRFS (p < 0.001 and 0.008, respectively), as well as for OS (p < 0.001 and 0.003, respectively). With regard to the current (IRT) and historical (ERT) series, for the LRFS at 3 years, dose-response relationships were established, significant, however, only for the BEDcor10 (p = 0.03). CONCLUSION: The 3-year LRFS of approximately 90% for TF and SP tumors reported here is comparable with the best results in the literature, particularly given the fact that 30% of the patients (11 of 38) presented with T3/4 tumors. When compared with our historical (ERT-only) controls, the patients treated with IRT had superior local control. A dose-response relationship was established for the BEDcor10.

Brachytherapy

Spatial temperature control with a 27 MHz current source interstitial hyperthermia system.

PURPOSE: This article gives an overview of the properties of a 27 MHz current source interstitial hyperthermia system, affecting temperature uniformity. METHODS AND MATERIALS: Applicators can be inserted in standard flexible afterloading catheters. Maximum temperatures are measured with seven-point constantan-manganin thermocouple probes inside each applicator. Temperature can be controlled automatically using a simple control algorithm. Three-dimensional power absorption and thermal models for inhomogeneous tissues are available to optimize applicator geometry and phase configuration. Properties of the interstitial heating system have been verified both in phantom experiments and in in vivo treatments of rhabdomyosarcomas implanted in the flank of a rat. RESULTS: An experiment with four electrodes in one catheter proves that longitudinal control of the specific absorption rate (SAR) is feasible. Local cooling applied by cold water circulation through a catheter perpendicular to the afterloading catheter could be compensated by independent control of electrode power. Furthermore, comparison of two different phase configurations using four dual electrode applicators shows that the SAR distribution can be manipulated significantly, utilizing the phase of the electrodes. Finally, the temperature can be controlled safely and model calculations are in fair agreement with the measurements. CONCLUSIONS: The features of the 27 MHz current source interstitial hyperthermia system enable spatial temperature control at approximately 1.5 cm.

Animals

Reconstruction accuracy of a dedicated localiser for filmless planning in intra-operative brachytherapy.

BACKGROUND AND PURPOSE: With the use of HDR and PDR afterloaders containing a single stepping source, brachytherapy dose distributions can be optimised by varying the source dwell time. With the goal of implementing 'conformal brachytherapy', i.e. ensuring that the dose distribution conforms as accurately as possible to the target volume, we evaluated a set-up which enabled on-line implant localisation and dose planning during implantation. MATERIALS AND METHODS: The set-up, designated as an integrated brachytherapy unit (IBU), consists of a shielded operating room equipped with an HDR afterloader and a dedicated brachytherapy localiser connected to a treatment planning computer. The localiser is isocentric and has an extra degree of freedom in comparison to conventional simulators (i.e. an L-arm in combination with a C-arm) and enables viewing of the implant from any direction. A reconstruction algorithm which takes into account both rotation axes, i.e. the L-arm and C-arm angle, was developed for the localiser. The reconstruction procedure was tested by using the IBU localiser to measure the reconstruction accuracy with a phantom (containing 25 markers at well defined positions) and using reconstruction from radiographs. These results were compared to simulations where the accuracy of reconstruction was determined as a function of the reconstruction angle and the accuracy of read-outs of the localiser settings. On-line localisation and dose planning during implantation is based on filmless planning, i.e. fluoroscopy images and the corresponding localiser settings are imported into the treatment planning computer during implantation. The accuracy of filmless planning was determined using fluoroscopy images in the same set-up as for the experiments with the radiographs. The effect of reconstruction inaccuracies on the total irradiation time and the dose in target or normal tissue points was elucidated for clinically relevant implant geometries. The treatment plans of two phantoms based on reconstruction from films as well as fluoroscopy images were compared with plans for implants defined by exact co-ordinates. RESULTS: The average reconstruction error due to the accuracy of the read-out of the localiser settings varied between -0.18 and 0.24 mm, with a standard deviation (arising from digitisation errors) ranging from 0.11 to 0.22 mm. Using filmless reconstruction and the 10 inch field of view of the image intensifier (without applying correction for the geometric distortions) the average reconstruction error ranged from 0.01 to 0.65 mm, and the standard deviation ranged from 0.40 to 0.73 mm. These errors arose as a consequence of the finite pixel size and geometric distortions. These limited errors did not influence the treatment time for clinical implant geometries and had only a minor effect (<1%) on the dose in markers during filmless planning. CONCLUSION: This IBU set-up, with a dedicated brachytherapy localiser, allows for a rapid and accurate filmless planning procedure based on implant localisation from fluoroscopy images.

Brachytherapy

Design of applicators for a 27 MHz multielectrode current source interstitial hyperthermia system; impedance matching and effective power.

In interstitial heating one of the main requirements for achieving a certain elevated temperature in a tumour is that the effective power per applicator (Peff), i.e. the power which is actually deposited in the tissue, is sufficiently high. In this paper this requirement is discussed for the applicators of the 27 MHz multielectrode current source (MECS) interstitial hyperthermia (IHT) system. To minimize power reflection, the applicator impedance was matched with the generator impedance by adjusting the length of the coaxial cable in between. Transmission line losses, applicator efficiency and subsequently Peff were computed for several applicator types. The actual Peff per electrode was obtained from calorimetric measurements. Experiments with RC loads, which can be seen as perfect applicators, were performed to investigate the effect of mismatching on Peff. Applicator losses were measured for clinically used applicators, both single- and dual-electrode, utilizing saline phantoms. A simple spherical tumour model, using the effective heat conductivity (keff) to account for heat transport, was used to estimate Peff for a given tumour size, implant size and applicator density. Computations of Peff of various MECS-IHT electrodes were in close agreement with the phantom measurements. Most of the initial generator power was absorbed in the transmission line (60-65%). The efficiency of the applicators was about 65%. For both single- and dual-electrode applicators the effective electrode power was found to be about 1 W. Model calculations show that Peff of 1 W is sufficient to reach a minimum tumour temperature of 43 degrees C in well perfused tumours (keff = 3 W m-1 degree C-1), using a typical implant with 2 cm electrodes and 1.5 cm spacing. Mismatching can considerably affect Peff. Both a reduction to almost zero and a two-fold increase are possible. However, because the matching theory is well understood, mismatching is not a serious problem in clinical practice and can even be used to increase Peff if necessary. We conclude that the applicator design and the impedance matching method chosen in the MECS system allow heating to temperatures in the therapeutic range with implants used in clinical practice.

Biophysical Phenomena

High-precision prostate cancer irradiation by clinical application of an offline patient setup verification procedure, using portal imaging.

PURPOSE: To investigate in three institutions, The Netherlands Cancer Institute (Antoni van Leeuwenhoek Huis [AvL]), Dr. Daniel den Hoed Cancer Center (DDHC), and Dr, Bernard Verbeeten Institute (BVI), how much the patient setup accuracy for irradiation of prostate cancer can be improved by an offline setup verification and correction procedure, using portal imaging. METHODS AND MATERIALS: The verification procedure consisted of two stages. During the first stage, setup deviations were measured during a number (Nmax) of consecutive initial treatment sessions. The length of the average three dimensional (3D) setup deviation vector was compared with an action level for corrections, which shrunk with the number of setup measurements. After a correction was applied, Nmax measurements had to be performed again. Each institution chose different values for the initial action level (6, 9, and 10 mm) and Nmax (2 and 4). The choice of these parameters was based on a simulation of the procedure, using as input preestimated values of random and systematic deviations in each institution. During the second stage of the procedure, with weekly setup measurements, the AvL used a different criterion ("outlier detection") for corrective actions than the DDHC and the BVI ("sliding average"). After each correction the first stage of the procedure was restarted. The procedure was tested for 151 patients (62 in AvL, 47 in DDHC, and 42 in BVI) treated for prostate carcinoma. Treatment techniques and portal image acquisition and analysis were different in each institution. RESULTS: The actual distributions of random and systematic deviations without corrections were estimated by eliminating the effect of the corrections. The percentage of mean (systematic) 3D deviations larger than 5 mm was 26% for the AvL and the DDHC, and 36% for the BVI. The setup accuracy after application of the procedure was considerably improved (percentage of mean 3D deviations larger than 5 mm was 1.6% in the AvL and 0% in the DDHC and BVI), in agreement with the results of the simulation. The number of corrections (about 0.7 on the average per patient) was not larger than predicted. CONCLUSION: The verification procedure appeared to be feasible in the three institutions and enabled a significant reduction of mean 3D setup deviations. The computer simulation of the procedure proved to be a useful tool, because it enabled an accurate prediction of the setup accuracy and the required number of corrections.

Feasibility Studies

A quality control study of the accuracy of patient positioning in irradiation of pelvic fields.

PURPOSE: Determining and improving the accuracy of patient positioning in pelvic fields. METHODS AND MATERIALS: Small pelvic fields were studied in 16 patients treated for urological cancers using a three-field isocentric technique. Large pelvic fields were studied in 17 gynecological cancer patients treated with anterior and posterior (AP-PA) parallel opposed fields. Quantitative analysis of 645 megavolt images and comparison to 82 simulation images were carried out. RESULTS: Small pelvic fields: for the position of the patient in the field, standard deviations of the difference between simulation (SIM) and treatment (MV) images were 3.4 mm in the lateral direction, 5.3 mm in the cranio-caudal direction, and 4.8 mm in the ventro-dorsal direction. Alterations in the positioning technique were made and tested. Large pelvic fields: differences between simulation and treatment images for the position of the patient in the field were 4 mm [1 standard deviation (SD)] in the lateral direction and 6.5 mm in the cranio-caudal direction. A systematic shift of the treatment field in the cranial direction had occurred in the majority of patients. A positioning technique using laser lines and marking of the caudal field border was shown to be more accurate. CONCLUSIONS: Studies of positioning accuracy in routine irradiation techniques are needed to obtain data for definition of the margins for each treatment site at each institution. Random variations should be kept at a minimum by monitoring and improving positioning techniques. Treatment verification by megavolt imaging or film should be used to detect and correct systematic variations early in the treatment series.

Endometrial Neoplasms

Pulsed dose rate and fractionated high dose rate brachytherapy: choice of brachytherapy schedules to replace low dose rate treatments.

PURPOSE: Pulsed dose rate (PDR) brachytherapy is a new type of afterloading brachytherapy (BT) in which a continuous low dose rate (LDR) treatment is simulated by a series of "pulses," i.e., fractions of short duration (less than 0.5 h) with intervals between fractions of 1 to a few hours. At the Dr. Daniel den Hoed Cancer Center, the term "PDR brachytherapy" is used for treatment schedules with a large number of fractions (at least four per day), while the term "fractionated high dose rate (HDR) brachytherapy" is used for treatment schedules with just one or two brachytherapy fractions per day. Both treatments can be applied as alternatives for LDR BT. This article deals with the choice between PDR and fractionated HDR schedules and proposes possible fractionation schedules. METHODS AND MATERIALS: To calculate HDR and PDR fractionation schedules with the intention of being equivalent to LDR BT, the linear-quadratic (LQ) model has been used in an incomplete repair formulation as given by Brenner and Hall, and by Thames. In contrast to earlier applications of this model, both the total physical dose and the overall time were not kept identical for LDR and HDR/PDR schedules. A range of possible PDR treatment schedules is presented, both for booster applications (in combination with external radiotherapy (ERT) and for BT applications as a single treatment. Because the knowledge of both alpha/beta values and the half time for repair of sublethal damage (T 1/2), which are required for these calculations, is quite limited, calculations regarding the equivalence of LDR and PDR treatments have been performed for a wide range of values of alpha/beta and T 1/2. The results are presented graphically as PDR/LDR dose ratios and as ratios of the PDR/LDR tumor control probabilities. RESULTS: If the condition that total physical dose and overall time of a PDR treatment must be exactly identical to the values for the corresponding LDR treatment regimen is not applied, there appears to be less need for strong fractionation in PDR schedules. If the overall time is at least as long as that of the LDR schedule and if the total physical dose is (slightly) adapted, PDR schedules can be designed using longer pulse intervals of up to 3 h. Schedules with sufficiently long intervals have significant logistic advantages in terms of patient care and treatment tolerance. However, in general, PDR schedules that apply more fractionation have a lower risk of overdosing normal tissues in comparison to fractionated HDR schedules. Applying probable ranges for the values of alpha/beta and T 1/2, the model calculations indicate that the differences in effects between the proposed fractionated HDR and PDR schedules could be rather small. To detect the magnitude of these differences, (randomized) clinical studies with rather large patient groups might be needed. CONCLUSIONS: Pulsed dose rate treatment schedules with longer intervals of up to 3 h appear adequate to replace LDR treatment schedules. Whether PDR schedules can, indeed, replace LDR treatment schedules and whether they offer detectable advantages over schedules with less fractionation (fractionated HDR) should be tested in clinical studies.

Brachytherapy

Constraints in the use of repair half times and mathematical modelling for the clinical application of HDR and PDR treatment schedules as an alternative for LDR brachytherapy.

Using theoretical models based on radiobiological principles for the design of new treatment schedules for HDR and PDR brachytherapy, it is important to realise the impact of assumptions regarding the kinetics of repair. Extrapolations based on longer repair half times in a continuous LDR reference scheme may lead to the calculation of dangerously high doses for alternative HDR and PDR treatment schedules. We used the clinical experience obtained with conventional ERT and LDR brachytherapy in head and neck cancer as a clinical guideline to check the impact of the radiobiological parameters used. Biologically equivalent dose (BED) values for the in clinical practice of LDR brachytherapy recommended dose of 65-70 Gy (prescribed at a dose rate between 30-50 cGy/h) are calculated as a function of the repair half time. These BED values are compared with the biological effect of a clinical reference dose of conventional ERT with 2 Gy/day and complete repair between the fractions. From this comparison of LDR and ERT treatment schedules, a range of values for the repair half times of acute or late responding tissues is demarcated with a reasonable fit to the clinical data. For the acute effects (or tumor control) the best fits are obtained for repair half times of about 0.5 h, while for late effects the repair half times are at least 1 h and can be as high as 3 h. Within these ranges of repair half times for acute and late effects, the outcome of "alternative' HDR or PDR treatment schedules are discussed. It is predominantly the late reacting normal tissue with the longer repair half time for which problems will be encountered and no or only marginal gain is to be expected of decreasing the dose rate per pulse in PDR brachytherapy.

Brachytherapy

Physical characteristics of a commercial electronic portal imaging device.

An electronic portal imaging device (EPID) for use in radiotherapy with high energy photons has been under development since 1985 and has been in clinical use since 1988. The x-ray detector consists of a metal plate/fluorescent screen combination, which is monitored by a charge-coupled device (CDD)-camera. This paper discusses the physical quantities governing image quality. A model which describes the signal and noise propagation through the detector is presented. The predicted contrasts and signal-to-noise ratios are found to be in agreement with measurements based on the EPID images. Based on this agreement the visibility of low contrast structures in clinical images has been calculated with the model. Sufficient visibility of relevant structures (4-10 mm water-equivalent thickness) has been obtained down to a delivered dose of 4 cGy at dose maximum. It is found that the described system is not limited by quantum noise but by camera read-out noise. In addition we predict that with a new type of CCD sensor the signal-to-noise ratio can be increased by a factor of 5 at small doses, enabling high quality imaging, for most relevant clinical situations, with a patient dose smaller than 4 cGy. The latter system would be quantum noise limited.

Equipment Design

Portal dose measurement in radiotherapy using an electronic portal imaging device (EPID).

Physical characteristics of a commercially available electronic portal imaging device (EPID), relevant to dosimetric applications in high-energy photon beams, have been investigated. The EPID basically consists of a fluorescent screen, mirrors and a CCD camera. Image acquisition for portal dose measurement has been performed with a special procedure, written in the command language that comes with the system. The observed day-to-day variation in local EPID responses, i.e. measured grey scale value (EPID signal) per unit of delivered portal dose, is 0.4% (1 SD); day-to-day variation in relative EPID responses (e.g. normalized to the on-axis response) are within 0.2% (1 SD). Measured grey scale values are linearly proportional to transmitted portal doses with a proportionality constant which is independent of the thickness of a flat, water-equivalent absorber in the beam, but which does significantly depend on the size of the applied x-ray beam. It is shown that the observed increased in EPID response with increasing field size is mainly due to contributions to the EPID signals from scattered light: visible photons produced by the x-ray beam in a point of the fluorescent screen not only generate a grey scale value in the corresponding point of the EPID image, but also lead (due to scatter from components of the EPID structure onto the CCD chip) to an increased grey scale value at all other points of the image. A point spread function, derived from measured data and describing the increase in EPID response at the beam axis due to off-axis irradiation of the fluorescent screen, has been successfully applied to connect portal doses with grey scale values measured with the EPID.

Analysis of Variance