Ranald I Mackay

Prediction of the benefits from dose-escalated hypofractionated intensity-modulated radiotherapy for prostate cancer

PURPOSE To estimate the benefits of dose escalation in hypofractionated intensity-modulated radiotherapy (IMRT) for prostate cancer, using radiobiologic modeling and incorporating positional uncertainties of organs. MATERIALS AND METHODS Biologically based mathematical models for describing the relationships between tumor control probability (TCP) and normal-tissue complication probability (NTCP) vs. dose were used to describe some of the results available in the literature. The values of the model parameters were then used together with the value of 1.5 Gy for the prostate cancer alpha/beta ratio to predict the responses in a hypofractionated 3 Gy/fraction IMRT trial at the Christie Hospital, taking into account patient movement characteristics between dose fractions. RESULTS Compared with the current three-dimensional conformal radiotherapy technique (total dose of 50 Gy to the planning target volume in 16 fractions), the use of IMRT to escalate the dose to the prostate was predicted to increase the TCP by 5%, 16%, and 22% for the three dose levels, respectively, of 54, 57, and 60 Gy delivered using 3 Gy per fraction while keeping the late rectal complications (>/=Grade 2 RTOG scale) at about the same level of 5%. Further increases in TCP could be achieved by reducing the uncertainty in daily target position, especially for the last stage of the trial, where up to 6% further increase in TCP should be gained. CONCLUSIONS Dose escalation to the prostate using IMRT to deliver daily doses of 3 Gy was predicted to significantly increase tumor control without increasing late rectal complications, and currently this prediction is being tested in a clinical trial.

Shading correction algorithm for improvement of cone-beam CT images in radiotherapy

Cone-beam CT (CBCT) images have recently become an established modality for treatment verification in radiotherapy. However, identification of soft-tissue structures and the calculation of dose distributions based on CBCT images is often obstructed by image artefacts and poor consistency of density calibration. A robust method for voxel-by-voxel enhancement of CBCT images using a priori knowledge from the planning CT scan has been developed and implemented. CBCT scans were enhanced using a low spatial frequency grey scale shading function generated with the aid of a planning CT scan from the same patient. This circumvents the need for exact correspondence between CBCT and CT and the process is robust to the appearance of unshared features such as gas pockets. Enhancement was validated using patient CBCT images. CT numbers in regions of fat and muscle tissue in the processed CBCT were both within 1% of the values in the planning CT, as opposed to 10-20% different for the original CBCT. Visual assessment of processed CBCT images showed improvement in soft-tissue visibility, although some cases of artefact introduction were observed.

Quantitative analysis of patient-specific dosimetric IMRT verification

Patient-specific dosimetric verification methods for IMRT treatments are variable, time-consuming and frequently qualitative, preventing evidence-based reduction in the amount of verification performed. This paper addresses some of these issues by applying a quantitative analysis parameter to the dosimetric verification procedure. Film measurements in different planes were acquired for a series of ten IMRT prostate patients, analysed using the quantitative parameter, and compared to determine the most suitable verification plane. Film and ion chamber verification results for 61 patients were analysed to determine long-term accuracy, reproducibility and stability of the planning and delivery system. The reproducibility of the measurement and analysis system was also studied. The results show that verification results are strongly dependent on the plane chosen, with the coronal plane particularly insensitive to delivery error. Unexpectedly, no correlation could be found between the levels of error in different verification planes. Longer term verification results showed consistent patterns which suggest that the amount of patient-specific verification can be safely reduced, provided proper caution is exercised: an evidence-based model for such reduction is proposed. It is concluded that dose/distance to agreement (e.g., 3%/3 mm) should be used as a criterion of acceptability. Quantitative parameters calculated for a given criterion of acceptability should be adopted in conjunction with displays that show where discrepancies occur. Planning and delivery systems which cannot meet the required standards of accuracy, reproducibility and stability to reduce verification will not be accepted by the radiotherapy community.

The required number of treatment imaging days for an effective off-line correction of systematic errors in conformal radiotherapy of prostate cancer - A radiobiological analysis

BACKGROUND AND PURPOSE To use radiobiological modelling to estimate the number of initial days of treatment imaging required to gain most of the benefit from off-line correction of systematic errors in the conformal radiation therapy of prostate cancer. MATERIALS AND METHODS Treatment plans based on the anatomical information of a representative patient were generated assuming that the patient is treated with a multi leaf collimator (MLC) four-field technique and a total isocentre dose of 72 Gy delivered in 36 daily fractions. Target position variations between fractions were simulated from standard deviations of measured data found in the literature. Off-line correction of systematic errors was assumed to be performed only once based on the measured errors during the initial days of treatment. The tumour control probability (TCP) was calculated using the Webb and Nahum model. RESULTS Simulation of daily variations in the target position predicted a marked reduction in TCP if the planning target volume (PTV) margin was smaller than 4 mm (TCP decreased by 3.4% for 2 mm margin). The systematic components of target position variations had greater effect on the TCP than the random components. Off-line correction of estimated systematic errors reduced the decrease in TCP due to target daily displacements, nevertheless, the resulting TCP levels for small margins were still less than the TCP level obtained with the use of an adequate PTV margin of approximately 10 mm. The magnitude of gain in TCP expected from the correction depended on the number of treatment imaging days used for the correction and the PTV margin applied. Gains of 2.5% in TCP were estimated from correction of systematic errors performed after 6 initial days of treatment imaging for a 2 mm PTV margin. The effect of various possible magnitudes of systematic and random components on the gain in TCP expected from correction and on the number of imaging days required was also investigated. CONCLUSIONS Daily variations of target position markedly reduced the TCP if small margins were used. Off-line correction of systematic errors can only partly compensate for these TCP reductions. The adequate number of treatment imaging days required for systematic error correction depends on the magnitude of the random component compared with the systematic component, and on the size of PTV margin used. For random components equal to or smaller than the systematic component, 3 consecutive treatment imaging days are estimated to be sufficient to gain most of the benefit from correction for current clinically used margins (6-10 mm); otherwise more days are required.

A novel imaging technique for fusion of high-quality immobilised MR images of the head and neck with CT scans for radiotherapy target delineation

Uncertainty and inconsistency are observed in target volume delineation in the head and neck for radiotherapy treatment planning based only on CT imaging. Alternative modalities such as MRI have previously been incorporated into the delineation process to provide additional anatomical information. This work aims to improve on previous studies by combining good image quality with precise patient immobilisation in order to maintain patient position between scans. MR images were acquired using quadrature coils placed over the head and neck while the patient was immobilised in the treatment position using a five-point thermoplastic shell. The MR image and CT images were automatically fused in the Pinnacle treatment planning system using Syntegra software. Image quality, distortion and accuracy of the image registration using patient anatomy were evaluated. Image quality was found to be superior to that acquired using the body coil, while distortion was < 1.0 mm to a radius of 8.7 cm from the scan centre. Image registration accuracy was found to be 2.2 mm (+/- 0.9 mm) and < 3.0 degrees (n = 6). A novel MRI technique that combines good image quality with patient immobilization has been developed and is now in clinical use. The scan duration of approximately 15 min has been well tolerated by all patients.

Patient positioning using detailed three-dimensional surface data for patients undergoing conformal radiation therapy for carcinoma of the prostate: A feasibility study

PURPOSE The increasing complexity of radiotherapy highlights the need for accurate setup. This paper assesses the potential of position corrections, derived from the three-dimensional (3D) surface of the patient, in reducing positioning errors in patients undergoing conformal radiation therapy of the prostate. METHODS AND MATERIALS Twenty patients undergoing conformal radiation therapy for prostate cancer had planning computed tomography (CT) scans and then weekly treatment CT scans over the course of their treatment. Patients were positioned on the CT table using three coplanar tattoo marks used for patient setup on the accelerator. Surfaces were computed from the planning CT (planning surface), and the treatment CT (treatment surfaces). Using a surface matching utility, the planning and treatment 3D surfaces were compared. The prostate was implicitly localized based on surface matching of the external contour and by matching the bony anatomy. The resultant prostate displacement after correction was assessed for the two localization methods. RESULTS Correcting patient position via the surface comparisons reduced the standard deviation of prostate displacement with respect to the patient isocenter in the lateral and anterior/posterior directions. In the lateral direction, prostate and surface motion was highly correlated (r = 0.96). In the anterior/posterior direction the corrections from the surface data were as effective as those derived from the bony anatomy. CONCLUSION Detailed surface data can aid the positioning of patients receiving conformal radiation therapy to the prostate by reducing the displacement of the target from the intended treatment position. This study shows that surface corrections can be as effective as those derived from bony anatomy, and may be exploited where definition of bony anatomy is difficult.

A model to calculate the induced dose rate around an 18 MV ELEKTA linear accelerator

The dose rate due to activity induced by (gamma, n) reactions around an ELEKTA Precise accelerator running at 18 MV is reported. A model to calculate the induced dose rate for a variety of working practices has been derived and compared to the measured values. From this model, the dose received by the staff using the machine can be estimated. From measured dose rates at the face of the linear accelerator for a 10 x 10 cm2 jaw setting at 18 MV an activation coefficient per MU was derived for each of the major activation products. The relative dose rates at points around the linac head, for different energy and jaw settings, were measured. Dose rates adjacent to the patient support system and portal imager were also measured. A model to calculate the dose rate at these points was derived, and compared to those measured over a typical working week. The model was then used to estimate the maximum dose to therapists for the current working schedule on this machine. Calculated dose rates at the linac face agreed to within +/- 12% of those measured over a week, with a typical dose rate of 4.5 microSv h(-1) 2 min after the beam has stopped. The estimated maximum annual whole body dose for a treatment therapist, with the machine treating at only 18 MV, for 60000 MUs per week was 2.5 mSv. This compares well with value of 2.9 mSv published for a Clinac 21EX. A model has been derived to calculate the dose from the four dominant activation products of an ELEKTA Precise 18 MV linear accelerator. This model is a useful tool to calculate the induced dose rate around the treatment head. The model can be used to estimate the dose to the staff for typical working patterns.

Animation and radiobiological analysis of 3D motion in conformal radiotherapy

PURPOSE To allow treatment plans to be evaluated against the range of expected organ motion and set up error anticipated during treatment. METHODS Planning tools have been developed to allow concurrent animation and radiobiological analysis of three dimensional (3D) target and organ motion in conformal radiotherapy. Surfaces fitted to structures outlined on CT studies are projected onto pre-treatment images or onto megavoltage images collected during the patient treatment. Visual simulation of tumour and normal tissue movement is then performed by the application of three dimensional affine transformations, to the selected surface. Concurrent registration of the surface motion with the 3D dose distribution allows calculation of the change in dose to the volume. Realistic patterns of motion can be applied to the structure to simulate inter-fraction motion and set-up error. The biologically effective dose for the structure is calculated for each fraction as the surface moves over the course of the treatment and is used to calculate the normal tissue complication probability (NTCP) or tumour control probability (TCP) for the moving structure. The tool has been used to evaluate conformal therapy plans against set up measurements recorded during patient treatments. NTCP and TCP were calculated for a patient whose set up had been corrected after systematic deviations from plan geometry were measured during treatment, the effect of not making the correction were also assessed. RESULTS TCP for the moving tumour was reduced if inadequate margins were set for the treatment. Modelling suggests that smaller margins could have been set for the set up corrected during the course of the treatment. The NTCP for the rectum was also higher for the uncorrected set up due to a more rectal tissue falling in the high dose region. CONCLUSION This approach provides a simple way for clinical users to utilise information incrementally collected throughout the whole of a patients treatment. In particular it is possible to test the robustness of a patient plan against a range of possible motion patterns. The methods described represent a move from the inspection of static pre-treatment plans to a review of the dynamic treatment.

Technologies for Delivery of Proton and Ion Beams for Radiotherapy

Recent developments for the delivery of proton and ion beam therapy have been significant, and a number of technological solutions now exist for the creation and utilisation of these particles for the treatment of cancer. In this paper we review the historical development of particle accelerators used for external beam radiotherapy and discuss the more recent progress towards more capable and cost-effective sources of particles.

Modelling the throughput capacity of a single-accelerator multitreatment room proton therapy centre

OBJECTIVE We describe a model for evaluating the throughput capacity of a single-accelerator multitreatment room proton therapy centre with the aims of (1) providing quantitative estimates of the throughput and waiting times and (2) providing insight into the sensitivity of the system to various physical parameters. METHODS A Monte Carlo approach was used to compute various statistics about the modelled centre, including the throughput capacity, fraction times for different groups of patients and beam waiting times. A method of quantifying the saturation level is also demonstrated. RESULTS Benchmarking against the MD Anderson Cancer Center showed good agreement between the modelled (140 ± 4 fractions per day) and reported (133 ± 35 fractions per day) throughputs. A sensitivity analysis of that system studied the impact of beam switch time, the number of treatment rooms, patient set-up times and the potential benefit of having a second accelerator. Finally, scenarios relevant to a potential UK facility were studied, finding that a centre with the same four-room, single-accelerator configuration as the MD Anderson Cancer Center but handling a more complex UK-type caseload would have a throughput reduced by approximately 19%, but still be capable of treating in excess of 100 fractions per 16-h treatment day. CONCLUSIONS The model provides a useful tool to aid in understanding the operating dynamics of a proton therapy facility, and for investigating potential scenarios for prospective centres. ADVANCES IN KNOWLEDGE The model helps to identify which technical specifications should be targeted for future improvements.