Mike Partridge

A cone-beam megavoltage CT scanner for treatment verification in conformal radiotherapy

PURPOSE A prototype scanner for large-volume megavoltage computed tomography (MVCT) in a clinical set-up is described. The ultimate aim is to improve treatment accuracy in conformal radiotherapy through patient set-up error reduction and transit dosimetry. MATERIALS AND METHODS The scanner consists of a custom-built 2D CsI(Tl) crystal array viewed by a lens and a CCD camera. Image acquisition is synchronized with radiation pulses. The 2D projections resulting from a single continuous 360 degrees gantry rotation are reconstructed using a cone-beam tomography algorithm. Prior to reconstruction, the raw projections are calibrated and corrected for centre of rotation movement and accelerator output fluctuation. The performance of the system has been evaluated by reconstructing projections of open fields, test objects and a humanoid phantom. RESULTS Hundreds of 2D projections can be acquired with a clinically-acceptable data collection time (about 2 min) and dose (approximately 40 cGy, with a possible four-fold reduction). A maximum density resolution of about 2% is achieved offering some soft tissue discrimination without using image enhancement tools. A spatial resolution of 2.5 mm is obtained. The reconstructed image intensity is linear with electron density over the range of interest. Coronal or sagittal slices through the 3D reconstruction of the humanoid phantom show a better delineation of structures than the corresponding portal images taken at the same orientation. CONCLUSIONS A similar image quality to our current single-slice MVCT scanner is achieved with the advantage of providing tens of tomographic slices for a single gantry rotation. This work demonstrates the feasibility of clinical cone-beam MVCT and indicates how this prototype can be improved.

The delivery of intensity modulated radiotherapy to the breast using multiple static fields

BACKGROUND AND PURPOSE To develop a method of using a multileaf collimator (MLC) to deliver intensity modulated radiotherapy (IMRT) for tangential breast fields, using an MLC to deliver a set of multiple static fields (MSFs). MATERIALS AND METHODS An electronic portal imaging device (EPID) is used to obtain thickness maps of medial and lateral tangential breast fields. From these IMRT deliveries are designed to minimize the volume of breast above 105% of prescribed dose. The deliveries are universally-wedged beams augmented with a set of low dose shaped irradiations. Dosimetric and planning QA of this method has been compared with the standard, wedged treatment and the corresponding treatment using physical compensators. Several options for delivering the MSF treatment are presented. RESULTS The MSF technique was found to be superior to the standard technique (P value=0.002) and comparable with the compensated technique. Both IMRT methods reduced the volume of breast above 105% dose from a mean value of 12.0% of the total breast volume to approximately 2.8% of the total breast volume. CONCLUSIONS This MSF method may be used to reduce the high dose volume in tangential breast irradiation significantly. This may have consequences for long-term side effects, particularly cosmesis.

A method for estimating the oxygen consumption rate in multicellular tumour spheroids

Hypoxia occurs when oxygen levels within a tissue drop below normal physiological levels. In tumours, hypoxia is associated with poor prognosis, increased likelihood of metastasis and resistance to therapy. Imaging techniques, for example, positron emission tomography, are increasingly used in the monitoring of tumour hypoxia and have the potential to help in the planning of radiotherapy. For this application, improved understanding of the link between image contrast and quantitative underlying oxygen distribution would be very useful. Mathematical models of tissue hypoxia and image formation can help understand this. Hypoxia is caused by an imbalance between vascular supply and tissue demand. While much work has been dedicated to the quantitative description of tumour vascular networks, consideration of tumour oxygen consumption is largely neglected. Oxidative respiration in standard two-dimensional cell culture has been widely studied. However, two-dimensional culture fails to capture the complexities of growing three-dimensional tissue which could impact on the oxygen usage. In this study, we build on previous descriptions of oxygen consumption and diffusion in three-dimensional tumour spheroids and present a method for estimating rates of oxygen consumption from spheroids, validated using stained spheroid sections. Methods for estimating the local partial pressure of oxygen, the diffusion limit and the extents of the necrotic core, hypoxic region and proliferating rim are also derived. These are validated using experimental data from DLD1 spheroids at different stages of growth. A relatively constant experimentally derived diffusion limit of 232 ± 22 μm and an O2 consumption rate of 7.29 ± 1.4 × 10−7 m3 kg−1 s−1 for the spheroids studied was measured, in agreement with laboratory measurements.

DOSE-VOLUME CONSTRAINTS TO REDUCE RECTAL SIDE EFFECTS FROM PROSTATE RADIOTHERAPY: EVIDENCE FROM MRC RT01 TRIAL ISRCTN 47772397

PURPOSE Radical radiotherapy for prostate cancer is effective but dose limited because of the proximity of normal tissues. Comprehensive dose-volume analysis of the incidence of clinically relevant late rectal toxicities could indicate how the dose to the rectum should be constrained. Previous emphasis has been on constraining the mid-to-high dose range (>/=50 Gy). Evidence is emerging that lower doses could also be important. METHODS AND MATERIALS Data from a large multicenter randomized trial were used to investigate the correlation between seven clinically relevant rectal toxicity endpoints (including patient- and clinician-reported outcomes) and an absolute 5% increase in the volume of rectum receiving the specified doses. The results were quantified using odds ratios. Rectal dose-volume constraints were applied retrospectively to investigate the association of constraints with the incidence of late rectal toxicity. RESULTS A statistically significant dose-volume response was observed for six of the seven endpoints for at least one of the dose levels tested in the range of 30-70 Gy. Statistically significant reductions in the incidence of these late rectal toxicities were observed for the group of patients whose treatment plans met specific proposed dose-volume constraints. The incidence of moderate/severe toxicity (any endpoint) decreased incrementally for patients whose treatment plans met increasing numbers of dose-volume constraints from the set of V30<or=80%, V40<or=65%, V50<or=55%, V60<or=40%, V65<or=30%, V70<or=15%, and V75<or=3%. CONCLUSION Considering the entire dose distribution to the rectum by applying dose-volume constraints such as those tested here in the present will reduce the incidence of late rectal toxicity.

Dose escalation for non-small cell lung cancer: analysis and modelling of published literature.

PURPOSE To review the published clinical data on non-small cell lung cancer treated with radical radiotherapy to confirm a dose-response relationship as a basis for further dose-escalation trials. METHODS Twenty-four published clinical trials were identified, 16 of which - with 29 different standard, hyper- and hypofractionated treatment schedules - were analysed. Prescription doses were converted to biologically-equivalent dose (BED), with a correction for repopulation. Disease-free survival data were corrected for the stage profile of each cohort to allow better comparison of results. We also analysed moderate (grade II and III) lung and oesophageal acute toxicity related to the corrected BED delivered to the tumour. RESULTS The clinical data analysed showed good agreement between the observed and modelled disease-free survival at 2 years when compared to the published models of Fenwick (correlation coefficient 0.525, p=0.003) and Martel (correlation coefficient 0.492, p=0.007), indicating a clear tumour dose-response. In the normally fractionated treatments (∼ 2 Gy per fraction), improved disease-free survival was generally observed in the shorter schedules (maximum around 6 weeks). However, the best outcomes were obtained for the hypofractionated schedules. No systematic relationship was seen between prescribed dose and lung or oesophageal acute toxicity, possibly due to dose selection depending on V(20) or MLD in some studies and the diversity of the patients analysed. CONCLUSIONS We have demonstrated a dose-response relationship for NSCLC based on clinical data. The clinical data provide a rational basis for selection of dose escalation schedules to be tested in future randomised trials.

Comparison of ghosting effects for three commercial a-Si EPIDs

Many studies have reported dosimetric characteristics of amorphous silicon electronic portal imaging devices (EPIDs). Some studies ascribed a non-linear signal to gain ghosting and image lag. Other reports, however, state the effect is negligible. This study compares the signal-to-monitor unit (MU) ratio for three different brands of EPID systems. The signal was measured for a wide range of monitor units (5-1000), dose-rates, and beam energies. All EPIDs exhibited a relative under-response for beams of few MUs; giving 4 to 10% lower signal-to-MU ratios relative to that of 1000 MUs. This under-response is consistent with ghosting effects due to charge trapping.

Rapid portal imaging with a high-efficiency, large field-of-view detector

The design, construction, and performance evaluation of an electronic portal imaging device (EPID) are described. The EPID has the same imaging geometry as the current mirror-based systems except for the x-ray detection stage, where a two-dimensional (2D) array of 1 cm thick CsI(Tl) detector elements are utilized. The approximately 18% x-ray quantum efficiency of the scintillation detector and its 30 x 40 cm2 field-of-view at the isocenter are greater than other area-imaging EPIDs. The imaging issues addressed are theoretical and measured signal-to-noise ratio, linearity of the imaging chain, influence of frame-summing on image quality and image calibration. Portal images of test objects and a humanoid phantom are used to measure the performance of the system. An image quality similar to the current devices is achieved but with a lower dose. With approximately 1 cGy dose delivered by a 6 MV beam, a 2 mm diam structure of 1.3% contrast and an 18 mm diam object of 0.125% contrast can be resolved without using image-enhancement methods. A spatial resolution of about 2 mm at the isocenter is demonstrated. The capability of the system to perform fast sequential imaging, synchronized with the radiation pulses, makes it suitable for patient motion studies and verification of intensity-modulated beams as well as its application in cone-beam megavoltage computed tomography.

Assessing correlations between the spatial distribution of the dose to the rectal wall and late rectal toxicity after prostate radiotherapy: an analysis of data from the MRC RT01 trial (ISRCTN 47772397)

Many studies have been performed to assess correlations between measures derived from dose-volume histograms and late rectal toxicities for radiotherapy of prostate cancer. The purpose of this study was to quantify correlations between measures describing the shape and location of the dose distribution and different outcomes. The dose to the rectal wall was projected on a two-dimensional map. In order to characterize the dose distribution, its centre of mass, longitudinal and lateral extent, and eccentricity were calculated at different dose levels. Furthermore, the dose-surface histogram (DSH) was determined. Correlations between these measures and seven clinically relevant rectal-toxicity endpoints were quantified by maximally selected standardized Wilcoxon rank statistics. The analysis was performed using data from the RT01 prostate radiotherapy trial. For some endpoints, the shape of the dose distribution is more strongly correlated with the outcome than simple DSHs. Rectal bleeding was most strongly correlated with the lateral extent of the dose distribution. For loose stools, the strongest correlations were found for longitudinal extent; proctitis was most strongly correlated with DSH. For the other endpoints no statistically significant correlations could be found. The strengths of the correlations between the shape of the dose distribution and outcome differed considerably between the different endpoints. Due to these significant correlations, it is desirable to use shape-based tools in order to assess the quality of a dose distribution.

Adaptive Radiotherapy for Locally Advanced Non–Small-Cell Lung Cancer Does Not Underdose the Microscopic Disease and has the Potential to Increase Tumor Control

PURPOSE To evaluate doses to the microscopic disease (MD) in adaptive radiotherapy (ART) for locally advanced non-small-cell lung cancer (NSCLC) and to model tumor control probability (TCP). METHODS AND MATERIALS In a retrospective planning study, three-dimensional conformal treatment plans for 13 patients with locally advanced NSCLC were adapted to shape and volume changes of the gross tumor volume (GTV) once or twice during conventionally fractionated radiotherapy with total doses of 66 Gy; doses in the ART plans were escalated using an iso-mean lung dose (MLD) approach compared to non-adapted treatment. Dose distributions to the volumes of suspect MD were simulated for a scenario with synchronous shrinkage of the MD and GTV and for a scenario of a stationary MD despite GTV shrinkage; simulations were performed using deformable image registration. TCP calculations considering doses to the GTV and MD were performed using three different models. RESULTS Coverage of the MD at 50 Gy was not compromised by ART. Coverage at 60 Gy in the scenario of a stationary MD was significantly reduced from 92% ± 10% to 73% ± 19% using ART; however, the coverage was restored by iso-MLD dose escalation. Dose distributions in the MD were sufficient to achieve a TCP >80% on average in all simulation experiments, with the clonogenic cell density the major factor influencing TCP. The combined TCP for the GTV and MD was 19.9% averaged over all patients and TCP models in non-adaptive treatment with 66 Gy. Iso-MLD dose escalation achieved by ART increased the overall TCP by absolute 6% (adapting plan once) and by 8.7% (adapting plan twice) on average. Absolute TCP values were significantly different between the TCP models; however, all TCP models suggested very similar TCP increase by using ART. CONCLUSIONS Adaptation of radiotherapy to the shrinking GTV did not compromise dose coverage of volumes of suspect microscopic disease and has the potential to increase TCP by >40% compared with radiotherapy planning without ART.

Direct measurement and analytical modeling of scatter in portal imaging

In this study a direct measurement of scatter in portal imaging for various air gaps and scatterer thicknesses at a beam energy of 6 MV is presented. The experimental data are compared with results from a Monte Carlo (MC) scatter model. In the regime where the air gap is larger than 9.3 cm the MC and the experiment agree. Based on this MC model an analytical model is developed, which takes all important interaction processes into account. It comprises a rigorous treatment of first order scattering and an estimation of photons scattered more than once within the phantom. This estimation is based on the assumption that higher order scattering can be considered as isotropically distributed around a certain scatter origin located in the midplane of the phantom. It is found that relative deviations between the MC model and the analytical model are of 2% to 3% in regions where scattering is very large.