Clinical and practical considerations for the use of intensity-modulated radiotherapy and image guidance in neuro-oncology.

Intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy offer significant opportunities to improve outcomes for our patients, although they are not yet as widely used as they might be. IMRT allows better target coverage and lower organ at risk doses than conformal therapy. It also allows inhomogeneous dose plans to be developed, where these can provide benefit, either to dose escalate the tumour or reduce dose to adjacent or overlapping organs at risk. Image guidance adds precision and the possibility of careful reduction in planning target volume margins. The technologies can be valuable both for patients with highly malignant tumours, such as glioblastoma, and those with less malignant or benign tumours. In glioblastoma, temozolomide chemotherapy and surgical developments have improved survival, and developments in radiotherapy techniques should also be used to optimise outcome. Target volume delineation, including calculation of the planning target volume margin is critical. Clear definitions of the gross tumour and clinical target volumes are essential, following established guidelines. Normal tissue volume delineation is also essential for IMRT. The planning organ at risk volume has become a valuable tool to manipulate dose away from organs at risk to avoid toxicities. This is distinct from 'optimising volumes' used to drive the computer optimiser during planning. Hard data on central nervous system (CNS) normal tissue tolerance is surprisingly slight, reflecting the clinical imperative to avoid serious complications in neurological tissues. The effect of chemotherapy on radiotherapy tolerance in the CNS remains obscure, and more needs to be done to develop the knowledge base. IMRT provides better conformation of the high dose treatment to the shape of the target, and reduces the dose to normal tissue structures. Image guidance improves the accuracy of dose delivery, which is particularly important where steep dose gradients are present. These technologies should be regarded as the state-of-the-art for our CNS patients.

Reference dosimetry on TomoTherapy: an addendum to the 1990 UK MV dosimetry code of practice.

The current UK code of practice for high-energy photon therapy dosimetry (Lillicrap et al 1990 Phys. Med. Biol. 35 1355-60) gives instructions for measuring absorbed dose to water under reference conditions for megavoltage photons. The reference conditions and the index used to specify beam quality require that a machine be able to set a 10 cm × 10 cm field at the point of measurement. TomoTherapy machines have a maximum collimator setting of 5 cm × 40 cm at a source to axis distance of 85 cm, making it impossible for users of these machines to follow the code. This addendum addresses the specification of reference irradiation geometries, the choice of ionization chambers and the determination of dosimetry corrections, the derivation of absorbed dose to water calibration factors and choice of appropriate chamber correction factors, for carrying out reference dosimetry measurements on TomoTherapy machines. The preferred secondary standard chamber remains the NE2611 chamber, which with its associated secondary standard electrometer, is calibrated at the NPL through the standard calibration service for MV photon beams produced on linear accelerators with conventional flattening filters. Procedures are given for the derivation of a beam quality index specific to the TomoTherapy beam that can be used in the determination of a calibration coefficient for the secondary standard chamber from its calibration certificate provided by the NPL. The recommended method of transfer from secondary standard to field instrument is in a static beam, at a depth of 5 cm, by sequential substitution or by simultaneous side by side irradiation in either a water phantom or a water-equivalent solid phantom. Guidance is given on the use of a field instrument in reference fields.

Image guidance protocols: balancing imaging parameters against scan time.

OBJECTIVE: Optimisation of imaging protocols is essential to maximise the use of image-guided radiotherapy. This article evaluates the time for daily online imaging with TomoTherapy® (Accuray®, Sunnyvale, CA), separating mechanical scan acquisition from radiographer-led image matching, to estimate the time required for a clinical research study (VoxTox). METHODS: Over 5 years, 18 533 treatments were recorded for 3 tumour sites of interest (prostate, head and neck and central nervous system). Data were collected for scan length, number of CT slices, slice thickness, scan acquisition time and image matching time. RESULTS: The proportion of coarse thickness scans increased over time, with a move of making coarse scans as the default. There was a strong correlation between scan time and scan length. Scan acquisition requires 40 s of processing time. For coarse scans, each additional centimetre requires 8 s for acquisition. Image matching takes approximately 1.5 times as long, so each additional centimetre needs 20 s extra in total. Modest changes to the imaging protocol have minimal impact over the course of the day. CONCLUSION: This work quantified the effect of changes to clinical protocols required for research. The results have been found to be reassuring in the busy National Institutes of Health department. ADVANCES IN KNOWLEDGE: This novel method of data collection and analysis provides evidence of the minimal impact of research on clinical turnover. Whilst the data relate specifically to TomoTherapy, some aspects may apply to other platforms in the future.

Consideration of the likely benefit from implementation of prostate image-guided radiotherapy using current margin sizes: a radiobiological analysis.

OBJECTIVE: To estimate the benefit of introduction of image-guided radiotherapy (IGRT) to prostate radiotherapy practice with current clinical target volume-planning target volume (PTV) margins of 5-10 mm. METHODS: Systematic error data collected from 50 patients were used together with a random error of σ=3.0 mm to model non-IGRT treatment. IGRT was modelled with residual errors of Σ=σ=1.5 mm. Population tumour control probability (TCP(pop)) was calculated for two three-dimensional conformal radiotherapy techniques: two-phase and concomitant boost. Treatment volumes and dose prescriptions were ostensibly the same. The relative field sizes of the treatment techniques, distribution of systematic errors and correlations between movement axes were examined. RESULTS: The differences in TCP(pop) between the IGRT and non-IGRT regimes were 0.3% for the two-phase and 1.5% for the concomitant boost techniques. A 2-phase plan, in each phase of which the 95% isodose conformed to its respective PTV, required fields that were 3.5 mm larger than those required for the concomitant boost plan. Despite the larger field sizes, the TCP (without IGRT) in the two-phase plan was only 1.7% higher than the TCP in the concomitant boost plan. The deviation of craniocaudal systematic errors (p=0.02) from a normal distribution, and the correlation of translations in the craniocaudal and anteroposterior directions (p<0.0001) were statistically significant. CONCLUSIONS: The expected population benefit of IGRT for the modelled situation was too small to be detected by a clinical trial of reasonable size, although there was a significant benefit to individual patients. For IGRT to have an observable population benefit, the trial would need to use smaller margins than those used in this study. Concomitant treatment techniques permit smaller fields and tighter conformality than two phases planned separately.

Practical aspects of implementation of helical tomotherapy for intensity-modulated and image-guided radiotherapy.

AIMS: Image-guided radiotherapy (IGRT) and intensity-modulated radiotherapy (IMRT) represent two important technical developments that will probably improve patient outcome. Helical tomotherapy, provided by the TomoTherapy HiArt system, provides an elegant integrated solution providing both technologies, although others are available. Here we report our experience of clinical implementation of daily online IGRT and IMRT using helical tomotherapy. MATERIALS AND METHODS: Methods were needed to select patients who would probably benefit. Machine-specific commissioning, a quality assurance programme and patient-specific delivery quality assurance were also needed. The planning target volume dose was prescribed as the median dose, with the added criterion that the 95% isodose should cover 99% of the target volume. Although back-up plans, for delivery on conventional linear accelerators, were initially prepared, this practice was abandoned because they were used very rarely. RESULTS: In the first 12 months, 114 patients were accepted for treatment, and 3343 fractions delivered. New starts averaged 2.6 per week, with an average of 17.5 fractions treated per day, and the total number capped at 22. This has subsequently been raised to 24. Of the first 100 patients, 96 were treated with radical intent. Five were considered to have been untreatable on our standard equipment. IGRT is radiographer led and all patients were imaged daily, with positional correction made before treatment, using an action level of 1mm. A formal training programme was developed and implemented before installation. The in-room time fell significantly during the year, reflecting increasing experience and a software upgrade. More recently, after a couch upgrade in April 2009, the mean in-room time fell to 18.6 min. CONCLUSIONS: Successful implementation of tomotherapy was the result of careful planning and effective teamwork. Treatment, including daily image guidance, positional correction and intensity-modulated delivery, is fast and efficient, and can be integrated into routine service. This should encourage the adoption of these technologies.

An assessment of action levels in imaging strategies in head and neck cancer using TomoTherapy. Are our margins adequate in the absence of image guidance?

AIMS: To assess the effectiveness of different on-treatment correction strategies on set-up accuracy in patients with head and neck cancer (HNC) treated on a TomoTherapy HiArt system. To assess the adequacy of clinical target volume (CTV) to planning target volume (PTV) treatment planning margins when treating with intensity-modulated radiotherapy without daily image guidance. MATERIALS AND METHODS: The set-up accuracy measured by daily online volumetric imaging was retrospectively reviewed for the first 15 patients with HNC treated on the TomoTherapy unit at Addenbrooke's Hospital. For each fraction, megavoltage computed tomography was carried out, any discrepancy from the planning scan was noted, and corrected, before treatment. These data were used to evaluate imaging correction protocols using three different action levels. The first three fractions were imaged and used to correct for systematic error, using a 5 mm action level (5 mmAL), a 3 mm action level (3 mmAL), and no action level (NAL). All imaging strategies were applied, to assess the number of fractions that would potentially have exceeded a 5 and 3 mm margin. Systematic and random errors were calculated for the population, assuming the NAL protocol had been applied, and minimum CTV-PTV margins, required to allow for errors attributable only to set-up, were calculated using van Herk's formula. RESULTS: In total, 490 fractions were analysed. Using a 5 mmAL imaging protocol, potentially 198/490 fractions (40%) were outside a 5 mm CTV-PTV margin and 400/490 (82%) were outside a 3 mm margin. Using a 3 mmAL imaging protocol, potentially 67/490 fractions (14%) were outside a 5 mm CTV-PTV margin and 253/490 (52%) were outside a 3 mm margin. A small systematic error was identified in the system; once corrected this would improve these results. Using the NAL imaging protocol, potentially 31/490 fractions (6%) were outside a 5 mm CTV-PTV margin and 143/490 fractions (29%) were outside a 3 mm margin. Estimated minimum CTV-PTV margins to account only for set-up errors, with three-fraction image-guided radiotherapy and a NAL protocol, were 2.8, 3.1 and 4.1 mm in the mediolateral, superior-inferior and anterior-posterior directions, respectively. CONCLUSION: Reducing the action level at which the systematic error is corrected improves the probability of treatment delivery accuracy. Using the NAL correction protocol reduces the number of fractions that have set-up displacements outside a 5 mm CTV-PTV margin. Although a 5 mm margin is probably sufficient for standard HNC radiotherapy, change to a 3 mm margin is not favoured at our centre without access to daily image-guided radiotherapy.

Equivalent squares for small field dosimetry.

The use of equivalent squares is of value when determining output and depth dose data for rectangular fields. We have looked at the variation with field shape of head scatter factors (S(c)), phantom scatter factors (S(p)) and tissue phantom ratios (TPRs) using measurements on a 6 MV linac with a Moduleaf mini-multileaf collimator. Measurements were made for fields with dimensions down to 1 cm. A different approach to calculating equivalent squares needs to be made depending on the quantity of interest. For TPRs, good agreement for rectangular fields can be obtained using the well established E = 2XY/(X+Y) formula where E is the equivalent square field size and X and Y are the field dimensions. For S(c) measurements, where a collimator exchange effect is observed, better agreement is obtained using E = (1+A)XY/(AX+Y), where A is an empirically determined constant. For S(p) measurements, E = 2XY/(X+Y) only gives agreement with measurements when the minimum field dimension is at least 2.5 cm. For smaller fields, the equivalent square overestimates S(p), with the difference being strongly related to the value of the smaller dimension. We propose an empirical formula, based on the size of the smaller dimension.

Comparison of rectal dose histograms under conditions of nonlinear isodoses.

Cumulative dose-volume histograms of organs-at-risk are commonly used as predictors of the likelihood and severity of toxicity. In the case of hollow organs such as the rectum, the dose-volume histogram of the organ disregarding the lumen (dose-wall histogram, DWH) can be difficult to outline, and where the voxel size approaches the wall thickness, poor dose statistics can result. Various surrogates for DWH have been proposed, including the dose-volume histogram of organ plus the lumen (DVH), the dose-surface histogram (DSH), the normalized dose-volume histogram of organ plus lumen (NDVH) and the normalized dose-surface histogram (NDSH). In order to test the relative relationships between these histogram types in the case of prostate radiotherapy, a cylindrical model of the rectum has been combined with an idealized nonlinear isodose model in order to allow typical isodose shapes from both conventional three-field radiotherapy and prostate IMRT to be studied. Analytic expressions for histogram values are derived, and implemented through a spreadsheet. Isodose shapes and positions from five patients are combined to generate typical isodose distributions for which histograms may be generated and compared. It is found that the plan type has little effect on the relative values of the histogram points, and that no other histogram acts as a robust estimate of the DWH under all conditions. However, if the irradiated portion of the rectum is empty, NDVH is a good surrogate for DWH.

Equivalent diameters of elliptical fields.

The equivalent field method is well established as a means of performing dose calculations in rectangular and irregular fields. There is, however, no consensus on the equivalent diameter (D) of elliptical fields, despite their common applications in kilovoltage radiotherapy. Measurements have been performed on 15 elliptical fields and 6 circular fields, comprising all possible combinations of 3 cm, 4 cm, 5 cm, 6 cm, 9 cm and 12 cm diameters, using 150 kV X-rays, with a half-value thickness of 8 mmAl. Equivalent diameters were calculated by a number of methods, including the equal area, ratio of perimeter to area, 2AB/(A+B) and sector integration. The best agreement with measurement was obtained using sector integration, which agreed with measurements within the limits of experimental error. The formula D=2AB/(A+B) was the best of the analytic formulae; at shallow depths it gave predictions of dose within better than 0.5%, whilst at 5 cm deep its greatest error was 1.6%. The equal area formula (D = square root AB) gave the worst predictions, with errors up to 5% at shallow depths, and 9% at a depth of 5 cm.