Separating components of variation in measurement series using maximum likelihood estimation. Application to patient position data in radiotherapy.

Maximum likelihood estimation (MLE) is presented as a statistical tool to evaluate the contribution of measurement error to any measurement series where the same quantity is measured using different independent methods. The technique was tested against artificial data sets; generated for values of underlying variation in the quantity and measurement error between 0.5 mm and 3 mm. In each case the simulation parameters were determined within 0.1 mm. The technique was applied to analyzing external random positioning errors from positional audit data for 112 pelvic radiotherapy patients. Patient position offsets were measured using portal imaging analysis and external body surface measures. Using MLE to analyze all methods in parallel it was possible to ascertain the measurement error for each method and the underlying positional variation. In the (AP / Lat / SI) directions the standard deviations of the measured patient position errors from portal imaging were (3.3 mm / 2.3 mm / 1.9 mm), arising from underlying variations of (2.7 mm / 1.5 mm / 1.4 mm) and measurement uncertainties of (1.8 mm / 1.8 mm / 1.3 mm), respectively. The measurement errors agree well with published studies. MLE used in this manner could be applied to any study in which the same quantity is measured using independent methods.

Survey of the availability and use of advanced radiotherapy technology in the UK.

AIMS: To determine the availability of intensity-modulated radiotherapy (IMRT) treatment in the UK and to assess the magnitude of the shortfall in terms of patient treatments. In addition, the availability of image-guided radiotherapy (IGRT) was also reviewed. MATERIALS AND METHODS: A survey was carried out between July and September 2008 of the use of advanced technology in radiotherapy. RESULTS: In total, 50 centres responded out of the 58 National Health Service centres canvassed, representing about 89% of patients treated in the UK. Forty-six centres had at least two machines capable of IMRT and 26 centres had at least one machine capable of IGRT. Thirty-two centres were carrying out forward-planned IMRT and 18 centres were carrying out the more complex inverse-planned IMRT. In all, 38 centres (76% of respondents) were offering either forward- or inverse-planned IMRT to some of their patients. All the centres with IGRT capability were using IGRT for at least some of their patients. Respondents were asked to list the total number of radical and palliative patients being treated according to the treatment site. Forty-two per cent of respondents took the option to list the total number of radical and palliative patients only. Based on these data, 10.7% of radical patients are currently being given forward-planned IMRT, mainly for breast cancer (18.6% of such patients) and 2.2% of radical patients are being given inverse-planned IMRT, mainly for prostate (7.5% of such patients) and head and neck cancer (6.7% of such patients). Whereas at present only 18 centres are able to treat with inverse-planned IMRT, 45 centres expected to be able to do so by 2010. Respondents were asked to estimate the percentage of patients who should be given IMRT for each site and this was used to estimate the shortfall in IMRT provision. CONCLUSIONS: Based on the consensus of opinion, 32% of radically treated patients should receive inverse-planned IMRT and 22% forward-planned IMRT, making a total of 55%. In fact, 2% receive inverse-planned IMRT and 11% the less complex forward-planned IMRT. Thus, with an estimated 75,948 radical treatments being carried out with megavoltage radiotherapy, the professional opinion is that 41,421 of patients would benefit from treatment with IMRT. In fact, only 9775 were so treated in 2008; a shortfall of 32,497 patients treated instead with conventional radiotherapy.

Geometric leaf placement strategies.

Geometric leaf placement strategies for multileaf collimators (MLCs) typically involve the expansion of the beam's-eye-view contour of a target by a uniform MLC margin, followed by movement of the leaves until some point on each leaf end touches the expanded contour. Film-based dose-distribution measurements have been made to determine appropriate MLC margins--characterized through an index d90--for multileaves set using one particular strategy to straight lines lying at various angles to the direction of leaf travel. Simple trigonometric relationships exist between different geometric leaf placement strategies and are used to generalize the results of the film work into d90 values for several different strategies. Measured d90 values vary both with angle and leaf placement strategy. A model has been derived that explains and describes quite well the observed variations of d90 with angle. The d90 angular variations of the strategies studied differ substantially, and geometric and dosimetric reasoning suggests that the best strategy is the one with the least angular variation. Using this criterion, the best straightforwardly implementable strategy studied is a 'touch circle' approach for which semicircles are imagined to be inscribed within leaf ends, the leaves being moved until the semicircles just touch the expanded target outline.

IPEM guidelines on dosimeter systems for use as transfer instruments between the UK primary dosimetry standards laboratory (NPL) and radiotherapy centres.

United Kingdom dosimetry codes of practice have traditionally specified one electrometer for use as a secondary standard, namely the Nuclear Enterprises (NE) 2560 NPL secondary standard therapy level exposure meter. The NE2560 will become obsolete in the foreseeable future. This report provides guidelines to assist physicists following the United Kingdom dosimetry codes of practice in the selection of an electrometer to replace the NE2560 when necessary. Using an internationally accepted standard (BS EN 60731:1997) as a basis, estimated error analyses demonstrate that the uncertainty (one standard deviation) in a charge measurement associated with the NE2560 alone is approximately 0.3% under specified conditions. Following a review of manufacturers' literature, it is considered that modern electrometers should be capable of equalling this performance. Additional constructural and operational requirements not specified in the international standard but considered essential in a modern electrometer to be used as a secondary standard are presented.

Acute toxicity in pelvic radiotherapy; a randomised trial of conformal versus conventional treatment.

BACKGROUND: A prospective, randomized clinical trial to assess the effect of reducing the volume of irradiated normal tissue on acute reactions in pelvic radiotherapy accured 266 evaluable patients between 1988 and 1993. PURPOSE: This is the definitive analysis to assess the differences between the conformal and conventional arms of the trial. MATERIALS AND METHODS: In both arms, patients were treated with 6 MV X-rays using a 3-field technique (in all but 5 cases) consisting of an anterior and two wedged lateral or posterior oblique fields; in the conventional arm, rectangular fields were employed, whereas in the conformal arm, the fields were shaped with customized blocks drawn according to the beam's-eye-view of the target volume. The most common dosage was 64 Gy in 2-Gy fractions 5 times a week, although a subgroup (of ca. bladder patients) were treated with 30-36 Gy in once-a-week 6 Gy fractions. Each patients completed a comprehensive acute toxicity scoring questionnaire concentrating on bowel and bladder problems, tiredness and nausea, before the start of treatment, weekly during and for 3 weeks after the end of treatment and then monthly for a further 2 months. compliance was excellent. RESULTS: There were no differences between the patients in the two arms with respect to age, gender, tumour type (52% prostate, 41% bladder, 5% rectum, 2% other) fractionation/dosage, anterior field size, weight, or baseline symptoms. Substantial differences in normal-tissue volumes (rectum, bladder, etc.) were achieved: median high-dose volume (HDV) of 689 cm3 for the conformal technique versus 792 cm3 for the conventional. A clear pattern of an increase in symptoms during RT, followed by a decrease after RT, was observed for the patient group as a whole. However, a very extensive analysis has not revealed any (statistically) significant differences between the two arms in level of symptoms, nor in medication prescribed. The disparity between our findings and those of other, non-randomized studies is discussed. CONCLUSIONS: The data on late effects must be collected and analyzed before any definite conclusions can be drawn on the benefits of conformal therapy in the pelvis.

The potential for increased sparing of normal tissue in parallel opposed techniques with a multileaf collimator.

A multileaf collimator (MLC) can be used in parallel opposed techniques as a direct replacement for standard-shaped beam blocks. However, improved shielding is possible if the MLC field is designed to fit a target rather than to mimic a straight-edged block. This study has compared the treatment areas produced by the MLC and by conventionally blocked fields with the target area for 43 parallel opposed treatments. It was found in every case that the MLC treated less than 10% excess tissue, and, in over 70% of patients, the excess was less than 5%. The conventional fields, however, treated more than 10% excess tissue in 70% of patients. The effect of MLC orientation and the benefits of using an MLC are discussed.

The influence of air cavities on the optic chiasm dose during pituitary radiotherapy for acromegaly.

The treatment planning of acromegalic patients can be complicated by the presence of abnormally large frontal air sinuses which allow increased anterior beam transmission causing increased dose to the optic nerve and chiasm which, if excessive, can result in blindness. This potential problem has been investigated by computer treatment planning exercises which have allowed for a variable thickness (1-3 cm) of air cavity beneath the frontal field and for different weightings of the lateral opposed fields relative to the anterior field. The resultant overdosage can be greater than 5% of the intended dose. The increased biological effect from errors of this magnitude is sufficient to increase the risk of optic nerve damage since neural tissue is very sensitive to small increments in fraction size. Even when the reduced attenuation is allowed for in the computer plan, the thickness of the air sinuses varies across the field so that irradiation through the frontal enlarged frontal air sinuses causes inhomogeneous dose distributions in the target volume. Acromegalic patients should therefore be treated with a more superior beam which would avoid the air sinuses altogether.

Design of compensators for breast radiotherapy using electronic portal imaging.

A novel method of designing intensity modulated beams (IMBs) to achieve compensation in external beam radiotherapy of the breast, without the need for CT scans, is presented. The design method comprises three parts: (1) an electronic portal image is used to generate a map of radiological thickness; (2) this map is then used to obtain an estimate of the breast and lung outline; (3) a TMR-based dose calculation algorithm is then used to determine the optimum beam profile to achieve the best dose distribution. The dose distributions calculated for IMBs were compared with those calculated for the use of simple wedges. The results for two patients studied indicate that the dose inhomogeneity for IMBs is +/- 5%, compared with a value of +/- 10% for a wedged plan. The uncertainty in radiological thickness measurement corresponds to a dosimetric error of +/- 2%. Other errors associated with outline estimation are typically less than 2%, with a largest value of +5% for one of the patients who had a large and highly asymmetrical breast. The results for the two patients studied suggest that the uncertainties in the method are significantly smaller than the improvement in dose uniformity produced.

The acceptability of a multileaf collimator as a replacement for conventional blocks.

A multileaf collimator (MLC) can be used as a replacement for conventional blocks as well as for conformal radiotherapy. This study has assessed the possibility of using a Philips MLC for 218 patients treated with conventionally blocked fields. It was found that MLC field shaping would have been appropriate for over 94% of such patients. The facility to treat large blocked fields has been found to be particularly useful. Use of the predefined shapes stored in the Regular Shape Library provided by Philips was evaluated and it was found that an appropriate shape was available in 52% of cases. The application of MLC fields to the treatment of different anatomical sites is discussed.

Factors affecting the precision of TLD dose measurements using an automatic TLD reader.

An increase in the variability of TLD dose measurements prompted a study of the precision of dose measurements with a Rialto automatic TLD reader. It was found that readings with the same chip measured using two different trays could differ by as much as 7%. In order to overcome this problem it was necessary to ensure that individual chips were correctly identified. Marking the chips with a hard graphite pencil was found to be a satisfactory method of identifying them, which, although it reduced the light output by approximately 3%, had no effect on the reproducibility of readings. Using marked chips and an individual tray for each chip, the reproducibility of a reading was reduced to a typical value of 1%. A system of quality assurance based on these findings is described.

Invited review: tangential breast irradiation--rationale and methods for improving dosimetry.

In recent years there have been great advances and innovations in all technical aspects of radiotherapy, including three dimensional (3D) computer planning, patient immobilization, radiation delivery and treatment verification. Despite this progress, the technique of tangential breast irradiation has changed little over this period and has not exploited these advances. There is increasing evidence that dose inhomogeneity within the breast is greater than at other anatomical sites, especially in women with large breasts. This paper is a review of the factors contributing to poor dosimetry in the breast, the clinical consequences of an inhomogeneous dose distribution, and how breast dosimetry could be improved by considering each of the stages from planning to accurate treatment delivery. It also highlights the particular problem of women with large breasts who may be more likely to have a poorer cosmetic outcome after a fractionated course of radiotherapy than women with small/medium-sized breasts, and supports the clinical impression that such women are also more likely to have greater dose inhomogeneity when 3D treatment plans are examined. Preliminary data from our current computed tomography (CT) planning study are presented to support these observations.

The influence of breast size on late radiation effects and association with radiotherapy dose inhomogeneity.

A prospective assessment of late changes in breast appearance in 559 patients after tumour excision and radiotherapy for early breast cancer noted a strong association with breast size. Only 3/48 (6%) patients with small breasts developed moderate or severe late changes compared with 94/423 (22%) with medium sized breasts and 34/88 (39%) patients with large breasts (p < 0.001). One possibility is that greater radiation changes are related to greater dose inhomogeneity in women with large breasts. To explore this hypothesis, radiation dose distributions were assessed in a separate group of 37 women in whom three-level transverse computer tomographic images of the breast in the treatment position were available. A significant correlation was found between breast size and dose inhomogeneity which may account for the marked changes in breast appearance reported in women with large breasts.

An investigation of the response of a simple design of plane-parallel chamber.

This paper reports the experimental investigation of a simple design of plane-parallel electron chamber, which has very thin layers of copper (0.018 or 0.035 mm) as conducting material. Measurements comparing the prototype chambers with other ionization chambers (PTW/Markus, NACP) have been carried out, both in a 60Co gamma-ray beam and in high-energy electron beams. The results show that the Ce factors (proportional to the product of water/air stopping-power ratio and perturbation factor) for converting the in-phantom air-kerma-calibrated chamber reading to the absorbed dose to water are nearly constant for incident electron energies between 4 and 11 MeV for prototype chambers with 0.018 mm thick copper layers and between 4 and 15 MeV for chambers with 0.035 mm thick copper layers. Other aspects concerning these prototype chambers, such as polarity effect, cable effect, collecting efficiency and angular response, have also been studied and the results are presented in this paper.

Conformal radiotherapy of the pelvis: assessment of acute toxicity.

During the last 3 years the Royal Marsden Hospital (RMH) has conducted a prospective randomised trial of conformal pelvic radiotherapy in which dose/volume data and acute toxicity scores have been determined prospectively. Pending completion of the trial, a preliminary analysis has been undertaken of the volume reductions achieved, and of some of the symptom scores. The average symptom score increased during radiotherapy, more markedly for bowel than bladder symptoms. In comparing total doses of 30-38 Gy with 56-65 Gy, watery bowel motions were more frequent with the higher doses (p = 0.013) but in the high-dose group neither this symptom nor tenesmus correlated with volume of rectum treated to at least 90% of the prescribed dose. We conclude that the assessment of the impact of volume on the level of acute symptoms in pelvic radiotherapy is complex, and requires analysis of a range of symptoms, dose levels and normal-tissue volumes. The degree of symptom reduction from conformal radiotherapy will emerge from the RMH randomised trial within the next 12 months.

The Royal Marsden Hospital pelvic radiotherapy trial: technical aspects and quality assurance.

Planning and quality control procedures are described for a randomised trial designed to measure the effect on normal tissue toxicity of reducing the volume of normal tissue irradiated through the introduction of Beams-Eye-View designed customised blocks. Consideration is given to the accuracy with which blocks can be designed and to the potential application of multi-leaf collimator technology.

Improved dose homogeneity in the breast using tissue compensators.

The improvements achievable by introducing individual tissue compensators in photon therapy of the breast were assessed. In 37 patients the dose ranged from +15% to -10% of the mid target dose using combinations of wedge filters and beam weights alone. With a tissue compensator the dose ranged from +4% to -11% provided that allowance was made for lung attenuation. A megavoltage imaging system is a potential source of the X-ray transmission data which can provide a basis for the calculation of thickness of the compensator.