A multicentre audit of HDR/PDR brachytherapy absolute dosimetry in association with the INTERLACE trial (NCT015662405).

A UK multicentre audit to evaluate HDR and PDR brachytherapy has been performed using alanine absolute dosimetry. This is the first national UK audit performing an absolute dose measurement at a clinically relevant distance (20 mm) from the source. It was performed in both INTERLACE (a phase III multicentre trial in cervical cancer) and non-INTERLACE brachytherapy centres treating gynaecological tumours. Forty-seven UK centres (including the National Physical Laboratory) were visited. A simulated line source was generated within each centre's treatment planning system and dwell times calculated to deliver 10 Gy at 20 mm from the midpoint of the central dwell (representative of Point A of the Manchester system). The line source was delivered in a water-equivalent plastic phantom (Barts Solid Water) encased in blocks of PMMA (polymethyl methacrylate) and charge measured with an ion chamber at 3 positions (120° apart, 20 mm from the source). Absorbed dose was then measured with alanine at the same positions and averaged to reduce source positional uncertainties. Charge was also measured at 50 mm from the source (representative of Point B of the Manchester system). Source types included 46 HDR and PDR 192Ir sources, (7 Flexisource, 24 mHDR-v2, 12 GammaMed HDR Plus, 2 GammaMed PDR Plus, 1 VS2000) and 1 HDR 60Co source, (Co0.A86). Alanine measurements when compared to the centres' calculated dose showed a mean difference (±SD) of +1.1% (±1.4%) at 20 mm. Differences were also observed between source types and dose calculation algorithm. Ion chamber measurements demonstrated significant discrepancies between the three holes mainly due to positional variation of the source within the catheter (0.4%-4.9% maximum difference between two holes). This comprehensive audit of absolute dose to water from a simulated line source showed all centres could deliver the prescribed dose to within 5% maximum difference between measurement and calculation.

The IPEM code of practice for determination of the reference air kerma rate for HDR (192)Ir brachytherapy sources based on the NPL air kerma standard.

This paper contains the recommendations of the high dose rate (HDR) brachytherapy working party of the UK Institute of Physics and Engineering in Medicine (IPEM). The recommendations consist of a Code of Practice (COP) for the UK for measuring the reference air kerma rate (RAKR) of HDR (192)Ir brachytherapy sources. In 2004, the National Physical Laboratory (NPL) commissioned a primary standard for the realization of RAKR of HDR (192)Ir brachytherapy sources. This has meant that it is now possible to calibrate ionization chambers directly traceable to an air kerma standard using an (192)Ir source (Sander and Nutbrown 2006 NPL Report DQL-RD 004 (Teddington: NPL) http://publications.npl.co.uk). In order to use the source specification in terms of either RAKR, Κ(R) (ICRU 1985 ICRU Report No 38 (Washington, DC: ICRU); ICRU 1997 ICRU Report No 58 (Bethesda, MD: ICRU)), or air kerma strength, S(K) (Nath et al 1995 Med. Phys. 22 209-34), it has been necessary to develop algorithms that can calculate the dose at any point around brachytherapy sources within the patient tissues. The AAPM TG-43 protocol (Nath et al 1995 Med. Phys. 22 209-34) and the 2004 update TG-43U1 (Rivard et al 2004 Med. Phys. 31 633-74) have been developed more fully than any other protocol and are widely used in commercial treatment planning systems. Since the TG-43 formalism uses the quantity air kerma strength, whereas this COP uses RAKR, a unit conversion from RAKR to air kerma strength was included in the appendix to this COP. It is recommended that the measured RAKR determined with a calibrated well chamber traceable to the NPL (192)Ir primary standard is used in the treatment planning system. The measurement uncertainty in the source calibration based on the system described in this COP has been reduced considerably compared to other methods based on interpolation techniques.

The UK Standardisation of Breast Radiotherapy (START) Trial B of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial.

BACKGROUND: The international standard radiotherapy schedule for early breast cancer delivers 50 Gy in 25 fractions of 2.0 Gy over 5 weeks, but there is a long history of non-standard regimens delivering a lower total dose using fewer, larger fractions (hypofractionation). We aimed to test the benefits of radiotherapy schedules using fraction sizes larger than 2.0 Gy in terms of local-regional tumour control, normal tissue responses, quality of life, and economic consequences in women prescribed post-operative radiotherapy. METHODS: Between 1999 and 2001, 2215 women with early breast cancer (pT1-3a pN0-1 M0) at 23 centres in the UK were randomly assigned after primary surgery to receive 50 Gy in 25 fractions of 2.0 Gy over 5 weeks or 40 Gy in 15 fractions of 2.67 Gy over 3 weeks. Women were eligible for the trial if they were aged over 18 years, did not have an immediate reconstruction, and were available for follow-up. Randomisation method was computer generated and was not blinded. The protocol-specified principal endpoints were local-regional tumour relapse, defined as reappearance of cancer at irradiated sites, late normal tissue effects, and quality of life. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN59368779. FINDINGS: 1105 women were assigned to the 50 Gy group and 1110 to the 40 Gy group. After a median follow up of 6.0 years (IQR 5.0-6.2) the rate of local-regional tumour relapse at 5 years was 2.2% (95% CI 1.3-3.1) in the 40 Gy group and 3.3% (95% CI 2.2 to 4.5) in the 50 Gy group, representing an absolute difference of -0.7% (95% CI -1.7% to 0.9%)--ie, the absolute difference in local-regional relapse could be up to 1.7% better and at most 1% worse after 40 Gy than after 50 Gy. Photographic and patient self-assessments indicated lower rates of late adverse effects after 40 Gy than after 50 Gy. INTERPRETATION: A radiation schedule delivering 40 Gy in 15 fractions seems to offer rates of local-regional tumour relapse and late adverse effects at least as favourable as the standard schedule of 50 Gy in 25 fractions.

The UK Standardisation of Breast Radiotherapy (START) Trial A of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial.

BACKGROUND: The international standard radiotherapy schedule for breast cancer treatment delivers a high total dose in 25 small daily doses (fractions). However, a lower total dose delivered in fewer, larger fractions (hypofractionation) is hypothesised to be at least as safe and effective as the standard treatment. We tested two dose levels of a 13-fraction schedule against the standard regimen with the aim of measuring the sensitivity of normal and malignant tissues to fraction size. METHODS: Between 1998 and 2002, 2236 women with early breast cancer (pT1-3a pN0-1 M0) at 17 centres in the UK were randomly assigned after primary surgery to receive 50 Gy in 25 fractions of 2.0 Gy versus 41.6 Gy or 39 Gy in 13 fractions of 3.2 Gy or 3.0 Gy over 5 weeks. Women were eligible if they were aged over 18 years, did not have an immediate surgical reconstruction, and were available for follow-up. Randomisation method was computer generated and was not blinded. The protocol-specified principal endpoints were local-regional tumour relapse, defined as reappearance of cancer at irradiated sites, late normal tissue effects, and quality of life. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN59368779. FINDINGS: 749 women were assigned to the 50 Gy group, 750 to the 41.6 Gy group, and 737 to the 39 Gy group. After a median follow up of 5.1 years (IQR 4.4-6.0) the rate of local-regional tumour relapse at 5 years was 3.6% (95% CI 2.2-5.1) after 50 Gy, 3.5% (95% CI 2.1-4.3) after 41.6 Gy, and 5.2% (95% CI 3.5-6.9) after 39 Gy. The estimated absolute differences in 5-year local-regional relapse rates compared with 50 Gy were 0.2% (95% CI -1.3% to 2.6%) after 41.6 Gy and 0.9% (95% CI -0.8% to 3.7%) after 39 Gy. Photographic and patient self-assessments suggested lower rates of late adverse effects after 39 Gy than with 50 Gy, with an HR for late change in breast appearance (photographic) of 0.69 (95% CI 0.52-0.91, p=0.01). From a planned meta-analysis with the pilot trial, the adjusted estimates of alpha/beta value for tumour control was 4.6 Gy (95% CI 1.1-8.1) and for late change in breast appearance (photographic) was 3.4 Gy (95% CI 2.3-4.5). INTERPRETATION: The data are consistent with the hypothesis that breast cancer and the dose-limiting normal tissues respond similarly to change in radiotherapy fraction size. 41.6 Gy in 13 fractions was similar to the control regimen of 50 Gy in 25 fractions in terms of local-regional tumour control and late normal tissue effects, a result consistent with the result of START Trial B. A lower total dose in a smaller number of fractions could offer similar rates of tumour control and normal tissue damage as the international standard fractionation schedule of 50 Gy in 25 fractions.

Treatment planning and delivery of involved field radiotherapy in advanced Hodgkin's disease: results from a questionnaire-based audit for the UK Stanford V regimen vs ABVD clinical trial quality assurance programme (ISRCTN 64141244).

This questionnaire forms the basis of the quality assurance (QA) programme for the UK randomized Phase III study of the Stanford V regimen versus ABVD for treatment of advanced Hodgkin's disease to assess differences between participating centres in treatment planning and delivery of involved-field radiotherapy for Hodgkin's lymphoma The questionnaire, which was circulated amongst 42 participating centres, consisted of seven sections: target volume definition and dose prescription; critical structures; patient positioning and irradiation techniques; planning; dose calculation; verification; and future developments The results are based on 25 responses. One-third plan using CT alone, one-third use solely the simulator and the rest individualize, depending on disease site. Eleven centres determine a dose distribution for each patient. Technique depends on disease site and whether CT or simulator planning is employed. Most departments apply isocentric techniques and use immobilization and customized shielding. In vivo dosimetry is performed in 7 centres and treatment verification occurs in 24 hospitals. In conclusion, the planning and delivery of treatment for lymphoma patients varies across the country. Conventional planning is still widespread but most centres are moving to CT-based planning and virtual simulation with extended use of immobilization, customized shielding and compensation.

What is the optimum breast plan: a study based on the START trial plans.

Each year thousands of women within the UK are treated with radiotherapy for breast cancer. The majority of these women are treated using a medial and lateral tangential field. This study evaluates the plans submitted to the quality assurance (QA) team of the START trial and investigates some of the differences between departments. Throughout the START trial, hardcopies of the radiotherapy dose distribution on the central slice for one in three women were submitted to the QA team for analysis. The QA team measured physical parameters including breast size and lung depth as well as noting parameters used for the radiotherapy delivery including beam energy, field size and wedge angle. Over 1400 plans from 36 centres were analysed. The mean patient separation was 19.7 cm (SD 2.7 cm) with a mean lung depth of 1.5 cm (SD 0.7 cm). The modal beam energy was 6 MV and the mean wedge angle was 23 degrees . Significant differences in the choice of wedge angle between departments were noted; however, in 90% of cases the resultant plan complied with the maximum dose gradient of 10% on the central axis specified by the trial protocol. Less than 3% (37 plans) had dose gradients of greater than 12%. This resulted in a mean dose gradient for all patients on the central axis of 5.7% (SD 2.9%).

Verification films: a study of the daily and weekly reproducibility of breast patient set-up in the START trial.

AIMS: Verification of patient position in radiotherapy by the use of portal images is a current practice in most radiotherapy departments. All patients within the Standardisation of Breast Radiotherapy Trial (START) were required to have on-treatment verification images. Measurements of maximum lung and breast depth from these were used to provide details for the case-report forms. This study was undertaken to validate these measurements, assess the reproducibility of patients' set-up within the START trial and to compare reproducibility on a day-to-day basis with reproducibility over a longer period. Analysis also included a subjective assessment of image quality. MATERIALS AND METHODS: Fifty-three patients from 29 departments were studied. Some centres used electronic portal imaging and others used film. Where film verification was the method of choice, information was collected about the type of film and cassette used. RESULTS: The correlation coefficients for inter- and intra-observer variability of breast and lung depth were 0.99. Comparing maximum breast depth on weekly and daily images, the median per cent standard deviation of breast depth was 4% and 3%, respectively. The mean standard deviation of breast depth for all patients, which gives an indication of the individual patient variability, was 5.5 +/- 2.2 mm for weekly and 3.9 +/- 1.5 mm for daily measurements. For lung depth, mean standard deviation was 6.8 +/- 2.5 mm for weekly and 6.8 +/- 2.8 mm for daily measurements. Images taken using Kodak X-omat V film were inferior to those taken with films in corresponding cassettes. CONCLUSION: Differences between lung depth measured in simulator and on the treatment unit were evident for many patients. There was little difference in the standard deviations of breast and lung depth for daily and weekly verification films on the treatment machine.

Irradiation of the heart during tangential breast treatment: a study within the START trial.

Radiotherapy to the breast is often given as a component of the treatment for women with breast cancer. It has been shown to increase overall survival although an increase in cardiac mortality has also been noted. This study was undertaken as part of the START trial quality assurance programme to record and evaluate the cardiac dose using modern radiotherapy techniques. Departments randomizing patients into the START trial and who had CT facilities for planning breast patients were invited to take part. 62 patients were included. CT slices were taken at the level of the maximum heart depth and on the treatment field central axis. Each patient was planned in the normal way and the distributions were analysed by the quality assurance team at Mount Vernon Hospital. The maximum heart position was found to be inferior to the central axis used for breast planning for the majority of patients; mean position 2.3 cm inferior with a mean maximum heart depth of 0.55 cm. For 45% of patients the maximum heart dose was less than 50% of the prescribed dose. The study showed that the volume of irradiated cardiac tissue has decreased compared with earlier studies, and also highlighted the need to scan away from the central axis if the dose to cardiac tissue is to be assessed.

Survey of tangential field planning and dose distribution in the UK: background to the introduction of the quality assurance programme for the START trial in early breast cancer.

A background survey of UK breast radiotherapy techniques was performed prior to the introduction of the quality assurance programme for the Standardization of Radiotherapy (START) trial in breast cancer, a UK multicentre randomized trial of different dose fractionations for breast radiotherapy. Analysis of patient treatment plans was performed at this initial stage of the quality assurance programme to ensure eventual uniformity of treatment within the randomized trial and hence ensure reliable end results. As an integral part of this initial survey, three patient outlines of different size and shape were circulated between November 1997 and January 1998 to 56 UK radiotherapy centres. Dose distributions were produced according to the routine planning protocol of each department to provide information on treatment planning techniques. Criteria used for treatment plan production and the resultant dose distributions were analysed. The dose distributions varied between centres. Dose inhomogeneity of no more than 10% was achieved, on the central axis, for all chest wall and medium breast size plans. The number of larger breast size distributions exceeding a 10% dose gradient across the treatment volume was 54% (26). Most centres in the UK determine the breast dose distribution by planning on a two-dimensional contour taken along the central plane of the breast. Variation in the breast contour either side of this central plane is not taken into account. Care with plan optimization by selecting the most appropriate beam parameters can lead to an improvement in breast dosimetry.

Survey of UK breast radiotherapy techniques: background prior to the introduction of the quality assurance programme for the START (standardisation of radiotherapy) trial in breast cancer.

As an integral part of a quality assurance programme, this survey was undertaken to establish precise details of breast radiation techniques used within centres expressing an interest to participate in the START Trial--a U.K. multi-centre randomised trial of different dose fractionation schedules for breast cancer. A questionnaire was circulated between November 1997 and January 1999 to 56 U.K. radiotherapy centres. This covered specific details of patient immobilisation, technique and dose fractionation when treating breast or chest wall, supraclavicular fossa and axilla and when directing a boost to the tumour bed. Variations in technique, incorporating immobilisation, treatment energy and dose prescription span the entire radiation treatment process from localisation to planning and subsequent treatment. A range of dose/fraction/time schedules were used for tangential fields, nodal fields and the tumour bed boost. As part of the quality assurance programme for the START Trial this independent review of breast radiotherapy practice has provided a baseline of techniques used by centres prior to participating in the trial. It has also presented a view of the complexity of the issues to enable the design of the next phase of the quality assurance programme. Adherence to the trial protocol will ensure acceptable technique and dosimetry across centres.

CT simulation for radiotherapy treatment planning.

The present status of CT simulation (CT sim) hardware, software and practice is reviewed, particularly with regard to the changes that have taken place over the last 5 years. The latest technology is discussed together with some recently developed techniques. The article concludes with a discussion of virtual simulation vs physical (conventional) simulation; in particular there is a review of the changes that have been made to the "Disadvantages table" presented by Conway and Robinson [1], which now make CT sim an attractive system for any radiotherapy department.

A survey of radiotherapy quality control practice in the United Kingdom for the START trial.

BACKGROUND AND PURPOSE: This paper compares the quality control checks performed in departments in the United Kingdom with those recommended by the Institute of Physics and Engineering in Medicine (IPEM) in Report 81. METHOD: The data were gathered by the quality assurance team for the START trial, during visits to individual departments. Data are compared with the frequencies suggested in IPEM report 81. Where applicable, data are also analyzed with respect to machine manufacturer. RESULTS: All departments with linear accelerators check the output at least weekly for both photons and electrons, however 11% of departments do not perform a constancy check of the output on a daily basis. The majority of departments check flatness at gantry zero on a monthly basis. However 27% of departments never check at non-zero gantry angles. In 51% of departments no fluoroscopy checks are performed on simulators on a daily basis. CONCLUSION: The majority of departments are following the frequencies suggested in IPEM report 81 although there are a number of discrepancies particularly for simulators. Accelerator type needs to be considered when designing quality assurance checks. In many departments more time than is currently allocated is needed on equipment, particularly simulators, to complete all of the checks suggested in Report 81.

The START trial-measurements in semi-anatomical breast and chest wall phantoms.

This paper describes dosimetry measurements performed prior to departments entering patients into the START Trial, a breast fractionation trial. Absolute and relative doses were measured in semi-anatomical breast and chest wall phantoms, as part of a quality assurance programme visit. Doses were measured using an ionization chamber and the resulting distributions were compared with those calculated by the department. The mean ratio of measured to calculated dose at the START reference point was found to be 0.981 for the breast phantom and 0.978 for the chest wall phantom. This average measured dose was significantly less than the prescribed dose (p < 0.001). Differences were found between 2D and 3D planning systems and for departments using cobalt 60 beams. A number of departments had deviations of greater than 4%, which was the tolerance applied for this trial. It is essential for dose measurements of this type to be performed for randomized clinical trials involving radiotherapy, particularly where dose fractionation regimes are being compared.

A purpose-built iodine-125 irradiation plaque for low dose rate low energy irradiation of cell lines in vitro.

The phenomenon of hyper-radiosensitivity (HRS) to very low acute single doses of radiation has been demonstrated in several cell lines in vitro and in vivo, and has been studied in theory and in practice. The theory suggests a similar hypersensitivity when cells are continuously exposed to radiation at very low dose rates. These low dose rates are used when radioactive seed (iodine-125 or palladium-103) implants of the prostate are used as an alternative to surgery or external beam radiotherapy. To investigate the radiobiology of hypersensitivity of this type on various cell lines in vitro, an iodine-125 seed irradiator has been designed and built for safe use in the Gray Laboratory. In practice, the calculated dose rate has been used for consistency. Discrepancies between calculated and measured dose rates are discussed.

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.

Breast radiotherapy phantom design for the START trial. START trial management group.

The design of phantoms for use in radiotherapy involves a number of complex issues. This paper describes breast and chest wall phantoms that have been designed and constructed for the START trial. Four phantoms have been manufactured, including two two-dimensional phantoms used on the first round of audit visits to assess the ability of departments to plan with the required accuracy. Two further phantoms have been constructed and will be used in the second round of audit visits; one is a water-filled three-dimensional phantom for investigating off-axis dosimetry, the other is to be used to assess dose in the junction region between the tangential fields and the supraclavicular fossa field. The manufacturing and design process for each of the phantoms is discussed.