Radiotherapy dosimetry audit: three decades of improving standards and accuracy in UK clinical practice and trials.

Dosimetry audit plays an important role in the development and safety of radiotherapy. National and large scale audits are able to set, maintain and improve standards, as well as having the potential to identify issues which may cause harm to patients. They can support implementation of complex techniques and can facilitate awareness and understanding of any issues which may exist by benchmarking centres with similar equipment. This review examines the development of dosimetry audit in the UK over the past 30 years, including the involvement of the UK in international audits. A summary of audit results is given, with an overview of methodologies employed and lessons learnt. Recent and forthcoming more complex audits are considered, with a focus on future needs including the arrival of proton therapy in the UK and other advanced techniques such as four-dimensional radiotherapy delivery and verification, stereotactic radiotherapy and MR linear accelerators. The work of the main quality assurance and auditing bodies is discussed, including how they are working together to streamline audit and to ensure that all radiotherapy centres are involved. Undertaking regular external audit motivates centres to modernize and develop techniques and provides assurance, not only that radiotherapy is planned and delivered accurately but also that the patient dose delivered is as prescribed.

A multicentre 'end to end' dosimetry audit for cervix HDR brachytherapy treatment.

PURPOSE: To undertake the first multicentre fully 'end to end' dosimetry audit for HDR cervix brachytherapy, comparing planned and delivered dose distributions around clinical treatment applicators, with review of local procedures. MATERIALS AND METHODS: A film-dosimetry audit was performed at 46 centres, including imaging, applicator reconstruction, treatment planning and delivery. Film dose maps were calculated using triple-channel dosimetry and compared to RTDose data from treatment planning systems. Deviations between plan and measurement were quantified at prescription Point A and using gamma analysis. Local procedures were also discussed. RESULTS: The mean difference between planned and measured dose at Point A was -0.6% for plastic applicators and -3.0% for metal applicators, at standard uncertainty 3.0% (k=1). Isodose distributions agreed within 1mm over a dose range 2-16Gy. Mean gamma passing rates exceeded 97% for plastic and metal applicators at 3% (local) 2mm criteria. Two errors were found: one dose normalisation error and one applicator library misaligned with the imaged applicator. Suggestions for quality improvement were also made. CONCLUSIONS: The concept of 'end to end' dosimetry audit for HDR brachytherapy has been successfully implemented in a multicentre environment, providing evidence that a high level of accuracy in brachytherapy dosimetry can be achieved.

Global harmonization of quality assurance naming conventions in radiation therapy clinical trials.

PURPOSE: To review the various radiation therapy quality assurance (RTQA) procedures used by the Global Clinical Trials RTQA Harmonization Group (GHG) steering committee members and present the harmonized RTQA naming conventions by amalgamating procedures with similar objectives. METHODS AND MATERIALS: A survey of the GHG steering committee members' RTQA procedures, their goals, and naming conventions was conducted. The RTQA procedures were classified as baseline, preaccrual, and prospective/retrospective data capture and analysis. After all the procedures were accumulated and described, extensive discussions took place to come to harmonized RTQA procedures and names. RESULTS: The RTQA procedures implemented within a trial by the GHG steering committee members vary in quantity, timing, name, and compliance criteria. The procedures of each member are based on perceived chances of noncompliance, so that the quality of radiation therapy planning and treatment does not negatively influence the trial measured outcomes. A comparison of these procedures demonstrated similarities among the goals of the various methods, but the naming given to each differed. After thorough discussions, the GHG steering committee members amalgamated the 27 RTQA procedures to 10 harmonized ones with corresponding names: facility questionnaire, beam output audit, benchmark case, dummy run, complex treatment dosimetry check, virtual phantom, individual case review, review of patients' treatment records, and protocol compliance and dosimetry site visit. CONCLUSIONS: Harmonized RTQA harmonized naming conventions, which can be used in all future clinical trials involving radiation therapy, have been established. Harmonized procedures will facilitate future intergroup trial collaboration and help to ensure comparable RTQA between international trials, which enables meta-analyses and reduces RTQA workload for intergroup studies.

Escalated-dose versus control-dose conformal radiotherapy for prostate cancer: long-term results from the MRC RT01 randomised controlled trial.

BACKGROUND: The aim of this trial was to compare dose-escalated conformal radiotherapy with control-dose conformal radiotherapy in patients with localised prostate cancer. Preliminary findings reported after 5 years of follow-up showed that escalated-dose conformal radiotherapy improved biochemical progression-free survival. Based on the sample size calculation, we planned to analyse overall survival when 190 deaths occurred; this target has now been reached, after a median 10 years of follow-up. METHODS: RT01 was a phase 3, open-label, international, randomised controlled trial enrolling men with histologically confirmed T1b-T3a, N0, M0 prostate cancer with prostate specific antigen of less than 50 ng/mL. Patients were randomly assigned centrally in a 1:1 ratio, using a computer-based minimisation algorithm stratifying by risk of seminal vesicle invasion and centre to either the control group (64 Gy in 32 fractions, the standard dose at the time the trial was designed) or the escalated-dose group (74 Gy in 37 fractions). Neither patients nor investigators were masked to assignment. All patients received neoadjuvant androgen deprivation therapy for 3-6 months before the start of conformal radiotherapy, which continued until the end of conformal radiotherapy. The coprimary outcome measures were biochemical progression-free survival and overall survival. All analyses were done on an intention-to-treat basis. Treatment-related side-effects have been reported previously. This trial is registered, number ISRCTN47772397. FINDINGS: Between Jan 7, 1998, and Dec 20, 2001, 862 men were registered and 843 subsequently randomly assigned: 422 to the escalated-dose group and 421 to the control group. As of Aug 2, 2011, 236 deaths had occurred: 118 in each group. Median follow-up was 10·0 years (IQR 9·1-10·8). Overall survival at 10 years was 71% (95% CI 66-75) in each group (hazard ratio [HR] 0·99, 95% CI 0·77-1·28; p=0·96). Biochemical progression or progressive disease occurred in 391 patients (221 [57%] in the control group and 170 [43%] in the escalated-dose group). At 10 years, biochemical progression-free survival was 43% (95% CI 38-48) in the control group and 55% (50-61) in the escalated-dose group (HR 0·69, 95% CI 0·56-0·84; p=0·0003). INTERPRETATION: At a median follow-up of 10 years, escalated-dose conformal radiotherapy with neoadjuvant androgen deprivation therapy showed an advantage in biochemical progression-free survival, but this advantage did not translate into an improvement in overall survival. These efficacy data for escalated-dose treatment must be weighed against the increase in acute and late toxicities associated with the escalated dose and emphasise the importance of use of appropriate modern radiotherapy methods to reduce side-effects. FUNDING: UK Medical Research Council.

Contribution to normal tissue dose from concomitant radiation for two common kV-CBCT systems and one MVCT system used in radiotherapy.

BACKGROUND AND PURPOSE: This study outlines the measured doses for three concomitant imaging modalities used in radiotherapy. MATERIAL AND METHODS: Doses were measured using thermo luminescent dosemeters within pelvis and thorax anthropomorphic phantoms for the Varian On Board Imager (OBI), Elekta X-ray Volume Imager (XVI) and Tomotherapy HiArt II systems. Organ sites were selected to include those organs which would be irradiated by the treatment beam during the therapy exposure. RESULTS: Doses for kilovoltage imaging systems are comparable within the pelvis phantom at 20-30 mGy. Thorax phantom doses are lower, especially where user specified protocols are used at 5-10 mGy. Tomotherapy doses are typically less than 10 mGy for both phantoms. CONCLUSIONS: Concomitant imaging dose is a small fraction of the therapy dose, however, for a high fraction technique, the imaging dose can become comparable to the therapy dose outside primary target volume. Recommendations for optimisation of imaging in radiotherapy are presented.

EORTC Radiation Oncology Group quality assurance platform: establishment of a digital central review facility.

OBJECTIVE: Quality assurance (QA) in clinical trials is essential to ensure treatment is safely and effectively delivered. As QA requirements have increased in complexity in parallel with evolution of radiation therapy (RT) delivery, a need to facilitate digital data exchange emerged. Our objective is to present the platform developed for the integration and standardization of QART activities across all EORTC trials involving RT. METHODS: The following essential requirements were identified: secure and easy access without on-site software installation; integration within the existing EORTC clinical remote data capture system; and the ability to both customize the platform to specific studies and adapt to future needs. After retrospective testing within several clinical trials, the platform was introduced in phases to participating sites and QART study reviewers. RESULTS: The resulting QA platform, integrating RT analysis software installed at EORTC Headquarters, permits timely, secure, and fully digital central DICOM-RT based data review. Participating sites submit data through a standard secure upload webpage. Supplemental information is submitted in parallel through web-based forms. An internal quality check by the QART office verifies data consistency, formatting, and anonymization. QART reviewers have remote access through a terminal server. Reviewers evaluate submissions for protocol compliance through an online evaluation matrix. Comments are collected by the coordinating centre and institutions are informed of the results. CONCLUSIONS: This web-based central review platform facilitates rapid, extensive, and prospective QART review. This reduces the risk that trial outcomes are compromised through inadequate radiotherapy and facilitates correlation of results with clinical outcomes.

Quality assurance for prospective EORTC radiation oncology trials: the challenges of advanced technology in a multicenter international setting.

The European Organization for the Research and Treatment of Cancer (EORTC) is a pan-European structure charged with improving cancer treatment through the testing of new therapeutic strategies in phases I-III clinical studies. Properly conducted trials in radiation oncology are required to demonstrate superiority of a new treatment over the current standard. The Radiation Oncology Group (ROG) has initiated a complex quality assurance (QA) program to ensure safe and effective treatment delivery. Most modern trials are multicenter and multidisciplinary, further increasing the importance of early, strict and consistent QA in radiotherapy (RT). QART measures confirm whether a site possesses minimum staff and equipment for participation. Dummy runs, reviews of patient treatment plans and complex dosimetry checks verify the ability of an institution to comply with the protocol. Data required for evaluation are increasingly exchanged digitally, allowing detailed plan reconstruction, evaluation of target volume delineation and recalculation of dose-volume parameters for comparison against predefined standards. The five tiers of QA implemented in EORTC trials are reviewed, along with past, current and future QART initiatives. As substantial human and financial resources are increasingly invested in QART, the importance of cost-benefit analysis of QA and its impact on clinical outcome cannot be overstated.

Radiation dose from volumetric helical perfusion CT of the thorax, abdomen or pelvis.

PURPOSE: To evaluate the radiation doses delivered during volumetric helical perfusion CT of the thorax, abdomen or pelvis. MATERIALS AND METHODS: The dose-length product (DLP) and CT dose index (CTDIvol) were recorded and effective dose (E) determined for patients undergoing CT (4D adaptive spiral) for tumour evaluation. Image noise and contrast to noise (CNR) at peak enhancement were also assessed for quality. RESULTS: Forty two consecutive examinations were included: thorax (16), abdomen (10), pelvis (16). Z-axis coverage ranged from 11.4 to 15.7 cm. Mean DLP was 1288.8 mGy.cm (range: 648 to 2456 mGy.cm). Mean CTDIvol was 96.2 mGy (range: 32.3 to 169.4 mGy). Mean effective dose was 19.6 mSv (range: 12.3 mSv to 36.7 mSv). In comparison mean DLP and effective dose was 885.2 mGy.cm (range: 504 to 1633 mGy.cm) and 13.3 mSV (range: 7.8 to 24.5 mSv) respectively for the standard staging CT thorax, abdomen and pelvis. Mean tumour CNR at peak enhancement was 1.87. CONCLUSION: The radiation dose imposed by perfusion CT was on average 1.5 times that of a CT thorax, abdomen and pelvis. The dose is not insubstantial, and must be balanced by the potential clinical utility of additional physiologic data. Further efforts towards dose reduction should be encouraged.

Dummy run and conformity indices in the ongoing EORTC low-grade glioma trial 22033-26033: First evaluation of quality of radiotherapy planning.

PURPOSE: Early assessment of radiotherapy (RT) quality in the ongoing EORTC trial comparing primary temozolomide versus RT in low-grade gliomas. MATERIALS AND METHODS: RT plans provided for dummy cases were evaluated and compared against expert plans. We analysed: (1) tumour and organs-at-risk delineation, (2) geometric and dosimetric characteristics, (3) planning parameters, compliance with dose prescription and Dmax for OAR (4) indices: RTOG conformity index (CI), coverage factor (CF), tissue protection factor (PF); conformity number (CN = PF x CF); dose homogeneity in PTV (U). RESULTS: Forty-one RT plans were evaluated. Only two (5%) centres were requested to repeat CTV-PTV delineations. Three (7%) plans had a significant under-dosage and dose homogeneity in one deviated > 10%. Dose distribution was good with mean values of 1.5, 1, 0.68, and 0.68 (ideal values = 1) for CI, CF, PF, and CN, respectively. CI and CN strongly correlated with PF and they correlated with PTV. Planning with more beams seems to increase PTV(Dmin), improving CF. U correlated with PTV(Dmax). CONCLUSION: Preliminary results of the dummy run procedure indicate that most centres conformed to protocol requirements. To quantify plan quality we recommend systematic calculation of U and either CI or CN, both of which measure the amount of irradiated normal brain tissue.

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

Dosimetry and field matching for radiotherapy to the breast and supraclavicular fossa.

PURPOSE: Early breast cancer radiotherapy aims for local disease control and reduced recurrence. Treatment is directed to breast or chest wall alone using tangential fields, or includes regional lymph nodes with a separate anterior field. The complex geometry of this region necessitates matching adjacent radiation fields in three-dimensions. Potential exists for overdosage or underdosage and cosmetic results may be compromised if fields are not accurately aligned. METHODS AND MATERIALS: A study of dosimetry across the match line region using different techniques, as reported in the multicentre START Trial Quality Assurance programme, was undertaken. A custom-made anthropomorphic phantom assessed dose distribution in three-dimensions using film dosimetry. RESULTS: Methods with varying degrees of complexity were employed for field matching. Techniques combined half beam blocking and machine rotations to achieve geometric alignment. Asymmetric beam matching allowed use of a single isocentre technique. Where field matching was not undertaken a gap between tangential and nodal fields was employed. Results demonstrated differences between techniques and variations for similar techniques in different centres. Geometric alignment techniques produced more homogenous dose distributions in the match region than gap techniques or those techniques not correcting for field divergence. CONCLUSIONS: Field matching techniques during the START trial varied between centres. Film dosimetry used in conjunction with a breast-shaped phantom provided relative dose information. The study highlighted difficulties in matching treatment fields to achieve homogenous dose distribution through the region of the match plane and the degree of inhomogeneity as a consequence of a gap between treatment fields.

Profile of European radiotherapy departments contributing to the EORTC Radiation Oncology Group (ROG) in the 21st century.

PURPOSE: Since 1982, the Radiation Oncology Group of the EORTC (EORTC ROG) has pursued an extensive Quality Assurance (QA) program involving all centres actively participating in its clinical research. The first step is the evaluation of the structure and of the human, technical and organisational resources of the centres, to assess their ability to comply with the current requirements for high-tech radiotherapy (RT). MATERIALS AND METHODS: A facility questionnaire (FQ) was developed in 1989 and adapted over the years to match the evolution of RT techniques. We report on the contents of the current FQ that was completed online by 98 active EORTC ROG member institutions from 19 countries, between December 2005 and October 2007. RESULTS: Similar to the data collected previously, large variations in equipment, staffing and workload between centres remain. Currently only 15 centres still use a Cobalt unit. All centres perform 3D Conformal RT, 79% of them can perform IMRT and 54% are able to deliver stereotactic RT. An external reference dosimetry audit (ERDA) was performed in 88% of the centres for photons and in 73% for electrons, but it was recent (<2 years) in only 74% and 60%, respectively. CONCLUSION: The use of the FQ helps maintain the minimum quality requirements within the EORTC ROG network: recommendations are made on the basis of the analysis of its results. The present analysis shows that modern RT techniques are widely implemented in the clinic but also that ERDA should be performed more frequently. Repeated assessment using the FQ is warranted to document the future evolution of the EORTC ROG institutions.

Quality assurance of dosimetry and the impact on sample size in randomized clinical trials.

BACKGROUND AND PURPOSE: The aim of this study was to investigate the impact of appropriate dosimetry quality assurance (QA) on patient number required in radiotherapy randomized control trials (RCT). MATERIALS AND METHODS: The steepness of clinical dose-response curves, gamma(clin.), was calculated by a convoluting a biological dose-response distribution and the distribution of technical and dosimetrical factors. Population size calculation was performed taking into account gamma(clin.) and expected difference in outcome between two arms of an RCT, for different levels of variation in dose to the patient population. RESULTS: Uncertainties in dose reduces gamma(clin.) to the largest extent when the initial gamma-value is high and less so for low gamma-value. Reduced uncertainty in dose led to a significant reduction in the number of patients required in an RCT if the expected difference between the experimental and conventional arm is small. The reduction in patient numbers is less when the differences between the conventional and experimental arm is larger. CONCLUSION: The number of patients required in an RCT may be reduced by introducing appropriate dosimetry QA as the risk of under-powering the study is minimized. Dosimetry QA in clinical studies is therefore cost-effective.

Escalated-dose versus standard-dose conformal radiotherapy in prostate cancer: first results from the MRC RT01 randomised controlled trial.

BACKGROUND: In men with localised prostate cancer, conformal radiotherapy (CFRT) could deliver higher doses of radiation than does standard-dose conventional radical external-beam radiotherapy, and could improve long-term efficacy, potentially at the cost of increased toxicity. We aimed to present the first analyses of effectiveness from the MRC RT01 randomised controlled trial. METHODS: The MRC RT01 trial included 843 men with localised prostate cancer who were randomly assigned to standard-dose CFRT or escalated-dose CFRT, both administered with neoadjuvant androgen suppression. Primary endpoints were biochemical-progression-free survival (bPFS), freedom from local progression, metastases-free survival, overall survival, and late toxicity scores. The toxicity scores were measured with questionnaires for physicians and patients that included the Radiation Therapy Oncology Group (RTOG), the Late Effects on Normal Tissue: Subjective/Objective/Management (LENT/SOM) scales, and the University of California, Los Angeles Prostate Cancer Index (UCLA PCI) scales. Analysis was done by intention to treat. This trial is registered at the Current Controlled Trials website http://www.controlled-trials.com/ISRCTN47772397. FINDINGS: Between January, 1998, and December, 2002, 843 men were randomly assigned to escalated-dose CFRT (n=422) or standard-dose CFRT (n=421). In the escalated group, the hazard ratio (HR) for bPFS was 0.67 (95% CI 0.53-0.85, p=0.0007). We noted 71% bPFS (108 cumulative events) and 60% bPFS (149 cumulative events) by 5 years in the escalated and standard groups, respectively. HR for clinical progression-free survival was 0.69 (0.47-1.02; p=0.064); local control was 0.65 (0.36-1.18; p=0.16); freedom from salvage androgen suppression was 0.78 (0.57-1.07; p=0.12); and metastases-free survival was 0.74 (0.47-1.18; p=0.21). HR for late bowel toxicity in the escalated group was 1.47 (1.12-1.92) according to the RTOG (grade >/=2) scale; 1.44 (1.16-1.80) according to the LENT/SOM (grade >/=2) scales; and 1.28 (1.03-1.60) according to the UCLA PCI (score >/=30) scale. 33% of the escalated and 24% of the standard group reported late bowel toxicity within 5 years of starting treatment. HR for late bladder toxicity according to the RTOG (grade >/=2) scale was 1.36 (0.90-2.06), but this finding was not supported by the LENT/SOM (grade >/=2) scales (HR 1.07 [0.90-1.29]), nor the UCLA PCI (score >/=30) scale (HR 1.05 [0.81-1.36]). INTERPRETATION: Escalated-dose CFRT with neoadjuvant androgen suppression seems clinically worthwhile in terms of bPFS, progression-free survival, and decreased use of salvage androgen suppression. This additional efficacy is offset by an increased incidence of longer term adverse events.

A versatile phantom for quality assurance in the UK Medical Research Council (MRC) RT01 trial (ISRCTN47772397) in conformal radiotherapy for prostate cancer.

Within the UK RT01 trial the MRC also funded a quality assurance (QA) programme. This included a planning and dosimetry audit at participating centres using a purpose built phantom. Geometrical setup was visually assessed via field shaping around the phantom GTV (to within the order of 1 mm). Within the phantom, ion chamber positional uncertainties were estimated as 0.6 mm (95% CL, k=2). This was the basis for ion chamber measurements in a variety of dose gradients around the PTV closely simulating a patient case. The design provides a representative but reproducible system for QA in the prostate radiotherapy process, from CT scan to treatment. Setup errors are not eliminated, but minimised and estimated.

Comparison of two dimensional and three dimensional radiotherapy treatment planning in locally advanced non-small cell lung cancer treated with continuous hyperfractionated accelerated radiotherapy weekend less.

BACKGROUND AND PURPOSE: Patients with inoperable non-small cell lung cancer being treated with continuous hyperfractionated accelerated radiotherapy weekend less (CHARTWEL) were planned and treated with a three dimensional (3D) conformal protocol and comparison made with two dimensional (2D) planning, as used previously, to compare past practice and methods. PATIENTS AND METHODS: Twenty-four patients were planned initially using 3D and then replanned using a 2D system. The 2D plans were transferred onto the 3D system and recalculated. Dose volume histograms could then be constructed of planning target volumes for phases 1 and 2 (PTV 1 and 2, respectively), lung and spinal cord for the 2D plans and compared with the 3D plans. RESULTS: There was a significantly lower absolute dose to the isocentre with 2D compared to 3D planning with dose reductions of 3.9% for phase 1, 4.4% for phase 2 and 4.7% for those treated with a single phase. Maximum dose to spinal cord was greater in 17 of the 24 2D plans with a median dose reduction of 0.82 Gy for 3D (P=0.04). The percentage volume of whole lung receiving > or =20 Gy (V20) was greater in 16 of the 24 2D plans with a median reduction in V20 of 2.4% for 3D (P=0.03). CONCLUSIONS: A lower dose to tumour was obtained using 2D planning due to the method of dose calculation and spinal cord and lung doses were significantly higher.

Questionnaire based quality assurance for the RT01 trial of dose escalation in conformal radiotherapy for prostate cancer (ISRCTN 47772397).

BACKGROUND AND PURPOSE: In order to ensure the validity of the outcome of the Medical Research Council's 'RTO1 trial' of dose escalation in conformal radiotherapy for prostate cancer it was considered important that the quality of treatment delivery should meet an adequate standard across all contributing centres. A questionnaire was therefore devised to ensure that all aspects of the planning and delivery process were adequately covered. PATIENTS AND METHODS: The questionnaire considered each step in the planning and delivery process and drew the attention of the participants to the specific requirements of the trial. Before entering patients into the trial each participating centre had to complete the questionnaire and an outlining exercise (reported elsewhere). RESULTS: It was not practicable to define a detailed universally acceptable protocol for the whole process of delivery of conformal radiotherapy, not least because of the different equipment available for planning and treatment in different centres. The questionnaire identified some areas of difference in practice between centres where there may be a need for the development of a consensus as to best practice, particularly in the area of patient set-up. Occasionally it was necessary to follow up responses to questions that had been misunderstood or inadequately answered, but in most cases these issues proved to be easily resolved. CONCLUSIONS: The questionnaire proved to be a useful self-assessment tool as well as enabling the quality assurance group to ensure that the standards of the trial were being met. Subsequent follow-up visits confirmed the usefulness and validity of this self assessment process.

Implementing the UK Medical Research Council (MRC) RT01 trial (ISRCTN 47772397): methods and practicalities of a randomised controlled trial of conformal radiotherapy in men with localised prostate cancer.

BACKGROUND AND PURPOSE: Radiotherapy is the most frequently used treatment for men with localised prostate cancer. Conformal radiotherapy (CFRT) is a relatively new development. MRC RT01 was set-up to explore optimum CFRT dose. PATIENTS AND METHODS: RT01 was an international multi-centre randomised controlled trial for men with T1b-T3a, N0, M0 prostate cancer that evolved from a single-centre pilot trial of similar design. All men received at least 3 months of pre-radiotherapy hormone treatment, before randomisation to standard (64 Gy) or high dose (74 Gy) radical CFRT. Accrual was completed in December 2001 with 843 men randomised from 25 centres in less than 4 years. RT01 has been a catalyst for implementing CFRT across UK. In addition to the Trial Management Group, independent Data Monitoring and Ethics Committee and independent Trial Steering Committee, a Quality of Life and Health Economics (QL/HE) group, a radiotherapy Quality Assurance (QA) Group and a Radiography Trial Implementation Group were set up. The QL/HE group ensured implementation, compliance, analysis and interpretation of the QL and HE data in the trial. The inauguration of QA and Radiography groups facilitated inter-centre collaboration. The QA Group ensured procedures were in place before and during trial participation, and monitored quality and consistency with systems including a physics questionnaire, a clinical examples exercise, a standard operating procedure document, designing and building a phantom, and convening a complications modelling subgroup. The Radiography group agreed and implemented technique improvements. RESULTS: More centres participated than initially predicted, enabling recruitment better than scheduled. The trial expedited the implementation of CFRT in many UK radiotherapy centres. Additionally, the QA and Radiography groups helped ensure smooth initiation and established consistency in planning, dosimetry and delivery of prostate CFRT services at participating UK centres. Considerable data has been collected; a series of papers will be produced, although mature clinical trial results are not anticipated until 2006-2008.

The use of in vivo thermoluminescent dosimeters in the quality assurance programme for the START breast fractionation trial.

BACKGROUND AND PURPOSE: The use of in vivo dosimetry for patient measurement is recommended in many publications. It provides an additional check to verify that the dose delivered to the patient corresponds to the prescribed dose. In the context of a clinical trial investigating the effects of different fractionation regimens, it is imperative that the dose given is that prescribed to ensure that noise in the data between centres does not mask the results of the trial. The methodology for in vivo measurement in a clinical trial of breast radiotherapy was developed and verified. MATERIALS AND METHODS: A cohort of patients in the STAndardisation of breast RadioTherapy (START) trial was monitored using postal thermoluminescent dosimeters chips (TLD). All TLD were processed and analysed at Mount Vernon Hospital. Patients for in vivo measurements were identified at randomisation as a random 1 in 9 samples for the first 2500 patients randomised (282 TLD) increasing to 1 in 3 thereafter. The TLD were left in place for the duration of the tangential field treatment and thus a composite entrance and exit dose was recorded. RESULTS: TLD measurements were performed on 429 patients from 33 hospitals. The average ratio of dose measured using TLD to that prescribed was 0.99+/-0.04. Eight patients had initial measurements more than 10% different to the prescribed dose. The mean TLD results for a given centre correlated well with dose measurements performed using an ionisation chamber in a breast shaped phantom at that centre as part of the START trial audit. CONCLUSION: Thermoluminescence dosimetry has provided useful quality assurance information on the doses received by patients in centres participating in the START trial.