Radiotherapy quality assurance: time for everyone to take it seriously

Like high-risk industries, radiotherapy requires intense attention to detail, alertness, precision, and adequate human and material resources to minimise the risk of irreversible consequences. Clinical trials data such as that generated by the Quality Assurance programme of the Radiotherapy Group of the European Organization for Research and Treatment of Cancer (EORTC) in this issue of the Journal have been instrumental in identifying problems with technical quality, the understanding of which can have a direct impact on improving the quality of care in the community. Consistency in absolute dosimetry, dose delivery, volume definition and reproducibility are paramount in radiotherapy quality assurance and have become even more important with the advent of conformal therapy. Extension of these principles to other oncological disciplines has added an additional dimension of improvement. Waiting times and measures of access must also be monitored if overall quality at the population level is to be assessed and enhanced. Lessons should be learned from clinical trials methodology in the use of intervention-specific guidelines, physician education and real time audit of treatment planning decisions. In the future, novel approaches, such as web based systems may further improve education and audit. Wider application and audit of evidence-based management guidelines about the use radiotherapy will bring to standard clinical practice the quality benefits that are considered a basic minimum standard for clinical trials.     

放疗自动计划研究进展

常规放疗计划设计是一个耗时耗力的过程,需要在计划优化中不断调整参数来寻找最优计划。此外,计划设计者之间的经验差异、投入计划设计的时间以及医疗机构的执行标准都会影响计划质量,从而影响临床治疗效果以及患者预后。近年来自动计划发展迅速,自动计划能够在保证计划质量前提下提升计划设计效率。当前已有一些方法致力于放疗计划设计的自动...     

Design of and technical challenges involved in a framework for multicentric radiotherapy treatment planning studies

This report introduces a framework for comparing radiotherapy treatment planning in multicentric in silico clinical trials. Quality assurance, data incompatibility, transfer and storage issues, and uniform analysis of results are discussed. The solutions that are given provide a useful guide for the set-up of future multicentric planning studies or public repositories of high quality data.     

Current status and perspectives of brachytherapy for cervical cancer

Standard definitive radiotherapy for cervical cancer consists of whole pelvic external beam radiotherapy (EBRT) and intracavitary brachytherapy (ICBT). In Japan, high-dose-rate ICBT (HDR-ICBT) has been utilized in clinical practice for more than 40 years. Several randomized clinical trials demonstrated that HDR-ICBT achieved comparative outcomes, both for pelvic control and incidences of late complications, to low-dose-rate (LDR) ICBT. In addition, HDR-ICBT has some potential advantages over LDR-ICBT, leading to further improvement in treatment results. Prior to the current computer planning systems, some excellent treatment planning concepts were established. At present, systems modified from these concepts, or novel approaches, such as image-guided brachytherapy (IGBT) are under investigation. One serious problem to be solved in HDR-ICBT for cervical cancer is that of the discrepancy in standard treatment schedules for combination HDR-ICBT and EBRT between the United States and Japan. Prospective studies are ongoing to assess the efficacy and toxicity of the Japanese schedule.     

Considerations for post-operative radiotherapy to the hemithorax following extrapleural pneumonectomy in malignant pleural mesothelioma

With growing interest in evaluating extrapleural pneumonectomy (EPP) and post-operative in selected patients with early stage malignant pleural mesothelioma, it is essential that clinical trials should be conducted using a clear and reproducible radiotherapy protocol. The considerations which have determined the policy of radiotherapy planning and treatment delivery for patients with mesothelioma in The Netherlands are given. As well as general considerations such as patient selection, target volume and critical organ delineation, a dose-fractionation scheme, constraints relating to normal tissue, treatment planning, the type of external beam equipment, treatment verification and radiation toxicity and scoring are all taken into account.     

The impact of introducing intensity modulated radiotherapy into routine clinical practice.

BACKGROUND AND PURPOSE: Intensity modulated radiotherapy (IMRT) at the Royal Marsden Hospital London was introduced in July 2001. Treatment delivery was dynamic using a single-phase technique. Concerns were raised regarding increased clinical workload due to introduction of new technology. The potential increased use of resources was assessed. PATIENTS AND METHODS: IMRT patient selection was within guidelines of clinical trials and included patients undergoing prostate plus pelvic lymph node (PPN) irradiation and head and neck cancer (HNC) treatment. Patient planning, quality assurance and treatment times were collected for an initial IMRT patient group. A comparative group of patients with advanced HNC undergoing two- or three-phase conventional radiotherapy, requiring matched photon and electron fields, were also timed. RESULTS: The median overall total planning time for IMRT was greater for HNC patients compared to the PPN cohort. For HNC the overall IMRT planning time was significantly longer than for conventional. The median treatment time for conventional two- or three-phase HNC treatments, encompassing similar volumes to those treated with IMRT, was greater than that for the IMRT HNC patient cohort. A reduction in radiographer man hours per patient of 4.8h was recorded whereas physics time was increased by 4.9h per patient. CONCLUSIONS: IMRT currently increases overall planning time. Additional clinician input is required for target volume localisation. Physics time is increased, a significant component of this being patient specific QA. Radiographer time is decreased. For HNC a single phase IMRT treatment has proven to be more efficient than a multiple phase conventional treatment. IMRT has been integrated smoothly and efficiently into the existing treatment working day. This preliminary study suggests that IMRT could be a routine treatment with efficient use of current radiotherapy resources.     

Quality assurance of radiotherapy in cancer treatment: toward improvement of patient safety and quality of care

The process of radiotherapy (RT) is complex and involves understanding of the principles of medical physics, radiobiology, radiation safety, dosimetry, radiation treatment planning, simulation and interaction of radiation with other treatment modalities. Each step in the integrated process of RT needs quality control and quality assurance (QA) to prevent errors and to give high confidence that patients will receive the prescribed treatment correctly. Recent advances in RT, including intensity-modulated and image-guided RT, focus on the need for a systematic RTQA program that balances patient safety and quality with available resources. It is necessary to develop more formal error mitigation and process analysis methods, such as failure mode and effect analysis, to focus available QA resources optimally on process components. External audit programs are also effective. The International Atomic Energy Agency has operated both an on-site and off-site postal dosimetry audit to improve practice and to assure the dose from RT equipment. Several countries have adopted a similar approach for national clinical auditing. In addition, clinical trial QA has a significant role in enhancing the quality of care. The Advanced Technology Consortium has pioneered the development of an infrastructure and QA method for advanced technology clinical trials, including credentialing and individual case review. These activities have an impact not only on the treatment received by patients enrolled in clinical trials, but also on the quality of treatment administered to all patients treated in each institution, and have been adopted globally; by the USA, Europe and Japan also.     

Indications, Integration, and Technical Aspects of Local-Regional Irradiation in the Management of Advanced Breast Cancer

This article reviews the indications for radiotherapy in advanced stage disease and discusses the recent prospective trials demonstrating a survival benefit by the addition of radiotherapy. Various treatment plans are reviewed with and without internal mammary node coverage. Although it is not clear whether internal mammary node irradiation can have a favorable impact on survival, it is clear that inadequate treatment planning of the parasternal region can result in excess cardiac morbidity and mortality. Careful planning using computed tomographic systems is required to optimize chest wall planning. With individualized treatment planning, it is hoped that the next generation of trials will show improved survival from further reduction in breast cancer deaths and significantly decreased cardiac toxicity.     

放射治疗计划自动化分级建议北大核心CSCD

在大数据和人工智能的助力下,放射治疗计划自动化的研究及临床应用发展迅速。放疗计划自动化系统的使用和监管等工作,需要仔细考虑自动化的程度及其适用环境。对于自动驾驶车辆,国内外定义了其自动化水平,但对于放疗计划自动化没有类似的定义。为了促进和规范放疗计划自动化发展,并激发行业讨论,我们参考汽车驾驶自动化分级制定了此分级建议,将放疗计划自动化分成6个等级(1级至6级)。     

Accrediting radiation technique in a multicentre trial of chemoradiation for pancreatic cancer

Before a multicentre trial of 3‐D conformal radiotherapy to treat cancer of the pancreas, participating clinicians were asked to complete an accreditation exercise. This involved planning two test cases according to the study protocol, then returning hard copies of the plans and dosimetric data for review. Any radiation technique that achieved the specified constraints was allowed. Eighteen treatment plans were assessed. Seven plans were prescribed incorrect doses and two of the planning target volumes did not comply with protocol guidelines. All plans met predefined normal tissue dose constraints. The identified errors were attributable to unforeseen ambiguities in protocol documentation. They were addressed by feedback and corresponding amendments to protocol documentation. Summary radiobiological measures including total weighted normal tissue equivalent uniform dose varied significantly between centres. This accreditation exercise successfully identified significant potential sources of protocol violations, which were then easily corrected. We believe that this process should be applied to all clinical trials involving radiotherapy. Due to the limitations of data analysis with hard‐copy information only, it is recommended that complete planning datasets from treatment‐planning systems be collected through a digital submission process.     

Use of 'sham' radiotherapy in randomized clinical trials

The objective of this systematic review was to identify quality trials that use sham radiotherapy in their design and review them to determine its potential value. The Cochrane Library, Pubmed and a Reference Search served as data sources. Trials were included if they met a minimum quality score of 3 on a validated assessment instrument (which assesses randomization, control and blinding) and if they compared sham radiotherapy to active treatment. External beam therapy and brachytherapy trials were considered. Twenty-six trials were identified, collectively including 2663 participants in the period of 1970-2004. All the trials studied the value of radiotherapy for treatment or prevention of benign diseases, including multiple sclerosis, coronary artery restenosis, age-related macular degeneration and Graves' ophthalmopathy. There were no trials relating to the use of radiotherapy in the treatment of malignancy. This review showed that it is possible to carry out sham radiotherapy with due regard for ethical concerns, with effective blinding and high levels of patient acceptance. Large sample sizes with multicentre trial designs were achievable. Although the statistical philosophy for using sham radiotherapy in trials is legitimate, it is no longer routinely used.     

Developments in Radiotherapy

A systematic assessment of radiotherapy for cancer was conducted by The Swedish Council on Technology Assessment in Health Care (SBU) in 2001. The assessment included a review of future developments in radiotherapy and an estimate of the potential benefits of improved radiotherapy in Sweden. The conclusions reached from this review can be summarized as: Successively better knowledge is available on dose-response relationships for tumours and normal tissues at different fractionation schedules and treated volumes. Optimization of dose levels and fractionation schedules should improve the treatment outcome.Improved treatment results may be expected with even more optimized fractionation schedules.The radiosensitivity of the tumour is dependent on the availability of free oxygen in the cells. The oxygen effect has been studied for a long time and new knowledge has emerged, but there is still no consensus on the best way to minimize its negative effect in the treatment of hypoxic tumours.Development in imaging techniques is rapid, improving accuracy in outlining targets and organs at risk. This is a prerequisite for advanced treatment planning.More accurate treatment can be obtained using all the computer techniques that are successively made available for calculating dose distributions, controlling the accelerator and multileaf collimator (MLC) and checking patient set-up. Optimized treatment plans can be achieved using inverse dose planning and intensity modulation radiation therapy (IMRT). Optimization algorithms based on biological data from clinical trials could be a part of future dose planning.New genetic markers might be developed that give a measure of the radiation responsiveness of tumours and normal tissue. This could lead to more individualized treatments.New types of radiation sources may be expected: protons, light ions, and improved beams (and compounds) for boron neutron capture therapy (BNCT). Proton accelerators with scanned-beam systems and energy modulation give good dose distribution. The results reported with carbon ions from Japan and Germany are promising. An interesting development is to verify the dose and position for the irradiated volume with PET on line. Safer margins are obtained and the treatment volume can thus be limited. Very large accelerators are needed to accelerate the carbon ions. Still, it should be possible to keep the costs per patient at the same level as those for other types of advanced radiotherapy, since far fewer treatments per patient are needed. It might also be possible to treat new groups of patients.Increased resources are needed to introduce all the currently available techniques. New types of particle accelerators require large investments and a new structure of radiotherapy in Sweden.     

Developments in radiotherapy

A systematic assessment of radiotherapy for cancer was conducted by The Swedish Council on Technology Assessment in Health Care (SBU) in 2001. The assessment included a review of future developments in radiotherapy and an estimate of the potential benefits of improved radiotherapy in Sweden. The conclusions reached from this review can be summarized as: Successively better knowledge is available on dose-response relationships for tumours and normal tissues at different fractionation schedules and treated volumes. Optimization of dose levels and fractionation schedules should improve the treatment outcome. Improved treatment results may be expected with even more optimized fractionation schedules. The radiosensitivity of the tumour is dependent on the availability of free oxygen in the cells. The oxygen effect has been studied for a long time and new knowledge has emerged, but there is still no consensus on the best way to minimize its negative effect in the treatment of hypoxic tumours. Development in imaging techniques is rapid, improving accuracy in outlining targets and organs at risk. This is a prerequisite for advanced treatment planning. More accurate treatment can be obtained using all the computer techniques that are successively made available for calculating dose distributions, controlling the accelerator and multileaf collimator (MLC) and checking patient set-up. Optimized treatment plans can be achieved using inverse dose planning and intensity modulation radiation therapy (IMRT). Optimization algorithms based on biological data from clinical trials could be a part of future dose planning. New genetic markers might be developed that give a measure of the radiation responsiveness of tumours and normal tissue. This could lead to more individualized treatments. New types of radiation sources may be expected: protons, light ions, and improved beams (and compounds) for boron neutron capture therapy (BNCT). Proton accelerators with scanned-beam systems and energy modulation give good dose distribution. The results reported with carbon ions from Japan and Germany are promising. An interesting development is to verify the dose and position for the irradiated volume with PET on line. Safer margins are obtained and the treatment volume can thus be limited. Very large accelerators are needed to accelerate the carbon ions. Still, it should be possible to keep the costs per patient at the same level as those for other types of advanced radiotherapy, since far fewer treatments per patient are needed. It might also be possible to treat new groups of patients. Increased resources are needed to introduce all the currently available techniques. New types of particle accelerators require large investments and a new structure of radiotherapy in Sweden.     

Conformal index and radiotherapy]

Goal of radiotherapy is to treat patient with the best therapeutic ratio, i.e. the highest local control and the lowest toxicity rates. The conformal approach, three-dimensional conformal radiotherapy or intensity-modulated radiotherapy, is based on imageries, up-dated 3-D treatment planning systems, immobilization systems, restricted quality assurance and treatment verification. The aim is to ensure a high dose distribution tailored to the limits of the target volume, while reducing exposure of normal tissues. The evaluation tools used for optimizing treatment are the visual inspection of the dose distribution in various planes, and the dose-volume histograms, but they do not fully quantify the conformity of dose distributions. The conformal index is a tool for scoring a given plan or for evaluating different treatment plans for the same patient. This paper describes the onset and evolution of conformal index and his potential application field.     

Health-related quality of life in high-grade glioma patients

Gliomas are malignant primary brain tumors and yet incurable. Palliation and the maintenance or improvement of the patient＇s quality of life is therefore of main importance. For that reason, health-related quality of life （HRQoL） has become an important outcome measure in clinical trials, next to traditional outcome measures such as overall and progression-free survivals, and radiological response to treatment. HRQoL is a multidimensional concept covering physical, psychological, and social domains, as well as symptoms induced by the disease and its treatment. HRQoL is assessed by using self-reported, validated questionnaires. Various generic HRQoL questionnaires, which can be supplemented with a brain tumor- specific module, are available. Both the tumor and its treatment can have a negative effect on HRQoL. However, treatment with surgery, radiotherapy, chemotherapy, and supportive treatment may also improve patients＇ HRQoL, in addition to extending survival. It is expected that the impact of HRQoL measurements in both clinical trials and clinical practice will increase. Hence, it is important that HRQoL data are collected, analyzed, and interpreted correctly. Methodological issues such as selection bias and missing data may hamper the interpretation of HRQoL data and should therefore be accounted. In clinical trials, HRQoL can be used to assess the benefits of a new treatment strategy, which should be weighed carefully against the adverse effects of that treatment. In daily clinical practice, HRQoL assessments of an individual patient can be used to inform physicians about the impact of a specific treatment strategy, and it may facilitate the communication between the physicians and the patients.     

Common challenges and problems in clinical trials of boron neutron capture therapy of brain tumors

Summary Clinical trials for binary therapies, like boron neutron capture therapy (BNCT), pose a number of unique problems and challenges in design, performance, and interpretation of results. In neutron beam development, different groups use different optimization parameters, resulting in beams being considerably different from each other. The design, development, testing, execution of patient pharmacokinetics and the evaluation of results from these studies differ widely. Finally, the clinical trials involving patient treatments vary in many aspects such as their dose escalation strategies, treatment planning methodologies, and the reporting of data. The implications of these differences in the data accrued from these trials are discussed. The BNCT community needs to standardize each aspect of the design, implementation, and reporting of clinical trials so that the data can be used meaningfully.