Special Report
imaging methodologies and cancer clinical trial designs and ultimately redefine standards for high level clinical trials in cancer.
In positron emission tomography (PET) imaging, optimal image quality is essential to ensure that acquired patient images are acceptable and interpretable by any clinician in another hospital. An EORTC, EANM (European Association of Nuclear Medicine), and EARL (EANM Research Ltd.) quantitative PET Imaging accreditation program has been established to set a minimum standard for acquisition and interpretation of PET scans within EORTC clinical trials.26
Personalised Medicine
Genetic markers set the stage for personalised medicine and enable clear identification of patients who could benefit from a more intense treatment.
It was an EORTC trial that established the first predictive marker, the methylation status of the MGMT (O6-methylguanine–DNA methyltransferase) promoter, for helping to identify an individualised patient treatment based on the specific genetics of the brain tumour.27 Methylation of the MGMT promoter adversely affects DNA repair and is linked to longer survival in patients with glioblastoma treated with temozolomide. The results of this trial enhanced the international recognition of European neuro-oncology research.
In women undergoing treatment for ovarian cancer, serum levels of CA125 often rise several months prior to clinical/symptomatic relapse; however, in an MRC/EORTC trial no evidence of a survival benefit or better QoL based on raised CA125 level alone was found. Routine measurement of CA125 during the follow-up of ovarian cancer patients who attain a complete response after first-line treatment is not believed to be of value, therefore.28
Until recently, the genes involved in the development of myelodysplastic syndrome remained largely unknown, although numerous chromosomal aberrations have been described. In a translational research study, several mutations were detected which could be indicative of early events during the evolution of this disease.29,30
The evaluation of response to treatment in children with ALL has been significantly advanced by studying genetic markers of this disease.31
Management and Assessment of Quality of Life in Cancer Clinical Trials
The EORTC has positioned itself as an international leader in methodological research in the measurement of health-related QoL in oncology, setting global standards for translation, cross cultural adaption and computer-adaptive testing at the individual patient level and as a prognostic factor.
Quality of life studies overseen by EORTC have led the way in showing how QoL data can be collected on an international basis and how the results can be used to influence clinical practice.32,33
The results of QoL
studies integrated into over 120 clinical trials have informed practice in the treatment of numerous diseases such as brain, breast, melanoma, lung and ovarian cancers.
The organisation’s efforts also led to a new situation in which children with ALL are now cured with a high rate of success while avoiding undesirable acute and long-term side effects associated
12 with irradiation of the central nervous system (CNS).34 The
deleterious side effects and long-term neurological deficits observed in survivors prompted investigators to seek other ways to reduce the risk of CNS relapse by avoiding the use of radiotherapy. In studies they found that radiotherapy could be safely spared in some groups of patients when replaced by adequate systemic and CNS-directed chemotherapy.
The key development in QoL studies over the last two decades has been the validation of EORTC QLQ-C30, a general cancer QoL questionnaire, and its incorporation into cancer clinical trials. Evidence indicates that this measurement system is now the most frequently-used QoL questionnaire in cancer clinical trials worldwide.35
Classifications and Guidelines
The European guidelines for the treatment of mycosis fungoides and Sezary syndrome, and the WHO–EORTC classification for cutaneous lymphomas have enabled a more uniform diagnosis, and hence a more uniform treatment, of patients with cutaneous lymphomas.36,37 The WHO–EORTC classification represented major progress in defining this type of cancer and enabled a more reliable distinction between indolent and more aggressive types to be made as well as facilitating the selection of radiotherapy or systemic chemotherapy for first-line treatment. These guidelines and classification have been revised recently.38,39
The EORTC has substantially contributed to the development of definitions for diagnosis and treatment of fungal disease, and to the development of the European Conference on Infections in Leukemia (ECIL) guidelines.40
The latter were created in order to elaborate existing guidelines for the management of infections in patients with leukaemia and those who had undergone stem cell transplants. As a result of an increasing life expectancy, the incidence of cancer cases in the older population is rising. Cancer diagnoses are 11 times more frequent in persons aged over 65 years than in younger people. The EORTC has developed specific methodology for clinical trials in the elderly41
and has,
in addition, established a standardised Elderly MinDS with the purpose of harmonising the collection of data relevant to the elderly. This should enable cross study/practice comparisons in the future.42
Using these guidelines, patients with minimal sentinel node tumour burden might therefore be safely spared routine completion lymph node dissection.
Sentinel node tumour burden has become an important stratification tool for new adjuvant studies in melanoma. Description of tumour burden using the Rotterdam Criteria and the microanatomic location of the are the most important prognostic factors for melanoma specific survival.43
International Cooperation
The EORTC has played an indispensible role in actions aimed at streamlining, simplifying and harmonising the legal environment in Europe with regard to the conduct of cancer clinical trials. These efforts are in progress with the Directorate General Health and Consumers. Moreover, the organisation has a common scientific agenda with US-based co-operative groups supported by the National Cancer Institute, with the National Cancer Institute of Canada, the Australian co-operative Groups and a number of national academic groups in individual European countries. Currently 20 intergroup trials are open, and the EORTC is the leading organisation in eleven of them.
EUROPEAN ONCOLOGY & HAEMATOLOGY
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