Search

Background: The role of real-world evidence (RWE) in the development of anticancer therapies has been gradually growing over time. Regulators, payers and health technology assessment agencies, spurred by the rise of the precision medicine model, are increasingly incorporating RWE into their decision-making regarding the authorization and reimbursement of novel antineoplastic treatments. However, it remains unclear how this trend is viewed by clinicians in the field. This study aimed to investigate the opinions of these stakeholders with respect to RWE and its suitability for informing regulatory, reimbursement-related and clinical decisions in oncology. Methods: An online survey was disseminated to clinicians belonging to the network of the European Organisation for Research and Treatment of Cancer between May and July 2021. Results: In total, 557 clinicians across 30 different countries participated in the survey, representing 13 distinct cancer domains. Despite seeing the methodological challenges associated with its interpretation as difficult to overcome, the respondents mostly (75.0%) perceived RWE positively, and believed such evidence could be relatively strong, depending on the designs and data sources of the studies from which it is produced. Few (4.6%) saw a future expansion of its influence on decision-makers as a negative evolution. Furthermore, nearly all (94.0%) participants were open to the idea of sharing anonymized or pseudonymized electronic health data of their patients with external parties for research purposes. Nevertheless, most clinicians (77.0%) still considered randomized controlled trials (RCTs) to be the gold standard for generating clinical evidence in oncology, and a plurality (49.2%) thought that RWE cannot fully address the knowledge gaps that remain after a new antitumor intervention has entered the market. Moreover, a majority of respondents (50.7%) expressed that they relied more heavily on RCT-derived evidence than on RWE for their own decision-making. Conclusion: While cancer clinicians have positive opinions about RWE and want to contribute to its generation, they also continue to hold RCTs in high regard as sources of actionable evidence. [ABSTRACT FROM AUTHOR]

Treatment optimisation studies (TOSs) are clinical trials which aim to tackle research questions that are often left unaddressed within the current drug development paradigm due to a lack of financial and regulatory incentives to undertake them. Examples include comparative effectiveness, therapeutic sequencing and dose de-escalation studies. Trials of this nature have historically been primarily carried out by academic institutions and not-for-profit organisations such as the European Organisation for Research and Treatment of Cancer (EORTC). Our objective was to conduct an in-depth analysis of the breast, lung and colorectal cancer TOSs that have been performed by the EORTC in the past four decades. We searched the EORTC clinical trials database for relevant studies and subsequently analysed them based on a number of predefined criteria relating to their design, organisation and scientific impact. The 113 EORTC TOSs examined in this analysis were mainly standard-sized, international, multicentre phase III trials using a relatively simple, randomised, open-label design and comparing pharmacological combination regimens against standard-of-care treatments in terms of their potential to improve overall survival of patients with cancer. Although they were typically financially and/or materially supported by the industry, their legal sponsor was nearly always an independent party that did not benefit monetarily from their outcomes. If meaningful findings were obtained, their results, regardless of whether positive or negative, were published in high-impact journals, and the corresponding articles usually received a considerable number of citations. Our analysis provides an empirical framework for setting up future TOSs based on the EORTC experience in oncology. • Treatment optimisation studies can address current evidence gaps in oncology. • Trials of this type remain poorly characterised in the existing literature. • The European Organisation for Research and Treatment of Cancer (EORTC) has decades of experience with conducting such studies. • An analysis of past EORTC trials offers insights into their key characteristics. • It yields an empirical framework for undertaking treatment optimisation studies. [ABSTRACT FROM AUTHOR]

The landscape for cancer research is profoundly different today from that only one decade ago. Basic science is moving rapidly and biotechnological revolutions in molecular targeting and immunology have completely modified the opportunities and concepts for cancer treatment. In contrast to the recent past where cytotoxic molecules were screened in the laboratory and then tested in early clinical studies with toxicity as endpoint instead of the often poorly defined mechanism for its potential anti-tumor effect, we now have entered the age of molecular therapeutics, rationally designed to target "strategic" checkpoints that underlie the malignant phenotype. Translational research in early clinical trials (Phase I and II) is an integral aspect of the development of the new generation of cancer drugs as it is necessary to implement radically different early phase clinical trial design and to validate new biological end-points if the full potential of these new agents is to be realized. The "proof of principle with mechanistic analysis" strategy will allow optimisation of therapy from the beginning, and provide important feedback to pre-clinical drug developers. Translational research is also essential in late (phase III) clinical trials in defining different patient populations that may benefit to differing degrees from new treatments, and thus provide further insight and refine clinical practice in a more and more patient-tailored approach. In this editorial we will discuss the integration of Translational Research in the Organization for Research and Treatment of Cancer (EORTC). [ABSTRACT FROM AUTHOR]

Focuses on the European Organization for Research and Treatment of Cancer, an organization which conducts and coordinates research on cancer in Europe. Staff; History; Committees.

The emergence of the precision medicine paradigm in oncology has led to increasing interest in the integration of real-world data (RWD) into cancer clinical research. As sources of real-world evidence (RWE), such data could potentially help address the uncertainties that surround the adoption of novel anticancer therapies into the clinic following their investigation in clinical trials. At present, RWE-generating studies which investigate antitumour interventions seem to primarily focus on collecting and analysing observational RWD, typically forgoing the use of randomisation despite its methodological benefits. This is appropriate in situations where randomised controlled trials (RCTs) are not feasible and non-randomised RWD analyses can offer valuable insights. Nevertheless, depending on how they are designed, RCTs have the potential to produce strong and actionable RWE themselves. The choice of which methodology to employ for RWD studies should be guided by the nature of the research question they are intended to answer. Here, we attempt to define some of the questions that do not necessarily require the conduct of RCTs. Moreover, we outline the strategy of the European Organisation for Research and Treatment of Cancer (EORTC) to contribute to the generation of robust and high-quality RWE by prioritising the execution of pragmatic trials and studies set up according to the trials-within-cohorts approach. If treatment allocation cannot be left up to random chance due to practical or ethical concerns, the EORTC will consider undertaking observational RWD research based on the target trial principle. New EORTC-sponsored RCTs may also feature concurrent prospective cohorts composed of off-trial patients. • The role of real-world data (RWD) in cancer clinical research is increasing. • A false dichotomy exists between RWD studies and randomised controlled trials (RCTs). • There are different methodologies for RWD studies, including RCT designs. • The methodology to be employed should be determined by the research question. • We outline the RWD strategy of a large academic clinical cancer research organisation. [ABSTRACT FROM AUTHOR]

In Europe, most of the cancer clinical research dedicated to therapeutic innovations aims primarily at regulatory approval. Once an anticancer drug enters the common market, each member state determines its real-world use based on its own criteria: pricing, reimbursement and clinical indications. Such an innovation-centred clinical research landscape might neglect patient-relevant issues in real-world setting, such as comparative effectiveness of distinct treatment options or long-term safety monitoring. The European Organisation for Research and Treatment of Cancer (EORTC) advocates reforming the current ‘innovation-centred’ system to a truly ‘patient-centred’ paradigm with systematically coordinated applied clinical research in conjunction with drug development, featuring the following strategy: (1) An interconnected partnership among key-stakeholders involved in the care delivery system, namely patients, health professionals, academia, pharmaceutical industry, regulators, payers and policy-makers, to optimise the transition from research to clinical practice and vice versa; (2) An independent research infrastructure host and coordination ensuring independent, high quality and sustainable research. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor regarding an editorial entitled, 'Who's afraid of the European Clinical Trials,' which appeared in the June 28, 2003 issue of 'The Lancet.'

The European Society for Paediatric Oncology (SIOPE) Radiation Oncology Working Group presents the QUARTET Project: a centralised quality assurance programme designed to standardise care and improve the quality of radiotherapy and imaging for international clinical trials recruiting children and adolescents with cancer throughout Europe. QUARTET combines the paediatric radiation oncology expertise of SIOPE with the infrastructure and experience of the European Organisation for Research and Treatment of Cancer to deliver radiotherapy quality assurance programmes for large, prospective, international clinical trials. QUARTET-affiliated trials include children and adolescents with brain tumours, neuroblastoma, sarcomas including rhabdomyosarcoma, and renal tumours including Wilms' tumour. With nine prospective clinical trials and two retrospective studies within the active portfolio in March 2022, QUARTET will collect one of the largest repositories of paediatric radiotherapy and imaging data, support the clinical assessment of radiotherapy, and evaluate the role and benefit of radiotherapy quality assurance for this cohort of patients within the context of clinical trials. • High-quality, protocol compliant radiotherapy is essential in clinical trials. • QUARTET is a platform for centralised prospective radiotherapy quality assurance. • QUARTET facilitates a strong collaborative network for paediatric radiation oncology. • QUARTET improves equity in access to paediatric radiotherapy expertise across Europe. • QUARTET supports central review of diagnostic imaging for treatment failure analysis. [ABSTRACT FROM AUTHOR]

The European Breast Cancer Council (EBCC) traditionally identifies controversies or major deficiencies in the management of patients with breast cancer and selects a multidisciplinary expert team to collaborate in setting crucial principles and recommendations to improve breast cancer care. The 2024 EBCC manifesto focuses on disparities in the care of patients with metastatic breast cancer. There are several reasons for existing disparities both between and within countries. Our recommendations aim to address the stigma of metastatic disease, which has led to significant disparities in access to innovative care regardless of the gross national income of a country. These recommendations are for different stakeholders to promote the care of patients with metastatic breast cancer across Europe and worldwide. • This manifesto strives for equal access to innovation for people in Europe with mBC. • To redress inequity it is critical to know how many people are living with mBC. • A priority is to overturn the stigma of living with mBC. • All patients deserve access to high-quality multidisciplinary information and care. [ABSTRACT FROM AUTHOR]

New technologies and techniques in radiation oncology and imaging offer opportunities to enhance the benefit of loco-regional treatments, expand treatment to new patient populations such as those with oligometastatic disease and decrease normal tissue toxicity. Furthermore, novel agents have become available which may be combined with radiation therapy, and identification of radiation-related biomarkers can be studied to refine treatment prescriptions. Finally, the use of artificial intelligence (AI) capabilities may also improve treatment quality assurance or the ease with which radiation dosing is prescribed. All of these potential advances present both opportunities and challenges for academic clinical researchers. Recently, the European Organisation for Research and Treatment of Cancer addressed these topics in a meeting of multiple stakeholders from Europe and North America. The following five themes radiobiology-based biomarkers, new technologies – particularly proton beam therapy, combination systemic and radiation therapy, management of oligometastatic disease and AI opportunities in radiation oncology were discussed in a State of Science format to define key controversies, unanswered questions and propose clinical trial priorities for development. Priorities for clinical trials implementing new science and technologies have been defined. Solutions to integrate the multidimensional complexity of data have been explored. New types of platforms and partnerships can support innovative approaches for clinical research in radiation oncology. • Biomarkers of radiation sensitivity are ready for randomised prospective evaluation. • RCTS (Randomised Clinical Trials) of proton therapy should examine impacts on toxicity and efficacy. • Artificial intelligence may improve the quality of radiation treatment delivery. • Cure is the key end-point for trials of ablative radiation in oligometastases. • New systemic therapy plus radiation should be evaluated to improve disease control. [ABSTRACT FROM AUTHOR]

In recent decades cancer care has seen improvements in the speed and accuracy of diagnostic procedures; the effectiveness of surgery, radiation therapy and medical treatments; the power of information technology; and the development of multidisciplinary, specialist-led approaches to care. Such innovations are essential if we are to continue improving the lives of cancer patients across Europe despite financial pressures on our healthcare systems. Investment in innovation must be balanced with the need to ensure the sustainability of healthcare budgets, and all health professionals have a responsibility to help achieve this balance. It requires scrutiny of the way care is delivered; we must be ready to discontinue practices or interventions that are inefficient, and prioritise innovations that may deliver the best outcomes possible for patients within the limits of available resources. Decisions on innovations should take into account their long-term impact on patient outcomes and costs, not just their immediate costs. Adopting a culture of innovation requires a multidisciplinary team approach, with the patient at the centre and an integral part of the team. It must take a whole-system and whole-patient perspective on cancer care and be guided by high-quality real-world data, including outcomes relevant to the patient and actual costs of care; this accurately reflects the impact of any innovation in clinical practice. The European CanCer Organisation is committed to working with its member societies, patient organisations and the cancer community at large to find sustainable ways to identify and integrate the most meaningful innovations into all aspects of cancer care. [ABSTRACT FROM AUTHOR]

Traditional dose-limiting toxicity (DLT) definition, which uses grade (G) 3-4 toxicity data from cycle 1 (C1) only, may not be appropriate for molecularly targeted agents (MTAs) of prolonged administration, for which late or lower grade toxicities also deserve attention. Patients and methods In collaboration with pharmaceutical companies and academia, an European Organisation for Research and Treatment of Cancer (EORTC)-led initiative, Dose-Limiting Toxicity and Toxicity Assessment Recommendation Group for Early Trials of Targeted therapies (DLT-TARGETT), collected data from completed phase 1 trials evaluating MTAs as monotherapy. All toxicities at least possibly related to the study drugs that occurred during C1-6, their type, grade (CTCAEv3.0), and duration as well as patients' relative dose-intensity (RDI), were recorded. Results The 54 eligible trials enrolled 2084 evaluable adult patients with solid tumours between 1999 and 2013, and evaluated small molecules (40), antibodies (seven), recombinant peptides (five) and antisense oligodeoxynucleotides (two). A maximum tolerated dose was set in 43 trials. Fifteen percent of the patients received <75% of the intended RDI in C1, but only 9.1% of them presented protocol-defined DLTs. After C1, 16-19% of patients received <75% of the intended RDI. A similar proportion of G < 3 toxicities was recorded in C1 and after C1 (936 and 1087 toxicities, respectively), with the first G < 3 toxicity occurring after C1 in 18.6% of patients. Conclusion Although protocol-defined DLT period is traditionally limited to C1, almost 20% of patients present significant reductions in RDI at any time in phase 1 trials of MTAs. Recommended phase 2 dose assessment should incorporate all available information from any cycle (notably lower grade toxicities leading to such RDI decrease), and be based on achieving >75% RDI. [ABSTRACT FROM AUTHOR]

Aims: BI 2536 is a selective and potent small-molecule inhibitor of polo-like kinase 1. We performed a multi-centre, multi-tumour phase II trial to investigate the efficacy, safety and pharmacokinetics of BI 2536 in five solid tumour types. Patients and methods: Patients with advanced head and neck, breast and ovarian cancer, soft tissue sarcoma and melanoma were selected according to protocol-defined general and tumour-specific criteria. They were ⩾18years old, had a good performance status, adequate bone marrow, renal and liver function, measurable progressive disease and had completed other relevant systemic treatments >4weeks ago. BI 2536 200–250mg was given intravenously on day 1 every 3 weeks until intolerance, progression or refusal. The study was based on a Simon two-stage design, with 12 patients entering in stage 1 and additional 25 patients to be entered in case of at least one response in the first stage. The rate of objective responses (RECIST criteria) was chosen as primary end-point. Results: Seventy six patients were included, 71 started treatment and received a median number of two cycles (four in ovarian cancer). Frequent grade 3–4 adverse events were neutropaenia (81.6%), thrombocytopaenia (19.7%), febrile neutropaenia (19.7%), anaemia (15.5%) and pain (9.9%). We did not observe confirmed objective responses. All cohorts were closed after the entry of 14–15 eligible non-responding patients. Pharmacokinetic analyses revealed multi-compartmental behaviour and a rapid distribution of BI 2536. Conclusions: BI 2536 showed limited antitumour activity according to the design of this trial in five different tumour types. Derivatives of BI 2536 with a more favourable pharmacological profile are currently explored further in prospective studies. [Copyright &y& Elsevier]

Key stakeholders from the cancer research continuum met in May 2021 at the European Cancer Research Summit in Porto to discuss priorities and specific action points required for the successful implementation of the European Cancer Mission and Europe's Beating Cancer Plan (EBCP). Speakers presented a unified view about the need to establish high-quality, networked infrastructures to decrease cancer incidence, increase the cure rate, improve patient's survival and quality of life, and deal with research and care inequalities across the European Union (EU). These infrastructures, featuring Comprehensive Cancer Centres (CCCs) as key components, will integrate care, prevention and research across the entire cancer continuum to support the development of personalized/precision cancer medicine in Europe. The three pillars of the recommended European infrastructures - namely translational research, clinical/prevention trials and outcomes research - were pondered at length. Speakers addressing the future needs of translational research focused on the prospects of multiomics assisted preclinical research, progress in Molecular and Digital Pathology, immunotherapy, liquid biopsy and science data. The clinical/prevention trial session presented the requirements for next-generation, multicentric trials entailing unified strategies for patient stratification, imaging, and biospecimen acquisition and storage. The third session highlighted the need for establishing outcomes research infrastructures to cover primary prevention, early detection, clinical effectiveness of innovations, health-related quality-of-life assessment, survivorship research and health economics. An important outcome of the Summit was the presentation of the Porto Declaration, which called for a collective and committed action throughout Europe to develop the cancer research infrastructures indispensable for fostering innovation and decreasing inequalities within and between member states. Moreover, the Summit guidelines will assist decision making in the context of a unique EU-wide cancer initiative that, if expertly implemented, will decrease the cancer death toll and improve the quality of life of those confronted with cancer, and this is carried out at an affordable cost., (© 2021 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

A comprehensive translational cancer research approach focused on personalized and precision medicine, and covering the entire cancer research-care-prevention continuum has the potential to achieve in 2030 a 10-year cancer-specific survival for 75% of patients diagnosed in European Union (EU) member states with a well-developed healthcare system. Concerted actions across this continuum that spans from basic and preclinical research through clinical and prevention research to outcomes research, along with the establishment of interconnected high-quality infrastructures for translational research, clinical and prevention trials and outcomes research, will ensure that science-driven and social innovations benefit patients and individuals at risk across the EU. European infrastructures involving comprehensive cancer centres (CCCs) and CCC-like entities will provide researchers with access to the required critical mass of patients, biological materials and technological resources and can bridge research with healthcare systems. Here, we prioritize research areas to ensure a balanced research portfolio and provide recommendations for achieving key targets. Meeting these targets will require harmonization of EU and national priorities and policies, improved research coordination at the national, regional and EU level and increasingly efficient and flexible funding mechanisms. Long-term support by the EU and commitment of Member States to specialized schemes are also needed for the establishment and sustainability of trans-border infrastructures and networks. In addition to effectively engaging policymakers, all relevant stakeholders within the entire continuum should consensually inform policy through evidence-based advice., (© 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.)

The European Network for Health Technology Assessment (EUnetHTA) organizes an annual Forum with stakeholders to receive feedback on its activities, processes, and outputs produced. The fourth edition of the EUnetHTA Forum brought together representatives of HTA bodies, patient organizations, healthcare professionals (HCPs), academia, payers, regulators, and industry. The aim of this paper is to provide an overview of the highlights presented at the 2019 EUnetHTA Forum, reporting the main items and themes discussed in the plenary panel and breakout sessions. The leading topic was the concept of unmet medical need seen from different stakeholders' perspectives. Breakout sessions covered the joint production of assessment reports and engagement with payers, patients, and HCPs. Synergies, pragmatism, and inclusiveness across Member States and stakeholders were emphasized as leading factors to put in place a collaboration that serves the interest of patients and public health in a truly European spirit.

Background: The academia-industry interface is important, and, despite challenges that inevitably occur, bears the potential for positive synergies to emerge. Perceived barriers to wider collaboration in academia-industry oncology research in Europe need to be addressed, current academic cooperative group and industry models for collaboration need to be discussed, and a common terminology to facilitate understanding of both sectors' concerns needs to be established with an eye towards improving academia-industry partnerships on clinical trials for the benefit of patients with cancer., Methodology: CAREFOR (Clinical Academic Cancer Research Forum), a multi-stakeholder platform formed to improve the direction for academic clinical trials in the field of oncology in Europe, formed the CAREFOR-Industry Working Group comprised of experienced professionals from European academic cooperative groups joined by industry representatives selected based on their activities in the area of medical oncology. They jointly discussed academic cooperative groups, clinical trials conducted between academic cooperative groups and industry, examples of successful collaborative models, common legal negotiation points in clinical trial contracts, data access, and principles of interaction., Results: Four principles of interaction between the academia and industry are proposed: (1) clarify the roles and responsibilities of all partners involved in the study, (2) involve legal teams from an early stage; (3) acknowledge that data is an important output of the study, (4) agree on the intent of the trial prior to its start., Conclusions: The CAREFOR-Industry Working Group describes current models, challenges, and effective strategies for academia-industry research in Europe with an eye towards improving academia-industry partnerships on clinical trials for patients with cancer. Current perceived challenges are explained, and future opportunities/recommendations for improvement are described for the areas of most significant impact. Challenges are addressed from both the academic and industry perspectives, and principles of interaction for the optimal alignment between academia and industry in selected areas are proposed., Competing Interests: Competing interests: RAS reports: In the past two years, I have received honoraria as a consultant at advisory boards from Abbvie, Astra Zeneca, MSD, Pfizer, Regeneron, Roche and Takeda. In the past two years, I have received honoraria as a speaker from Astra Zeneca, Boehringer Ingelheim, Eli Lilly, MSD and Roche. DMC in the last two years: Genentech/Roche and Takeda Financial Support of ETOP trials (president and scientific chair): AstraZeneca, BMS, Boehringer Ingelheim, Genentech, MSD, Roche and Pfizer; FC reports personal fees from Amgen, personal fees from Astellas/Medivation, personal fees from AstraZeneca, personal fees from Celgene, personal fees from Daiichi-Sankyo, personal fees from Eisai, personal fees from GE Oncology, personal fees from Genentech, personal fees from GlaxoSmithKline, personal fees from Macrogenics, personal fees from Medscape, personal fees from Merck-Sharp, personal fees from Merus BV, personal fees from Mylan, personal fees from Mundipharma, personal fees from Novartis, personal fees from Pfizer, personal fees from Pierre-Fabre, personal fees from prIME Oncology, personal fees from Roche, personal fees from Sanofi, personal fees from Seattle Genetics, personal fees from Teva, outside the submitted work; PGC reports personal fees from Bayer, personal fees from Deciphera, personal fees from Eisai, personal fees from Eli Lilly, personal fees from Nektar Ther, personal fees from Pfizer, grants from Advenchen Lab, grants from Amgen Dompé, grants from AROG, grants from Bayer, grants from Bluerint, grants from Daiichi Sankyo, grants from Deciphera, grants from Eisai, grants from Eli Lilly, grants from Epizyme, grants from Glaxo, grants from Karyopharm, grants from Novartis, grants from Pfizer, grants from PharmaMar, outside the submitted work; RM reports personal fees from Pfizer, outside the submitted work; AH reports grants and non-financial support from Abbott Molecular Inc, grants from Amgen (Europe) GmbH, grants and non-financial support from Amgen Inc, grants and non-financial support from Amgen Ltd, grants and non-financial support from AstraZeneca AG Switzerland, grants and non-financial support from AstraZeneca UK Ltd, grants from AstraZeneca Wilmington, grants and non-financial support from Biodesix Inc, grants and non-financial support from Boehringer Ingelheim RCV GmbH & Co. KG, grants from Boehringer Ingelheim (Schweiz) GmbH, grants from Bristol-Myers Squibb Company, grants and non-financial support from Bristol-Myers Squibb International Corporation, grants and non-financial support from Eli Lilly Export SA, grants from Eli Lilly Regional Operations GmbH, grants and non-financial support from F. Hoffmann-La Roche Ltd, grants and non-financial support from Genentech Inc, grants from Merck KGaA, grants and non-financial support from MSD MERCK SHARP & DOHME AG, grants from Pfizer Inc, grants from Pfizer Pharma GmbH, grants from Takeda, outside the submitted work., (© Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology.)

For over 50years the European Organization for Research and Treatment of Cancer (EORTC) has delivered major advances in cancer clinical research and cancer therapeutics. The introduction of molecularly targeted agents has led to significant improvements in outcome for patients with specific tumor types; however conventional chemotherapy remains the mainstay of treatment for the majority of patients. Due to increasing knowledge about the diversity of molecular pathways driving malignant progression, strategies to integrate biology into clinical research and development are continuously evolving. The challenges and the experience of the EORTC regarding how translational research is to be an indispensable component of the clinical research environment, which aims to deliver more sophisticated treatment approaches will be discussed in this perspective article., (Copyright © 2017 National Cancer Institute, Cairo University. Production and hosting by Elsevier B.V. All rights reserved.)

Background: The prognosis of patients with anaplastic oligodendrogliomas (AOD) and oligoastrocytomas (AOA) is variable. Biomarkers might be helpful to identify more homogeneous disease subtypes and improve therapeutic index. The aim of this study is to develop new clinical, pathological and molecular prognostic models for locally diagnosed anaplastic gliomas with oligodendroglial features (AOD or AOA)., Methods: Data from 368 patients with AOD or AOA recruited in The European Organisation for Research and Treatment of Cancer (EORTC) trial 26951 on adjuvant PCV (Procarbazine, CCNU, Vincristine) chemotherapy in anaplastic oligodendroglial tumours were used to develop multifactor models to predict progression free survival (PFS) and overall survival (OS). Different models were compared by their percentage of explained variation (PEV). Prognostic calculators were derived from these new models., Results: Treatment (for PFS only), younger age, confirmed absence of residual tumour on imaging, frontal location, good World Health Organisation (WHO) performance status, absence of endothelial abnormalities and/or necrosis, 1p/19q codeletion and Isocitrate dehydrogenase 1 (IDH1) mutation were independent factors that predicted better PFS and OS., Conclusions: We identified important prognostic factors for AOD and AOA and showed that molecular markers added a major contribution to clinical and pathological factors in explaining PFS and OS. With a positive predictive value of 92% for PFS and 94% for OS, our models allow physicians to precisely identify high risk patients and aid in making therapeutic decisions., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Purpose: O6-methylguanine-methyltransferase (MGMT) promoter methylation has been shown to predict survival of patients with glioblastomas if temozolomide is added to radiotherapy (RT). It is unknown if MGMT promoter methylation is also predictive to outcome to RT followed by adjuvant procarbazine, lomustine, and vincristine (PCV) chemotherapy in patients with anaplastic oligodendroglial tumors (AOT)., Patients and Methods: In the European Organisation for the Research and Treatment of Cancer study 26951, 368 patients with AOT were randomly assigned to either RT alone or to RT followed by adjuvant PCV. From 165 patients of this study, formalin-fixed, paraffin-embedded tumor tissue was available for MGMT promoter methylation analysis. This was investigated with methylation specific multiplex ligation-dependent probe amplification., Results: In 152 cases, an MGMT result was obtained, in 121 (80%) cases MGMT promoter methylation was observed. Methylation strongly correlated with combined loss of chromosome 1p and 19q loss (P = .00043). In multivariate analysis, MGMT promoter methylation, 1p/19q codeletion, tumor necrosis, and extent of resection were independent prognostic factors. The prognostic significance of MGMT promoter methylation was equally strong in the RT arm and the RT/PCV arm for both progression-free survival and overall survival. In tumors diagnosed at central pathology review as glioblastoma, no prognostic effect of MGMT promoter methylation was observed., Conclusion: In this study, on patients with AOT MGMT promoter methylation was of prognostic significance and did not have predictive significance for outcome to adjuvant PCV chemotherapy. The biologic effect of MGMT promoter methylation or pathogenetic features associated with MGMT promoter methylation may be different for AOT compared with glioblastoma.

The European Organisation for Research and Treatment of Cancer (EORTC) has carried out clinical trials for nearly 30 years. During this time, several disease-oriented groups within the EORTC have been shaped by rapidly changing regulations in the area of drug development. Continual networking, dissemination of knowledge, and the establishment of specialized administrative units have allowed the EORTC to play a leading role in the development of improved treatment options for patients with brain tumors. Recently, the EORTC Brain Tumor Group and the EORTC New Drug Development Group have been integrated to create a network of institutions dedicated to screening new chemotherapy agents for the treatment of high-grade gliomas. Indeed, several new regimens and agents have already been investigated by this collaboration. Most notable are the recently closed study on temozolomide (Temodar [US], Temodal [international]; Schering-Plough Corporation, Kenilworth, NJ) in the adjuvant setting and in combination with radiotherapy in patients newly diagnosed with glioblastoma multiforme, and the ongoing study on oral STI571 for the treatment of gliomas. Within the current networks, a well-defined strategy has been implemented to select specific and targeted agents for the drug screening process. By sharing their expertise with the EORTC networks, medical oncologists, neuro-oncologists, and radiologists can assist in the clinical development of potentially active agents in patients with brain tumors.