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P Therasse

Publications and source records attributed to P Therasse.

At least 19 recordsLinked to original sources
PubMed2006

TuBaFrost 3: regulatory and ethical issues on the exchange of residual tissue for research across Europe.

The regulatory regimes for research with residual tissue and accompanying data differ widely between countries in the European Union (EU): from specific consent to opt-out or even no consent at all. This could greatly hamper research where the exchange of tissue and accompanying data has become the gold standard, like in TubaFrost. Instead of adhering to international guidelines, which have a democratic deficit, or an attempt for a new set of possible harmonising rules, TubaFrost chose to create a coordinating rule: if tissue may legitimately be used for a certain kind of research in the country where it was taken and under whose jurisdiction the patient falls, it may also be used for such research in the country where it is sent to in the context of a scientific program even if in that other country other regulations would apply for research with residual tissue taken from patients under their jurisdiction. This coordinating rule has a sound basis in EU law in general and will solve the problems related to diverging national regulatory regimes in the case of cross national research with residual tissue.

Ethics, Research↗
PubMed2006

TuBaFrost 5: multifunctional central database application for a European tumor bank.

Developing a tissue bank database has become more than just logically arranging data in tables combined with a search engine. Current demand for high quality samples and data, and the ever-changing legal and ethical regulations mean that the application must reflect TuBaFrost rules and protocols for the collection, exchange and use of tissue. To ensure continuation and extension of the TuBaFrost European tissue bank, the custodianship of the samples, and hence the decision over whether to issue samples to requestors, remains with the local collecting centre. The database application described in this article has been developed to facilitate this open structure virtual tissue bank model serving a large group. It encompasses many key tasks, without the requirement for personnel, hence minimising operational costs. The Internet-accessible database application enables search, selection and request submission for requestors, whereas collectors can upload and edit their collection. Communication between requestor and involved collectors is started with automatically generated e-mails.

Computer Simulation↗
PubMed2006

TuBaFrost 2: Standardising tissue collection and quality control procedures for a European virtual frozen tissue bank network.

Tumour Bank Networking presents a great challenge for oncological research as in order to carry out large-scale, multi-centre studies with minimal intrinsic bias, each tumour bank in the network must have some fundamental similarities and be using the same standardised and validated procedures. The European Human Frozen Tumour Tissue Bank (TuBaFrost) has responded to this need by the promotion of an integrated platform of tumour banks in Europe. The operational framework for TuBaFrost has drawn upon the best practice of standard workflows and operating procedures employed by members of the TuBaFrost project and key initiatives worldwide.

Biological Specimen Banks↗
PubMed2006

TuBaFrost 4: access rules and incentives for a European tumour bank.

When designing infrastructure for a networked virtual tumour bank (samples remain at the collector institutes and sample data are collected in a searchable central database), it is apparent that this can only function properly after developing an adequate set of rules for use and access. These rules must include sufficient incentives for the tissue sample collectors to remain active within the network and maintain sufficient sample levels in the local bank. These requirements resulted in a key TuBaFrost rule, stating that the custodianship of the samples remains under the authority of the local collector. As a consequence, the samples and the decision to issue the samples to a requestor are not transferred to a large organisation but instead remain with the collector, thus allowing autonomous negotiation between collector and requestor, potential co-authorship in publications or compensation for collection and processing costs. Furthermore, it realises a streamlined cost effective network, ensuring tissue visibility and accessibility thereby improving the availability of large amounts of samples of highly specific or rare tumour types as well as providing contact opportunities for collaboration between scientists with cutting edge technology and tissue collectors. With this general purpose in mind, the rules and responsibilities for collectors, requestors and central office were generated.

Europe↗
PubMed2006

TuBaFrost 1: Uniting local frozen tumour banks into a European network: an overview.

TuBaFrost is the consortium responsible for the creation of a virtual European human frozen tumour tissue bank: a collection of high quality frozen residual, accurately classified tumour tissue samples, which are stored in European cancer centres and universities. This virtual tissue bank, searchable on the internet, has rules for access and use, and a code of conduct to comply with the various legal and ethical regulations in European countries. The easy accessibility and the European scale of the bank will result in the availability of a large number of samples even of rarer tumour types. Standardisation of collection, storage and quality control throughout the network is achieved minimising inter-institutional variability. A website providing access to upload, search and request samples is a key tool of the tissue bank. The search engine makes use of virtual microscopy. An overview of the development of the European virtual frozen tissue bank infrastructure is described in this paper. The various key aspects are described in more detail in a series of articles to appear in this Journal.

Biological Specimen Banks↗
PubMed2006

TuBaFrost 6: virtual microscopy in virtual tumour banking.

Many systems have already been designed and successfully used for sharing histology images over large distances, without transfer of the original glass slides. Rapid evolution was seen when digital images could be transferred over the Internet. Nowadays, sophisticated Virtual Microscope systems can be acquired, with the capability to quickly scan large batches of glass slides at high magnification and compress and store the large images on disc, which subsequently can be consulted through the Internet. The images are stored on an image server, which can give simple, easy to transfer pictures to the user specifying a certain magnification on any position in the scan. This offers new opportunities in histology review, overcoming the necessity of the dynamic telepathology systems to have compatible software systems and microscopes and in addition, an adequate connection of sufficient bandwidth. Consulting the images now only requires an Internet connection and a computer with a high quality monitor. A system of complete pathology review supporting bio-repositories is described, based on the implementation of this technique in the European Human Frozen Tumor Tissue Bank (TuBaFrost).

Computer Simulation↗
PubMed2006

Update in methodology and conduct of cancer clinical trials.

Many interesting changes are regularly brought into the methodology of cancer clinical trials. This position paper focuses on three topics which are felt to appear as recurrent problems which deserve more attention from the scientific community. RECIST guidelines were published five years ago and have since then been largely implemented and used in clinical trials. Although the criteria were initially designed for screening phase II trials they have been used also in most phase III studies aiming at determining the efficacy of new treatments. Problems have been identified some of which require further clarifications and others deserve further research which is being undertaken. Overall RECIST is well accepted and a revised version is being considered for 2007. Interim analysis is also an important issue revealed recently through many large adjuvant or advanced trials being prematurely discontinued at the time of an interim analysis. In most instances trials were stopped because of evidence of superiority of the investigational treatment over the standard treatment. Premature discontinuation of trial poses a number of challenges addressed in this paper. Finally, the consequences of the implementation of the EU clinical trial directive are being discussed. The conclusions are without equivoque. There is much less academic research conducted in Europe, there is a lot of discrepancy and inconsistency in the implementation of the directive across member states and there is no apparent direct benefit for the patients.

Antineoplastic Agents↗
PubMed2006

RECIST revisited: a review of validation studies on tumour assessment.

The response evaluation criteria in solid tumours (RECIST) was developed in the late 1990s to replace the WHO criteria for response evaluation. The new criteria included important changes such as unidimensional tumour measurement, selection of target lesions with a minimum size, details concerning imaging modalities and a new threshold for assignment of objective progression. RECIST was published in February 2000 and very quickly came into operation first in clinical trials performed under the auspices of EORTC, US NCI or NCI Canada Clinical Trials Group but was adopted quickly thereafter by the entire cancer clinical research community. As several key features of RECIST were based on analysis of retrospective clinical data, it was felt important to carefully monitor the implementation of the guidelines and stimulate prospective validation studies. This paper reviews the literature that has been published on RECIST from 2000 up to November 2005. In total 60 papers and ASCO, abstracts directly refer to research studies or reviews related to RECIST and its implementation. Amongst the 60 references identified for this review, 11 papers refer to validation studies (seven prospective and four retrospective), six papers refer to the comparison of unidimensional measurements versus bi or tri-dimensional measurements, 12 papers address issues raised with the implementation of RECIST in Mesothelioma and Gastro-Intestinal Stromal Tumours and four papers report on an adaptation of RECIST for specific tumour types. In general, RECIST has been well received by the scientific community and most validation studies fully support the implementation of the new criteria. As expected, however, some issues have been identified. In keeping with the mathematical differences in definition of progression, RECIST delays the identification of progression as compared to WHO criteria in some instances. RECIST criteria are not easily applicable in some types of trials such as those in paediatric tumours and in mesothelioma. Furthermore, anatomical changes in the tumour as described by RECIST may be detected later than functional changes in some circumstances, as for example in Gastro-Intestinal Stromal Tumours treated with Imatinib. However, there is no other universal method of tumour assessment as yet and functional imaging methods have not been validated and will not be widely available for some time. The findings of this review, together with experience acquired thus far and the results of some ongoing research projects, have paved the way for RECIST 2.0 to be hopefully announced later this year.

Clinical Trials as Topic↗
PubMed2006

Clinical trials design and treatment tailoring: general principles applied to breast cancer research.

Nowadays tailored therapy tends to replace standard cancer treatment approaches. Tailoring treatment is possible thanks to clinical trials results that identified subgroups of patients benefiting most from some treatments. Treatment can be tailored on the basis of specific clinical characteristics of the population or on the basis of predictive or prognostic markers. Finally treatment can be tailored for specific molecular targets. This evolution in cancer treatment has triggered the development of innovative trial designs to validate these new hypotheses. The real challenge of the next coming years resides in recruiting large number of patients from specific subgroups to validate tailored therapies.

Biomarkers, Tumor↗
PubMed2006

TuBaFrost: European virtual tumor tissue banking.

TuBaFrost is a consortium responsible for the task to create a virtual European human frozen tumor tissue bank, composed of high quality frozen tumor tissue collections with corresponding accurate diagnosis stored in European cancer centers and universities, searchable on the Internet, providing rules for access and use and a code of conduct to comply with the various legal and ethical regulations in European countries. Such infrastructure would enlarge tissue availability and accessibility in large amounts of specified or even rare tumor samples. Design of an infrastructure for European residual tissue banking with the described characteristics, clear focus points emerge that can be broken down in dedicated subjects: (1) standardization and quality assurance (QA) to avoid inter-institute quality variation; (2) law and ethics enabling exchange of tissue samples possible between institutes in the different European countries, where law and ethics are characterized by a strong variability; (3) rules for access, with sufficient incentives for collectors; (4) central database application containing innovations on search and selection procedures; (5) support when needed with histology images; and (6) Internet access to search and upload, with in addition a solid website giving proper information on the procedures, intentions and activities not only to the scientific community, but also to the general public. One consortium decision, part of the incentives for collectors, had major impact on the infrastructure; custodianship over the tissues as well as the tissues stay with the collector institute. Resulting in specimens that are not given to an organization, taking decisions on participation of requests, but instead the local collected tissues stay very easy to access by the collector and allows autonomous negotiation between collector and requestor on cooperation, coauthorship in publication or compensation in costs. Thereby, improving availability of large amounts of high quality samples of a highly specified or rare tumor types and contact opportunities for cooperation with other institutes.

Databases, Factual↗
PubMed2006

Virtual microscopy in virtual tumor banking.

Many systems have already been designed and successfully used for sharing histology images over large distances, without transfer of the original glass slides. Rapid evolution was seen when digital images could be transferred over the Internet. Nowadays, sophisticated virtual microscope systems can be acquired, with the capability to quickly scan large batches of glass slides at high magnification and compress and store the large images on disc, which subsequently can be consulted through the Internet. The images are stored on an image server, which can give simple, easy to transfer pictures to the user specifying a certain magnification on any position in the scan. This offers new opportunities in histology review, overcoming the necessity of the dynamic telepathology systems to have compatible software systems and microscopes and in addition, an adequate connection of sufficient bandwidth. Consulting the images now only requires an Internet connection and a computer with a high quality monitor. A system of complete pathology review supporting biorepositories is described, based on the implementation of this technique in the European Human Frozen Tumor Tissue Bank (TuBaFrost).

Databases, Factual↗
PubMed2005

RECIST vs. WHO: prospective comparison of response criteria in an EORTC phase II clinical trial investigating ET-743 in advanced soft tissue sarcoma.

The present study was set up just after the publication of the response evaluation criteria in solid tumors (RECIST) as a prospective validation exercise in soft tissue sarcoma. Forty-nine patients were entered into a phase II clinical trial aiming at determining the activity and safety of ET-743 (Ecteinascidin) in second line advanced soft tissue sarcoma. Response to treatment and progression were monitored following the WHO criteria and RECIST. Discordances between WHO and RECIST criteria for the best response were reported for two cases: one no-change (WHO) reported as partial response (RECIST) and one progression (WHO) reported as no-change (RECIST). In terms of date of progression, 3 patients progressed on WHO criteria while they were still stable with RECIST. Overall the results of the study would not have changed if RECIST had been used instead of WHO criteria. In conclusion, response criteria as defined by RECIST are adequate to measure response and progression in non-GIST soft tissue sarcoma and can be used instead of the modified WHO criteria.

Antineoplastic Agents, Alkylating↗
PubMed2005

Health related quality of life outcomes in cancer clinical trials.

Over the last decade, health related quality of life (HRQOL) investigations have become an increasingly important part of many cancer clinical trial research programs. This paper presents a review of all HRQOL studies published by the European Organisation for Research and Treatment of Cancer (EORTC), one of the largest clinical trials organisations in Europe. The findings highlight 24 clinical trials that have been published to date, enrolling over 9000 patients. HRQOL is fully integrated into EORTC phase III trials. In many trials, HRQOL provides a valuable source of additional information useful to both clinician and patient when making treatment decisions. Furthermore, several trials have found that the combined use of clinical information along with HRQOL data has led to the development of new standards of care in several different cancer sites. With more than 40 ongoing HRQOL studies in the EORTC, we expect HRQOL to play an even greater role over the coming decade in helping establish the optimal treatment and care approach for cancer patients.

Clinical Trials as Topic↗
PubMed2004

Adjuvant chemotherapy in elderly patients with breast cancer: a survey of the Breast International Group (BIG).

BACKGROUND: To collect oncologists' experience and opinion on adjuvant chemotherapy in elderly breast cancer patients. MATERIALS AND METHODS: A questionnaire was circulated among the members of the Breast International Group. RESULTS: A total of 277 oncologists from 28 countries participated in the survey. Seventy years is the age cut-off commonly used to define a patient as elderly. Biological age and the biological characteristics of the tumor are the most frequently used criteria to propose adjuvant chemotherapy to an elderly patient. Combination therapy with cyclophosphamide, methotrexate and fluorouracil on days 1 and 8 is the most frequently prescribed regimen. Great interest exists in oral chemotherapy. CONCLUSION: There is interest among those who responded to the survey to validate a comprehensive geriatric assessment for use as a predictive instrument of toxicity and/or activity of anticancer therapy and to evaluate the role of a treatment option that is potentially less toxic and possibly as effective as polychemotherapy.

Aged↗
PubMed2003

Medical fellowship programme within the Gynaecological Cancer Group of the European Organisation for Research and Treatment of Cancer.

In 1962, the European Organisation for Research and Treatment of Cancer (EORTC) was founded, and in the course of the years it developed into the leading European organisation in cancer research. Currently, the EORTC is organised into (Pre-)Clinical Groups and Task Forces consisting of scientists and/or clinicians. One of these groups with a specific area of interest in cancer research is the Gynaecological Cancer Group (GCG). The EORTC offers fellowship programmes to physicians and scientists from all over the world to create a possibility to be temporarily linked to an EORTC group or a specific research project. Over the past decade, 76 research fellowships have been appointed at the EORTC Data Center. This paper shows an overview of the activities of one EORTC/GCG medical fellow.

Biomedical Research↗
PubMed2003

Final results of a randomized phase III trial comparing cyclophosphamide, epirubicin, and fluorouracil with a dose-intensified epirubicin and cyclophosphamide + filgrastim as neoadjuvant treatment in locally advanced breast cancer: an EORTC-NCIC-SAKK multicenter study.

PURPOSE: To compare the efficacy of a standard anthracycline-based regimen to a dose-intensified anthracycline regimen in locally advanced breast cancer. PATIENTS AND METHODS: Locally advanced breast cancer patients were randomly assigned onto a study comparing cyclophosphamide (C; 75 mg/m(2) orally days 1 to 14), epirubicin (E; 60 mg/m(2) intravenously [IV] days 1, 8), and fluorouracil (F; 500 mg/m(2) IV days 1, 8) six cycles every 28 days versus E (120 mg/m(2) IV day 1), C (830 mg/m(2) IV day 1), and granulocyte colony-stimulating factor (filgrastim; 5 micro g/kg/d subcutaneously days 2 to 13) six cycles every 14 days. The study was designed to detect a 15% improvement; that is, from 50% to 65% in median progression-free survival (PFS) in favor of the dose-intensified regimen. RESULTS: A total of 448 patients were enrolled over a period of 3 years. The median dose intensity delivered for C and E reached, respectively, 85% and 87% of that planned in the CEF arm and 96% and 95% of that planned in the EC arm. The dose-intensified arm was slightly more emetogenic and generated more grade 3 to 4 anemia but less febrile neutropenia episodes. After a median follow-up of 5.5 years, 277 events have been reported. The median PFS was 34 and 33.7 months for CEF and EC, respectively (P =.68), and the 5-year survival rate was 53% and 51% for CEF and EC, respectively (P =.94). CONCLUSION: Dose-intensified EC does not provide a measurable therapeutic benefit over CEF as neoadjuvant chemotherapy for unselected locally advanced breast cancer patients.

Adolescent↗