المؤلفون: Cecilia Liberatoscioli, Catherine Fortpied, Jan Bogaerts

المصدر: Anti-cancer drugs. 22(7)

مصطلحات موضوعية: Research design, Cancer Research, medicine.medical_specialty, Pathology, Endpoint Determination, Population, MEDLINE, medicine, Clinical endpoint, Humans, Pharmacology (medical), Medical physics, education, Pharmacology, education.field_of_study, business.industry, Patient Selection, Head and neck cancer, medicine.disease, Causality, Clinical trial, Oncology, Clinical Trials, Phase III as Topic, Head and Neck Neoplasms, Research Design, Data Interpretation, Statistical, business, Statistician

الوصف: The purpose of this article is to present some of the challenges the trial statistician meets when designing a clinical trial of the head and neck cancer. In recent years, the field of head and neck cancer has been facing some exciting evolutions, such as the arrival of newly targeted therapies and findings of disease causality and prognosis. These evolutions are accompanied by challenges in trial methodology that continue even today, and will most likely grow in importance in the future. This article focuses essentially on the design of phase III trials and discusses three major topics: should the trial be designed for a broad or a targeted population? Is there a concern for lack of equipoise and if so, how will it affect the trial results? What are the key elements that need to be taken into consideration when choosing, defining, and measuring the primary endpoint?

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2772cbb72ac59b07afb2081616def292Test
https://pubmed.ncbi.nlm.nih.gov/21709617Test

المؤلفون: Lynda Wyld, Hans Wildiers, Matti Aapro, Andrea Luciani, Bjorn Penninckx, A Timmer-Bonte, Ulrich Wedding, Catherine Fortpied, M C Van Nes, G Vonminckwitz, Lazzaro Repetto, Franck Bonnetain, Alistair Ring, Athanasios G. Pallis, Colin D. Johnson

المصدر: Annals of Oncology, 22, 1922-6
Annals of Oncology, 22, 8, pp. 1922-6

مصطلحات موضوعية: education.field_of_study, medicine.medical_specialty, Age-related aspects of cancer [ONCOL 2], business.industry, Population, MEDLINE, Cancer, Hematology, Aetiology, screening and detection [ONCOL 5], medicine.disease, Clinical trial, Quality of life (healthcare), Oncology, Geriatric oncology, Multidisciplinary approach, Global health, Physical therapy, medicine, education, business

الوصف: Item does not contain fulltext BACKGROUND: Due to the aging of the population, the number of older patients diagnosed with a malignant disease is increasing. A multidisciplinary approach to the senior adult cancer patient is mandatory, to assure optimal diagnosis and therapeutic management. DESIGN: European Organisation for Research and Treatment of Cancer (EORTC) has currently defined senior adult oncology as one of its priorities and has established an active Elderly Task Force (ETF). Under the auspices of the EORTC, the ETF organized a workshop on clinical trial methodology in older cancer patients and in this article, we present the conclusions of this workshop. RESULTS: Besides the 'classical' efficacy end points, quality of life, functional status and independence of the patient should be assessed in clinical trials in older patients. The participants of the workshop agreed on the use of a minimum dataset for the assessment of global health and functional status in older cancer patients. The panel also recommended that optimization of collaboration with pharmaceutical industry requires reporting of age-related data (subgroup analyses of clinical trials, age-related pooled analyses and obligatory post-marketing studies in vulnerable and frail older patients). CONCLUSION: The identification of proper clinical outcomes and the validation of geriatric screening tools are needed for conducting sound and comparable clinical trials. 01 augustus 2011

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8ecbce91ed5d976da483c38545bcc1afTest
http://hdl.handle.net/2066/97843Test

المؤلفون: Igor, Aurer, Houchingue, Eghbali, John, Raemaekers, Hussein M, Khaled, Catherine, Fortpied, Liliana, Baila, Richard W M, van der Maazen

المصدر: European journal of haematology. 86(2)

مصطلحات موضوعية: Adult, Male, Time Factors, Lymphoma, Non-Hodgkin, Prednisolone, Middle Aged, Prognosis, Deoxycytidine, Gemcitabine, Europe, Treatment Outcome, Doxorubicin, Vincristine, Antineoplastic Combined Chemotherapy Protocols, Humans, Female, Cyclophosphamide, Aged, Neoplasm Staging

الوصف: Despite recent improvements, many patients with aggressive non-Hodgkin's lymphoma (NHL) ultimately succumb to their disease. Therefore, improvements in front-line chemotherapy of aggressive NHL are needed. Gemcitabine is active in lymphoma.We performed a randomized phase II trial of the addition of gemcitabine to standard CHOP chemotherapy with or without rituximab [(R)CHOP]. The trial was also designed to determine the maximal tolerated dose (MTD) of gemcitabine in this combination. Patients with previously untreated aggressive NHL were randomized to receive either eight cycles of (R)CHOP given every 3 wk or (R)CHOP combined with gemcitabine [Gem-(R)CHOP].Twenty-five patients were enrolled in the trial before early closure. Twelve were randomized to Gem-(R)CHOP and 13 to (R)CHOP. MTD of gemcitabine was 800 mg/m(2) given on days 1 and 8; dose-limiting toxicity was hematologic. Five patients (42%) treated with Gem-(R)CHOP achieved complete response in comparison with 10 (77%) treated with (R)CHOP. Median time to treatment failure was 1.5 yr for Gem-(R)CHOP and 3.1 yr for (R)CHOP. Three patients receiving Gem-(R)CHOP had serious pulmonary toxicity, when compared to none receiving (R)CHOP. One patient died of pneumonitis.In this group of patients, addition of gemcitabine did not seem to improve outcomes. Gem-(R)CHOP in previously untreated patients with aggressive NHL occasionally results in severe, potentially fatal, pulmonary toxicity.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid________::08bd48137f4ab7a67ab2540429bc6a4fTest
https://pubmed.ncbi.nlm.nih.gov/20942843Test

المؤلفون: Maria Gomes da Silva, Ruth Pettengell, Carmit Rubin, Bernice Oberman, Peter Dreger, Sami Bousseta, Hailun Li, Ofer Shpilberg, Umberto Vitolo, Gilles Salles, Laurence S. Freedman, Mathias Witzens-Harig, Thomas M. Habermann, Liat Vidal, Anat Gafter-Gvili, Marinus H. J. van Oers, Catherine Fortpied, Andrea Evangelista

المصدر: Blood. 124:4462-4462

مصطلحات موضوعية: medicine.medical_specialty, Performance status, business.industry, Immunology, Hazard ratio, Cell Biology, Hematology, Biochemistry, Chemotherapy regimen, Surgery, law.invention, Log-rank test, Maintenance therapy, Randomized controlled trial, Median follow-up, law, Internal medicine, medicine, Progression-free survival, business

الوصف: Background Rituximab in combination with chemotherapy has been shown to improve overall survival (OS) in pts with FL compared with chemotherapy alone. The effect of MR was evaluated in randomized clinical trials (RCTs) with conflicting results regarding OS. In a previous systematic review and meta-analysis of summary (aggregate) data we demonstrated an OS benefit of MR treatment in pts with relapsed or refractory FL and an improved progression free survival (PFS) in both untreated and relapsed refractory FL. However, pts' disease and treatment characteristics may interact with the effect of MR. To improve identification of sub-groups of pts who may benefit from MR treatment, and to evaluate factors that interact with the effect of MR we conducted an international IPD (raw data) meta-analysis of RCTs of MR for pts with FL. We present the first analysis of this meta-database. Methods In June 2014, we updated an electronic search in Pubmed and the Cochrane Library, conference proceedings and database of clinical trials for randomized trials comparing MR to observation. The investigators of eleven trials that fulfilled inclusion criteria were invited to cooperate. Results of one trial were not reported and this trial could not be included in the meta-analysis. Seven study groups participated in this collaborative project and contributed data on individual pts, including disease characteristics, past treatment, response, survival and adverse events. We examined the effect of pt, disease and treatment characteristics by performing a series of Cox regression analyses stratified by trial. In a sensitivity analysis we combined the assessed log hazard ratios (HR) using a log-rank test for each study and combined the results using a fixed effect meta-analysis. Results We obtained data for 2323 patients randomized in 7 trials of MR compared to observation after induction therapy. The median follow up ranged from 28-114 months. The median age was 57 years (23 - 85 years), and 41% were older than 60 years. 50% of pts were women, 97% had WHO performance status 0-1; 1195 (53%) pts received CHOP/RCHOP, 453 (20%) CVP/R CVP; 1755 (77%) received rituximab containing induction; 33% of pts received 1st induction, 67% ≥2nd. Overall, pts less than 60 years of age (vs. ≥60 years) (p < 0.0001), and women (p = 0.001) had a better prognosis. There was no interaction between sex and the effect of MR (p = 0.65). Pts treated with MR had an improved OS compared to observation (HR 0.76, 95% CI 0.62-0.93, p=0.008, Figure). This was demonstrated also in a sensitivity analysis of 10 studies fulfilling inclusion criteria. There was no statistically significant heterogeneity of treatment effect between trials (p=0.15). In an analysis by treatment line (1st vs. ≥2nd), the estimated effect of MR among patients who received ≥2nd induction was HR of 0.70 (95% CI 0.55 - 0.91), compared to 0.90 (95% CI 0.65 - 1.25) among patients who received 1st induction. However, this difference was not statistically significant (p=0.25). Analysis by the inclusion of rituximab in induction demonstrated among patients who received rituximab in induction a HR of 0.82 (95% CI 0.63 – 1.06), and among those who received induction without rituximab a HR of 0.68 (95% CI 0.49 – 0.93). This difference was not statistically significant (p= 0.35). Analysis by chemotherapy regimen demonstrated an estimated effect for MR among patients who received RCHOP/CHOP of 0.79, 95% CI 0.58 – 1.06, and after RCVP/CVP of 0.65, 95% CI 0.42 – 1.02, with no statistically significant difference between these sub-groups (p = 0.50). Conclusions This is the first report of the collaborative group of maintenance therapy for FL patients. Based on individual patient data, this study demonstrated an improved OS with MR therapy for patients with FL. A sensitivity analysis with all 10 eligible trials supported these results. Results support the effectiveness of MR among patients after their 1st induction as well as after ≥2nd induction, and irrespective of inclusion of rituximab in induction, and the chemotherapy regimen. These results are consistent with those of the summary data meta-analysis that was previously published. The wider CI and lack of statistical significance within sub-groups could be attributed to the sample size. Figure: Pooled HR of death of MR compared to observation in patients with follicular lymphoma. In one study there were no events in one group and it is not represented in the forest plot. Figure:. Pooled HR of death of MR compared to observation in patients with follicular lymphoma. In one study there were no events in one group and it is not represented in the forest plot. Disclosures Vidal: Roche: unrestricted grant Other. Shpilberg:Roche: Consultancy, Research Funding.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::ac24a38445f1d28ad0b6aede9232d104Test
https://doi.org/10.1182/blood.v124.21.4462.4462Test

المؤلفون: Pauline Brice, Richard W.M. van der Maazen, Marc André, John M. M. Raemaekers, T. Girinski, Monica Bellei, Massimo Federico, Annibale Versari, Christophe Fermé, Michel Meignan, Oumedaly Reman, Catherine Fortpied, Catherine Sebban, Martin Hutchings, Aspasia Stamatoulas, Franck Morschhauser, Elly Lugtenburg, Ercole Brusamolino

المصدر: Blood. 120:549-549

مصطلحات موضوعية: medicine.medical_specialty, business.industry, medicine.medical_treatment, Standard treatment, Immunology, Hazard ratio, Cell Biology, Hematology, Interim analysis, Biochemistry, Chemotherapy regimen, Radiation therapy, ABVD, Statistical significance, Medicine, Radiology, Stage (cooking), business, Nuclear medicine, medicine.drug

الوصف: Abstract 549 Introduction Early stage classical Hodgkin lymphoma (cHL) is highly curable with a combination of chemotherapy and radiotherapy (RT). Late toxicities due to RT are altering the outcome. FDG-PET (PET) has emerged as a potential new tool to early select good prognosis patients after a few cycles of chemotherapy. In the current trial, PET is used to guide early response-adapted therapy. Main objective is to evaluate whether chemotherapy alone is as effective as standard combined modality treatment in patients with an early PET negative status. In addition we evaluate whether intensification of chemotherapy is more effective than standard chemotherapy in early PET positive patients. This abstract concerns the results of the pre-planned interim safety analysis. Patients and methods All patients with a stage I and II supra-diaphragmatic cHL, between 15 and 70 years old are eligible for the study and stratified according to LYSA/EORTC criteria. Unfavorable (U) prognostic factors included patients with: CSII ≥ 4 nodal areas or age ≥ 50 yrs or MT ratio ≥ 0.35 or ESR ≥ 50 (without B-symptoms) or ESR ≥ 30 (with B-symptoms). All others are considered favorable (F). In the F group, the standard treatment is ABVDx3 and 30Gy involved-node RT (IN-RT); the early PET scan after 2 cycles is made solely for sake of comparison with the experimental arm but will not affect treatment. The experimental arm consisted of ABVDx2 followed by a PET: if the PET is negative, patients receive 2 additional cycles of ABVD and no RT. If the PET is positive, patients received BEACOPPesc x2 and 30 Gy IN-RT. In the U group, the same principles were used, the standard treatment is ABVDx4 and 30Gy IN-RT; a PET is performed for all patients after cycle 2 with no modification of treatment. The experimental arm is ABVDx2 followed by a PET: if the PET is negative, patients receive 4 additional cycles of ABVD and no RT. If the PET is positive, patients receive BEACOPPesc x2 and 30 Gy IN-RT. This report discloses the IA performed on the early PET negative patients. Results The trial opened in October 2006 and in July 2009, 1137 patients were included with a median follow-up of 1.1 years with sufficient events to allow for the planned IA. In the F early PET negative group, 188 patients were included in the standard arm, and 193 in the experimental arm. A total of 10 events occurred: one in the standard arm and nine in the experimental arm. All these events were progressions or relapses, no deaths occurred in this group. Based on the actual information fraction (10 out of the 26 events required for the final analysis) and the resulting one-sided significance level to perform the statistical test (0.102), futility was declared (p-value=0.017 To exclude bias caused by differences in interpretation of the early PET scans by the various central reviewers, a new blind PET review was performed on all patients with an event and an equal number of randomly selected patients without event. Six patients from this group considered negative in the first review turned positive in the new review. This did no significantly alter the outcome of the IA. Conclusion The planned futility IA of the H10 trial shows that the risk of early relapse in non-irradiated patients with stage I-II cHL was significantly higher than in standard combined modality treated patients, even in this selected group of patients with an early negative PET. Consequently, accrual was stopped for this part of the trial. Disclosures: No relevant conflicts of interest to declare.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::0c487ddcdb2b69cef6d48eac788b2d30Test
https://doi.org/10.1182/blood.v120.21.549.549Test

المؤلفون: Patrice Carde, Bertrand Coiffier, Catherine Fortpied, Christophe Fermé, Guy Cantin, Matthias Karrasch, Franck Morschhauser, Anna Sureda, Bengt Glimelius, Hussein M. Khaled, Igor Aurer, Max Wolf, Serge Bologna, Isabelle Gaillard, Matthew D. Seftel, Nicolas Mounier, Pauline Brice, Pieternella J. Lugtenburg, Denis Caillot

المصدر: Journal of Clinical Oncology. 30:8002-8002

مصطلحات موضوعية: BEACOPP, Oncology, Cancer Research, medicine.medical_specialty, business.industry, medicine.medical_treatment, COPP, Surgery, Clinical trial, ABVD, Internal medicine, medicine, Overall survival, Hodgkin lymphoma, Stage (cooking), business, Time to treatment failure, medicine.drug

الوصف: 8002 Background: Escalated BEACOPP and derivatives achieved superior time to treatment failure (FFTF) over COPP/ABVD, resulting in higher overall survival (OS) for advanced HL. However, later clinical trials have failed to confirm OS superiority over ABVD. Methods: Eligibility criteria: clinical stage III/IV HL, International prognostic score (IPS) ≥ 3, age

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::551634cbe4f71df1ff2d1204ab3aac05Test
https://doi.org/10.1200/jco.2012.30.15_suppl.8002Test

المؤلفون: Jan B. Vermorken, J S W Stewart, C.M.L. van Herpen, Catherine Fortpied, Éva Remenár, R. Karra Gurunath, M. Degardin

المصدر: Journal of Clinical Oncology. 29:5530-5530

مصطلحات موضوعية: Oncology, Cisplatin, Cancer Research, medicine.medical_specialty, business.industry, Induction chemotherapy, Long term results, Surgery, Fluorouracil, Internal medicine, medicine, Basal cell, In patient, Head and neck, business, medicine.drug

الوصف: 5530 Background: At a median follow-up (FU) of 32.5 months, the original EORTC24971/TAX323 study showed that compared with standard cisplatin/infusional fluorouracil (PF), induction chemotherapy (I...

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::6e4a35ed81c79abdf42998c74dd36654Test
https://doi.org/10.1200/jco.2011.29.15_suppl.5530Test

المؤلفون: Franck Morschhauser, Monica Bellei, Liliana Baila, Aspasia Stamatoullas, Pauline Brice, J M Raemaekers, Oumedaly Reman, Marc André, Massimo Federico, Catherine Fortpied, Catherine Sebban, Richard vander Maazen, Théodore Girinski, Ercole Brusamolino, Michel Meignan, Elly Lugtenburg, Christophe Fermé

المصدر: Blood. 114:97-97

مصطلحات موضوعية: medicine.medical_specialty, Chlorambucil, business.industry, medicine.medical_treatment, Standard treatment, Immunology, Cell Biology, Hematology, medicine.disease, Hodgkin's lymphoma, Biochemistry, Surgery, Lymphoma, law.invention, Radiation therapy, Randomized controlled trial, ABVD, law, Internal medicine, medicine, Stage (cooking), business, medicine.drug

الوصف: Abstract 97 Introduction Early stage classical Hodgkin lymphoma (cHL) is highly curable with a combination of chemotherapy and radiotherapy. However, long term toxicities due to radiotherapy, mainly secondary tumors and cardiovascular events, are altering the outcome. FDG-PET has emerged as a potential new tool to early select good prognosis patients after a few cycles of chemotherapy. We use it as an experimental tool to adapt therapy in the current trial. Patients and methods All patients with a stage I or II supra-diaphragmatic cHL, between 15 and 70 years-old, are eligible for the study and stratified according to GELA/EORTC criteria. Unfavorable (U) prognostic factors included patients with: CSII ≥ 4 nodal areas or age ≥ 50 yrs or MT ratio ≥ 0.35 or ESR ' 50 (without B-symptoms) or ESR ≥ 30 (with B-symptoms). All others are considered favorable (F). In the F group, the standard treatment is ABVDx3 and 30Gy involved-node radiotherapy (IN-RT); the interim FDG-PET scan after 2 cycles is made solely for sake of comparison with the experimental arm but will not affect treatment. The experimental arm consist of ABVDx2 followed by an FDG-PET: if the FDG-PET is negative, patients receive 2 additional cycles of ABVD and no radiotherapy. If the FDG-PET is positive, patients receive BEACOPPesc x2 and 30 Gy IN-RT. In the U group, the same principles are used, the standard treatment is ABVDx4 and 30Gy IN-RT; an FDG-PET is performed for all patients after cycle 2 with no modification of treatment. The experimental arm is ABVDx2 followed by an FDG-PET: if the FDG-PET is negative, patients receive 4 additional cycles of ABVD and no radiotherapy. If the FDG-PET is positive, patients receive BEACOPPesc x2 and 30 Gy IN-RT. Results The trial started in December 2006 and at the end of July 2009, 1097 patients were included. A total of 530 patients have been entered during the last year. The main patients characteristics are as follows: median age 31 years-old (range 15-70), stage I: 16%, stage II: 84%. Thirty-nine % of the patients are in the F group and 61% in the U group. A baseline FDG-PET is not mandatory in the trial but highly recommended; it is available for 93% of patients entered with an improvement over time (from 88% during the first year of accrual to 96% during the last year). A central FDG-PET review is performed after cycle 2 by a panel of 6 nuclear medicine experts according to Juweid's criteria (J Clin Oncol 2007;25,571).The agreement between experts is good with a k=0.63 (95% CI 0.58-0.64) and 85% agreement (95% CI 83-87%), p=0.0008 (J Clin Oncol 2009;27;2739). On the first 485 cases centrally reviewed, a difference of interpretation between the local site reader and the central review panel is observed in 8% of the cases, in 58% of which PET after 2 cycles result was altered from “negative” to “positive”. Results of FDG-PET are available for the first 894 included patients. In the F group (355 patients), 14% are positive and 86% are negative. In the U group (539 patients), 24% are positive and 76% negative. Conclusion FDG-PET treatment adaptation is feasible in a large intergroup randomized trial and a baseline FDG-PET was shown to be available for most and recently all included patients. A centralized FDG-PET is feasible within 72 hours with an excellent agreement between involved experts and a low level of discrepancy with local nuclear physician Disclosures: No relevant conflicts of interest to declare.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::fc2bdf45ab2a1e0cb850e7470f7fc71bTest
https://doi.org/10.1182/blood.v114.22.97.97Test

المؤلفون: Luc Duchateau, Paul Janssen, Iva Kezic, Catherine Fortpied

الوصف: Summary. To model the time evolution of the event rate in recurrent event data a crucial role is played by the timescale that is used. Depending on the timescale selected the interpretation of the time evolution will be entirely different, both in parametric and semiparametric frailty models. The gap timescale is more appropriate when studying the recurrent event rate as a function of time since the last event, whereas the calendar timescale keeps track of actual time. We show both timescales in action on data from an asthma prevention trial in young children. The frailty model is further extended to include both timescales simultaneously as this might be most relevant in practice.

العلاقة: https://doi.org/10.1111/1467-9876.00409Test

الإتاحة: https://doi.org/10.1111/1467-9876.00409Test

المؤلفون: Andrea Luciani, Sjoukje F. Oosting, Vincent Grégoire, Christian Simon, Isacco Desideri, Silke Tribius, Catherine Fortpied, Susanne Singer, Dominiek Staelens, Carmela Caballero

المساهمون: Guided Treatment in Optimal Selected Cancer Patients (GUTS)

المصدر: Web of Science
Annals of Oncology, 29(Suppl_8), 393-393. Oxford University Press

مصطلحات موضوعية: 0301 basic medicine, Oncology, medicine.medical_specialty, business.industry, Locally advanced, Hematology, medicine.disease, Head and neck squamous-cell carcinoma, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, medicine, business

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::868a031d2f8e1d845e91185331d41c1bTest
https://publons.com/wos-op/publon/27066948Test/