Jean-Yves Blay

Cancer Research Center of Lyon, Lyons, Rhône-Alpes, France

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Publications (283)1802.36 Total impact

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    ABSTRACT: Epithelioid hemangioendothelioma is a rare connective tissue tumor of vascular origin. It is most commonly found in young to middle aged women, and its clinical behavior is remakably variable from an indolent metastatic tumor to an aggressive rapidly growing neoplasm. Most tumors are diagnosed in an advanced unresectable phase and when clinically aggressive, require systemic cytotoxic treatment of sarcoma. Then, the 5-year survival rate after chemotherapy does not exceed 30%. Antiangiogenics are active in selected sarcoma subtypes: pazopanib, the only anti angiogenic registered agent for sarcoma provides a median PFS of 4.5 months only in the pivotal study. Their activity in EHE has been reported but long term outcome of these patients remain unreported. We report a case of a female patient with HEH who was treated with pazopanib for almost 8 years. Pazopanib therapy resulted in clinical improvement of symptoms and durable stabilization of liver tumors and lung lesions. Conclusion: Pazopanib is a promising therapeutic option in patients with HEH.
    12/2015; 5(1). DOI:10.1186/s13569-014-0018-3
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    ABSTRACT: Angiogenesis, among other signaling pathways, plays a key-role in sarcoma biology. Regorafenib (RE) has recently been shown to be effective in imatinib and sunitinib-refractory GIST in a phase III trial. We are conducting an international trial (France, Austria and Germany) consisting in 4 parallel double-blind placebo-controlled randomized (1/1) phase II trials to assess the activity and safety of RE in doxorubicin-refractory STS (ClinicalTrials.gov: NCT01900743). Each phase II trial is dedicated to one of the 4 following histological subgroups: liposarcoma, leiomyosarcoma, synovial sarcoma and other sarcoma. Within each randomized trial the following stratification factors will be applied: countries and prior exposure to pazopanib. Key-eligibility criteria are: measurable disease, age ≥18, not > 3 previous systemic treatment lines for metastatic disease, metastatic disease not amenable to surgical resection. The primary endpoint is progression-free survival (PFS) according to central radiological review. Secondary endpoints are: Toxicity (NCI-CTC AE V4.0); time to progression; Growth modulation index in pts receiving RE after randomization; 3 and 6 months PFS-Rates, best response rate and overall survival. Each phase II trial will be separately analyzed. In 3 trials, statistical assumptions are: PFS0 = 1.6 & PFS1 = 4.6 months; 1-sided α = 0.1; β = 0.05 with a total sample size of 192 pts. To take into account the rarity of synovial sarcoma, the statistical assumptions are: PFS0 = 1.6 & PFS1 = 4.6 months; 1-sided α = 0.1; β = 0.2 Tumor assessment is done monthly during the 4 first months, and every 3 months thereafter. After central radiological confirmation of tumor progression, an optional open-label option is offered to eligible patients. The design of this trial allows an assessment of regorafenib activity over placebo in four sarcoma strata and might provide evidence for launching a phase III trial. This study includes both integrative and exploratory translational research program. The study is enrolling since June 2013 (TRIAL REGISTRATION NUMBER: EudraCT N°: 2012-005743-24, on the 15(th) February 2012).
    BMC Cancer 12/2015; 15(1):1143. DOI:10.1186/s12885-015-1143-y · 3.32 Impact Factor
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    ABSTRACT: Primary cutaneous/subcutaneous Ewing sarcoma (scEWS) is extremely rare. We describe clinical features, treatment, and outcome of this Ewing localization. Retrospective study (1996-2012) on 56 patients. Most primary scEWS occurred in late adolescent/young adult females (F/M = 1.9; median age 21.5 years), with primary tumor in the extremity/trunk (48.5%/39%). Only 35/56 samples had Real-Time-Polymerase-Chain-Reaction/Fluorescent-In-Situ-Hybridization analysis, 32/35 had EWS-translocation. Most of them exhibited known favorable prognostic factors: localized disease (54/56), initial tumor volume < 200 ml (51/53). Thirty and 25 patients received chemotherapy according to Euro-Ewing99 or a shorter/less intense chemotherapy regimen associated with milder toxicity. One patient had not received chemotherapy. Surgery was performed at diagnosis in 37 patients (18/37 marginal/intra-lesional resections) followed by secondary surgery in 8/37 (three remained marginal). Nineteen other patients had an initial biopsy followed by chemotherapy, 15/19 underwent late surgery (4/15 marginal/intra-lesional resections). Overall, 27/56 patients received radiotherapy. Median follow-up was six years (1-15). Two patients with metastatic disease progressed at metastatic sites. Four patients with localized disease experienced progression/relapse (local n = 3, metastatic n = 1). Survival was excellent: 5y-OS and 5y-EFS were 93.8% (95%CI = 83-98%) and 88.5% (95%CI-= 77-95), respectively. Unplanned primary surgery should be avoided to try to minimize potential long term sequels due to secondary surgery or radiotherapy. Biopsy with molecular analysis and staging should be performed at diagnosis to inform treatment recommendations. Patients with metastases should be treated aggressively as for other metastatic EWS. Further studies are necessary to clarify whether a less intensive chemotherapy regimen could be safely used in localized disease to minimize acute/late toxicities. Pediatr Blood Cancer © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    Pediatric Blood & Cancer 04/2015; DOI:10.1002/pbc.25535 · 2.56 Impact Factor
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    ABSTRACT: Because desmoid tumors (DT) exhibit an unpredictable clinical course, translational research is crucial to identify the predictive factors of progression in addition to the clinical parameters. The main issue is to detect patients who are at a higher risk of progression. The aim of this work was to identify molecular markers that can predict Progression-Free Survival (PFS). Gene-expression screening was conducted on 115 available independent untreated primary desmoid tumors using cDNA microarray. We established a prognostic gene expression signature composed of 36 genes. To test robustness, we randomly generated 1000 36-gene signatures and compared their outcome association to our define 36-genes molecular signature and we calculated Positive Predictive Value and Negative Predictive Value. Multivariate analysis showed that our molecular signature had a significant impact on PFS while no clinical factor had any prognostic value. Among the 1000 random signatures generated, 56.7% were significant and none was more significant than our 36-gene molecular signature. Positive and negative predictive value was high (75.58% and 81.82% respectively). Finally, the top two genes down-regulated in no-recurrence were FECH and STOML2 and the top gene up-regulated in no-recurrence was TRIP6. By analyzing expression profiles, we have identified a gene expression signature that is able to predict Progression-Free Survival. This tool may be useful for prospective clinical studies. Copyright © 2015, American Association for Cancer Research.
    Clinical Cancer Research 04/2015; DOI:10.1158/1078-0432.CCR-14-2910 · 8.19 Impact Factor
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    ABSTRACT: Nilotinib inhibits the tyrosine kinase activity of ABL1/BCR-ABL1 and KIT, platelet-derived growth factor receptors (PDGFRs), and the discoidin domain receptor. Gain-of-function mutations in KIT or PDGFRα are key drivers in most gastrointestinal stromal tumours (GISTs). This trial was designed to test the efficacy and safety of nilotinib versus imatinib as first-line therapy for patients with advanced GISTs. In this randomised, open-label, multicentre, phase 3 trial (ENESTg1), participants from academic centres were aged 18 years or older and had previously untreated, histologically confirmed, metastatic or unresectable GISTs. Patients were stratified by previous adjuvant therapy and randomly assigned (1:1) via a randomisation list to receive oral imatinib 400 mg once daily or oral nilotinib 400 mg twice daily. The primary endpoint was centrally reviewed progression-free survival. Efficacy endpoints were assessed by intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT00785785. Because the futility boundary was crossed at a preplanned interim analysis, trial accrual terminated in April, 2011. Between March 16, 2009, and April 21, 2011, 647 patients were enrolled; of whom 324 were allocated nilotinib and 320 were allocated imatinib. At final analysis of the core study (data cutoff, October, 2012), 2-year progression-free survival was higher in the imatinib group (59·2% [95% CI 50·9-66·5]) than in the nilotinib group (51·6% [43·0-59·5]; hazard ratio 1·47 [95% CI 1·10-1·95]). In the imatinib group, the most common grade 3-4 adverse events were hypophosphataemia (19 [6%]), anaemia (17 [5%]), abdominal pain (13; 4%), and elevated lipase level (15; 5%), and in the nilotinib group were anaemia (18; 6%), elevated lipase level (15; 5%), elevated alanine aminotransferase concentration (12; 4%), and abdominal pain (11; 3%). The most common serious adverse event in both groups was abdominal pain (11 [4%] in the imatinib group, 14 [4%] in the nilotinib group). Nilotinib cannot be recommended for broad use to treat first-line GIST. However, future studies might identify patient subsets for whom first-line nilotinib could be of clinical benefit. Novartis Pharmaceuticals. Copyright © 2015 Elsevier Ltd. All rights reserved.
    The Lancet Oncology 04/2015; 16(5). DOI:10.1016/S1470-2045(15)70105-1 · 24.73 Impact Factor
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    ABSTRACT: Ombrabulin (AVE8062) disrupts the vasculature of established tumours and has shown preclinical synergistic anti-tumour activity when combined with cisplatin. In this phase 3 trial, we aimed to assess the efficacy and safety of ombrabulin plus cisplatin compared with placebo plus cisplatin in patients with advanced soft-tissue sarcomas. We did this multinational, randomised, double-blind, placebo-controlled phase 3 study at 44 centres in ten countries. Patients aged 18 years and older with metastatic soft-tissue sarcomas, an Eastern Cooperative Oncology Group performance status of 0-2, and who had previously received treatment with anthracycline and ifosfamide were randomly assigned (1:1) to intravenous infusion of ombrabulin 25 mg/m(2) plus cisplatin 75 mg/m(2) or intravenous infusion of placebo plus cisplatin 75 mg/m(2) every 3 weeks. Patients were allocated to treatment using a permuted blocks randomisation scheme (block size of four) via an interactive voice-response system, and stratified by histological subtype. Patients, medical staff, study investigators, and individuals who handled and analysed the data were masked to treatment assignment. Our primary endpoint was median progression-free survival in the intention-to-treat population. Safety analyses were done on all randomised patients who received at least one dose of study drug. This trial is now closed, and is registered with ClinicalTrials.gov, number NCT00699517. Between June 13, 2008, and April 26, 2012, we randomly assigned 355 patients to ombrabulin plus cisplatin (n=176) or placebo plus cisplatin (n=179). Median duration of follow-up was 27·9 (IQR 20·9-33·2) in the placebo group and 30·5 months (20·7-37·6) in the ombrabulin group. Progression-free survival was slightly, but significantly, improved in the ombrabulin group compared with the placebo group (median 1·54 months [95% CI 1·45-2·69] vs 1·41 [1·38-1·58] months; hazard ratio 0·76 [95% CI 0·59-0·98]; p=0·0302). Grade 3 or 4 adverse events occurred more frequently in individuals in the ombrabulin group than in those in the placebo group and included neutropenia (34 [19%] in the ombrabulin group vs 14 [8%] in the placebo group) and thrombocytopenia (15 [8%] vs six [3%] for placebo). Adverse events leading to death occurred in 18 patients in the ombrabulin group and 10 patients in the placebo group. The combination of ombrabulin and cisplatin significantly improved progression-free survival; however, it did not show a sufficient clinical benefit in patients with advanced soft-tissue sarcomas to support its use as a therapeutic option. Predictive biomarkers are needed for the rational clinical development of tumour vascular-disrupting drugs for soft-tissue sarcomas. Sanofi. Copyright © 2015 Elsevier Ltd. All rights reserved.
    The Lancet Oncology 04/2015; 16(5). DOI:10.1016/S1470-2045(15)70102-6 · 24.73 Impact Factor
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    ABSTRACT: Treatment options for patients with metastatic synovial sarcoma are limited. Over recent years, trabectedin has emerged as an effective agent for patients with advanced soft tissue sarcomas resistant to anthracyclines and ifosfamide. The aim of this retrospective analysis was to study the efficacy of trabectedin in the subgroup of synovial sarcomas. A retrospective analysis was carried out on patients with advanced synovial sarcoma treated with trabectedin at four European reference sarcoma centers and within the Italian Rare Cancer Network between 2000 and 2013. Radiological response, progression-free, and overall survival, as well as serious and unexpected adverse events were retrospectively assessed. Sixty-one patients with metastatic synovial sarcoma were identified. The median number of previous chemotherapy regimens was 2 (range 1-6). Nine patients had a partial response, in addition to two minor responses, and 19 patients had stable disease, for an overall response rate of 15% and a tumor control rate of 50%. The median progression-free survival was 3 months, with 23% of patients free from progression at 6 months. The median progression-free survival in responding patients was 7 months. Trabectedin is a therapeutic option for palliative treatment of a subset of patients with metastatic synovial sarcoma.
    Anti-Cancer Drugs 03/2015; DOI:10.1097/CAD.0000000000000228 · 1.89 Impact Factor
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    ABSTRACT: Non-small cell lung cancer (NSCLC) is a leading cause of death worldwide. Targeted monotherapies produce high regression rates, albeit for limited patient subgroups, who inevitably succumb. We present a novel strategy for identifying customized combinations of triplets of targeted agents, utilizing a simplified interventional mapping system (SIMS) that merges knowledge about existent drugs and their impact on the hallmarks of cancer. Based on interrogation of matched lung tumor and normal tissue using targeted genomic sequencing, copy number variation, transcriptomics, and miRNA expression, the activation status of 24 interventional nodes was elucidated. An algorithm was developed to create a scoring system that enables ranking of the activated interventional nodes for each patient. Based on the trends of co-activation at interventional points, combinations of drug triplets were defined in order to overcome resistance. This methodology will inform a prospective trial to be conducted by the WIN consortium, aiming to significantly impact survival in metastatic NSCLC and other malignancies.
    Oncotarget 03/2015; · 6.63 Impact Factor
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    ABSTRACT: Gastrointestinal stromal tumour (GIST), while relatively rare, is the most common mesenchymal tumour of the gastrointestinal tract. These tumours are largely resistant to cytotoxic chemotherapy and, in the past, were typically managed surgically. However, as a result of the identification of activating mutations in the proto-oncogene KIT and the development of compounds that inhibit the KIT receptor tyrosine kinase, GISTs have, in the last 14 years, become the archetype of a targeted agent-responsive tumour. Due to the almost continual emergence of new data from clinical trials and other studies on GIST diagnosis and treatment, the management of this disease requires regular review. The 2013 ArcheoloGIST summit was convened in Prague, Czech Republic. Interaction between attending physicians and the expert faculty was a core component of the summit. The current article is based on discussions held during two interactive sessions at ArcheoloGIST 2013 in which the authors aimed to: (1) reach a consensus on the current management of GIST and (2) provide a vision for the future diagnosis and treatment of this disease. © 2015 S. Karger AG, Basel.
    Oncology 02/2015; DOI:10.1159/000374120 · 2.61 Impact Factor
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    ABSTRACT: Desmoid tumor (DT) is a rare connective tissue tumor with locoregional aggressiveness but unpredictable behaviour. The miRNA profile was ascertained for 26 patients included in the Desminib phase II trial and an independent validation cohort of 15 patients. Predictive and prognostic supervised analysis on the Desminib cohort failed to identify miRNAs differentially expressed between progressive and non-progressive patients under imatinib treatment or between progressive and non-progressive patients after discontinuation of imatinib. However, an unsupervised hierarchical clustering of the Desminib cohort identified 2 groups (A and B) of 13 patients each, where only the number of previous lines of treatment before inclusion in the study differed significantly between the 2 groups. Time to progression after discontinuation of imatinib is longer in group B than in group A. Fifteen miRNAs were highly statistically differentially expressed between groups A and B, targeting more than 3000 genes, including AGO1, BCL2, CDK6, SMAD4, PTEN, CCND1, VEGFA, RB1. These results were confirmed in the independent validation cohort: hierarchical clustering of these 15 miRs identified 2 groups, whose time to recurrence is statistically different (28.8 months vs 68.8 months). These results provide the first demonstration of the prognostic value of miRNA expression profile with a possible direct impact on patient management. A more precise miRNA signature must now be determined to select patients who would not benefit from surgical resection of their tumor and who ought to be monitored without treatment. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Cancer Science 02/2015; DOI:10.1111/cas.12640 · 3.53 Impact Factor
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    ABSTRACT: The benefit or harm of trabectedin discontinuation in patients with non-progressive soft-tissue sarcoma remains unclear. We report the final analysis of a phase 2 trial investigating the clinical benefit of continuation of trabectedin treatment until progression versus interruption of therapy after six treatment cycles in patients with advanced soft-tissue sarcoma. For this open-label, non-comparative, multicentre, phase 2 study, eligible adult patients with advanced soft-tissue sarcomas, who had previously received doxorubicin-based chemotherapy and were able to receive trabectedin, were enrolled from 14 centres of the French Sarcoma Group. Trabectedin was administered at a dose of 1·5 mg/m(2) through a central venous line as a 24-h continuous infusion every 3 weeks. After the initial six cycles of trabectedin, patients who were free from progressive disease were randomly assigned in a 1:1 ratio either to continuous treatment or therapy interruption. Randomisation was done centrally by a computer-generated system using permuted blocks of four patients, stratified by tumour grade and performance status. Patients allocated to the interruption group were allowed to restart trabectedin in case of progressive disease. The primary endpoint was progression-free survival at 6 months after randomisation, analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01303094. In 178 evaluable patients, 91 (51%) patients had not progressed after six cycles. Of these patients, 53 patients were randomly assigned to the two treatment groups: 27 to the continuation group and 26 to the interruption group. Overall, patients in the two groups received a similar median number of trabectedin cycles (continuation group: 11 cycles [range 6-31+] vs interruption group: 11 [range 6-23+]). After randomisation, progression-free survival at 6 months was 51·9% (95% CI 31·9-68·6) in the continuation group versus 23·1% (9·4-40·3) in the interruption group (p=0·0200). The occurrence of treatment-related grade 3 adverse events (four [16%] of 25 patients in the continuation group vs three [14%] of 21 in the interruption group) and grade 4 adverse events (one [4%] vs none) was similar in both groups. The most common grade 3 and 4 toxicities were alanine aminotransferase or aspartate aminotransferase increases (one [4%] in the interruption group vs three [14%] in the continuation group), neutropenia (two [8%] vs two [10%]), and intestinal occlusion (one [4%] vs one [5%]). We do not recommend trabectedin discontinuation in patients with advanced, doxorubicin-refractory soft-tissue sarcoma who have not progressed after six cycles of treatment. The French National Cancer Institute (INCa) and PharmaMar SA. Copyright © 2015 Elsevier Ltd. All rights reserved.
    The Lancet Oncology 02/2015; 16(3). DOI:10.1016/S1470-2045(15)70031-8 · 24.73 Impact Factor
  • Bulletin du cancer 01/2015; 102(1). DOI:10.1016/j.bulcan.2014.11.002 · 0.64 Impact Factor
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    ABSTRACT: Understanding the cell of origin of cancer is pivotal for a better prevention and more efficient cure of the disease. Some examples of cancers arising from the transformation of stem cells have been shown, but in most cases, the cell of origin remains unknown. In healthy tissue, the microenvironment (niche) governs the fate of stem cells by balancing their self-renewal and differentiation through the regulation of the availability of soluble molecules, cell-cell contact, cell-matrix interactions, and physical constraints (Maguer-Satta, 2011). Increasing evidence indicates that the microenvironment plays an active role in cancer, such as alterations of mesenchymal stem cells that promote the proliferation and dissemination of cancer cells (McLean et al., 2011). However, the role of the microenvironment in the initial steps of cell transformation remains unexplored.
    Stem Cell Reports 01/2015; 26(2). DOI:10.1016/j.stemcr.2014.12.007
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    ABSTRACT: The mainstay of first line treatment in metastatic sarcomas is chemotherapy with response rates of ≈25% but the optimal management of further events is debated. We assessed the benefit of local metastatic treatment in metastatic sarcomas.
    Critical Reviews in Oncology/Hematology 01/2015; DOI:10.1016/j.critrevonc.2015.01.004 · 4.05 Impact Factor
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    ABSTRACT: Soft tissue sarcomas (STS) are a set of very heterogeneous tumors with numerous histological categories. The development of the molecular biology allowed identifying recurring molecular anomalies in certain subgroups of sarcomas, being able to represent diagnostic, prognosis and therapeutic tools. The molecular classification of STS includes until today 5 main groups of abnormalities: sarcomas with "simple genomic profile" showing reciprocal (1) chromosomal translocations, (2) activating mutation, (3) inhibitive mutation or (4) simple amplification; (5) sarcomas with "complex genomic profile" can include several tens of molecular abnormalities. The development of new-targeted therapies is based on the identification of a target, specific of a tumors subgroup and involved in carcinogenesis mechanisms and/or tumoral growth. Then, the aim of clinical research is to establish the proof of the concept through clinical trials, demonstrating the benefit brought to the patient and ending in the marketing of the drug. This proof of the concept was clearly established for imatinib, sunitinib and regorafenib in gastrointestinal stromal tumors, for imatinib in dermatofibrosarcoma protuberans and pigmented vilo-nodular synovitis, for denosumab in giant cell tumors of the bone, ending in the authorization to use these new therapies in these indications. It is in progress and promising for anti-IGF-1R in Ewing sarcomas, for crizotinib in myofibroblastic inflammatory tumors, for mTOR inhibitor in PEComas… The role of molecular abnormalities identified in the mechanisms of tumoral progress for sarcomas and their potential therapeutic impact will be detailed. Copyright © 2015. Published by Elsevier Masson SAS.
  • Cancer Research 01/2015; 75(1 Supplement):PR04-PR04. DOI:10.1158/1538-7445.CHTME14-PR04 · 9.28 Impact Factor
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    ABSTRACT: The past three decades have seen rapid improvements in the diagnosis and treatment of most cancers and the most important contributor has been research. Progress in rare cancers has been slower, not least because of the challenges of undertaking research. The International Rare Cancers Initiative (IRCI) is a partnership which aims to stimulate and facilitate the development of international clinical trials for patients with rare cancers. It is focused on interventional - usually randomised - clinical trials with the clear goal of improving outcomes for patients. The key challenges are organisational and methodological. A multi-disciplinary workshop to review the methods used in ICRI portfolio trials was held in Amsterdam in September 2013. Other as-yet unrealised methods were also discussed. The IRCI trials are each presented to exemplify possible approaches to designing credible trials in rare cancers. Researchers may consider these for use in future trials and understand the choices made for each design. Trials can be designed using a wide array of possibilities. There is no 'one size fits all' solution. In order to make progress in the rare diseases, decisions to change practice will have to be based on less direct evidence from clinical trials than in more common diseases. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.
    European journal of cancer (Oxford, England: 1990) 12/2014; DOI:10.1016/j.ejca.2014.10.027 · 4.82 Impact Factor
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    ABSTRACT: During the past decades, anticancer immunotherapy has evolved from a promising therapeutic option to a robust clinical reality. Many immunotherapeutic regimens are now approved by the US Food and Drug Administration and the European Medicines Agency for use in cancer patients, and many others are being investigated as standalone therapeutic interventions or combined with conventional treatments in clinical studies. Immunotherapies may be subdivided into "passive" and "active" based on their ability to engage the host immune system against cancer. Since the anticancer activity of most passive immunotherapeutics (including tumor-targeting monoclonal antibodies) also relies on the host immune system, this classification does not properly reflect the complexity of the drug-host-tumor interaction. Alternatively, anticancer immunotherapeutics can be classified according to their antigen specificity. While some immunotherapies specifically target one (or a few) defined tumor-associated antigen(s), others operate in a relatively non-specific manner and boost natural or therapy-elicited anticancer immune responses of unknown and often broad specificity. Here, we propose a critical, integrated classification of anticancer immunotherapies and discuss the clinical relevance of these approaches.
    Oncotarget 12/2014; 5(24). · 6.63 Impact Factor
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    ABSTRACT: Few targeted therapies (TTs) are registered for sarcoma treatment despite numerous phase II studies and yet there are potential treatment options for patients after standard treatment escape. The French Sarcoma Group - Bone Tumor Study Group (GSF-GETO) created a national registry to evaluate the outcome of patients treated with off-label TTs. Every consecutive sarcoma-patient receiving an off-label TT outside a clinical trial was included. The objective was to describe this patient efficacy and safety data in routine practice. From October 2008 to October 2011, 249 patients in 24 centers received 278 treatment lines with TTs. Twenty-five histological subtypes were included: most frequent were leiomyosarcoma (n =48, receiving sorafenib in 63%, and sunitinib in 27%), GIST (n =39, receiving sorafenib in 79%), and angiosarcoma (n =18, receiving sorafenib in 78%). The overall response rate to TTs was 15% (95%CI [10,6-20,2]), the disease control rate at 2 months was 59%. The median progression-free survival was 4,1 months (IC95% [3,2-4,8]). Three complete responses were observed. No toxic death occurred, grade 3 and 4 toxicities were reported in 74 (27%) and 14 patients (5%) respectively. Off-label TTs can be used for sarcoma patients in routine practice with an acceptable toxicity profile and efficacy similar to that reported in non-randomized clinical trials.
    BMC Cancer 11/2014; 14(1):870. DOI:10.1186/1471-2407-14-870 · 3.32 Impact Factor
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    ABSTRACT: Background The transferability of economic evaluation in health care is of increasing interest in today¿s globalized environment. Here, we propose a methodology for assessing the variability of data elements in cost evaluations in oncology. This method was tested in the context of the European Network of Excellence ¿Connective Tissues Cancers Network¿.Methods Using a database that was previously aimed at exploring sarcoma management practices in Rhône-Alpes (France) and Veneto (Italy), we developed a model to assess the transferability of health cost evaluation across different locations. A nested data structure with 60 final factors of variability (e.g., unit cost of chest radiograph) within 16 variability areas (e.g., unit cost of imaging) within 12 objects (e.g., diagnoses) was produced in Italy and France, separately. Distances between objects were measured by Euclidean distance, Mahalanobis distance, and city-block metric. A hierarchical structure using cluster analysis (CA) was constructed. The objects were also represented by their projections and area of variability through correlation studies using principal component analysis (PCA). Finally, a hierarchical clustering based on principal components was performed.ResultsCA suggested four clusters of objects: chemotherapy in France; follow-up with relapse in Italy; diagnosis, surgery, radiotherapy, chemotherapy, and follow-up without relapse in Italy; and diagnosis, surgery, and follow-up with or without relapse in France. The variability between clusters was high, suggesting a lower transferability of results. Also, PCA showed a high variability (i.e. lower transferability) for diagnosis between both countries with regard to the quantities and unit costs of biopsies.ConclusionCA and PCA were found to be useful for assessing the variability of cost evaluations across countries. In future studies, regression methods could be applied after these methods to elucidate the determinants of the differences found in these analyses.
    BMC Health Services Research 11/2014; 14(1):537. DOI:10.1186/s12913-014-0537-x · 1.66 Impact Factor

Publication Stats

8k Citations
1,802.36 Total Impact Points

Institutions

  • 2013–2015
    • Cancer Research Center of Lyon
      Lyons, Rhône-Alpes, France
    • HELIOS Klinik Ahrenshoop
      Ahrenshöft, Schleswig-Holstein, Germany
  • 2009–2015
    • Claude Bernard University Lyon 1
      Villeurbanne, Rhône-Alpes, France
    • Leiden University
      Leyden, South Holland, Netherlands
    • Catholic University of Louvain
      Лувен-ла-Нев, Walloon, Belgium
  • 2002–2015
    • Centre Léon Bérard
      Lyons, Rhône-Alpes, France
  • 2008–2014
    • University of Lyon
      Lyons, Rhône-Alpes, France
    • Erasmus MC
      • Department of Internal Oncology
      Rotterdam, South Holland, Netherlands
    • Centre Jean Perrin
      Clermont, Auvergne, France
  • 2012
    • Dana-Farber Cancer Institute
      • Center for Sarcoma and Bone Oncology
      Brookline, MA, United States
  • 2011
    • University of Tours
      Tours, Centre, France
    • Assistance Publique Hôpitaux de Marseille
      Marsiglia, Provence-Alpes-Côte d'Azur, France
  • 2004–2011
    • CHU de Lyon - Groupement Hospitalier Edouard Herriot
      Lyons, Rhône-Alpes, France
    • Institut de Cancérologie Gustave Roussy
      • Department of Clinical Biology
      Île-de-France, France
  • 2007–2009
    • Erasmus Universiteit Rotterdam
      • Department of Medical Oncology
      Rotterdam, South Holland, Netherlands
  • 2004–2005
    • Hospices Civils de Lyon
      Lyons, Rhône-Alpes, France