Jean-Yves Blay

Claude Bernard University Lyon 1, Villeurbanne, Rhône-Alpes, France

Are you Jean-Yves Blay?

Claim your profile

Publications (309)2083.24 Total impact

  • Source
    [Show abstract] [Hide abstract]
    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
  • Source
    [Show abstract] [Hide abstract]
    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 ( 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 · 3.36 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: BRAF V600 mutations occur in various nonmelanoma cancers. We undertook a histology-independent phase 2 "basket" study of vemurafenib in BRAF V600 mutation-positive nonmelanoma cancers. We enrolled patients in six prespecified cancer cohorts; patients with all other tumor types were enrolled in a seventh cohort. A total of 122 patients with BRAF V600 mutation-positive cancer were treated, including 27 patients with colorectal cancer who received vemurafenib and cetuximab. The primary end point was the response rate; secondary end points included progression-free and overall survival. In the cohort with non-small-cell lung cancer, the response rate was 42% (95% confidence interval [CI], 20 to 67) and median progression-free survival was 7.3 months (95% CI, 3.5 to 10.8). In the cohort with Erdheim-Chester disease or Langerhans'-cell histiocytosis, the response rate was 43% (95% CI, 18 to 71); the median treatment duration was 5.9 months (range, 0.6 to 18.6), and no patients had disease progression during therapy. There were anecdotal responses among patients with pleomorphic xanthoastrocytoma, anaplastic thyroid cancer, cholangiocarcinoma, salivary-duct cancer, ovarian cancer, and clear-cell sarcoma and among patients with colorectal cancer who received vemurafenib and cetuximab. Safety was similar to that in prior studies of vemurafenib for melanoma. BRAF V600 appears to be a targetable oncogene in some, but not all, nonmelanoma cancers. Preliminary vemurafenib activity was observed in non-small-cell lung cancer and in Erdheim-Chester disease and Langerhans'-cell histiocytosis. The histologic context is an important determinant of response in BRAF V600-mutated cancers. (Funded by F. Hoffmann-La Roche/Genentech; number, NCT01524978.).
    New England Journal of Medicine 08/2015; 373(8):726-36. DOI:10.1056/NEJMoa1502309 · 55.87 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Although gastrointestinal stromal tumors (GISTs) are a rare type of cancer, they are the commonest sarcoma in the gastrointestinal tract. Molecularly targeted therapy, such as imatinib therapy, has revolutionized the treatment of advanced GIST and facilitates scientific research on GIST. Nevertheless, surgery remains a mainstay of treatment to obtain a permanent cure for GIST even in the era of targeted therapy. Many GIST guidelines have been published to guide the diagnosis and treatment of the disease. We review current versions of GIST guidelines published by the National Comprehensive Cancer Network, by the European Society for Medical Oncology, and in Japan. All clinical practice guidelines for GIST include recommendations based on evidence as well as on expert consensus. Most of the content is very similar, as represented by the following examples: GIST is a heterogeneous disease that may have mutations in KIT, PDGFRA, HRAS, NRAS, BRAF, NF1, or the succinate dehydrogenase complex, and these subsets of tumors have several distinctive features. Although there are some minor differences among the guidelines-for example, in the dose of imatinib recommended for exon 9-mutated GIST or the efficacy of antigen retrieval via immunohistochemistry-their common objectives regarding diagnosis and treatment are not only to improve the diagnosis of GIST and the prognosis of patients but also to control medical costs. This review describes the current standard diagnosis, treatment, and follow-up of GISTs based on the recommendations of several guidelines and expert consensus.
    Gastric Cancer 08/2015; DOI:10.1007/s10120-015-0526-8 · 3.72 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Gastrointestinal stromal tumours (GISTs) are the most common gastrointestinal sarcomas. This global, prospective registry followed patients with advanced or localised GIST (2007-2011). Current and evolving diagnostics, treatments and outcome measures in patients with GIST were assessed. Eligible patients were diagnosed with advanced or localised GIST within 15months of registry entry. No treatment plan was prescribed, and no visit schedule was mandated. Treating physicians recorded patient information, including tumour response, diagnostic methods, medications, surgeries performed, mutation status and adverse events leading to dose/medication changes. Survival outcomes were estimated using the Kaplan-Meier method. Other data were analysed using descriptive statistics. The registry included 1663 patients (advanced GIST, n=1095; localised GIST, n=537). Medications (e.g. tyrosine kinase inhibitor use and dosing), disease progression or recurrence and physician assessment of response to treatment in registry patients were consistent with controlled trials and prevailing clinical recommendations. In advanced GIST, estimated 30-month progression-free survival (PFS) (59.8%) and overall survival (OS) (82.7%) were higher than results from previously reported trials (≈40% and ≈70%, respectively). Consistent with treatment guidelines, the most common initial treatments were imatinib for advanced GIST, and complete surgical resection for localised GIST. Computed tomography scans were the most common imaging technique used at diagnosis and follow-up. Mutation analysis was performed at diagnosis in only 15.3% and 14.5% of patients with advanced and localised GIST, respectively. In this real-world GIST registry, patients with advanced GIST were treated with imatinib and patients with localised GIST received surgical resection, in accordance with prevailing clinical recommendations. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
    European journal of cancer (Oxford, England: 1990) 08/2015; 130. DOI:10.1016/j.ejca.2015.07.010 · 5.42 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a highly aggressive neoplasm occurring in young females. Paraneoplastic hypercalcaemia is associated in two-third of cases. Recent studies demonstrated that this rare tumor harbors molecular features of a malignant rhabdoid tumor secondary to SMARCA4/BRG1 mutations. We illustrate herein a typical bilateral case of SCCOHT in a 14 year-old girl comprehensively molecularly characterized . We also discuss the invaluable input of SMARCA4 immunostaining in the diagnostic approach of undifferentiated ovarian and pelvic malignancies in routine practice.
    Pediatric and Developmental Pathology 07/2015; DOI:10.2350/15-04-1624-CR.1 · 0.87 Impact Factor
  • Jean-Yves Blay · Eunjuh Hurh · Steven Green · Steven Novick
    The Lancet Oncology 07/2015; 16(7). DOI:10.1016/S1470-2045(15)00016-9 · 24.69 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this randomized, phase II trial was to explore the activity and safety of adding bevacizumab to paclitaxel once per week in treatment of angiosarcomas (AS). Patients were treated with paclitaxel alone (90 mg/m(2) per week for six cycles of 28 days each; arm A) or with paclitaxel combined with bevacizumab (10 mg/kg once every 2 weeks; arm B). In the combination treatment arm, bevacizumab was administered after the six cycles of chemotherapy as maintenance therapy (15 mg/kg once every 3 weeks) until intolerance or progression occurred. Stratification factors were superficial versus visceral AS and de novo versus radiation-induced AS. The primary end point was the 6-month progression-free survival (PFS) rate, which was based on RECIST, version 1.1. Statistical assumptions were P0 = 20%, P1 = 40%, a = 10%, and b = 20%. P0 was the PFS rate at 6 months defining inactive drug, and P1 was the PFS rate at 6 months defining promising drug. A total of 52 patients were enrolled, and 50 were randomly assigned in 14 centers. The most common primary sites were the breast (49%) and skin (12%). There were 17 (34%) visceral and 24 (49%) radiation-induced AS. The performance status was 0 in 24 patients (49%) and 1 in the remaining 25 patients (51%). The median follow-up time was 14.5 months. Both treatment regimens were considered active, with 6-month PFS rates of 54% (14 of 26) in arm A and 57% (14 of 24) in arm B. The median overall survival rates were 19.5 months in arm A and 15.9 months in arm B. Toxicity was higher with the combination arm and included one fatal drug-related toxicity (intestinal occlusion). The primary objective was met in both treatment arms. However, the present data do not support additional clinical investigation of combined paclitaxel/bevacizumab for the treatment of advanced AS. © 2015 by American Society of Clinical Oncology.
    Journal of Clinical Oncology 07/2015; 33(25). DOI:10.1200/JCO.2015.60.8505 · 18.43 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Validated predictive biomarkers for multi-tyrosine kinase inhibitors (MTKI) efficacy are lacking. We hypothesized that interindividual response variability is partially dependent on somatic DNA copy number alterations (SCNAs), particularly those of genes encoding the protein tyrosines targeted by MTKI (called target genes). Genomic alterations were investigated in MTKI responsive and non responsive patients with different histological subtypes included in the ProfiLER protocol (NCT 01774409). From March 2013 to August 2014, 58 patients with advanced cancer treated with one of 7 MTKIs were included in the ProfiLER trial and split into one discovery cohort (n = 13), and 2 validation cohorts (n = 12 and 33). An analysis of the copy number alterations of kinase-coding genes for each of 7 MTKIs was conducted. A prediction algorithm (SUMSCAN) based on the presence of specific gene gains (Tumor Target Charge, TTC) and losses (Tumor Target Losses, TTL) was conceived and validated in 2 independent validation cohorts. MTKI sensitive tumors present a characteristic SCNA profile including a global gain profile, and specific gains for target genes while MTKI resistant tumors present the opposite. SUMSCAN favorable patients achieved longer progression-free and overall survival. This work shows that the copy number sum of kinase-coding genes enables the prediction of response of cancer patients to MTKI, opening a novel paradigm for the treatment selection of these patients.
    Oncotarget 07/2015; 6(28). DOI:10.18632/oncotarget.4557 · 6.36 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Diffuse-type tenosynovial giant cell tumour (dt-GCT) of the soft tissue (alternatively known as pigmented villonodular synovitis), an orphan disease with unmet medical need, is characterised by an overexpression of colony-stimulating factor 1 (CSF1), and is usually caused by a chromosomal translocation involving CSF1. CSF1 receptor (CSF1R) activation leads to the recruitment of CSF1R-expressing cells of the mononuclear phagocyte lineage that constitute the tumor mass in dt-GCT. Emactuzumab (RG7155) is a novel monoclonal antibody that inhibits CSF1R activation. We have assessed the safety, tolerability and activity of emactuzumab in patients with Dt-GCT of the soft tissue. In this phase 1, first-in-human dose-escalation and dose-expansion study, eligible patients were aged 18 years or older with dt-GCT of the soft tissue with locally advanced disease or resectable tumours requiring extensive surgery, an Eastern Cooperative Oncology Group performance status of 1 or less, measurable disease according to Response Evaluation Criteria In Solid Tumors version 1.1, and adequate end-organ function. Patients with GCT of the bone were not eligible. Patients received intravenous emactuzumab at 900 mg, 1350 mg, or 2000 mg every 2 weeks in the dose-escalation phase and at the optimal biological dose in a dose-expansion phase. The primary objective was to evaluate the safety and tolerability of emactuzumab, and to determine the maximum tolerated dose or optimal biological dose. All treated patients were included in the analyses. Expansion cohorts are currently ongoing. This study is registered with, number NCT01494688. Between July 26, 2012, and Oct 21, 2013, 12 patients were enrolled in the dose-escalation phase. No dose-limiting toxicities were noted in the dose-escalation cohort; on the basis of pharmacokinetic, pharmacodynamic, and safety information, we chose a dose of 1000 mg every 2 week for the dose-expansion cohort, into which 17 patients were enrolled. Owing to different cutoff dates for safety and efficacy readouts, the safety population comprised 25 patients. Common adverse events after emactuzumab treatment were facial oedema (16 [64%] of 25 patients), asthenia (14 [56%]), and pruritus (14 [56%]). Five serious adverse events (periorbital oedema, lupus erythematosus [occurring twice], erythema, and dermohypodermitis all experienced by one [4%] patient each) were reported in five patients. Three of the five serious adverse events-periorbital oedema (one [4%]), lupus erythematosus (one [4%]), and dermohypodermitis (one [4%])-were assessed as grade 3. Two other grade 3 events were reported: mucositis (one [4%]) and fatigue (one [4%]). 24 (86%) of 28 patients achieved an objective response; two (7%) patients achieved a complete response. Further study of dt-GCT is warranted and different possibilities, such as an international collaboration with cooperative groups to assure appropriate recruitment in this rare disease, are currently being assessed. F Hoffmann-La Roche. Copyright © 2015 Elsevier Ltd. All rights reserved.
    The Lancet Oncology 07/2015; 16(8). DOI:10.1016/S1470-2045(15)00132-1 · 24.69 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: After the revelation of kinase targeting with orally available small molecules, the use of imatinib in chronic myelogenous leukemia and in gastrointestinal stromal tumor (GIST) has now become commonplace and just two of many examples of the use of kinase inhibitors in cancer. In this article, we discuss important practice points that may impact upon questions of therapy of primary and metastatic GIST, with the hope that the questions addressed in this rare solid tumor can serve as examples of what can be achieved with kinase-directed therapies in other cancers. We present cases that highlight some of the key issues in GIST management and afterward discuss both points of consensus and controversial issues in what is now recognized as one of the most common forms of sarcoma. ©AlphaMed Press.
    The Oncologist 06/2015; 20(7). DOI:10.1634/theoncologist.2014-0471 · 4.87 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: One of the current goals of the French national cancer plan is to reduce healthcare inequalities. This study investigated the potential links between vulnerable social status, exposure to lung cancer risk factors and access to healthcare to highlight ways to improve lung cancer control in this population. The nationwide observational study EDIFICE 3 was carried out through phone interviews of a representative sample of 1603 individuals (age 40-75 years). The EPICES validated questionnaire was used to assess and classify vulnerable respondents. The vulnerable population identified represented 33% of the sample. Compared with nonvulnerable individuals, they had more risk factors for cancer: a higher BMI (26.0 vs. 24.8, P≤0.01), 38% were active smokers (vs. 23%, P≤0.01) with a heavier and longer-lasting tobacco consumption (16.0 cigarettes/day vs. 10.1, P≤0.01 and 29.4 vs. 26.3 years of smoking, P≤0.01) and they were less likely to undertake any physical activities (42 vs. 77%, P≤0.01). They also presented more comorbidities (on average 2.2 vs. 1.8, P≤0.01). Access to healthcare, however, was not discriminatory: vulnerable individuals declared consulting a general practitioner or an oncologist more often than the nonvulnerable subgroup (5.4 vs. 3.7 and 6.7 vs. 2.5 consultations in the previous 12 months, respectively, P≤0.01). Because access to healthcare and screening attendance show no signs of discrimination against vulnerable populations, efforts to reduce inequities in lung cancer control should focus on prevention.
    European journal of cancer prevention: the official journal of the European Cancer Prevention Organisation (ECP) 06/2015; 24 Suppl:S82-6. DOI:10.1097/CEJ.0000000000000143 · 3.03 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cancers can now be classified by multidimensional criteria including tumour site, histology, primary - "driver" - molecular alterations, secondary molecular alterations, characteristics of the immune stroma, and genetic profile of the patient. The development of tools for the characterisation of the cancers, as well as novel molecular and immune therapeutics are evolving at an unprecedented pace. In 2012, a list of future challenges was identified at the occasion of the European Organisation for Research and Treatment of Cancer (EORTC) 50(th) anniversary. Three years after, it is interesting to look back at the questions addressed then and to assess the progress of these questions. We propose here a novel set questions which have emerged from the recent publications in this area. Copyright © 2015 Société Françise du Cancer. Publié par Elsevier Masson SAS. Tous droits réservés. Published by Elsevier Masson SAS. All rights reserved.
    Bulletin du cancer 06/2015; 102(6 Suppl 1):S22-6. DOI:10.1016/S0007-4551(15)31214-5 · 0.60 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: This analysis aimed to assess the extent to which exposure to cancer risk factors and attendance of screening programmes are influenced by social characteristics. The validated Evaluation of deprivation and health inequalities in public health centres (EPICES) index was used to measure social deprivation. A sample of the general population (N=1603) was assessed to search for potential correlations between screening attendance, risk factors and any components of the EPICES score. In 2011, 33% of the population studied was classified as 'vulnerable'. Sex had no significant impact on this rating (32% men, 35% women), whereas occupational status did. Vulnerable individuals were more likely already to have cancer (10 vs. 7%; nonsignificant difference; odds ratio 1.43 [0.98-2.10]). The mean BMI was 26.0 kg/m (SD 4.9) for the vulnerable population versus 24.8 kg/m (SD 3.9) in the nonvulnerable population (P<0.01). The prevalence of current smoking was higher in the vulnerable group (38 vs. 23%, odds ratio 2.03 [1.61-2.56]). In contrast, no statistically significant difference was observed between attendance rates for nationwide organized cancer screening programmes (breast and colorectal; target age group 50-74 years) by the vulnerable and nonvulnerable groups. Social indicators of vulnerable populations are associated with increased rates of risk factors for cancer, but not with screening attendance. Our data support the previously reported marked impact of organized programmes that reduce or even remove inequalities in access to cancer screening. However, although the organized programmes have indeed enabled population-wide, nonselective access to screening, primary prevention as it stands today remains inadequate in the underserved population and further improvements are warranted.
    European journal of cancer prevention: the official journal of the European Cancer Prevention Organisation (ECP) 06/2015; 24 Suppl:S77-81. DOI:10.1097/CEJ.0000000000000144 · 3.03 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The Cochrane analysis exploring the risk/benefit ratio of breast cancer screening resulted in a controversy worldwide spread by the mass media. Our survey sought to assess the impact of this controversy in terms of breast cancer screening awareness and attendance. A nationwide observational study, recorded in the EDIFICE iterative surveys, with a representative sample of 451 women aged 40-75 years, living in France, was carried out in the 3 months after the start of the controversy in January 2013. Of the 405 women with no personal history of cancer, 69 (17%) declared having heard of the controversy (aware group). Women remembering the controversy were more likely to belong to higher socioprofessional categories and to have a higher level of education. The most frequently remembered issues were overdiagnosis (38%), unreliability (16%) and radiation risk (9%). Compared with women who were unaware of the controversy, the aware group knew more about the limits of breast cancer screening (undiagnosed cancers, 20 vs. 7%, P<0.05 and risk of false positives, 20 vs. 2%, P<0. 05) and were more likely to change their opinion for the worse over the mass media debate (8.7 vs. 1.2%, P<0.05). Nevertheless, only 1% of the aware-group declared their intention to subsequently undergo screening less frequently. The low impact of the controversy on the behaviour of women with respect to screening suggests that it should not be seen as a threat to screening attendance rates, but more as an opportunity to improve awareness.
    European journal of cancer prevention: the official journal of the European Cancer Prevention Organisation (ECP) 06/2015; 24 Suppl:S73-6. DOI:10.1097/CEJ.0000000000000145 · 3.03 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The EDIFICE programme began in 2005 and set out to provide a clearer insight over time into the participation of the French population in cancer screening. EDIFICE 3 was conducted in 2011 by phone interviews among a representative sample of 1603 individuals aged between 40 and 75 years using the quota method. The analysis focused on the target populations (50-74 years) of the national screening programmes for breast and colorectal cancer. The same populations were also assessed with respect to prostate cancer screening. In 2005, 93% of the sample population had undergone at least one mammogram in their lifetime; this figure reached 94% in 2008 and 95% in 2011. Compliance with recommended intervals improved between 2005 and 2011, and significantly so for women aged 65-74 years. In 2005, 25% of respondents reported having undergone at least one colorectal cancer screening test; this figure reached 38% in 2008 and 59% in 2011. Recommended intervals were respected by 30 and 51% in 2008 and 2011, respectively. In 2005, 2008 and 2011, a total of 36, 49 and 50% of men reported having undergone at least one prostate cancer screening test. This rate decreased significantly in men aged 50-59 years between 2008 and 2011 (44 vs. 37%, P≤0.05). Attendance rates in national screening programmes are high and stable for breast cancer, and although currently improving for colorectal cancer, the European guideline target has not yet been reached. Despite the absence of recommendations for prostate cancer screening, participation remains constant.
    European journal of cancer prevention: the official journal of the European Cancer Prevention Organisation (ECP) 06/2015; 24 Suppl:S68-72. DOI:10.1097/CEJ.0000000000000146 · 3.03 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Health-related quality of life (HRQoL) was an exploratory endpoint in the PALETTE trial, a global, double-blind, randomized, phase 3 trial of pazopanib 800 mg versus placebo as second-line or later treatment for patients with advanced soft tissue sarcoma (N = 369). In that trial, progression-free survival was significantly improved in the pazopanib arm (median, 4.6 vs 1.6 months; hazard ratio, 0.31; P < .001), and toxicity of pazopanib consisted mainly of fatigue, diarrhea, nausea, weight loss, and hypertension. HRQoL was assessed using the 30-item core European Organization for the Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire (EORTC QLQ-C30) at baseline and at weeks 4, 8, and 12 in patients who received treatment on protocol. The primary HRQoL endpoint was the EORTC QLQ-C30 global health status scale. Compliance with HRQoL assessments was good, ranging from 94% at baseline to 81% at week 12. Differences in scores on the EORTC QLQ-C30 global health status subscale between the 2 treatment arms were not statistically significant and did not exceed the predetermined, minimal clinically important difference of 10 points (P = .291; maximum difference, 3.8 points). Among the other subscales, the pazopanib arm reported significantly worse symptom scores for diarrhea (P < .001) loss of appetite (P < .001), nausea/vomiting (P < .001), and fatigue (P = .012). In general, HRQoL scores tended to decline over time in both arms. HRQoL did not improve with the receipt of pazopanib. However, the observed improvement in progression-free survival without impairment of HRQoL was considered a meaningful result. The toxicity profile of pazopanib was reflected in the patients' self-reported symptoms but did not translate into significantly worse overall global health status during treatment. Cancer 2015. © 2015 American Cancer Society. © 2015 American Cancer Society.
    Cancer 05/2015; 121(17). DOI:10.1002/cncr.29426 · 4.89 Impact Factor
  • [Show abstract] [Hide abstract]
    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; 62(9). DOI:10.1002/pbc.25535 · 2.39 Impact Factor
  • [Show abstract] [Hide abstract]
    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; 21(18). DOI:10.1158/1078-0432.CCR-14-2910 · 8.72 Impact Factor
  • [Show abstract] [Hide abstract]
    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, 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 · 24.69 Impact Factor

Publication Stats

9k Citations
2,083.24 Total Impact Points


  • 2008–2015
    • Claude Bernard University Lyon 1
      Villeurbanne, Rhône-Alpes, France
  • 2002–2015
    • Centre Léon Bérard
      Lyons, Rhône-Alpes, France
  • 2013–2014
    • Cancer Research Center of Lyon
      Lyons, Rhône-Alpes, France
    • HELIOS Klinik Ahrenshoop
      Ahrenshöft, Schleswig-Holstein, Germany
  • 2008–2014
    • University of Lyon
      Lyons, Rhône-Alpes, France
  • 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
  • 2009
    • Leiden University
      Leyden, South Holland, Netherlands
    • Unité Inserm U1077
      Caen, Lower Normandy, France
    • Catholic University of Louvain
      Лувен-ла-Нев, Walloon, Belgium
  • 2007
    • Erasmus Universiteit Rotterdam
      Rotterdam, South Holland, Netherlands
  • 2006
    • CHU de Lyon - Hôpital de la Croix-Rousse
      Lyons, Rhône-Alpes, France
  • 2004–2005
    • Hospices Civils de Lyon
      Lyons, Rhône-Alpes, France