Jean-Yves Blay

Centre Léon Bérard, Lyons, Rhône-Alpes, France

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Publications (248)1452.92 Total impact

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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. · 1.77 Impact Factor
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    ABSTRACT: Solitary Fibrous Tumors of the Pleura (SFTP) refer as to a heterogeneous group of mesenchymal malignancies with various anatomic and histology features. Upfront surgical resection is the standard approach, but recurrences may be aggressive and difficult to treat. The most widely accepted staging system has been proposed by De Perrot et al. Because SFTPs are rare, evidence to support a role for perioperative chemotherapy is scarce. Likewise, the predictive or prognostic relevance of the De Perrot system may be questioned.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 10/2014; · 4.55 Impact Factor
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    ABSTRACT: Purpose: While the mutational status in gastrointestinal stromal tumors (GIST) can predict the response to treatment with tyrosine kinase inhibitors, the role of tumor genotype as a prognostic factor remains controversial. The ConticaGIST study sought to determine the pathologic and molecular factors associated with the disease-free survival (DFS) in patients with the operable, imatinib-naive GIST. Experimental Design: Clinicopathological and molecular data from 1056 patients with localized GIST who underwent surgery with curative intention (R0/R1) and were registered in the European ConticaGIST database were prospectively obtained and reviewed. Risk of tumor recurrence was stratified using the modified NIH criteria. The median follow-up was 52 months. Results: On testing for potential prognostic parameters, primary non-gastric site, size >10cm, mitotic index >10 mitoses per 50 high power field, and the KIT exon 9 duplication [hazard ratio (HR) 1.47 (95% CI 0.9-2.5); p=0.037] and KIT exon 11 deletions involving codons 557 and/or 558 [KITdel-inc557/558; HR 1.45 (95% CI 1.0-2.2); p=0.004] were associated with inferior DFS on multivariable Cox model analysis. Conversely, the PDGFRA exon 18 mutations were indicators of better prognosis [HR 0.23 (95% CI 0.1-0.6); p=0.002]. KITdel-inc557/558 were an adverse indicator only in GIST localized in the stomach (p<0.001) but not in tumors with non-gastric origin. In gastric GIST, all other mutations presented remarkably superior 5-years DFS. Conclusions: In conclusion, tumor genotype is an independent molecular prognostic variable associated with gastric GIST, and should be used for optimizing tailored adjuvant imatinib treatment.
    Clinical cancer research : an official journal of the American Association for Cancer Research. 10/2014;
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    ABSTRACT: To the authors' knowledge, the incidence of late recurrence (> 5 years after initial management) is unknown and no prognostic factors for late events have been characterized in patients with soft tissue sarcomas.
    Cancer 06/2014; · 5.20 Impact Factor
  • Jean-Yves Blay
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    ABSTRACT: ABSTRACT Trabectedin is indicated for the treatment of advanced soft tissue sarcoma (STS) after failure of standard therapy with anthracyclines and ifosfamide, or as first-line therapy for patients who are unsuited to receive these agents. Since trabectedin first became available for clinical investigation in 1995, numerous retrospective analyses and Phase II studies have documented its activity and provided useful insights into its unique clinical profile. An extensive research program of randomized studies was subsequently undertaken to identify methods of optimizing the use of trabectedin in clinical practice. Some main areas of interest involved its use in the first-line setting, its use in combination regimens and its activity in specific sarcoma subtypes. In this article, clinical trial results are reviewed with the aim of continually refining trabectedin's place in the therapy of advanced STS.
    Future oncology (London, England). 06/2014; 10(8s):s7-s12.
  • Jean-Yves Blay
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    ABSTRACT: ABSTRACT The approval of trabectedin in Europe in 2007 for the treatment of advanced soft tissue sarcoma (STS) was based on four Phase II trials. The extensive clinical trials program currently underway with trabectedin indicates clearly the extent to which this novel agent remains a topic of scientific and clinical interest in the treatment of advanced STS. Results of several retrospective studies examining outcomes of patients treated beyond clinical trials and under everyday practice conditions, including compassionate use programs, were disclosed in 2013. These analyses complement the knowledge about trabectedin gained from previous and ongoing clinical studies. Collectively, the results confirm the activity of trabectedin in inoperable/metastatic STS and extend current knowledge about several aspects of its profile, highlighting in particular improved outcomes when trabectedin is used in earlier lines of therapy and when treatment is maintained in the absence of disease progression. Evidence that the safety profile of trabectedin does not differ materially between elderly (≥65 years) and younger patients suggests no need to discriminate on the basis of age; elderly patients who are sufficiently fit to receive chemotherapy and considered by their physicians as unsuited to receive doxorubicin/ifosfamide can be treated with trabectedin in the same manner as younger patients.
    Future oncology (London, England). 06/2014; 10(8s):s13-s17.
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    ABSTRACT: Macrophage infiltration has been identified as an independent poor prognostic factor in several cancer types. The major survival factor for these macrophages is macrophage colony-stimulating factor 1 (CSF-1). We generated a monoclonal antibody (RG7155) that inhibits CSF-1 receptor (CSF-1R) activation. In vitro RG7155 treatment results in cell death of CSF-1-differentiated macrophages. In animal models, CSF-1R inhibition strongly reduces F4/80(+) tumor-associated macrophages accompanied by an increase of the CD8(+)/CD4(+) T cell ratio. Administration of RG7155 to patients led to striking reductions of CSF-1R(+)CD163(+) macrophages in tumor tissues, which translated into clinical objective responses in diffuse-type giant cell tumor (Dt-GCT) patients.
    Cancer cell. 05/2014;
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    ABSTRACT: Regorafenib is an oral multikinase inhibitor that inhibits several kinases relevant to tumor biology in several cancers, including colorectal carcinoma (CRC) and gastrointestinal stromal tumor (GIST). In phase III trials, regorafenib significantly improved overall survival versus placebo in patients with metastatic CRC progressing after all available standard therapies, and significantly prolonged progression-free survival in patients with advanced GIST in whom at least imatinib and sunitinib had failed. Thus, this agent holds promise as a new standard of care for CRC and GIST patients after disease progression following all other approved therapies. The clinical trials reported to date show that this new treatment has a consistent adverse event profile that is quite different from that of traditional cytotoxic chemotherapies. The most common adverse events of regorafenib include dermatologic and mucosal toxicities (especially hand-foot skin reaction, rash, and oral mucositis), constitutional symptoms (e.g., fatigue, nausea, and weight loss), vascular effects (especially hypertension), and gastrointestinal symptoms (e.g., diarrhea). To help health care professionals anticipate and manage the adverse events associated with regorafenib, we describe our experiences in clinical trials and show that such toxicities can be effectively managed with close observation of patients from initiation of dosing, along with prompt appropriate interventions, including dose modifications, if necessary.
    The Oncologist 05/2014; · 4.10 Impact Factor
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    ABSTRACT: This phase II study evaluated the efficacy and safety/tolerability of sunitinib plus trastuzumab in patients with HER2-positive advanced breast cancer (ABC). Eligible patients received sunitinib 37.5 mg/day and trastuzumab administered either weekly (loading, 4 mg/kg; then weekly 2 mg/kg) or 3-weekly (loading, 8 mg/kg; then 3-weekly 6 mg/kg). Prior trastuzumab and/or lapatinib treatment were permitted. The primary endpoint was objective response rate (ORR). Sixty patients were enrolled and evaluable for safety; 57 were evaluable for efficacy. The majority of patients (58%) had received no prior chemotherapy in the metastatic setting. The ORR was 37%; the clinical benefit rate (CBR; percent objective response plus stable disease >= 24 weeks) was 56%. Among patients who were treatment-naive or had received only adjuvant therapy, the ORR was 44% and the CBR was 59%. Overall, median overall survival had not been reached and the 1-year survival rate was 91%. The majority of adverse events (AEs) were mild to moderate in severity. Forty percent of patients experienced AEs related to measured left ventricular ejection fraction (LVEF) declines, which occurred more frequently in patients who had received prior anthracycline treatment. Ten percent of patients exhibited symptoms related to LVEF declines. One patient died on study from cardiogenic shock. Antitumor response and several safety parameters appeared to correlate with sunitinib exposure. Sunitinib plus trastuzumab demonstrated antitumor activity in patients with HER2-positive ABC, particularly those who were treatment-naive or had only received prior adjuvant treatment. Sunitinib plus trastuzumab had acceptable safety and tolerability in patients with HER2-positive ABC who had not received prior anthracycline therapy.Trial registration: NCT00243503.
    BMC Cancer 03/2014; 14(1):166. · 3.33 Impact Factor
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    ABSTRACT: Background Effective targeted treatment is unavailable for most sarcomas and doxorubicin and ifosfamide—which have been used to treat soft-tissue sarcoma for more than 30 years—still have an important role. Whether doxorubicin alone or the combination of doxorubicin and ifosfamide should be used routinely is still controversial. We assessed whether dose intensification of doxorubicin with ifosfamide improves survival of patients with advanced soft-tissue sarcoma compared with doxorubicin alone. Methods We did this phase 3 randomised controlled trial (EORTC 62012) at 38 hospitals in ten countries. We included patients with locally advanced, unresectable, or metastatic high-grade soft-tissue sarcoma, age 18–60 years with a WHO performance status of 0 or 1. They were randomly assigned (1:1) by the minimisation method to either doxorubicin (75 mg/m² by intravenous bolus on day 1 or 72 h continuous intravenous infusion) or intensified doxorubicin (75 mg/m²; 25 mg/m² per day, days 1–3) plus ifosfamide (10 g/m² over 4 days with mesna and pegfilgrastim) as first-line treatment. Randomisation was stratified by centre, performance status (0 vs 1), age (<50 vs ≥50 years), presence of liver metastases, and histopathological grade (2 vs 3). Patients were treated every 3 weeks till progression or unacceptable toxic effects for up to six cycles. The primary endpoint was overall survival in the intention-to-treat population. The trial is registered with ClinicalTrials.gov, number NCT00061984. Findings Between April 30, 2003, and May 25, 2010, 228 patients were randomly assigned to receive doxorubicin and 227 to receive doxorubicin and ifosfamide. Median follow-up was 56 months (IQR 31–77) in the doxorubicin only group and 59 months (36–72) in the combination group. There was no significant difference in overall survival between groups (median overall survival 12·8 months [95·5% CI 10·5–14·3] in the doxorubicin group vs 14·3 months [12·5–16·5] in the doxorubicin and ifosfamide group; hazard ratio [HR] 0·83 [95·5% CI 0·67–1·03]; stratified logrank test p=0·076). Median progression-free survival was significantly higher for the doxorubicin and ifosfamide group (7·4 months [95% CI 6·6–8·3]) than for the doxorubicin group (4·6 months [2·9–5·6]; HR 0·74 [95% CI 0·60–0·90], stratified log-rank test p=0·003). More patients in the doxorubicin and ifosfamide group than in the doxorubicin group had an overall response (60 [26%] of 227 patients vs 31 [14%] of 228; p<0·0006). The most common grade 3 and 4 toxic effects—which were all more common with doxorubicin and ifosfamide than with doxorubicin alone—were leucopenia (97 [43%] of 224 patients vs 40 [18%] of 223 patients), neutropenia (93 [42%] vs 83 [37%]), febrile neutropenia (103 (46%) vs 30 [13%]), anaemia (78 [35%] vs 10 [5%]), and thrombocytopenia (75 [33%]) vs one [<1%]). Interpretation Our results do not support the use of intensified doxorubicin and ifosfamide for palliation of advanced soft-tissue sarcoma unless the specific goal is tumour shrinkage. These findings should help individualise the care of patients with this disease.
    The Lancet Oncology 03/2014; 15:415-423. · 25.12 Impact Factor
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    ABSTRACT: Rectal and pararectal gastrointestinal stromal tumors (GISTs) are rare. The optimal management strategy for primary localized GISTs remains poorly defined. We conducted a retrospective analysis of 41 patients with localized rectal or pararectal GISTs treated between 1991 and 2011 in 13 French Sarcoma Group centers. Of 12 patients who received preoperative imatinib therapy for a median duration of 7 (2-12) months, 8 experienced a partial response, 3 had stable disease, and 1 had a complete response. Thirty and 11 patients underwent function-sparing conservative surgery and abdominoperineal resection, respectively. Tumor resections were mostly R0 and R1 in 35 patients. Tumor rupture occurred in 12 patients. Eleven patients received postoperative imatinib with a median follow-up of 59 (2.4-186) months. The median time to disease relapse was 36 (9.8-62) months. The 5-year overall survival rate was 86.5%. Twenty patients developed local recurrence after surgery alone, two developed recurrence after resection combined with preoperative and/or postoperative imatinib, and eight developed metastases. In univariate analysis, the mitotic index (<=5) and tumor size (<=5 cm) were associated with a significantly decreased risk of local relapse. Perioperative imatinib was associated with a significantly reduced risk of overall relapse and local relapse. Perioperative imatinib therapy was associated with improved disease-free survival. Preoperative imatinib was effective. Tumor shrinkage has a clear benefit for local excision in terms of feasibility and function preservation. Given the complexity of rectal GISTs, referral of patients with this rare disease to expert centers to undergo a multidisciplinary approach is recommended.
    BMC Cancer 03/2014; 14(1):156. · 3.33 Impact Factor
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    ABSTRACT: Effective targeted treatment is unavailable for most sarcomas and doxorubicin and ifosfamide-which have been used to treat soft-tissue sarcoma for more than 30 years-still have an important role. Whether doxorubicin alone or the combination of doxorubicin and ifosfamide should be used routinely is still controversial. We assessed whether dose intensification of doxorubicin with ifosfamide improves survival of patients with advanced soft-tissue sarcoma compared with doxorubicin alone. We did this phase 3 randomised controlled trial (EORTC 62012) at 38 hospitals in ten countries. We included patients with locally advanced, unresectable, or metastatic high-grade soft-tissue sarcoma, age 18-60 years with a WHO performance status of 0 or 1. They were randomly assigned (1:1) by the minimisation method to either doxorubicin (75 mg/m(2) by intravenous bolus on day 1 or 72 h continuous intravenous infusion) or intensified doxorubicin (75 mg/m(2); 25 mg/m(2) per day, days 1-3) plus ifosfamide (10 g/m(2) over 4 days with mesna and pegfilgrastim) as first-line treatment. Randomisation was stratified by centre, performance status (0 vs 1), age (<50 vs ≥50 years), presence of liver metastases, and histopathological grade (2 vs 3). Patients were treated every 3 weeks till progression or unacceptable toxic effects for up to six cycles. The primary endpoint was overall survival in the intention-to-treat population. The trial is registered with ClinicalTrials.gov, number NCT00061984. Between April 30, 2003, and May 25, 2010, 228 patients were randomly assigned to receive doxorubicin and 227 to receive doxorubicin and ifosfamide. Median follow-up was 56 months (IQR 31-77) in the doxorubicin only group and 59 months (36-72) in the combination group. There was no significant difference in overall survival between groups (median overall survival 12·8 months [95·5% CI 10·5-14·3] in the doxorubicin group vs 14·3 months [12·5-16·5] in the doxorubicin and ifosfamide group; hazard ratio [HR] 0·83 [95·5% CI 0·67-1·03]; stratified log-rank test p=0·076). Median progression-free survival was significantly higher for the doxorubicin and ifosfamide group (7·4 months [95% CI 6·6-8·3]) than for the doxorubicin group (4·6 months [2·9-5·6]; HR 0·74 [95% CI 0·60-0·90], stratified log-rank test p=0·003). More patients in the doxorubicin and ifosfamide group than in the doxorubicin group had an overall response (60 [26%] of 227 patients vs 31 [14%] of 228; p<0·0006). The most common grade 3 and 4 toxic effects-which were all more common with doxorubicin and ifosfamide than with doxorubicin alone-were leucopenia (97 [43%] of 224 patients vs 40 [18%] of 223 patients), neutropenia (93 [42%] vs 83 [37%]), febrile neutropenia (103 (46%) vs 30 [13%]), anaemia (78 [35%] vs 10 [5%]), and thrombocytopenia (75 [33%]) vs one [<1%]). Our results do not support the use of intensified doxorubicin and ifosfamide for palliation of advanced soft-tissue sarcoma unless the specific goal is tumour shrinkage. These findings should help individualise the care of patients with this disease. Cancer Research UK, EORTC Charitable Trust, UK NHS, Canadian Cancer Society Research Institute, Amgen.
    The Lancet Oncology 03/2014; · 25.12 Impact Factor
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    ABSTRACT: Rare cancer issues have not been much explored yet because of their low incidence. That is why epidemiological studies have difficulties in identifying indisputable etiological risk factors. An expert opinion, mainly concentrated in some establishments, is required for these cancers' management. However, on account of the potential remoteness of these therapeutic resources, the patients' way of care remains also unstudied. By means of a geographical analysis of a regional exhaustive cohort of sarcoma, diagnosed in 2006 and 2007 and followed during five years at least, we can make progress on these different issues. Gastro-Intestinal and Stromal Tumors (GIST) occur more frequently in privileged territories while liposarcomas arise in more deprived areas. The association between liposarcomas and areas deprivation is significant (P=0.05). Moreover, pre-operative biopsy and some clinical patient characteristics, age, grade or tumor localization, are associated with an increase in the distance covered by patients for the first-line treatment (p ≤ 0,001). In the scope of an interdisciplinary collaboration, the geographical approach develops some hypothesis for rare cancers research, which must be tested by other larger scale studies.
    Bulletin du cancer 02/2014; · 0.61 Impact Factor
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    ABSTRACT: Many data are presented each year during the American Society of Clinical Oncology meeting and others international major meetings. This article is proposed by the editorial board of the Bulletin du Cancer as a synthesis of important new data. The purpose is to identify in these results those who may have an immediate impact on our clinical practices.
    Bulletin du cancer 01/2014; 101(1):75-92. · 0.61 Impact Factor
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    ABSTRACT: Aim This randomised phase III trial evaluated first-line trabectedin versus doxorubicin-based chemotherapy (DXCT) in patients with advanced/metastatic translocation-related sarcomas (TRS). Methods Patients were randomly assigned (1:1) to receive trabectedin 1.5 mg/m2 24-h intravenous (i.v.) infusion every 3 weeks (q3wk) (Arm A), or doxorubicin 75 mg/m2 i.v. q3wk, or doxorubicin 60 mg/m2 i.v. plus ifosfamide (range, 6–9 g/m2) i.v. q3wk (Arm B). Progression-free survival (PFS) by independent review was the primary efficacy end-point. Results One hundred and twenty-one patients were randomised; 88 of them had TRS confirmed by central pathology review (efficacy population). Twenty-nine PFS events were assessed by independent review (16 with trabectedin; 13 with DXCT). PFS showed non-significant difference between arms (stratified log rank test, p = 0.9573; hazard ratio = 0.86, p = 0.6992). At the time of this analysis, 63.9% and 58.3% of patients were alive in trabectedin and DXCT arms, respectively. There was no statistically significant difference in survival curves. Response rate according to Response Evaluation Criteria in Solid Tumours (RECIST) v.1.0 was significantly higher in DXCT arm (27.0% versus 5.9%), but response according to Choi criteria showed fewer differences between treatment arms (45.9% versus 37.3%). Safety profile was as expected for both arms, with higher incidence of severe neutropenia, alopecia and mucositis in the DXCT arm. Conclusion Neither trabectedin nor doxorubicin-based chemotherapy showed significant superiority in the first-line treatment of patients with advanced translocation-related sarcoma.
    European journal of cancer (Oxford, England: 1990) 01/2014; · 4.12 Impact Factor
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    ABSTRACT: We retrospectively reviewed data from nine pre-treated metastatic desmoplastic small round cell tumour (DSRCT) patients who received pazopanib.
    Clinical sarcoma research. 01/2014; 4:7.
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    ABSTRACT: The current refinement of nosological classification of sarcoma which integrates molecular typing with a growing number of subtypes contrasts with the one-size-fits-all approach proposed in clinical practice guidelines for both local treatment and systemic treatment in the past. However, there is a growing proportion of sarcomas in which specific treatment strategies are proposed as standard. As a consequence, central review by expert sarcoma pathologists should be organised to ensure the optimal management of all patients. The key parameters in the pathology report influencing treatment decisions are therefore rapidly evolving. First a diagnostic biopsy, ideally an imaged guided microbiopsy performed by an experienced team, is a recommended practice. On the resection specimen, the size, histological grade, location, depth, surgical margins and tumour fragmentation are essential parameters to guide the treating physician. Molecular characterisation of the driving genomic event is becoming increasingly important for treatment decision making, in routine practice and in clinical trials. Molecular grade is a research tool with potentially high utility, and requires further evaluation and validation in prospective clinical trials.
    Pathology 12/2013; · 2.66 Impact Factor
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    ABSTRACT: Soft tissue sarcomas (STS) are a heterogeneous group of cancers comprising over 50 histological subtypes. Current treatment strategies for sarcomas are increasingly adapted to histological and molecular subtype, and several patient- and tumour-related factors influence treatment decision. Seven oncologists specialising in the management of STS, from Europe, the United States of America and Japan, met to develop a practical model to identify parameters guiding treatment decision-making in advanced STS. Literature searches were carried out to identify key published evidence, in particular phase II and III randomised trials, to validate the model, and extensive clinical experience was used as expert evidence. A document was developed to provide a logical approach to advanced STS management and was analysed critically by a second group of STS specialists. Broad consensus was reached during this exercise and the following parameters were identified as key factors influencing treatment decision: chemosensitivity of histological subtype, natural history of the diagnosis, tumour burden, tumour site, locally advanced primary and/or metastases, patient's general condition, relevant comorbidities, previous chemotherapy, treatment goal and patient acceptance. These parameters, judged useful for treatment selection, were based on published literature, the selection process within clinical trials and expert opinion (some factors have not been formerly defined in published literature). A model describing factors affecting treatment decisions in sarcoma was established. The model requires validation and several of its parameters require standardisation.
    European journal of cancer (Oxford, England: 1990) 11/2013; · 4.12 Impact Factor
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    ABSTRACT: We have carried out a stratified phase II study of sorafenib (So) in patients with advanced angiosarcoma (n = 32) and epithelioid hemangioendothelioma (n = 13). This report concerns the correlative analysis of the predictive values of circulating pro/anti-angiogenetic biomarkers. Using the ELISA method (R&D Systems), circulating biomarkers (VEGF-A, in picograms per milliliter), thrombospondin-1 (TSP1, in micrograms per milliliter), stem cell factor (SCF, in picograms per milliliter), placental growth factor (PlGF, in picograms per milliliter), VEGF-C (in picograms per milliliter), and E-selectin (in nanograms per milliliter) were measured before So treatment and after 7 days. VEGF-A (mean value 475 vs. 541, p = 0.002), TSP1 (16 vs. 24, p = 0.0002), and PlGF (20.9 vs. 40.7, p = 0.0001) significantly increased during the treatment. Treatment did not affect the levels of SCF, VEGF-C, and E-selectin. Only two biomarkers were associated with better outcome as follows: VEGF-A and PlGF. Best objective response and non-progression at 180 days were associated with low level of VEGF-A at baseline (p = 0.04 and 0.03, respectively). There was a correlation between the circulating level of VEGF-A and time to progression (TTP) (r = -0.47, p = 0.001). Best objective response and non-progression at 180 days were not associated with baseline level of PIGF, but there was a correlation between the circulating level of PIGF at baseline and TTP. Low level of VEGF-A at baseline (<500) was significantly associated with better outcome.
    Targeted Oncology 11/2013; · 3.46 Impact Factor
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    ABSTRACT: The oral tyrosine kinase inhibitor (TKI) imatinib has revolutionized the treatment of gastrointestinal stromal tumors (GISTs), most of which harbor oncogenic mutation in genes that encode the receptor tyrosine kinases KIT or PDGFA. Imatinib is the standard of care for patients with advanced GIST and for patients with primary GIST at significant risk of recurrence after surgery. This review discusses data supporting continuous kinase suppression with imatinib and key issues, including response to imatinib reintroduction, effect of treatment interruption on secondary resistance to imatinib, and prognostic factors associated with sustained response to imatinib. Long-term follow-up results of the B2222 study and updated results of the BFR14 trial demonstrate that continuous imatinib treatment in patients with advanced GIST is associated with reduced risk of progression. For patients progressing on or intolerant of imatinib, continuing therapy with TKIs sunitinib followed by regorafenib is recommended. In the adjuvant setting, final results of the trial by the Scandinavian Sarcoma Group and the Sarcoma Group of the Arbeitsgemeinschaft Internistische Onkologie demonstrate that 3 years of adjuvant imatinib, compared with 1 year, significantly reduces the risk of recurrence and improves overall survival of patients with KIT-positive GIST at high risk of recurrence. Maintenance of therapy with TKIs is the key to successful treatment of GIST. Results from recent studies provide a strong rationale for continuous imatinib treatment for 3 years following surgical resection and long-term continuous administration in advanced or metastatic GIST.
    The Oncologist 10/2013; · 4.10 Impact Factor

Publication Stats

6k Citations
1,452.92 Total Impact Points

Institutions

  • 2002–2014
    • Centre Léon Bérard
      Lyons, Rhône-Alpes, France
  • 2013
    • Hôpital La Pitié Salpêtrière (Groupe Hospitalier "La Pitié Salpêtrière - Charles Foix")
      Lutetia Parisorum, Île-de-France, France
    • HELIOS Klinikum Duisburg
      Duisburg-Hamborn, North Rhine-Westphalia, Germany
    • Université de Versailles Saint-Quentin
      • Laboratoire Épidémiologie et Oncogenèse des Tumeurs Digestives (ONCO)
      Versailles, Île-de-France, France
  • 2012–2013
    • Unicancer
      Lutetia Parisorum, Île-de-France, France
    • Cancer Research Center of Lyon
      Lyons, Rhône-Alpes, France
    • Radboud University Nijmegen
      • Department of Medical Oncology
      Nijmegen, Provincie Gelderland, Netherlands
    • Cea Leti
      Grenoble, Rhône-Alpes, France
    • Partners HealthCare
      Boston, Massachusetts, United States
  • 2010–2013
    • Claude Bernard University Lyon 1
      Villeurbanne, Rhône-Alpes, France
    • University Hospital München
      München, Bavaria, Germany
  • 2004–2013
    • Institut de Cancérologie Gustave Roussy
      • Department of Radiotherapy
      Île-de-France, France
  • 2011–2012
    • Dana-Farber Cancer Institute
      • Center for Sarcoma and Bone Oncology
      Brookline, MA, United States
    • University of Lyon
      Lyons, Rhône-Alpes, France
    • Institut de France
      Lutetia Parisorum, Île-de-France, France
    • Sarcoma Oncology Center
      Santa Monica, California, United States
    • KU Leuven
      • Department of Oncology
      Leuven, VLG, Belgium
    • University of Franche-Comté
      Becoinson, Franche-Comté, France
    • Clinique Du Parc
      Croix, Nord-Pas-de-Calais, France
  • 2008–2011
    • Institut Paoli Calmettes
      Marsiglia, Provence-Alpes-Côte d'Azur, France
    • Leiden University Medical Centre
      • Department of Clinical Pharmacy and Toxicology
      Leiden, South Holland, Netherlands
  • 2003–2011
    • Assistance Publique Hôpitaux de Marseille
      Marsiglia, Provence-Alpes-Côte d'Azur, France
  • 2009
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 2007–2009
    • Erasmus MC
      • Department of Internal Oncology
      Rotterdam, South Holland, Netherlands
    • The Bracton Centre, Oxleas NHS Trust
      Дартфорде, England, United Kingdom
    • Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
      Milano, Lombardy, Italy
  • 2005–2009
    • French Institute of Health and Medical Research
      • Unité d’Immunologie des Tumeurs et Immunothérapie U1015
      Paris, Ile-de-France, France
  • 2004–2009
    • Erasmus Universiteit Rotterdam
      • Department of Medical Oncology
      Rotterdam, South Holland, Netherlands
  • 2004–2008
    • CHU de Lyon - Groupement Hospitalier Edouard Herriot
      Lyons, Rhône-Alpes, France
  • 2006
    • Centre Jean Perrin
      Clermont, Auvergne, France
    • Hôpital Européen Georges-Pompidou (Hôpitaux Universitaires Paris-Ouest)
      Lutetia Parisorum, Île-de-France, France
  • 2004–2005
    • Hospices Civils de Lyon
      Lyons, Rhône-Alpes, France