68 results on '"Robin YM"'
Search Results
2. Abstract P3-08-15: Proteomic profile of PAM50 intermediate risk early breast cancers
- Author
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Hajjaji, N, primary, Aboulouard, S, additional, Robin, YM, additional, Bertin, D, additional, Fournier, I, additional, Bonneterre, J, additional, and Salzet, M, additional
- Published
- 2019
- Full Text
- View/download PDF
3. Abstract P3-08-19: Proteomic tracking of breast cancer metastasis progression
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Hajjaji, N, primary, Aboulouard, S, additional, Robin, YM, additional, Bertin, D, additional, Fournier, I, additional, Bonneterre, J, additional, and Salzet, M, additional
- Published
- 2019
- Full Text
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4. Variation of early auditory evoked potentials (EAEP) in severe hyponatremia
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Dusson, C, primary, Van der Linden, T, additional, Cabaret, P, additional, Fournet, X, additional, Gallois, P, additional, Forzy, G, additional, Robin, YM, additional, and Lepoutre, B, additional
- Published
- 2000
- Full Text
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5. Variation of early auditory evoked potentials (EAEP) in severe hyponatremia
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Dusson, C, Van der Linden, T, Cabaret, P, Fournet, X, Gallois, P, Forzy, G, Robin, YM, and Lepoutre, B
- Published
- 1999
- Full Text
- View/download PDF
6. Investigating the prognostic impact of NY-ESO-1 expression and HLA subtypes in metastatic synovial sarcoma.
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Dufresne A, Pokras S, Meurgey A, Chabaud S, Toulmonde M, Bompas E, Le Cesne A, Robin YM, Duffaud F, Valentin T, El Zein S, Leroux A, Dubray-Longeras P, Firmin N, de Pinieux G, Noal S, Delfour C, Bollard J, Tonon L, Biette A, Gadot N, Attignon V, Jean-Denis M, Woessner M, Klohe E, Thayaparan T, Eleftheriadou I, Blouch K, Nathenson MJ, and Blay JY
- Subjects
- Humans, Male, Female, Retrospective Studies, Prognosis, Middle Aged, Adult, Aged, Biomarkers, Tumor metabolism, Neoplasm Metastasis, Sarcoma, Synovial genetics, Sarcoma, Synovial metabolism, Sarcoma, Synovial pathology, Sarcoma, Synovial mortality, Membrane Proteins metabolism, Antigens, Neoplasm metabolism
- Abstract
Background: To better understand the importance of the New York esophageal squamous cell carcinoma 1 (NY-ESO-1) and human leukocyte antigen (HLA) subtypes in treatment decision-making, further investigation of their prevalence and prognostic impact among patients with metastatic synovial sarcoma (mSS) is needed., Patients and Methods: This was a retrospective clinico-biological cohort study of adults with mSS. Patient data were collected from the French Sarcoma Group NetSARC database and supplemented by electronic medical records. Primary tumor samples were collected and analyzed for NY-ESO-1 expression by immunohistochemistry (IHC) and HLA-A∗02 status by RNA sequencing (RNA-seq). The primary cohort included patients with available primary tumor samples; the impact of a larger sample size was explored by including patients who had either a primary or metastatic sample (termed the exploratory cohort). P values are provided for descriptive purposes., Results: In 92 patients with primary tumor samples, ∼25% (n = 23) were positive for NY-ESO-1 and HLA-A∗02 expression (dual positive). Among 106 patients with IHC data, 61% (n = 65) were NY-ESO-1 positive, and among 94 patients with RNA-seq data, 45% (n = 42) were HLA-A∗02 positive. The median overall survival (OS) for positive versus negative NY-ESO-1 status was 35.3 and 21.7 months, respectively (unadjusted P = 0.0428). We observed no difference in median OS for HLA-A∗02-positive versus -negative and dual-positive patients versus others (both unadjusted P > 0.05). Multivariate analyses of OS showed no prognostic impact for NY-ESO-1 among primary tumor samples and in the exploratory cohort. However, in the latter we observed an association between NY-ESO-1 expression and OS in the first-line (P = 0.0041) but not in the second-line setting., Conclusions: The primary tumor cohort showed no association between NY-ESO-1 expression and OS (including stratification by HLA-A∗02 subtype and treatment line) when adjusting for important prognostic factors, possibly due to small sample sizes., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2024
- Full Text
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7. Fallopian tube lesions as potential precursors of early ovarian cancer: a comprehensive proteomic analysis.
- Author
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Wisztorski M, Aboulouard S, Roussel L, Duhamel M, Saudemont P, Cardon T, Narducci F, Robin YM, Lemaire AS, Bertin D, Hajjaji N, Kobeissy F, Leblanc E, Fournier I, and Salzet M
- Subjects
- Female, Humans, Fallopian Tubes, Tumor Suppressor Protein p53, Proteomics, Fallopian Tube Neoplasms genetics, Fallopian Tube Neoplasms chemistry, Fallopian Tube Neoplasms pathology, Cystadenocarcinoma, Serous genetics, Cystadenocarcinoma, Serous pathology, Ovarian Neoplasms genetics, Ovarian Neoplasms pathology
- Abstract
Ovarian cancer is the leading cause of death from gynecologic cancer worldwide. High-grade serous carcinoma (HGSC) is the most common and deadliest subtype of ovarian cancer. While the origin of ovarian tumors is still debated, it has been suggested that HGSC originates from cells in the fallopian tube epithelium (FTE), specifically the epithelial cells in the region of the tubal-peritoneal junction. Three main lesions, p53 signatures, STILs, and STICs, have been defined based on the immunohistochemistry (IHC) pattern of p53 and Ki67 markers and the architectural alterations of the cells, using the Sectioning and Extensively Examining the Fimbriated End Protocol. In this study, we performed an in-depth proteomic analysis of these pre-neoplastic epithelial lesions guided by mass spectrometry imaging and IHC. We evaluated specific markers related to each preneoplastic lesion. The study identified specific lesion markers, such as CAVIN1, Emilin2, and FBLN5. We also used SpiderMass technology to perform a lipidomic analysis and identified the specific presence of specific lipids signature including dietary Fatty acids precursors in lesions. Our study provides new insights into the molecular mechanisms underlying the progression of ovarian cancer and confirms the fimbria origin of HGSC., (© 2023. The Author(s).)
- Published
- 2023
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8. Multicenter Harmonization Study of Pan-Trk Immunohistochemistry for the Detection of NTRK3 Fusions.
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Adam J, Stang NL, Uguen A, Badoual C, Chenard MP, Lantuéjoul S, Maran-Gonzalez A, Robin YM, Rochaix P, Sabourin JC, Soubeyran I, Sturm N, Svrcek M, Vincent-Salomon A, Radosevic-Robin N, and Penault-Llorca F
- Subjects
- Humans, Immunohistochemistry, Oncogene Proteins, Fusion metabolism, Receptor, trkA, Biomarkers, Tumor genetics
- Abstract
Pan-Trk immunohistochemistry has been described as a screening test for the detection of NTRK fusions in a broad spectrum of tumor types. However, pan-Trk testing in the clinical setting may be limited by many factors, including analytical parameters such as clones, platforms, and protocols used. This study aimed to harmonize pan-Trk testing using various clones and immunohistochemical (IHC) platforms and to evaluate the level of analytical variability across pathology laboratories. We developed several IHC pan-Trk assays using clones EPR17341 (Abcam) and A7H6R (Cell Signaling Technology) on Ventana/Roche, Agilent, and Leica platforms. To compare them, we sent unstained sections of a tissue microarray containing 9 cases with NTRK3 fusions to participating laboratories, to perform staining on Ventana/Roche (10 centers), Agilent (4 centers), and Leica (3 centers) platforms. A ready-to-use pan-Trk IVD assay (Ventana/Roche) was also performed in 3 centers. All slides were centrally and blindly reviewed for the percentage of stained tumor cells. Laboratory-developed tests with clone EPR17341 were able to detect pan-Trk protein expression in all cases, whereas lower rates of positivity were observed with clone A7H6R. Moderate to strong variability of the positive cases rate was observed with both antibodies in each IHC platforms type and each of the positivity cut points evaluated (≥1%, ≥10%, and ≥50% of stained tumor cells). The rate of false-negative cases was lower when pan-Trk staining was assessed with the lowest positivity threshold (≥1%). In conclusion, most evaluated pan-Trk IHC laboratory-developed tests were able to detect NTRK3-fusion proteins; however, a significant analytical variability was observed between antibodies, platforms, and centers., (Copyright © 2023 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
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9. A lesion suspected of being a desmoid tumor in the context of familial adenomatous polyposis should be biopsied.
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Lebellec L, Cren PY, Robin YM, and Penel N
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- Biopsy, Humans, Adenomatous Polyposis Coli, Fibromatosis, Aggressive diagnostic imaging
- Abstract
Competing Interests: Conflict of interest None declared.
- Published
- 2022
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10. Path to Clonal Theranostics in Luminal Breast Cancers.
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Hajjaji N, Aboulouard S, Cardon T, Bertin D, Robin YM, Fournier I, and Salzet M
- Abstract
Integrating tumor heterogeneity in the drug discovery process is a key challenge to tackle breast cancer resistance. Identifying protein targets for functionally distinct tumor clones is particularly important to tailor therapy to the heterogeneous tumor subpopulations and achieve clonal theranostics. For this purpose, we performed an unsupervised, label-free, spatially resolved shotgun proteomics guided by MALDI mass spectrometry imaging (MSI) on 124 selected tumor clonal areas from early luminal breast cancers, tumor stroma, and breast cancer metastases. 2868 proteins were identified. The main protein classes found in the clonal proteome dataset were enzymes, cytoskeletal proteins, membrane-traffic, translational or scaffold proteins, or transporters. As a comparison, gene-specific transcriptional regulators, chromatin related proteins or transmembrane signal receptor were more abundant in the TCGA dataset. Moreover, 26 mutated proteins have been identified. Similarly, expanding the search to alternative proteins databases retrieved 126 alternative proteins in the clonal proteome dataset. Most of these alternative proteins were coded mainly from non-coding RNA. To fully understand the molecular information brought by our approach and its relevance to drug target discovery, the clonal proteomic dataset was further compared to the TCGA breast cancer database and two transcriptomic panels, BC360 (nanoString
® ) and CDx (Foundation One® ). We retrieved 139 pathways in the clonal proteome dataset. Only 55% of these pathways were also present in the TCGA dataset, 68% in BC360 and 50% in CDx. Seven of these pathways have been suggested as candidate for drug targeting, 22 have been associated with breast cancer in experimental or clinical reports, the remaining 19 pathways have been understudied in breast cancer. Among the anticancer drugs, 35 drugs matched uniquely with the clonal proteome dataset, with only 7 of them already approved in breast cancer. The number of target and drug interactions with non-anticancer drugs (such as agents targeting the cardiovascular system, metabolism, the musculoskeletal or the nervous systems) was higher in the clonal proteome dataset (540 interactions) compared to TCGA (83 interactions), BC360 (419 interactions), or CDx (172 interactions). Many of the protein targets identified and drugs screened were clinically relevant to breast cancer and are in clinical trials. Thus, we described the non-redundant knowledge brought by this clone-tailored approach compared to TCGA or transcriptomic panels, the targetable proteins identified in the clonal proteome dataset, and the potential of this approach for drug discovery and repurposing through drug interactions with antineoplastic agents and non-anticancer drugs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hajjaji, Aboulouard, Cardon, Bertin, Robin, Fournier and Salzet.)- Published
- 2022
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11. [2021 update of the GEFPICS' recommendations for HER2 status assessment in invasive breast cancer in France].
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Franchet C, Djerroudi L, Maran-Gonzalez A, Abramovici O, Antoine M, Becette V, Berghian A, Blanc-Fournier C, Brabencova E, Charafe-Jauffret E, Chenard MP, Dauplat MM, Delrée P, Duprez-Paumier R, Fleury C, Ghnassia JP, Haudebourg J, Leroux A, MacGrogan G, Mathieu MC, Michenet P, Penault-Llorca F, Poulet B, Robin YM, Roger P, Russ E, Tixier L, Treilleux I, Valent A, Verriele V, Vincent-Salomon A, Arnould L, and Lacroix-Triki M
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- Biomarkers, Tumor, Female, Humans, Immunohistochemistry, In Situ Hybridization, Fluorescence, Receptor, ErbB-2 genetics, Breast Neoplasms diagnosis, Breast Neoplasms genetics
- Abstract
The last international guidelines on HER2 determination in breast cancer have been updated in 2018 by the American Society of Clinical Oncology and College of American Pathologists, on the basis of a twenty-year practice and results of numerous clinical trials. Moreover, the emerging HER2-low concept for 1+ and 2+ non amplified breast cancers lead to refine French practices for HER2 status assessment. The GEFPICS group, composed of expert pathologists, herein presents the latest French recommendations for HER2 status evaluation in breast cancer, taking into account the ASCO/CAP guidelines and introducing the HER2-low concept. In the era of personalized medicine, HER2 status assessment remains one of the most important biomarkers in breast cancer and its quality guaranties the optimal patients' care. French pathologists' commitment in theranostic biomarker quality is more than ever required to provide the most efficient cares in oncology., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)
- Published
- 2021
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12. Direct Water-Assisted Laser Desorption/Ionization Mass Spectrometry Lipidomic Analysis and Classification of Formalin-Fixed Paraffin-Embedded Sarcoma Tissues without Dewaxing.
- Author
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Ogrinc N, Caux PD, Robin YM, Bouchaert E, Fatou B, Ziskind M, Focsa C, Bertin D, Tierny D, Takats Z, Salzet M, and Fournier I
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- Animals, Dogs, Formaldehyde chemistry, Humans, Lasers, Paraffin Embedding, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization methods, Tissue Fixation methods, Water, Lipidomics, Sarcoma
- Abstract
Background: Formalin-fixed paraffin-embedded (FFPE) tissue has been the gold standard for routine pathology for general and cancer postoperative diagnostics. Despite robust histopathology, immunohistochemistry, and molecular methods, accurate diagnosis remains difficult for certain cases. Overall, the entire process can be time consuming, labor intensive, and does not reach over 90% diagnostic sensitivity and specificity. There is a growing need in onco-pathology for adjunct novel rapid, accurate, reliable, diagnostically sensitive, and specific methods for high-throughput biomolecular identification. Lipids have long been considered only as building blocks of cell membranes or signaling molecules, but have recently been introduced as central players in cancer. Due to sample processing, which limits their detection, lipid analysis directly from unprocessed FFPE tissues has never been reported., Methods: We present a proof-of-concept with direct analysis of tissue-lipidomic signatures from FFPE tissues without dewaxing and minimal sample preparation using water-assisted laser desorption ionization mass spectrometry and deep-learning., Results: On a cohort of difficult canine and human sarcoma cases, classification for canine sarcoma subtyping was possible with 99.1% accuracy using "5-fold" and 98.5% using "leave-one-patient out," and 91.2% accuracy for human sarcoma using 5-fold and 73.8% using leave-one-patient out. The developed classification model enabled stratification of blind samples in <5 min and showed >95% probability for discriminating 2 human sarcoma blind samples., Conclusion: It is possible to create a rapid diagnostic platform to screen clinical FFPE tissues with minimal sample preparation for molecular pathology., (© American Association for Clinical Chemistry 2021.)
- Published
- 2021
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13. Two cases of rare late onset life-threatening pseudoprogression with immune check point inhibitors in advanced cancer patients - a case report.
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Coudert V, Robin YM, Tessier W, Forestier A, and Penel N
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- Adult, Aged, Disease Progression, Female, Humans, Male, Nivolumab, Immune Checkpoint Inhibitors therapeutic use, Neoplasms drug therapy
- Published
- 2021
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14. Nationwide incidence of sarcomas and connective tissue tumors of intermediate malignancy over four years using an expert pathology review network.
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de Pinieux G, Karanian M, Le Loarer F, Le Guellec S, Chabaud S, Terrier P, Bouvier C, Batistella M, Neuville A, Robin YM, Emile JF, Moreau A, Larousserie F, Leroux A, Stock N, Lae M, Collin F, Weinbreck N, Aubert S, Mishellany F, Charon-Barra C, Croce S, Doucet L, Quintin-Rouet I, Chateau MC, Bazille C, Valo I, Chetaille B, Ortonne N, Brouchet A, Rochaix P, Demuret A, Ghnassia JP, Mescam L, Macagno N, Birtwisle-Peyrottes I, Delfour C, Angot E, Pommepuy I, Ranchere D, Chemin-Airiau C, Jean-Denis M, Fayet Y, Courrèges JB, Mesli N, Berchoud J, Toulmonde M, Italiano A, Le Cesne A, Penel N, Ducimetiere F, Gouin F, Coindre JM, and Blay JY
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- Adolescent, Adult, Aged, Female, France epidemiology, Humans, Incidence, Male, Middle Aged, Neoplasm Grading, Prospective Studies, Sarcoma classification, Sarcoma diagnosis, World Health Organization, Young Adult, Sarcoma epidemiology, Sarcoma pathology
- Abstract
Background: Since 2010, nationwide networks of reference centers for sarcomas (RREPS/NETSARC/RESOS) collected and prospectively reviewed all cases of sarcomas and connective tumors of intermediate malignancy (TIM) in France., Methods: The nationwide incidence of sarcoma or TIM (2013-2016) was measured using the 2013 WHO classification and confirmed by a second independent review by expert pathologists. Simple clinical characteristics, yearly variations and correlation of incidence with published clinical trials are presented and analyzed., Results: Over 150 different histological subtypes are reported from the 25172 patients with sarcomas (n = 18712, 74,3%) or TIM (n = 6460, 25.7%), with n = 5838, n = 6153, n = 6654, and n = 6527 yearly cases from 2013 to 2016. Over these 4 years, the yearly incidence of sarcomas and TIM was therefore 70.7 and 24.4 respectively, with a combined incidence of 95.1/106/year, higher than previously reported. GIST, liposarcoma, leiomyosarcomas, undifferentiated sarcomas represented 13%, 13%, 11% and 11% of tumors. Only GIST, as a single entity had a yearly incidence above 10/106/year. There were respectively 30, 64 and 66 different histological subtypes of sarcomas or TIM with an incidence ranging from 10 to 1/106, 1-0.1/106, or < 0.1/106/year respectively. The 2 latter incidence groups represented 21% of the patients with 130 histotypes. Published phase III and phase II clinical trials (p<10-6) are significantly higher with sarcomas subtypes with an incidence above 1/106 per., Conclusions: This nationwide registry of sarcoma patients, with exhaustive histology review by sarcoma experts, shows that the incidence of sarcoma and TIM is higher than reported, and that tumors with a very low incidence (1<106/year) are less likely to be included in clinical trials., Competing Interests: No competing interests.
- Published
- 2021
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15. Specific immune landscapes and immune checkpoint expressions in histotypes and molecular subtypes of sarcoma.
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Dufresne A, Lesluyes T, Ménétrier-Caux C, Brahmi M, Darbo E, Toulmonde M, Italiano A, Mir O, Le Cesne A, Le Guellec S, Valentin T, Chevreau C, Bonvalot S, Robin YM, Coindre JM, Caux C, Blay JY, and Chibon F
- Subjects
- Adult, Humans, Prognosis, Liposarcoma, Myxoid, Sarcoma genetics, Sarcoma, Synovial, Soft Tissue Neoplasms genetics
- Abstract
Soft tissue sarcomas are a group of rare and aggressive connective tissue neoplasms for which curative therapeutic opportunities are limited in advanced phase. Clinical trials assessing immunotherapy in these tumors have so far reported limited efficacy. The objective of this study is to provide a description of the immunologic landscape of sarcomas to guide the next clinical trials of immunotherapy in these diseases. The gene expression profile of 93 immune checkpoint (ICP) and membrane markers (MM) of immune cells was analyzed in a series of 253 soft tissue sarcoma (synovial sarcoma, myxoid liposarcoma, sarcoma with complex genomic and GIST) using Agilent Whole Human Genome Microarrays. The unsupervised hierarchical clustering of gene expression level was found able to properly group patients according to the histological subgroup of sarcoma, indicating that each sarcoma subgroup is associated with a specific immune signature defined by its gene expression pattern. Using the prognostic impact of CIBERSORT signature on metastatic-free survival in each subgroup, specific target could be proposed for each of the four groups: Treg through ICOS and GITR in GIST, M0 macrophages in all four sarcoma subtypes, OX40 in SS, CD40 in GIST and SS. The immune landscape of sarcoma was found to be as heterogeneous as the histotypes and molecular subtypes, but strongly correlated to the histotype. Histotype adapted immunotherapeutic approaches in each sarcoma subtypes must be considered in view of these results, consistently with the already reported specific response of histotypes of ICPs., (© 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.)
- Published
- 2020
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16. Overview of « druggable » alterations by histological subtypes of sarcomas and connective tissue intermediate malignancies.
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Penel N, Lebellec L, Blay JY, and Robin YM
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- Humans, Imatinib Mesylate, Neoplasms, Connective Tissue metabolism, Neoplasms, Connective Tissue pathology, Sarcoma metabolism, Sarcoma pathology, Soft Tissue Neoplasms metabolism, Soft Tissue Neoplasms pathology, Antineoplastic Agents therapeutic use, Molecular Targeted Therapy methods, Neoplasms, Connective Tissue drug therapy, Sarcoma drug therapy, Soft Tissue Neoplasms drug therapy
- Abstract
We summarize herein the literature data about molecular targeted therapies in sarcomas and conjunctive tissue intermediate malignancies. For each clinical setting, the level of evidence, the mechanism of action and the target are described. The two major axes include (i) identification of subgroups of tumors with druggable alteration irrespective of the histological diagnosis (e.g. NTRK), and (ii) druggable target of pathway related to the physiopathology of the tumor: denosumab and bone giant cell tumor, imatinib and soft tissue giant cell tumor, mTOR inhibitor and PECOMA., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Published
- 2020
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17. Intrathecal liposomal cytarabine plus systemic therapy versus systemic chemotherapy alone for newly diagnosed leptomeningeal metastasis from breast cancer.
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Le Rhun E, Wallet J, Mailliez A, Le Deley MC, Rodrigues I, Boulanger T, Lorgis V, Barrière J, Robin YM, Weller M, and Bonneterre J
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- Antineoplastic Combined Chemotherapy Protocols therapeutic use, Cytarabine, Humans, Injections, Spinal, Quality of Life, Breast Neoplasms drug therapy, Meningeal Carcinomatosis
- Abstract
Background: DEPOSEIN (NCT01645839) was a randomized open-label phase III study to explore the role of intrathecal chemotherapy in patients with newly diagnosed leptomeningeal metastasis (LM), a common manifestation of breast cancer., Methods: Patients with newly diagnosed LM defined by tumor cells in the cerebrospinal fluid or combination of clinical and neuroimaging signs of LM were randomized to receive systemic therapy alone (control group) or systemic therapy plus intrathecal liposomal cytarabine (experimental group). Progression-free survival related to LM (LM-PFS) was the primary endpoint., Results: Thirty-seven and 36 patients were assigned to the control and the experimental groups. Median number of liposomal cytarabine injections in the experimental group was 5 (range 1-20). Focal radiotherapy was performed in 6 (16%) and 3 (8%) patients in the control and experimental groups. In the intent-to-treat population, median LM-PFS was 2.2 months (95% CI: 1.3-3.1) in the control versus 3.8 months (95% CI: 2.3-6.8) in the experimental group (hazard ratio 0.61, 95% CI: 0.38-0.98) (P = 0.04). Seventy-one patients have died. Median overall survival was 4.0 months (95% CI: 2.2-6.3) in the control versus 7.3 months (95% CI: 3.9-9.6) in the experimental group (hazard ratio 0.85, 95% CI: 0.53-1.36) (P = 0.51). Serious adverse events were reported in 22 and 30 patients, respectively. Quality of life until progression did not differ between groups., Conclusion: The addition of intrathecal liposomal cytarabine to systemic treatment improves LM-related PFS. Confirmatory trials with optimized patient selection criteria and more active drugs may be required to demonstrate a survival benefit from intrathecal pharmacotherapy., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2020
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18. Water-assisted laser desorption/ionization mass spectrometry for minimally invasive in vivo and real-time surface analysis using SpiderMass.
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Ogrinc N, Saudemont P, Balog J, Robin YM, Gimeno JP, Pascal Q, Tierny D, Takats Z, Salzet M, and Fournier I
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- Animals, Cell Line, Dogs, Equipment Design, Frozen Sections, Humans, Neoplasms chemistry, Rats, Skin chemistry, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization instrumentation, Water chemistry, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization methods
- Abstract
Rapid, sensitive, precise and accurate analysis of samples in their native in vivo environment is critical to better decipher physiological and physiopathological mechanisms. SpiderMass is an ambient mass spectrometry (MS) system designed for mobile in vivo and real-time surface analyses of biological tissues. The system uses a fibered laser, which is tuned to excite the most intense vibrational band of water, resulting in a process termed water-assisted laser desorption/ionization (WALDI). The water molecules act as an endogenous matrix in a matrix-assisted laser desorption ionization (MALDI)-like scenario, leading to the desorption/ionization of biomolecules (lipids, metabolites and proteins). The ejected material is transferred to the mass spectrometer through an atmospheric interface and a transfer line that is several meters long. Here, we formulate a three-stage procedure that includes (i) a laser system setup coupled to a Waters Q-TOF or Thermo Fisher Q Exactive mass analyzer, (ii) analysis of specimens and (iii) data processing. We also describe the optimal setup for the analysis of cell cultures, fresh-frozen tissue sections and in vivo experiments on skin. With proper optimization, the system can be used for a variety of different targets and applications. The entire procedure takes 1-2 d for complex samples.
- Published
- 2019
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19. Hormonal therapies in uterine sarcomas, aggressive angiomyxoma, and desmoid-type fibromatosis.
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Pannier D, Cordoba A, Ryckewaert T, Robin YM, and Penel N
- Subjects
- Aromatase Inhibitors therapeutic use, Endometrial Neoplasms drug therapy, Endometrial Neoplasms pathology, Female, Fibromatosis, Aggressive drug therapy, Fibromatosis, Aggressive pathology, Humans, Leiomyosarcoma drug therapy, Leiomyosarcoma pathology, Sarcoma pathology, Sarcoma, Endometrial Stromal pathology, Uterine Neoplasms pathology, Antineoplastic Agents, Hormonal therapeutic use, Sarcoma drug therapy, Uterine Neoplasms drug therapy
- Abstract
We review the role of hormonal therapy in the management of different conjunctive tumors. Progestin and aromatase inhibitors seem active in low-grade endometrial stromal sarcoma, but larger case-series are needed. There is no evidence to support the use of hormonal therapy as an adjuvant treatment for low-grade endometrial stromal sarcoma. We did not find relevant data on the use of hormonal therapy for other uterine sarcomas (e.g., high-grade endometrial sarcoma, undifferentiated uterine sarcoma, and adenosarcoma). Gonadotropin-releasing hormone agonist, anti-estrogens and aromatase inhibitor seem active in advanced aggressive angiomyxoma, but larger studies are warranted. The use of aromatase inhibitor in estrogen-receptor-positive uterine leiomyosarcoma requires further clinical investigation. There is no evidence supporting the use of hormonal therapy in desmoid-type fibromatosis. International collaboration efforts are warranted to better explore the role of hormonal therapies in management of estrogen-receptor-positive uterine leiomyosarcoma, low-grade endometrial stromal sarcoma, and aggressive angiomyxoma., (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Published
- 2019
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20. Adjuvant management of operated uterine sarcomas: A single institution experience.
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Cordoba A, Prades J, Basson L, Robin YM, Taïeb S, Narducci F, Hudry D, Bresson L, Chevalier A, Le Tinier F, Mirabel X, Lartigau É, Penel N, and Leblanc É
- Subjects
- Adult, Aged, Aged, 80 and over, Antineoplastic Agents therapeutic use, Brachytherapy, Chemotherapy, Adjuvant statistics & numerical data, Combined Modality Therapy, Female, Humans, Hysterectomy, Kaplan-Meier Estimate, Leiomyosarcoma drug therapy, Leiomyosarcoma radiotherapy, Leiomyosarcoma surgery, Lymph Node Excision, Middle Aged, Neoplasm Metastasis, Neoplasm Recurrence, Local epidemiology, Neoplasm Recurrence, Local prevention & control, Prognosis, Progression-Free Survival, Proportional Hazards Models, Sarcoma, Uterine Neoplasms drug therapy, Uterine Neoplasms surgery, Radiotherapy, Adjuvant statistics & numerical data, Uterine Neoplasms radiotherapy
- Abstract
Purpose: The purpose of this study was to describe the adjuvant management of high grade uterine sarcoma and highlight prognostic factors for overall survival and progression-free survival., Material and Methods: Between 01/2000 and 01/2015, 91 patients undergoing surgery were presented at the multidisciplinary team meeting of our institution. The type of surgery, the anatomopathological features, adjuvant treatments, dates and sites of recurrence were collected. The prognostic value of the various factors was evaluated with the multivariate Cox model., Results: A total of 50 women with uterine sarcoma were identified and lesions included 43 leiomyosarcomas (86%) and seven high grade sarcomas (14%). Eighteen patients received adjuvant pelvic radiotherapy (36%) and six adjuvant systemic therapy (12%). The median follow-up time was 63 months. Thirty-nine patients (78%) had a recurrence: 22 had only metastatic recurrence (58%), two had isolated pelvic recurrence (5%) and 15 had pelvic and metastatic recurrence (38%). Adjuvant radiotherapy was associated with survival without pelvic recurrence in univariate analysis (P=0.005, hazard ratio [HR]=0.15); age greater than 55 years and adjuvant radiotherapy were associated with metastatic free survival in multivariate analysis (P=0.015, HR=2.37, and P=0.013, HR=0.41 respectively) CONCLUSION: According to the results of our series, there is a benefit of radiotherapy after surgery in terms of local control of uterine sarcoma. It is necessary to identify the subgroup of patients who will benefit from an adjuvant radiotherapy in order to provide them with more optimal care., (Copyright © 2019 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)
- Published
- 2019
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21. Should a Multigene Signature be Used in all Luminal Early Breast Cancers.
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Hajjaji N, Robin YM, and Bonneterre J
- Abstract
Background: Multigene signatures refine the risk of recurrence and guide adjuvant chemotherapy decision in luminal breast cancers. The decision to perform the assay is highly variable among oncologists. In order to guide the appropriate clinical group in whom to perform a genomic signature, our study analyzed in a homogeneous cohort which clinical risk groups triggered the use of the PAM50-based signature and their concordance with the genomic risk. Methods: A real life cohort of 222 early breast cancer patients with hormone receptor positive and HER2 negative disease had a commercial PAM50-based assay (Prosigna®) performed at our institution. The assay provided the risk group, the 10-year risk of distant recurrence and the intrinsic molecular subtype of breast cancer. Results: Based on nodal involvement, Ki67, tumor grade, mitotic index, and tumor size, no clinical pattern could identify a specific genomic risk group. The discordance with the genomic risk was high in patients with clinical low risk tumors, both in node negative and node positive patients. Up to 60% of them had a 10% or more risk of distant recurrence. Moreover, we identified a subgroup of luminal A tumors with a high genomic risk of recurrence. Genomic risk and intrinsic subtype were strong determinants of chemotherapy decision. Conclusions: Clinical profiles could not reliably identify genomic risk groups and guide the decision to use a multigene signature. Significant discordance with the genomic risk was observed within low clinical risk and luminal A tumors.
- Published
- 2019
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22. Personalised management of alveolar soft part sarcoma: a promising phase 2 study.
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Penel N, Robin YM, and Blay JY
- Subjects
- Antibodies, Monoclonal, Humanized, Axitinib, Humans, Sarcoma, Alveolar Soft Part
- Published
- 2019
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23. Real-Time Molecular Diagnosis of Tumors Using Water-Assisted Laser Desorption/Ionization Mass Spectrometry Technology.
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Saudemont P, Quanico J, Robin YM, Baud A, Balog J, Fatou B, Tierny D, Pascal Q, Minier K, Pottier M, Focsa C, Ziskind M, Takats Z, Salzet M, and Fournier I
- Subjects
- Animals, Dogs, Neoplasm Grading methods, Early Detection of Cancer methods, Lipids analysis, Molecular Diagnostic Techniques methods, Sarcoma diagnosis, Sarcoma pathology, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization methods
- Abstract
Histopathological diagnosis of biopsy samples and margin assessment of surgical specimens are challenging aspects in sarcoma. Using dog patient tissues, we assessed the performance of a recently developed technology for fast ex vivo molecular lipid-based diagnosis of sarcomas. The instrument is based on mass spectrometry (MS) molecular analysis through a laser microprobe operating under ambient conditions using excitation of endogenous water molecules. Classification models based on cancer/normal/necrotic, tumor grade, and subtypes showed a minimum of 97.63% correct classification. Specific markers of normal, cancer, and necrotic regions were identified by tandem MS and validated by MS imaging. Real-time detection capabilities were demonstrated by ex vivo analysis with direct interrogation of classification models., (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Published
- 2018
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24. [Dermatofibrosarcoma: Management].
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Penel N, El Bedoui S, Robin YM, and Decanter G
- Subjects
- Chromosomes, Human, Pair 17 genetics, Chromosomes, Human, Pair 22 genetics, Collagen Type I genetics, Collagen Type I, alpha 1 Chain, Genetic Markers, Humans, Neoplasm Recurrence, Local, Proto-Oncogene Proteins c-sis genetics, Translocation, Genetic, Dermatofibrosarcoma diagnostic imaging, Dermatofibrosarcoma genetics, Dermatofibrosarcoma pathology, Dermatofibrosarcoma therapy, Rare Diseases diagnostic imaging, Rare Diseases genetics, Rare Diseases pathology, Rare Diseases therapy, Skin Neoplasms diagnostic imaging, Skin Neoplasms genetics, Skin Neoplasms pathology, Skin Neoplasms therapy
- Abstract
Dematofibrosarcoma protuberans (DFSP) are very rare (1 to 4 incident cases per million of inhabitants). The local spreading of DFSP is underestimated. The histological diagnosis is challenging but we now know a specific marker (translocation t(17;22)(q22;q13) (COL1A1;PDGFB)). The risk of metastatic relapse is low (and related to fibrosarcoma component); the risk of local relapse depends on the quality of surgery. Management of localized DFSP is based on large resection with meticulous analysis of margins (with or without Mohs microsurgery). Advanced stages not amenable to surgery or metastatic DFSP (with presence of COL1A1;PDGFB) are best treated with imatinib. Locally advanced DFSP potentially amenable to curative intent surgery could be treated with imatinib as neo-adjuvant treatment. The management of these tumours requires multidisciplinary expertise., (Copyright © 2018 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)
- Published
- 2018
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25. Perfusion MR imaging at 3-Tesla: Can it predict tumor grade and histologic necrosis rate of musculoskeletal sarcoma?
- Author
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Gondim Teixeira PA, Renaud A, Aubert S, Ben Haj Amor M, Robin YM, Cotten A, and Ceugnart L
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Child, Female, Humans, Male, Middle Aged, Necrosis, Neoplasm Grading, Predictive Value of Tests, Retrospective Studies, Young Adult, Bone Neoplasms diagnostic imaging, Bone Neoplasms pathology, Magnetic Resonance Angiography, Muscle Neoplasms diagnostic imaging, Muscle Neoplasms pathology, Sarcoma diagnostic imaging, Sarcoma pathology
- Abstract
Purpose: To identify quantitative perfusion parameters that are best associated with tumor grade and tumor necrosis at magnetic resonance (MR) imaging at 3-Tesla., Methods: MR perfusion studies of 31 patients with a musculoskeletal sarcoma were retrospectively evaluated by two readers. There were 18 men and 13 women with a mean age of 34.9±24.4 (standard deviation [SD] years) (range: 6-87 years). All patients underwent carcinologic tumor resection less than 3 months after MR imaging. For all patients six perfusion parameters (three semi-quantitative and three permeability parameters) were analyzed. The percentage of tumor necrosis was estimated using MR imaging. Perfusion data were compared between groups of tumors with different grades and necrosis ratios. Interobserver variability was calculated using intraclass correlation coefficient (ICC)., Results: Interobserver variability among the perfusion parameters was good to excellent (ICC: 0.72-0.9). The area under the curve and maximum slope values showed a significant association with the degree of tumor necrosis (P=0.02-0.04). When tumors with low necrosis ratios were compared to those with high ratios the former parameter was 80% lower. In the same groups, the imaging necrosis index was 56.9-59.8% higher in patients with grade 2 necrosis (P=0.01). Extracellular space volume (V
e ) was 31.4% to 55.8% lower in tumors with high grade while the backflow constant (Kep ) was 33.6% to 40.1%% higher in tumors with high grade., Conclusion: Semi-quantitative MR perfusion parameters have an excellent reproducibility and are associated with the degree of histologic tumor necrosis in musculoskeletal sarcomas. The utility of permeability parameters for determining tumor grade needs further investigations., (Copyright © 2018 Soci showét showé françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.)- Published
- 2018
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26. [Neuroendocrine tumors of the breast: Myth or reality? A systematic review].
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Cheymol C, Abramovici O, Do Cao C, Dumont A, Robin YM, El Hajbi F, Dansin E, Bonneterre J, and Lauridant G
- Subjects
- Chromogranin A metabolism, Female, Humans, Incidence, Synaptophysin metabolism, Breast Neoplasms diagnosis, Breast Neoplasms epidemiology, Breast Neoplasms metabolism, Breast Neoplasms pathology, Neuroendocrine Tumors diagnosis, Neuroendocrine Tumors epidemiology, Neuroendocrine Tumors metabolism, Neuroendocrine Tumors pathology, Rare Diseases diagnosis, Rare Diseases epidemiology, Rare Diseases metabolism, Rare Diseases pathology
- Abstract
Primary neuroendocrine breast carcinomas are rare and little-known tumors. Only a limited number of studies on neuroendocrine breast carcinomas have been reported in the literature, and the vast majority of them are small retrospective series or case reports. According to the World Health Organization (WHO), they account for only 2 % to 5 % of breast cancers. Their diagnosis relies on the presence of a neuroendocrine architecture and the expression of neuroendocrine markers (chromogranin A and/or synaptophysin). The revised 2012 WHO classification subdivides them into three categories: (i) well-differentiated neuroendocrine carcinomas, (ii) poorly differentiated neuroendocrine carcinomas or small-cell carcinomas, and (iii) invasive breast carcinomas with neuroendocrine differentiation. Their clinical features and radiological characteristics are not different from those of other types of breast cancer. Because of discordant results, their clinical outcome is still poorly defined. So far, no standard treatment has been established, and most clinicians draw on their experience of invasive ductal cancer. The role of specific treatments like platinum-based chemotherapy, somatostatin analogues, peptide receptor radionucleide therapy or temozolomide remains unclear. A better knowledge of the molecular pathways involved in their carcinogenesis could help to identify new potential therapeutic targets. The efficacy of targeted therapies has to be studied., (Copyright © 2018 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)
- Published
- 2018
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27. Presentation and outcome of frequent and rare sarcoma histologic subtypes: A study of 10,262 patients with localized visceral/soft tissue sarcoma managed in reference centers.
- Author
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Penel N, Coindre JM, Giraud A, Terrier P, Ranchere-Vince D, Collin F, Guellec SLE, Bazille C, Lae M, de Pinieux G, Ray-Coquard IL, Bonvalot S, Cesne ALE, Robin YM, Stoeckle E, Toulmonde M, and Blay JY
- Subjects
- Adult, Age Factors, Aged, Chemotherapy, Adjuvant methods, Chemotherapy, Adjuvant statistics & numerical data, Female, France epidemiology, Humans, Male, Middle Aged, Neoadjuvant Therapy statistics & numerical data, Neoplasm Recurrence, Local pathology, Neoplasm Recurrence, Local prevention & control, Radiotherapy, Adjuvant methods, Radiotherapy, Adjuvant statistics & numerical data, Retrospective Studies, Sarcoma genetics, Sarcoma mortality, Sarcoma therapy, Soft Tissue Neoplasms genetics, Soft Tissue Neoplasms mortality, Soft Tissue Neoplasms therapy, Translocation, Genetic, Treatment Outcome, Young Adult, Neoplasm Recurrence, Local epidemiology, Sarcoma pathology, Soft Tissue Neoplasms pathology
- Abstract
Background: The objective of this study was to describe characteristics at diagnosis and outcomes of adults with soft tissue sarcoma., Methods: The authors conducted a retrospective multicenter study of 12,262 patients who were treated between January 1980 and 31 December 2013 in French Sarcoma Group centers and enrolled in the "Conticabase." Diagnoses were systematically reviewed by expert pathologists, and entities were classified according to the 2013 World Health Organization classification. Diagnostic characteristics, treatments, and outcomes are described for the entire cohort, for the subgroup of patients with translocation-related sarcomas, and for 9 different histologic subtypes., Results: The results stressed the magnitude of heterogeneity among adult sarcomas. For example, compared with other sarcomas, translocation-related sarcomas (2143 tumors; 20.8%) were associated with a younger age at presentation (40.6 vs 60.0 years; P < .0001), a low rate of predisposing conditions (0.01% vs 22.3%; P < .0001), a higher rate of lymph node involvement (4.7% vs 1.3%; P < .0001), and a higher rate of synchronous metastasis (11.9% vs 6.7%; P < .001); and complete (R0) resection (41.6% vs 31.9%; P < .0001), receipt of (neo)adjuvant radiation therapy (62.6% vs 42.2%; P < .0001), and receipt of (neo)adjuvant chemotherapy (36.6% vs 22.3%; P < .0001) were significantly more frequent. Overall, translocation-related sarcomas were associated with a lower rate of local relapse (18.1% vs 26.0%; P < .0001) but a higher rate of metastatic relapse (42.0% vs 30.7%; P < .0001)., Conclusions: Collaborative efforts are urgently needed to better assess the natural history and management options for every histologic subtype of sarcoma. Cancer 2018;124:1179-87. © 2017 American Cancer Society., (© 2017 American Cancer Society.)
- Published
- 2018
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28. Combined Mass Spectrometry Imaging and Top-down Microproteomics Reveals Evidence of a Hidden Proteome in Ovarian Cancer.
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Delcourt V, Franck J, Leblanc E, Narducci F, Robin YM, Gimeno JP, Quanico J, Wisztorski M, Kobeissy F, Jacques JF, Roucou X, Salzet M, and Fournier I
- Subjects
- Biomarkers, Female, Humans, Systems Biology methods, Tumor Microenvironment, Mass Spectrometry methods, Ovarian Neoplasms metabolism, Proteome, Proteomics methods
- Abstract
Background: Recently, it was demonstrated that proteins can be translated from alternative open reading frames (altORFs), increasing the size of the actual proteome. Top-down mass spectrometry-based proteomics allows the identification of intact proteins containing post-translational modifications (PTMs) as well as truncated forms translated from reference ORFs or altORFs., Methods: Top-down tissue microproteomics was applied on benign, tumor and necrotic-fibrotic regions of serous ovarian cancer biopsies, identifying proteins exhibiting region-specific cellular localization and PTMs. The regions of interest (ROIs) were determined by MALDI mass spectrometry imaging and spatial segmentation., Findings: Analysis with a customized protein sequence database containing reference and alternative proteins (altprots) identified 15 altprots, including alternative G protein nucleolar 1 (AltGNL1) found in the tumor, and translated from an altORF nested within the GNL1 canonical coding sequence. Co-expression of GNL1 and altGNL1 was validated by transfection in HEK293 and HeLa cells with an expression plasmid containing a GNL1-FLAG
(V5) construct. Western blot and immunofluorescence experiments confirmed constitutive co-expression of altGNL1-V5 with GNL1-FLAG., Conclusions: Taken together, our approach provides means to evaluate protein changes in the case of serous ovarian cancer, allowing the detection of potential markers that have never been considered., (Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.)- Published
- 2017
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29. The long non-coding RNA 91H increases aggressive phenotype of breast cancer cells and up-regulates H19/IGF2 expression through epigenetic modifications.
- Author
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Vennin C, Spruyt N, Robin YM, Chassat T, Le Bourhis X, and Adriaenssens E
- Subjects
- Aged, Animals, Breast Neoplasms metabolism, Breast Neoplasms pathology, Cell Line, Tumor, Cell Movement, Cell Proliferation, DNA Methylation, Female, Genetic Predisposition to Disease, Genomic Imprinting, Humans, Insulin-Like Growth Factor II metabolism, Mice, SCID, Middle Aged, Neoplasm Invasiveness, Phenotype, RNA Interference, RNA, Long Noncoding metabolism, Time Factors, Transfection, Tumor Burden, Breast Neoplasms genetics, Epigenesis, Genetic, Gene Expression Regulation, Neoplastic, Insulin-Like Growth Factor II genetics, RNA, Long Noncoding genetics
- Abstract
Numerous genomic imprinting loci are regulated by long non-coding RNA (lncRNA). We have previously identified a new lncRNA at the H19/IGF2 locus transcribed in H19 antisense orientation and named 91H. This RNA is conserved among mammals. In mice, 91H regulates positively IGF2 expression from a novel promoter. However, in human the function of 91H at the H19/IGF2 locus remains largely undeciphered. Here, we observed that 91H, H19 and IGF2 are overexpressed in breast tumors. By using 91H-knockdown breast cancer cells, we demonstrated that 91H exerts oncogenic properties by promoting cell growth, migration and invasion as well as tumor growth in xenografted immunodeficient mouse model. Moreover, 91H-knockdown reduces the expression of H19 and IGF2 in breast cancer cells. By chromatin-immunoprecipitation and methylation studies, we found that 91H expression prevents histone and DNA methylation on the maternal allele at the H19/IGF2 locus. These results indicate that 91H, through epigenetic modifications, is responsible of the maintenance of H19/IGF2 genomic imprinting allowing the allele-specific expression of H19 and IGF2. Taken together, overexpression of 91H in breast cancer and 91H-induced epigenetic modifications on H19/IGF2 locus suggest that 91H may play essential role in breast cancer development. Further studies are needed to investigate their role in terms of diagnosis and therapeutic., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2017
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30. Malignant Peripheral Nerve Sheath Tumor Is a Challenging Diagnosis: A Systematic Pathology Review, Immunohistochemistry, and Molecular Analysis in 160 Patients From the French Sarcoma Group Database.
- Author
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Le Guellec S, Decouvelaere AV, Filleron T, Valo I, Charon-Barra C, Robin YM, Terrier P, Chevreau C, and Coindre JM
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Biomarkers, Tumor analysis, Child, Databases, Factual, Female, France, Humans, Immunohistochemistry, In Situ Hybridization, Fluorescence, Kaplan-Meier Estimate, Male, Middle Aged, Neoplasm Recurrence, Local pathology, Neurilemmoma mortality, Prognosis, Proportional Hazards Models, Young Adult, Neurilemmoma diagnosis
- Abstract
An accurate histopathologic diagnosis is essential for an adequate treatment of soft tissue sarcomas. The diagnosis of malignant peripheral nerve sheath tumor (MPNST) can be complex, particularly outside the neurofibromatosis type 1 (NF1) context. MPNST is a rare malignancy, and due to the lack of specific histologic criteria, several differential diagnoses must be considered. A total of 350 patients diagnosed with MPNST (from 1990 to 2013) were retrieved from the French sarcoma network (RRePS) and the Conticabase (Connective Tissue Cancer Network database). Tumor samples were available for 160 cases (45.2%). Pathology review, immunohistochemistry (IHC), and molecular analysis (when dealing with a monomorphic sarcoma) were systematically performed. Patient, tumor, and treatment characteristics were evaluated to identify prognostic factors for the definitive primary MPNST (n=106) cohort. Twenty-nine tumors (18.1%) initially diagnosed as MPNST were reclassified on the basis of histologic review, IHC, and molecular analysis. Patients with NF1 disease comprised 64% of the remaining cohort. The 5-year overall survival for patients from the entire cohort was 47%, 34.8% for NF1 patients, and 68.5% for patients without NF1 disease, making NF1 syndrome an independent poor prognostic factor of survival. Positive margins and lack of radiation therapy were independent predictors of local recurrence. The Fédération Nationale des Centres de Lutte Contre le Cancer tumor grade was an independent prognostic indicator of metastasis. Given the therapeutic implications of a misdiagnosis, the systematic pathology review, IHC, and molecular analysis (when dealing with monomorphic sarcoma) strategy allowed reclassification of 20% of cases, mainly the sporadic MPNSTs.
- Published
- 2016
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31. Management of desmoid tumours: A nationwide survey of labelled reference centre networks in France.
- Author
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Penel N, Coindre JM, Bonvalot S, Italiano A, Neuville A, Le Cesne A, Terrier P, Ray-Coquard I, Ranchere-Vince D, Robin YM, Isambert N, Ferron G, Duffaud F, Bertucci F, Rios M, Stoeckle E, Le Pechoux C, Guillemet C, Courreges JB, and Blay JY
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Biomarkers, Tumor genetics, Biopsy, Large-Core Needle, Child, Cooperative Behavior, DNA Mutational Analysis, Databases, Factual, Early Detection of Cancer, Female, Fibromatosis, Aggressive genetics, Fibromatosis, Aggressive mortality, Fibromatosis, Aggressive pathology, France epidemiology, Genetic Predisposition to Disease, Health Care Surveys, Humans, Incidence, Male, Middle Aged, Mutation, Patient Care Team, Phenotype, Predictive Value of Tests, Program Evaluation, Quality Improvement, Quality Indicators, Health Care, Referral and Consultation, Time Factors, Time-to-Treatment, Treatment Outcome, Young Adult, beta Catenin genetics, Delivery of Health Care, Integrated organization & administration, Delivery of Health Care, Integrated standards, Fibromatosis, Aggressive therapy
- Abstract
Purpose: The optimal management of rare tumours (i.e. from accurate diagnosis to management in reference centres) is a public health challenge. In 2009, the French National Cancer Institute (INCa) identified and financially supported the two expert networks for pathological and clinical diagnosis and management of soft tissue tumours., Methods: The activities of both networks were prospectively collected using a nationwide database (rreps.org). Data describing the diagnosis management of 863 successive cases of desmoids tumours (DT) were prospectively collected from 2010 to 2013 and analysed., Results: The number of confirmed DT constantly improved from January 2010 to December 2013 (from 173 to 273 cases per year); the expected incidence ranged from 132 to 330 cases/year. The rate of cases diagnosed with core-needle biopsies and CTNNB1 mutational status analysis increased from 30.6 to 40.7% and from 87.8 to 94.1%, respectively. The mean delay for pathological diagnosis confirmation constantly decreased from 107 to 47 d. Among the 846 adult patients, 414 (48.9%) patients were treated by reference centres. The rate of patients managed by reference centres constantly increased with time from 36.9 to 49.5% since 2010. The median management time of the referral centres constantly decreased from 440 to 67 d., Conclusion: The two expert networks worked synergistically and improved diagnosis modalities of rare desmoid tumours at a national level. The impact of management by expert networks on the outcome will be prospectively analysed in the future., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2016
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32. Improvement of the initial management of sarcomas after the dissemination of evidence-based guidelines depends on the primary sarcoma location: a population-based study.
- Author
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Ligier K, Maynou C, Leroy X, Robin YM, Martin P, Clisant S, Richard F, and Penel N
- Subjects
- Aged, Bone Neoplasms epidemiology, Female, Guidelines as Topic, Humans, Male, Middle Aged, Neoplasm Metastasis, Neoplasm Staging, Quality of Health Care, Sarcoma epidemiology, Sarcoma secondary, Soft Tissue Neoplasms epidemiology, Bone Neoplasms pathology, Sarcoma pathology, Soft Tissue Neoplasms pathology
- Abstract
Background: Improvement of the initial management of sarcomas after the dissemination of evidence-based guidelines depends on the primary sarcoma location: a population-based study. To improve the initial management of adult sarcomas, a regional expert team in Northern France performed two actions: dissemination of evidence-based guidelines (EBG) for the management of soft tissue/visceral sarcoma and yearly educational symposia. The aim of this study was to measure the impact of the dissemination of EBG on the key-indicators of adult sarcoma management., Methods: We conducted a before-after population-based study (before: 2005 with 63 cases, after: 2008-2009 with 86 cases) in the Lille area (Northern France urban/sub-urban area with 800,000 inhabitants). The following were the key-indicators of adult sarcoma management: pre-therapeutic biopsy, appropriate tumour and chest imaging, expert interdisciplinary discussion, expert interdisciplinary discussion before the first treatment and in operated cases, the rate of R0 resection., Results: There was no statistically significant difference in patient and tumour characteristics for the two time periods in terms of gender, prior cancer, primary location, histological subtype, grade, size, metastasis and lymph node involvement. There was no statistically significant improvement in primary tumour imaging (83 versus 87%), chest imaging (67 vs 71%), pre-therapeutic biopsy (57 vs 58%). There was an improvement in expert multidisciplinary discussion (37 vs 45%) or discussion before the first treatment (26 vs 44%) but no statistically significant. However, when soft tissue and bone sarcomas were analysed separately, we observed statistically significant improvements in expert multidisciplinary discussion (50 vs 74%, p = 0.02) and R0 resection rate (58 vs 91%, p = 0.002). In contrast, in cases of visceral sarcoma, there was no improvement in expert multidisciplinary discussion (10 vs 16%, p = 0.7) or in R0 resection (88 vs 81%, p = 0.7)., Conclusions: The dissemination of EBG was associated with a limited improvement in sarcoma management when measured in this before-after population-based study, and this improvement was dependent on the primary location of the tumour. Efforts to implement these guidelines by all surgical teams that could treat sarcoma, including visceral sarcoma, need to be made.
- Published
- 2015
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33. EGFR-Mutated Breast Metastasis of Lung Adenocarcinoma: A Case Report.
- Author
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Dansin E, Carnot A, Servent V, Daussay D, Robin YM, Surmei-Pintilie E, Lauridant G, Descarpentries C, Révillion F, and Delattre C
- Abstract
Breast metastasis from other primary carcinoma is very rare and could be difficult to identify despite immunohistochemistry analysis. Breast metastasis from lung adenocarcinoma can mimic triple-negative breast cancer. Given the prognosis and therapeutic challenges, a correct diagnosis appears essential, and molecular biomarkers could be useful. We report the case of a 52-year-old woman with a breast mass initially diagnosed as primary breast cancer and secondarily attached to breast metastasis from an EGFR-mutated lung adenocarcinoma. The same activating EGFR mutations were identified in both the primary lung carcinoma and the breast metastasis.
- Published
- 2015
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34. Prognostic factors and impact of adjuvant treatments on local and metastatic relapse of soft-tissue sarcoma patients in the competing risks setting.
- Author
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Italiano A, Le Cesne A, Mendiboure J, Blay JY, Piperno-Neumann S, Chevreau C, Delcambre C, Penel N, Terrier P, Ranchere-Vince D, Lae M, Le Guellec S, Michels JJ, Robin YM, Bellera C, and Bonvalot S
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Chemoradiotherapy, Adjuvant, Female, Humans, Male, Middle Aged, Neoplasm Metastasis, Neoplasm Recurrence, Local mortality, Neoplasm Recurrence, Local pathology, Prognosis, Risk Factors, Sarcoma mortality, Sarcoma pathology, Treatment Outcome, Neoplasm Recurrence, Local drug therapy, Neoplasm Recurrence, Local radiotherapy, Sarcoma drug therapy, Sarcoma radiotherapy
- Abstract
Background: In the medical literature many analyses of outcomes of sarcoma patients were performed without regard to the problem of "competing risks.", Methods: We analyzed local relapse-free and metastasis-free survival in a population of 3255 adult patients with a primary soft-tissue sarcoma (STS) included in the French Sarcoma Group database. Cumulative incidence of local and metastatic relapse was estimated by accounting for death as a competing event., Results: On multivariate analysis, age, tumor site, histological subtype, and grade were independent adverse prognostic factors for local relapse, whereas tumor depth and size had no influence. Histological subtype, tumor depth, tumor size, and grade were independent adverse prognostic factors for metastatic relapse. Despite a higher incidence of competing deaths in patients managed with adjuvant radiotherapy than in patients not receiving radiotherapy, adjuvant radiotherapy was associated with a significant benefit in terms of local relapse-free survival. Despite a similar cumulative incidence of competing deaths in patients with grade 2 and grade 3 disease, we found that the benefit of adjuvant chemotherapy was present only in patients with grade 3 and not in patients with grade 2 disease., Conclusions: In the setting of competing risks, tumor biology reflected by histological grade is a crucial predictor of local relapse, whereas tumor depth and size have poor if any influence. Grade could also predict the benefit of adjuvant chemotherapy in patients with STS., (© 2014 American Cancer Society.)
- Published
- 2014
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35. Long-term recurrence of soft tissue sarcomas: prognostic factors and implications for prolonged follow-up.
- Author
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Toulmonde M, Le Cesne A, Mendiboure J, Blay JY, Piperno-Neumann S, Chevreau C, Delcambre C, Penel N, Terrier P, Ranchère-Vince D, Lae M, Le Guellec S, Michels JJ, Robin YM, Bellera C, and Italiano A
- Subjects
- Adult, Combined Modality Therapy, Disease-Free Survival, Female, Follow-Up Studies, Humans, Male, Medical Records, Middle Aged, Neoplasm Grading, Predictive Value of Tests, Prognosis, Retroperitoneal Neoplasms pathology, Risk Assessment, Risk Factors, Sarcoma therapy, Soft Tissue Neoplasms therapy, Time Factors, Neoplasm Recurrence, Local, Population Surveillance, Sarcoma pathology, Soft Tissue Neoplasms pathology
- Abstract
Background: 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., Methods: Follow-up data from patients with localized soft tissue sarcoma who were included in the French Sarcoma Group database from January 1990 to June 2005 were reviewed. The outcomes of interest were the cumulative probabilities of late (> 5 years) local and metastatic disease recurrence with death as a competing event. Estimations and 95% confidence intervals (95% CIs) were computed with the cumulative incidence function., Results: A total of 719 patients who were alive and event free > 5 years after their initial diagnosis were included in the current study. Sixty-seven patients (9.3%) developed a late local recurrence and 42 patients (5.8%) developed a late metastatic recurrence, respectively. On multivariate analysis, internal trunk location (hazard ratio [HR], 3.9; 95% CI, 2.2-6.7 [P < .001]) and tumor size > 100 mm (HR, 2.1; 95% CI, 1.1-4 [P = .035]) were the 2 factors found to be independently associated with an increased risk of late local recurrence. Grade > 1 (graded according to the French Federation of Cancer Centers Sarcoma Group) (HR, 4.7; 95% CI 1.1-21 [P = .04]) was the sole factor found to be independently associated with an increased risk of late metastatic recurrence., Conclusions: Late recurrence of soft tissue sarcoma is relatively uncommon. However, the results of the current study emphasize the critical role of long-term follow-up to detect late local disease recurrence in patients with retroperitoneal or very large soft tissue sarcomas, and late metastatic recurrence in patients with high-grade disease. Conversely, the prolonged follow-up of patients with grade 1 disease is not needed., (© 2014 American Cancer Society.)
- Published
- 2014
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36. Low level of baseline circulating VEGF-A is associated with better outcome in patients with vascular sarcomas receiving sorafenib: an ancillary study from a phase II trial.
- Author
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Penel N, Ray-Coquard I, Bal-Mahieu C, Chevreau C, Le Cesne A, Italiano A, Bompas E, Clisant S, Baldeyrou B, Lansiaux A, Robin YM, Bay JO, Piperno-Neumann S, Blay JY, and Fournier C
- Subjects
- Antineoplastic Agents therapeutic use, Biomarkers, Tumor blood, Enzyme-Linked Immunosorbent Assay, Humans, Niacinamide therapeutic use, Sorafenib, Treatment Outcome, Hemangioendothelioma, Epithelioid blood, Hemangioendothelioma, Epithelioid drug therapy, Hemangiosarcoma blood, Hemangiosarcoma drug therapy, Niacinamide analogs & derivatives, Phenylurea Compounds therapeutic use, Vascular Endothelial Growth Factor A blood
- 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.
- Published
- 2014
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37. Are peripheral purely undifferentiated pleomorphic sarcomas with MDM2 amplification dedifferentiated liposarcomas?
- Author
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Le Guellec S, Chibon F, Ouali M, Perot G, Decouvelaere AV, Robin YM, Larousserie F, Terrier P, Coindre JM, and Neuville A
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Biomarkers, Tumor genetics, Diagnosis, Differential, Disease Progression, Disease-Free Survival, Female, Gene Expression Profiling, Genetic Predisposition to Disease, Genetic Testing methods, Humans, Immunohistochemistry, In Situ Hybridization, Fluorescence, Kaplan-Meier Estimate, Liposarcoma classification, Liposarcoma genetics, Liposarcoma mortality, Liposarcoma pathology, Male, Middle Aged, Phenotype, Predictive Value of Tests, Proto-Oncogene Proteins c-mdm2 genetics, Retrospective Studies, Sarcoma classification, Sarcoma genetics, Sarcoma mortality, Sarcoma pathology, Terminology as Topic, Time Factors, Treatment Outcome, Young Adult, Biomarkers, Tumor analysis, Cell Dedifferentiation, Cell Differentiation, Gene Amplification, Liposarcoma chemistry, Proto-Oncogene Proteins c-mdm2 analysis, Sarcoma chemistry
- Abstract
Dedifferentiated liposarcoma (DDLPS) has been defined as a tumor composed of well-differentiated liposarcoma associated with a nonlipogenic undifferentiated sarcoma and is genetically characterized by a 12q13-15 amplicon with MDM2 amplification. Some peripheral (extremities, trunk wall, head/neck) undifferentiated pleomorphic sarcomas (UPS) without areas of well-differentiated liposarcoma present an MDM2 amplification. We addressed whether they are true DDLPS or not. We compared the clinical data, histologic data, MDM2 status (immunohistochemistry [IHC], fluorescence in situ hybridization [FISH]), genomic profile (array comparative genomic hybridization), and follow-up of 19 patients with peripheral UPS with MDM2 amplification and 62 with peripheral conventional DDLPS retrieved from the French sarcoma network (RRePS) and the Conticabase (Connective Tissue Cancer Network database). For a control cohort, we described 153 patients from the Conticabase, with peripheral UPS without expression of MDM2 by IHC. By IHC, tumor cells were positive for MDM2 in 59 conventional DDLPS and in all UPS with MDM2 amplification. FISH analysis and/or quantitative polymerase chain reaction showed amplification of MDM2 in 54 conventional DDLPS and in all UPS with MDM2 amplification. The 2-year overall survival rates of UPS with MDM2 amplification, conventional DDLPS, and UPS without expression of MDM2 were 93.3%, 90.7%, and 73.9%, respectively. Such similarities in the clinical characteristics, morphology, genomic profile, and follow-up of peripheral UPS with MDM2 amplification and peripheral conventional DDLPS strongly suggest that peripheral UPS with MDM2 amplification are in fact DDLPS. Faced with histologic diagnosis of UPS, a systematic IHC evaluation of MDM2 allows a selection of cases for FISH analysis permitting the diagnosis of DDLPS.
- Published
- 2014
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38. CSF CA 15-3 in breast cancer-related leptomeningeal metastases.
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Le Rhun E, Kramar A, Salingue S, Girot M, Rodrigues I, Mailliez A, Zairi F, Bakhache E, Robin YM, Taillibert S, Dubois F, Bonneterre J, and Chamberlain MC
- Subjects
- Adult, Aged, Brain Neoplasms blood, Brain Neoplasms cerebrospinal fluid, Brain Neoplasms metabolism, Feasibility Studies, Female, France, Humans, Immunoenzyme Techniques, Male, Meningeal Neoplasms blood, Meningeal Neoplasms diagnosis, Middle Aged, Mucin-1 blood, Multivariate Analysis, Prospective Studies, Reproducibility of Results, Sensitivity and Specificity, Breast Neoplasms pathology, Meningeal Neoplasms cerebrospinal fluid, Meningeal Neoplasms secondary, Mucin-1 cerebrospinal fluid
- Abstract
Unlabelled: The sensitivity of CSF cytology, the standard method for diagnosis of leptomeningeal metastases (LM), is low. Serum cancer antigen 15-3 (CA 15-3) is frequently used for the monitoring of patients with breast cancer (BC) and is a laboratory test available in most centers. The aim of the current study was to determine the feasibility of measuring CSF CA 15-3 and CA 15-3 CSF/serum ratio in patients with BC-related LM. Serum and CSF CA 15-3 values were evaluated in 20 BC patients with LM (Group 1), 20 patients with LM from other primary cancers (Group 2), 20 BC patients with parenchymal brain metastases only (Group 3) and 20 controls (Group 4). CSF and serum were collected on the same day. Serum and CSF CA 15-3 were assessed by an automatized immuno-enzymatic technology (TRACE(®) technology, KRYPTOR Automate, Brahms Society, France). In univariate analysis, BC patients with LM (Group 1) compared to other groups, a significantly elevated serum CA 15-3 (median 51 U/ml, range 12-2819) and CSF CA 15-3 (median 8.7 U/ml, range 0.1-251) was observed. Additionally, the CSF/serum ratio of CA 15-3 was significantly higher in this group of patients (median 0.18, range 0.002-4.40). Multivariate analysis identified a cut-off for CSF CA15-3 with 80 % sensitivity and 70 % specificity., Conclusions: The current study confirms the feasibility of determining CSF CA 15-3 using a widely available technology. Evaluation of the CSF CA 15-3 may be useful in the diagnosis and management of BC-related LM but further studies are needed.
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- 2014
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39. Pure flat epithelial atypia: is there a place for routine surgery?
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Ceugnart L, Doualliez V, Chauvet MP, Robin YM, Bachelle F, Chaveron C, Rocourt N, Pouliquen G, Jarraya H, and Taieb S
- Subjects
- Adult, Aged, Biopsy, Large-Core Needle, Breast pathology, Breast Neoplasms genetics, Calcinosis pathology, Calcinosis surgery, Carcinoma in Situ genetics, Carcinoma, Intraductal, Noninfiltrating genetics, Carcinoma, Intraductal, Noninfiltrating pathology, Carcinoma, Intraductal, Noninfiltrating surgery, Diagnosis, Differential, Epithelial Cells pathology, Female, Follow-Up Studies, Genetic Predisposition to Disease genetics, Humans, Male, Mastectomy, Segmental, Middle Aged, Precancerous Conditions genetics, Prognosis, Breast Neoplasms pathology, Breast Neoplasms surgery, Carcinoma in Situ pathology, Carcinoma in Situ surgery, Mammography, Precancerous Conditions pathology, Precancerous Conditions surgery
- Abstract
Purpose: To determine whether it is appropriate to routinely undertake surgery if flat epithelial atypia (FEA) or pure flat epithelial atypia (pFEA) is found on large-core biopsy., Patients and Methods: Between 2005 and 2010, 1678 large-core biopsy procedures were carried out, which led to 136 FEA sites being identified, 63 of which across 59 patients were pFEA (four patients had two sites of pFEA each). Forty-eight patients underwent further surgical excision, equating to 52 excised sites of pFEA., Results: Of the 52 operated sites, there were 20 benign lesions (38%), 26 borderline lesions (56%), and three ductal carcinomas in situ (6%). The rate of histologic underestimation was put at 3.8%. Of the three cases that were underestimated, one was discarded because the definitive histology was not representative of the site from which microcalcifications had initially been taken. The other two cases that were underestimated were found in patients with an increased individual risk of breast cancer., Conclusion: In patients with no personal or first-degree family history of breast cancer, after complete or subtotal excision under radiology of the radiological lesion, and while excluding images fitting BI-RADS 5, annual monitoring may be offered as an alternative to surgical excision in view of the absence of underestimation found in our study., (Copyright © 2013 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.)
- Published
- 2013
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40. SISH/CISH or qPCR as alternative techniques to FISH for determination of HER2 amplification status on breast tumors core needle biopsies: a multicenter experience based on 840 cases.
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Jacquemier J, Spyratos F, Esterni B, Mozziconacci MJ, Antoine M, Arnould L, Lizard S, Bertheau P, Lehmann-Che J, Fournier CB, Krieger S, Bibeau F, Lamy PJ, Chenard MP, Legrain M, Guinebretière JM, Loussouarn D, Macgrogan G, Hostein I, Mathieu MC, Lacroix L, Valent A, Robin YM, Revillion F, Triki ML, Seaume A, Salomon AV, de Cremoux P, Portefaix G, Xerri L, Vacher S, Bièche I, and Penault-Llorca F
- Subjects
- Biopsy, Large-Core Needle, Female, Gene Amplification, Humans, Immunohistochemistry, Middle Aged, Predictive Value of Tests, Breast Neoplasms genetics, Genes, erbB-2 genetics, In Situ Hybridization methods, Real-Time Polymerase Chain Reaction methods
- Abstract
Background: Until now, FISH has been the gold standard technique to identify HER2 amplification status in ambiguous cases of breast cancer. Alternative techniques have been developed to increase the capacities of investigating HER2 amplification status. The aims of this multicenter study in a large series of breast cancer patients were to prospectively compare the level of performance of CISH, SISH, and qPCR alternative techniques on paraffin-embedded core biopsies with "gold standard FISH" for evaluation of HER2 amplification status., Methods: This study was performed on 840 cases scored by immunohistochemistry (IHC): 0=317 (38%), 1+=183 (22%), 2+=109 (13%), 3+=231 (27%). Each of the 15 French centers participating in the study analyzed 56 breast carcinoma cases diagnosed on fixed paraffin-embedded core biopsies. HER2 amplification status was determined by commercially available FISH used as the reference technique with determination of the HER2/CEN17 ratio or HER2 copy number status. The alternative techniques performed on the same cases were commercially available SISH or CISH and a common qPCR method especially designed for the study including a set of 10 primer pairs: 2 for HER2 (exons 8 and 26), 5 to evaluate chromosome 17 polysomy TAOK1, UTP6, MRM1, MKS1, SSTR2 and 3 for diploidy control TSN, LAP3 and ADAMTS16., Results: The concordance between IHC and FISH was 96% to 95% based on the HER2/CEN17 ratio (n=766) or HER2 copy number (n=840), respectively. The concordance of the alternative techniques with FISH was excellent: 97% and 98% for SISH (498 and 587 cases), 98% and 75% for CISH (108 and 204 cases) and 95% and 93% (699 and 773 cases) for qPCR based on the HER2/CEN17 ratio or HER2 copy number, respectively. Similarly, sensitivity ranged from 99% to 95% for SISH, 100% to 99% for CISH and 89% to 80% for qPCR. The concordance with FISH (ratio) in the 2+ cases was 89% for SISH, 100% for CISH and 93% for qPCR., Conclusion: These alternative techniques showed an excellent concordance with FISH in core biopsies allowing their use in routine clinical practice. This newly designed qPCR on paraffin-embedded core biopsies deserves special attention, as it is reliable, easy to perform and less expensive than ISH tests.
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- 2013
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41. Sorafenib in patients with progressive epithelioid hemangioendothelioma: a phase 2 study by the French Sarcoma Group (GSF/GETO).
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Chevreau C, Le Cesne A, Ray-Coquard I, Italiano A, Cioffi A, Isambert N, Robin YM, Fournier C, Clisant S, Chaigneau L, Bay JO, Bompas E, Gauthier E, Blay JY, and Penel N
- Subjects
- Adult, Aged, Antineoplastic Agents administration & dosage, Antineoplastic Agents adverse effects, Disease Progression, Disease-Free Survival, Drug Administration Schedule, Female, France, Head and Neck Neoplasms drug therapy, Hemangioendothelioma, Epithelioid secondary, Humans, Liver Neoplasms drug therapy, Male, Middle Aged, Niacinamide administration & dosage, Niacinamide adverse effects, Niacinamide therapeutic use, Phenylurea Compounds administration & dosage, Phenylurea Compounds adverse effects, Protein Kinase Inhibitors therapeutic use, Rare Diseases, Sorafenib, Time Factors, Treatment Outcome, Antineoplastic Agents therapeutic use, Hemangioendothelioma, Epithelioid drug therapy, Niacinamide analogs & derivatives, Phenylurea Compounds therapeutic use
- Abstract
Background: There is no standard treatment for progressive epithelioid hemangioendothelioma (EHE). To investigate the significant vascularization of EHE, the activity/toxicity of sorafenib in patients with progressive EHE was explored., Methods: In this multicenter, 1-stage, phase 2 trial of sorafenib (800 mg daily), the primary endpoint, which was chosen by default, was the 9-month progression-free rate. All patients had documented progressive disease at the time of study entry., Results: Fifteen patients were enrolled between June 2009 and February 2011. The median age was 57 years (range, 31-76 years), and the ratio of men to women was 9:6. The performance status was zero in 10 patients and 1 in 5 patients. Twelve patients had metastases, mainly in the lung (12 patients), liver (5 patients), and bone (3 patients). Five patients had received prior chemotherapy (doxorubicin in 5 patients and taxane in 3 patients). The median sorafenib treatment duration was 124 days (range, from 27 to >271 days). Seven patients required dose reductions or transient treatment discontinuation. The 9-month progression-free rate was 30.7% (4 of 13 patients). The 2-month, 4-month, and 6-month progression-free rate was 84.6% (11 of 13 patients), 46.4% (6 of 13 patients), and 38.4% (5 of 13 patients), respectively. Two partial responses were observed that lasted 2 months and 9 months., Conclusions: Further clinical trials exploring sorafenib as treatment of progressive EHE are needed., (© 2013 American Cancer Society.)
- Published
- 2013
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42. Transgelin is a novel marker of smooth muscle differentiation that improves diagnostic accuracy of leiomyosarcomas: a comparative immunohistochemical reappraisal of myogenic markers in 900 soft tissue tumors.
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Robin YM, Penel N, Pérot G, Neuville A, Vélasco V, Ranchère-Vince D, Terrier P, and Coindre JM
- Subjects
- Cell Differentiation, Humans, Immunohistochemistry, Leiomyosarcoma metabolism, Microfilament Proteins analysis, Muscle Proteins analysis, Muscle, Smooth pathology, Predictive Value of Tests, Soft Tissue Neoplasms metabolism, Tissue Array Analysis, Biomarkers, Tumor analysis, Leiomyosarcoma diagnosis, Microfilament Proteins biosynthesis, Muscle Proteins biosynthesis, Soft Tissue Neoplasms diagnosis
- Abstract
Immunohistochemical use of myogenic markers serves to define smooth or skeletal muscle differentiation in soft tissue tumors. Establishing smooth muscle differentiation in malignant lesions can be challenging in some cases. We immunohistochemically examined 900 soft tissue tumors selected from the French Sarcoma Group's archived tissue collection, which contains a large number of leiomyosarcomas. The four most widely used smooth muscle diagnostic markers were evaluated (smooth muscle actin, desmin, h-caldesmon and calponin), and compared with a novel marker, transgelin. The diagnostic performance of each marker was statistically assessed in terms of sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV) and accuracy (A), in leiomyosarcomas versus all other sarcomas including gastrointestinal stromal tumors (GIST), and second in leiomyosarcomas versus specific tumor types. In leiomyosarcomas versus all other sarcomas including GIST, transgelin emerged as the best diagnostic marker (Se: 83%, Sp: 82%, PPV: 67%, NPV: 92%, A: 83%), compared with smooth muscle actin (Se: 75%, Sp: 83, PPV: 66%, NPV: 89%, A: 81%), desmin (Se: 45%, Sp: 88%, PPV: 62%, NPV: 79%, A: 75%), h-caldesmon (Se: 50%, Sp: 90%, PPV: 67%, NPV: 81%, A: 78%) and calponin (Se: 76%, Sp: 70, PPV: 52%, NPV: 87%, A: 71%). In leiomyosarcomas compared with other specific tumor types such as undifferentiated pleomorphic sarcoma and myxofibrosarcoma, the accuracy for transgelin varied from 80 to 87% whereas it was lower for all other markers (between 51 and 80%). These results indicate that transgelin could be used in practice as an additional marker useful for decision making, especially in those tumors with incomplete immunophenotypes.
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- 2013
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43. Predictive factors of positive circumferential resection margin after radiochemotherapy for rectal cancer: the French randomised trial ACCORD12/0405 PRODIGE 2.
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Rullier A, Gourgou-Bourgade S, Jarlier M, Bibeau F, Chassagne-Clément C, Hennequin C, Tisseau L, Leroux A, Ettore F, Peoc'h M, Diebold MA, Robin YM, Kleinclaus I, Mineur L, Petitjean C, Mosnier JF, Soubeyran I, Padilla N, Lemaistre AI, Bérille J, Denis B, Conroy T, and Gérard JP
- Subjects
- Chemoradiotherapy, Digestive System Surgical Procedures, Female, France, Humans, Male, Middle Aged, Neoadjuvant Therapy, Neoplasm Staging, Prognosis, Rectal Neoplasms pathology, Rectal Neoplasms therapy
- Abstract
Circumferential resection margin (CRM) appears as a new powerful prognostic factor of survival after surgery for rectal cancer. We aimed to evaluate predictive factors of positive CRM following preoperative radiochemotherapy in a French trial. Patients with rectal cancer were randomised in long course preoperative radiotherapy 45 Gy plus capecitabine versus 50 Gy plus capecitabine and oxaliplatin. Mesorectal excision was performed 6 weeks after treatment. Impact of clinical, pathological and surgical variables on positive CRM (≤1 mm) were analysed by multivariate analysis. Of 565 randomised patients, CRM was recorded in 390 cases and was positive in 8% (30/390). Patients with 50 Gy plus capecitabine and oxaliplatin had a 6% rate of positive CRM while those treated by 45 Gy plus capecitabine had a 10% rate (p=0.128). Three independent predictive factors of positive CRM were identified: abdominoperineal resection (APR) (odds ratio OR=3.24; p=0.004), vascular tumour invasion (OR=2.78; p=0.026) and poor histological response (modified Dworak 0-2) (OR=9.01; p=0.003). Significant predictive factors of positive CRM are related to type of surgery, especially APR, and poor histological prognostic factors. Intensification of neoadjuvant radiochemotherapy does not seem to have a major role in this study., (Copyright © 2012 Elsevier Ltd. All rights reserved.)
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- 2013
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44. Localised angiosarcomas: the identification of prognostic factors and analysis of treatment impact. A retrospective analysis from the French Sarcoma Group (GSF/GETO).
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Lindet C, Neuville A, Penel N, Lae M, Michels JJ, Trassard M, Terrier P, Birtwisle-Peyrottes I, Valo I, Collin F, Chateau MC, Robin YM, and Coindre JM
- Subjects
- Adult, Age Factors, Aged, Aged, 80 and over, Female, France, Hemangiosarcoma drug therapy, Humans, Kaplan-Meier Estimate, Lymphedema pathology, Male, Middle Aged, Neoadjuvant Therapy, Prognosis, Retrospective Studies, Survival Analysis, Treatment Outcome, Young Adult, Hemangiosarcoma pathology, Hemangiosarcoma therapy
- Abstract
Background: Angiosarcomas represent less than 2% of all adult soft tissue sarcomas. Prognostic factors and the role of (neo-) adjuvant treatments in the management of localised angiosarcomas require further investigation., Methods: We have conducted a retrospective multicenter study (June 1980 to October 2009) of 107 patients with localised angiosarcomas. All of the cases were centrally reviewed by a certified pathologist. Univariate and multivariate analyses were conducted to identify independent poor prognostic factors (PF). Overall survival (OS) and Local Recurrence-Free Survival (LRFS) were estimated using the Kaplan-Meier method. The effect of treatments was explored using the Cox model after adjusting for the PF., Results: The median age was 71 years. 22.4% and 62.6% developed an angiosarcoma in pre-existing lymphoedema and within irradiated tissue respectively. The median OS, LRFS and Disease Recurrence-Free Survival (DRFS) were 38.8, 27 and 36.1 months, respectively. In multivariate analysis, the following parameters influenced the OS: lymphoedema (Hazard ratio (HR)=2.0) and size >5cm (HR=1.5). After adjustment to these PF, R0 margins was the only treatment parameter that improving the OS (HR=0.2). In the multivariate analysis, the LRFS was influenced by an age >70 (HR=1.8) and pre-existing lymphoedema (HR=2.0). After adjustment for these PF, R0 margins (HR=0.5) and adjuvant radiotherapy (HR=0.3) improved the LRFS., Conclusions: Our results suggest the following points: (i) pre-existing lymphoedema, tumour size and age >70 are probably the major prognostic factors in patients with localised angiosarcomas; (ii) the achievement of R0 margins is probably of major importance for improving the patient outcome and (iii) adjuvant radiotherapy probably decreased the risk of local recurrence., (Copyright © 2012 Elsevier Ltd. All rights reserved.)
- Published
- 2013
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45. Assessment of human epidermal growth factor receptor 2 status in urothelial carcinoma of the upper urinary tract: a study using dual-color in situ hybridization and immunohistochemistry.
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Vershasselt-Crinquette M, Colin P, Ouzzane A, Gnemmi V, Robin YM, Aubert S, Villers A, and Leroy X
- Subjects
- Aged, Carcinoma mortality, Carcinoma pathology, Female, Gene Expression Regulation, Neoplastic, Humans, Immunohistochemistry, In Situ Hybridization, Male, Middle Aged, Molecular Targeted Therapy, Neoplasm Staging, Receptor, ErbB-2 genetics, Receptor, ErbB-2 immunology, Recurrence, Survival Analysis, Up-Regulation, Urologic Neoplasms mortality, Urologic Neoplasms pathology, Urothelium pathology, Carcinoma diagnosis, Receptor, ErbB-2 metabolism, Urologic Neoplasms diagnosis, Urothelium metabolism
- Abstract
Aim: Upper urinary tract urothelial carcinoma (UUTUC) is an uncommon neoplasm frequently discovered at a high-stage disease. The prognosis of disseminated UUTUCs is poor despite the use of platinum-based chemotherapy. The aim of the study was to evaluate HER2 overexpression and amplification in a series of 83 UUTUCs., Materials and Methods: All tumors were formalin fixed. TNM stage, grade, lymphovascular invasion, surgical margins, morphologic variants were reviewed by 2 pathologists. All tumors were immunostained with anti-HER2 antibody. HER2 gene amplification was determined by dual-color in situ hybridization. Gene amplification was defined by an HER2/CEN 17 ratio >2.2., Results: HER2 immunostaining was observed in 33/83 tumors. Twelve cases were 2+ score and 2 cases were 3+ score. HER2 in situ hybridization was evaluable in 75/83 cases. Amplification was observed in 6 (7%) cases. All amplified tumors were of high grade and 4/6 were stage pT3. A strong correlation between HER2 overexpression and amplification was noted (P<0.0001). HER2 overexpression and amplification were correlated with the pN+ stage but not with specific survival or recurrence., Conclusions: These results suggest that HER2 amplification is a rare event in UUTUC but may be of interest for targeted therapy in selected high-grade and high-stage tumors.
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- 2012
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46. Metastatic angiosarcomas: doxorubicin-based regimens, weekly paclitaxel and metastasectomy significantly improve the outcome.
- Author
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Penel N, Italiano A, Ray-Coquard I, Chaigneau L, Delcambre C, Robin YM, Bui B, Bertucci F, Isambert N, Cupissol D, Bompas E, Bay JO, Duffaud F, Guillemet C, and Blay JY
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Child, Doxorubicin administration & dosage, Female, Hemangiosarcoma secondary, Humans, Male, Middle Aged, Paclitaxel administration & dosage, Prognosis, Retrospective Studies, Treatment Outcome, Young Adult, Antineoplastic Agents administration & dosage, Hemangiosarcoma drug therapy, Hemangiosarcoma surgery
- Abstract
Background: Angiosarcomas are a rare but aggressive form of soft tissue sarcoma. At metastatic stage, the clinical benefit of therapeutic intervention remains debatable., Patients and Methods: We have carried a retrospective analysis of 149 cases treated between 1996 and 2009 in the French Sarcoma Group., Results: The median age was 60; the sex ratio was 0.80. Sixty-two percentage of cases presented with metastasis at the diagnosis. About 20% arose in irradiated fields. The median overall survival was 11 months. Treatment consisted in metastasectomy (5.4%), doxorubicin-based regimen (46.9%), weekly paclitaxel (Taxol) (31.5%), other chemotherapy regimens (10.7%) or exclusive palliative care (10.9%). Clinical prognostic factors identified by univariate analysis were presence of bone metastasis (P = 0.0107), presence of other metastasis (P = 0.0327) and performance status (P < 0.0001). The Cox model retained a performance status of two or more as the sole independent prognostic factor (HR [hazard ratio] = 2.49, P < 0.0001). After adjustment to the performance status and compared with exclusive palliative care, the following treatments significantly improve the outcome: doxorubicin-based regimen as first-line chemotherapy (HR = 0.38, P = 0.0165), weekly paclitaxel as first-line regimen (HR = 0.36, P = 0.0146) and metastasectomy (HR = 0.09, P = 0.0221)., Conclusions: This retrospective analysis indicates that some therapeutic interventions may significantly improve the outcome of this aggressive disease. Doxorubicin-based regimens and weekly paclitaxel seem to provide the same range of efficacy.
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- 2012
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47. Sorafenib for patients with advanced angiosarcoma: a phase II Trial from the French Sarcoma Group (GSF/GETO).
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Ray-Coquard I, Italiano A, Bompas E, Le Cesne A, Robin YM, Chevreau C, Bay JO, Bousquet G, Piperno-Neumann S, Isambert N, Lemaitre L, Fournier C, Gauthier E, Collard O, Cupissol D, Clisant S, Blay JY, and Penel N
- Subjects
- Adult, Aged, Aged, 80 and over, Antineoplastic Agents adverse effects, Benzenesulfonates adverse effects, Endpoint Determination, Female, Hemangiosarcoma mortality, Humans, Male, Middle Aged, Niacinamide analogs & derivatives, Phenylurea Compounds, Pyridines adverse effects, Sorafenib, Vascular Endothelial Growth Factor Receptor-2 genetics, Antineoplastic Agents therapeutic use, Benzenesulfonates therapeutic use, Hemangiosarcoma drug therapy, Pyridines therapeutic use
- Abstract
Background: Angiosarcomas account for <2% of all soft tissue sarcomas. This subtype is one of the most aggressive forms of soft tissue sarcoma. The prognosis for angiosarcoma patients in the advanced phase remains poor with current cytotoxic agents (progression-free survival [PFS] time of ∼4 months and overall survival [OS] time of ∼8 months). We investigated the antitumor activity of sorafenib in patients with metastatic or advanced angiosarcomas in a phase II trial., Methods: We conducted a stratified phase II trial. The primary endpoint was the progression-free rate (PFR) at 9 months according to the Response Evaluation Criteria in Solid Tumors. A two-stage design (optimal Simon design) was used. Patients received sorafenib (400 mg twice daily) for 9 months until unacceptable toxicity or tumor progression. Central pathological and radiological reviews were performed. Data on stratum A (superficial angiosarcoma) and stratum B (visceral angiosarcoma) are currently available. This trial is registered with ClinicalTrials.gov (identifier, NCT00874874)., Findings: Strata A and B recruited 26 and 15 patients, respectively. The median age was 63 years (range, 31-82 years), with 17 male and 24 female patients. Fourteen cases arose in irradiated fields. Thirty patients (73.0%) had been pretreated with conventional chemotherapy. No unexpected toxicity occurred. The PFR at 9 months was 3.8% in stratum A and 0.0% in stratum B. The median PFS times were 1.8 months and 3.8 months, respectively, whereas the median OS times were 12.0 months and 9.0 months, respectively. No responses were observed in chemotherapy-naïve patients, whereas a 40% tumor control rate and 23% response rate were observed in the pretreated population. In this cohort, no activating mutation of the KDR gene (exons 15, 16, 24) was detected., Interpretation: Sorafenib showed limited antitumor activity in pretreated patients only, for both visceral and superficial angiosarcoma, but tumor control was of short duration.
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- 2012
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48. Solitary fibrous tumors and so-called hemangiopericytoma.
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Penel N, Amela EY, Decanter G, Robin YM, and Marec-Berard P
- Abstract
We have reviewed the literature data regarding the spectrum of tumors including solitary fibrous tumor and hemangiopericytoma with special focus on definition of the disease, discussion of the criteria for malignancy, and the key elements of standard treatment of localized disease. We have discussed the emerging concepts on the tumor biology and the different systemic treatments (chemotherapy and molecular-targeted therapies).
- Published
- 2012
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49. Angiosarcoma: state of the art and perspectives.
- Author
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Penel N, Marréaud S, Robin YM, and Hohenberger P
- Subjects
- Animals, Hemangiosarcoma pathology, Humans, Antineoplastic Agents therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bridged-Ring Compounds therapeutic use, Doxorubicin therapeutic use, Hemangiosarcoma drug therapy, Hemangiosarcoma epidemiology, Taxoids therapeutic use
- Abstract
We propose a literature review of available data on angiosarcoma (AS). AS account for 1% of adult soft tissue sarcoma. Two risk factors are well-establish chronic lymhoedema, previous radiotherapy. Clinical presentations of AS are heterogeneous. Large resection followed, if possible, by adjuvant radiotherapy is the cornerstone of curative intent treatment of localized forms. There are no convincing data supporting the administration of adjuvant chemotherapy. For metastatic or locally advanced AS, doxorubicin and weekly paclitaxel seem to provide the longer progression-free survival. Three phase II or parts of phase II trials have been published in the last 2 years, investigating weekly paclitaxel, sorafenib and imatinib, demonstrating that clinical trials are feasible for such rare diseases. Biological evidences for the key role of angiogentic factors have been accumulated during the last years and support the further investigation of anti-angiogenetic agents alone and almost combination with chemotherapy in such disease., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2011
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50. [Intraoperative molecular assessment of sentinel nodes in the breast cancer using the Gene Search BLN Assay technique: our experience about 126 patients].
- Author
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Houpeau JL, Baranzelli MC, Giard S, Chauvet MP, Robin YM, Farre I, Andre C, Vilain MO, and Bonneterre J
- Subjects
- Breast Neoplasms pathology, Female, Humans, Predictive Value of Tests, Sensitivity and Specificity, Breast Neoplasms genetics, Breast Neoplasms surgery, Intraoperative Care methods, Reverse Transcriptase Polymerase Chain Reaction, Sentinel Lymph Node Biopsy
- Abstract
Introduction: Intraoperative molecular assay Gene Search BLN Assay (BLN) detects sentinel lymph node (SLN) metastasis in breast cancer. Our objective was to compare BLN to the definitive conventional histologic methods and to experiment the management of BLN in routine., Material and Methods: Each SLN was cut into alternate slabs. Half slabs were analysed with the intraoperative BLN molecular method, and the other slabs with the definitive histologic method., Results: Two hundred and thirty four SLN have been analysed (124 patients). Thirty-five SLN had metastasis for 29 patients (23.4%). BLN correctly identified 28 patients. Two cases of discordance between BLN and standard method were found, probably explained by a sample bias. The sensibility of BLN is 96.4%, the sensitivity is 99%, the predictive positive value is 96.4%, the predictive negative value is 99% and the concordance is 98.4%. The surgery time increases and there is a need to adapt the theatre organization accordingly., Conclusion: The Gene Search BLN Assay gives a great interest for the patient, the surgeon and the pathologist because it increases the quality of the intraoperative analysis by comparison with the intraoperative conventional histology., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)
- Published
- 2011
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