20 results on '"Scoazec, Jean-Yves"'
Search Results
2. Exceptional Response to Dual Colony-Stimulating Factor 1 Receptor/PD-L1 Targeting After Primary Resistance to PD-1 Inhibition in a Patient With a Metastatic Uveal Melanoma.
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Champiat, Stéphane, Salaün, Hélène, Lucibello, Francesca, Scoazec, Jean-Yves, Besse, Benjamin, Lalanne, Ana Ines, Rouleau, Etienne, Metzger, Nolwenn, Saint-Ghislain, Mathilde, Ryckewaert, Thomas, Gardrat, Sophie, Barnhill, Raymond, Cassoux, Nathalie, Stern, Marc-Henri, Lantz, Olivier, de Koning, Leanne, Marabelle, Aurélien, and Rodrigues, Manuel
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MACROPHAGE colony-stimulating factor ,IPILIMUMAB ,PROGRAMMED cell death 1 receptors ,MELANOMA ,METASTASIS - Abstract
Targeting CSF-1R may revert resistance to PD1inh in uveal melanoma, a report from @institut_curie, @GustaveRoussy, and #OscarLambret @GroupeUnicancer [ABSTRACT FROM AUTHOR]
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- 2023
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3. Netrin-1 Expression Confers a Selective Advantage for Tumor Cell Survival in Metastatic Breast Cancer
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Fitamant, Julien, Guenebeaud, Céline, Coissieux, Marie-May, Guix, Catherine, Treilleux, Isabelle, Scoazec, Jean-Yves, Bachelot, Thomas, Bernet, Agnès, and Mehlen, Patrick
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- 2008
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4. Screening for Prognostic Biomarkers in Metastatic Adrenocortical Carcinoma by Tissue Micro Arrays Analysis Identifies P53 as an Independent Prognostic Marker of Overall Survival.
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Hescot, Segolene, Faron, Matthieu, Kordahi, Manal, Do Cao, Christine, Naman, Annabelle, Lamartina, Livia, Hadoux, Julien, Leboulleux, Sophie, Pattou, Francois, Aubert, Sébastien, Scoazec, Jean-Yves, Al Ghuzlan, Abir, and Baudin, Eric
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TISSUE arrays ,ONCOGENES ,EARLY detection of cancer ,METASTASIS ,RETROSPECTIVE studies ,WNT proteins ,TUMOR markers ,ADRENAL tumors ,OVERALL survival - Abstract
Simple Summary: The aim of our retrospective study was to identify and prioritize potential prognostic parameters in a well characterized metastatic ACC population. We identified for the first time P53 as an independent prognostic marker of metastatic adrenocortical carcinoma after mENSAT-GRAS parameter adjustment. This biomarker is easily available and should be considered in clinical practice together with Ki67 for the management of patient with advanced ACC. Moreover, this study underlies the importance of adjustment of potential biomarkers to validated prognostic factors in order to avoid the accumulation of invalidated biomarkers not usable in clinical practice. Advanced adrenocortical carcinoma (ACC) has poor but heterogeneous prognosis. Apart from Ki67 index, no prognostic or predictive biomarker has been validated in advanced ACC, so far. We aimed at analyzing expression of a large panel of proteins involved in known altered pathways in ACC (cell cycle, Wnt/ß-catenin, methylation) to identify and prioritize potential prognostic or predictive parameters metastatic ACC population. We conducted a retrospective multicentric study. Overall survival (OS) and partial response according to RECIST 1.1 were primary endpoints. TMA was set up and 16 markers were analyzed. Modified ENSAT and GRAS parameters were characterized for prognostic adjustment. Results: We included 66 patients with a mean age at metastatic diagnosis of 48.7 ± 15.5 years. Median survival was 27.8 months. After adjustment to mENSAT-GRAS parameters, p53 and PDxK were prognostic of OS. No potential biomarker has been identified as predictive factor of response. We identified for the first time P53 as an independent prognostic marker of metastatic adrenocortical carcinoma after mENSAT-GRAS parameter adjustment. Prognostic impact of Wnt/ß-catenin alterations was not confirmed in this cohort of metastatic ACC. [ABSTRACT FROM AUTHOR]
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- 2022
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5. TWIST1 expression is associated with high-risk neuroblastoma and promotes primary and metastatic tumor growth.
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Sepporta, Maria-Vittoria, Praz, Viviane, Balmas Bourloud, Katia, Joseph, Jean-Marc, Jauquier, Nicolas, Riggi, Nicolò, Nardou-Auderset, Katya, Petit, Audrey, Scoazec, Jean-Yves, Sartelet, Hervé, Renella, Raffaele, and Mühlethaler-Mottet, Annick
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TUMOR growth ,NEUROBLASTOMA ,COMBINED modality therapy ,METASTASIS ,COLONIZATION (Ecology) - Abstract
The embryonic transcription factors TWIST1/2 are frequently overexpressed in cancer, acting as multifunctional oncogenes. Here we investigate their role in neuroblastoma (NB), a heterogeneous childhood malignancy ranging from spontaneous regression to dismal outcomes despite multimodal therapy. We first reveal the association of TWIST1 expression with poor survival and metastasis in primary NB, while TWIST2 correlates with good prognosis. Secondly, suppression of TWIST1 by CRISPR/Cas9 results in a reduction of tumor growth and metastasis colonization in immunocompromised mice. Moreover, TWIST1 knockout tumors display a less aggressive cellular morphology and a reduced disruption of the extracellular matrix (ECM) reticulin network. Additionally, we identify a TWIST1-mediated transcriptional program associated with dismal outcome in NB and involved in the control of pathways mainly linked to the signaling, migration, adhesion, the organization of the ECM, and the tumor cells versus tumor stroma crosstalk. Taken together, our findings confirm TWIST1 as promising therapeutic target in NB. TWIST1 and TWIST2 were found to display an opposed expression pattern, with TWIST1 associated with poor survival and TWIST2 with good prognosis. Functional studies revealed that TWIST1 promotes both primary and metastatic neuroblastoma (NB) tumor growth. Further, a transcriptional signature of NB tumors with high levels of TWIST1 and associated with dismal outcome is provided, confirming TWIST1 as a promising therapeutic target in NB. [ABSTRACT FROM AUTHOR]
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- 2022
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6. Are we reproducible in measurement of NET liver metastasis?
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Moalla, Salma, Arfi Rouche, Julia, Foulon, Stéphanie, Caramella, Caroline, Ternes, Nils, Planchard, David, Goere, Diane, Ducreux, Michel, Scoazec, Jean Yves, Deschamps, Frederic, Dromain, Clarisse, and Baudin, Eric
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Accurate measurement of well-differentiated neuroendocrine tumours (NET) liver metastases is critical to determine tumour slope and to assess treatment efficacy. Our objectives were to determine which CT or MRI sequence is the most reproducible to measure NET liver metastases and to assess the percentage of variability of measurements. Intra and inter-observer variability were studied on triphasic abdominal CT or liver MRI in 22 and 32 NET patients respectively. Patients were treatment-naïve or under somatostatin analogues. A maximum of 5 liver target lesions per patient was defined and three radiologists measured them on each sequence. Reproducibility were analysed by calculating the relative variation (RV) as defined by RECIST criteria. We analysed 1656 target measurements for CT and 3384 for MRI. Intra-observers RV were better than inter-observers. T2 for MRI and portal-phase for CT were associated with the lowest measurement variability. The MRI sequence offering the best intra and inter-observer reproducibility is the T2W-sequence. MRI allows more reproducible measurement than CT (inter-observer RV <20% in 96.8% for MRI and 81% for CT). Our study demonstrates intermediate to high imaging reproducibility of liver metastases measurements in NET patients. Non-enhanced MRI should be preferred to triphasic-CT for follow-up, assessment of treatment and trials. [ABSTRACT FROM AUTHOR]
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- 2017
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7. Can endoscopic papillectomy be curative for early ampullary adenocarcinoma of the ampulla of Vater?
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Alvarez-Sanchez, María-Victoria, Oria, Inés, Luna, Olivia, Pialat, Jean, Gincul, Rodica, Lefort, Christine, Bourdariat, Raphael, Fumex, Fabien, Lepilliez, Vincent, Scoazec, Jean, Salgado-Barreira, Angel, Lemaistre, Anne, Napoléon, Bertrand, Alvarez-Sanchez, María-Victoria, Oria, Inés, Luna, Olivia B, Scoazec, Jean Yves, Lemaistre, Anne Isabelle, and Napoléon, Bertrand
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ADENOCARCINOMA ,AMPULLA of Vater ,LYMPH node diseases ,PANCREATICODUODENECTOMY ,DYSPLASIA ,DUODENUM surgery ,DUODENUM ,ENDOSCOPIC retrograde cholangiopancreatography ,LONGITUDINAL method ,METASTASIS ,SURGICAL complications ,BILE duct tumors ,DUODENAL tumors ,TREATMENT effectiveness ,RETROSPECTIVE studies ,DIGESTIVE system endoscopic surgery - Abstract
Background: The therapeutic role of endoscopic papillectomy (EP) for early ampullary cancer (AC) is still controversial. The aim of the present study was to evaluate the curative potential of EP for early AC and to identify predictors of lymph node metastases (LNMs).Methods: We retrospectively reviewed 173 patients who were prospectively included in a database and who underwent EP between 1999 and 2013. Adenocarcinoma was present in 28 resected specimens. An additional surgery was proposed in cases of duodenal submucosal infiltration, duct ingrowth, R1 resection or lymphovascular invasion. Clinicopathological information and outcomes were collected, and predictors of LNMs were evaluated.Results: Duodenal submucosal invasion was present in 16/28 cases and LNMs, in 9/28 cases. ACs of the biliopancreatic subtype were smaller (NS); 100 % had submucosal invasion, and 71 % had LNMs. Smaller tumour size, biliopancreatic subtype and submucosal invasion were significantly correlated with LNMs (p < 0.028, p < 0.028 and p < 0.014). Predictive factors of LNMs in the multivariate analysis were submucosal invasion and tumour size (OR 0.032, p < 0.023 and OR 0.711, p < 0.035). EP was curative in 100 % of cancers with R0 resection and no evidence of submucosal or lymphovascular invasion.Conclusion: EP may be curative for patients with AC limited to the duodenal mucosa or the sphincter of Oddi without lymphovascular invasion. Due to the presence of more invasive stages at diagnosis, EP may not be curative for ACs of the biliopancreatic subtype. The significance of tumour size is limited by other confounders, such as the histological subtype. [ABSTRACT FROM AUTHOR]- Published
- 2017
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8. Treatment of metastatic pancreatic neuroendocrine tumors: relevance of ENETS 2016 guidelines.
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Foulfoin, Margaux, Graillot, Emmanuelle, Adham, Mustapha, Rousset, Pascal, Forestier, Julien, Hervieu, Valérie, Robinson, Philip, Scoazec, Jean-Yves, Lombard-Bohas, Catherine, and Walter, Thomas
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NEUROENDOCRINE tumors ,PANCREATIC tumors ,METASTASIS ,SOMATOSTATIN ,CANCER chemotherapy ,THERAPEUTICS ,TUMOR treatment - Abstract
The choice of first-line treatment for metastatic pancreatic neuroendocrine tumors (mP-NET) is mainly based on prognostic factors. ENETS-2016 guidelines stratified treatment according to 3 groups: Group 1, patients in whom all lesions could be removed; Group 2, patients with Ki67 <10%, low tumor burden, no symptoms and stable disease, for whom a watch-and-wait strategy or somatostatin analogs are proposed; Group 3, symptomatic patients or with Ki67 >10% or significant tumor burden or progressive disease, for whom a systemic chemotherapy is proposed. This retrospective study aimed to determine patient distribution, characteristics and outcome among these 3 groups. Patients with mP-NET diagnosis from 2004 to 2016 were categorized into the three groups. Prognosis was calculated using the Kaplan-Meier method. All treatments were recorded, and consistency with ENETS guidelines was explored. 104 patients were analyzed: 64% synchronous mP-NET, 80% grade 2 tumors and median overall survival (OS) of 104 (95% CI: 65-143) months. There were 15 patients in ENETS Group 1, 16 in Group 2 and 73 in Group 3. Median OS was not reached in Groups 1 and 2 and was 64 months (35-93) in Group 3. High liver tumor volume, high-grade tumor and progressive disease were associated with worse OS in multivariate analysis. The first-line treatment was in accordance with guidelines in 82%. 77% percent of deceased patients received less than 4 lines of treatment. Most patients are in Group 3 and do not receive all available treatments. Thus, trials are warranted to improve first-line chemotherapy. Alternative treatments may be considered for less aggressive disease. [ABSTRACT FROM AUTHOR]
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- 2017
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9. Endoscopic treatment of sporadic small duodenal and ampullary neuroendocrine tumors.
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Gincul, Rodica, Ponchon, Thierry, Napoleon, Bertrand, Scoazec, Jean-Yves, Guillaud, Olivier, Saurin, Jean-Christophe, Ciocirlan, Mihai, Lepilliez, Vincent, Pioche, Mathieu, Lefort, Christine, Adham, Mustapha, Pialat, Jean, Chayvialle, Jean-Alain, and Walter, Thomas
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ENDOSCOPIC surgery ,DUODENAL diseases ,NEUROENDOCRINE tumors ,HEALTH outcome assessment ,SURGICAL excision ,ASPIRATORS ,THERAPEUTICS ,TUMOR treatment ,CANCER relapse ,CARCINOGENESIS ,ANTHROPOMETRY ,COMPARATIVE studies ,RESEARCH methodology ,MEDICAL cooperation ,METASTASIS ,PROGNOSIS ,REOPERATION ,RESEARCH ,SURVIVAL ,TUMOR classification ,BILE duct tumors ,DUODENAL tumors ,PILOT projects ,EVALUATION research ,TUMOR grading ,DIAGNOSIS - Abstract
Background and study aim: As duodenal neuroendocrine tumors (NETs) are rare, their optimal management has not been clearly established. The aim of this study was to evaluate the feasibility and outcome of endoscopic treatment of duodenal NETs. Patients and methods: We reviewed the files of all patients who underwent endoscopic resection of a sporadic duodenal or ampullary NET between 1996 and 2014 at two centers. Results: A total of 29 patients with 32 uT1N0M0 NETs < 20 mm were included. Treatment consisted of endoscopic mucosal resection in 19 cases, and cap aspiration in 13 cases. Prior submucosal saline injection was used in 15 cases. Mortality was 3 % (one severe bleeding). Morbidity was 38 % (11/29). At post-resection analysis, mean tumor size was 8.9 mm (range 3 - 17 mm), 29 lesions were stage pT1, one was pT2, and 2 were pTx because of piecemeal resection. All NETs were well differentiated. A total of 27 lesions were classified as grade 1 and 5 were grade 2. The resection was R0, R1, and Rx for 16, 14, and 2 lesions, respectively. Three R1 patients underwent additional surgical treatment, with no residual tumor on the surgical specimen but with positive metastatic lymph nodes in two cases. One patient was lost to follow-up. Finally, 24 patients were included in the follow-up analysis. The median follow-up period was 56 months (range 6 - 175 months). Two patients presented a tumor recurrence during the follow-up period. Conclusions: Endoscopic treatment of small duodenal NETs was associated with significant morbidity, a difficulty in obtaining an R0 specimen, and the risk of lymph node metastasis. Nevertheless, it represents an interesting alternative in small grade 1 duodenal lesions and in patients at high surgical risk. [ABSTRACT FROM AUTHOR]
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- 2016
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10. Evaluating digestive neuroendocrine tumor progression and therapeutic responses in the era of targeted therapies: state of the art.
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de Mestier Clarisse Dromain, Louis, d'Assignies, Gaspard, Scoazec, Jean-Yves, Lassau, Nathalie, Lebtahi, Rachida, Brixi, Hedia, Mitry, Emmanuel, Guimbaud, Rosine, Courbon, Frédéric, d'Herbomez, Michèle, and Cadiot, Guillaume
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NEUROENDOCRINE tumors ,CANCER invasiveness ,METASTASIS ,BIOMARKERS ,ANTINEOPLASTIC agents - Abstract
Well-differentiated neuroendocrine tumors (NETs) are a group of heterogeneous rare tumors. They are often slow-growing and patients can have very long survival, even at the metastatic stage. The evaluation of tumor progression and therapeutic responses is currently based on Response Evaluation Criteria In Solid Tumors v1.1 (RECIST) criteria. As for other malignancies, RECIST criteria are being reexamined for NETs in the era of targeted therapies because tumor response to targeted therapies is rarely associated with shrinkage, as opposed to prolonged progression-free survival. Therefore, size-based criteria no longer seem to be suitable to the assessment of NET progression and therapeutic responses, especially considering targeted therapies. New imaging criteria, combining morphological and functional techniques, have proven relevant for other malignancies treated with targeted therapies. To date, such studies have rarely been conducted on NETs. Moreover, optimizing the management of NET patients also requires considering clinical, biological, and pathological aspects of tumor evolution. Our objectives herein were to comprehensively review current knowledge on the assessment of tumor progression and early prediction of therapeutic responses and to broaden the outlook on well-differentiated NETs, in the era of targeted therapies. [ABSTRACT FROM AUTHOR]
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- 2014
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11. Hepar lobatum carcinomatosum revealing an occult metastatic lobular carcinoma of the breast.
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Graber, Ivan, Dumortier, Jérôme, Poncet, Gilles, Queneau, Pierre-Edouard, Mathevet, Patrice, and Scoazec, Jean-Yves
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BREAST cancer ,METASTASIS ,LIVER failure ,CIRRHOSIS of the liver ,BIOPSY ,CARCINOGENESIS ,DISEASES in older women - Abstract
Abstract: Hepar lobatum carcinomatosum is an unusual cause of chronic liver failure, usually maskerading as cirrhosis. The pathogenesis of this syndrome is unclear. We report a case of liver failure revealing an occult lobular carcinoma of the breast, which offers the opportunity to gain further insight into the mechanisms of this rare cause of chronic liver disease. A 57-year-old woman, without history of malignancy, presented with hepatomegaly, ascites and altered liver tests (serum transaminase activity >5 N and hyperbilirubinemia). The transjugular liver biopsy performed at diagnosis showed an extensive fibrosis, containing scattered tumor cells, typical of metastatic lobular carcinoma of the breast. Four months later, after discovery of a rectal adenocarcinoma, a laparoscopy was performed; peritoneal carcinomatosis was discovered. A surgical biopsy of the liver was taken during the procedure: it showed histological features suggestive of chronic Budd-Chiari syndrome, with venocentric fibrosis and reversed lobulation. Intraluminal invasion of small hepatic veins and sinusoidal obstruction by neoplastic cells were observed. A small focus of lobular carcinoma was eventually discovered in the left mammary gland. The present case report expands the spectrum of clinical presentations associated with hepar lobatum carcinomatosum and points out to the importance of vascular injury in the pathogenesis of this rare cause of chronic liver disease. [Copyright &y& Elsevier]
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- 2010
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12. ENETS Consensus Guidelines for the Management of Peritoneal Carcinomatosis from Neuroendocrine Tumors.
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Kianmanesh, Reza, Ruszniewski, Philippe, Rindi, Guido, Kwekkeboom, Dik, Pape, Ulrich-Frank, Kulke, Matthew, Garcia, Isabel Sevilla, Scoazec, Jean-Yves, Nilsson, Ola, Fazio, Nicola, Lesurtel, Mickael, Eriksson, Barbro, Yuan-Jia Chen, Cioppi, Federica, and O'Toole, Dermot
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PANCREATIC tumors ,METASTASIS ,CANCER ,NEUROENDOCRINE tumors ,CARCINOID - Abstract
No abstract available Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]
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- 2010
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13. Long Term Efficacy and Assessment of Tumor Response of Transarterial Chemoembolization in Neuroendocrine Liver Metastases: A 15-Year Monocentric Experience.
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Touloupas, Caroline, Faron, Matthieu, Hadoux, Julien, Deschamps, Frédéric, Roux, Charles, Ronot, Maxime, Yevich, Steven, Joskin, Julien, Gelli, Maximiliano, Barbé, Rémy, Lamartina, Livia, Tissot, Hubert, Scoazec, Jean-Yves, Malka, David, Ducreux, Michel, Baudin, Eric, de Baère, Thierry, and Tselikas, Lambros
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LIVER radiography ,EVALUATION of medical care ,DISEASE progression ,LIVER tumors ,ACQUISITION of data methodology ,CONFIDENCE intervals ,ARTERIES ,TIME ,LOG-rank test ,MULTIVARIATE analysis ,AGE distribution ,LIVER ,METASTASIS ,CHEMOEMBOLIZATION ,RETROSPECTIVE studies ,CANCER patients ,NEUROENDOCRINE tumors ,MEDICAL records ,KAPLAN-Meier estimator ,DESCRIPTIVE statistics ,SOMATOSTATIN ,STATISTICAL correlation ,TUMOR grading ,EVALUATION - Abstract
Simple Summary: Neuroendocrine tumors (NET) are rare tumors, with long-term survival even for patients with liver metastases. Transarterial chemoembolization (TACE) is one of the most widely used treatments in this setting. The aim of the study was to assess the long-term efficacy of TACE in a large cohort of patients with NET liver metastases and to correlate imaging findings with survival. In our study including 202 patients with NET liver metastases and a mean follow-up of 8.2 years, TACE was effective to provide disease control for 26 months and a 5.3-year median overall survival (OS). Imaging responses using RECIST and mRECIST criteria were significantly correlated to OS: the median-OS was twice as long among mRECIST responders versus non-responders, with 80.5 months and 39.6 months respectively. These findings are of major importance for everyday practice as they confirm TACE's effectiveness and usefulness of imaging evaluation to better tailor patient treatment and repeat TACE sessions whenever necessary. Background: transarterial chemoembolization (TACE) is an established treatment for neuroendocrine tumor (NET) liver metastases. The aim was to evaluate the long-term treatment efficacy of TACE for NET liver metastases, and correlate imaging response with survival. Methods: this IRB-approved, single-center, retrospective study evaluated all TACE procedures performed for NET liver metastases from 2003–2017 for imaging tumor response (RECIST and mRECIST), time to liver progression (TT
L P), time to untreatable progression with TACE (TTUP), and overall survival (OS). Patient, tumor, and treatment characteristics were analyzed as prognostic factors. Survival curves according to the Kaplan–Meier method were compared by Log-rank test. Tumor responses according to RECIST and mRECIST were correlated with OS. Results: 555 TACE procedures were performed in 202 NET patients (38% grade 1, 60% grade 2) with primary tumors originating from pancreas, small bowel, and lung (39, 26, and 22% respectively). Median follow-up was 8.2 years (90–139 months). Median TTL P and TTUP were 19.3 months (95%CI 16.3–22.3) and 26.2 months (95%CI 22.3–33.1), respectively. Median OS was 5.3 years (95%CI 4.2–6.7), and was higher among mRECIST responders (80.5 months; 95%CI 64.6–89.8) than in non-responders (39.6 months; 95%CI = 32.8–60.2; p < 0.001). In multivariable analysis, age, tumor grade and liver involvement predicted worse OS, whereas administration of somatostatin analogs correlated with improved OS. Conclusion: TACE for NET liver metastases provides objective response and sustained local disease control rates. RECIST and mRECIST responses correlate with OS. [ABSTRACT FROM AUTHOR]- Published
- 2021
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14. Well-differentiated pancreatic islet cell carcinoma: Is there reversibility in mTOR inhibitor resistance?
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Walter, Thomas, Scoazec, Jean-Yves, Couderc, Christophe, Forestier, Julien, Roche, Colette, Chayvialle, Jean-Alain, and Lombard-Bohas, Catherine
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CANCER chemotherapy , *COMBINATION drug therapy , *DRUG resistance , *GLUCAGONOMA , *METASTASIS , *HEALTH outcome assessment , *SOMATOSTATIN , *RAPAMYCIN , *TREATMENT effectiveness - Abstract
A letter to the editor is presented which is concerned with well-differentiated pancreatic islet cell carcinoma.
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- 2011
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15. Molecular profiling and target actionability for precision medicine in neuroendocrine neoplasms: real-world data.
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Boilève, Alice, Faron, Matthieu, Fodil-Cherif, Sarah, Bayle, Arnaud, Lamartina, Livia, Planchard, David, Tselikas, Lambros, Kanaan, Christina, Scoazec, Jean Yves, Ducreux, Michel, Italiano, Antoine, Baudin, Eric, and Hadoux, Julien
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THERAPEUTIC use of antineoplastic agents , *INDIVIDUALIZED medicine , *RETROSPECTIVE studies , *METASTASIS , *CANCER patients , *NEUROENDOCRINE tumors , *GENE expression profiling - Abstract
Key molecular alterations (MA) of neuroendocrine neoplasm (NEN) of various grade/primaries have been described but the applicability of molecular profiling (MP) for precision medicine in NEN remains to be demonstrated. We conducted a retrospective study of all patients with metastatic NEN who had MP on tumour tissue at Gustave Roussy. The primary objective was to assess the clinical applicability of MP by evaluating the growth modulator index (GMI) as the primary end-point. MPs were obtained in 114 out of 156 eligible patients, including 12% NET-G1, 42% NET-G2, 13% NET-G3 and 35% neuroendocrine carcinoma (NEC). Primary sites were lung/thymus (40%), pancreas (19%), gastro-intestinal (16%), head&neck (10%), unknown (10%) and others (10%) with synchronous metastases in 61% of the patients. Most frequent MA were: MEN1 (25%), PTEN (13%), TP53 (11%) and TSC2 (9%), in neuroendocrine tumour (NET), and TP53 (50%) and RB1 (18%) in NEC. ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT) classification of these MA were: I(5%), III(20%), IV(23%), X(27%); a putative actionable MA was identified in 48% patients. Median TMB was 5.7 Mut/Mb, with 3 TMB > 10 and 1 MSI NET. No MA was found in 26% patients. Molecularly matched treatment was administered to 19 patients (4 NEC, 15 NET): immunotherapy (n = 3), tipifarnib (n = 1), NOTCHi (n = 1), EGFRi (n = 2), HER2i (n = 1) and everolimus (n = 11). Overall, 67% of patients had a clinical benefit defined as a GMI over 1.3 with a 78% disease control rate. We report 48% of NEN with a putative actionable MA of which 35% received molecularly matched treatment, with a clinical benefit in 67% of the cases. • Molecular alterations of NEN of various grade/primaries have been described. • Applicability of molecular profiling in NEN remains to be demonstrated. • We describe the largest cohort of metastatic NENs molecularly characterised. • We report the clinical benefit obtained in NENs with molecular profiling. • Our results put in a routine perspective the impact of precision medicine in NENs. [ABSTRACT FROM AUTHOR]
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- 2023
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16. Antitumour activity of somatostatin analogues in sporadic, progressive, metastatic pulmonary carcinoids.
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Sullivan, Ivana, Le Teuff, Gwénaël, Guigay, Joël, Caramella, Caroline, Berdelou, Amandine, Leboulleux, Sophie, Déandréis, Désirée, Hadoux, Julien, Ducreux, Michel, Duvillard, Pierre, Adam, Julien, Scoazec, Jean-Yves, Baudin, Eric, and Planchard, David
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CARCINOID , *CONFIDENCE intervals , *LUNG tumors , *METASTASIS , *NEUROENDOCRINE tumors , *PROBABILITY theory , *PROGNOSIS , *SOMATOSTATIN , *GASTROINTESTINAL tumors , *TREATMENT effectiveness , *RETROSPECTIVE studies , *DISEASE progression - Abstract
Purpose Antiproliferative activity of somatostatin analogues (SSAs) has been demonstrated in digestive neuroendocrine tumours but few data have been published on pulmonary carcinoids (PC). The aim of this retrospective study was to report the antitumour activity of SSAs in patients with progressive, metastatic PC. Methods Patients with PC and treated with SSA monotherapy were reviewed. Disease was classified according to the tumour slope prior to SSA initiation as rapidly progressive (at least 20% increase in the sum of the longest diameter of target lesions or the appearance of one or more new lesions within 6 months) or slowly progressive (if progression occurred over 6 months). Survival outcomes were progression-free survival (PFS) and overall survival (OS). We additionally examined the overall response rate and safety. Prognostic factors associated with PFS and OS were sought. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using the Cox model. Results Among 67 patients reviewed, 61 were included in the study. Forty-one (67%) of them exhibited slowly progressive disease prior to SSAs, 41 (67%) had atypical carcinoids and 29 (48%) had functioning tumours. Forty-six (76%) patients had received SSAs as first-line therapy. The best overall response was stable disease in 47 (77%) patients. The median duration of SSAs was 13.7 months. With a median follow-up of 5.8 years, median PFS and OS were 17.4 (95% CI: 8.7–26.0) and 58.4 (95% CI: 44.2–102.7) months, respectively. Functioning tumours and slowly progressive disease were significantly associated with longer PFS: HR = 0.48 ([95% CI: 0.24–0.95], p = 0.03) and HR = 7.43 ([95% CI: 3.02–18.25], p < 0.0001), respectively. Only functioning tumours remained significantly associated with OS: HR = 0.33 ([95% CI: 0.14–0.79], p = 0.01). Treatment had been discontinued in two patients due to side-effects. Conclusions Median PFS observed in our study is encouraging for PC patients. Patients with functioning tumours and slowly progressive disease treated with SSAs have better prognosis. [ABSTRACT FROM AUTHOR]
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- 2017
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17. Bevacizumab combined with 5-FU/streptozocin in patients with progressive metastatic well-differentiated pancreatic endocrine tumours (BETTER trial) – A phase II non-randomised trial.
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Ducreux, Michel, Dahan, Laetitia, Smith, Denis, O’Toole, Dermot, Lepère, Céline, Dromain, Clarisse, Vilgrain, Valérie, Baudin, Eric, Lombard-Bohas, Catherine, Scoazec, Jean-Yves, Seitz, Jean-François, Bitoun, Laurence, Koné, Sébastien, and Mitry, Emmanuel
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BEVACIZUMAB , *COMBINATION drug therapy , *CLINICAL trials , *CONFIDENCE intervals , *METASTASIS , *PANCREATIC tumors , *SURVIVAL , *DESCRIPTIVE statistics - Abstract
Aim of the study Neuroendocrine tumours are highly vascular neoplasms known to overexpress vascular endothelial growth factor (VEGF) and its receptor. Bevacizumab, an inhibitor of VEGF, was assessed in combination with chemotherapy in pancreatic neuroendocrine tumour (P-NET). Patients and methods BETTER was a multicentre, open-label, non-randomised, two-group phase II trial. Patients with progressive metastatic, well-differentiated P-NET received a minimum of 6 month treatment of bevacizumab at 7.5 mg/kg IV on d1 q3w with 5-FU at 400 mg/m 2 /day and streptozocin at 500 mg/m 2 /day IV from d1 to d5 every 42 days. The primary end-point was progression-free survival (PFS); secondary end-points were overall survival (OS), overall response rate, safety and quality of life. Results A total of 34 patients were included. Median age was 55 years, 65% of patients were men, 97% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and 97% had a Ki-67 proliferative index of <15%. After a maximum of 24 month follow-up per patient, the median PFS assessed by investigators was 23.7 months [95% confidence interval (CI): 13.1; not reached], 19 (56%) patients had a partial response and 15 (44%) had stable disease as best response. OS rate at 24 months was 88%. The most frequently reported grade 3–4 adverse events were hypertension (21% patients), abdominal pain (12%) and thromboembolic events (9%). Conclusion Bevacizumab with 5-FU/streptozocin in the treatment of pancreatic NETs seems to be feasible with a PFS of 23.7 months, which deserves further attention. No unexpected toxicity was observed. [ABSTRACT FROM AUTHOR]
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- 2014
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18. Is the combination of chromogranin A and pancreatic polypeptide serum determinations of interest in the diagnosis and follow-up of gastro-entero-pancreatic neuroendocrine tumours?
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Walter, Thomas, Chardon, Laurence, Chopin-laly, Xavier, Raverot, Véronique, Caffin, Anne-Gaelle, Chayvialle, Jean-Alain, Scoazec, Jean-Yves, and Lombard-Bohas, Catherine
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PANCREATIC tumors , *BIOMARKERS , *METASTASIS , *PEPTIDES , *CHROMOGRANINS , *DESCRIPTIVE statistics , *DIAGNOSIS - Abstract
Abstract: Introduction: Chromogranin A (CgA) is the principal tumour marker for gastroenteropancreatic neuroendocrine tumours (GEPNET). Combining serum CgA and pancreatic polypeptide (PP) levels may increase the sensitivity of tumour markers in the diagnosis of GEPNET. Objectives: (1) To evaluate the sensitivity of PP and CgA in GEPNET. (2) To compare changes in serum CgA and PP levels with the morphological evolution of the tumours. Patients and methods: Sixty-six pancreatic and 49 gastrointestinal NET, with at least one serum determination of CgA and PP at the same time were retrieved from an institutional data base. Secondly, the variations in serum CgA or PP at successive determinations were compared to Response Evaluation Criteria in Solid Tumours (RECIST) criteria in 57 patients (112 follow-up visits) with high serum CgA levels and in 21 patients (37 follow-up visits) with high serum PP levels. Results: Among the 115 patients included in the study group, an increase in serum CgA (normal <98μg/L) or PP (normal <100pmol/L) was found in respectively 79 (69%) and 36 (31%) cases. Seven patients had normal CgA and elevated PP levels. Both markers were significantly more elevated in metastatic disease (74% versus 51% for CgA and 37% versus 18% for PP). The concordance rates between serum markers and RECIST criteria were 51% for CgA and 54% for PP. Conclusions: Serum PP determination identify few false-negative results of serum CgA determination in GEPNET. Our study does not validate the use of CgA or PP as surrogate markers for detecting changes in tumour burden. [Copyright &y& Elsevier]
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- 2012
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19. Angiogenesis and Tumor Progression in Neuroendocrine Digestive Tumors
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Poncet, Gilles, Villaume, Karine, Walter, Thomas, Pourreyron, Céline, Theillaumas, Aurélie, Lépinasse, Florian, Hervieu, Valérie, Cordier-Bussat, Martine, Scoazec, Jean-Yves, and Roche, Colette
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NEOVASCULARIZATION , *CANCER invasiveness , *NEUROENDOCRINE tumors , *XENOGRAFTS , *VASCULAR endothelial growth factors , *LABORATORY mice , *CELL proliferation - Abstract
Background: Clinical observations suggest that in neuroendocrine digestive tumors a high intratumoral microvascular density is associated with good prognosis. We used an experimental orthotopic xenograft model to analyze the relations between angiogenic activity and tumor progression in this tumor subset. Material and methods: We compared 2 endocrine cell lines: STC-1, a low vascular endothelial growth factor (VEGF)-producing cell line, and INS-r3, a high VEGF-producing cell line. Tumor cells were grafted in the adventitial layer of the caecal wall of nude mice, sacrificed after 8 wk. Results: At 8 wk, “primary” tumors were present in all animals. STC-1 derived tumors were morphologically moderately differentiated, with high proliferative and apoptotic activities; in contrast, INS-r3 derived tumors were well differentiated, with low proliferative and apoptotic activities. VEGF was expressed in <50% grafted STC-1 cells but in >90% of grafted INS-r3 cells. Microvascular density was significantly higher in INS-r3 derived tumors than in STC-1 derived tumors. All STC-1 derived tumors (n = 8) have invaded the mucosa, in contrast to none of the INS-r3 derived tumors (n = 8); liver metastases were detected in 7/8 animals bearing STC-1 derived tumors and in 0/8 animals with INS-r3 derived tumors, despite the presence of lymph node metastases. Conclusions: Our experimental data concur with clinical findings to suggest that in well differentiated digestive neuroendocrine tumors angiogenesis is disconnected from tumor progression: the development of a highly vascular tumor microenvironment is correlated with VEGF secretion but is not associated with invasive and metastatic properties; it must therefore be regarded as an indirect marker of differentiation. [Copyright &y& Elsevier]
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- 2009
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20. The Role of Angiogenesis in Endocrine Liver Metastases: An Experimental Study
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Pourreyron, Céline, Poncet, Gilles, Roche, Colette, Gouysse, Géraldine, Nejjari, Mimoun, Walter, Thomas, Villaume, Karine, Jacquier, Marie-France, Bernard, Christine, Dumortier, Jérôme, Chayvialle, Jean-Alain, Bachelot, Thomas, and Scoazec, Jean-Yves
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METASTASIS , *NEOVASCULARIZATION , *CANCER invasiveness , *TUMORS - Abstract
Liver metastases are a major adverse event during the evolution of digestive endocrine tumors. However, little is known about their natural history and the determinants of their growth. In particular, whereas liver endocrine metastases, like their primary counterparts, are hypervascular, the role of tumor-associated angiogenesis has been little explored. We therefore designed an experimental model to study the intrahepatic growth of tumor endocrine cells; murine enteroendocrine STC-1 cells were injected into the spleen of nude mice to obtain their hepatic dissemination through the portal vein. Three stages of intrahepatic tumor growth were identified. Engraftment stage, until day 4 after intrasplenic injection of STC-1 cells, was avascular. Early growth, until day 17, resulted in small, infralobular nodules. Late growth, after day 17, was characterized by the development of large nodules associated with peritumoral vessels and containing abnormal intratumoral vessels. To test the effects of potentially anti-angiogenic agents on tumor growth, we then used STC-1 cells stably transfected with the endostatin-coding sequence. Intrahepatic tumor volume showed no significant change at days 4 and 8, but a dramatic decrease at day 28 (9.7 ± 1.7% of liver tissue versus 25.2 ± 2.4% in controls), because of a markedly lower number of large nodules (11 ± 1.8% versus 42 ± 5.8%) likely to result from an increased apoptotic index (39.4 ± 5.6% versus 18.3 ± 3.4). Our results suggest that active angiogenesis is not necessary for the engraftment and early growth of endocrine cells metastatic to the liver but is required at a later stage of progression. [Copyright &y& Elsevier]
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- 2008
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