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Pancreatic Neoplasms: HELP
Articles by Ramón Salazar
Based on 13 articles published since 2008
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Between 2008 and 2019, R. Salazar wrote the following 13 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Guideline ENETS Consensus Guidelines Update for the Management of Distant Metastatic Disease of Intestinal, Pancreatic, Bronchial Neuroendocrine Neoplasms (NEN) and NEN of Unknown Primary Site. 2016

Pavel, M / O'Toole, D / Costa, F / Capdevila, J / Gross, D / Kianmanesh, R / Krenning, E / Knigge, U / Salazar, R / Pape, U-F / Öberg, K / Anonymous6880853. ·Charite Virchow Klinikum, Berlin, Germany. ·Neuroendocrinology · Pubmed #26731013.

ABSTRACT: -- No abstract --

2 Review Translational research in neuroendocrine tumors: pitfalls and opportunities. 2017

Capdevila, J / Casanovas, O / Salazar, R / Castellano, D / Segura, A / Fuster, P / Aller, J / García-Carbonero, R / Jimenez-Fonseca, P / Grande, E / Castaño, J P. ·Medical Oncology Department, Vall d'Hebron University Hospital, Vall d'Hebron, Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona, Spain. · ProCURE Research Program, Instituto Catalán de Oncología - IDIBELL, Barcelona, Spain. · Oncology Department, Catalan Institute of Oncology-IDIBELL, Universitat de Barcelona, Barcelona, Spain. · Oncology Department, Hospital Universitario 12 de Octubre, Madrid, Spain. · Oncology Department, Hospital Universitari i Politècnic La Fe, Valencia, Spain. · Oncology Department, Hospital Universitari Son Espases, Palma de Mallorca, Spain. · Department of Endocrinology, Puerta de Hierro University Hospital, Madrid, Spain. · Medical Oncology Department, Hospital Universitario Doce de Octubre, Center affiliated to the Red Tematica de Investigacion Cooperativa en Cancer (RTICC), Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, Madrid, Spain. · Department of Medical Oncology, Central Asturias University Hospital, Oviedo, Spain. · Oncology Department, Hospital Universitario Ramón y Cajal, Madrid, Spain. · Maimónides Institute of Biomedical Research at Córdoba (IMIBIC); Reina Sofía University Hospital; Department of Cell Biology, Physiology and Immunology, University of Córdoba; CIBER Fisiopatología de la Obesidad y Nutrición, Córdoba, Spain. ·Oncogene · Pubmed #27641330.

ABSTRACT: Interest in research on neuroendocrine tumors (NETs) has grown in the past 10 years, coinciding with improvements in our understanding of the molecular pathogenesis of NETs. In addition, NETs have become one of the most exciting settings for drug development. Two targeted agents for the management of advanced pancreatic NETs have been approved, but the development of targeted agents for NETs is limited by problems with both patient selection and demonstration of activity. In this review, we analyze these limitations and discuss ways to increase the predictive value of preclinical models for target discovery and drug development. The role of translational research and 'omics' methodologies is emphasized, with the final aim of developing personalized medicine. Because NETs usually grow slowly and metastatic tumors are found at easily accessible locations, and owing to improvements in techniques for liquid biopsies, NETs provide a unique opportunity to obtain tumor samples at all stages of the evolution of the disease and to adapt treatment to changes in tumor biology. Combining clinical and translational research is essential to achieve progress in the NET field. Slow growth and genetic stability limit and challenge both the availability and further development of preclinical models of NETs, one of the most crucial unmet research needs in the field. Finally, we suggest some useful approaches for improving clinical drug development for NETs: moving from classical RECIST-based response end points to survival parameters; searching for different criteria to define response rates (for example, antiangiogenic effects and metabolic responses); implementing randomized phase II studies to avoid single-arm phase II studies that produce limited data on drug efficacy; and using predictive biomarkers for patient selection.

3 Review Combination of cross-sectional and molecular imaging studies in the localization of gastroenteropancreatic neuroendocrine tumors. 2014

Toumpanakis, Christos / Kim, Michelle K / Rinke, Anja / Bergestuen, Deidi S / Thirlwell, Christina / Khan, Mohid S / Salazar, Ramon / Oberg, Kjell. ·Neuroendocrine Tumour Unit, Royal Free Hospital, London, UK. ·Neuroendocrinology · Pubmed #24458014.

ABSTRACT: Molecular imaging modalities exploit aspects of neuroendocrine tumors (NET) pathophysiology for both diagnostic imaging and therapeutic purposes. The characteristic metabolic pathways of NET determine which tracers are useful for their visualization. In this review, we summarize the diagnostic value of all available molecular imaging studies, present data about their use in daily practice in NET centers globally, and finally make recommendations about the appropriate use of those modalities in specific clinical scenarios. Somatostatin receptor scintigraphy (SRS) continues to have a central role in the diagnostic workup of patients with NET, as it is also widely available. However, and despite the lack of prospective randomized studies, many NET experts predict that Gallium-68 ((68)Ga)-DOTA positron emission tomography (PET) techniques may replace SRS in the future, not only because of their technical advantages, but also because they are superior in patients with small-volume disease, in patients with skeletal metastases, and in those with occult primary tumors. Carbon-11 ((11)C)-5-hydroxy-L-tryptophan (5-HTP) PET and (18)F-dihydroxyphenylalanine ((18)F-DOPA) PET are new molecular imaging techniques of limited availability, and based on retrospective data, their sensitivities seem to be inferior to that of (68)Ga-DOTA PET. Glucagon-like-peptide-1 (GLP-1) receptor imaging seems promising for localization of the primary in benign insulinomas, but is currently available only in a few centers. Fluorine-18 ((18)F)-fluorodeoxyglucose ((18)F-FDG) PET was initially thought to be of limited value in NET, due to their usually slow-growing nature. However, according to subsequent data, (18)F-FDG PET is particularly helpful for visualizing the more aggressive NET, such as poorly differentiated neuroendocrine carcinomas, and well-differentiated tumors with Ki67 values >10%. According to limited data, (18)F-FDG-avid tumor lesions, even in slow-growing NET, may indicate a more aggressive disease course. When a secondary malignancy has already been established or is strongly suspected, combining molecular imaging techniques (e.g. (18)F-FDG PET and (68)Ga-DOTA PET) takes advantage of the diverse avidities of different tumor types to differentiate lesions of different origins. All the above-mentioned molecular imaging studies should always be reviewed and interpreted in a multidisciplinary (tumor board) meeting in combination with the conventional cross-sectional imaging, as the latter remains the imaging of choice for the evaluation of treatment response and disease follow-up.

4 Review Pancreatic NETs: where do we stand now? 2014

Faivre, S / Castellano, D / Strosberg, J / González, E / Salazar, R. ·Department Medical Oncology, Beaujon University Hospital, Clichy, France, sandrine.faivre@bjn.aphp.fr. ·Cancer Metastasis Rev · Pubmed #24452757.

ABSTRACT: The systemic management of patients with pancreatic neuroendocrine tumors includes chemotherapy and targeted agents such as everolimus and sunitinib. Which treatment to favor in a particular patient is not known. The most commonly used chemotherapy agents are streptozocin and temozolamide, often prescribed in combination with fluoropyrimidines. A potential biomarker for selection of temozolomide-based chemotherapy is O-6-methylguanine-DNA-methyltrasferase expression. Chemotherapy yields higher response rates and may be preferable in patients with higher-grade tumors and those who are symptomatic. The mammalian target of rapamycin inhibitor everolimus has shown improvement in progression-free survival (PFS) in a robust, well-conducted phase III study. Everolimus, however, can induce limiting toxicities that may result in treatment discontinuation and does not improve survival. However, the objective response rate is very low. Sunitinib, likewise, increases PFS but the data comes from a smaller trial which was terminated early. Sunitinib displays a different toxicity profile and is associated with a trend towards improved overall survival. It is clear that biomarkers to properly select the most effective agents in an individual patient are needed.

5 Review Incidence, patterns of care and prognostic factors for outcome of gastroenteropancreatic neuroendocrine tumors (GEP-NETs): results from the National Cancer Registry of Spain (RGETNE). 2010

Garcia-Carbonero, R / Capdevila, J / Crespo-Herrero, G / Díaz-Pérez, J A / Martínez Del Prado, M P / Alonso Orduña, V / Sevilla-García, I / Villabona-Artero, C / Beguiristain-Gómez, A / Llanos-Muñoz, M / Marazuela, M / Alvarez-Escola, C / Castellano, D / Vilar, E / Jiménez-Fonseca, P / Teulé, A / Sastre-Valera, J / Benavent-Viñuelas, M / Monleon, A / Salazar, R. ·Department of Medical Oncology, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío, Sevilla. rgcarbonero@hotmail.com ·Ann Oncol · Pubmed #20139156.

ABSTRACT: BACKGROUND: Neuroendocrine tumors (NETs) are an unusual family of neoplasms with a wide and complex spectrum of clinical behavior. Here, we present the first report of a National Cancer Registry of gastroenteropancreatic neuroendocrine tumors from a Southern European country. PATIENTS AND METHODS: Data was provided online at www.retegep.net by participating centers and assessed for internal consistency by external independent reviewers. RESULTS: The study cohort comprised 907 tumors. The most common tumor types were carcinoids (55%), pancreatic nonfunctional tumors (20%), metastatic NETs of unknown primary (9%), insulinomas (8%) and gastrinomas (4%). Forty-four percent presented with distant disease at diagnosis, most often those from small intestine (65%), colon (48%), rectum (40%) and pancreas (38%), being most unusual in appendix primaries (1.3%). Stage at diagnosis varied significantly according to sex, localization of primary tumor, tumor type and grade. Overall 5-year survival was 75.4% (95% confidence interval 71.3% to 79.5%) and was significantly greater in women, younger patients and patients with hormonal syndrome and early stage or lower grade tumors. Prognosis also differed according to tumor type and primary tumor site. However, stage and Ki-67 index were the only independent predictors for survival. CONCLUSION: This national database reveals relevant information regarding epidemiology, current clinical practices and prognosis of NETs in Spain, providing valuable insights that may contribute to understand regional disparities in the incidence, patterns of care and survival of this heterogeneous disease across different continents and countries.

6 Review Gastroenteropancreatic neuroendocrine tumours. 2008

Modlin, Irvin M / Oberg, Kjell / Chung, Daniel C / Jensen, Robert T / de Herder, Wouter W / Thakker, Rajesh V / Caplin, Martyn / Delle Fave, Gianfranco / Kaltsas, Greg A / Krenning, Eric P / Moss, Steven F / Nilsson, Ola / Rindi, Guido / Salazar, Ramon / Ruszniewski, Philippe / Sundin, Anders. ·Department of Gastroenterological Surgery, Yale University, New Haven, CT 06520-8062, USA. imodlin@optonline.net ·Lancet Oncol · Pubmed #18177818.

ABSTRACT: Gastroenteropancreatic (GEP) neuroendocrine tumours (NETs) are fairly rare neoplasms that present many clinical challenges. They secrete peptides and neuroamines that cause distinct clinical syndromes, including carcinoid syndrome. However, many are clinically silent until late presentation with mass effects. Investigation and management should be highly individualised for a patient, taking into consideration the likely natural history of the tumour and general health of the patient. Management strategies include surgery for cure (which is achieved rarely) or for cytoreduction, radiological intervention (by chemoembolisation and radiofrequency ablation), chemotherapy, and somatostatin analogues to control symptoms that result from release of peptides and neuroamines. New biological agents and somatostatin-tagged radionuclides are under investigation. The complexity, heterogeneity, and rarity of GEP NETs have contributed to a paucity of relevant randomised trials and little or no survival increase over the past 30 years. To improve outcome from GEP NETs, a better understanding of their biology is needed, with emphasis on molecular genetics and disease modeling. More-reliable serum markers, better tumour localisation and identification of small lesions, and histological grading systems and classifications with prognostic application are needed. Comparison between treatments is currently very difficult. Progress is unlikely to occur without development of centers of excellence, with dedicated combined clinical teams to coordinate multicentre studies, maintain clinical and tissue databases, and refine molecularly targeted therapeutics.

7 Guideline SEOM clinical guidelines for the diagnosis and treatment of gastroenteropancreatic neuroendocrine tumours (GEP NETS). 2011

García-Carbonero, Rocío / Salazar, Ramón / Sevilla, Isabel / Isla, Dolores. ·Medical Oncology Department, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBIS), Sevilla, Spain. rgcarbonero@hotmail.com ·Clin Transl Oncol · Pubmed #21821488.

ABSTRACT: Gastroenteropancreatic neuroendocrine tumours (GEP NETs) represent a heterogenous family of tumours with growing incidence and challenging clinical management. Unlike other solid tumours, they have the ability to secrete different peptides and neuramines that cause distinct clinical syndromes. However, many are clinically silent until advanced disease. This guideline aims to provide practical recommendations for the diagnosis and treatment of GEP NETs. Most recent histological and staging classifications, as well as available therapeutic approaches, such as surgery, locoregional therapy, peptide receptor radionuclide therapy (PRRT) and hormonal or systemic therapy, are discussed in this manuscript, including some recent relevant achievements with novel targeted agents. Clinical presentation (with or without hormonal syndrome), histological tumour features (including proliferation index (Ki-67) and the presence or not of somatostatin receptors), tumour stage, and location of primary tumour and distant metastasis are all key issues that shall be taken into consideration to properly design and integrate the most adequate therapeutic strategy.

8 Clinical Trial A randomized, open-label, phase 2 study of everolimus in combination with pasireotide LAR or everolimus alone in advanced, well-differentiated, progressive pancreatic neuroendocrine tumors: COOPERATE-2 trial. 2017

Kulke, M H / Ruszniewski, P / Van Cutsem, E / Lombard-Bohas, C / Valle, J W / De Herder, W W / Pavel, M / Degtyarev, E / Brase, J C / Bubuteishvili-Pacaud, L / Voi, M / Salazar, R / Borbath, I / Fazio, N / Smith, D / Capdevila, J / Riechelmann, R P / Yao, J C. ·Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, USA. · Department of Gastroenterology and Pancreatology University of Paris VII and Beaujon Hospital, Paris, France. · Department of Digestive Oncology, University Hospitals Gasthuisberg/Leuven and KU Leuven, Leuven, Belgium. · Department of Medical Oncology, Edouard Herriot Hospital, Lyon, France. · Department of Medical Oncology, University of Manchester/The Christie Hospital, Manchester, UK. · Department of Endocrine Oncology, Erasmus University Medical Center, Rotterdam, The Netherlands. · Department of Hepatology and Gastroenterology, Charité University of Medicine, Berlin, Germany. · Department of Oncology, Novartis AG, Basel, Switzerland. · Department of Oncology, Novartis Pharmaceuticals Corporation, East Hanover, USA. · Department of Medical Oncology, Catalan Institute of Oncology, IDIBELL, Hospital of Barcelona, Barcelona, Spain. · Department of Gastroenterology Saint-Luc University Hospital, Brussels, Belgium. · Department of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, Milan, Italy. · Department of Oncology, St. Andrew Hospital, Bordeaux, France. · Department of Medical Oncology, Vall d'Hebron University Hospital, Barcelona, Spain. · Department of Oncology, Cancer Institute of the State of São Paulo, São Paulo, Brazil. · Department of Gastrointestinal and Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, USA. ·Ann Oncol · Pubmed #28327907.

ABSTRACT: Background: Several studies have demonstrated the antitumor activity of first-generation somatostatin analogs (SSAs), primarily targeting somatostatin receptor (sstr) subtypes 2 and 5, in neuroendocrine tumors (NET). Pasireotide, a second-generation SSA, targets multiple sstr subtypes. We compared the efficacy and safety of pasireotide plus everolimus to everolimus alone in patients with advanced, well-differentiated, progressive pancreatic NET. Patients and methods: Patients were randomized 1 : 1 to receive a combination of everolimus (10 mg/day, orally) and pasireotide long-acting release (60 mg/28 days, intramuscularly) or everolimus alone (10 mg/day, orally); stratified by prior SSA use, and baseline serum chromogranin A and neuron-specific enolase. The primary end point was progression-free survival (PFS). Secondary end points included overall survival, objective response rate, disease control rate, and safety. Biomarker response was evaluated in an exploratory analysis. Results: Of 160 patients enrolled, 79 were randomized to the combination arm and 81 to the everolimus arm. Baseline demographics and disease characteristics were similar between the treatment arms. No significant difference was observed in PFS: 16.8 months in combination arm versus 16.6 months in everolimus arm (hazard ratio, 0.99; 95% confidence interval, 0.64-1.54). Partial responses were observed in 20.3% versus 6.2% of patients in combination arm versus everolimus arm; however, overall disease control rate was similar (77.2% versus 82.7%, respectively). No significant improvement was observed in median overall survival. Adverse events were consistent with the known safety profile of both the drugs; grade 3 or 4 fasting hyperglycemia was seen in 37% versus 11% of patients, respectively. Conclusions: The addition of pasireotide to everolimus was not associated with the improvement in PFS compared with everolimus alone in this study. Further studies to delineate mechanisms by which SSAs slow tumor growth in NET are warranted.

9 Article Prognostic factors and long-term outcome of pancreatic neuroendocrine neoplasms: Ki-67 index shows a greater impact on survival than disease stage. The large experience of the Spanish National Tumor Registry (RGETNE). 2013

Martin-Perez, Elena / Capdevila, Jaume / Castellano, Daniel / Jimenez-Fonseca, Paula / Salazar, Ramon / Beguiristain-Gomez, Adolfo / Alonso-Orduña, Vicente / Martinez Del Prado, Purificacion / Villabona-Artero, Carles / Diaz-Perez, Jose A / Monleon, Antonio / Marazuela, Monica / Pachon, Vanessa / Sastre-Valera, Javier / Sevilla, Isabel / Castaño, Angel / Garcia-Carbonero, Rocio. ·Department of Surgery, University Hospital La Princesa, Madrid, Spain. ·Neuroendocrinology · Pubmed #23988576.

ABSTRACT: INTRODUCTION: Pancreatic neuroendocrine neoplasms (PNENs) are uncommon neoplasms with a wide spectrum of clinical behavior. The objective of this study was to assess in a large cohort of patients the relative impact of prognostic factors on survival. METHODS: From June 2001 through October 2010, 1,271 patients were prospectively registered online (www.getne.org) at the Spanish National Cancer Registry for Gastroenteropancreatic Neuroendocrine Tumors (RGETNE) by participating centers. Clinical and histopathological features were assessed as potential prognostic factors by uni- and multivariate analyses. RESULTS: Of 483 PNENs, 171 (35%) were functional (F) and 312 (65%) non-functional (NF). NF-PNENs were associated with a higher incidence of histological features denoting more aggressive disease, such as poor tumor differentiation, Ki-67 >20%, or vascular invasion (NF- vs. F-PNENs, respectively, p < 0.05). Nevertheless, functionality was not a significant predictor of survival (p = 0.19). Stage at diagnosis, Ki-67 index, tumor differentiation and surgical resection of the primary tumor were all significant prognostic factors in univariate analysis. However, Ki-67 (>20 vs. ≤2%) (hazard ratio (HR) 2.21, p = 0.01) and surgical resection (yes vs. no) (HR 0.92, p = 0.001) were the only independent predictors of survival in multivariate analysis. Among patients who underwent surgery, high Ki-67 index (HR 10.37, p = 0.02) and poor differentiation (HR 8.16, p = 0.03) were the only independent predictors of clinical outcome. CONCLUSION: Ki-67 index and tumor differentiation are key prognostic factors influencing survival of patients with PNENs and, in contrast to what it is observed for other solid malignancies, they seem to have a greater impact on survival than the extent of disease. This should be borne in mind by physicians in order to appropriately tailor therapeutic strategies and surveillance of these patients.

10 Article ENETS Consensus Guidelines for the management of patients with digestive neuroendocrine neoplasms: functional pancreatic endocrine tumor syndromes. 2012

Jensen, Robert T / Cadiot, Guillaume / Brandi, Maria L / de Herder, Wouter W / Kaltsas, Gregory / Komminoth, Paul / Scoazec, Jean-Yves / Salazar, Ramon / Sauvanet, Alain / Kianmanesh, Reza / Anonymous60716. ·Digestive Diseases Branch, NIH, Bethesda, MD 20892, USA. robertj@bdg10.niddk.nih.gov ·Neuroendocrinology · Pubmed #22261919.

ABSTRACT: -- No abstract --

11 Article ENETS Consensus Guidelines for the management of patients with digestive neuroendocrine neoplasms of the digestive system: well-differentiated pancreatic non-functioning tumors. 2012

Falconi, Massimo / Bartsch, Detlef Klaus / Eriksson, Barbro / Klöppel, Günter / Lopes, José M / O'Connor, Juan M / Salazar, Ramón / Taal, Babs G / Vullierme, Marie Pierre / O'Toole, Dermot / Anonymous30716. ·Department of General Surgery, University of Verona, Verona, Italy. massimo.falconi@univr.it ·Neuroendocrinology · Pubmed #22261872.

ABSTRACT: -- No abstract --

12 Article [Retinal capillary hemangioma and von Hippel-Lindau disease: diagnostic and therapeutic implications]. 2011

Salazar, R / González-Castaño, C / Rozas, P / Castro, J. ·Servicio de Oftalmología, Hospital Universitario Central de Asturias, Oviedo, Principado de Asturias, España. lbenito@vissum.com ·Arch Soc Esp Oftalmol · Pubmed #21798408.

ABSTRACT: CLINICAL CASE: Man carrier of the von Hippel-Lindau (VHL) gene, with long-onset loss of vision in left eye. He had a retinal capillary hemangioma (HCR) and diffuse cystic edema in posterior pole. The systemic study revealed bilateral kidney tumors. Laser photocoagulation was performed which produced a subretinal and vitreous hemorrhage that required vitrectomy. DISCUSSION: Retinal capillary hemangioma (HCR) is the earliest and most frequent manifestation of the von Hippel-Lindau disease. Its detection requires it to be treated early and to rule out other visceral lesions. Laser photocoagulation is the most recommended treatment of small-size HCR. The most frequent complications are vitreous and subretinal haemorrhages.

13 Article PRL-3 overexpression in epithelial cells is induced by surrounding stromal fibroblasts. 2009

Molleví, David G / Aytes, Alvaro / Berdiel, Mireia / Padullés, Laura / Martínez-Iniesta, Maria / Sanjuan, Xavier / Salazar, Ramon / Villanueva, Alberto. ·Translational Research Laboratory, Institut Català d'Oncologia, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), 08907 L'Hospitalet de Llobregat, Barcelona, Spain. dgmollevi@iconcologia.net ·Mol Cancer · Pubmed #19586538.

ABSTRACT: We isolate and culture carcinoma-associated fibroblasts (CAFs) from primary tumour (CAFpt), CAFs from corresponding synchronous liver metastasis (CAFlm) as well as normal colonic fibroblasts (NCF) from the same patient. From these cultures, conditioned media (CM) was obtained. Culture of a wide panel of colorectal and pancreatic cell lines in CM from CAFlm resulted in overexpression of mRNA PRL-3 and higher overexpression in CAFs than in non-activated fibroblasts. Moreover PRL-3 mRNA expression correlates with expression of alpha-SMA and deposition of collagen fibrils in the stroma. We demonstrate that products secreted by CAFs trigger PRL-3 overexpression in cancer cells. Identification of these factors may contribute to new stroma-targeted therapies for desmoplastic tumours.