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Pancreatic Neoplasms: HELP
Articles by Rocío Garcia-Carbonero
Based on 21 articles published since 2009
(Why 21 articles?)
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Between 2009 and 2019, R. García-Carbonero wrote the following 21 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Guideline ENETS Consensus Guidelines for High-Grade Gastroenteropancreatic Neuroendocrine Tumors and Neuroendocrine Carcinomas. 2016

Garcia-Carbonero, R / Sorbye, H / Baudin, E / Raymond, E / Wiedenmann, B / Niederle, B / Sedlackova, E / Toumpanakis, C / Anlauf, M / Cwikla, J B / Caplin, M / O'Toole, D / Perren, A / Anonymous6950853. ·Medical Oncology Department, Hospital Universitario Doce de Octubre, Madrid, Spain. ·Neuroendocrinology · Pubmed #26731334.

ABSTRACT: -- No abstract --

2 Guideline SEOM clinical guidelines for the diagnosis and treatment of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) 2014. 2014

Garcia-Carbonero, R / JImenez-Fonseca, P / Teulé, A / Barriuso, J / Sevilla, I / Anonymous2520805. ·Medical Oncology Department, Hospital Universitario Virgen del Rocio, Instituto de Biomedicina de Sevilla (IBIS) (Universidad de Sevilla, CSIC, HUVR), Center affiliated to the Red Temática de Investigación Cooperativa en Cancer (RTICC), Instituto Carlos III, Spanish Ministry of Science and Innovation, Av. Manuel Siurot, s/n, 41013, Seville, Spain, rgcarbonero@gmail.com. ·Clin Transl Oncol · Pubmed #25183048.

ABSTRACT: GEP-NENs are a challenging family of tumors of growing incidence and varied clinical management and behavior. Diagnostic techniques have substantially improved over the past decades and significant advances have been achieved in the understanding of the molecular pathways governing tumor initiation and progression. This has already translated into relevant advances in the clinic. This guideline aims to provide practical recommendations for the diagnosis and treatment of GEP-NENs. Diagnostic workup, histological and staging classifications, and the different available therapeutic approaches, including surgery, liver-directed ablative therapies, peptide receptor radionuclide therapy, and systemic hormonal, cytotoxic or targeted therapy, are briefly discussed in this manuscript. Clinical presentation (performance status, comorbidities, tumor-derived symptoms and hormone syndrome in functioning tumors), histological features [tumor differentiation, proliferation rate (Ki-67), and expression of somatostatin receptors], disease localization and extent, and resectability of primary and metastatic disease, are all key issues that shall be taken into consideration to appropriately tailor therapeutic strategies and surveillance of these patients.

3 Editorial Gastroenteropancreatic neuroendocrine tumors: current perspectives and future challenges. 2014

Garcia-Carbonero, Rocio. ·Oncology Department, Hospital Universitario Virgen del Rocío Instituto de Biomedicina de Sevilla (IBIS) [Universidad de Sevilla, CSIC, HUVR], Avenida Manuel Siurot S/N, 41013, Sevilla, Spain, rgcarbonero@gmail.com. ·Cancer Metastasis Rev · Pubmed #24357057.

ABSTRACT: -- No abstract --

4 Review Optimizing Somatostatin Analog Use in Well or Moderately Differentiated Gastroenteropancreatic Neuroendocrine Tumors. 2017

Carmona-Bayonas, Alberto / Jiménez-Fonseca, Paula / Custodio, Ana / Grande, Enrique / Capdevila, Jaume / López, Carlos / Teule, Alex / Garcia-Carbonero, Rocío / Anonymous24040919. ·Department of Hematology and Medical Oncology, Morales Meseguer University Hospital, Calle Marqués de los Vélez, s/n, CP 30008, Murcia, Spain. alberto.carmonabayonas@gmail.com. · Department of Medical Oncology, Central Asturias University Hospital, Oviedo, Spain. · Department of Medical Oncology, La Paz University Hospital, Madrid, Spain. · Department of Medical Oncology, Ramón y Cajal University Hospital, Madrid, Spain. · Department of Medical Oncology, Vall D'Hebrón University Hospital, Vall D'Hebrón Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, center affiliated with the Red Temática de Investigación Cooperativa en Cáncer (RTICC), Instituto Carlos III, Spanish Ministry of Science and Innovation, Barcelona, Spain. · Department of Medical Oncology, Marqués de Valdecilla University Hospital, Santander, Spain. · Department of Medical Oncology, Institut Català d'Oncologia, L'Hospitalet de Llobregat, center affiliated with the Red Temática de Investigación Cooperativa en Cáncer (RTICC), Instituto Carlos III, Spanish Ministry of Science and Innovation, Barcelona, Spain. · Department of Medical Oncology, Doce de Octubre University Hospital, center affiliated with the Red Temática de Investigación Cooperativa en Cáncer (RTICC), Instituto Carlos III, Spanish Ministry of Science and Innovation, Madrid, Spain. ·Curr Oncol Rep · Pubmed #28920153.

ABSTRACT: BACKGROUND: Somatostatin analogues, aiming to control tumor secretion or growth, constitute the most attractive therapeutic option for patients with well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs). The objective of this article is to provide a comprehensive review of the current state-of-the-art knowledge gaps and potential opportunities for future development and optimization of this therapeutic modality. METHOD: A contextualized systematic review with a narrative component was conducted using PubMed, The Cochrane Library, EMBASE, and Google Scholar. Titles were screened, and non-English, duplicate, or irrelevant entries were excluded. Selection criteria for articles included the following: publication in English between 1995 and 2016, patients with GEP-NETs, analysis of efficacy, safety, practical management considerations, predictive factors, and/or strategies for overcoming resistance, concerning somatostatin analogs. RESULTS: Ninety-seven studies out of 2771 screened publications met the inclusion criteria (16 randomized clinical trials, 27 phase II trials, 3 phase I trials, 3 subgroup analyses of clinical trials, 1 open-label extension of a randomized trial, 1 phase IV trial, 32 observational studies, and 14 basic research articles). The nature and scope of literature was diverse with most articles dedicated to drug efficacy or indications of use (n = 49), pharmacological issues (n = 8), assessment or predictors of response (n = 4), practical management (n = 11), combination therapy or other means to overcome resistance (n = 19), receptors and signaling pathways (n = 3), and subgroup analyses (n = 3). CONCLUSION: In this appraisal, we have found some practical aspects that can help to the optimization of somatostatin analog (SSA) therapy in patients with well-differentiated GEP-NETs. We have also identified areas of uncertainty in an effort to guide clinical research in the coming years.

5 Review The Antiproliferative Role of Lanreotide in Controlling Growth of Neuroendocrine Tumors: A Systematic Review. 2017

Michael, Michael / Garcia-Carbonero, Rocio / Weber, Matthias M / Lombard-Bohas, Catherine / Toumpanakis, Christos / Hicks, Rodney J. ·Neuorendocrine Service & Division of Cancer Medicine, Peter MacCallum Cancer Centre, St. Andrews Place, East Melbourne, Australia Michael.Michael@petermac.org. · Hospital Universitario Doce de Octubre, Madrid, Spain. · University Hospital Mainz, Mainz, Germany. · Hôpital Édouard-Herriot, Fédération des spécialités digestives, Lyon, France. · Neuroendocrine Tumour Unit, Royal Free Hospital, London, United Kingdom. · Cancer Imaging & Neuroendocrine Service & Molecular Imaging and Targeted Therapeutics Laboratory, Peter MacCallum Cancer Centre, St. Andrews Place, East Melbourne, Australia. ·Oncologist · Pubmed #28220021.

ABSTRACT: BACKGROUND: Neuroendocrine tumors (NETs) are a heterogeneous group of tumors, with >50% of cases involving the gastrointestinal system or pancreas. Somatostatin analogs (SSAs) are used for treating NET-related secretory syndromes and, more recently, for their antiproliferative effects. We conducted a systematic review of published literature on the antiproliferative efficacy and safety of the SSA lanreotide Autogel in the management of NETs to gain a fuller understanding of the evidence and identify future areas of research. METHODS: Searches were conducted in PubMed up to March 16, 2016, and in the proceedings of four congresses from 2013 to 2016. RESULTS: Screening of 1,132 publications identified in the searches found 40 relevant publications, including 27 full-length publications and 13 congress abstracts. Twenty-four of these publications reported antiproliferative efficacy data for lanreotide Autogel. The CLARINET study showed that 120 mg lanreotide Autogel every 4 weeks improves progression-free survival (PFS) in patients with gastroenteropancreatic (GEP)-NETs, with grade 1 or grade 2 (Ki-67 <10%) disease, providing class I evidence of its antiproliferative effects. The CLARINET open-label extension study reported a median PFS of 32.8 months with lanreotide Autogel. Other smaller studies generally support CLARINET. CONCLUSION: Current clinical evidence shows that lanreotide Autogel has good antiproliferative activity with favorable safety and tolerability in patients with GEP-NETs, suggesting it should be considered as an early first-line treatment in this population. Further studies are needed to assess the potential benefits of higher doses and the use of lanreotide Autogel in combination therapy and as maintenance therapy in the absence of disease progression following other therapies.

6 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.

7 Review Imaging approaches to assess the therapeutic response of gastroenteropancreatic neuroendocrine tumors (GEP-NETs): current perspectives and future trends of an exciting field in development. 2015

Garcia-Carbonero, Rocio / Garcia-Figueiras, Roberto / Carmona-Bayonas, Alberto / Sevilla, Isabel / Teule, Alex / Quindos, Maria / Grande, Enrique / Capdevila, Jaume / Aller, Javier / Arbizu, Javier / Jimenez-Fonseca, Paula / Anonymous5380844. ·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, Av. Cordoba km 5.4, 28041, Madrid, Spain. rgcarbonero@gmail.com. · Radiology Department, Complexo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, Spain. · Hematology and Medical Oncology Department, Hospital Universitario Morales Meseguer, Murcia, Spain. · Medical Oncology Department, Hospital Universitario Virgen de la Victoria y Hospital Regional Universitario, Málaga, Spain. · Medical Oncology Department, Instituto Catalán de Oncología (ICO), Center affiliated to the Red Tematica de Investigacion Cooperativa en Cancer (RTICC), Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, Seville, Spain. · Medical Oncology Department, Complejo Hospitalario Universitario, A Coruña, Spain. · Medical Oncology Department, Hospital Ramon y Cajal, Madrid, Spain. · Medical Oncology Department, Hospital Vall d'Hebron, Center affiliated to the Red Tematica de Investigacion Cooperativa en Cancer (RTICC), Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, Barcelona, Spain. · Endocrinology Department, Hospital Puerta de Hierro, Madrid, Spain. · Nuclear Medicine Department, Clinica Universidad de Navarra, Navarra, Spain. · Medical Oncology Department, Hospital Universitario Central de Asturias, Oviedo, Spain. ·Cancer Metastasis Rev · Pubmed #26433592.

ABSTRACT: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a family of neoplasms with a complex spectrum of clinical behavior. Although generally more indolent than carcinomas, once they progress beyond surgical resectability, they are essentially incurable. Systemic treatment options have substantially expanded in recent years for the management of advanced disease. Imaging plays a major role in new drug development, as it is the main tool used to objectively evaluate response to novel agents. However, current standard response criteria have proven suboptimal for the assessment of the antiproliferative effect of many targeted agents, particularly in the context of slow-growing tumors such as well-differentiated NETs. The aims of this article are to discuss the advantages and limitations of conventional radiological techniques and standard response assessment criteria and to review novel imaging modalities in development as well as alternative cancer- and therapy-specific criteria to assess drug efficacy in the field of GEP-NETs.

8 Review Health-related quality of life in well-differentiated metastatic gastroenteropancreatic neuroendocrine tumors. 2015

Jiménez-Fonseca, P / Carmona-Bayonas, A / Martín-Pérez, E / Crespo, G / Serrano, R / Llanos, M / Villabona, C / García-Carbonero, R / Aller, J / Capdevila, J / Grande, E / Anonymous5620838. ·Department of Medical Oncology, Central Asturias University Hospital, C/ Avenida de Roma sn, Oviedo, 33011, Asturias, Spain. palucaji@hotmail.com. · Department of Hematology and Medical Oncology, Morales Meseguer University Hospital, Murcia, Spain. · Department of General Surgery, La Princesa University Hospital, Madrid, Spain. · Department of Medical Oncology, Burgos University Hospital, Burgos, Spain. · Department of Medical Oncology, Reina Sofia University Hospital, Córdoba, Spain. · Department of Medical Oncology, Canarias University Hospital, Tenerife, Spain. · Department of Endocrinology, Bellvitge University Hospital, Hospitalet de Llobregat, Barcelona, Spain. · Department of Medical Oncology, Virgen del Rocio University Hospital, Instituto de Biomedicina de Sevilla (IBIS) [Universidad de Sevilla, CSIC, HUVR], Center affiliated with the Red Temática de Investigación Cooperativa en Cancer (RTICC), Instituto Carlos III, Spanish Ministry of Science and Innovation, Sevilla, Spain. · Department of Endocrinology, Puerta de Hierro University Hospital, Madrid, Spain. · Department of Medical Oncology, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Center affiliated with the Red Temática de Investigación Cooperativa en Cancer (RTICC), Instituto Carlos III, Spanish Ministry of Science and Innovation, Barcelona, Spain. · Department of Medical Oncology, Ramon y Cajal University Hospital, Madrid, Spain. ·Cancer Metastasis Rev · Pubmed #26245646.

ABSTRACT: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare neoplasms capable of producing hormones. The development of new treatments has improved progression-free survival, albeit with increased toxicity. Health-related quality of life (HRQoL) has become an important endpoint in clinical research to evaluate patients' well-being in such a contradictory scenario. In this review, we examine key reported outcomes across clinical studies exploring HRQoL in patients with GEP-NETs. We have conducted a review of the literature using PubMed, The Cochrane Library, EMBASE, and Google Scholar. Selection criteria for articles were (1) publication in English between 1995 and 2014, (2) patients with GEP-NET, and (3) analysis of HRQoL, including mental health and psychological symptoms. Forty-nine studies met the inclusion criteria (31 clinical trials, 14 observational studies, and 4 developments of NET-specific HRQoL instruments). The scope and nature of the literature was diverse with 27 instruments used to measure aspects of HRQoL. EORTC QLQ-C30 was the most frequently used, in 38 of the 49 studies. Standardized measures revealed that in spite of generally good HRQoL, GEP-NET patients have specific psychological and physical complaints. The clinical benefit of somatostatin analogs and sunitinib has been clearly supported by HRQoL assessment. Improvement in HRQoL scores or symptom relief over time was also reported in 14 trials of peptide receptor radionuclide therapy, however the absence of randomized studies obviate definitive conclusions. We have also identified several unanswered questions that should be addressed in further research concerning chemotherapy, everolimus, surgery, local ablative therapies, and chemoembolization. Future research should incorporate GEP-NET-specific HRQoL instruments into phase III trials. This review may help both clinicians and researchers to select the most appropriate tools to assess changes in HRQoL in this population.

9 Review Systemic therapeutic strategies for GEP-NETS: what can we expect in the future? 2014

Raymond, E / García-Carbonero, R / Wiedenmann, B / Grande, E / Pavel, M. ·Department of Medical Oncology, Beaujon University Hospital, Clichy, France, eric.raymond@bjn.aphp.fr. ·Cancer Metastasis Rev · Pubmed #24375390.

ABSTRACT: Over the last few years, there have been important advances in the understanding of the molecular biology of neuroendocrine tumors (NETs) that have already translated into relevant advances in the clinic. Several studies have extensively assessed the mutational profile of NETs, and have shown the key roles that angiogenesis and the PI3K-AKT-mTOR pathway play in the pathogenesis of these tumors. Recent data has also revealed the potential relevance of transcription factors such as death domain-associated protein, x-linked mental retardation, and α-thalassemia syndrome protein or ataxia telangiectasia-mutated in NETs of pancreatic origin. This fast progress is leading to a rapidly increasing number of new agents being explored in the field of NETs. However, and despite some unquestionable success, objective remission rates remain low, and evidence of a substantial survival impact is lacking. Thus, there is an important need to improve our ability to identify patients most likely to benefit from specific therapies, and to incorporate biomarkers in the management of NETs. In addition, further efforts to understand mechanisms of escape and acquired resistance to the different available agents is of utmost importance, and will likely require performing paired tumor biopsies (prior and after treatment) or sequential sampling of surrogate tissues. Combinations of approved agents with new agents, either in a rational or biomarker-driven manner, are certainly warranted in this field. Likewise, sequential strategies to modulate and compensate for escape phenomenons are also of great interest. It should also be noted, however, that targeted agents are not innocuous and frequently yield toxicities that need to be adequately addressed by experienced specialists, particularly when drug combinations are considered. This review summarizes the salient data on biomarker and new agent development for the treatment of NETs.

10 Review New targeted agents in gastroenteropancreatic neuroendocrine tumors. 2012

Benavent, Marta / de Miguel, Maria Jose / Garcia-Carbonero, Rocio. ·Department of Medical Oncology, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBIS) [HUVR, CSIC, Universidad de Sevilla], Av. Manuel Siurot, s/n, 41013, Sevilla, Spain. ·Target Oncol · Pubmed #22585431.

ABSTRACT: Neuroendocrine carcinomas are rare neoplasms although of increasing incidence and concern. While traditionally considered of indolent nature, once they progress beyond surgical resectability, the outcome is ultimately fatal for the majority of patients. Somatostatin analogs are useful to control symptoms in functioning tumors and may slow tumor progression in certain disease settings, but sensitivity to conventional cytotoxic chemotherapy is rather limited. In this context, results of the recently published randomized trials with sunitinib and everolimus have demonstrated for the first time that there are agents able to positively impact on the natural history of this complex disease. In this review, we will discuss available data on angiogenesis and mammalian target of rapamycin inhibitors for the treatment of advanced well-differentiated gastroenteropancreatic neuroendocrine tumors.

11 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.

12 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.

13 Clinical Trial Pazopanib in pretreated advanced neuroendocrine tumors: a phase II, open-label trial of the Spanish Task Force Group for Neuroendocrine Tumors (GETNE). 2015

Grande, E / Capdevila, J / Castellano, D / Teulé, A / Durán, I / Fuster, J / Sevilla, I / Escudero, P / Sastre, J / García-Donas, J / Casanovas, O / Earl, J / Ortega, L / Apellaniz-Ruiz, M / Rodriguez-Antona, C / Alonso-Gordoa, T / Díez, J J / Carrato, A / García-Carbonero, R. ·Department of Medical Oncology, Ramón y Cajal University Hospital, Madrid egrande@oncologiahrc.com. · Department of Medical Oncology, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona. · Department of Medical Oncology, I + 12 Research Institute, 12 de Octubre University Hospital, Madrid. · Department of Medical Oncology, IDIBELL, Catalan Institute of Oncology L'Hospitalet, Barcelona. · Department of Medical Oncology, Instituto de Biomedicina de Sevilla (IBIS) [HUVR, CSIC, University of Seville], Virgen del Rocío University Hospital, Seville. · Department of Medical Oncology, Son Espases Hospital, Palma de Mallorca. · Department of Medical Oncology, Virgen de la Victoria University Hospital, Malaga. · Department of Medical Oncology, Clínico Lozano Blesa University Hospital, Zaragoza. · Department of Medical Oncology, Clínico San Carlos Hospital, Madrid. · Department of Medical Oncology, Centro Integral Oncológico Clara Campal, Madrid. · Tumor Angiogenesis Group, IDIBELL, Catalan Institute of Oncology L'Hospitalet, Barcelona. · Department of Medical Oncology Research Laboratory, Ramón y Cajal University Hospital, Madrid. · Department of Pathology, Clínico San Carlos Hospital, Madrid. · Hereditary Endocrine Cancer Group, Spanish National Cancer Research Center, ISCIII Center for Biomedical Research on Rare Disease (CIBERER) Madrid, Madrid. · Department of Medical Oncology, Ramón y Cajal University Hospital, Madrid. · Department of Endocrinology, Ramón y Cajal University Hospital, Madrid, Spain. ·Ann Oncol · Pubmed #26063633.

ABSTRACT: BACKGROUND: The management of advanced neuroendocrine tumors (NETs) has recently changed. We assessed the activity of pazopanib after failure of other systemic treatments in advanced NETs. METHODS: This was a multicenter, open-label, phase II study evaluating pazopanib as a single agent in advanced NETs (PAZONET study). The clinical benefit rate (CBR) at 6 months was the primary end point. Translational correlation of radiological response and progression-free survival (PFS) with circulating and tissue biomarkers was also evaluated. RESULTS: A total of 44 patients were enrolled. Twenty-five patients (59.5%) were progression-free at 6 months (4 partial responses, 21 stable diseases) with a median PFS of 9.5 months [95% confidence interval (CI) 4.8-14.1]. The CBR varied according to prior therapy received, with 73%, 60% and 25% in patients treated with prior multitarget inhibitors, prior mTOR inhibitors and both agents, respectively. A nonsignificant increase in PFS was observed in patients presenting lower baseline circulating tumor cell (CTC) counts (9.1 versus 5.8 months; P = 0.22) and in those with decreased levels of soluble-vascular endothelial growth factor receptor-2 (sVEGFR-2) (12.6 versus 9.1 months; P = 0.067). A trend toward reduced survival was documented in patients with VEGFR3 rs307821 and rs307826 missense polymorphisms [hazard ratio (HR): 12.3; 95% CI 1.09-139.2; P = 0.042 and HR: 6.9; 95% CI 0.96-49.9; P = 0.055, respectively]. CONCLUSIONS: Pazopanib showed clinical activity in patients with advanced NETs regardless of previous treatments. Additionally, CTCs, soluble-s VEFGR-2 and VEGFR3 gene polymorphisms constitute potential biomarkers for selecting patients for pazopanib (NCT01280201). CLINICAL TRIAL NUMBER: NCT01280201.

14 Article SEOM clinical guidelines for the diagnosis and treatment of gastroenteropancreatic and bronchial neuroendocrine neoplasms (NENs) (2018). 2019

González-Flores, E / Serrano, R / Sevilla, I / Viúdez, A / Barriuso, J / Benavent, M / Capdevila, J / Jimenez-Fonseca, P / López, C / Garcia-Carbonero, R. ·Department of Medical Oncology, Hospital Universitario Virgen de las Nieves, Granada, Spain. · Department of Medical Oncology, Hospital Reina Sofía, Córdoba, IMIBIC, CIBERONC, Córdoba, Spain. · Department of Medical Oncology, Instituto de Investigaciones Biomédicas de Málaga (IBIMA)/Hospitales Universitarios Regional y Virgen de la Victoria de Málaga, Málaga, Spain. · Department of Medical Oncology, Complejo Hospitalario de Navarra (CHN), OncobionaTras Unit, Navarrabiomed, IdiSNA, Pamplona, Spain. · Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK. · Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK. · Department of Medical Oncology, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina, Seville, Spain. · Department of Medical Oncology, Vall Hebron University Hospital, Vall Hebron Institute of Oncology (VIHO), Barcelona, Spain. · Department of Medical Oncology, Hospital Universitario Central de Asturias, Oviedo, Spain. · Department of Medical Oncology, Hospital Universitario Marqués de Valdecilla, Santander, Spain. · Department of Medical Oncology, Hospital Universitario 12 de Octubre, IIS imas12, UCM, CNIO, CIBERONC, Av. de Córdoba, s/n, 28041, Madrid, Spain. rgcarbonero@gmail.com. ·Clin Transl Oncol · Pubmed #30535553.

ABSTRACT: NENs are a heterogeneous family of tumors of challenging diagnosis and clinical management. Their incidence and prevalence continue to rise across all sites, stages and grades. Although improved diagnostic techniques have led to earlier detection and stage migration, the improved prognosis documented over time for advanced gastrointestinal and pancreatic neuroendocrine tumors also reflect improvements in therapy. The aim of this guideline is to update practical recommendations for the diagnosis and treatment of gastroenteropancreatic and lung NENs. Diagnostic procedures, histological classification and therapeutic options are briefly discussed, including surgery, liver-directed therapy, peptide receptor radionuclide therapy, and systemic hormonal, cytotoxic or targeted therapy, and treatment algorithms are provided.

15 Article Management of controversial gastroenteropancreatic neuroendocrine tumour clinical situations with somatostatin analogues: results of a Delphi questionnaire panel from the NETPraxis program. 2016

Sevilla, Isabel / Segura, Ángel / Capdevila, Jaume / López, Carlos / García-Carbonero, Rocío / Grande, Enrique / Anonymous1511016. ·Oncology Unit. Hospital Clínico y Regional de Málaga, Colonia Santa Inés s/n, Málaga, 29010, Spain. isevilla02@yahoo.es. · Oncology Unit. Hospital Universitario La Fe, Avda. de Fernando Abril Martorell 106, 46026, Valencia, Spain. · Oncology Unit. Hospital Vall d'Hebron, Pg de la Vall d'Hebron 119-129, 08035, Barcelona, Spain. · Oncology Unit. Hospital Marqués de Valdecilla, Avda. Valdecilla 25, 39008, Santander, Spain. · Oncology Unit. Hospital Universitario 12 de Octubre, Avda. de Córdoba s/n, 28041, Madrid, Spain. · Oncology Unit. Hospital Universitario Ramón y Cajal, Ctra. de Colmenar Viejo km. 9.100, 28034, Madrid, Spain. ·BMC Cancer · Pubmed #27821081.

ABSTRACT: BACKGROUND: There are clinical situations (CS) in which the use of somatostatin analogs (SSAs) in patients with neuroendocrine tumors (NET) is controversial due to lack of evidence. A Delphi study was conducted to develop common treatment guidelines for these CS, based on clinical practice and expert opinion of Spanish oncologists. METHODS: A scientific committee identified 5 CS with a common core (c-c) [non-functioning NET, not susceptible of surgery/locoregional therapy, Ki67 < 10 % (except for CS5: >10 %), ECOG ≤ 2], and controversy regarding use of SSAs, and prepared a Delphi questionnaire of 48 treatment statements. Statements were rated on a 1 (completely disagree) to 9 (completely agree) scale. Responses were grouped by tertiles: 1-3: Disagreement, 4-6: Neutral, 7-9: Agreement. Consensus was reached when the responses of ≥2/3 participants were located in the same tertile as the median value of all reported responses for that statement. RESULTS: Sixty five (81.2 %) of 80 invited oncologists with experience in the management of NETs answered a first round of the questionnaire and 57 (87.7 %) of those 65 answered a second round (mean age 43.5 years; 53.8 % women; median time of experience 9 years). Consensus was obtained in 42 (36 agreement and 6 disagreement) of the 48 statements (87.5 %). Regarding CS1 (Enteropancreatic NET, c-c, non-progressive in the last 3-6 months), overall, SSA treatment is recommended (a wait and see approach is anecdotal and reserved for fragile patients or with low tumor load or ki-67 < 2 %); CS2 (Pancreatic NET, c-c), overall, SSA monotherapy is recommended, except when high tumor load or tumor progression exists, where combination therapy would be considered; CS3 [Gastroenteropancreatic (GEP)-NET, c-c, in treatment with anti-proliferative dose of SSA and progressing], overall, SSA maintenance is recommended at the time of progression, with or without adding molecular targeted drugs; CS4 (GEP-NET, c-c, and negative octreoscan®), SSA in monotherapy is only considered in low-risk patients (low tumor load and Ki-67 < 5 %); CS5 [GEP-NET, c-c (ki67 > 10 %), and positive octreoscan®], monotherapy with SSA is mainly considered in patients with comorbidities. CONCLUSION: Several recommendations regarding use of SSAs in controversial NET CS were reached in consensus and might be considered as treatment guideline.

16 Article Guidelines for biomarker testing in gastroenteropancreatic neuroendocrine neoplasms: a national consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology. 2014

García-Carbonero, R / Vilardell, F / Jiménez-Fonseca, P / González-Campora, R / González, E / Cuatrecasas, M / Capdevila, J / Aranda, I / Barriuso, J / Matías-Guiu, X / Anonymous4350760 / Anonymous4360760. ·Medical Oncology Department, Virgen del Rocío University Hospital, Biomedicine Institute of Sevilla (IBIS) [University of Sevilla, CSIC, HUVR], Avenida Manuel Siurot, S/N, 41013, Seville, Spain, rgcarbonero@gmail.com. ·Clin Transl Oncol · Pubmed #23749327.

ABSTRACT: The annual incidence of neuroendocrine tumours in the Caucasian population ranges from 2.5 to 5 new cases per 100,000 inhabitants. Gastroenteropancreatic neuroendocrine tumours is a family of neoplasms widely variable in terms of anatomical location, hormone composition, clinical syndromes they cause and in their biological behaviour. This high complexity and clinical heterogeneity, together with the known difficulty of predicting their behaviour from their pathological features, are reflected in the many classifications that have been developed over the years in this field. This article reviews the main tissue and clinical biomarkers and makes recommendations for their use in medical practice. This document represents a consensus reached jointly by the Spanish Society of Medical Oncology (SEOM) and the Spanish Society of Pathology (SEAP).

17 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.

18 Article Epithelial-mesenchymal transition markers in the differential diagnosis of gastroenteropancreatic neuroendocrine tumors. 2013

Galván, Jose A / Astudillo, Aurora / Vallina, Aitana / Fonseca, Paula J / Gómez-Izquierdo, Lourdes / García-Carbonero, Rocío / González, Maria Victoria. ·Laboratorio del Banco de Tumores-Anatomia Patológica, c/ Celestino Villamil, s/n, 33006 Oviedo, Spain. galvanjose@uniovi.es ·Am J Clin Pathol · Pubmed #23765535.

ABSTRACT: OBJECTIVES: To elucidate the role of epithelial-mesenchymal transition markers in gastroenteropancreatic neuroendocrine tumors (GEP NETs) and the potential usefulness in their clinical management. METHODS: One hundred ten GEP NET paraffin-embedded samples were immunohistochemically analyzed for E-cadherin, N-cadherin, β-catenin, vimentin, Snail1, Snail2, Twist, and Foxc2 protein expression. RESULTS: The 5-year survival rate was reduced for those patients showing high Snail1 protein levels, a cytoplasmic E-cadherin pattern, reduced N-cadherin expression, and loss of E-cadherin/β-catenin adhesion complex integrity at the cell membrane. Interestingly, high β-catenin expression was useful in identifying a grade 1 NET subgroup with a favorable clinical course. Importantly, it also helped to discriminate small-cell vs large-cell grade 3 neuroendocrine carcinomas. CONCLUSIONS: β-Catenin and N-cadherin immunohistochemical detection might be a useful tool in the differential diagnosis of small-cell vs large-cell G3 neuroendocrine carcinomas. High Snail1 and Foxc2 expression is associated with the invasion and metastatic spread of GEP NETs.

19 Article Immunohistochemical assessment of Pax8 expression during pancreatic islet development and in human neuroendocrine tumors. 2011

Lorenzo, Petra I / Jimenez Moreno, Carmen M / Delgado, Irene / Cobo-Vuilleumier, Nadia / Meier, Raphael / Gomez-Izquierdo, Lourdes / Berney, Thierry / Garcia-Carbonero, Rocio / Rojas, Anabel / Gauthier, Benoit R. ·Pancreatic Islet Development and Regeneration Unit, Department of Stem Cells, Andalusian Center for Molecular Biology and Regenerative Medicine, Seville, Spain. ·Histochem Cell Biol · Pubmed #21932072.

ABSTRACT: The paired box transcription factor Pax8 is critical for development of the eye, thyroid gland as well as the urinary and reproductive organs. In adult, Pax8 overexpression is associated with kidney, ovarian and thyroid tumors and has emerged as a specific marker for these cancers. Recently, Pax8 expression was also reported in human pancreatic islets and in neuroendocrine tumors, identifying Pax8 as a novel member of the Pax family expressed in the pancreas. Herein, we sought to provide a comprehensive analysis of Pax8 expression during pancreogenesis and in adult islets. Immunohistochemical analysis using the most employed Pax8 polyclonal antibody revealed strong nuclear staining in the developing mouse pancreas and in mature human and mouse islets. Astonishingly, Pax8 mRNA in mouse islets was undetectable while human islets exhibited low levels. These discrepancies raised the possibility of antibody cross-reactivity. This premise was confirmed by demonstrating that the polyclonal Pax8 antibody also recognized the islet-enriched Pax6 protein both by Western blotting and immunohistochemistry. Thus, in islets polyclonal Pax8 staining corresponds mainly to Pax6. In order to circumvent this caveat, a novel Pax8 monoclonal antibody was used to re-evaluate whether Pax8 was indeed expressed in islets. Surprisingly, Pax8 was not detected in neither the developing pancreas or in mature islets. Reappraisal of pancreatic neuroendocrine tumors using this Pax8 monoclonal antibody exhibited no immunostaining as compared to the Pax8 polyclonal antibody. In conclusion, Pax8 is not expressed in the pancreas and cast doubts on the value of Pax8 as a pancreatic neuroendocrine tumor marker.

20 Article Therapy innovations: tyrosine kinase inhibitors for the treatment of pancreatic neuroendocrine tumors. 2011

Raymond, Eric / Hobday, Timothy / Castellano, Daniel / Reidy-Lagunes, Diane / García-Carbonero, Rocío / Carrato, Alfredo. ·Medical Oncology Department, Beaujon University Hospital, INSERM U728, APHP, Paris 7 University, 100 bd du Général Leclerc, 92880, Clichy, France. eric.raymond@bjn.aphp.fr ·Cancer Metastasis Rev · Pubmed #21308478.

ABSTRACT: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) show limited sensitivity to cytotoxic agents, requiring the search for novel therapies. Recently, data from a phase III trial demonstrated that sunitinib produces a clinically significant improvement in progression-free survival in patients with unresectable, advanced, or metastatic GEP-NETs. Based on this finding, sunitinib became the first targeted drug approved for the treatment of GEP-NETs, paving the way for the approval of other anticancer agents in this drug-orphan disease. To date, results of trials involving other multitargeted tyrosine kinase inhibitors, such as sorafenib, the monoclonal antibody bevacizumab, and insulin-like growth factor 1 receptor inhibitors, have also shown promising results, and some are already being studied in phase III trials. This review updates the results of ongoing trials using inhibitors of growth factors and tyrosine kinase receptors involved in the carcinogenesis of GEP-NETs.

21 Minor Pax8 detection in well-differentiated pancreatic endocrine tumors: how reliable is it? 2011

Moreno, Carmen M Jimenez / Lorenzo, Petra I / Delgado, Irene / Cobo-Vuilleumier, Nadia / Gomez-Izquierdo, Lourdes / Garcia-Carbonero, Rocio / Rojas, Anabel / Gauthier, Benoit R. · ·Am J Surg Pathol · Pubmed #22067332.

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