12 results on '"Valverde, Claudia"'
Search Results
2. Genomic Profiling and Clinical Outcomes of Targeted Therapies in Adult Patients with Soft Tissue Sarcomas.
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Kokkali, Stefania, Georgaki, Eleni, Mandrakis, Georgios, Valverde, Claudia, and Theocharis, Stamatios
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SARCOMA ,NUCLEOTIDE sequencing ,EPITHELIAL tumors ,GASTROINTESTINAL stromal tumors ,TREATMENT effectiveness ,ISOLATION perfusion - Abstract
Genomic profiling has improved our understanding of the pathogenesis of different cancers and led to the development of several targeted therapies, especially in epithelial tumors. In this review, we focus on the clinical utility of next-generation sequencing (NGS) to inform therapeutics in soft tissue sarcoma (STS). The role of NGS is still controversial in patients with sarcoma, given the low mutational burden and the lack of recurrent targetable alterations in most of the sarcoma histotypes. The clinical impact of genomic profiling in STS has not been investigated prospectively. A limited number of retrospective, mainly single-institution, studies have addressed this issue using various NGS technologies and platforms and a variety of criteria to define a genomic alteration as actionable. Despite the detailed reports on the different gene mutations, fusions, or amplifications that were detected, data on the use and efficacy of targeted treatment are very scarce at present. With the exception of gastrointestinal stromal tumors (GISTs), these targeted therapies are administered either through off-label prescription of an approved drug or enrollment in a matched clinical trial. Based mainly on anecdotal reports, the outcome of targeted therapies in the different STS histotypes is discussed. Prospective studies are warranted to assess whether genomic profiling improves the management of STS patients. [ABSTRACT FROM AUTHOR]
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- 2023
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3. REGISTRI: Regorafenib in first-line of KIT/PDGFRA wild type metastatic GIST: a collaborative Spanish (GEIS), Italian (ISG) and French Sarcoma Group (FSG) phase II trial.
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Martin-Broto, Javier, Valverde, Claudia, Hindi, Nadia, Vincenzi, Bruno, Martinez-Trufero, Javier, Grignani, Giovanni, Italiano, Antoine, Lavernia, Javier, Vallejo, Ana, Tos, Paolo Dei, Le Loarer, Francois, Gonzalez-Campora, Ricardo, Ramos, Rafael, Hernández-Jover, Diana, Gutierrez, Antonio, Serrano, Cesar, Monteagudo, Maria, Letón, Rocio, Robledo, Mercedes, and Moura, David S.
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GASTROINTESTINAL stromal tumors , *REGORAFENIB , *C-kit protein , *COVID-19 pandemic , *PROTEIN-tyrosine kinase inhibitors , *SARCOMA , *DASATINIB - Abstract
Background: Approximately 15% of adult GIST patients harbor tumors that are wild-type for KIT and PDGFRα genes (KP-wtGIST). These tumors usually have SDH deficiencies, exhibit a more indolent behavior and are resistant to imatinib. Underlying oncogenic mechanisms in KP-wtGIST include overexpression of HIF1α high IGFR signaling through the MAPK pathway or BRAF activating mutation, among others. As regorafenib inhibits these signaling pathways, it was hypothesized that it could be more active as upfront therapy in advanced KP-wtGIST. Methods: Adult patients with advanced KP-wtGIST after central confirmation by NGS, naïve of systemic treatment for advanced disease, were included in this international phase II trial. Eligible patients received regorafenib 160 mg per day for 21 days every 28 days. The primary endpoint was disease control rate (DCR), according to RECIST 1.1 at 12 weeks by central radiological assessment. Results: From May 2016 to October 2020, 30 patients were identified as KP-wtGIST by Sanger sequencing and 16 were confirmed by central molecular screening with NGS. Finally, 15 were enrolled and received regorafenib. The study was prematurely closed due to the low accrual worsened by COVID outbreak. The DCR at 12 weeks was 86.7% by central assessment. A subset of 60% experienced some tumor shrinkage, with partial responses and stabilization observed in 13% and 87% respectively, by central assessment. SDH-deficient GIST showed better clinical outcome than other KP-wtGIST. Conclusions: Regorafenib activity in KP-wtGIST compares favorably with other tyrosine kinase inhibitors, especially in the SDH-deficient GIST subset and it should be taken into consideration as upfront therapy of advanced KP-wtGIST. Trial registration: ClinicalTrials.gov Identifier: NCT02638766. [ABSTRACT FROM AUTHOR]
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- 2023
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4. Working to improve the management of sarcoma patients across Europe: a policy checklist
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Kasper, Bernd, Lecointe-Artzner, Estelle, Wait, Suzanne, Boldon, Shannon, Wilson, Roger, Gronchi, Alessandro, Valverde, Claudia, Eriksson, Mikael, Dumont, Sarah, Drove, Nora, Kanli, Athanasia, and Wartenberg, Markus
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- 2018
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5. Ripretinib in gastrointestinal stromal tumor: the long-awaited step forward.
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Lostes-Bardaji, M. Julia, García-Illescas, David, Valverde, Claudia, and Serrano, César
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Gastrointestinal stromal tumor (GIST) represents a paradigm for clinically effective targeted inhibition of oncogenic driver mutations in cancer. Five drugs are currently positioned as the standard of care for the treatment of advanced or metastatic GIST patients. This is the result of continuous, deep understanding of KIT and PDGFRA GIST oncogenic drivers as well as the resistance mechanisms associated to tumor progression. However, the complexity of GIST molecular heterogeneity is an evolving field, and critical questions remain open. Specifically, the clinical benefit of approved and/or investigated targeted agents is strikingly modest at advanced stages of the disease when compared with the activity of first-line imatinib. Ripretinib is a novel switch-pocket inhibitor with broad activity against KIT and PDGFRA oncoproteins and has recently demonstrated antitumoral activity across phase I to phase III clinical trials. Therefore, ripretinib has emerged as a new standard of care for advanced, multi-resistant GIST patients. Based on this data, the Food and Drug Administration has granted in 2020 the approval of ripretinib for GIST patients after progression to imatinib, sunitinib and regorafenib. This, in turn, constitutes a major breakthrough in sarcoma drug development, as there have not been new treatment approvals in GIST for nearly a decade. Herein, we provide a critical review on the preclinical and clinical development of ripretinib in GIST. Furthermore, we seek to assess the biological and clinical impact of this new standard of care on the course of the disease, aiming to provide an insight on future treatments strategies for the next coming years. [ABSTRACT FROM AUTHOR]
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- 2021
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6. Optimization of the Therapeutic Approach to Patients with Sarcoma: Delphi Consensus.
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Álvarez Álvarez, Rosa, Cruz Jurado, Josefina, del Muro Solans, Xavier García, Giner, Javier Lavernia, López Pousa, Antonio, Martín-Broto, Javier, and Valverde, Claudia María
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DISEASE risk factors ,MORTALITY risk factors ,CONSENSUS (Social sciences) ,DELPHI method ,HEALTH care teams ,MEDICAL protocols ,MEDICAL specialties & specialists ,SARCOMA ,DECISION making in clinical medicine ,DISEASE management - Abstract
Soft tissue sarcomas (STS) constitute a heterogeneous group of rare solid tumors associated with significant morbidity and mortality. The evaluation and treatment of STS require a multidisciplinary team with extensive experience in the management of these types of tumors. National and international clinical practice guidelines for STS do not always provide answers to a great many situations that specialists have to contend with in their everyday practice. This consensus provides a series of specific recommendations based on available scientific evidence and the experience of a group of experts to assist in decision-making by all the specialists involved in the management of STS. [ABSTRACT FROM AUTHOR]
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- 2019
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7. Relevance of Reference Centers in Sarcoma Care and Quality Item Evaluation: Results from the Prospective Registry of the Spanish Group for Research in Sarcoma (GEIS).
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Martin‐Broto, Javier, Hindi, Nadia, Cruz, Josefina, Martinez‐Trufero, Javier, Valverde, Claudia, De Sande, Luis M., Sala, Angeles, Bellido, Lorena, De Juan, Ana, Rubió‐Casadevall, Jordi, Diaz‐Beveridge, Roberto, Cubedo, Ricardo, Tendero, Oscar, Salinas, Diego, Gracia, Isidro, Ramos, Rafael, Baguè, Silvia, Gutierrez, Antonio, Duran‐Moreno, José, and Lopez‐Pousa, Antonio
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BIOPSY ,CANCER chemotherapy ,REPORTING of diseases ,HEALTH facilities ,LONGITUDINAL method ,SARCOMA ,SOFT tissue tumors ,TUMOR classification ,TREATMENT effectiveness ,PREOPERATIVE period ,PERIOPERATIVE care ,TUMOR risk factors ,CANCER risk factors - Abstract
Background: Reference centers (RCs) are a key point for improving the survival of patients with soft‐tissue sarcomas (STS). The aim of this study was to evaluate selected items in the management of patients with STS, comparing results between RC and local hospitals (LHs). Materials and Methods: Diagnostic and therapeutic data from patients diagnosed between January 2004 and December 2011 were collected. Correlation with outcome was performed. Results: A total of 622 sarcomas were analyzed, with a median follow‐up of 40 months. Imaging of primary tumor preoperatively (yes vs. no) correlated with a higher probability of free surgical margins (77.4% versus 53.7%; p =.006). The provenance of the biopsy (RC vs. LH) significantly affected relapse‐free survival (RFS; 3‐year RFS 66% vs. 46%, respectively; p =.019). Likewise, 3‐year RFS was significantly worse in cases with infiltrated (55.6%) or unknown (43.4%) microscopic surgical margins compared with free margins (63.6%; p <.001). Patients managed by RCs had a better 3‐year overall survival compared with those managed by LHs (82% vs. 70.4%, respectively; p =.003). Perioperative chemotherapy in high‐risk STS, more frequently administered in RCs than in LHs, resulted in significantly better 3‐year RFS (66% vs. 44%; p =.011). In addition, patients with stage IV disease treated in RCs survived significantly longer compared with those in LHs (30.4 months vs. 18.5 months; p =.036). Conclusion: Our series indicate that selected quality‐of‐care items were accomplished better by RCs over LHs, all with significant prognostic value in patients with STS. Early referral to an RC should be mandatory if the aim is to improve the survival of patients with STS. Implications for Practice: This prospective study in patients diagnosed with soft‐tissue sarcoma shows the prognostic impact of reference centers in the management of these patients. The magnitude of this impact encompasses all steps of the process, from the initial management (performing diagnostic biopsy) to the advanced disease setting. This is the first prospective evidence showing improvement in outcomes of patients with metastatic disease when they are managed in centers with expertise. This study provides extra data supporting referral of patients with sarcoma to reference centers. Management of soft‐tissue sarcoma is challenging. This article reports on sarcoma clinical management in cancer centers in Spain, based on information from a prospective registry launched by the Spanish Group for Research in Sarcoma. [ABSTRACT FROM AUTHOR]
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- 2019
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8. Clinicopathological and Molecular Characterization of Metastatic Gastrointestinal Stromal Tumors with Prolonged Benefit to Frontline Imatinib.
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Serrano, César, García‐del‐Muro, Xavier, Valverde, Claudia, Sebio, Ana, Durán, José, Manzano, Aránzazu, Pajares, Isabel, Hindi, Nadia, Landolfi, Stefania, Jiménez, Laura, Rubió‐Casadevall, Jordi, Estival, Anna, Lavernia, Javier, Safont, María José, Pericay, Carles, Díaz‐Beveridge, Roberto, Martínez‐Marín, Virginia, Vicente‐Baz, David, Vivancos, Ana, and Hernández‐Losa, Javier
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GASTROINTESTINAL tumors ,CYTOGENETICS ,SARCOMA ,DRUG side effects ,SYMPTOMS ,TREATMENT effectiveness ,TREATMENT duration ,CANCER patients ,METASTASIS ,CONNECTIVE tissue tumors ,LONGITUDINAL method ,IMATINIB ,GENETIC mutation ,DISEASE progression - Abstract
Background: Oncogenic KIT/PDGFRA signaling inhibition with imatinib achieves disease control in most patients with advanced/metastatic gastrointestinal stromal tumor (GIST), but resistance eventually develops after 20–24 months. Notably, a small subset of these patients obtain durable benefit from imatinib therapy. Methods: We analyzed clinical, pathological, and molecular characteristics and long‐term outcomes in patients with metastatic GIST treated with continuous daily dosing of frontline imatinib in a cohort of patients benefiting for ≥5 years. A control group was obtained from the national Spanish Group for Sarcoma Research database and used as comparator. Results: Sixty‐four imatinib long‐term responders (LTRs) and 70 control cases were identified. Compared with controls, LTRs at baseline had better performance status (PS) 0–1 (100% vs. 81%), lower mitotic count (median, 8 vs. 15), and tumor burden (number of metastases, 3 vs. 7). KIT exon 11 was the only region found mutated in LTRs. LTRs achieved 34% complete responses and a median progression‐free survival of 11 years, compared with 4% and 2 years, respectively, in the control cohort. Prognostic factors that independently predicted long‐term benefit with imatinib were PS, number of metastases prior to imatinib, and response to imatinib. Fifteen LTR patients developed new side effects attributable to imatinib after ≥5 years of continuous treatment. No resistance mutations were found in metastatic samples from three patients progressing on imatinib. Conclusion: GISTs in LTRs are a distinctive entity with less aggressive behavior and marked sensitivity to KIT inhibition. Patients reaching 5 or more years on imatinib have a higher chance of remaining progression free over time. Implications for Practice: This work demonstrates that clinical and inherent tumor characteristics define a subset of patients with gastrointestinal stromal tumor (GIST) with increased likelihood to achieve durable response to first‐line imatinib therapy. Patients reaching ≥5 years on imatinib have a greater chance of remaining progression free over time, although the disease is unlikely to be cured. Imatinib is well tolerated for >5 years, and emergent toxicities are overall manageable. Resistance to imatinib emerging in patients with GISTs after long‐term imatinib treatment does not involve polyclonal expansion of KIT secondary mutations. This article identifies distinctive clinicopathological and molecular features in long‐term responders to imatinib treatment compared with patients with gastrointestinal stromal tumors reaching the usual median progression‐free survival. Clinical insights from this subgroup collected during the long‐term follow‐up are also provided. [ABSTRACT FROM AUTHOR]
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- 2019
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9. Malignant bone tumors (other than Ewing's): clinical practice guidelines for diagnosis, treatment and follow-up by Spanish Group for Research on Sarcomas (GEIS).
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Redondo, Andrés, Bagué, Silvia, Bernabeu, Daniel, Ortiz-Cruz, Eduardo, Valverde, Claudia, Alvarez, Rosa, Martinez-Trufero, Javier, Lopez-Martin, Jose, Correa, Raquel, Cruz, Josefina, Lopez-Pousa, Antonio, Santos, Aurelio, García del Muro, Xavier, Martin-Broto, Javier, Redondo, Andrés, Bagué, Silvia, Lopez-Martin, Jose A, and García Del Muro, Xavier
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BONE tumors ,OSTEOSARCOMA ,GIANT cell tumors ,CANCER chemotherapy ,DIAGNOSIS ,THERAPEUTICS ,HISPANIC Americans ,LONGITUDINAL method ,MEDICAL research ,SARCOMA - Abstract
Primary malignant bone tumors are uncommon and heterogeneous malignancies. This document is a guideline developed by the Spanish Group for Research on Sarcoma with the participation of different specialists involved in the diagnosis and treatment of bone sarcomas. The aim is to provide practical recommendations with the intention of helping in the clinical decision-making process. The diagnosis and treatment of bone tumors requires a multidisciplinary approach, involving as a minimum pathologists, radiologists, surgeons, and radiation and medical oncologists. Early referral to a specialist center could improve patients' survival. The multidisciplinary management of osteosarcoma, chondrosarcoma, chordoma, giant cell tumor of bone and other rare bone tumors is reviewed in this guideline. Ewing's sarcoma will be the focus of a separate guideline because of its specific biological, clinical and therapeutic features. Each statement has been accompanied by the level of evidence and grade of recommendation on the basis of the available data. Surgical excision is the mainstay of treatment of a localized bone tumor, with various techniques available depending on the histologic type, grade and location of the tumor. Chemotherapy plays an important role in some chemosensitive subtypes (such as high-grade osteosarcoma). In other subtypes, historically considered chemoresistant (such as chordoma or giant cell tumor of bone), new targeted therapies have emerged recently, with a very significant efficacy in the case of denosumab. Radiation therapy is usually necessary in the treatment of chordoma and sometimes of other bone tumors. [ABSTRACT FROM AUTHOR]
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- 2017
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10. RAS/MAPK pathway hyperactivation determines poor prognosis in undifferentiated pleomorphic sarcomas.
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Serrano, César, Romagosa, Cleofé, Hernández-Losa, Javier, Simonetti, Sara, Valverde, Claudia, Moliné, Teresa, Somoza, Rosa, Pérez, Manuel, Vélez, Roberto, Vergés, Ramona, Domínguez, Rosa, Carles, Joan, and Ramón y Cajal, Santiago
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MITOGEN-activated protein kinases ,RENIN-angiotensin system ,PHOSPHOINOSITIDES ,RAPAMYCIN ,BIOMARKERS ,CELL proliferation ,SARCOMA ,DNA mutational analysis ,PROTEIN metabolism ,CELLULAR signal transduction ,PROGNOSIS ,PROTEINS ,TRANSFERASES - Abstract
Background: Undifferentiated pleomorphic sarcoma (UPS) constitutes the most common subtype of soft tissue sarcoma. However, UPS is clinically and molecularly poorly understood, in great extent due to its intrinsic phenotypic and cytogenetic complexity, which in turn results in the absence of specific prognostic or predictive biomarkers. The RAS/mitogen-activated protein kinases (MAPK) and phosphoinositide 3-kinase inhibitor (PI3K)/mammalian target of rapamycin (mTOR) pathways are considered to be 2 major mechanisms for sarcoma proliferation and survival and to the authors' knowledge their role in UPS remains unclear. The objective of the current study was to investigate whether the RAS/MAPK and PI3K/mTOR pathways are activated in UPS, and whether pathway activation is associated with outcome.Methods: Records for patients diagnosed and treated for UPS in the study institution between 2000 and 2009 were reviewed. Phosphorylation status of 4E-binding protein (4E-BP1), eukaryotic translation initiation factor 4E (eIF-4E), S6-RP, and ERK 1/2, together with total forms of 4E-BP1 and eIF-4E, were assessed using immunohistochemistry in paraffin-embedded tumor tissue. Mutational analysis for KRAS; NRAS; BRAF; and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) oncogenic mutations was performed as well.Results: Critical lymph nodes within the RAS/MAPK and PI3K/mTOR pathways were found to be activated in >80% of UPS cases. Hyperactivation of the RAS/MAPK pathway, as assessed by expression of phosphorylated ERK 1/2, was found to independently predict a higher risk of disease recurrence and impaired overall survival. Only a KRAS A146V mutation was detected in 1 tumor.Conclusions: The RAS/MAPK and PI3K/mTOR pathways are activated in the majority of cases of UPS. The RAS/MAPK pathway distinguishes a subgroup of patients with localized UPS with a worse outcome. [ABSTRACT FROM AUTHOR]- Published
- 2016
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11. Clinical practice guidelines for the diagnosis and treatment of patients with soft tissue sarcoma by the Spanish group for research in sarcomas (GEIS).
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Garcia del Muro, Xavier, Alava, Enrique, Artigas, Vicenç, Bague, Silvia, Braña, Alejandro, Cubedo, Ricardo, Cruz, Josefina, Mulet-Margalef, Nuria, Narvaez, Jose, Martinez Tirado, Oscar, Valverde, Claudia, Verges, Ramona, Viñals, Joan, Martin-Broto, Javier, de Alava, Enrique, Artigas, Vicenç, Braña, Alejandro, Narvaez, Jose A, Viñals, Joan, and Spanish Group for Research on Sarcoma
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TISSUE wounds ,CANCER treatment ,SARCOMA ,TUMOR diagnosis ,BIOPSY ,INTERDISCIPLINARY research ,ANTINEOPLASTIC agents ,COMBINED modality therapy ,SOFT tissue tumors ,DIAGNOSIS ,TUMOR treatment - Abstract
Soft tissue sarcomas (STS) constitute an uncommon and heterogeneous group of tumours, which require a complex and specialized multidisciplinary management. The diagnostic approach should include imaging studies and core needle biopsy performed prior to undertaking surgery. Wide excision is the mainstay of treatment for localized sarcoma, and associated preoperative or postoperative radiotherapy should be administered in high-risk patients. Adjuvant chemotherapy was associated with a modest improvement in survival in a meta-analysis and constitutes a standard option in selected patients with high-risk STS. In metastatic patients, surgery must be evaluated in selected cases. In the rest of patients, chemotherapy and, in some subtypes, targeted therapy often used in a sequential strategy constitutes the treatment of election. Despite important advances in the understanding of the pathophysiology of the disease, the advances achieved in therapeutic results may be deemed still insufficient. Moreover, due to the rarity and complexity of the disease, the results in clinical practice are not always optimal. For this reason, the Spanish Group for Research on Sarcoma (GEIS) has developed a multidisciplinary clinical practice guidelines document, with the aim of facilitating the diagnosis and treatment of these patients in Spain. In the document, each practical recommendation is accompanied by level of evidence and grade of recommendation on the basis of the available data. [ABSTRACT FROM AUTHOR]
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- 2016
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12. GEIS 2013 guidelines for gastrointestinal sarcomas (GIST).
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Poveda, Andrés, Muro, Xavier, López-Guerrero, Jose, Martínez, Virginia, Romero, Ignacio, Valverde, Claudia, Cubedo, Ricardo, and Martín-Broto, Javier
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SARCOMA ,GASTROINTESTINAL stromal tumors ,SOFT tissue tumors ,GENETIC mutation ,DRUG development ,PLATELET-derived growth factor receptors ,DIAGNOSIS - Abstract
Gastrointestinal stromal tumors (GIST) are the most common mesenchymal soft tissue sarcoma of the gastrointestinal tract. Correct diagnosis with thorough use of pathologic and molecular tools of GIST mutations has been of the foremost importance. GIST are usually (95 %) KIT positive and harbor frequent KIT or platelet-derived growth factor receptor α-activating mutations. This deep molecular understanding has allowed the correct classification into risk groups with implications regarding prognosis, essential use in the development of targeted therapies and even response prediction to this drugs. Treatment has been evolving and an update to include lessons learned from recent trials in advanced disease as well as controversies in the adjuvant setting that are changing daily practice, is reviewed here. An effort from the Spanish Group for Sarcoma Research with investigators from the group has been undertaken to launch this third version of the GIST guidelines and provide a practical means for the different disciplines that treat this complex disease. [ABSTRACT FROM AUTHOR]
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- 2014
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