title: [Advanced gastrointestinal stromal tumors : What role does surgery currently play in multimodal concepts?].
abstract: BACKGROUND
  Gastrointestinal stromal tumors (GIST) have an incidence of 1-2/100,000 and thus constitute the most common mesenchymal neoplasm of the digestive tract. Their specific tumor biology with mutations in the protooncogenes c-KIT and PDGFR α acting as drivers of tumor growth facilitate targeted therapy with tyrosine kinase inhibitors. In this context, there are several specific indications for surgery in patients with advanced GIST.
  
  
  OBJECTIVE
  This article discusses the importance of surgery within multimodal therapeutic concepts for advanced GIST.
  
  
  METHODS
  The results of a selective literature search including own studies and case reports are presented.
  
  
  RESULTS
  For large GIST at unfavorable anatomical locations, which are not amenable to organ-sparing resection, neoadjuvant imatinib therapy is the standard upfront treatment prior to surgery in the case of imatinib-sensitive mutations in the c-KIT protooncogene. This usually reduces the extent of resection without increasing perioperative morbidity. In the metastatic setting, surgery can constitute a significant part of multimodal therapy in patients with a generalized response to drug therapy by resection of residual tumor masses, although there are no prospective studies to prove a beneficial effect on overall survival. In patients with focal progression on anti-proliferative therapy, local therapeutic measures can make an important contribution to multimodal tumor control. In patients with generalized progression, an operation should only be performed in highly selected cases with the goal of symptom control. Local ablative therapies, such as radiofrequency ablation (RFA), irreversible electroporation (IRE) and selective internal radiotherapy (SIRT) are a therapeutic option particularly for liver metastases.
  
  
  CONCLUSIONS
  Surgery plays an important role in the multimodal therapy of advanced GIST particularly in the neoadjuvant setting. Its role is more limited in metastatic stages where systemic treatment represents the frontline therapeutic approach.
authors.affiliation: Sektion Spezielle Chirurgische Onkologie und Thoraxchirurgie, Chirurgische Klinik, Universitätsmedizin Mannheim, Theodor-Kutzer-Ufer 1-3, 68135, Mannheim, Deutschland.
authors.forename: U
authors.initials: U
authors.lastname: Ronellenfitsch
authors.affiliation: Institut für Klinische Radiologie und Nuklearmedizin, Universitätsmedizin Mannheim, Mannheim, Deutschland.
authors.forename: T
authors.initials: T
authors.lastname: Henzler
authors.affiliation: Sektion Spezielle Chirurgische Onkologie und Thoraxchirurgie, Chirurgische Klinik, Universitätsmedizin Mannheim, Theodor-Kutzer-Ufer 1-3, 68135, Mannheim, Deutschland.
authors.forename: F
authors.initials: F
authors.lastname: Menge
authors.affiliation: Klinische Kooperationseinheit Nuklearmedizin, Deutsches Krebsforschungszentrum (DKFZ) Heidelberg, Heidelberg, Deutschland.
authors.forename: A
authors.initials: A
authors.lastname: Dimitrakopoulou-Strauss
authors.affiliation: Sektion Spezielle Chirurgische Onkologie und Thoraxchirurgie, Chirurgische Klinik, Universitätsmedizin Mannheim, Theodor-Kutzer-Ufer 1-3, 68135, Mannheim, Deutschland. peter.hohenberger@umm.de.
authors.forename: P
authors.initials: P
authors.lastname: Hohenberger
mesh_terms: D001918:Brachytherapy; D017115:Catheter Ablation; D003131:Combined Modality Therapy; D004252:DNA Mutational Analysis; D018450:Disease Progression; D018572:Disease-Free Survival; D053672:Electrochemotherapy; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D009367:Neoplasm Staging; D018365:Neoplasm, Residual / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics
chemical_list: D011505:Protein-Tyrosine Kinases; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha
keywords: GIST; Mutation analysis; Neoadjuvant therapy; Radiofrequency ablation; Systemic therapy