title: Good survival outcome of metastatic SDH-deficient gastrointestinal stromal tumors harboring SDHA mutations.
abstract: OBJECTIVE
  A subset of patients with KIT/PDGFRA wild-type gastrointestinal stromal tumors show loss of function of succinate dehydrogenase, mostly due to germ-line mutations of succinate dehydrogenase subunits, with a predominance of succinate dehydrogenase subunit A. The clinical outcome of these patients seems favorable, as reported in small series in which patients were individually described. This work evaluates a retrospective survival analysis of a series of patients with metastatic KIT/PDGFRA wild-type succinate dehydrogenase-deficient gastrointestinal stromal tumors.
  
  
  METHODS
  Sixty-nine patients with metastatic gastrointestinal stromal tumors were included in the study (11 KIT/PDGFRA wild-type, of whom 6 were succinate dehydrogenase deficient, 5 were non-succinate dehydrogenase deficient, and 58 were KIT/PDGFRA mutant). All six succinate dehydrogenase-deficient patients harbored SDHA mutations. Kaplan-Meier curves and log-rank tests were used to compare the survival of patients with succinate dehydrogenase subunit A-mutant gastrointestinal stromal tumors with that of KIT/PDGFRA wild-type patients without succinate dehydrogenase deficiency and patients with KIT/PDGFRA-mutant gastrointestinal stromal tumors.
  
  
  RESULTS
  Follow-up ranged from 8.5 to 200.7 months. The difference between succinate dehydrogenase subunit A-mutant gastrointestinal stromal tumors and KIT/PDGFRA-mutant or KIT/PDGFRA wild-type non-succinate dehydrogenase deficient gastrointestinal stromal tumors was significant considering different analyses (P = 0.007 and P = 0.033, respectively, from diagnosis of gastrointestinal stromal tumor for the whole study population; P = 0.005 and P = 0.018, respectively, from diagnosis of metastatic disease for the whole study population; P = 0.007 for only patients who were metastatic at diagnosis).
  
  
  CONCLUSIONS
  Patients with metastatic KIT/PDGFRA wild-type succinate dehydrogenase-deficient gastrointestinal stromal tumors harboring succinate dehydrogenase subunit A mutations present an impressively long survival. These patients should be identified in clinical practice to better tailor treatments and follow-up over time.
authors.affiliation: 1] Department of Specialized, Experimental and Diagnostic Medicine, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy [2] "Giorgio Prodi" Cancer Research Center, University of Bologna, Bologna, Italy.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Pantaleo
authors.affiliation: Department of Specialized, Experimental and Diagnostic Medicine, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Cristian
authors.initials: C
authors.lastname: Lolli
authors.affiliation: Department of Specialized, Experimental and Diagnostic Medicine, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Nannini
authors.affiliation: 8220;Giorgio Prodi" Cancer Research Center, University of Bologna, Bologna, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Astolfi
authors.affiliation: 8220;Giorgio Prodi" Cancer Research Center, University of Bologna, Bologna, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Indio
authors.affiliation: Department of Specialized, Experimental and Diagnostic Medicine, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Maristella
authors.initials: M
authors.lastname: Saponara
authors.affiliation: 8220;Giorgio Prodi" Cancer Research Center, University of Bologna, Bologna, Italy.
authors.forename: Milena
authors.initials: M
authors.lastname: Urbini
authors.affiliation: NIER Ingegneria SpA, Bologna, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: La Rovere
authors.affiliation: Department of Anatomical Pathology, Royal North Shore Hospital, Australia and University of Sydney, Sydney, Australia.
authors.forename: Antony
authors.initials: A
authors.lastname: Gill
authors.affiliation: 1] Prince of Wales Hospital, Sydney, Australia [2] Prince of Wales Clinical School, University of New South Wales, New South Wales, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Goldstein
authors.affiliation: Pathology Unit, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Ceccarelli
authors.affiliation: Pathology Unit, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Santini
authors.affiliation: Section of Pathologic Anatomy and Division of Oncology, Modena University Hospital Trust, Modena, Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: Rossi
authors.affiliation: Laboratory of Oncological and Transplant Molecular Pathology, Pathology Unit, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Fiorentino
authors.affiliation: Department of Radiology, Sant'Orsola Malpighi Hospital, Bologna University, Bologna, Italy.
authors.forename: Valerio
authors.initials: V
authors.lastname: Di Scioscio
authors.affiliation: GI Unit, Department of Medical and Surgical Sciences, University of Bologna/Hospital of Imola , Bologna, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Fusaroli
authors.affiliation: Department of Specialized, Experimental and Diagnostic Medicine, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Mandrioli
authors.affiliation: Department of Specialized, Experimental and Diagnostic Medicine, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Lidia
authors.initials: L
authors.lastname: Gatto
authors.affiliation: Department of Surgery and Transplantation, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Fausto
authors.initials: F
authors.lastname: Catena
authors.affiliation: Medical Oncology 1, Veneto Oncology Institute, IRCCS, Padua, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Basso
authors.affiliation: Department of Surgery and Transplantation, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Ercolani
authors.affiliation: Department of Surgery and Transplantation, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Antonio Daniele
authors.initials: AD
authors.lastname: Pinna
authors.affiliation: 1] Department of Specialized, Experimental and Diagnostic Medicine, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy [2] "Giorgio Prodi" Cancer Research Center, University of Bologna, Bologna, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Biasco
mesh_terms: D000328:Adult; D000368:Aged; D042963:Electron Transport Complex II / Q000235:genetics*; D005091:Exons; D005260:Female; D005500:Follow-Up Studies; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D063868:Patient Outcome Assessment; D011379:Prognosis; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics; D055815:Young Adult
chemical_list: D042963:Electron Transport Complex II; C511268:SDHA protein, human; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha