Maria A Pantaleo1, Cristian Lolli2, Margherita Nannini2, Annalisa Astolfi3, Valentina Indio3, Maristella Saponara2, Milena Urbini3, Stefano La Rovere4, Antony Gill5, David Goldstein6, Claudio Ceccarelli7, Donatella Santini7, Giulio Rossi8, Michelangelo Fiorentino9, Valerio Di Scioscio10, Pietro Fusaroli11, Anna Mandrioli2, Lidia Gatto2, Fausto Catena12, Umberto Basso13, Giorgio Ercolani12, Antonio Daniele Pinna12, Guido Biasco1. 1. 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. 2. Department of Specialized, Experimental and Diagnostic Medicine, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy. 3. 8220;Giorgio Prodi" Cancer Research Center, University of Bologna, Bologna, Italy. 4. NIER Ingegneria SpA, Bologna, Italy. 5. Department of Anatomical Pathology, Royal North Shore Hospital, Australia and University of Sydney, Sydney, Australia. 6. 1] Prince of Wales Hospital, Sydney, Australia [2] Prince of Wales Clinical School, University of New South Wales, New South Wales, Australia. 7. Pathology Unit, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy. 8. Section of Pathologic Anatomy and Division of Oncology, Modena University Hospital Trust, Modena, Italy. 9. Laboratory of Oncological and Transplant Molecular Pathology, Pathology Unit, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy. 10. Department of Radiology, Sant'Orsola Malpighi Hospital, Bologna University, Bologna, Italy. 11. GI Unit, Department of Medical and Surgical Sciences, University of Bologna/Hospital of Imola , Bologna, Italy. 12. Department of Surgery and Transplantation, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy. 13. Medical Oncology 1, Veneto Oncology Institute, IRCCS, Padua, Italy.
Abstract
PURPOSE: 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). CONCLUSION: 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.
PURPOSE: 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). CONCLUSION: 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.
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