BACKGROUND: Recent breakthroughs regarding the oncogenesis of gastrointestinal stromal tumors (GISTs) have led to the wider use of imatinib mesylate in the treatment of advanced GISTs. However, the role of imatinib in an adjuvant setting has yet to be established, mainly owing to the lack of an accurate system to prognosticate recurrences and/or metastases. The aims of this study were to identify factors prognostic for an unfavorable postoperative outcome, and to enhance the current NIH-consensus risk-group stratification system (Fletcher's system). METHODS: A retrospective review was conducted in 303 consecutive patients who had undergone surgical resection of primary GISTs during the study period (1987-2003). In addition to Fletcher's system, which is based on morphologic variables (tumor size and mitotic count), with four risk groups: very low risk, low risk, intermediate risk, and high risk, the predictive potential of any major preoperative, intraoperative, or postoperative clinical factor was statistically evaluated. RESULTS: In addition to tumor size and mitosis, four operative variables were found to affect disease-free survival: peritoneal dissemination, metastasis, invasion, and tumor rupture. Patients presenting with at least one of these "clinically malignant factors" had an unfavorable outcome (i.e., they were potential candidates for adjuvant therapy). We therefore modified Fletcher's system by adding a new patient group, termed the "clinically malignant group," (patients having at least one of the "clinically malignant factors"). With this modification, the outcomes of patients in the "new" very-low-risk and low-risk groups remained favorable, but the outcomes of patients in the "clinically malignant group" and the "new" high-risk group bceame unfavorable. CONCLUSION: This modified Fletcher's system, enhanced by the addition of "clinically malignant factors," can distinguish patients with a possible unfavorable outcome from those who require no therapy other than surgery. Patients in the "clinically malignant group" could be potential candidates for adjuvant therapy using imatinib.
BACKGROUND: Recent breakthroughs regarding the oncogenesis of gastrointestinal stromal tumors (GISTs) have led to the wider use of imatinib mesylate in the treatment of advanced GISTs. However, the role of imatinib in an adjuvant setting has yet to be established, mainly owing to the lack of an accurate system to prognosticate recurrences and/or metastases. The aims of this study were to identify factors prognostic for an unfavorable postoperative outcome, and to enhance the current NIH-consensus risk-group stratification system (Fletcher's system). METHODS: A retrospective review was conducted in 303 consecutive patients who had undergone surgical resection of primary GISTs during the study period (1987-2003). In addition to Fletcher's system, which is based on morphologic variables (tumor size and mitotic count), with four risk groups: very low risk, low risk, intermediate risk, and high risk, the predictive potential of any major preoperative, intraoperative, or postoperative clinical factor was statistically evaluated. RESULTS: In addition to tumor size and mitosis, four operative variables were found to affect disease-free survival: peritoneal dissemination, metastasis, invasion, and tumor rupture. Patients presenting with at least one of these "clinically malignant factors" had an unfavorable outcome (i.e., they were potential candidates for adjuvant therapy). We therefore modified Fletcher's system by adding a new patient group, termed the "clinically malignant group," (patients having at least one of the "clinically malignant factors"). With this modification, the outcomes of patients in the "new" very-low-risk and low-risk groups remained favorable, but the outcomes of patients in the "clinically malignant group" and the "new" high-risk group bceame unfavorable. CONCLUSION: This modified Fletcher's system, enhanced by the addition of "clinically malignant factors," can distinguish patients with a possible unfavorable outcome from those who require no therapy other than surgery. Patients in the "clinically malignant group" could be potential candidates for adjuvant therapy using imatinib.
Authors: Jaap Verweij; Paolo G Casali; John Zalcberg; Axel LeCesne; Peter Reichardt; Jean-Yves Blay; Rolf Issels; Allan van Oosterom; Pancras C W Hogendoorn; Martine Van Glabbeke; Rossella Bertulli; Ian Judson Journal: Lancet Date: 2004 Sep 25-Oct 1 Impact factor: 79.321
Authors: Christopher D M Fletcher; Jules J Berman; Christopher Corless; Fred Gorstein; Jerzy Lasota; B Jack Longley; Markku Miettinen; Timothy J O'Leary; Helen Remotti; Brian P Rubin; Barry Shmookler; Leslie H Sobin; Sharon W Weiss Journal: Hum Pathol Date: 2002-05 Impact factor: 3.466
Authors: George D Demetri; Margaret von Mehren; Charles D Blanke; Annick D Van den Abbeele; Burton Eisenberg; Peter J Roberts; Michael C Heinrich; David A Tuveson; Samuel Singer; Milos Janicek; Jonathan A Fletcher; Stuart G Silverman; Sandra L Silberman; Renaud Capdeville; Beate Kiese; Bin Peng; Sasa Dimitrijevic; Brian J Druker; Christopher Corless; Christopher D M Fletcher; Heikki Joensuu Journal: N Engl J Med Date: 2002-08-15 Impact factor: 91.245
Authors: Michael C Heinrich; Christopher L Corless; Anette Duensing; Laura McGreevey; Chang-Jie Chen; Nora Joseph; Samuel Singer; Diana J Griffith; Andrea Haley; Ajia Town; George D Demetri; Christopher D M Fletcher; Jonathan A Fletcher Journal: Science Date: 2003-01-09 Impact factor: 47.728
Authors: J Verweij; A van Oosterom; J-Y Blay; I Judson; S Rodenhuis; W van der Graaf; J Radford; A Le Cesne; P C W Hogendoorn; E D di Paola; M Brown; O S Nielsen Journal: Eur J Cancer Date: 2003-09 Impact factor: 9.162
Authors: Michael C Heinrich; Christopher L Corless; George D Demetri; Charles D Blanke; Margaret von Mehren; Heikki Joensuu; Laura S McGreevey; Chang-Jie Chen; Annick D Van den Abbeele; Brian J Druker; Beate Kiese; Burton Eisenberg; Peter J Roberts; Samuel Singer; Christopher D M Fletcher; Sandra Silberman; Sasa Dimitrijevic; Jonathan A Fletcher Journal: J Clin Oncol Date: 2003-12-01 Impact factor: 44.544
Authors: Olga Martinho; António Gouveia; Paula Silva; Amadeu Pimenta; Rui Manuel Reis; José Manuel Lopes Journal: Virchows Arch Date: 2009-08-25 Impact factor: 4.064