BACKGROUND: The exon 11 KIT mutant gastrointestinal stromal tumors (GIST) is a heterogeneous cohort with variable biological behavior based on different mutational subtypes. METHODS: Patients with histologically proven GIST with KIT exon 11 mutations were selected from a prospectively maintained database, and evaluated for clinical characteristics and event free survival (EFS). Patients were divided into mutations upstream to codon 557 (G1), mutations involving codon 557-558 (G2) and mutation downstream to codon 558 (G3). RESULTS: A total of 90 patients satisfied the inclusion criteria for study. Substitutions, indels and duplications were seen in 23 patients. Deletions were seen in 67 patients, of which 44 patients had large deletions (>6 base pairs), while 23 has small deletions (<6 base pairs). Complex mutations were seen in 15 patients. G2 mutations were noted in 33 patients, while G1 and G3 mutations were seen 32 and 25 patients respectively. With a median follow-up of 26 months, estimated median EFS for the entire cohort was 55 months. The G2 cohort had an inferior EFS compared to the G1 and G3 cohorts (46 vs. 55 months), but this did not achieve statistical significance (univariate analysis: P=0.075). On multivariate analysis, patients undergoing radical intent surgery vs. no surgery (58 vs. 55 months; P=0.005) and G1 or G3 vs. G2 cohort (P=0.058) showed trend towards improved EFS. CONCLUSIONS: In patients with GIST exon 11 codon 557-558 mutation subset there is a trend towards an inferior survival even when treated with imatinib mesylate (IM).
BACKGROUND: The exon 11 KIT mutant gastrointestinal stromal tumors (GIST) is a heterogeneous cohort with variable biological behavior based on different mutational subtypes. METHODS:Patients with histologically proven GIST with KIT exon 11 mutations were selected from a prospectively maintained database, and evaluated for clinical characteristics and event free survival (EFS). Patients were divided into mutations upstream to codon 557 (G1), mutations involving codon 557-558 (G2) and mutation downstream to codon 558 (G3). RESULTS: A total of 90 patients satisfied the inclusion criteria for study. Substitutions, indels and duplications were seen in 23 patients. Deletions were seen in 67 patients, of which 44 patients had large deletions (>6 base pairs), while 23 has small deletions (<6 base pairs). Complex mutations were seen in 15 patients. G2 mutations were noted in 33 patients, while G1 and G3 mutations were seen 32 and 25 patients respectively. With a median follow-up of 26 months, estimated median EFS for the entire cohort was 55 months. The G2 cohort had an inferior EFS compared to the G1 and G3 cohorts (46 vs. 55 months), but this did not achieve statistical significance (univariate analysis: P=0.075). On multivariate analysis, patients undergoing radical intent surgery vs. no surgery (58 vs. 55 months; P=0.005) and G1 or G3 vs. G2 cohort (P=0.058) showed trend towards improved EFS. CONCLUSIONS: In patients with GIST exon 11 codon 557-558 mutation subset there is a trend towards an inferior survival even when treated with imatinib mesylate (IM).
Authors: Ronald P DeMatteo; Karla V Ballman; Cristina R Antonescu; Christopher Corless; Violetta Kolesnikova; Margaret von Mehren; Martin D McCarter; Jeffrey Norton; Robert G Maki; Peter W T Pisters; George D Demetri; Murray F Brennan; Kouros Owzar Journal: Ann Surg Date: 2013-09 Impact factor: 12.969
Authors: Christopher L Corless; Karla V Ballman; Cristina R Antonescu; Violetta Kolesnikova; Robert G Maki; Peter W T Pisters; Martin E Blackstein; Charles D Blanke; George D Demetri; Michael C Heinrich; Margaret von Mehren; Shreyaskumar Patel; Martin D McCarter; Kouros Owzar; Ronald P DeMatteo Journal: J Clin Oncol Date: 2014-03-17 Impact factor: 44.544
Authors: J Martin-Broto; A Gutierrez; X Garcia-Del-Muro; J A Lopez-Guerrero; J Martinez-Trufero; L M de Sande; N Lainez; J Maurel; A De Juan; F Losa; R Andres; A Casado; P G Tejido; R Blanco; J Carles; J Bellmunt; A Gomez-España; R Ramos; J Martinez-Serra; A Llombart-Bosch; A Poveda Journal: Ann Oncol Date: 2010-03-15 Impact factor: 32.976
Authors: Agnieszka Wozniak; Piotr Rutkowski; Patrick Schöffski; Isabelle Ray-Coquard; Isabelle Hostein; Hans-Ulrich Schildhaus; Axel Le Cesne; Elzbieta Bylina; Janusz Limon; Jean-Yves Blay; Janusz A Siedlecki; Eva Wardelmann; Raf Sciot; Jean-Michel Coindre; Maria Debiec-Rychter Journal: Clin Cancer Res Date: 2014-10-07 Impact factor: 12.531
Authors: Heikki Joensuu; Piotr Rutkowski; Toshirou Nishida; Sonja E Steigen; Peter Brabec; Lukas Plank; Bengt Nilsson; Chiara Braconi; Andrea Bordoni; Magnus K Magnusson; Jozef Sufliarsky; Massimo Federico; Jon G Jonasson; Isabelle Hostein; Pierre-Paul Bringuier; Jean-Francois Emile Journal: J Clin Oncol Date: 2015-01-20 Impact factor: 44.544
Authors: Charles D Blanke; George D Demetri; Margaret von Mehren; Michael C Heinrich; Burton Eisenberg; Jonathan A Fletcher; Christopher L Corless; Christopher D M Fletcher; Peter J Roberts; Daniela Heinz; Elisabeth Wehre; Zariana Nikolova; Heikki Joensuu Journal: J Clin Oncol Date: 2008-02-01 Impact factor: 44.544
Authors: Piotr Rutkowski; Alessandro Gronchi; Peter Hohenberger; Sylvie Bonvalot; Patrick Schöffski; Sebastian Bauer; Elena Fumagalli; Pawel Nyckowski; Buu-Phuc Nguyen; Jan Martijn Kerst; Marco Fiore; Elzbieta Bylina; Mathias Hoiczyk; Annemieke Cats; Paolo G Casali; Axel Le Cesne; Jürgen Treckmann; Eberhard Stoeckle; Johannes H W de Wilt; Stefan Sleijfer; Ronald Tielen; Winette van der Graaf; Cornelis Verhoef; Frits van Coevorden Journal: Ann Surg Oncol Date: 2013-06-13 Impact factor: 5.344