OBJECTIVES: Alkylating agents have activity in well-differentiated pancreatic neuroendocrine tumors (WD panNETs). In glioblastoma multiforme, decreased activity of O-methylguanine DNA methyltransferase (MGMT) predicts response; in panNETs, MGMT relevance is unknown. METHODS: We identified patients with WD panNETs treated with alkylating agents, determined best overall response by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, and performed MGMT activity testing. RESULTS: Fifty-six patients were identified; 26 (46%) of the 56 patients experienced partial response, 24 (43%) of 56 experienced stable disease, and 6 (11%) of 56 experienced progression of disease. O-methylguanine DNA methyltransferase status was available for 36 tumors. For tumors with partial response, 10 (67%) of 15 were MGMT deficient, and 5 (33%) of 15 were MGMT intact. For tumors with stable disease, 7 (47%) of 15 were MGMT deficient, and 8 (53%) of 15 were MGMT intact. For tumors with progression of disease, 3 (50%) of 6 were MGMT deficient, and 3 (50%) of 6 were MGMT intact. CONCLUSIONS: We observed response and resistance to alkylating agents in MGMT-deficient and MGMT-intact tumors. O-methylguanine DNA methyltransferase status should not guide alkylating agent therapy in WD panNETs.
OBJECTIVES: Alkylating agents have activity in well-differentiated pancreatic neuroendocrine tumors (WD panNETs). In glioblastoma multiforme, decreased activity of O-methylguanine DNA methyltransferase (MGMT) predicts response; in panNETs, MGMT relevance is unknown. METHODS: We identified patients with WD panNETs treated with alkylating agents, determined best overall response by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, and performed MGMT activity testing. RESULTS: Fifty-six patients were identified; 26 (46%) of the 56 patients experienced partial response, 24 (43%) of 56 experienced stable disease, and 6 (11%) of 56 experienced progression of disease. O-methylguanine DNA methyltransferase status was available for 36 tumors. For tumors with partial response, 10 (67%) of 15 were MGMT deficient, and 5 (33%) of 15 were MGMT intact. For tumors with stable disease, 7 (47%) of 15 were MGMT deficient, and 8 (53%) of 15 were MGMT intact. For tumors with progression of disease, 3 (50%) of 6 were MGMT deficient, and 3 (50%) of 6 were MGMT intact. CONCLUSIONS: We observed response and resistance to alkylating agents in MGMT-deficient and MGMT-intact tumors. O-methylguanine DNA methyltransferase status should not guide alkylating agent therapy in WD panNETs.
Authors: Michael Weller; Roger Stupp; Guido Reifenberger; Alba A Brandes; Martin J van den Bent; Wolfgang Wick; Monika E Hegi Journal: Nat Rev Neurol Date: 2009-12-08 Impact factor: 42.937
Authors: M Cives; M Ghayouri; B Morse; M Brelsford; M Black; A Rizzo; A Meeker; J Strosberg Journal: Endocr Relat Cancer Date: 2016-09 Impact factor: 5.678
Authors: Eric Raymond; Laetitia Dahan; Jean-Luc Raoul; Yung-Jue Bang; Ivan Borbath; Catherine Lombard-Bohas; Juan Valle; Peter Metrakos; Denis Smith; Aaron Vinik; Jen-Shi Chen; Dieter Hörsch; Pascal Hammel; Bertram Wiedenmann; Eric Van Cutsem; Shem Patyna; Dongrui Ray Lu; Carolyn Blanckmeister; Richard Chao; Philippe Ruszniewski Journal: N Engl J Med Date: 2011-02-10 Impact factor: 91.245
Authors: Jonathan R Strosberg; Robert L Fine; Junsung Choi; Aejaz Nasir; Domenico Coppola; Dung-Tsa Chen; James Helm; Larry Kvols Journal: Cancer Date: 2010-09-07 Impact factor: 6.860
Authors: James C Yao; Manal Hassan; Alexandria Phan; Cecile Dagohoy; Colleen Leary; Jeannette E Mares; Eddie K Abdalla; Jason B Fleming; Jean-Nicolas Vauthey; Asif Rashid; Douglas B Evans Journal: J Clin Oncol Date: 2008-06-20 Impact factor: 44.544
Authors: T Walter; B van Brakel; C Vercherat; V Hervieu; J Forestier; J-A Chayvialle; Y Molin; C Lombard-Bohas; M-O Joly; J-Y Scoazec Journal: Br J Cancer Date: 2015-01-13 Impact factor: 7.640
Authors: Louis de Mestier; Thomas Walter; Camille Evrard; Paul de Boissieu; Olivia Hentic; Jérôme Cros; David Tougeron; Catherine Lombard-Bohas; Vinciane Rebours; Pascal Hammel; Philippe Ruszniewski Journal: Neuroendocrinology Date: 2019-05-10 Impact factor: 4.914