Mark Fairweather1,2, Vinod P Balachandran3, George Z Li1, Monica M Bertagnolli1,2, Cristina Antonescu4, William Tap5, Samuel Singer3, Ronald P DeMatteo3, Chandrajit P Raut1,2. 1. Department of Surgery, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, MA. 2. Center for Sarcoma and Bone Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, MA. 3. Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY. 4. Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY. 5. Department of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, NY.
Abstract
OBJECTIVE: To refine treatment recommendations for patients with metastatic gastrointestinal stromal tumors (GISTs) treated with tyrosine kinase inhibitors (TKIs) and surgery. BACKGROUND: Early reports suggested that patients with metastatic GIST responding to TKIs treated with surgery may have favorable outcomes. However, identification of prognostic factors was limited by small cohorts. METHODS: Progression-free survival (PFS) and overall survival (OS) from time of surgery and from start of initial TKI was determined. Multivariate analysis was conducted on all patients undergoing GIST metastasectomy between 2001 and 2014 at 2 institutions. RESULTS: We performed 400 operations on 323 patients with metastatic GIST on TKIs. Radiographic response at time of surgery was classified as responsive disease (RD, n = 64, 16%), stable disease (SD, n = 100, 25%), unifocal progressive disease (UPD, n = 132, 33%), and multifocal progressive disease (MPD, n = 104, 26%). For patients on imatinib before surgery, radiographic response was predictive of PFS from time of surgery (RD 36 months, SD 30 months, UPD 11 months, MPD 6 months; P < 0.001) and from imatinib initiation (RD 71 months, SD 51 months, UPD 47 months, MPD 33 months; P < 0.001). Radiographic response was predictive of OS from time of surgery (RD not reached, SD 110 months, UPD 59 months, MPD 24 months; P < 0.001), and from imatinib initiation (RD not reached, SD 144 months, UPD 105 months, MPD 66 months; P = 0.005). Radiographic response was not predictive of PFS/OS for patients on sunitinib. Metastatic mitotic index ≥5/50 HPF, MPD, and R2 resection were prognostic of worse PFS/OS; primary mutation was not. CONCLUSIONS: Surgery in metastatic GIST patients in the absence of MPD on imatinib is associated with outcomes at least comparable with second-line sunitinib and may be considered in select patients.
OBJECTIVE: To refine treatment recommendations for patients with metastatic gastrointestinal stromal tumors (GISTs) treated with tyrosine kinase inhibitors (TKIs) and surgery. BACKGROUND: Early reports suggested that patients with metastatic GIST responding to TKIs treated with surgery may have favorable outcomes. However, identification of prognostic factors was limited by small cohorts. METHODS: Progression-free survival (PFS) and overall survival (OS) from time of surgery and from start of initial TKI was determined. Multivariate analysis was conducted on all patients undergoing GIST metastasectomy between 2001 and 2014 at 2 institutions. RESULTS: We performed 400 operations on 323 patients with metastatic GIST on TKIs. Radiographic response at time of surgery was classified as responsive disease (RD, n = 64, 16%), stable disease (SD, n = 100, 25%), unifocal progressive disease (UPD, n = 132, 33%), and multifocal progressive disease (MPD, n = 104, 26%). For patients on imatinib before surgery, radiographic response was predictive of PFS from time of surgery (RD 36 months, SD 30 months, UPD 11 months, MPD 6 months; P < 0.001) and from imatinib initiation (RD 71 months, SD 51 months, UPD 47 months, MPD 33 months; P < 0.001). Radiographic response was predictive of OS from time of surgery (RD not reached, SD 110 months, UPD 59 months, MPD 24 months; P < 0.001), and from imatinib initiation (RD not reached, SD 144 months, UPD 105 months, MPD 66 months; P = 0.005). Radiographic response was not predictive of PFS/OS for patients on sunitinib. Metastatic mitotic index ≥5/50 HPF, MPD, and R2 resection were prognostic of worse PFS/OS; primary mutation was not. CONCLUSIONS: Surgery in metastatic GIST patients in the absence of MPD on imatinib is associated with outcomes at least comparable with second-line sunitinib and may be considered in select patients.
Authors: H Joensuu; P J Roberts; M Sarlomo-Rikala; L C Andersson; P Tervahartiala; D Tuveson; S Silberman; R Capdeville; S Dimitrijevic; B Druker; G D Demetri Journal: N Engl J Med Date: 2001-04-05 Impact factor: 91.245
Authors: P Therasse; S G Arbuck; E A Eisenhauer; J Wanders; R S Kaplan; L Rubinstein; J Verweij; M Van Glabbeke; A T van Oosterom; M C Christian; S G Gwyther Journal: J Natl Cancer Inst Date: 2000-02-02 Impact factor: 13.506
Authors: Mark Fairweather; Jiping Wang; Phillip M Devlin; Jorgen Hansen; Elizabeth H Baldini; John E Ready; David J Sugarbaker; Monica M Bertagnolli; Chandrajit P Raut Journal: Ann Surg Oncol Date: 2014-10-24 Impact factor: 5.344
Authors: Courtney L Scaife; Kelly K Hunt; Shreyaskumar R Patel; Robert S Benjamin; Michael A Burgess; Lei L Chen; Jonathan Trent; A Kevin Raymond; Janice N Cormier; Peter W T Pisters; Raphael E Pollock; Barry W Feig Journal: Am J Surg Date: 2003-12 Impact factor: 2.565
Authors: Charles D Blanke; Cathryn Rankin; George D Demetri; Christopher W Ryan; Margaret von Mehren; Robert S Benjamin; A Kevin Raymond; Vivien H C Bramwell; Laurence H Baker; Robert G Maki; Michael Tanaka; J Randolph Hecht; Michael C Heinrich; Christopher D M Fletcher; John J Crowley; Ernest C Borden Journal: J Clin Oncol Date: 2008-02-01 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: 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: Christina L Roland; Brian K Bednarski; Kelsey Watson; Keila E Torres; Janice N Cormier; Wei-Lien Wang; Alexander J Lazar; Neeta Somaiah; Kelly K Hunt; Barry W Feig Journal: J Surg Oncol Date: 2018-02-15 Impact factor: 3.454
Authors: César Serrano; Xavier García-Del-Muro; Claudia Valverde; Ana Sebio; José Durán; Aránzazu Manzano; Isabel Pajares; Nadia Hindi; Stefania Landolfi; Laura Jiménez; Jordi Rubió-Casadevall; Anna Estival; Javier Lavernia; María José Safont; Carles Pericay; Roberto Díaz-Beveridge; Virginia Martínez-Marín; David Vicente-Baz; Ana Vivancos; Javier Hernández-Losa; Joaquín Arribas; Joan Carles Journal: Oncologist Date: 2018-08-20
Authors: Michael J Cavnar; Kenneth Seier; Christina Curtin; Vinod P Balachandran; Daniel G Coit; Sam S Yoon; Aimee M Crago; Vivian E Strong; William D Tap; Mithat Gönen; Cristina R Antonescu; Murray F Brennan; Sam Singer; Ronald P DeMatteo Journal: Ann Surg Date: 2021-01-01 Impact factor: 13.787