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Cytoreductive Surgery for Metastatic Gastrointestinal Stromal Tumors Treated With Tyrosine Kinase Inhibitors: A 2-institutional Analysis

Fairweather, Mark, MD*,†; Balachandran, Vinod P., MD; Li, George Z., MD*; Bertagnolli, Monica M., MD*,†; Antonescu, Cristina, MD§; Tap, William, MD; Singer, Samuel, MD; DeMatteo, Ronald P., MD; Raut, Chandrajit P., MD, MSc*,†

doi: 10.1097/SLA.0000000000002281

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.

*Department of Surgery, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, MA

Center for Sarcoma and Bone Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, MA

Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY

§Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY

Department of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, NY.

Reprints: Chandrajit P. Raut, MD, MSc, Department of Surgery, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115. E-mail:

Presented in part at the Connective Tissue Oncology Society annual meeting, Salt Lake City, Utah, November 6, 2015.

M.F. and V.P.B. are co-first authors.

Source of funding: This work was supported by NIH R01 CA102613 (R.P.D.), the David and Monica Gorin Award of Courage (V.P.B.), and the Cancer Center Support Grant P30 CA008748 (MSKCC).

Conflicts of interest: Dr William Tap has the following disclosures: Consulting or Advisory Role: Advaxis, ARIAD Pharmaceuticals, EMD Serono, Plexxikon, Janssen Pharmaceuticals, Eli Lilly, Daiichi Sankyo, Eisai; Travel, Accommodations, Expenses: Boehringer Ingelheim; other relationships: Morphotek. The rest of the authors have no conflicts of interest.

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