The management of advanced gastrointestinal stromal tumors (GISTs) has evolved in the modern era due to the discovery of mutations and the development of tyrosine kinase inhibitors (TKIs). of TKIs, surgical resection was the primary treatment for localized GIST. However, even in patients with resectable disease, the prognosis was unfavorable, as 5-12 months survival was only 54% (1,3). Furthermore, between 40% and 70% would develop recurrent or metastatic disease, with the median time from resection to recurrence being 2.4 years. Recurrence overwhelmingly occurs in the peritoneum, the liver, or both (3). Resection for recurrent disease was associated with a median survival of 15 months (4). While multiple chemotherapy brokers had been trialed, none experienced any significant effect, as (-)-Gallocatechin response rates were 10% (5). Resection of recurrent disease had mixed results. Resection of liver only recurrence was associated with 1- and 3-12 months survivals of 90% and 58%, respectively (6). Rabbit polyclonal to OGDH Resection of metastatic disease resulted in a modest survival improvement with median survival being 27 months (1). Post-TKI era Prognosis for patients diagnosed with GIST changed radically in 2002 with the approval of imatinib meslyate by the FDA as a treatment option. The landmark study by Demetri showed the efficacy of imatinib to produce a sustained objective response for unresectable and metastatic GIST translating to 24-month progression free survival (PFS) and 57-month overall survival (OS) (7). These results were confirmed by the B2222 trial. These two studies have established TKI therapy as the first collection treatment of unresectable and metastatic GIST. Cytoreduction surgery following a positive response to TKI therapy was then shown to further improve (-)-Gallocatechin survival. Fiore exhibited neoadjuvant TKI therapy to result in a 34% reduction in tumor size and 77% 3-12 months PFS in patients with unresectable or metastatic GIST (8). In another study performed by Blesius TKI alone (13). Change observed an improvement in 1-, 3-, and 5-12 months PFS in patients undergoing cytoreductive surgery followed by TKI therapy compared to TKI therapy alone; however, this did not translate into any significant improvement in OS (14). Intolerance of TKI therapy While TKIs are generally well tolerated, they are not without potential adverse effects. Most adverse effects are nonlife threatening: nausea, vomiting, diarrhea, muscle mass cramps, fatigue, hypothyroidism and fluid retention can be typically managed with ancillary treatment. However, while severe adverse effects, such as leukopenia and cardiotoxicity, can often be managed, occasionally they are severe enough to require dose reductions or cessation of treatment (15-17). Development of TKI resistance GIST resistance to TKIs evolves in two patterns: main and secondary. Main resistance is defined as evidence of progression during the first 6 months of TKI therapy and is primarily seen in patients with wild-type GISTs that lack the or mutations. Secondary resistance is seen in patients who have been on TKI therapy for 6 months with an initial response or disease stabilization, which is usually then followed by progression. This resistance pattern is due to the outgrowth of tumor clones with secondary mutations in (18-21). As far as time on therapy before surgery, the NCCN estimates the EORTC trial, which exhibited a median time to secondary resistance of 2 years. They recommend discussing medical procedures around 6C12 months of disease stability or response. Finally, NCCN recommends continuation of imatinib therapy post-operatively based on a study by Rutkowski that showed recurrent disease in patients who did not restart therapy. Indications There are several retrospective studies examining the role for surgical resection after imatinib therapy (13,22-28); these revealed a higher total resection rate and improved PFS and OS after surgery in patients who (-)-Gallocatechin responded to TKI therapy versus those who were resistant. One of the most recent and largest studies by Fairweather reported a 14-12 months experience [2001C2014] from 2.