Skip to Main Content

INTRODUCTION

In Chapter 33, Drs. Look Hong and Raut review gastrointestinal stromal tumor (GIST). Historically, metastatic GIST carried a median survival of 12 months, but this has improved to 5 years with the introduction of tyrosine kinase inhibitors (TKIs).1,2 The landmark finding of the effectiveness of imatinib in GIST has transformed a disease for which little treatment beyond surgery existed into a chronic disease for which multimodality therapy can give patients prolonged survival with good quality of life and possibly even cure. Following the success of imatinib in GIST, the paradigm of targeted molecular therapy has rapidly expanded, with US Food and Drug Administration (FDA) approval of orally available targeted molecular therapy agents for multiple targets in multiple solid tumors. Initial success with targeting tyrosine kinase receptors in non–small-cell lung cancer (EGFR and later ALK) and renal cell carcinoma (VEGFR) has now been broadened to include approval of drugs for breast cancer, colorectal cancer, thyroid cancer, soft tissue sarcoma, and pancreatic neuroendocrine tumor. In some instances, just 1 or 2 kinases are targeted, whereas in others, multiple kinases are inhibited. Additional available agents are now also widely used for targets downstream of tyrosine kinases, including BRAF in melanoma; mTOR in breast cancer, angiomyolipoma, and pancreatic neuroendocrine tumors; CDK4/6 in breast cancer; PARP in ovarian cancer; and Hedgehog in basal cell carcinoma.3 While experience gained in the treatment of GIST has paved the way for the introduction of targeted therapy in many other cancers, it has also taught us valuable lessons as to complex issues that may arise. The simplicity of targeting KIT or PDGFRA in GIST has turned out to be far more complex than initially thought, with response to therapy dependent on the specific mutation and the nearly inevitable development of secondary mutations and other mechanisms of resistance in advanced and recurrent disease.

While molecular therapy is highly effective, it is important to recognize that surgery remains the only chance for cure in patients with GIST. We now know from the placebo arm of the American College of Surgeons Oncology Group (ACOSOG) Z9001 trial that 70% of patients with GISTs ≥3 cm appear to be cured by surgery with 74 months of follow-up.4 Given the diverse anatomic locations of primary and metastatic disease, a variety of technical issues must be mastered for appropriate and safe treatment of GIST. Although surgical resection is the central component of treating GIST with curative intent, the surgeon treating GIST must also become knowledgeable in 3 key elements of the molecular therapy for this disease, which we highlight here: (1) appropriate patient selection and duration of neoadjuvant therapy; (2) adjuvant therapy in an increasingly well-defined subset of intermediate- and high-risk patients; and (3) surgical resection in well-selected patients with recurrent or metastatic disease.

SPECIFIC SURGICAL ISSUES

For the surgeon planning to resect a GIST, it is important to understand a number ...

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.