Comprehensive Overview of Gastrointestinal Stromal Tumor (GIST) Treatment

Gastrointestinal Stromal Tumors (GISTs) are rare mesenchymal tumors originating from the interstitial cells of Cajal in the gastrointestinal tract.

While they account for a small percentage of gastrointestinal cancers, their management requires a multidisciplinary approach due to their unique biological behavior and molecular characteristics. Diagnosis and Risk Stratification Accurate diagnosis of GISTs involves a combination of imaging techniques, such as computed tomography (CT) and magnetic resonance imaging (MRI), along with endoscopic ultrasound (EUS) to assess tumor size, location, and potential for metastasis. Histopathological examination, including immunohistochemistry for markers like CD117 (c-KIT) and DOG1, is essential for confirming the diagnosis. Genetic testing for mutations in KIT and PDGFRA genes provides critical information for treatment planning and prognosis assessment. Risk stratification is based on tumor size, mitotic index, and location, guiding decisions regarding the necessity of adjuvant therapy and surveillance protocols. Surgical Treatment Surgical resection remains the cornerstone of treatment for localized GISTs. The goal is to achieve complete (R0) resection with negative margins to minimize the risk of recurrence. Laparoscopic techniques are preferred for tumors amenable to minimally invasive approaches, offering benefits like reduced recovery time and hospital stay. However, for larger or more complex tumors, open surgery may be necessary to ensure complete removal and to manage potential complications such as bleeding or tumor rupture. In cases where complete surgical resection is not feasible due to tumor size or involvement of critical structures, neoadjuvant therapy with tyrosine kinase inhibitors may be considered to reduce tumor size and facilitate surgical intervention. Targeted Therapy The discovery of KIT and PDGFRA mutations has

revolutionized the treatment of GISTs. Imatinib mesylate, a tyrosine kinase inhibitor, is the standard first-line therapy for patients with tumors harboring these mutations. For patients with KIT exon 9 mutations, higher doses of imatinib (800 mg daily) may be required to achieve optimal therapeutic effects. For patients with PDGFRA D842V mutations, which are resistant to imatinib, avapritinib has shown efficacy as a second-line treatment. Other second-line options include sunitinib and regorafenib, particularly for patients who have progressed on imatinib therapy. Adjuvant therapy with imatinib is recommended for high-risk patients following complete surgical resection to reduce the risk of recurrence. The standard duration of adjuvant therapy is three years, with ongoing evaluation to assess the need for continuation beyond this period. Emerging Therapies and Clinical Trials Ongoing research into the molecular underpinnings of GISTs has led to the development of novel therapeutic agents targeting specific mutations and pathways involved in tumorigenesis. Clinical trials investigating the efficacy of combination therapies, immune checkpoint inhibitors, and other targeted agents are underway, offering hope for improved outcomes in patients with resistant or metastatic GISTs. Participation in clinical trials may provide access to cutting-edge therapies and contribute to the advancement of knowledge in GIST treatment. Conclusion Management of GISTs requires a personalized approach that considers the tumor's molecular profile, risk stratification, and individual patient factors. A combination of surgical intervention and targeted therapy has significantly improved outcomes for many patients. Ongoing research and clinical trials hold promise for further advancements in the treatment of GISTs, underscoring the importance of a multidisciplinary team in providing optimal care.