Adjuvant therapy of gastrointestinal stromal tumors (GIST).
ABSTRACT Imatinib was proven to be effective for the adjuvant treatment of localized, surgically excised, gastrointestinal stromal tumors (GIST). Currently, there is proof that it is able to delay relapse and prolong survival. An effect on cure rate of localized GIST is still to be proven, given the shape of relapse-free survival curves, which apparently tend to overlap after 2-3 years from completion of the adjuvant period. Although observation for a longer follow-up is needed, attempts to prolong adjuvant therapy beyond the currently standard 3 years have been made and the results are awaited. However, the impact of more prolonged adjuvant intervals on secondary resistance is unknown, so that standard practice is still 3 years in most institutions. The adjuvant choice should be based on a rather precise identification of the relapse risk of the single patient, reserving treatment to the high-risk subgroups. The choice also should be personalized on the basis of genotype: generally, PDGFRA D842V mutated and wild-type GIST are excluded. Additional results from completed trials on a longer follow-up are awaited to further refine such "precision" decision-making. There are several instances in which part of the "adjuvant" treatment may be administered preoperatively, even on the face of a surgically resectable GIST, to make surgery more limited and/or safer.
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ABSTRACT: Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors arising in the gastrointestinal tract. Over the last decade, the management and prognosis of GISTs has changed dramatically with molecular characterization of the c-kit mutation and the adoption of targeted systemic therapy. Currently, the standard of care for resectable tumors is surgery, followed by adjuvant imatinib for tumors at high risk for recurrence. Inoperable or metastatic tumors are treated primarily with imatinib. Despite excellent initial response rates, resistance to targeted therapy has emerged as a common clinical problem, with relatively few therapeutic solutions. While the treatment of GISTs does not commonly include radiotherapy, radiation therapy could be a valuable contributing modality. Several case reports indicate that radiation can control locally progressive, drug-resistant disease. Further study is necessary to define whether radiation could potentially prevent or delay the onset of drug resistance, or improve outcomes when given in combination with imatinib.OncoTargets and Therapy 01/2014; 7:713-8. · 2.07 Impact Factor
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ABSTRACT: In the past few years, several targeted therapies have been approved for the treatment of advanced renal cell carcinoma. This has led to an improvement in the progression-free survival and quality of life of these patients. Nevertheless, the use of these and other therapies in the adjuvant setting has failed to demonstrate a clear benefit. Immune therapies as well as hormonal or targeted therapies have been studied in this indication, and there are clinical trials currently enrolling patients with high risk of relapse. This article reviews the available data and the ongoing trials exploring the role of adjuvant therapy for kidney cancer.Clinical Genitourinary Cancer 06/2014; · 1.43 Impact Factor
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ABSTRACT: Gastrointestinal stromal tumor (GIST) is known for its wide variability in biological behaviors and it is difficult to predict its malignant potential. The aim of this study is to explore the characteristics and prognostic factors of GIST. Clinical and pathological data of 497 GIST patients in our center between 1997 and 2012 were reviewed. Patients were categorized into very low-, low-, intermediate- and high-risk groups according to modified National Institutes of Health (NIH) consensus classification system. Among the 401 patients untreated with imatinib mesylate (IM), 5-year overall survival (OS) in very low-, low-, intermediate- and high-risk groups was 100%, 100%, 89.6% and 65.9%; and 5-year relapse-free survival (RFS) was 100%, 98.1%, 90.9% and 44.5%, respectively. Univariate analysis revealed that sex, tumor size, mitotic rate, risk grade, CD34 expression, and adjacent involvement were predictors of OS or RFS. COX hazard proportional model (Forward LR) showed that large tumor size, high mitotic rate, and high risk grade were independent risk factors to OS, whereas high mitotic rate, high risk grade and adjacent organ involvement were independent risk factors to RFS. The intermediate-high risk patients who received IM adjuvant therapy (n = 87) had better 5-year OS and RFS than those who did not (n = 188) (94.9% vs. 72.1; 82.3% vs. 56.3%, respectively). Similarly, advanced GIST patients underwent IM therapy (n = 45) had better 3-year OS and 1-year progression-free survival (PFS) than those who didn't (n = 42) (75.6% vs. 6.8%; 87.6% vs. 12.4%, respectively). Very low- and low-risk GISTs can be treated with surgery alone. Large tumor size, high mitotic rate, high risk grade, and adjacent organ involvement contribute to the poor outcome. IM therapy significantly improves the survival of intermediate-high risk or advanced GIST patients.BMC Surgery 11/2014; 14(1):93. · 1.97 Impact Factor