Surgical Management of Advanced Gastrointestinal Stromal Tumors After Treatment With Targeted Systemic Therapy Using Kinase Inhibitors

2006 ◽  
Vol 24 (15) ◽  
pp. 2325-2331 ◽  
Author(s):  
Chandrajit P. Raut ◽  
Matthew Posner ◽  
Jayesh Desai ◽  
Jeffrey A. Morgan ◽  
Suzanne George ◽  
...  
Keyword(s):  
Overall Survival ◽  
Disease Progression ◽  
Stable Disease ◽  
Systemic Therapy ◽  
Gastrointestinal Stromal Tumors ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Residual Disease ◽  
Stromal Tumors ◽  
Surgical Result

PurposeWhile targeted inhibitors of tyrosine kinase activity demonstrate dramatic efficacy in the majority of patients with advanced gastrointestinal stromal tumors (GISTs), cure remains elusive and resistance to systemic therapy is a challenge. To assess the role of surgery in multimodality management of GISTs, we studied postoperative outcomes in patients treated with targeted kinase inhibitors for advanced GIST.MethodsWe evaluated outcomes in a single institution series of 69 consecutive patients who underwent surgery for advanced GISTs while receiving kinase inhibitors. Patients were categorized based on extent of disease before surgery (stable disease, limited disease progression, generalized disease progression) and surgical result (no evidence of disease, minimal residual disease, bulky residual disease).ResultsDisease status before surgery was associated with surgical result (P < .0001; median follow-up, 14.6 months). After surgery, there was no evidence of disease in 78%, 25%, and 7% of patients with stable disease, limited progression, and generalized progression, respectively. Bulky residual disease remained after surgery in 4%, 16%, and 43% of the patients with stable disease, limited progression, and generalized progression. Twelve-month progression-free survival was 80%, 33%, and 0% for patients with stable disease, limited progression, and generalized progression (P < .0001). Twelve-month overall survival was 95%, 86%, and 0% for patients with stable disease, limited progression, and generalized progression (P < .0001).ConclusionPatients with advanced GISTs exhibiting stable disease or limited progression on kinase inhibitor therapy have prolonged overall survival after debulking procedures. Surgery has little to offer in the setting of generalized progression.

Treatment of nonresectable and metastatic gastrointestinal stromal tumors: Experience with the use of tyrosine kinase inhibitors in a third-level hospital in Mexico city.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 224-224
Author(s):  
Abdel Karim Dip Borunda ◽  
Alejandro J. Silva
Keyword(s):  
Overall Survival ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Gastrointestinal Stromal Tumors ◽  
Poor Prognosis ◽  
Kinase Inhibitors ◽  
Systemic Treatment ◽  
Progression Free Survival ◽  
Free Survival ◽  
Stromal Tumors

224 Background: Stromal tumors of the digestive tract are uncommon malignant diseases, and are subclassified as leiomyosarcomas and gastrointestinal stromal tumors (GIST) depending on the molecular expression of CD117 (KIT). GISTs represent 1% of malignant tumors affecting this anatomical site. Located diseases are reasonably well controlled by surgical resection and several criteria define the need for adjuvant therapy. In the case of metastatic disease a poor prognosis has been reported with systemic treatment based on chemotherapy. Recently, significant advances have been shown since Tyrosine – kinase inhibitors were introduced, with median overall survival close to 5 years. Unfortunately in Mexico, even though the therapy has been long used there are no published data of the experience in the treatment of these tumors. Methods: We used an electronic data base to obtain clinical, radiological and histological data of patients diagnosed with GIST and treated in the oncological center of the Mexican Institute of Social Security, patients were subclassified by stage, symptoms at diagnosis as well as the initial and subsequent systemic treatment. Finally we made an analysis for progression free survival and overall survival identifying prognostic factors. Results: We obtained information of 71 patients with metastatic, nonresectable or recurrent GIST, treated with a TKI, we observed a predominant relation for women (60.4%), with median age of 58 years. Stage at diagnosis was predominantly metastatic (46.5%) most frequently affected sites were lung, liver and retroperitoneum. Median progression free survival was 23.6m and overall survival was 81.3 months. All patients were initially treated with imatinib at a dose of 400mg per day. Treatment was well tolerated in most cases. Conclusions: Metastatic GIST evaluated in our center shows a different affection in gender and age, our population shows a different response to TKI’s, than reported in other series with superior overall survival, Poor prognosis is associated with lung affection. Biological studies will be started for the molecular evaluation of these tumors.

scholarly journals Why tyrosine kinase inhibitor resistance is common in advanced gastrointestinal stromal tumors

F1000Research ◽  
2013 ◽  
Vol 2 ◽  
pp. 152 ◽  
Author(s):  
Cristian Tomasetti ◽  
George D Demetri ◽  
Giovanni Parmigiani
Keyword(s):  
Tyrosine Kinase ◽  
Gastrointestinal Stromal Tumors ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Chronic Phase ◽  
Genetic Changes ◽  
Stromal Tumors ◽  
Mathematical Formulas ◽  
Inhibitor Resistance

Background: Most patients with advanced gastrointestinal stromal tumors (GIST) develop drug resistance to tyrosine kinase inhibitors (TKIs) within two years of starting therapy, whereas most chronic myeloid leukemia (CML) patients in chronic phase still exhibit disease control after a decade on therapy. This article aims to explain this divergence in long term outcomes.Methods and results: By combining clinical and experimental observations with mathematical formulas we estimate that, in advanced GIST, the genetic changes responsible for resistance are generally already present at disease detection.Conclusion: This result has relevant clinical implications by providing support for the exploration of combination therapies.

scholarly journals Gigantic GIST: A Case of the Largest Gastrointestinal Stromal Tumor Found to Date

2018 ◽  
Vol 2018 ◽  
pp. 1-5 ◽  
Author(s):  
Abdalla Mohamed ◽  
Youssef Botros ◽  
Paul Hanna ◽  
Sang Lee ◽  
Walid Baddoura ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Gastrointestinal Stromal Tumor ◽  
Gastrointestinal Stromal Tumors ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Stromal Tumor ◽  
Definitive Treatment ◽  
Gastrointestinal Neoplasms ◽  
Mesenchymal Tumors ◽  
Stromal Tumors

Gastrointestinal stromal tumors are uncommon when compared to all gastrointestinal neoplasms but are the most common mesenchymal tumors of the gastrointestinal tract. The largest gastrointestinal stromal tumor ever recorded in literature weighed approximately 6.1 kg and measured 39 cm × 27 cm × 14 cm. About two-thirds of GISTs are malignant. The tumor size, mitotic rate, cellularity, and nuclear pleomorphism are the most important parameters when considering prognosis and recurrence. The definitive treatment for these tumors is resection. In the year 2000, the first patient was treated with the tyrosine kinase inhibitor imatinib and since then, gastrointestinal stromal tumors with high-risk features have been treated successfully with tyrosine kinase inhibitors. We present the largest gastrointestinal stromal tumor recorded in medical literature measuring 42.0 cm × 31.0 cm × 23.0 cm in maximum dimensions and weighing in at approximately 18.5 kg in a 65-year-old African-American male who presented with increased abdominal distention. The mass was successfully excised, and the patient was treated with imatinib without local or distant recurrence 1.5 years postoperatively.

scholarly journals 18F-FDG PET Imaging in the Evaluation of Treatment Response to New Chemotherapies beyond Imatinib for Patients with Gastrointestinal Stromal Tumors

2011 ◽  
Vol 2011 ◽  
pp. 1-4 ◽  
Author(s):  
Antonella Stefanelli ◽  
Giorgio Treglia ◽  
Paoletta Mirk ◽  
Barbara Muoio ◽  
Alessandro Giordano
Keyword(s):  
Tyrosine Kinase ◽  
Treatment Response ◽  
Pet Imaging ◽  
Fdg Pet ◽  
Gastrointestinal Stromal Tumors ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Therapy Response ◽  
Ct Imaging ◽  
Stromal Tumors

Aim. 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) is a powerful tool for staging and defining “good responders” to chemotherapy in tumor setting. Gastrointestinal stromal tumors (GISTs) are sarcoma involving gastrointestinal tract and may require a chemotherapy including imatinib, a tyrosine kinase inhibitor agent. Some GIST patients become refractory to imatinib; therefore, other tyrosine kinase inhibitors or concomitant chemotherapy may be considered for treatment. The aim of this paper is to assess if 18F-FDG PET imaging is a useful tool to evaluate treatment response to new chemotherapies beyond imatinib for GIST patients. Methods. We performed a review of the literature about the role of 18F-FDG PET in the evaluation of treatment response to new chemotherapies beyond imatinib for GIST patients. Results and Conclusions. 18F-FDG PET seems to be able to assess therapy response earlier than computed tomography (CT) imaging in imatinib refractory GIST patients treated with other agents. However, a dual modality PET-CT imaging is recommendable to achieve a better detection of all lesions.

Stage IV gastrointestinal stromal tumors: Epidemiology, treatment and outcomes in adult US patients.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 462-462
Author(s):  
Johannes Uhlig ◽  
Stacey Stein ◽  
Jill Lacy ◽  
Michael Cecchini ◽  
Kevin Kim
Keyword(s):  
Overall Survival ◽  
Small Intestine ◽  
Surgical Resection ◽  
Systemic Therapy ◽  
Gastrointestinal Stromal Tumors ◽  
Cancer Site ◽  
Tumor Diameter ◽  
Combined Surgery ◽  
Stromal Tumors ◽  
Stage 4

462 Background: To evaluate epidemiology, treatment and outcomes of stage 4 gastrointestinal stromal tumors (GIST). Methods: The 2010-2016 United States National Cancer Database was queried for adult patients diagnosed with invasive GIST (ICD code 8936) at AJCC stage 4, without prior malignant disease. Overall survival (OS) was evaluated using Cox proportional hazards regression, accounting for potential confounders in multivariable models. Results: A total of 1,578 stage 4 GIST were included (13.3% of all GIST) with a male:female ratio of 1.38:1. The most common cancer site was the stomach (55.4%) and small intestine (40% of stage 4 GIST). At diagnosis, median age was 62 years and median tumor diameter 10 cm. Distant organ metastases were reported in 58.7%, the most frequent being hepatic (n = 801, 50.8% of stage 4 GIST). The majority of stage 4 GIST patients received systemic therapy (78.6%), either alone (35.4%) or combined surgery+systemic therapy (43.3%). Systemic therapy was administered neoadjuvant in 6.9%, adjuvant in 32%, and neoadjuvant+adjuvant in 5.1% of surgically resected patients. Another n = 204 patients (12.9% of all stage 4 GIST) were treated with surgical resection alone. GIST overall survival rates were 88%, 77%, 67% and 51% at 1, 2, 3, and 5 years, respectively. On multivariable Cox proportional hazard models, primary GIST treatment independently affected OS: compared to combined surgery+systemic therapy, OS was shorter for patients receiving systemic therapy alone (HR = 2.77 (95% CI: 2.12-3.61, p < 0.001)) and no treatment (HR = 4.2 (95% CI: 2.75-6.43, p < 0.001)). No significant OS difference was evident comparing surgery+systemic therapy and surgery alone (HR = 1.23 (95% CI: 0.88-1.72, p = 0.227)). In subgroup analyses of patients undergoing surgical resection, no statistically significant OS difference was evident comparing neoadjuvant, adjuvant and combined neoadjuvant+adjuvant systemic therapy on multivariable analyses. Treatment at non-academic vs. academic centers was associated with shorter OS (multivariable HR = 1.36 (95% CI: 1.1-1.69, p = 0.005)). Further independent OS predictors were male sex (vs. female HR = 1.28 (95% CI: 1.03-1.59, p = 0.023)), older age, higher comorbidities, higher cancer grade, and larger cancer diameter. Conclusions: Stage 4 GIST is a rare gastrointestinal malignancy that most commonly manifests in the stomach and small intestine in male patients, with frequent hepatic metastases and excellent 5-year OS rates of up to 51%. Combined surgery+systemic therapy demonstrates best outcomes, although surgical resection alone might yield comparable results in selected patients.

scholarly journals Gastrointestinal Stromal Tumors (GISTs): Novel Therapeutic Strategies with Immunotherapy and Small Molecules

2021 ◽  
Vol 22 (2) ◽  
pp. 493
Author(s):  
Christos Vallilas ◽  
Panagiotis Sarantis ◽  
Anastasios Kyriazoglou ◽  
Evangelos Koustas ◽  
Stamatios Theocharis ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Gastrointestinal Stromal Tumors ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Survival Rates ◽  
Cancer Therapeutics ◽  
Gastrointestinal Neoplasms ◽  
Mesenchymal Tumors ◽  
Stromal Tumors

Gastrointestinal stromal tumors (GISTs) are the most common types of malignant mesenchymal tumors in the gastrointestinal tract, with an estimated incidence of 1.5/100.000 per year and 1–2% of gastrointestinal neoplasms. About 75–80% of patients have mutations in the KIT gene in exons 9, 11, 13, 14, 17, and 5–10% of patients have mutations in the platelet-derived growth factor receptor a (PDGFRA) gene in exons 12, 14, 18. Moreover, 10–15% of patients have no mutations and are classified as wild type GIST. The treatment for metastatic or unresectable GISTs includes imatinib, sunitinib, and regorafenib. So far, GIST therapies have raised great expectations and offered patients a better quality of life, but increased pharmacological resistance to tyrosine kinase inhibitors is often observed. New treatment options have emerged, with ripretinib, avapritinib, and cabozantinib getting approvals for these tumors. Nowadays, immune checkpoint inhibitors form a new landscape in cancer therapeutics and have already shown remarkable responses in various tumors. Studies in melanoma, non-small-cell lung cancer, and renal cell carcinoma are very encouraging as these inhibitors have increased survival rates. The purpose of this review is to present alternative approaches for the treatment of the GIST patients, such as combinations of immunotherapy and novel inhibitors with traditional therapies (tyrosine kinase inhibitors).

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