Excision of a Large Gastrointestinal Stromal Tumour Following 16 Months of Neoadjuvant Therapy with Imatinib (Case Report).
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ABSTRACT: Introduction
Although the standard treatment for stromal tumours is surgery, in locally advanced forms, it is often necessary to achieve tumour downstaging to improve surgical outcomes. Neoadjuvant treatment in gastrointestinal stromal tumours (GISTs) with tyrosine kinase inhibitors, including imatinib, has been shown to be effective in several studies, but the duration of this treatment is still a subject of debate.Case report
We report a case of a large GIST of the stomach in a 51-year-old patient with atypical presentation that was initially unresectable. Neoadjuvant treatment with imatinib for 16 months resulted in a good response, allowing secondary surgical excision.Conclusion
Imatinib in neoadjuvant therapy should be continued as long as there is a good response and tolerance to the medication to obtain tumour downsizing compatible with carcinologic excision.
SUBMITTER: Alassani F
PROVIDER: S-EPMC7359978 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:IntroductionNeoadjuvant imatinib (Neo-IM) therapy may facilitate R0 resection in primary gastrointestinal stromal tumors (GISTs) that are large or in difficult anatomic locations. While response to preoperative tyrosine kinase inhibitors is associated with better outcome in metastatic GIST, little is known about prognostic factors after Neo-IM in primary GIST.Study designPatients with primary GIST with or without synchronous metastases who underwent Neo-IM were retrospectively analyzed from a prospective maintained institutional database for Response Evaluation Criteria in Solid Tumors (RECIST), tumor viability, and mitotic rate. Overall survival (OS) was estimated by Kaplan-Meier and compared by log-rank test. Cox proportionate hazard models were used for univariate and multivariate analysis.ResultsOne hundred and fifty patients were treated for a median of 7.1 months (range 0.2-160). By RECIST, partial response, stable disease, and progressive disease were seen in 40%, 51%, and 9%, respectively. By pathologic analysis, ≤ 50% of the tumor was viable in 72%, and the mitotic rate was ≤ 5/50HPF in 74%. On multivariate analysis, RECIST response and tumor viability were not associated with OS, while post-treatment high mitotic rate (hazard ratio (HR) for death 5.3, CI 2.3-12.4), R2 margins (HR 6.0, CI 2.3-15.5), and adjuvant imatinib (HR 0.4, CI 0.2-0.9) were (p < 0.05). Five-year OS was 81 vs. 38% for low vs. high mitotic rate; 81, 59, and 39% for R0, R1, and R2 margins; and 75 vs 61% for adjuvant vs. no adjuvant imatinib therapy (p < 0.05).ConclusionsIn primary GIST undergoing Neo-IM therapy, progression was uncommon, but substantial down-sizing occurred in the minority. High tumor mitotic rate and incomplete resection following Neo-IM were associated with poor outcome, while adjuvant imatinib was associated with prolonged survival.
| S-EPMC8386278 | biostudies-literature
Project description:Neoadjuvant imatinib for gastrointestinal stromal tumours (GISTs) is increasingly used nowadays. As oesophagectomy is associated with high morbidity and mortality, a preoperative downsizing of an oesophageal GIST to limit the extent of resection would be ideal. Because these tumours are rare and neoadjuvant treatment with imatinib is recent, there is limited literature available regarding neoadjuvant administration of imatinib in patients with oesophageal GISTs. A 50-year-old woman presented with total dysphagia. An upper endoscopy and biopsy revealed a large submucosal KIT-positive GIST obstructing the mid oesophagus. CT confirmed a lesion measuring 99 mm × 50 mm × 104 mm. Because the size and location of the tumour increased the risk of intraoperative rupture, it was decided to administer preoperative imatinib. The patient had an excellent clinical and radiological response. Her dysphagia gradually resolved and the follow-up CT scans of the first 10 months showed a gradually reducing tumour size to 54 mm × 33 mm × 42 mm. The patient underwent an uneventful laparoscopic-assisted Ivor-Lewis oesophagectomy. Postoperatively, the patient continued with adjuvant imatinib. At the last follow-up, 1 year from operation and 38 months from the diagnosis, the patient is disease free.
| S-EPMC4436469 | biostudies-literature
Project description:IntroductionA duodenal Gastrointestinal Stromal Tumour (GIST) is a rare finding and until recently advanced disease had a poor prognosis. A PubMed search revealed no reports of more than five years survival of inoperable GIST on chemotherapy with WHO performance status zero.Case presentationA 68 year old female was diagnosed with unresectable GIST in the duodenum with metastasis to liver, pancreas and omentum in November 2001. She was commenced on imatinib mesylate (Glivec) chemotherapy. This case report was prepared from the medical records and radiology reports. She had good tolerance with stable disease. After six years her CT scan showed no disease progression and her WHO performance status was zero.ConclusionThis report supports the view that imatinib is a safe and effective drug in controlling disease progression in advanced metastatic GIST and plays an important role in improving the patient's quality of life.
| S-EPMC2386476 | biostudies-literature
Project description:AimTo evaluate endoscopic ultrasound (EUS)-guided biopsies for the pretreatment characterization of gastrointestinal stromal tumors (GIST) to personalize the management of patients.MethodsAll patients with lesions suspected to be GIST who were referred for EUS-sampling at a tertiary Swedish center were eligible for inclusion 2006-2015. During the observational study phase (2006-2011), routine fine-needle-aspiration (EUS-FNA) was performed. In 2012-2015, we converted to an interventional, randomized protocol with dual sampling EUS-FNA and fine-needle-biopsy-sampling (EUS-FNB) for all lesions. c-KIT- and DOG-1-immunostaining was attempted in all samples and a manual count of the Ki-67-index was performed. FNB-sampled tissue and the resected specimens were subjected to Sanger sequencing of the KIT and platelet-derived growth factor alpha (PDGFRA) genes.ResultsIn all, 64 unique patients with GIST were included, and of these, 38 were subjected to pretreatment dual sampling. EUS-FNB had a higher diagnostic sensitivity when compared head-to-head with EUS-FNA (98% vs 58%, P < 0.001) and was more adequate for Ki-67-indexing (Ki-67EUS) (92% vs 40%, P < 0.001). Sequencing of EUS-biopsies was successful in 43/44 (98%) patients, and the mutation profiles (KIT-mutation 73%, PDGFRA-mutation 18%, wild-type 7%) were fully congruent with those detected in the corresponding resected specimens. In imatinib-naïve patients, the Ki-67EUS was comparable with the Ki-67-index in the corresponding surgical specimens (Ki-67SURG) (2.7% vs 2.9%, P = 0.68). In patients treated with neoadjuvant imatinib who also carried mutations indicating sensitivity, the Ki-67EUS was higher than the Ki-67SURG (2.5% vs 0.2%, P = 0.005), with a significant reduction in the Ki-67-index of -91.5% (95%CI: -82.4 to -96.0, P = 0.005).ConclusionEUS-guided biopsy sampling is accurate for the pretreatment diagnosis and characterization of GISTs and allows the prediction and evaluation of tumor response to neoadjuvant imatinib therapy.
| S-EPMC5583577 | biostudies-literature
Project description:BACKGROUND:Neoadjuvant imatinib therapy has been proposed for routine practice with favorable long-term results for patients with locally advanced gastrointestinal stromal tumors (GISTs). However, clarification of the optimal duration, safety, and oncological outcomes of neoadjuvant imatinib use before surgical intervention remains necessary. METHODS:We prospectively analyzed the treatment outcomes of 51 patients with locally advanced, nonmetastatic GISTs treated with neoadjuvant imatinib followed by surgery. The optimal duration was defined as the timepoint when there was a <10% change in the treatment response or a size decrease of less than 5 mm between two consecutive computed tomography scans. RESULTS:Primary tumors were located in the stomach (23/51; 45%), followed by the rectum (17/51; 33%), ileum/jejunum (9/51; 18%), and esophagus (2/51; 4%). The median maximal shrinkage time was 6.1 months, beyond which further treatment may not be beneficial. However, the maximal shrinkage time was 4.3 months for the stomach, 8.6 months for the small bowel and 6.9 months for the rectum. The R0 tumor resection rate in 27 patients after neoadjuvant imatinib and surgery was 81.5%, and 70.4% of resection procedures succeeded in organ preservation. However, 10 of 51 patients (19.6%) had complications following neoadjuvant imatinib use (six from imatinib and four from surgery). CONCLUSION:Our analysis supports treating GIST patients with neoadjuvant imatinib, which demonstrated favorable long-term results of combined therapy. However, careful monitoring of complications is necessary. The optimal duration of neoadjuvant imatinib use before surgical intervention is, on average, 6.1 months.
| S-EPMC6468640 | biostudies-literature
Project description:Vatalanib (PTK787/ZK 222584) inhibits a few tyrosine kinases including KIT, platelet-derived growth factor receptors (PDGFRs) and vascular endothelial growth factor receptors (VEGFRs). We report efficacy and safety results of vatalanib in advanced gastrointestinal stromal tumour (GIST) resistant to imatinib or both imatinib and sunitinib.Forty-five patients whose metastatic GIST had progressed on imatinib were enrolled. Nineteen (42.2%) patients had received also prior sunitinib. Vatalanib 1250 mg was administered orally daily.Eighteen patients (40.0%; 95% confidence interval (CI), 25.7-54.3%) had clinical benefit including 2 (4.4%) confirmed partial remissions (PR; duration, 9.6 and 39.4 months) and 16 (35.6%) stabilised diseases (SDs; median duration, 12.5 months; range, 6.0-35.6+ months). Twelve (46.2%) out of the 26 patients who had received prior imatinib only achieved either PR or SD compared with 6 (31.6%, all SDs) out of the 19 patients who had received prior imatinib and sunitinib (P=0.324). The median time to progression was 5.8 months (95% CI, 2.9-9.5 months) in the subset without prior sunitinib and 3.2 (95% CI, 2.1-6.0) months among those with prior imatinib and sunitinib (P=0.992). Vatalanib was generally well tolerated.Vatalanib is active despite its narrow kinome interaction spectrum in patients diagnosed with imatinib-resistant GIST or with imatinib and sunitinib-resistant GIST.
| S-EPMC3111164 | biostudies-literature
Project description:The purpose of the study is to determine the efficacy of hepatic artery embolization (HAE) as a therapy for gastrointestinal stromal tumor (GIST) in patients who are refractory to imatinib and sunitinib.After institutional review board approval, a retrospective review revealed 11 patients with GIST metastatic to the liver who underwent 15 HAEs between February 2002 and May 2013. These patients were stratified into two groups according to the previous treatment: (a) those treated with HAE as second-line treatment after failing first-line imatinib (n?=?3) and (b) those treated with HAE as third-line therapy after failing first-line imatinib and second-line sunitinib (n?=?8). Initial therapeutic response, overall survival (OS), progression-free survival (PFS), and safety were evaluated.Initial therapeutic response rates at 3 months after HAE were 27.3 % (95 % confidence interval (CI), 6.0-61.0 %) by Response Evaluation Criteria in Solid Tumor (RECIST) version 1.0 and 45.5 % (95 % CI, 16.7-76.6 %) by modified RECIST (mRECIST). The median OS and PFS after HAE were 14.9 and 3.9 months in group A and 23.8 and 3.4 months in group B, respectively. No procedure-related mortality or major complication was observed.HAE is an effective and well-tolerated therapeutic option for GIST liver metastases. Although larger studies are necessary, HAE should be considered as an alternative or adjuvant to third-line or even second-line systemic treatment.
| S-EPMC5637522 | biostudies-literature
Project description: Not available
| S-EPMC6824868 | biostudies-literature
Project description:BackgroundGastrointestinal stromal tumour is the most common sarcoma of the intestinal tract. Imatinib mesylate is a small molecule that inhibits activation of the KIT and platelet-derived growth factor receptor alpha proteins, and is effective in first-line treatment of metastatic gastrointestinal stromal tumour. We postulated that adjuvant treatment with imatinib would improve recurrence-free survival compared with placebo after resection of localised, primary gastrointestinal stromal tumour.MethodsWe undertook a randomised phase III, double-blind, placebo-controlled, multicentre trial. Eligible patients had complete gross resection of a primary gastrointestinal stromal tumour at least 3 cm in size and positive for the KIT protein by immunohistochemistry. Patients were randomly assigned, by a stratified biased coin design, to imatinib 400 mg (n=359) or to placebo (n=354) daily for 1 year after surgical resection. Patients and investigators were blinded to the treatment group. Patients assigned to placebo were eligible to crossover to imatinib treatment in the event of tumour recurrence. The primary endpoint was recurrence-free survival, and analysis was by intention to treat. Accrual was stopped early because the trial results crossed the interim analysis efficacy boundary for recurrence-free survival. This study is registered with ClinicalTrials.gov, number NCT00041197.FindingsAll randomised patients were included in the analysis. At median follow-up of 19.7 months (minimum-maximum 0-56.4), 30 (8%) patients in the imatinib group and 70 (20%) in the placebo group had had tumour recurrence or had died. Imatinib significantly improved recurrence-free survival compared with placebo (98% [95% CI 96-100] vs 83% [78-88] at 1 year; hazard ratio [HR] 0.35 [0.22-0.53]; one-sided p<0.0001). Adjuvant imatinib was well tolerated, with the most common serious events being dermatitis (11 [3%] vs 0), abdominal pain (12 [3%] vs six [1%]), and diarrhoea (ten [2%] vs five [1%]) in the imatinib group and hyperglycaemia (two [<1%] vs seven [2%]) in the placebo group.InterpretationAdjuvant imatinib therapy is safe and seems to improve recurrence-free survival compared with placebo after the resection of primary gastrointestinal stromal tumour.FundingUS National Institutes of Health and Novartis Pharmaceuticals.
| S-EPMC2915459 | biostudies-literature
Project description:The increasing use of patient-administered oral anticancer drugs is paralleled by new challenges in maintaining treatment adherence. These challenges are particularly significant with adjuvant therapies for prevention of disease recurrence, where the benefits of ongoing treatment are not readily apparent to patients. Nurse practitioners and physician assistants (collectively referred to as advanced practitioners) play integral roles in providing education on disease and treatment to patients that can increase adherence to oral therapies and ideally improve outcomes. For patients with gastrointestinal stromal tumor (GIST), the oral targeted therapy imatinib has become the mainstay of treatment for advanced and recurrent disease and as adjuvant therapy following surgical resection. Recent data indicate significantly improved overall survival with 3 years vs. 1 year of adjuvant imatinib therapy. Continuous dosing with imatinib is needed for optimal efficacy and to limit additional health-care costs associated with management of disease progression in GIST. However, longer duration of therapy increases the risk of nonadherence. Imatinib adherence rates, as well as factors contributing to nonadherence to adjuvant therapy in routine clinical practice, are discussed in this review. Also explored are practical approaches for improving adherence to adjuvant imatinib therapy through greater patient education, in light of the increased duration of therapy in select patients.
| S-EPMC4093429 | biostudies-literature