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Prospective Evaluation of Neoadjuvant Imatinib Use in Locally Advanced Gastrointestinal Stromal Tumors: Emphasis on the Optimal Duration of Neoadjuvant Imatinib Use, Safety, and Oncological Outcome.

ABSTRACT: 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.

SUBMITTER: Wang SY

PROVIDER: S-EPMC6468640 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Prospective Evaluation of Neoadjuvant Imatinib Use in Locally Advanced Gastrointestinal Stromal Tumors: Emphasis on the Optimal Duration of Neoadjuvant Imatinib Use, Safety, and Oncological Outcome.

Wang Shang-Yu SY Wu Chiao-En CE Lai Chun-Chi CC Chen Jen-Shi JS Tsai Chun-Yi CY Cheng Chi-Tung CT Yeh Ta-Sen TS Yeh Chun-Nan CN

Cancers 20190325 3

<h4>Background</h4>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.<h4>Methods</h4>We prospectively analyzed the treatment outcomes of 51 patients with locally advanced, nonmetastatic GISTs treated with neoadjuvant ...[more]

PMID: 30934606

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Project description:To evaluate endoscopic ultrasound (EUS)-guided biopsies for the pretreatment characterization of gastrointestinal stromal tumors (GIST) to personalize the management of patients.All 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.In 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).EUS-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.

Dataset Information

Prospective Evaluation of Neoadjuvant Imatinib Use in Locally Advanced Gastrointestinal Stromal Tumors: Emphasis on the Optimal Duration of Neoadjuvant Imatinib Use, Safety, and Oncological Outcome.

Publications

Prospective Evaluation of Neoadjuvant Imatinib Use in Locally Advanced Gastrointestinal Stromal Tumors: Emphasis on the Optimal Duration of Neoadjuvant Imatinib Use, Safety, and Oncological Outcome.

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