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Neoadjuvant Therapy to Downstage the Extent of Resection of Gastrointestinal Stromal Tumors.

ABSTRACT: Introduction:Gastrointestinal stromal tumors (GIST) are rare malignant tumors in terms of incidence, and they are not linked to specific symptoms. Often, primary tumors, particularly of the stomach, rectum, or rectovaginal space, are quite large when detected, and multivisceral resection seems to be the treatment of choice as the mainstay of therapy is complete tumor removal. If a gain-of-function mutation in the KIT gene is present, drug therapy with receptor tyrosine kinase inhibitors (RTKIs) might significantly downstage primary GIST tumors. Methods:A review of the literature was performed to identify the current evidence for preoperative treatment of GIST regarding toxicity, efficacy, and oncological outcome, including mutational data from our own database. Results:Four phase II as well as several cohort studies showed acceptable toxicity and no increased perioperative morbidity of preoperative imatinib. Progressive disease during preoperative treatment was a rare event, and partial response was achieved in 40-80% of all patients. For methodological reasons, the trials cannot prove an oncological long-term superiority of preoperative treatment. Conclusion:Preoperative therapy with imatinib is safe and recommended for patients with locally advanced GIST. Neoadjuvant imatinib therapy may enable less invasive and organ-sparing surgery, avoid tumor rupture during extensive resectional procedures, and improve the quality of perioperative RTKI treatment.

SUBMITTER: Jakob J

PROVIDER: S-EPMC6257203 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Neoadjuvant Therapy to Downstage the Extent of Resection of Gastrointestinal Stromal Tumors.

Jakob Jens J Hohenberger Peter P

Visceral medicine 20181009 5

<h4>Introduction</h4>Gastrointestinal stromal tumors (GIST) are rare malignant tumors in terms of incidence, and they are not linked to specific symptoms. Often, primary tumors, particularly of the stomach, rectum, or rectovaginal space, are quite large when detected, and multivisceral resection seems to be the treatment of choice as the mainstay of therapy is complete tumor removal. If a gain-of-function mutation in the <i>KIT</i> gene is present, drug therapy with receptor tyrosine kinase inhi ...[more]

PMID: 30498703

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Project description:BackgroundDespite the recent large number of studies comparing endoscopic and laparoscopic resection for small gastrointestinal stromal tumors (GISTs) (diameter ≤ 5 cm), the results remain conflicting. The objective of this work was to perform a cumulative meta-analysis to assess the advantages and disadvantages of endoscopic resection vs. laparoscopic resection.MethodsThe meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We searched medical databases up to January 2020. Meta-analytical random or fixed effects models were used in pooled analyses. Meta-regression, cumulative meta-analyses, and subgroup analyses were performed to improve the accuracy of the conclusion. Sensitivity analyses were applied to assess the robustness of the results.ResultsA total of 12 cohort studies with 1383 participants comparing endoscopic resection and laparoscopic resection were identified, while three cohort studies with 167 participants comparing endoscopic resection and laparoscopic and endoscopic cooperative surgery were found. We found that endoscopic resection had shorter operation times (weighted mean difference [WMD] = -27.1 min, 95% confidence interval [CI]: -40.8 min to -13.4 min) and lengths of hospital stay (WMD = -1.43 d, 95% CI: -2.31 d to -0.56 d) than did laparoscopic resection. The results were stable and reliable. There were no significant differences in terms of blood loss, hospitalization costs, incidence of complications or recurrence rates. For tumor sizes 2 - 5 cm, endoscopic resection increased the risk of positive margins (relative risk [RR] = 5.78, 95% CI: 1.31 - 25.46). Although operation times for endoscopic resection were shorter than those of laparoscopic and endoscopic cooperative surgery (WMD = -41.03 min, 95% CI: -59.53 min to -22.54 min), there was a higher incidence of complications (RR = 4.03, 95% CI: 1.57 - 10.34).ConclusionsIn general, endoscopic resection is an alternative method for gastric GISTs ≤ 5 cm. Laparoscopic and endoscopic cooperative surgery may work well in combination. Further randomized controlled trials are recommended to validate or update these results.

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.

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Neoadjuvant Therapy to Downstage the Extent of Resection of Gastrointestinal Stromal Tumors.

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Neoadjuvant Therapy to Downstage the Extent of Resection of Gastrointestinal Stromal Tumors.

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