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The Role of Surgical Resection Following Tyrosine Kinase Inhibitors Treatment in Patients with Advanced Gastrointestinal Stromal Tumors: A Systematic Review and Meta-analysis.

ABSTRACT: Background The benefit of surgical resection for advanced gastrointestinal stromal tumors (GISTs) following tyrosine kinase inhibitors (TKIs) treatment was still under debate. The present meta-analysis was designed to assess the value of surgical resection for the prognosis of patients with metastatic, recurrence and unresectable GISTs. Methods A systematic search of PubMed Central, PubMed, EMBASE and the Cochrane Library database was performed. Relevant studies of the role of surgery in advanced GISTs published before 1 May 2019 were identified. The quality of studies was assessed by the Newcastle-Ottawa Quality Assessment Scale. The progression-free survival (PFS) and overall survival (OS) were assessed through software Stata 15.0. Results A total of 6 retrospective studies including 655 patients were analyzed. The pooled result revealed that surgical resection group was associated with better PFS (HR = 2.08; 95% CI: 1.58 to 2.76; P<0.001) and better OS (HR = 2.13; 95% CI: 1.59 to 2.85; P<0.001) compared with TKIs treatment alone group. Conclusions Surgical resection following TKIs treatment could significantly improve the prognosis of patients with advanced GISTs.

SUBMITTER: Guo Y

PROVIDER: S-EPMC6843877 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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The Role of Surgical Resection Following Tyrosine Kinase Inhibitors Treatment in Patients with Advanced Gastrointestinal Stromal Tumors: A Systematic Review and Meta-analysis.

Guo Yinghao Y Liu Jinqiang J Wang Fei F Wang Qiao Q Zheng Gaozan G Liu Shushang S Lian Xiao X Zhang Hongwei H Feng Fan F

Journal of Cancer 20191006 23

<b>Background</b> The benefit of surgical resection for advanced gastrointestinal stromal tumors (GISTs) following tyrosine kinase inhibitors (TKIs) treatment was still under debate. The present meta-analysis was designed to assess the value of surgical resection for the prognosis of patients with metastatic, recurrence and unresectable GISTs. <b>Methods</b> A systematic search of PubMed Central, PubMed, EMBASE and the Cochrane Library database was performed. Relevant studies of the role of surg ...[more]

PMID: 31737115

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Project description:Simple Summary Gastrointestinal stromal tumors (GISTs) are rare mesenchymal neoplasms arising in the gastrointestinal tract, especially in the stomach (60–65%). The development of most cases of GISTs is associated with activating mutations in the receptor tyrosine kinase genes KIT and PDGFRA. The discovery of mutations leads to the approval of tyrosine kinase inhibitors (TKIs) for GISTs. Considering the recent approval of the last two TKIs and given their increased use in clinical practice, a spontaneous reporting system (SRS) database, the main tool in pharmacovigilance, takes a remarkable role in promptly characterizing the benefit/risk profile of these new drugs and consequently improve the quality of life of patients affected by GISTs. Abstract Tyrosine kinase inhibitors (TKIs) are widely used in gastrointestinal stromal tumors (GISTs). The aim of this study is to evaluate the reporting frequency of neuropsychiatric adverse drug reactions (ADRs) for TKIs through the analysis of European individual case safety reports (ICSRs). All ICSRs collected in EudraVigilance up to 31 December 2021 with one TKI having GISTs as an indication (imatinib (IM), sunitinib (SU), avapritinib (AVA), regorafenib (REG), and ripretinib (RIP)) were included. A disproportionality analysis was performed to assess the frequency of reporting for each TKI compared to all other TKIs. The number of analyzed ICSRs was 8512, of which 57.9% were related to IM. Neuropsychiatric ADRs were reported at least once in 1511 ICSRs (17.8%). A higher reporting probability of neuropsychiatric ADRs was shown for AVA. Most neuropsychiatric ADRs were known, except for a higher frequency of lumbar spinal cord and nerve root disorders (reporting odds ratio, ROR 4.46; confidence interval, CI 95% 1.58–12.54), olfactory nerve disorders (8.02; 2.44–26.33), and hallucinations (22.96; 8.45–62.36) for AVA. The analyses of European ICSRs largely confirmed the safety profiles of TKIs in GISTs, but some ADRs are worthy of discussion. Further studies are needed to increase the knowledge of the neuropsychiatric disorders of newly approved TKIs.

Project description:Gastrointestinal stromal tumors (GISTs) are the most commonly diagnosed mesenchymal tumors of the gastrointestinal tract. The risk of recurrence following surgical resection of GISTs is typically reported from the date of surgery. However, disease-free survival (DFS) over time is dynamic and changes based on disease-free time already accumulated following surgery.To assess the comparative performance of established GIST recurrence risk prognostic scoring systems and to characterize conditional DFS following surgical resection of GISTs.A retrospective cohort study of 502 patients who underwent surgery for a primary, nonmetastatic GIST between January 1, 1998, and December 31, 2012, at 7 major academic cancer centers in the United States and Canada.Disease-free survival of the patients was classified according to 5 prognostic scoring systems, including the National Institutes of Health criteria, modified National Institutes of Health criteria, Memorial Sloan Kettering Cancer Center GIST nomogram, and American Joint Committee on Cancer gastric and nongastric categories. The concordance index (also known as the C statistic or the area under the receiver operating curve) of established GIST recurrence risk prognostic scoring systems. Conditional DFS estimates were calculated.Overall 1-year, 3-year, and 5-year DFS following resection of GISTs was 95%, 83%, and 74%, respectively. All the prognostic scoring systems had fair prognostic ability. For all tumor sites, the American Joint Committee on Cancer gastric category demonstrated the best discrimination (C?=?0.79). Using conditional DFS, the probability of remaining disease free for an additional 3 years given that a patient was disease free at 1 year, 3 years, and 5 years was 82%, 89%, and 92%, respectively. Patients with the highest initial recurrence risk demonstrated the greatest increase in conditional survival as time elapsed.Conditional DFS improves over time following resection of GISTs. This is valuable information about long-term prognosis to communicate to patients who are disease free after a period following surgery.

Dataset Information

The Role of Surgical Resection Following Tyrosine Kinase Inhibitors Treatment in Patients with Advanced Gastrointestinal Stromal Tumors: A Systematic Review and Meta-analysis.

Publications

The Role of Surgical Resection Following Tyrosine Kinase Inhibitors Treatment in Patients with Advanced Gastrointestinal Stromal Tumors: A Systematic Review and Meta-analysis.

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