Dataset Information

Excision of a Large Gastrointestinal Stromal Tumour Following 16 Months of Neoadjuvant Therapy with Imatinib (Case Report).

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 | 2019 Dec

REPOSITORIES: biostudies-literature

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Publications

Excision of a Large Gastrointestinal Stromal Tumour Following 16 Months of Neoadjuvant Therapy with Imatinib (Case Report).

Alassani Fousséni F Tchangai Boyodi B Bagny Aklesso A Adani-Ife Ablavi A AA Amavi Kossigan A KA Darre Tchin T Attipou Komla K

Oncology and therapy 20191102 2

<h4>Introduction</h4>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.<h4>Case report</h4>We report a case of a large GIST of the stomach in a ...[more]

PMID: 32699986

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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.

Project description:BackgroundAlthough imatinib is a well-established first-line drug for treating a vast majority of gastrointestinal stromal tumours (GIST), GISTs acquire secondary resistance during therapy. Multi-omics approaches provide an integrated perspective to empower the development of personalised therapies through a better understanding of functional biology underlying the disease and molecular-driven selection of the best-targeted individualised therapy. In this study, we applied integrative metabolomic and transcriptomic analyses to elucidate tumour biochemical processes affected by imatinib treatment.Materials and methodsA GIST xenograft mouse model was used in the study, including 10 mice treated with imatinib and 10 non-treated controls. Metabolites in tumour extracts were analysed using gas chromatography coupled with mass spectrometry (GC-MS). RNA sequencing was also performed on the samples subset (n=6).ResultsMetabolomic analysis revealed 21 differentiating metabolites, whereas next-generation RNA sequencing data analysis resulted in 531 differentially expressed genes. Imatinib significantly changed the profile of metabolites associated mainly with purine and pyrimidine metabolism, butanoate metabolism, as well as alanine, aspartate, and glutamate metabolism. The related changes in transcriptomic profiles included genes involved in kinase activity and immune responses, as well as supported its impact on the purine biosynthesis pathway.ConclusionsOur multi-omics study confirmed previously known pathways involved in imatinib anticancer activity as well as correlated imatinib-relevant downregulation of expression of purine biosynthesis pathway genes with the reduction of respectful metabolites. Furthermore, considering the importance of the purine biosynthesis pathway for cancer proliferation, we identified a potentially novel mechanism for the anti-tumour activity of imatinib. Based on the results, we hypothesise metabolic modulations aiming at the reduction in purine and pyrimidine pool may ensure higher imatinib efficacy or re-sensitise imatinib-resistant tumours.

Dataset Information

Excision of a Large Gastrointestinal Stromal Tumour Following 16 Months of Neoadjuvant Therapy with Imatinib (Case Report).

Introduction

Case report

Conclusion

Publications

Excision of a Large Gastrointestinal Stromal Tumour Following 16 Months of Neoadjuvant Therapy with Imatinib (Case Report).

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