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Cancers
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Gastrointestinal Stromal Tumors (GIST): Opportunity and Challenges in Diagnosis and...
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Gastrointestinal Stromal Tumors (GIST): Opportunity and Challenges in Diagnosis and Treatment

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (1 June 2023) | Viewed by 10147

Special Issue Editors

Prof. Dr. Antonio Russo

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Guest Editor
Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, 90127 Palermo, Italy
Interests: predictive and prognostic factors in solid tumors; identification of therapeutic target; pancreatic cancer; hereditary breast and ovarian cancer; meta-analysis; liquid biopsy; precision oncology
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Giuseppe Badalamenti

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Guest Editor
Department of Surgical, Oncological, and Oral Sciences, Section of Medical Oncology, University of Palermo, Via Del Vespro 127, Palermo, Italy
Interests: soft tissue sarcomas; gastrointestinal stromal tumors; neuroendocrine tumors
Special Issues, Collections and Topics in MDPI journals
Dr. Lorena Incorvaia

E-Mail Website
Guest Editor
Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90127 Palermo, Italy
Interests: soft tissue sarcomas; gastrointestinal stromal tumors; gynecological and genitourinary tumors; cancer genetics; hereditary breast and ovarian cancers; prognostic and predictive biomarkers; molecular mechanisms of targeted therapy and immunotherapy resistance
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

GISTs (gastrointestinal stromal tumors) are a subgroup of mesenchymal tumors originating from the interstitial cells of Cajal, which can arise from any part of the gastrointestinal tract, most frequently from the stomach and small intestine, characterized by the expression of the cell–surface transmembrane receptor KIT with tyrosine kinase activity in approximately 95% of tumors. Tumor mutational status is biologically and clinically important in GISTs and makes this tumor a paradigmatic model of oncogene addiction. Constitutively activating mutations in the gene coding for KIT proto-oncogene receptor tyrosine kinase (KIT) or in platelet-derived growth factor receptor alpha (PDGFRA) oncogenes are alternative and mutually exclusive, highlighting their important role in the pathogenesis of GISTs. KIT and PDGFRA mutations represent known prognostic and predictive biomarkers for GISTs and are useful in driving the choice of therapy in the adjuvant and metastatic setting. Notably, evidence to support the prognostic role of mutational status is growing.

We are pleased to invite experts in this field to review the current approaches to managing patients with GIST and focus on the molecular and immunological aspects of this heterogeneous group of neoplasms. In this Special Issue, original research articles and reviews are welcome.

We look forward to receiving your contributions.

Dr. Antonio Russo 
Dr. Giuseppe Badalamenti
Dr. Lorena Incorvaia
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • sarcomas
  • GIST
  • target therapy
  • immunotherapy

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Published Papers (4 papers)

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Research

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19 pages, 850 KiB  
Article
Neuropsychiatric Adverse Drug Reactions with Tyrosine Kinase Inhibitors in Gastrointestinal Stromal Tumors: An Analysis from the European Spontaneous Adverse Event Reporting System
by Maria Antonietta Barbieri, Emanuela Elisa Sorbara, Giulia Russo, Giuseppe Cicala, Tindara Franchina, Mariacarmela Santarpia, Nicola Silvestris and Edoardo Spina
Cancers 2023, 15(6), 1851; https://doi.org/10.3390/cancers15061851 - 20 Mar 2023
Cited by 8 | Viewed by 2539
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Gastrointestinal Stromal Tumors (GIST): Opportunity and Challenges in Diagnosis and Treatment)
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10 pages, 4619 KiB  
Article
Intraoperative Near-Infrared Fluorescence Imaging with Indocyanine Green for Identification of Gastrointestinal Stromal Tumors (GISTs), a Feasibility Study
by Gijsbert M. Kalisvaart, Ruben P. J. Meijer, Okker D. Bijlstra, Hidde A. Galema, Wobbe O. de Steur, Henk H. Hartgrink, Cornelis Verhoef, Lioe-Fee de Geus-Oei, Dirk J. Grünhagen, Yvonne M. Schrage, Alexander L. Vahrmeijer and Jos A. van der Hage
Cancers 2022, 14(6), 1572; https://doi.org/10.3390/cancers14061572 - 18 Mar 2022
Cited by 5 | Viewed by 2157
Abstract
Background: Optimal intraoperative tumor identification of gastrointestinal stromal tumors (GISTs) is important for the quality of surgical resections. This study aims to assess the potential of near-infrared fluorescence (NIRF) imaging with indocyanine green (ICG) to improve intraoperative tumor identification. Methods: Ten GIST patients, [...] Read more.
Background: Optimal intraoperative tumor identification of gastrointestinal stromal tumors (GISTs) is important for the quality of surgical resections. This study aims to assess the potential of near-infrared fluorescence (NIRF) imaging with indocyanine green (ICG) to improve intraoperative tumor identification. Methods: Ten GIST patients, planned to undergo resection, were included. During surgery, 10 mg of ICG was intravenously administered, and NIRF imaging was performed at 5, 10, and 15 min after the injection. The tumor fluorescence intensity was visually assessed, and tumor-to-background ratios (TBRs) were calculated for exophytic lesions. Results: Eleven GIST lesions were imaged. The fluorescence intensity of the tumor was visually synchronous and similar to the background in five lesions. In one lesion, the tumor fluorescence was more intense than in the surrounding tissue. Almost no fluorescence was observed in both the tumor and healthy peritoneal tissue in two patients with GIST lesions adjacent to the liver. In three GISTs without exophytic growth, no fluorescence of the tumor was observed. The median TBRs at 5, 10, and 15 min were 1.0 (0.4–1.2), 1.0 (0.5–1.9), and 0.9 (0.7–1.2), respectively. Conclusion: GISTs typically show similar fluorescence intensity to the surrounding tissue in NIRF imaging after intraoperative ICG administration. Therefore, intraoperatively administered ICG is currently not applicable for adequate tumor identification, and further research should focus on the development of tumor-specific fluorescent tracers for GISTs. Full article
(This article belongs to the Special Issue Gastrointestinal Stromal Tumors (GIST): Opportunity and Challenges in Diagnosis and Treatment)
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Review

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14 pages, 1645 KiB  
Review
Exploring the Dynamic Crosstalk between the Immune System and Genetics in Gastrointestinal Stromal Tumors
by Alessandra Dimino, Chiara Brando, Laura Algeri, Valerio Gristina, Erika Pedone, Marta Peri, Alessandro Perez, Ida De Luca, Roberta Sciacchitano, Luigi Magrin, Tancredi Didier Bazan Russo, Marco Bono, Nadia Barraco, Silvia Contino, Maria La Mantia, Antonio Galvano, Giuseppe Badalamenti, Antonio Russo, Viviana Bazan and Lorena Incorvaia
Cancers 2023, 15(1), 216; https://doi.org/10.3390/cancers15010216 - 29 Dec 2022
Cited by 8 | Viewed by 1881
Abstract
Gastrointestinal Stromal Tumors (GISTs) represent a paradigmatic model of oncogene addiction. Despite the well-known impact of the mutational status on clinical outcomes, we need to expand our knowledge to other factors that influence behavior heterogeneity in GIST patients. A growing body of studies [...] Read more.
Gastrointestinal Stromal Tumors (GISTs) represent a paradigmatic model of oncogene addiction. Despite the well-known impact of the mutational status on clinical outcomes, we need to expand our knowledge to other factors that influence behavior heterogeneity in GIST patients. A growing body of studies has revealed that the tumor microenvironment (TME), mostly populated by tumor-associated macrophages (TAMs) and lymphocytes (TILs), and stromal differentiation (SD) have a significant impact on prognosis and response to treatment. Interestingly, even though the current knowledge of the role of immune response in this setting is still limited, recent pre-clinical and clinical data have highlighted the relevance of the TME in GISTs, with possible implications for clinical practice in the near future. Moreover, the expression of immune checkpoints, such as PD-L1, PD-1, and CTLA-4, and their relationship to the clinical phenotype in GIST are emerging as potential prognostic biomarkers. Looking forward, these variables related to the underlying tumoral microenvironment in GIST, though limited to still-ongoing trials, might lead to the potential use of immunotherapy, alone or in combination with targeted therapy, in advanced TKI-refractory GISTs. This review aims to deepen understanding of the potential link between mutational status and the immune microenvironment in GIST. Full article
(This article belongs to the Special Issue Gastrointestinal Stromal Tumors (GIST): Opportunity and Challenges in Diagnosis and Treatment)
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14 pages, 1115 KiB  
Review
Latest Advances in the Management of Pediatric Gastrointestinal Stromal Tumors
by Marta Andrzejewska, Jakub Czarny and Katarzyna Derwich
Cancers 2022, 14(20), 4989; https://doi.org/10.3390/cancers14204989 - 12 Oct 2022
Cited by 6 | Viewed by 2360
Abstract
Gastrointestinal stromal tumor is the most common mesenchymal neoplasm of the gastrointestinal tract, usually found in elderly adults. It is infrequent among pediatric patients and usually differs biologically from adult-type diseases presenting mutations of KIT and PDGFR genes. In this population, more frequent [...] Read more.
Gastrointestinal stromal tumor is the most common mesenchymal neoplasm of the gastrointestinal tract, usually found in elderly adults. It is infrequent among pediatric patients and usually differs biologically from adult-type diseases presenting mutations of KIT and PDGFR genes. In this population, more frequent is the wild-type GIST possessing SDH, TRK, RAS, NF1 mutations, among others. Both tumor types require individualized treatment with kinase inhibitors that are still being tested in the pediatric population due to the different neoplasm biology. We review the latest updates to the management of pediatric gastrointestinal tumors with a particular focus on the advances in molecular biology of the disease that enables the definition of possible resistance. Emerging treatment with kinase inhibitors that could serve as targeted therapy is discussed, especially with multikinase inhibitors of higher generation, the effectiveness of which has already been confirmed in the adult population. Full article
(This article belongs to the Special Issue Gastrointestinal Stromal Tumors (GIST): Opportunity and Challenges in Diagnosis and Treatment)
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