scholarly journals Recent Progress and Challenges in the Diagnosis and Treatment of Gastrointestinal Stromal Tumors

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3158
Author(s):  
Toshirou Nishida ◽  
Shigetaka Yoshinaga ◽  
Tsuyoshi Takahashi ◽  
Yoichi Naito
Keyword(s):  
Gastrointestinal Stromal Tumors ◽  
Kinase Inhibitors ◽  
Genetic Diagnosis ◽  
Mesenchymal Tumors ◽  
True Incidence ◽  
Stromal Tumors ◽  
Molecular Alterations ◽  
Initial Work ◽  
Rare Gene ◽  
Permanent Cure

Gastrointestinal stromal tumors (GISTs) are the most frequent malignant mesenchymal tumors in the gastrointestinal tract. The clinical incidence of GISTs is estimated 10/million/year; however, the true incidence is complicated by frequent findings of tiny GISTs, of which the natural history is unknown. The initial work-up with endoscopy and endoscopic ultrasonography plays important roles in the differential diagnosis of GISTs. Surgery is the only modality for the permanent cure of localized GISTs. In terms of safety and prognostic outcomes, laparoscopy is similar to laparotomy for GIST treatment, including tumors larger than 5 cm. GIST progression is driven by mutations in KIT or PDGFRA or by other rare gene alterations, all of which are mutually exclusive. Tyrosine kinase inhibitors (TKIs) are the standard therapy for metastatic/recurrent GISTs. Molecular alterations are the most reliable biomarkers for TKIs and for other drugs, such as NTRK inhibitors. The pathological and genetic diagnosis prior to treatment has been challenging; however, a newly developed endoscopic device may be useful for diagnosis. In the era of precision medicine, cancer genome profiling by targeted gene panel analysis may enable potential targeted therapy even for GISTs without KIT or PDGFRA mutations.

scholarly journals Gastrointestinal Stromal Tumors (GISTs): Novel Therapeutic Strategies with Immunotherapy and Small Molecules

2021 ◽  
Vol 22 (2) ◽  
pp. 493
Author(s):  
Christos Vallilas ◽  
Panagiotis Sarantis ◽  
Anastasios Kyriazoglou ◽  
Evangelos Koustas ◽  
Stamatios Theocharis ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Gastrointestinal Stromal Tumors ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Survival Rates ◽  
Cancer Therapeutics ◽  
Gastrointestinal Neoplasms ◽  
Mesenchymal Tumors ◽  
Stromal Tumors

Gastrointestinal stromal tumors (GISTs) are the most common types of malignant mesenchymal tumors in the gastrointestinal tract, with an estimated incidence of 1.5/100.000 per year and 1–2% of gastrointestinal neoplasms. About 75–80% of patients have mutations in the KIT gene in exons 9, 11, 13, 14, 17, and 5–10% of patients have mutations in the platelet-derived growth factor receptor a (PDGFRA) gene in exons 12, 14, 18. Moreover, 10–15% of patients have no mutations and are classified as wild type GIST. The treatment for metastatic or unresectable GISTs includes imatinib, sunitinib, and regorafenib. So far, GIST therapies have raised great expectations and offered patients a better quality of life, but increased pharmacological resistance to tyrosine kinase inhibitors is often observed. New treatment options have emerged, with ripretinib, avapritinib, and cabozantinib getting approvals for these tumors. Nowadays, immune checkpoint inhibitors form a new landscape in cancer therapeutics and have already shown remarkable responses in various tumors. Studies in melanoma, non-small-cell lung cancer, and renal cell carcinoma are very encouraging as these inhibitors have increased survival rates. The purpose of this review is to present alternative approaches for the treatment of the GIST patients, such as combinations of immunotherapy and novel inhibitors with traditional therapies (tyrosine kinase inhibitors).

scholarly journals The importance of molecular biology in development, prognosis, treatment and resistance to targeted therapy in gastrointestinal stromal tumors

2011 ◽  
pp. 69-79
Author(s):  
Alessandro Comandone ◽  
Elisa Berno ◽  
Simona Chiadò Cutin ◽  
Antonella Boglione
Keyword(s):  
Tyrosine Kinase ◽  
Gastrointestinal Stromal Tumors ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Neoplastic Transformation ◽  
Response To Therapy ◽  
Mesenchymal Tumors ◽  
Kit Mutation ◽  
Stromal Tumors ◽  
Receive Treatment

Gastrointestinal stromal tumors (GISTs) are the commonest mesenchymal tumors of the gastroenteric tract, and are generally believed to originate from the neoplastic transformation of the interstitial cells of Cajal, the pacemaker structures of the stomach and intestine. Exon and genetic mutations (point/deletions) are fundamental for the development of GISTs: the constitutional characteristic of this neoplasm is the presence of the cell surface Kit receptor. Kit is the product of the proto-oncogene cKit, situated in chromosome 4. Ninety-eight percent of GISTs express mutated isoforms of Kit or of PDGFRA (Platelet growth factor receptor a). Kit mutation is the basic condition for autophosphorylation of tyrosine kinase residues in proteins. Autophosphorylation initiates pathogenetic processes in Cajal cells, toward a neoplastic transformation. Imatinib mesilate and, more recently, sunitinib are tyrosine kinase inhibitors, specific antagonists for Kit and PDGFRA, with good activity against GISTs. Most molecular and clinical data currently available concern imatinib. Exon mutations are strategic as prognostic and as predictive factors. In recent years, much evidence suggests that survival, response to therapy and resistance to imatinib are related to different mutations. In the near future, GIST patients will receive treatment differentiated by expressed Kit and PDGFRA mutations, thus truly individualized therapy.

scholarly journals Mutation status and immunohistochemical correlation of EGFR mutations in gastrointestinal stromal tumors

2021 ◽  
Vol 24 (1) ◽  
pp. 67-72
Author(s):  
H Ozkayalar ◽  
MC Ergoren ◽  
G Tuncel ◽  
S Kurt ◽  
E Cevik ◽  
...  
Keyword(s):  
Gastrointestinal Stromal Tumors ◽  
Kinase Inhibitors ◽  
Treatment Options ◽  
Growth Factor Receptor ◽  
Egfr Mutations ◽  
Stromal Tumors ◽  
Molecular Alterations ◽  
Treatment Regimes ◽  
Research Areas ◽  
Turkish Patients

Abstract Being one of the leading causes of cancer deaths worldwide and their resistance to conventional treatment methods, made gastrointestinal stromal tumors (GISTs) one of the hot topics in medical research areas in the past decade. To investigate molecular alterations underlying the tumor is of great importance to be able to develop new, targeted treatment options. In this study, GIST samples obtained from 40 Turkish patients were analyzed for actionable epidermal growth factor receptor (EGFR) mutations that are related to treatment regimes in non small cell lung cancer (NSCLC) to understand whether EGFR expression is altered in GISTs. Established alterations in EGFR can make the use of tyrosine kinase inhibitors possible, which are currently used in cancer therapy, especially in NSCLC. Our results indicated that EGFR mutations are rare in GISTs. Further research is needed to sequence whole coding regions of the gene to investigate new actionable mutations in EGFR in an increased sample size.

scholarly journals The importance of molecular biology in development, prognosis, treatment and resistance to targeted therapy in gastrointestinal stromal tumors

2011 ◽  
Vol 2 (2) ◽  
pp. 69
Author(s):  
Alessandro Comandone ◽  
Elisa Berno ◽  
Simona Chiadò Cutin ◽  
Antonella Boglione
Keyword(s):  
Tyrosine Kinase ◽  
Gastrointestinal Stromal Tumors ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Neoplastic Transformation ◽  
Response To Therapy ◽  
Mesenchymal Tumors ◽  
Kit Mutation ◽  
Stromal Tumors ◽  
Receive Treatment

Gastrointestinal stromal tumors (GISTs) are the commonest mesenchymal tumors of the gastroenteric tract, and are generally believed to originate from the neoplastic transformation of the interstitial cells of Cajal, the pacemaker structures of the stomach and intestine. Exon and genetic mutations (point/deletions) are fundamental for the development of GISTs: the constitutional characteristic of this neoplasm is the presence of the cell surface Kit receptor. Kit is the product of the proto-oncogene cKit, situated in chromosome 4. Ninety-eight percent of GISTs express mutated isoforms of Kit or of PDGFRA (Platelet growth factor receptor a). Kit mutation is the basic condition for autophosphorylation of tyrosine kinase residues in proteins. Autophosphorylation initiates pathogenetic processes in Cajal cells, toward a neoplastic transformation. Imatinib mesilate and, more recently, sunitinib are tyrosine kinase inhibitors, specific antagonists for Kit and PDGFRA, with good activity against GISTs. Most molecular and clinical data currently available concern imatinib. Exon mutations are strategic as prognostic and as predictive factors. In recent years, much evidence suggests that survival, response to therapy and resistance to imatinib are related to different mutations. In the near future, GIST patients will receive treatment differentiated by expressed Kit and PDGFRA mutations, thus truly individualized therapy.

scholarly journals A Novel Kindred with Familial Gastrointestinal Stromal Tumors Caused by a Rare KIT Germline Mutation (N655K): Clinico-Pathological Presentation and TKI Sensitivity

2020 ◽  
Vol 10 (4) ◽  
pp. 234
Author(s):  
Mara Fornasarig ◽  
Daniela Gasparotto ◽  
Luisa Foltran ◽  
Michele Campigotto ◽  
Sara Lombardi ◽  
...  
Keyword(s):  
Germline Mutation ◽  
Gastrointestinal Stromal Tumors ◽  
Kinase Inhibitors ◽  
Age Of Onset ◽  
Mesenchymal Tumors ◽  
Kit Mutation ◽  
Stromal Tumors ◽  
Activating Mutations ◽  
Imatinib Resistant

Gastrointestinal stromal tumors (GISTs), the most common mesenchymal tumors of the gastrointestinal tract, are characterized by activating mutations in KIT or PDGFRA genes. The vast majority of GISTs are sporadic, but rare hereditary forms have been reported, often featuring multifocality and younger age of onset. We here report the identification of a novel kindred affected by familial GIST caused by a KIT germline mutation in exon 13 (N655K). No family affected by hereditary GIST due to this KIT variant has been reported in literature so far. We were able to track the mutation in three members of the family (proband, mother, and second-degree cousin), all affected by multiple GISTs. Due to its rarity, the N655K variant is poorly characterized. We conducted in vitro drug sensitivity assays that indicated that most tyrosine kinase inhibitors (TKIs) currently included in the therapeutic armamentarium for GISTs have a limited inhibitory activity toward this mutation. However, when compared to a classical imatinib-resistant KIT mutation (T670I), N655K was slightly more sensitive to imatinib, and encouraging responses were observed with last-generation TKIs.

scholarly journals Gigantic GIST: A Case of the Largest Gastrointestinal Stromal Tumor Found to Date

2018 ◽  
Vol 2018 ◽  
pp. 1-5 ◽  
Author(s):  
Abdalla Mohamed ◽  
Youssef Botros ◽  
Paul Hanna ◽  
Sang Lee ◽  
Walid Baddoura ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Gastrointestinal Stromal Tumor ◽  
Gastrointestinal Stromal Tumors ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Stromal Tumor ◽  
Definitive Treatment ◽  
Gastrointestinal Neoplasms ◽  
Mesenchymal Tumors ◽  
Stromal Tumors

Gastrointestinal stromal tumors are uncommon when compared to all gastrointestinal neoplasms but are the most common mesenchymal tumors of the gastrointestinal tract. The largest gastrointestinal stromal tumor ever recorded in literature weighed approximately 6.1 kg and measured 39 cm × 27 cm × 14 cm. About two-thirds of GISTs are malignant. The tumor size, mitotic rate, cellularity, and nuclear pleomorphism are the most important parameters when considering prognosis and recurrence. The definitive treatment for these tumors is resection. In the year 2000, the first patient was treated with the tyrosine kinase inhibitor imatinib and since then, gastrointestinal stromal tumors with high-risk features have been treated successfully with tyrosine kinase inhibitors. We present the largest gastrointestinal stromal tumor recorded in medical literature measuring 42.0 cm × 31.0 cm × 23.0 cm in maximum dimensions and weighing in at approximately 18.5 kg in a 65-year-old African-American male who presented with increased abdominal distention. The mass was successfully excised, and the patient was treated with imatinib without local or distant recurrence 1.5 years postoperatively.

Incidence of gastrointestinal stromal tumors (GISTs) in France: Results of the PROGIST survey conducted among pathologists

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 10047-10047 ◽  
Author(s):  
G. Monges ◽  
J. Coindre ◽  
J. Scoazec ◽  
A. Bouvier ◽  
J. Blay ◽  
...  
Keyword(s):  
Gastrointestinal Stromal Tumors ◽  
Epidemiologic Study ◽  
Mitotic Rate ◽  
Annual Incidence ◽  
Mesenchymal Tumors ◽  
True Incidence ◽  
Stromal Tumors ◽  
One Year ◽  
First Time ◽  
Risk Categories

10047 Background: GISTs are the most common mesenchymal tumors of the gastrointestinal tract but data on the annual incidence of this tumor is scarce due to previous lack of well-defined pathologic criteria. The aim of this study was to investigate the incidence of GISTs in France and describe the distribution according to age, sex, circumstances of discovery, localization and risk categories. Methods: This prospective epidemiologic study was performed among pathologists who were asked to declare all the cases of GIST over a one year period. All pathology centers (330 centers) in France were proposed to participate and asked to report exhaustively the cases diagnosed from 1 December 2004 to 30 November 2005. Results: 591 cases of GISTs were reported, 535 new cases and 56 cases of relapse. However, some large centers were not able to participate. So, the annual estimated incidence was 12 cases/million inhabitants in France. The main characteristics of the new cases of GIST were as follows: mean age 65 (± 13.2) (range: 16–93) years, 48.6% men and 51.4% women, circumstances of discovery: fortuitous 163 (30.5%), symptomatic 249 (46.5%), unknown 123 (23%). The primary tumor locations were: stomach 341 (63.7 %), small intestine 115 (21.5%), mesentery 35 (6.5%), colon/rectum 17 (3.2%), esophagus 4 (0.7%), unknown 23 (4.3%). 95.3% of GISTs were cKIT (CD117) + and 3.7 % were cKIT -. According to the Fletcher consensus criteria, based on tumor size and mitotic rate, among the 490 localized GISTs 14.7% were considered to be at very low prognostic risk, 25.5% at low-risk, 23.1 % at intermediate risk and 23.1 % at high-risk. For 13.6 % data were missing. Conclusions: This study is providing for the first time an estimation of the annual incidence of GISTs and a description of the characteristics of these tumors in France based on pathology registration. The true incidence may be slightly higher as some large centers were not able to reported their cases. These results are comparable to what has been reported in recent studies in other European countries. No significant financial relationships to disclose.

Resection of esophageal gastrointestinal stromal tumors.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e20503-e20503
Author(s):  
Vladimir Trifanov ◽  
Oleg I Kit ◽  
Liubov Yu Vladimirova ◽  
Dmitriy Trifanov ◽  
Vadim Kasatkin
Keyword(s):  
Gastrointestinal Tract ◽  
Gastrointestinal Stromal Tumors ◽  
Kinase Inhibitors ◽  
Mitotic Rate ◽  
Endoscopic Biopsy ◽  
Surrounding Tissue ◽  
Mesenchymal Tumors ◽  
Management Guidelines ◽  
Stromal Tumors ◽  
Right Lobe

e20503 Background: Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of gastrointestinal tract. GISTs account for 0,1% to 0,3% of all tumors in the gastrointestinal tract. Two thirds of these tumors arise from the stomach, 25% arise from the small intestine and less than 5% arise from esophagus. Use of tyrosine kinase inhibitors has revolutionized therapy for GISTs but complete resection remains the treatment of choice. Methods: We report our experience (from 2005 to 2011) with five patients who underwent resection of esophageal GIST. Reviewed consensus management guidelines and performed a literature review for reported cases. Results: All five patients underwent surgery intervention at our institute. Four patients had no metastasis and they underwent tumor enucleation. Due to submucosal location only one of them was diagnosed with GIST by endoscopic biopsy before surgery. One patient had a giant liver metastasis invading totally all segments of right lobe of liver. He underwent transhiatal extirpation simultaneously combined with extended right-sided hemihepatectomy. That patient suffered from total dysphagia, 15 kg weight loss, gastrointestinal bleeding and a big lump in his right hypochondrium. After laparotomy we diagnosed big metastatic nodule invading the whole right lobe of liver 25 cm in diameter. After diaphragmotomy we diagnosed tumor of the lower third of esophagus. Consequently, we performed extended right-sided hemihepatectomy and transhiatal esophagus extirpation. Two months later esophageal plastics by means of ileocaecal segment of colon was performed. The pathological diagnosis was confirmed in all five cases by microscopic examination (KIT+; CD17+, mitotic rate). In adjuvant regime imatinib (400 mg/body/day) was administered for a year for all five patients. The patients are alive now, they were followed up every six months with CT for two years. Fortunately, no new tumors were observed during this period of time. Conclusions: Esophagectomy is the treatment of choice for esophageal GISTs but requires attention to operative details that emphasize complete en block excision of surrounding tissue and metastatic nodules.

Multislice imaging of gastrointestinal stromal tumors

2018 ◽  
pp. 3-14
Keyword(s):  
Computed Tomography ◽  
Key Words ◽  
Gold Standard ◽  
Gastrointestinal Stromal Tumors ◽  
Mesenchymal Tumors ◽  
Stromal Tumors ◽  
Preferential Localization ◽  
Multislice Imaging ◽  
Computed Tomography Diagnosis

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the digestive tract (1%). These tumors express the CD 117 in 95% of cases. The stomach is the preferential localization (70%). Diagnosis is difficult and sometimes late. Progress of imaging has greatly improved the management and the prognosis. Computed tomography (CT) is the gold standard for diagnosis, staging, and treatment follow-up. The increasing recognition of GIST’s histopathology and the prolonged survival revealed some suggestive imaging aspects. Key words: gastro-intestinal stromal tumors; computed tomography; diagnosis

scholarly journals Prognostic value of Onodera’s nutritional index for intermediate- and high-risk gastrointestinal stromal tumors treated with or without tyrosine kinase inhibitors

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Feng Wang ◽  
Tingting Tao ◽  
Heng Yu ◽  
Yingying Xu ◽  
Zhi Yang ◽  
...  
Keyword(s):  
Propensity Score ◽  
Propensity Score Matching ◽  
Prognostic Marker ◽  
Gastrointestinal Stromal Tumors ◽  
Prognostic Value ◽  
Kinase Inhibitors ◽  
Rank Test ◽  
Stromal Tumors ◽  
Lymphocyte Ratio ◽  
Nutritional Index

Abstract Background Immunoinflammatory and nutritional markers, such as the peripheral blood neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and Onodera’s prognostic nutritional index (OPNI), have gained considerable attention and have been preliminarily revealed as prognostic markers of gastrointestinal stromal tumors (GISTs). Methods In this study, we first investigated the prognostic value of OPNI in GISTs treated with or without TKIs based on the propensity score matching (PSM) method. All of the patients had received surgical resection for primary GIST, and data from 2010 to 2018 were initially and retrospectively identified from our gastrointestinal center. Recurrence-free survival (RFS) was calculated by the Kaplan–Meier method and compared by the log-rank test. Results The patients were divided into groups treated and not treated with TKIs, and we used the propensity score matching method to homogenize their baseline data. Multivariate Cox proportional hazard regression models were applied to identify associations with outcome variables. A total of 563 GISTs were initially chosen, and 280 of them were included for analysis under the inclusion criteria. After PSM, there were 200 patients included. Multivariate analyses identified OPNI as an independent prognostic marker that was associated with primary site, tumor size, mitotic index, tumor rupture, necrosis, and modified NIH risk classification. Low OPNI (< 42.6; HR 0.409; P < 0.001) was associated with worse RFS. Conclusions Preoperative OPNI is a novel and useful prognostic marker for GISTs both treated and not treated with TKIs. Higher NLR and PLR have negative effects on RFS.

Sign in / Sign up

Export Citation Format

Share Document