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2.
BMC Cancer ; 24(1): 828, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38992597

ABSTRACT

BACKGROUND: Most gastrointestinal stromal tumors (GISTs) harbor c-KIT or PDGFRA mutations. Administration of tyrosine kinase inhibitors (TKIs) has significantly improved the survival of patients with GISTs. We aimed to evaluate the clinical outcome of advanced or recurrent GIST patients in Taiwan. METHODS: Patients diagnosed between 2010 and 2020 were enrolled. The collected data included baseline characteristics, treatment pattern, treatment outcome, genetic aberrations and survival status. Progression-free survival (PFS) and overall survival (OS) were analyzed and plotted with the Kaplan-Meier method. Cox regression analysis was used to analyze the prognostic factors of survival. RESULTS: A total of 224 patients with advanced or recurrent GISTs treated with TKIs were enrolled. All patients received imatinib treatment. Ninety-three and 42 patients received sunitinib and regorafenib treatment, respectively. The 48-month PFS and OS rates for patients treated with imatinib were 50.5% and 79.5%, respectively. c-KIT exon 9 and PDGFRA mutations were prognostic factors for a poor PFS and PDGFRA mutation was a prognostic factor for a poor OS in patients treated with imatinib in multivariate Cox regression analysis. The median PFS of patients who received sunitinib treatment was 12.76 months (95% confidence interval (CI), 11.01-14.52). Patients with c-KIT exon 9 mutations had a longer PFS than those with other genetic aberrations. The median PFS of patients treated with regorafenib was 7.14 months (95% CI, 3.39-10.89). CONCLUSIONS: We present real-world clinical outcomes for advanced GIST patients treated with TKIs and identify mutational status as an independent prognostic factor for patient survival.


Subject(s)
Gastrointestinal Stromal Tumors , Mutation , Neoplasm Recurrence, Local , Protein Kinase Inhibitors , Proto-Oncogene Proteins c-kit , Receptor, Platelet-Derived Growth Factor alpha , Registries , Humans , Gastrointestinal Stromal Tumors/drug therapy , Gastrointestinal Stromal Tumors/mortality , Gastrointestinal Stromal Tumors/genetics , Gastrointestinal Stromal Tumors/pathology , Female , Male , Taiwan/epidemiology , Middle Aged , Protein Kinase Inhibitors/therapeutic use , Aged , Proto-Oncogene Proteins c-kit/genetics , Adult , Receptor, Platelet-Derived Growth Factor alpha/genetics , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/genetics , Sunitinib/therapeutic use , Imatinib Mesylate/therapeutic use , Prognosis , Aged, 80 and over , Gastrointestinal Neoplasms/drug therapy , Gastrointestinal Neoplasms/mortality , Gastrointestinal Neoplasms/genetics , Gastrointestinal Neoplasms/pathology , Phenylurea Compounds/therapeutic use , Pyridines/therapeutic use , Survival Rate , Progression-Free Survival , Kaplan-Meier Estimate
4.
BMC Nephrol ; 25(1): 229, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39030472

ABSTRACT

BACKGROUND: Hypercalcaemia is a common manifestation of sarcoidosis but is sparingly described in gastrointestinal stromal tumours (GISTs). We describe a case of acute kidney injury and hypercalcemia resulting from simultaneous diagnosis of GIST and sarcoidosis, the presentation of which has not yet been reported. CASE PRESENTATION: A 61-year-old male presented with acute kidney injury and hypercalcemia, with elevated 1,25-dihydroxyvitamin D levels. Investigations demonstrated a large gastric antral mass which was resected and proven to be GIST. Histopathology of incidentally found liver nodules revealed non-necrotising epithelioid granulomas consistent with concomitant sarcoidosis. The hypercalcemia was successfully treated with bisphosphonate therapy, resection of the GIST and a four month course of corticosteroids, which was truncated due to a mycobacterial infection. CONCLUSIONS: Our case report is the first to describe hypercalcemia due to GIST and biopsy-proven sarcoidosis, thereby raising the possibility of a common pathophysiological pathway relating the two entities. We review the literature describing the mechanisms of hypercalcaemia in GIST and the association between GIST and sarcoidosis.


Subject(s)
Gastrointestinal Stromal Tumors , Hypercalcemia , Sarcoidosis , Humans , Hypercalcemia/etiology , Male , Sarcoidosis/complications , Middle Aged , Gastrointestinal Stromal Tumors/complications
5.
Ann Afr Med ; 23(3): 501-504, 2024 Jul 01.
Article in French, English | MEDLINE | ID: mdl-39034580

ABSTRACT

Gastrointestinal stromal tumors (GISTs) are uncommon mesenchymal neoplasms primarily found in the gastrointestinal (GI) tract. While they typically occur in older adults, GISTs can manifest in individuals of any age. This publication paper presents a case study of a rare occurrence: a spontaneously ruptured duodenal GIST in a young female. Through an in-depth review of the literature, we aim to provide insights into the clinical presentation, diagnostic challenges, management strategies, and long-term outcomes associated with this unique clinical scenario.


RésuméLes tumeurs stromales gastro-intestinales (GIST) sont des néoplasmes mésenchymateux peu communs principalement trouvés dans le tractus gastro-intestinal (GI). Bien qu'elles surviennent généralement chez les adultes plus âgés, les GIST peuvent se manifester chez des individus de tout âge. Cet article présente une étude de cas d'une occurrence rare: une GIST duodénale spontanément rompue chez une jeune femme. À travers une revue approfondie de la littérature, nous visons à fournir des éclairages sur la présentation clinique, les défis diagnostiques, les stratégies de prise en charge et les résultats à long terme associés à ce scénario clinique unique.


Subject(s)
Duodenal Neoplasms , Gastrointestinal Stromal Tumors , Humans , Female , Gastrointestinal Stromal Tumors/diagnosis , Gastrointestinal Stromal Tumors/pathology , Gastrointestinal Stromal Tumors/diagnostic imaging , Duodenal Neoplasms/pathology , Duodenal Neoplasms/diagnosis , Duodenal Neoplasms/diagnostic imaging , Adult , Rupture, Spontaneous , Treatment Outcome , Tomography, X-Ray Computed
7.
PLoS One ; 19(7): e0306598, 2024.
Article in English | MEDLINE | ID: mdl-38968220

ABSTRACT

The ideal surgical approach for treating cardia gastrointestinal stromal tumor (GIST) is not clearly established. This study aimed to assess the long-term survival results among patients who received endoscopic therapy (ET) or surgical resection (SR) for cardia GIST. Cardia GIST patients from 2000 to 2019 were selected from the surveillance, epidemiology, and end result (SEER) database. Multiple imputation (MI) was applied to handle missing data, and propensity score matching (PSM) was carried out to mitigate selection bias during comparisons. Demographic and clinical characteristics' effects on overall survival (OS) and cancer-specific survival (CSS) were assessed using Kaplan-Meier analyses and multivariate Cox proportional hazard models. A total of 330 patients with cardia GIST were enrolled, including 47 (14.2%) patients with ET and 283 (85.8%) patients with SR. The 5-year OS and CSS rates in the ET and SR groups were comparable [before PSM, (OS) (76.1% vs. 81.2%, P = 0.722), (CSS) (95.0% vs. 89.3%, P = 0.186); after PSM, (OS) (75.4% vs. 85.4%, P = 0.540), (CSS) (94.9% vs. 92.0%, P = 0.099)]. Moreover, there was no significant difference between ET and SR in terms of long-term OS (hazard ratio [HR] 0.735, 95% confidence interval [CI] 0.422-1.282) and CSS (HR 1.560, 95% CI 0.543-4.481). Our study found no significant disparity in long-term survival outcomes between ET and SR in cardia GIST patients, implying that ET could be a valid surgical strategy for treating cardia GIST.


Subject(s)
Cardia , Gastrointestinal Stromal Tumors , Humans , Gastrointestinal Stromal Tumors/surgery , Gastrointestinal Stromal Tumors/mortality , Gastrointestinal Stromal Tumors/pathology , Male , Female , Middle Aged , Cardia/surgery , Cardia/pathology , Aged , Stomach Neoplasms/surgery , Stomach Neoplasms/mortality , Stomach Neoplasms/pathology , Treatment Outcome , SEER Program , Adult , Kaplan-Meier Estimate , Propensity Score , Proportional Hazards Models , Survival Rate , Retrospective Studies
8.
Can Vet J ; 65(6): 553-558, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38827592

ABSTRACT

Gastrointestinal stromal tumors arising from gastric cardia are uncommon in dogs. A few studies have shown the effectiveness of tyrosine kinase inhibitors in the treatment of canine gastrointestinal stromal tumors, but no standardized protocols are currently available. An 11-year-old spayed female Maltese dog was diagnosed with a gastrointestinal stromal tumor using histopathological and immunohistochemical analyses. An adenosine triphosphate-based tumor chemosensitivity assay revealed that imatinib at lower concentrations had a stronger inhibitory effect than toceranib. Based on the results of the assay, the dog was treated with imatinib after surgery. After 28 mo of therapy, there was no recurrence of the tumor. Key clinical message: Adenosine triphosphate-based tumor chemosensitivity assays may help clinicians to select appropriate postoperative chemotherapeutic drugs for incompletely resected gastrointestinal stromal tumors in dogs.


Gestion réussie à la suite d'une résection incomplète d'une tumeur stromale gastro-intestinale à l'aide de l'imatinib basée sur un test de sensibilité tumorale à base d'adénosine triphosphate chez un chien. Les tumeurs stromales gastro-intestinales résultant du cardia gastrique sont rares chez le chien. Quelques études ont montré l'efficacité des inhibiteurs de la tyrosine kinase dans le traitement des tumeurs stromales gastrointestinales canines, mais aucun protocole standardisé n'est actuellement disponible. Une chienne maltaise stérilisée de 11 ans a reçu un diagnostic de tumeur stromale gastro-intestinale à l'aide d'analyses histopathologiques et immunohistochimiques. Un test de chimiosensibilité tumorale à base d'adénosine triphosphate a révélé que l'imatinib à des concentrations plus faibles avait un effet inhibiteur plus fort que le tocéranib. Sur la base des résultats du test, le chien a été traité avec de l'imatinib après l'opération. Après 28 mois de traitement, il n'y a eu aucune récidive de la tumeur.Message clinique clé :Les tests de chimiosensibilité tumorale à base d'adénosine triphosphate peuvent aider les cliniciens à sélectionner les médicaments chimiothérapeutiques postopératoires appropriés pour les tumeurs stromales gastro-intestinales incomplètement réséquées chez le chien.(Traduit par Dr Serge Messier).


Subject(s)
Antineoplastic Agents , Dog Diseases , Gastrointestinal Stromal Tumors , Imatinib Mesylate , Animals , Gastrointestinal Stromal Tumors/veterinary , Gastrointestinal Stromal Tumors/surgery , Gastrointestinal Stromal Tumors/drug therapy , Gastrointestinal Stromal Tumors/pathology , Dogs , Imatinib Mesylate/therapeutic use , Dog Diseases/drug therapy , Dog Diseases/surgery , Female , Antineoplastic Agents/therapeutic use , Adenosine Triphosphate/therapeutic use , Indoles , Pyrroles
9.
Korean J Intern Med ; 39(4): 603-611, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38867644

ABSTRACT

BACKGROUND/AIMS: There is limited knowledge regarding the management of duodenal subepithelial lesions (SELs) owing to a lack of understanding of their natural course. This study aimed to assess the natural course of asymptomatic duodenal SELs and provide management recommendations. METHODS: Patients diagnosed with duodenal SELs and followed up for a minimum of 6 months were retrospectively investigated. RESULTS: Among the 443,533 patients who underwent esophagogastroduodenoscopy between 2008 and 2020, duodenal SELs were identified in 0.39% (1,713 patients). Among them, 396 duodenal SELs were monitored for a median period of 72.5 months (interquartile range, 37.7-111.3 mo). Of them, 16 SELs (4.0%) showed substantial changes in size or morphology at a median follow-up of 35.1 months (interquartile range, 21.7-51.4 mo). Of these SELs with substantial changes, tissues of two SELs were acquired using endoscopic ultrasound-guided fine needle aspiration biopsy: one was a lipoma and the other was non-diagnostic. Three SELs were surgically or endoscopically removed; two were diagnosed as gastrointestinal stromal tumors, and one was a lipoma. An initial size of 20 mm or larger was associated with substantial changes during follow-up (p = 0.016). CONCLUSION: While the majority of duodenal SELs may not exhibit substantial interval changes, regular follow-up with endoscopy may be necessary for cases with an initial size of 20 mm or larger, considering a possibility of malignancy.


Subject(s)
Asymptomatic Diseases , Duodenal Neoplasms , Endoscopy, Digestive System , Humans , Retrospective Studies , Female , Male , Middle Aged , Duodenal Neoplasms/pathology , Duodenal Neoplasms/surgery , Aged , Adult , Lipoma/pathology , Lipoma/surgery , Lipoma/diagnostic imaging , Disease Progression , Gastrointestinal Stromal Tumors/pathology , Gastrointestinal Stromal Tumors/surgery , Gastrointestinal Stromal Tumors/diagnostic imaging , Time Factors , Endoscopic Ultrasound-Guided Fine Needle Aspiration , Duodenal Diseases/pathology , Duodenal Diseases/surgery
10.
J Surg Oncol ; 130(1): 40-46, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38924626

ABSTRACT

INTRODUCTION: Patients with high-risk resected gastrointestinal stromal tumors (GIST) receiving adjuvant imatinib have improved recurrence-free survival (RFS), however whether a complete cytocidal effect exists is unknown. We investigated this using a normalized recurrence timeline measured from end of oncologic treatment (EOOT), defined as the later of resection or end of adjuvant therapy. METHODS: We reviewed patients with resected high-risk GIST at our cancer center from 2003 to 2018. RFS (measured from resection and EOOT), overall survival (OS), and time to imatinib resistance (TTIR) were analyzed using Kaplan-Meier analysis and multivariable Cox proportional hazards modeling. The performance of the Memorial Sloan Kettering (MSK) GIST nomogram was assessed. RESULTS: We identified 86 patients with high-risk GIST with a median 106 months of postsurgical follow-up. One-third (n = 29; 34%) did not receive adjuvant imatinib, while 57 (66%) did for a median of 3 years. The MSK nomogram-predicted 5-year RFS for patients receiving adjuvant imatinib was similar to those who did not (29% vs. 31%, p = 0.64). When RFS was measured from EOOT, the MSK-predicted RFS was independently associated with EOOT RFS (hazard ratio 0.22, p = 0.02), while adjuvant imatinib receipt and duration were not. Neither receipt nor duration of adjuvant imatinib were associated with TTIR or OS (all p > 0.05). CONCLUSIONS: Treatment with adjuvant imatinib delays, but does not clearly impact ultimate recurrence, TTIR, or OS, suggesting many patients with high-risk GIST may receive adjuvant imatinib unnecessarily. Additional studies are needed to establish the benefit of adjuvant therapy versus initiating therapy at first radiographic recurrence.


Subject(s)
Antineoplastic Agents , Gastrointestinal Neoplasms , Gastrointestinal Stromal Tumors , Imatinib Mesylate , Neoplasm Recurrence, Local , Humans , Gastrointestinal Stromal Tumors/surgery , Gastrointestinal Stromal Tumors/drug therapy , Gastrointestinal Stromal Tumors/pathology , Gastrointestinal Stromal Tumors/mortality , Imatinib Mesylate/therapeutic use , Female , Male , Middle Aged , Chemotherapy, Adjuvant , Antineoplastic Agents/therapeutic use , Aged , Gastrointestinal Neoplasms/surgery , Gastrointestinal Neoplasms/drug therapy , Gastrointestinal Neoplasms/pathology , Gastrointestinal Neoplasms/mortality , Retrospective Studies , Neoplasm Recurrence, Local/pathology , Survival Rate , Adult , Follow-Up Studies
11.
J Med Case Rep ; 18(1): 286, 2024 Jun 22.
Article in English | MEDLINE | ID: mdl-38907357

ABSTRACT

BACKGROUND: Due to rarity of duodenal GISTs, clinicians have few information about its clinical features, diagnosis, management and prognosis. CASE REPORT: We report a case of promptly diagnosed duodenal GIST in a 61-year-old Egyptian man presented shocked with severe attack of hematemesis and melena. Upper gastroduodenal endoscopy was done and revealed a large ulcerating bleeding mass at first part of duodenum 4 hemo-clips were applied with good hemostasis. An exploratory laparotomy and distal gastrectomy, duodenectomy and gastrojejunostomy were performed. The morphology of the mass combined with immunohistochemistry was consistent with duodenal gastrointestinal stromal tumours (GISTs) of high risk type. The patient is on amatinib one tablet daily and he was well with no evidence of tumor recurrence. CONCLUSION: despite being rare, emergency presentation with sudden severe, life-threatening hemorrhagic shock duodenal GISTs might be a cause of potentially lethal massive combined upper and lower gastrointestinal bleeding which is the key feature of this rare and challenging tumor.


Subject(s)
Duodenal Neoplasms , Gastrointestinal Hemorrhage , Gastrointestinal Stromal Tumors , Shock, Hemorrhagic , Humans , Gastrointestinal Stromal Tumors/complications , Gastrointestinal Stromal Tumors/pathology , Gastrointestinal Stromal Tumors/diagnosis , Gastrointestinal Stromal Tumors/surgery , Male , Middle Aged , Gastrointestinal Hemorrhage/etiology , Duodenal Neoplasms/complications , Duodenal Neoplasms/surgery , Duodenal Neoplasms/pathology , Shock, Hemorrhagic/etiology , Melena/etiology , Hematemesis/etiology , Gastrectomy
12.
Int J Mol Sci ; 25(12)2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38928487

ABSTRACT

Tissue biopsy remains the standard for diagnosing gastrointestinal stromal tumors (GISTs), although liquid biopsy is emerging as a promising alternative in oncology. In this pilot study, we advocate for droplet digital PCR (ddPCR) to diagnose GIST in tissue samples and explore its potential for early diagnosis via liquid biopsy, focusing on the PDGFRA D842V mutation and SEPT9 hypermethylated gene. We utilized ddPCR to analyze the predominant PDGFRA mutation (D842V) in surgical tissue samples from 15 GIST patients, correlating with pathologists' diagnoses. We expanded our analysis to plasma samples to compare DNA alterations between tumor tissue and plasma, also investigating SEPT9 gene hypermethylation. We successfully detected the PDGFRA D842V mutation in GIST tissues by ddPCR. Despite various protocols to enhance mutation detection in early-stage disease, it remained challenging, likely due to the low concentration of DNA in plasma samples. Additionally, the results of Area Under the Curve (AUC) for the hypermethylated SEPT9 gene, analyzing concentration, ratio, and abundance were 0.74 (95% Confidence Interval (CI): 0.52 to 0.97), 0.77 (95% CI: 0.56 to 0.98), and 0.79 (95% CI: 0.59 to 0.99), respectively. As a rare disease, the early detection of GIST through such biomarkers is particularly crucial, offering significant potential to improve patient outcomes.


Subject(s)
DNA Methylation , Gastrointestinal Stromal Tumors , Mutation , Polymerase Chain Reaction , Receptor, Platelet-Derived Growth Factor alpha , Septins , Humans , Septins/genetics , Gastrointestinal Stromal Tumors/genetics , Gastrointestinal Stromal Tumors/pathology , DNA Methylation/genetics , Liquid Biopsy/methods , Pilot Projects , Receptor, Platelet-Derived Growth Factor alpha/genetics , Female , Male , Middle Aged , Polymerase Chain Reaction/methods , Aged , Gastrointestinal Neoplasms/genetics , Gastrointestinal Neoplasms/pathology , Biomarkers, Tumor/genetics , Adult
13.
Rev Med Suisse ; 20(878): 1158-1162, 2024 Jun 12.
Article in French | MEDLINE | ID: mdl-38867560

ABSTRACT

Gastrointestinal Stromal Tumors (GISTs) account for 1 to 2% of gastrointestinal malignant tumors. They are characterized by overexpression of the tyrosine kinase (KIT). 60% of GISTs originate in the stomach. Managing them remains complex and varies depending on several factors such as location, size, molecular biology, type of clinical presentation, and the risks/benefits of surgical treatment. Surgery remains the only curative treatment, while tyrosine kinase inhibitors have demonstrated their efficacy as systemic treatment in the perioperative context. Risk stratification for recurrence guides the choice of adjuvant treatment, with a recommended duration of 3 years for high-risk patients.


Les tumeurs stromales gastro-intestinales (GIST) constituent entre 1 et 2 % des tumeurs malignes gastro-intestinales. Elles se caractérisent par une surexpression de la tyrosine kinase (KIT). 60 % des GIST sont d'origine gastrique. Leur prise en charge reste complexe et varie selon plusieurs facteurs tels que la localisation, la taille, la biologie moléculaire, le type de manifestation clinique et les risques/bénéfices du traitement chirurgical. La chirurgie demeure le seul traitement curatif, tandis que les inhibiteurs de tyrosine kinase ont démontré leur efficacité comme traitement systémique dans le contexte périopératoire. La stratification du risque de récidive guide le choix du traitement adjuvant, avec une durée recommandée de 3 ans pour les patients à haut risque.


Subject(s)
Gastrointestinal Stromal Tumors , Stomach Neoplasms , Gastrointestinal Stromal Tumors/surgery , Gastrointestinal Stromal Tumors/diagnosis , Humans , Stomach Neoplasms/surgery , Stomach Neoplasms/pathology , Stomach Neoplasms/diagnosis , Neoplasm Recurrence, Local
14.
Surg Endosc ; 38(7): 3905-3916, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38831215

ABSTRACT

BACKGROUND: Small intestinal stromal tumors (SISTs) are a rare type of mesenchymal tumor. Gender is known to influence the incidence and prognosis of various tumors, but its role on the survival of SISTs at the population level remains unclear. Therefore, we aim to explore the relationship between gender and the prognosis of SISTs using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: Data on SISTs patients from 2000 to 2019 were derived from the SEER database. Multiple imputation was used to address missing data. Kaplan-Meier analyses and Cox proportional hazard models were applied to evaluate the impact of demographic and clinical characteristics on overall survival (OS) and cancer-specific survival (CSS). RESULTS: A total of 3513 patients with SISTs were analyzed, including 1921 males and 1592 females. Kaplan-Meier analysis coupled with log-rank testing demonstrated a significantly higher mortality rate among male patients compared to females (P < 0.001). Notably, female patients exhibited superior OS (hazard ratio [HR] 0.808, 95% confidence interval [CI] 0.724-0.902, P < 0.001) and CSS (HR 0.801, 95% CI 0.692-0.927, P = 0.003) compared to male patients. While the mean 1-year CSS rates were comparable between genders (95.3% for males vs. 96.0% for females, P = 0.332), male patients consistently showed lower mean survival rates at 3-, 5-, and 10-year intervals. Surgical intervention significantly boosted 5-year OS and CSS rates in both male and female patients (P < 0.001). Multivariate Cox regression analysis identified age, sex, grade, TNM stage, surgery, and mitotic rate as independent risk factors for OS and CSS in patients with SISTs. CONCLUSIONS: Our findings suggest that male patients with SISTs have a higher risk of mortality compared to female patients, indicating that gender may serve as a predictive indicator for survival in this patient population.


Subject(s)
Gastrointestinal Stromal Tumors , SEER Program , Humans , Male , Female , Middle Aged , Gastrointestinal Stromal Tumors/mortality , Gastrointestinal Stromal Tumors/surgery , Gastrointestinal Stromal Tumors/pathology , Sex Factors , Aged , Survival Rate , Prognosis , Intestinal Neoplasms/mortality , Intestinal Neoplasms/pathology , Adult , Kaplan-Meier Estimate , Intestine, Small/pathology , United States/epidemiology , Proportional Hazards Models , Retrospective Studies
15.
ESMO Open ; 9(6): 103477, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38833964

ABSTRACT

BACKGROUND: Sunitinib is an oral anticancer drug approved for the treatment of among others gastrointestinal stromal tumor (GIST). Previous analyses demonstrated an exposure-response relationship at the standard dose, and minimum target levels of drug exposure have been defined above which better treatment outcomes are observed. Therapeutic drug monitoring (TDM) could be used as a tool to optimize the individual dose, aiming at sunitinib trough concentrations ≥37.5 ng/ml for continuous dosing. Nonetheless, data on the added value of TDM-guided dosing on clinical endpoints are currently lacking. Therefore, we evaluate the effect of TDM in patients with advanced and metastatic GIST treated with sunitinib in terms of efficacy and toxicity. PATIENTS AND METHODS: A TDM-guided cohort was compared to a non-TDM-guided cohort in terms of median progression-free survival (mPFS) and overall survival (mOS). Also, mPFS between patients with and without dose-limiting toxicities (DLTs) was compared. Patients in the prospective cohort were included in two studies on TDM-guided dosing (the DPOG-TDM study and TUNE study). The retrospective cohort consisted of patients from the Dutch GIST Registry who did not receive TDM-guided dosing. RESULTS: In total, 51 and 106 patients were included in the TDM-guided cohort and non-TDM-guided cohort, respectively. No statistical difference in mPFS was observed between these two cohorts (39.4 versus 46.9 weeks, respectively; P = 0.52). Patients who experienced sunitinib-induced DLTs had longer mPFS compared to those who did not (51.9 versus 28.9 weeks, respectively; P = 0.002). CONCLUSIONS: Our results do not support the routine use of TDM-guided dose optimization of sunitinib in patients with advanced/metastatic GIST to improve survival.


Subject(s)
Antineoplastic Agents , Drug Monitoring , Gastrointestinal Stromal Tumors , Sunitinib , Humans , Sunitinib/administration & dosage , Sunitinib/therapeutic use , Sunitinib/pharmacology , Gastrointestinal Stromal Tumors/drug therapy , Gastrointestinal Stromal Tumors/pathology , Female , Male , Middle Aged , Aged , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/administration & dosage , Retrospective Studies , Drug Monitoring/methods , Adult , Treatment Outcome , Gastrointestinal Neoplasms/drug therapy , Gastrointestinal Neoplasms/pathology , Gastrointestinal Neoplasms/mortality , Dose-Response Relationship, Drug , Aged, 80 and over , Prospective Studies , Progression-Free Survival
16.
Gan To Kagaku Ryoho ; 51(5): 549-552, 2024 May.
Article in Japanese | MEDLINE | ID: mdl-38881066

ABSTRACT

An 80-year-old male patient presented with a 2.5 cm-sized submucosal tumor on the greater curvature side of the upper gastric body during an endoscopic examination in 200X. We diagnosed gastric GIST by biopsy and performed laparoscopic- assisted partial gastrectomy. Imatinib was started as postoperative adjuvant therapy, but was discontinued after 1 month due to eyelid edema. The patient was followed up with a contrast-enhanced CT scan and a PET-CT scan. A 7 cm-sized mass in the gastrosplenic region was discovered on a 200X+7 years CT scan; this mass was thought to be possible recurrence of peritoneal dissemination. The patient did not want to undergo surgery or drug treatment, and was followed up. Five months later he complained of abdominal pain. The CT scan showed that the mass had shrunk slightly, but a small amount of ascites was observed, and tumor rupture was suspected. Therefore, we performed resection of the tumor in the office. Numerous disseminated nodules were found in the intra-abdominal cavity. Pathological examination revealed recurrence of GIST, and the patient was started on imatinib 200 mg/day. The dose was temporarily increased to 300 mg/day, but was reduced again to 200 mg/day 1 month later due to eyelid edema. Thereafter, the dose was temporarily discontinued due to stomatitis, and from 200X+8 years, 200 mg/day was administered for 2 weeks and then discontinued for 2 weeks. At present, 14 years after the first surgery and 6 years after recurrence, he remains alive thanks to imatinib continuation.


Subject(s)
Antineoplastic Agents , Gastrectomy , Gastrointestinal Stromal Tumors , Imatinib Mesylate , Recurrence , Stomach Neoplasms , Humans , Male , Gastrointestinal Stromal Tumors/surgery , Gastrointestinal Stromal Tumors/drug therapy , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery , Stomach Neoplasms/drug therapy , Aged, 80 and over , Imatinib Mesylate/therapeutic use , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/administration & dosage , Time Factors , Combined Modality Therapy
17.
Rev Prat ; 74(5): 537-541, 2024 May.
Article in French | MEDLINE | ID: mdl-38833239

ABSTRACT

MANAGEMENT OF GASTROINTESTINAL STROMAL TUMORS. Gastrointestinal stromal tumors (GIST) are the most frequent sarcoma subtype. More than 80% of GIST are characterized by activating mutations in KIT or PDGFRA genes, but rare molecular subtypes exist. Localized GIST can be cured by surgery. Adjuvant treatment with imatinib is the gold standard in high-risk GIST presenting mutations sensitive to this tyrosine kinase inhibitor. The development of tyrosine kinase inhibitors targeting KIT and PDGFRA has revolutionized the prognosis of metastatic GIST, by increasing the median overall survival: from less than 18 months to more than 70 months within 20 years. Similary to other histological subtypes, the diagnostic and therapeutic management of GIST must be referred to sarcoma reference centers.


PRISE EN CHARGE DES TUMEURS STROMALES GASTRO-INTESTINALES. Les tumeurs stromales gastro-intestinales (GIST) représentent le sous-type de sarcomes le plus fréquent. Plus de 80 % des GIST sont caractérisées par des mutations activatrices des gènes KIT ou PDGFRA, mais des soustypes moléculaires plus rares existent. Au stade localisé, les GIST sont des maladies curables par exérèse chirurgicale. Le traitement adjuvant par imatinib est un standard thérapeutique dans les GIST associées à un haut risque de récidive et présentant des mutations sensibles au traitement. Au stade métastatique, le développement des inhibiteurs de tyrosine kinase ciblant KIT et PDGFRA a bouleversé la prise en charge et le pronostic des patients, en augmentant la survie globale : de moins de dix-huit mois il y a une vingtaine d'années à plus de soixante-dix mois aujourd'hui. Comme pour les autres sous-types histologiques, la prise en charge diagnostique et thérapeutique des GIST doit être réalisée dans des centres experts pour la prise en charge des sarcomes.


Subject(s)
Gastrointestinal Stromal Tumors , Gastrointestinal Stromal Tumors/diagnosis , Gastrointestinal Stromal Tumors/therapy , Humans , Gastrointestinal Neoplasms/therapy , Gastrointestinal Neoplasms/diagnosis , Imatinib Mesylate/therapeutic use , Antineoplastic Agents/therapeutic use
18.
Br J Cancer ; 131(2): 299-304, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38862742

ABSTRACT

BACKGROUND: Patients with ruptured gastrointestinal stromal tumour (GIST) have poor prognosis. Little information is available about how adjuvant imatinib influences survival. METHODS: We explored recurrence-free survival (RFS) and overall survival (OS) of patients with ruptured GIST who participated in a randomised trial (SSG XVIII/AIO), where 400 patients with high-risk GIST were allocated to adjuvant imatinib for either 1 year or 3 years after surgery. Of the 358 patients with confirmed localised GIST, 73 (20%) had rupture reported. The ruptures were classified retrospectively using the Oslo criteria. RESULTS: Most ruptures were major, four reported ruptures were reclassified unruptured. The 69 patients with rupture had inferior RFS and OS compared with 289 patients with unruptured GIST (10-year RFS 21% vs. 55%, OS 59% vs. 78%, respectively). Three-year adjuvant imatinib did not significantly improve RFS or OS of the patients with rupture compared with 1-year treatment, but in the largest mutational subset with KIT exon 11 deletion/indel mutation OS was higher in the 3-year group than in the 1-year group (10-year OS 94% vs. 54%). CONCLUSIONS: About one-fifth of ruptured GISTs treated with adjuvant imatinib did not recur during the first decade of follow-up. Relatively high OS rates were achieved despite rupture. CLINICAL TRIAL REGISTRATION: NCT00116935.


Subject(s)
Antineoplastic Agents , Gastrointestinal Stromal Tumors , Imatinib Mesylate , Humans , Gastrointestinal Stromal Tumors/drug therapy , Gastrointestinal Stromal Tumors/mortality , Gastrointestinal Stromal Tumors/pathology , Imatinib Mesylate/therapeutic use , Female , Male , Chemotherapy, Adjuvant , Middle Aged , Aged , Antineoplastic Agents/therapeutic use , Adult , Gastrointestinal Neoplasms/drug therapy , Gastrointestinal Neoplasms/mortality , Gastrointestinal Neoplasms/pathology , Disease-Free Survival , Aged, 80 and over , Rupture, Spontaneous
19.
Neoplasia ; 55: 101022, 2024 09.
Article in English | MEDLINE | ID: mdl-38943997

ABSTRACT

Gastrointestinal stromal tumor (GIST) is the most prevalent mesenchymal tumor of the digestive tract. Its growth is primarily influenced by mutations in KIT or PDGFRA. Surgery is the primary treatment option for GIST; however, KIT inhibitors, such as imatinib, are used for inoperable cases. Resistance to imatinib is an upcoming challenge, especially because the effectiveness of alternative drugs is limited. Enhancement of the glycolysis pathway in cancer cells has been identified as a key feature in cancer. This unique metabolic activity has implications on tumor growth, prognosis, and resistance to therapy, even in GIST. Members of the glucose transporter (GLUT) family (particularly GLUT-1) play a significant role in GIST progression and response to treatment. Diagnostic imaging using 18F-fluorodeoxyglucose positron emission tomography/computed tomography, which enables visualization of glucose metabolism, can aid in GIST diagnosis and risk assessment. The interplay between glycolysis and GIST can lead to the development of various therapeutic strategies, especially those involving glycolysis-related molecules, such as hexokinase and lactate dehydrogenase. However, further research is required to understand the full spectrum of glycolysis in GIST and its therapeutic potential. Herein, we present an exhaustive overview and analysis of the role of glycolysis in GIST, especially as a therapeutic target.


Subject(s)
Gastrointestinal Stromal Tumors , Glycolysis , Gastrointestinal Stromal Tumors/metabolism , Gastrointestinal Stromal Tumors/genetics , Gastrointestinal Stromal Tumors/pathology , Gastrointestinal Stromal Tumors/diagnosis , Humans , Gastrointestinal Neoplasms/metabolism , Gastrointestinal Neoplasms/pathology , Gastrointestinal Neoplasms/genetics , Gastrointestinal Neoplasms/diagnosis , Gastrointestinal Neoplasms/therapy , Animals
20.
BMJ Case Rep ; 17(6)2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38885996

ABSTRACT

Drug-induced pleural effusion is one of the rare causes of exudative pleural effusion and a high index of suspicion is necessary to lead to early diagnosis. We hereby present the case of a young male in his late 30s, known case of metastatic gastrointestinal stromal tumour on sunitinib therapy, who presented with right-sided mild pleural effusion. Diagnostic thoracentesis showed the effusion to be a monomorphic exudate with low adenosine deaminase, which was negative for malignant cells on cytopathology. A contrast-enhanced CT chest revealed an enlarged lymph node (LN) at the 4R station, cytological analysis of which was suggestive of reactive lymphoid hyperplasia. Infective workup of the LN aspirate and bronchoalveolar lavage taken from the right middle lobe was negative. After systematically excluding the usual causes of exudative pleural effusion, sunitinib was considered to be a possible cause and was, therefore, withheld. A repeat chest X-ray after 3 weeks of stopping the drug showed resolution of the pleural effusion.


Subject(s)
Antineoplastic Agents , Pleural Effusion , Sunitinib , Humans , Male , Sunitinib/adverse effects , Sunitinib/therapeutic use , Pleural Effusion/chemically induced , Pleural Effusion/diagnostic imaging , Adult , Antineoplastic Agents/adverse effects , Gastrointestinal Stromal Tumors/drug therapy , Tomography, X-Ray Computed , Thoracentesis , Indoles/adverse effects , Indoles/therapeutic use
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