UNASSIGNED: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the digestive tract, with surgery and tyrosine kinase inhibitor (TKI) therapy being its main treatment options. However, long-term use of TKIs may lead to drug resistance, which poses a challenge to the long-term survival of patients. We explore a new combination of transcatheter arterial chemoembolization (TACE) with TKI for liver metastasis (LM) of GIST to provide patients with more treatment options and better prognosis.
UNASSIGNED: This case report describes the application of 6 TACE sessions in the 12-year treatment of multiple LM from small intestinal stromal tumors that were resistant to multiple TKIs. The patient, a 58-year-old male, underwent multiple surgical resections and drug therapies for the LM after a primary small bowel stromal tumor had been identified and resected following an onset symptom of abdominal pain in February 2012. Despite the challenges of drug resistance and economic considerations, 6 TACE sessions effectively controlled the tumor, winning valuable treatment time for the patient. Since the initiation of ripretinib 150 mg once daily in July 2023, the tumor has continued to shrink, with satisfactory drug tolerance.
UNASSIGNED: For GIST patients with LM, TACE combined with various TKI drugs could effectively control intrahepatic tumor progression and prolong patient survival. During six TACE sessions, the patient experienced liver tumor rupture and massive bleeding. However, the bleeding was completely stopped by embolization, and the lesion shrank. Our findings provide a new perspective and treatment strategy for the treatment of LM from GIST.

UNASSIGNED: Imatinib mesylate (IM) is a first-line treatment option for the majority of patients diagnosed with gastrointestinal stromal tumors (GISTs). Although the clinical benefit is high, interindividual response is variable. This study thus aimed to assess how genetic polymorphisms can affect the blood levels of IM and treatment outcomes in patients with GIST.
UNASSIGNED: A total of 31 single-nucleotide polymorphisms (SNPs) in selected cytochrome P450 (P450), ATP-binding cassette transporter (ABC), solute carrier family (SLC), interleukin-4 receptor (IL4R), and vascular endothelial growth factor (VEGF) genes were genotyped using an SNP mass array platform. A total of 192 consecutive patients with GIST who received 400 mg of IM daily were enrolled into the study, with 1,485 blood samples being analyzed. According to genotypes, IM trough concentrations were tested and compared. Progression-free survival (PFS) and overall survival (OS) were also assessed.
UNASSIGNED: With a mean follow-up of 75.99 months, trough concentrations of imatinib were examined at average time points of 7.73 for each patient. Polymorphism in ABCB1 rs1045642 was found to be associated with steady-state IM trough plasma levels (P=0.008). Patients with the C genotype (CT + CC) of rs1045642 exhibited higher IM trough concentrations (1,271.09±306.69 ng/mL) compared to those with the TT genotype (1,106.60±206.05 ng/mL). No statistically significant differences in IM plasma concentration were observed for the other SNPs tested. None of the tested SNPs displayed a significant association with patients\' survival in this study.
UNASSIGNED: This is the largest cohort study evaluating the associations of SNP and imatinib blood trough levels. The ABCB1 rs1045642 genetic polymorphism may exert an effect on the pharmacokinetics of imatinib. The presence of the C allele in ABCB1 rs1045642 is predictive of a higher plasma concentration of IM.

UNASSIGNED: Gastrointestinal stromal tumor (GIST) is a common mesenchymal tumor of the gastrointestinal system. They originate from the interstitial cells of Cajal located within the muscle layer and are characterized by over-expression of the tyrosine kinase receptor KIT.
UNASSIGNED: Data from the Surveillance Epidemiology, and End Results (SEER) database of 1,213 patients diagnosed with GIST between 2010 and 2019 were dichotomized into a modeling set and a validation set at a 2:1 ratio. For the modeling set, both univariate and multivariate Cox regression analyses were used to identify independent prognostic factors. A nomogram was then constructed based on these determinants. Model efficacy was tested using receiver operating characteristic (ROC) curves, calibration curves, clinical decision curves, and risk stratification analysis in both subsets.
UNASSIGNED: Identified prognostic determinants included age, sex, pathological differentiation level, tumor-node-metastasis (TNM) stage, surgical intervention, radiotherapy, and marital status. The constructed nomogram showed area under the ROC curve (AUC) values of 0.822, 0.793, and 0.779 for 1-, 3-, and 5-year overall survival (OS) in the modeling set, respectively, while in the validation set, the values were 0.796, 0.823, and 0.806, respectively. Calibration plots from both sets confirmed the concordance between predicted and observed survival. Decision curve analysis (DCA) indicated significant clinical utility for the nomogram. Risk stratification of the patient data revealed distinct survival differences between high-risk and low-risk cohorts in both sets (P<0.001).
UNASSIGNED: A novel and potent nomogram for the prognosis of GIST has been introduced. This model\'s precision offers crucial insights for clinical decisions, yet further external validation remains essential.

UNASSIGNED: Some patients with high-risk gastrointestinal stromal tumor (GIST) experience disease progression after complete resection and adjuvant therapy. It is of great significance to distinguish these patients among those with high-risk GIST. Radiomics has been demonstrated as a promising tool to predict various tumors prognosis.
UNASSIGNED: From January 2006 to December 2018, a total of 100 high-risk GIST patients (training cohort: 60; validation cohort: 40) from Guangdong Provincial People\'s Hospital with preoperative enhanced computed tomography (CT) images were enrolled. The radiomics features were extracted and a risk score was built using least absolute shrinkage and selection operator-Cox model. The clinicopathological factors were analyzed and a nomogram was established with and without radiomics risk score. The concordance index (C-index), calibration plot, and decision curve analysis (DCA) were used to evaluate the performance of the radiomics nomograms.
UNASSIGNED: We selected 11 radiomics features associated with recurrence or metastasis. The risk score was calculated and significantly associated with disease-free survival (DFS) in both the training and validation group. Cox regression analysis showed that Ki67 was an independent risk factor for DFS [P=0.004, hazard ratio 4.615, 95% confidence interval (CI): 1.624-13.114]. The combined radiomics nomogram, which integrated the radiomics risk score and significant clinicopathological factors, showed good performance in predicting DFS, with a C-index of 0.832 (95% CI: 0.761-0.903), which was better than the clinical nomogram (C-index 0.769, 95% CI: 0.679-0.859) in training cohort. The calibration curves and the DCA plot suggested satisfying accuracy and clinical utility of the model.
UNASSIGNED: The CT-based radiomics nomogram, combined with the clinicopathological factors and risk score, has good potential to assess the recurrence or metastasis of patients with high-risk GIST.

UNASSIGNED: Gastrointestinal (GI) bleeding is one of the common symptoms of GI stromal tumor (GIST). Although several studies have highlighted its prognostic role, conclusions have been inconsistent. This study aimed to investigate the prognosis of GIST patients with GI bleeding.
UNASSIGNED: Primary GIST patients who underwent complete resection and did not receive adjuvant imatinib therapy from January 2003 to December 2008 were reviewed. The Kaplan-Meier method was used to estimate recurrence-free survival (RFS), and multivariate analysis was performed using the Cox proportional hazard model. Propensity score matching (PSM) was conducted to reduce confounders. A systematic review of the published articles in the PubMed, Embase, Cochrane Collaboration, and Medline databases was also conducted, and the inclusion criteria were determined using PICOS (patients, intervention, comparison, outcomes, and study design) principles.
UNASSIGNED: In total, 84 patients presenting with GI bleeding and 90 patients without GI bleeding were enrolled in this study. The median time of follow-up was 140 months (range, 10-196 months), and 38 patients developed tumor recurrence/metastasis. For all patients, the multivariate analysis indicated that tumor location [hazard ratio (HR) =3.48, 95% confidence interval (CI): 1.78-6.82, P<0.001], tumor size (HR =1.91, 95% CI: 1.05-3.47, P=0.035), mitotic index (MI; HR =5.69, 95% CI: 2.77-11.67, P<0.001), and age (HR =2.68, 95% CI: 1.49-4.82, P=0.001) were the independent prognostic factors for poor RFS. However, GI bleeding was not associated with RFS (HR =1.21, 95% CI: 0.68-2.14, P=0.518). After PSM, 45 patients from each group were included, and it was found that GI bleeding was still not the independent prognostic factor (HR =1.23, 95% CI: 0.51-2.97, P=0.642). Moreover, the pooled results of our study and six previously reported studies showed that GI bleeding was not the independent prognostic factor (HR =1.45, 95% CI: 0.73-2.86, P=0.287).
UNASSIGNED: In this study, tumor location, tumor size, MI, and age were independent prognostic factors in primary GIST patients who underwent radical resection. However, GI bleeding was not associated with worse RFS.

Gastrointestinal stromal tumors (GISTs) carrying different KIT exon 11 (KIT-11) mutations exhibit varying prognoses and responses to Imatinib. Herein, we aimed to determine whether computed tomography (CT) radiomics can accurately stratify KIT-11 mutation genotypes to benefit Imatinib therapy and GISTs monitoring.
Overall, 1143 GISTs from 3 independent centers were separated into a training cohort (TC) or validation cohort (VC). In addition, the KIT-11 mutation genotype was classified into 4 categories: no KIT-11 mutation (K11-NM), point mutations or duplications (K11-PM/D), KIT-11 557/558 deletions (K11-557/558D), and KIT-11 deletion without codons 557/558 involvement (K11-D). Subsequently, radiomic signatures (RS) were generated based on the arterial phase of contrast CT, which were then developed as KIT-11 mutation predictors using 1408 quantitative image features and LASSO regression analysis, with further evaluation of its predictive capability.
The TC AUCs for K11-NM, K11-PM/D, K11-557/558D, and K11-D ranged from 0.848 (95% CI 0.812-0.884), 0.759 (95% CI 0.722-0.797), 0.956 (95% CI 0.938-0.974), and 0.876 (95% CI 0.844-0.908), whereas the VC AUCs ranged from 0.723 (95% CI 0.660-0.786), 0.688 (95% CI 0.643-0.732), 0.870 (95% CI 0.824-0.918), and 0.830 (95% CI 0.780-0.878). Macro-weighted AUCs for the KIT-11 mutant genotype ranged from 0.838 (95% CI 0.820-0.855) in the TC to 0.758 (95% CI 0.758-0.784) in VC. TC had an overall accuracy of 0.694 (95%CI 0.660-0.729) for RS-based predictions of the KIT-11 mutant genotype, whereas VC had an accuracy of 0.637 (95%CI 0.595-0.679).
CT radiomics signature exhibited good predictive performance in estimating the KIT-11 mutation genotype, especially in prediction of K11-557/558D genotype. RS-based classification of K11-NM, K11-557/558D, and K11-D patients may be an indication for choice of Imatinib therapy.

Ferroptosis, as a novel-induced programmed cell death, plays critical roles in the pathogenesis of cancers. However, the promising biomarkers of ferroptosis in gastrointestinal stromal tumor (GIST) remain to be elucidated. Herein, the expression of ferroptosis-related genes was analyzed in GIST. Among the 64 ferroptosis-related genes, transferrin receptor (TFRC) expression presented a remarkable upregulation in high-risk patients through Gene Expression Omnibus (GEO) dataset analysis, as well as its significant change after imatinib was treated. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of TFRC-relevant genes revealed that TFRC expression was closely associated with cell growth pathways and metabolism-related pathways. Furthermore, patients at high risk of recurrence were more likely to exhibit high TFRC expression by immunohistochemistry. Additionally, high TFRC expression indicated an undesirable state of patient relapse, which could serve as a powerful significant independent predictor of recurrence-free survival (RFS). In summary, we systematically summarize the expression characteristics and clinical relevance of TFRC and show that TFRC can be used as a prognostic factor, which can be considered a potential therapeutic target in GIST.

To establish and validate a radiomics nomogram model for preoperative prediction of KIT exon 9 mutation status in patients with gastrointestinal stromal tumors (GISTs).
Eighty-seven patients with pathologically confirmed GISTs were retrospectively enrolled in this study. Imaging and clinicopathological data were collected and randomly assigned to the training set (n = 60) and test set (n = 27) at a ratio of 7:3. Based on contrast-enhanced CT (CE-CT) arterial and venous phase images, the region of interest (ROI) of the tumors were manually drawn layer by layer, and the radiomics features were extracted. The intra-class correlation coefficient (ICC) was used to test the consistency between observers. Least absolute shrinkage and selection operator regression (LASSO) were used to further screen the features. The nomogram of integrated radiomics score (Rad-Score) and clinical risk factors (extra-gastric location and distant metastasis) was drawn on the basis of multivariate logistic regression. The area under the receiver operating characteristic (AUC) curve and decision curve analysis were used to evaluate the predictive efficiency of the nomogram, and the clinical benefits that the decision curve evaluation model may bring to patients.
The selected radiomics features (arterial phase and venous phase features) were significantly correlated with the KIT exon 9 mutation status of GISTs. The AUC, sensitivity, specificity, and accuracy in the radiomics model were 0.863, 85.7%, 80.4%, and 85.0% for the training group (95% confidence interval [CI]: 0.750-0.938), and 0.883, 88.9%, 83.3%, and 81.5% for the test group (95% CI: 0.701-0.974), respectively. The AUC, sensitivity, specificity, and accuracy in the nomogram model were 0.902 (95% confidence interval [CI]: 0.798-0.964), 85.7%, 86.9%, and 91.7% for the training group, and 0.907 (95% CI: 0.732-0.984), 77.8%, 94.4%, and 88.9% for the test group, respectively. The decision curve showed the clinical application value of the radiomic nomogram.
The radiomics nomogram model based on CE-CT can effectively predict the KIT exon 9 mutation status of GISTs and may be used for selective gene analysis in the future, which is of great significance for the accurate treatment of GISTs.

Background: This case report presents two clinical cases of metastatic refractory gastrointestinal stromal tumor (GIST) with treatment history of 6-14 years. The follow-up treatment of both cases comprised ripretinib dose escalation and its combination with other tyrosine kinase inhibitors (TKIs). To the best of our knowledge, this is the first report that explored ripretinib combination therapy in the late-line treatment of GISTs. Case description: Case-1 represents a 57-year-old female patient who underwent surgical resection for retroperitoneal GIST in 2008. After tumor recurrence in 2009, imatinib was started with complete response for 8 years. Imatinib was followed by sunitinib and regorafenib treatment. In March 2021, due to progressive disease (PD), the patient started ripretinib (150 mg QD) and achieved partial response (PR). Six months later, the patient showed PD. Subsequently, ripretinib dose was increased (150 mg BID) followed by ripretinib (100 mg QD) and imatinib (200 mg QD) combination. CT performed in February 2022 revealed stable lesions with internal visible necrosis. Combination therapy achieved stable disease (SD) for 7 months. On further follow-up in July 2022, the patient showed PD and died in September 2022. Case-2: represents a 73-year-old female patient diagnosed with unresectable duodenal GIST with liver, lung, and lymph node metastases in 2016. After treatment with imatinib, followed by sunitinib, regorafenib, and imatinib rechallenge, ripretinib (150 mg QD) was administered in May 2021, and SD was achieved. Ripretinib dose was increased (200 mg QD) due to PD in December 2021. The tumor showed heterogeneous manifestations, with overall size increase and regression in right posterior lobe. In February 2022, ripretinib (150 mg) plus sunitinib (25 mg) QD was commenced. On follow-up in April 2022, the patient showed slightly improved symptoms with stable hematologic parameters. Combination therapy achieved SD for 5 months and the patient showed PD in July 2022 and discontinued the treatment later. The patient was in poor general condition and was receiving nutritional therapy until last follow-up in October 2022. Conclusion: This case report provides evidence that combination therapy of ripretinib with other TKIs could be an effective late-line treatment option for refractory GIST patients.

BACKGROUND: Whether to escalate imatinib dosage or directly switch to sunitinib in gastrointestinal stromal tumors (GISTs) failing on standard dose 400 mg/d of imatinib is still controversial.
METHODS: We evaluated progression-free survival (PFS), overall survival (OS), and time to sunitinib failure (TTSF) of patients selecting imatinib dose escalation or directly switching to sunitinib after the failure of imatinib 400 mg/d therapy from 3 tertery referring centers between January 2008 to December 2016.
RESULTS: A total of 240 patients receiving sunitinib (37.5 mg continuous daily dose or 50 mg 4 weeks on with 2 weeks off) for at least 8 weeks were examined. After failure on imatinib 400 mg/d, 100 (49.3%) patients had dose escalation to 600 mg or 800 mg per day (IM group, imatinib group), and 103 (50.7%) directly switched to sunitinib (SU group, sunitinib group). The PFS in the SU and IM groups was 12 months and 5.0 months (P < 0.001), respectively. TTSF or OS in both groups was not statistically significantly different.
CONCLUSIONS: After the progression of imatinib standard-dose treatment in recurrent/metastatic GISTs, the PFS of patients directly switching to sunitinib was significantly longer compared with the PFS of patients with imatinib dose escalation. However, when the patients continued with sunitinib therapy after the failure of IM dose escalation, TTSF and OS in the IM group were similar to those in the SU group. Further exploration of the characteristics of the population benefiting from imatinib dose escalation are warranted.