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.

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: 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.

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.

OBJECTIVE: To retrospectively analyze the clinical characteristics of patients undergoing surgical treatment for gastrointestinal stromal tumors (GISTs) in Ruijin Hospital and explore the relevant prognosis clinical factors after surgical treatment.
METHODS: We screened out 1015 patients with GISTs diagnosed and treated during January 2010 to December 2019. We performed univariate analysis by the log-rank test and multivariate analysis by COX regression. The Kaplan-Meier method was used to estimate the disease-free survival (DFS) and overall survival (OS) of the whole group.
RESULTS: All 1015 patients in the whole group received radical surgery, and the proportion of patients with high, intermediate, and low risk was 31.1%, 21.7%, and 47.3%, respectively. Among the 480 low-risk patients, surgery could achieve radical therapy; only the Ki-67 index was related to DFS and OS (DFS: p = 0.032, OS: p = 0.009) among the 140 intermediate-risk patients with tumors located in the stomach, whether received Tyrosine kinase inhibitors (TKIs) therapy did not affect the prognosis of patients (DFS: p = 0.716, OS: p = 0.848). Among the 331 high-risk patients, those with non-gastric tumors (those outside the stomach, duodenum, and small intestine, HR 1.55, 95% CI 1.19-2.00, p < 0.001), tumor diameter > 10 cm (hazard ratio, HR 2.63, 95% confidence interval, CI 2.09-4.03, p < 0.001), as well as high-risk patients with mitotic rate > 10/50 HPF (HR 2.74, 95% CI 2.00-3.76, p < 0.001), the overall prognosis was obviously worse than that of other patients. For some high-risk patients, prolonged postoperative imatinib therapy could significantly improve the survival of patients (HR 0.43, 95% CI 0.15-0.66, p < 0.001).
CONCLUSIONS: For the vast majority of GIST patients, surgery can be curative; but in intermediate-risk patients, the Ki-67 index and postoperative TKI treatment are closely related to prognosis. For intermediate-risk patients whose primary tumor is the stomach, the value of TKI-targeted therapy after surgery seem be not necessary in our study. However, for some high-risk patients, the prognosis of patients can be improved by appropriately prolonging the treatment time of TKI.

UNASSIGNED: Gastrointestinal stromal tumors (GISTs) are malignant mesenchymal tumors arising in the gastrointestinal tract. Their systemic treatment is based on the use of tyrosine kinase inhibitors (TKIs) with imatinib, sunitinib, and regorafenib being the preferred agents. Assessment of tumor response to TKI treatment in GISTs is traditionally done according the Response Evaluation Criteria in Solid Tumors (RECIST), while Choi criteria have also been proposed as alternative tool assessing both volumetric and density changes on computer tomography (CT) scans. EORTC STBSG 1317 \'CaboGIST\' was a single-arm prospective Phase 2 trial which met its primary endpoint, as 60% of patients previously treated with imatinib and sunitinib were progression-free at 12 weeks (95% CI 45-74%) based on local RECIST assessment.
UNASSIGNED: We report here an exploratory analysis of local versus central RECIST version 1.1 assessment and a comparison of RECIST version 1.1 versus Choi criteria.
UNASSIGNED: Comparisons between local and central RECIST version 1.1 at week 12 revealed discrepancies in 17/43 evaluable cases (39.5%). When comparing Choi with local and central RECIST version 1.1, discrepancies were observed in 27/43 (62.8%) and 21/43 (48.8%) cases, respectively. A total of 68% of evaluable patients were progression-free and alive at week 12 based on local RECIST, 84% according to central RECIST analysis and 81% when applying Choi criteria. Central assessment upgraded the treatment response both with RECIST version 1.1 and Choi.
UNASSIGNED: The results of this exploratory analysis support the conclusion that cabozantinib is active in patients with metastatic or recurrent GIST after treatment with imatinib and sunitinib and confirm once again the limitations of RECIST to capture response to TKI in GIST, and the importance to include density changes in the response evaluation in this setting. Clinical trial number: EORTC 1317, NCT02216578.

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.
CONCLUSIONS: 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.

BACKGROUND: The role of surgery and non-surgical locoregional treatments (LRT) such as radiation therapy (RT) and local ablation techniques in patients with metastatic gastrointestinal stromal tumor (GIST) is unclear. This study examines LRT practice patterns in metastatic GIST and their clinical outcomes in British Columbia (BC).
METHODS: Patients diagnosed with either recurrent or de novo metastatic GIST from January 2008 to December 2017 were identified. Clinical characteristics and outcomes were analyzed in patients who underwent LRT, including surgical resection of the primary tumor or metastectomy, RT, or other local ablative procedures.
RESULTS: 127 patients were identified: 52 (41%) had de novo metastasis and 75 (59%) had recurrent metastasis. Median age was 67 (23-90 years), 58.2% were male, primary site was 33.1% stomach, 40.2% small intestine, 11% rectum/pelvis, and 15.7% others. 37 (29.1%) of patients received palliative surgery, the majority of which had either primary tumor removal only (43.3%) or both primary tumor removal and metastectomy (35.1%). A minority of patients underwent metastectomy only (21.6%). A total of 12 (9.5%) patients received palliative RT to metastatic sites only (58.3%) or primary tumors only (41.7%), mostly for symptomatic control (n = 9). A few patients (n = 3) received local ablation for liver metastatic deposits with 1 patient receiving microwave ablation (MWA) and 2 receiving radiofrequency ablation (RFA). Most patients (n = 120, 94.5%) received some type of systemic treatment. It is notable that prolonged progression free survival (PFS) was observed for the majority of patients who underwent surgery in the metastatic setting with a median PFS of 20.5 (95% confidence interval (CI): 14.29-40.74) months. In addition, significantly higher median overall survival (mOS) was observed in patients who underwent surgery (97.15 months; 95% CI: 77.7-not reached) and LRT (78.98 months; 95% CI: 65.58-not reached) versus no surgery (45.37 months; 95% CI: 38.7-64.69) and no LRT (45.27 months; 95% CI: 33.25-58.66). Almost all patients (8 out of 9) achieved symptomatic improvement after palliative RT. All 3 patients achieved partial response and 2 out of 3 patients had relatively durable responses of 1 year or more after local ablation.
CONCLUSIONS: This study is among the first to systematically examine the use of various LRT in metastatic GIST management. Integration of LRT with systemic treatments may potentially provide promising durable response and prolonged survival for highly selected metastatic GIST patients with low volume disease, limited progression and otherwise well controlled on systemic treatments. These observations, consistent with others, add to the growing evidence that supports the judicious use of LRT in combination with systemic treatments to further optimize the care of metastatic GIST patients.

Gastrointestinal stromal tumors (GISTs) are soft tissue sarcomas that can occur anywhere in the GI tract. There are roughly 4,000 to 6,000 cases diagnosed in the United States annually. GISTs are often asymptomatic early on and can evade detection, occasionally resulting in malignancy. Due to their insidious growth and location, it is suspected that they are more common than currently reported. It is important to know how difficult it is to identify a GIST and the various methods to treat it in a patient. Our case presents a 62-year-old male with incidental findings of multiple GISTs during workup for kidney stones. The patient was fortunate that these tumors were detected before developing into a greater health concern and this case highlights the insidious nature with which they develop.