A randomized study of 6 versus 3 years of adjuvant imatinib in patients with localized GIST at high risk of relapse.

BACKGROUND: The administration of adjuvant imatinib during 3 years is indicated after resection of primary localized GIST at high risk of recurrence, but many patients relapse afterwards. METHODS: IMADGIST (NCT02260505) was a multicenter, open-label, randomized phase III study evaluating the maintenance of imatinib for 3 more years (6-year arm) compared with interruption (3-year arm) from the day of randomization, conducted in the French Sarcoma Group. The primary endpoint was intent-to-treat disease-free survival. Secondary endpoints included overall survival, time to imatinib resistance, response after imatinib reintroduction at relapse, and safety. RESULTS: From 24 December 2014 to 4 April 2023, 136 patients aged ≥18 years, Eastern Cooperative Oncology Group performance status ≤2, with a localized gastrointestinal stromal tumor with an R0 or R1 surgery, and a risk of tumor recurrence ≥35% according to National Comprehensive Cancer Network (NCCN) risk classification were randomized in 14 centers. Sixty-five patients were randomized to the 3-year arm versus 71 to the 6-year arm. There were 68 males and females. Primary sites were gastric and small bowel in 60 (44%) and 64 (47%) patients, respectively. Respectively, 52 (38%) and 71 (52%) patients had a risk of relapse of 35%-70% and >70%. With a median follow-up of 55 months (interquartile range 46-59 months) after randomization, disease-free survival was significantly superior in the 6-year arm [hazard ratio: 0.40 (0.20-0.69), P = 0.0008]. Time to imatinib resistance, survival, adverse events, and quality of life were not different in the two arms. CONCLUSIONS: Three additional years of adjuvant imatinib reduces the risk of relapse in patients who have received 3 years of adjuvant imatinib with an acceptable tolerance.

Demographic Trends, Co-Alterations, and Imatinib Resistance across Genomic Variants in Gastrointestinal Stromal Tumors: An AACR Project GENIE Analysis.

INTRODUCTION: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasm of the gastrointestinal tract, the treatment of which represents a significant breakthrough in targeted cancer therapy. Given its overall rare nature, genomic differences and clinical implications between demographic groups have not been previously investigated. METHODS: Anonymized demographic, clinical, and genomic data from 1,559 GIST patients in the American Association for Cancer Research Project GENIE database were analyzed using cBioPortal and custom Python scripts. Data on patient demographics, genomic alterations, and co-occurrence genetic alerations were collected and classified according to clinical implications using the OncoKB database. χ2 tests for differences in genomic alterations were used across various demographic factors and mutual exclusivity analysis was employed to identify co-mutation patterns. RESULTS: Male patients demonstrated higher incidence of PDGFRA mutation (14.56% vs. 8.05%; p < 0.001), while female patients had higher likelihood of NF1 mutations (7.46% vs. 3.23%; p = 0.001). Asian patients had higher alteration rates at KIT (85.59%; p = 0.002). Co-occurrence analysis revealed KIT alterations frequently co-occurred with CDKN2A (q < 0.001), MTAP (q = 0.045), and PTEN (q = 0.056), while there was mutual exclusivity with PDGFRA (q < 0.001), NF1 (q < 0.001), and BRAF (q = 0.015). CDKN2A alterations co-occurred with MTAP (q < 0.001) and PIK3CA (q = 0.015), while being mutually exclusive with TP53 (q = 0.002) and NF1 (q = 0.007). Trends were similar among patients who had received no prior medical treatment. Imatinib-resistant mutations were more common among male patients (25.6% vs. 18.9%; p = 0.0056) and individuals under 55 (27.3% vs. 20.9%; p = 0.0228). Among patients with imatinib-resistant mutations, 77.78% had sunitinib resistance, while 70.25% maintained sensitivity to ripretinib. CONCLUSION: Sex and race/ethnic differences in genomic alterations, as well as co-mutations, were prevalent among patients with GIST. Variations in mutational profiles highlight the importance of distinct genetic drivers that may be targeted to treat different patient populations.

CT assessed morphological features can predict higher mitotic index in gastric gastrointestinal stromal tumors.

OBJECTIVES: To investigate the correlation of the mitotic index (MI) of 1-5 cm gastric gastrointestinal stromal tumors (gGISTs) with CT-identified morphological and first-order radiomics features, incorporating subgroup analysis based on tumor size. METHODS: We enrolled 344 patients across four institutions, each pathologically diagnosed with 1-5 cm gGISTs and undergoing preoperative contrast-enhanced CT scans. Univariate and multivariate analyses were performed to investigate the independent CT morphological high-risk features of MI. Lesions were categorized into four subgroups based on their pathological LD: 1-2 cm (n = 69), 2-3 cm (n = 96), 3-4 cm (n = 107), and 4-5 cm (n = 72). CT morphological high-risk features of MI were evaluated in each subgroup. In addition, first-order radiomics features were extracted on CT images of the venous phase, and the association between these features and MI was investigated. RESULTS: Tumor size (p = 0.04, odds ratio, 1.41; 95% confidence interval: 1.01-1.96) and invasive margin (p < 0.01, odds ratio, 4.55; 95% confidence interval: 1.77-11.73) emerged as independent high-risk features for MI > 5 of 1-5 cm gGISTs from multivariate analysis. In the subgroup analysis, the invasive margin was correlated with MI > 5 in 3-4 cm and 4-5 cm gGISTs (p = 0.02, p = 0.03), and potentially correlated with MI > 5 in 2-3 cm gGISTs (p = 0.07). The energy was the sole first-order radiomics feature significantly correlated with gGISTs of MI > 5, displaying a strong correlation with CT-detected tumor size (Pearson's ρ = 0.85, p < 0.01). CONCLUSIONS: The invasive margin stands out as the sole independent CT morphological high-risk feature for 1-5 cm gGISTs after tumor size-based subgroup analysis, overshadowing intratumoral morphological characteristics and first-order radiomics features. KEY POINTS: Question How can accurate preoperative risk stratification of gGISTs be achieved to support treatment decision-making? Findings Invasive margins may serve as a reliable marker for risk prediction in gGISTs up to 5 cm, rather than surface ulceration, irregular shape, necrosis, or heterogeneous enhancement. Clinical relevance For gGISTs measuring up to 5 cm, preoperative prediction of the metastatic risk could help select patients who could be treated by endoscopic resection, thereby avoiding overtreatment.

Prediction of high Ki-67 proliferation index of gastrointestinal stromal tumors based on CT at non-contrast-enhanced and different contrast-enhanced phases.

OBJECTIVES: To evaluate and analyze radiomics models based on non-contrast-enhanced computed tomography (CT) and different phases of contrast-enhanced CT in predicting Ki-67 proliferation index (PI) among patients with pathologically confirmed gastrointestinal stromal tumors (GISTs). METHODS: A total of 383 patients with pathologically proven GIST were divided into a training set (n = 218, vendor 1) and 2 validation sets (n = 96, vendor 2; n = 69, vendors 3-5). Radiomics features extracted from the most recent non-contrast-enhanced and three contrast-enhanced CT scan prior to pathological examination. Random forest models were trained for each phase to predict tumors with high Ki-67 proliferation index (Ki-67>10%) and were evaluated using the area under the receiver operating characteristic curve (AUC) and other metrics on the validation sets. RESULTS: Out of 107 radiomics features extracted from each phase of CT images, four were selected for analysis. The model trained using the non-contrast-enhanced phase achieved an AUC of 0.792 in the training set and 0.822 and 0.711 in the two validation sets, similar to models trained on different contrast-enhanced phases (p > 0.05). Several relevant features, including NGTDM Busyness and tumor size, remained predictive in non-contrast-enhanced and different contrast-enhanced images. CONCLUSION: The results of this study indicate that a radiomics model based on non-contrast-enhanced CT matches that of models based on different phases of contrast-enhanced CT in predicting the Ki-67 PI of GIST. GIST may exhibit similar radiological patterns irrespective of the use of contrast agent, and such radiomics features may help quantify these patterns to predict Ki-67 PI of GISTs. CLINICAL RELEVANCE STATEMENT: GIST may exhibit similar radiomics patterns irrespective of contrast agent; thus, radiomics models based on non-contrast-enhanced CT could be an alternative for risk stratification in GIST patients with contraindication to contrast agent. KEY POINTS: • Performance of radiomics models in predicting Ki-67 proliferation based on different CT phases is evaluated. • Non-contrast-enhanced CT-based radiomics models performed similarly to contrast-enhanced CT in risk stratification in GIST patients. • NGTDM Busyness remains stable to contrast agents in GISTs in radiomics models.

Deep learning analysis for differential diagnosis and risk classification of gastrointestinal tumors.

OBJECTIVES: Recently, artificial intelligence (AI) has been applied to clinical diagnosis. Although AI has already been developed for gastrointestinal (GI) tract endoscopy, few studies have applied AI to endoscopic ultrasound (EUS) images. In this study, we used a computer-assisted diagnosis (CAD) system with deep learning analysis of EUS images (EUS-CAD) and assessed its ability to differentiate GI stromal tumors (GISTs) from other mesenchymal tumors and their risk classification performance. MATERIALS AND METHODS: A total of 101 pathologically confirmed cases of subepithelial lesions (SELs) arising from the muscularis propria layer, including 69 GISTs, 17 leiomyomas and 15 schwannomas, were examined. A total of 3283 EUS images were used for training and five-fold-cross-validation, and 827 images were independently tested for diagnosing GISTs. For the risk classification of 69 GISTs, including very-low-, low-, intermediate- and high-risk GISTs, 2,784 EUS images were used for training and three-fold-cross-validation. RESULTS: For the differential diagnostic performance of GIST among all SELs, the accuracy, sensitivity, specificity and area under the receiver operating characteristic (ROC) curve were 80.4%, 82.9%, 75.3% and 0.865, respectively, whereas those for intermediate- and high-risk GISTs were 71.8%, 70.2%, 72.0% and 0.771, respectively. CONCLUSIONS: The EUS-CAD system showed a good diagnostic yield in differentiating GISTs from other mesenchymal tumors and successfully demonstrated the GIST risk classification feasibility. This system can determine whether treatment is necessary based on EUS imaging alone without the need for additional invasive examinations.

The impact of contour maps on estimating the risk of gastrointestinal stromal tumor recurrence: indications for adjuvant therapy: an analysis of the Kinki GIST registry.

INTRODUCTION: Contour maps enable risk classification of GIST recurrence in individual patients within 10 postoperative years. Although contour maps have been referred to in Japanese guidelines, their usefulness and role in determining indications for adjuvant therapy is still unclear in Japanese patients. The aims of this study are to investigate the validity of contour maps in Japanese patients with GIST and explore the new strategy for adjuvant therapy. MATERIALS AND METHODS: A total of 1426 Japanese GIST patients who were registered to the registry by the Kinki GIST Study Group between 2003 and 2012 were analyzed. Patients who had R0 surgery without perioperative therapy were included in this study. The accuracy of contour maps was validated. RESULTS: Overall, 994 patients have concluded this study. Using contour maps, we validated the patients. The 5-year recurrence-free survival rates of patients within the GIST classification groups of 0-10%, 10-20%, 20-40%, 40-60%, 60-80%, 80-90%, and 90-100% were 98.1%, 96.6%, 92.3%, 48.0%, 37.3%, 41.0% and 42.4%, respectively. We confirmed that this classification by contour maps was well reflected recurrence prediction. Further, in the high-risk group stratified by the modified National Institutes of Health consensus criteria (m-NIHC), the 10-year RFS rate was remarkably changed at a cutoff of 40% (0-40% group vs. 40-100% group: 88.7% vs. 50.3%, p < 0.001). CONCLUSION: Contour maps are effective in predicting individual recurrence rates. And it may be useful for the decision of individual strategy for high-risk patients combined with m-NIHC.

Pimitespib for the treatment of advanced gastrointestinal stromal tumors and other tumors.

Pimitespib (TAS-116) is the first heat shock protein 90 (HSP90) inhibitor approved in Japan, and it is indicated for the treatment of gastrointestinal stromal tumors (GIST) that have progressed after treatment with imatinib, sunitinib and regorafenib. This review describes the preclinical and clinical research with pimitespib, including its mechanism of action, pharmacokinetics, clinical antitumour activity and safety. In a phase III study, pimitespib significantly prolonged progression-free survival compared with placebo (median 2.8 vs 1.4 months; hazard ratio 0.51; 95% CI 0.30-0.87; p = 0.006). Common treatment-related adverse events were diarrhoea, decreased appetite, increase in serum creatinine, malaise, nausea and eye disorders. The efficacy and safety of pimitespib are being investigated in other tumour types and in combination with other anticancer therapies.

What is this article about? This article provides information about pimitespib, a drug that recently became available in Japan for the treatment of advanced gastrointestinal stromal tumors, or 'GISTs'. GISTs are a type of cancer found in the gastrointestinal tract, and those that are considered 'advanced' have stopped responding to other treatments and have spread to other parts of the body. What have studies shown? Pimitespib works in a way unlike other drug treatments for cancer ­ it inhibits a protein called heat shock protein 90, and this stops cancer cells from developing and growing. Pimitespib is taken by mouth. Studies in Japanese patients with advanced GISTs showed an increase in the time taken for the cancer to progress further and in the length of time that patients survived among those treated with pimitespib, compared with patients who did not receive the drug. These studies also found that pimitespib was not associated with serious side effects, although diarrhoea occurred frequently. Eye disorders developed in some patients, but they could be managed by interrupting or stopping treatment with pimitespib. Pimitespib is also being studied for the treatment of other cancers, alone and in combination with other anticancer drugs. What conclusions can be made from these studies? There are very few treatments available for patients with advanced GISTs and, therefore, pimitespib is an important new option for such patients in Japan. If the results of ongoing studies are positive, pimitespib may become a treatment option for a wider range of cancer patients in the future.

Endoscopic resection for the treatment of gastric gastrointestinal stromal tumors: a retrospective study from a large tertiary hospital in China.

BACKGROUND AND AIMS: With the continuous development of endoscopic technology, endoscopic resection (ER) has gradually become an optional method for the treatment of gastric gastrointestinal stromal tumors (GISTs). However, studies with a large sample or a long follow-up are lacking. Therefore, this research aims to evaluate the efficacy and safety of ER for gastric GISTs in the real-world setting with more than 300 enrolled patients and a follow-up period longer than 45 months. METHODS: From January 2013 to February 2023, 409 patients with a pathological diagnosis of GISTs after ER were retrospectively enrolled in this study. After excluding 86 patients with non-gastric GISTs, we assessed 323 patients with gastric GISTs. The main outcome measures were en bloc resection, complete resection, residual disease, recurrence, and complications. RESULTS: There were 194 (60.06%) females and 129 (39.94%) males, and the median age of the included patients was 58 years (51, 63). The median tumor size was 15.0 (10.0, 20.0) mm. According to the modified NIH criteria, 246 (75.85%) patients were classified as very low risk, 62 (19.20%) were classified as low risk, 12 (3.72%) were classified as moderate risk, and 3 (0.93%) were classified as high risk. A total of 287 (88.85%) patients achieved en bloc resection, and 287 (88.85%) also achieved complete resection. Only one patient showed residual and no recurrent lesions were noted during the follow-up. Regarding complications, three patients had complications, with a complication rate of 0.93%, and no severe complications requiring surgical intervention occurred. CONCLUSION: ER is an appropriate alternative method for the treatment of gastric GISTs, with an en bloc resection rate of 88.85% and a complication rate of 0.93%. No recurrence was noted during follow-up, even for GISTs with piecemeal resection.

Efficacy and Safety of Endoscopic Resection for Gastric Gastrointestinal Stromal Tumors Originating from the Muscularis Propria.

BACKGROUND: The role of endoscopic resection (ER) in gastric gastrointestinal stromal tumors (GISTs) has not been fully elucidated. AIMS: The purpose of this work was to evaluate the clinical effectiveness and safety of ER in patients with GISTs originating from the muscularis propria (MP). METHODS: A total of 233 consecutive patients with gastric GISTs originating from the MP layer, who underwent ER between February 2012 and May 2023, were included in this study. Clinical characteristics, tumor features, and outcomes were recorded and compared between patients who underwent en bloc resection and piecemeal resection. RESULTS: Among the 233 patients, the median size of GISTs was 12 mm (range 5-60 mm). Risk assessment categorized 190 patients as very low risk, 26 as low risk, 10 as moderate risk, and 7 as high risk. The procedures performed included endoscopic submucosal excavation (127 cases), endoscopic full-thickness resection (103 cases), and submucosal tunneling endoscopic resection (3 cases). The complete and R0 resection rate was 93.1%. Complications occurred in 4.7% of cases (perioperative perforations 1.7%, perioperative bleeding 1.3%, both 0.9%), resulting in conversion to surgery in 1.3% of cases. Risk factors associated with piecemeal resection were tumor size [odds ratio (OR) 0.402, 95% confidence interval (CI) 0.207-0.783; P = 0.007] and shape (OR 0.045, 95% CI 0.009-0.235; P < 0.001). CONCLUSIONS: ER is proven to be an effective and reasonably safe approach for gastric GISTs originating from the MP. Notably, larger tumor size and irregular shape are identified as risk factors for piecemeal resection during ER procedures.

Single-port intragastric wedge resection using the tunnel method: a novel surgical approach for treating endophytic gastric subepithelial tumors.

BACKGROUND: Intragastric wedge resection is an effective method for treating endophytic gastric subepithelial tumors (SETs). However, retracting the stomach wall to the umbilicus is difficult in certain patients. In response, we developed a novel surgical technique for single-port intragastric wedge resection, which we termed the "tunnel method." METHODS: A transumbilical incision is made, and a wound retractor is applied. After diagnostic laparoscopy, a gastrostomy is made on the greater curvature, lower body. Another small wound retractor is inserted into the gastrostomy, and extracted through the transumbilical incision, creating a tunnel from the gastrostomy site to the umbilicus. Articulating laparoscopic instruments are inserted via the tunnel, and intragastric wedge resection is performed. We collected and analyzed the clinicopathologic and operative data of patients who underwent intragastric wedge resection via the tunnel method. RESULTS: Twenty-seven patients who underwent single-port intragastric wedge resection via the tunnel method in a single tertiary referral hospital were included in this study. The mean age of the patients was 54.6 ± 11.4 years, body mass index was 26.5 ± 3.4 kg/m2. Twenty-four (88.9%) patients had tumors located in the upper third of the stomach. The average operative time was 65.0 ± 24.2 min. None of the patients experienced Clavien-Dindo grade IIIa or higher postoperative complications. The average postoperative hospital stay length was 2.5 ± 0.8 days. Thirteen gastrointestinal stromal tumors, nine leiomyomas, and one neuroendocrine carcinoma, schwannoma, lipoma, spindle cell proliferative lesion, and fibrotic lesion were pathologically diagnosed. The average tumor size was 2.6 ± 1.3 cm. All cases had negative resection margins. CONCLUSIONS: Single-port intragastric wedge resection by the tunnel method is a feasible and safe approach for treating endophytic gastric SETs.

Population-based long-term prognosis analysis of subcutaneous gastrointestinal stromal tumors.

BACKGROUND: Subcutaneous gastrointestinal stromal tumors (scGISTs) are extremely rare tumors, and the analysis of their long-term prognosis remains unreported. Therefore, our objective is to analyze the long-term prognosis of patients with scGISTs using the Surveillance, Epidemiology, and End Results database. METHODS: Patients diagnosed with GISTs between 2000 and 2019 were included in the study. To handle missing data, multiple imputation techniques were employed. Kaplan-Meier analysis and Cox proportional hazards models were used to evaluate overall survival (OS) and cancer-specific survival (CSS), and subgroup analyses were conducted for various variables. RESULTS: A total of 12,882 patients were enrolled, with 12,636 diagnosed with GISTs and 246 with scGISTs. In comparison to GISTs patients, scGISTs patients exhibited inferior OS [hazard ratio (HR) 1.69, 95% confidence interval (CI) 1.45-1.98, P < 0.001] and CSS (HR 2.16, 95% CI 1.78-2.61, P < 0.001). Across various subgroups, including age, sex, surgical intervention, marital status, and chemotherapy, scGISTs patients consistently demonstrated significantly poorer OS and CSS outcomes compared to GISTs patients (P < 0.05). The 1-, 3-, and 5-year OS rates for scGISTs patients were 78.4%, 60.3%, and 49.3%, respectively, with corresponding CSS rates of 83.3%, 67.8%, and 57.4%. Notably, scGISTs patients who received surgical treatment had significantly higher 5-year OS rates (62.1% vs 30.9%, P < 0.001) and CSS rates (67.8% vs 40.0%, P < 0.001) compared to those who did not undergo surgery. Multivariate Cox regression analysis identified age, surgical status, and mitotic rate as risk factors influencing OS in scGISTs patients, while surgical status and mitotic rate were identified as risk factors affecting CSS. CONCLUSIONS: Compared to GISTs patients, scGIST patients exhibit a less favorable prognosis; nonetheless, surgical intervention has been demonstrated to enhance their prognosis.

Comparative Analysis of Enbloc or Piecemeal Removal After Enbloc Resection of Gastrointestinal Stromal Tumors.

OBJECTIVE: To investigate the safety and prognosis of enbloc or piecemeal removal after enbloc resection of a gastric GIST by comparing the clinical data of endoscopic en block resection and piecemeal removal (EP) and en block resection and complete removal (EC) of gastric GISTs. METHODS: A total of 111 (43 endoscopic piecemeal, and 68 complete removal) patients with gastric GIST's ≥ 2 cm in diameter who underwent endoscopic therapy from January 2016 to June 2020 at the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. In all cases, it was ensured that the tumor was intact during the resection, however, it was divided into EP group and EC group based on whether the tumor was completely removed or was cut into pieces which were then removed. The patients' recurrence-free survival rate and recurrence-free survival (RFS) were recorded. RESULTS: There was no statistically significant difference in RFS rates between the two groups (P = 0.197). The EP group had relatively high patient age, tumor diameter, risk classification, and operation time. However, there was no statistically significant difference in the number of nuclear fission images, postoperative hospitalization time, postoperative fasting time, complication rate and complication grading between the two groups (P > 0.05). CONCLUSION: Endoscopic piecemeal removal after en block resection of gastric GIST is safe and effective and achieves similar clinical outcomes as complete removal after en block resection.

A systematic review and meta-analysis of neoadjuvant imatinib use in locally advanced and metastatic gastrointestinal stromal tumors.

BACKGROUND: Several doubts remain regarding the optimal use of neoadjuvant imatinib in gastrointestinal stromal tumors (GISTs), such as ideal treatment duration, patient selection, and long-term survival outcomes. This manuscript provides a comprehensive review on neoadjuvant imatinib treatment outcomes and facilitate evidence-based decision-making for the use of imatinib therapy in GISTs. METHODS: Four databases (PubMed, EMBASE, Scopus, and Cochrane Library) were searched from inception to September 9, 2023. Meta-analyses of proportions were performed for the outcomes of R0 resection, disease responses, and 1-year, 3-year, and 5-year overall survival (OS) as well as 1-year, 3-year, and 5-year disease free survival (DFS). Sensitivity analyses in the form of leave-one-out analyses, meta-regression, and subgroup analyses were performed for outcomes with substantial statistical heterogeneity. RESULTS: The search yielded 1254 articles, and 36 studies were included in our analysis. Meta-analysis of proportions revealed that 1-year, 3-year, and 5-year OS was 100%, 94%, and 88%, while 1-year, 3-year and 5-year DFS was 99%, 89%, and 79%, respectively. An R0 resection rate of 89% and a disease response rate of 67% was achieved after a mean duration of treatment of 8.41 ± 0.367 months. KIT exon 9 mutation was significantly associated with poorer 5-year DFS. CONCLUSION: This study quantified key outcomes for neoadjuvant imatinib in locally advanced and metastatic or recurrent GIST. Patients with gastric and rectal tumous stand to benefit from neoadjuvant imatinib with an optimal treatment duration of 8 months. Furthermore, the potential utility of mutational analysis in guiding treatment with neoadjuvant imatinib was demonstrated.

Performance of radiomics in preoperative determination of malignant potential and Ki-67 expression levels in gastrointestinal stromal tumors: a systematic review and meta-analysis.

Empirical evidence for radiomics predicting the malignant potential and Ki-67 expression in gastrointestinal stromal tumors (GISTs) is lacking. The aim of this review article was to explore the preoperative discriminative performance of radiomics in assessing the malignant potential, mitotic index, and Ki-67 expression levels of GISTs. We systematically searched PubMed, EMBASE, Web of Science, and the Cochrane Library. The search was conducted up to 30 September 2023. Quality assessment was performed using the Radiomics Quality Score (RQS). A total of 35 original studies were included in the analysis. Among them, 26 studies focused on determining malignant potential, three studies on mitotic index discrimination, and six studies on Ki-67 discrimination. In the validation set, the sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) of radiomics in the determination of high malignant potential were 0.74 (95% CI=0.69-0.78), 0.90 (95% CI=0.83-0.94), and 0.81 (95% CI=0.14-0.99), respectively. For moderately to highly malignant potential, the sensitivity, specificity, and AUC were 0.86 (95% CI=0.83-0.88), 0.73 (95% CI=0.67-0.78), and 0.88 (95% CI=0.27-0.99), respectively. Regarding the determination of high mitotic index, the sensitivity, specificity, and AUC of radiomics were 0.86 (95% CI=0.83-0.88), 0.73 (95% CI=0.67-0.78), and 0.88 (95% CI=0.27-0.99), respectively. When determining high Ki-67 expression, the combined sensitivity, specificity, and AUC were 0.74 (95% CI=0.65-0.81), 0.81 (95% CI=0.74-0.86), and 0.84 (95% CI=0.61-0.95), respectively. Radiomics demonstrates promising discriminative performance in the preoperative assessment of malignant potential, mitotic index, and Ki-67 expression levels in GISTs.

N6-methyladenosine-modified microRNA-675 advances the development of gastrointestinal stromal tumors via inhibiting myosin phosphatase targeting protein 1.

RNA N6-methyladenosine (m6A) modifications influence gastrointestinal stromal tumors (GISTs) development, but the detailed molecular mechanisms have not been fully studied. Here, microRNA-675 was found to be aberrantly elevated in cancerous tissues and cells of GISTs, compared to the corresponding normal counterparts, and GISTs patients with high-expressed microRNA-675 have worse outcomes. Additional experiments confirmed that silencing of microRNA-675 hindered cell division, mobility and tumorigenesis in vitro and in vivo, whereas triggered apoptotic cell death in GISTs cells. Furthermore, microRNA-675-ablation increased the expression levels of myosin phosphatase targeting protein 1 (MYPT1) to inactivate the tumor-initiating RhoA/NF2/YAP1 signal pathway, and downregulation of MYPT1 recovered the malignant phenotypes in microRNA-675-silenced GISTs cells. In addition, we evidenced that METTL3-mediated m6A modifications were essential for sustaining the stability of microRNA-675, and silencing of METTL3 restrained tumorigenesis of GISTs cells by regulating the microRNA-675/MYPT1 axis. To summarize, theMETTL3/m6A/microRNA-675/MYPT1 axis could be used as novel biomarkers for the diagnosis and treatment of GISTs.

Isolated liver gastrointestinal stromal tumor: A case report.

Gastrointestinal stromal tumors (GISTs) originate from the gastrointestinal tract. GISTs originate outside the gastrointestinal tract, referred to as extra GISTs, which is rare. Primary liver gastrointestinal stromal tumor (PLGIST) and liver metastasis of gastrointestinal stromal tumor (LMGIST) may present isolated liver lesion, making it difficult to determine their origin. A 38-year-old man who presented with isolated multiple giant cystic-solid liver lesions, ultimately diagnosed as liver GIST through CT-guided fine-needle aspiration. However, distinguishing between PLGIST and LMGIST in this case is challenging due to the absence of detailed medical records of emergency small intestine resection 5 years ago. Over 2-year follow-up period, the maximum lesion size increased from 16 to 21 cm, still, no extra liver lesions were observed. This study aims to provide a review to enhance understanding of this rare liver entity, aiding in tumor diagnosis and staging.

Clinical features and prognosis of malignant small bowel tumors: Experience from a university hospital in Chile.

BACKGROUND: Small bowel tumors (SBT) are infrequent and represent a small proportion of digestive neoplasms. There is scarce information about SBT in Latin America. AIM: To describe the epidemiology, clinical characteristics, diagnostic methods, and survival of malignant SBTs. METHODS: Retrospective observational study of adult patients with histopathological diagnosis of SBT between 2007 and 2021 in a university hospital in Chile. RESULTS: A total of 104 patients [51.9% men; mean age 57 years] with SBT. Histological type: neuroendocrine tumor (NET) (43.7%, n=38), gastrointestinal stromal tumors (GIST) (21.8%, n=19), lymphoma (17.2%, n=15) and adenocarcinoma (AC) (11.5%, n=10). GIST was more frequent in duodenum (50%; n=12) and NET in the ileum (65.8%; n=25). Metastasis was observed in 17 cases, most commonly from colon and melanoma. Nausea and vomiting were significantly more often observed in AC (p=0.035), as well as gastrointestinal bleeding in GIST (p=0.007). The most common diagnostic tools were CT and CT enteroclysis with an elevated diagnostic yield (86% and 94% respectively). The 5-year survival of GIST, NET, lymphoma and AC were 94.7% (95%CI: 68.1-99.2), 82.2% (95%CI: 57.6-93.3), 40.0% (95%CI: 16.5-82.8) and 25.9% (95%CI: 4.5-55.7%), respectively. NET (HR 6.1; 95%CI: 2.1-17.2) and GIST (HR 24.4; 95%CI: 3.0-19.8) were independently associated with higher survival compared to AC, adjusted for age and sex. CONCLUSIONS: Malignant SBT are rare conditions and NETs are the most common histological subtype. Clinical presentation at diagnosis, location or complications may suggest a more probable diagnosis. GIST and NET are associated with better survival compared to other malignant subtypes.

Endoscopic Ultrasound and Gastric Sub-Epithelial Lesions: Ultrasonographic Features, Tissue Acquisition Strategies, and Therapeutic Management.

Background and objectives: Subepithelial lesions (SELs) of the gastrointestinal (GI) tract present a diagnostic challenge due to their heterogeneous nature and varied clinical manifestations. Usually, SELs are small and asymptomatic; generally discovered during routine endoscopy or radiological examinations. Currently, endoscopic ultrasound (EUS) is the best tool to characterize gastric SELs. Materials and methods: For this review, the research and the study selection were conducted using the PubMed database. Articles in English language were reviewed from August 2019 to July 2024. Results: This review aims to summarize the international literature to examine and illustrate the progress in the last five years of endosonographic diagnostics and treatment of gastric SELs. Conclusions: Endoscopic ultrasound is the preferred option for the diagnosis of sub-epithelial lesions. In most of the cases, EUS-guided tissue sampling is mandatory; however, ancillary techniques (elastography, CEH-EUS, AI) may help in both diagnosis and prognostic assessment.

Diagnosis, Treatment, and Prognosis of Patients with Primary Familial Gastrointestinal Stromal Tumor: A Case Report and Literature Review.

Gastrointestinal stromal tumors are the most common mesenchymal tumors of the digestive tract, most of which are sporadic, and familial GISTs with germline mutations are rarely seen. Here, we report a 26-year-old female with a germline p. W557R mutation in exon 11 of the KIT gene. The proband and her father and sister presented with multifocal GIST and pigmented nevi. All 3 patients underwent surgery and imatinib therapy. To date, only 49 kindreds with germline KIT mutations and 6 kindreds with germline PDGFRA mutations have been reported. Summarizing the reported kindreds, the majority of familial GISTs manifest as multiple primary GISTs complicated with special clinical manifestations, including cutaneous hyperpigmentation, dysphagia, mastocytosis, inflammatory fibrous polyps, and large hands. Familial GISTs are generally thought to exhibit TKI sensitivity similar to that of sporadic GISTs with the same mutation.

Efficacy and Safety of Avapritinib in Treating Unresectable or Metastatic Gastrointestinal Stromal Tumors: A Phase I/II, Open-Label, Multicenter Study.

BACKGROUND: Avapritinib is a type 1 kinase inhibitor designed to potently and selectively inhibit oncogenic KIT/PDGFRA mutants by targeting the kinase active conformation. This multicenter, single-arm, open-label, phase I/II bridging study of NAVIGATOR in Chinese patients evaluated the safety and the antineoplastic activity of avapritinib in Chinese patients with unresectable/metastatic gastrointestinal stromal tumors (GIST). METHODS: Phase I comprised dose escalation for safety and phase II dose determination. Phase II comprised dose expansion for safety/efficacy evaluations in patients with PDGFRA D842V mutations or patients having received at least 3 lines of therapy without PDGFRA D842V mutations. The primary endpoints were recommended phase II dose, safety, and Independent Radiology Review Committee (IRRC)-assessed objective response rate (ORR). RESULTS: No dose-limiting toxicities occurred (n = 10); the recommended phase II dose was avapritinib 300 mg once daily orally. Fifty-nine patients initially received avapritinib 300 mg. Common grade ≥3 treatment-related adverse events were anemia, decreased white blood cell count, increased blood bilirubin levels, and decreased neutrophil count. In patients with PDGFRA D842V mutations, IRRC- and investigator-assessed ORRs were 75% and 79%, respectively; clinical benefit rates were both 86%. Median duration of response/progression-free survival were not reached. IRCC- and investigator-assessed ORRs in patients in the fourth- or later-line setting were 22% and 35%, respectively. Median progression-free survivals were 5.6 months for both. Overall survival data were immature and not calculated. CONCLUSION: Avapritinib was generally well tolerated and showed marked anti-tumor activity in Chinese patients with GIST bearing PDGFRA D842V mutations and notable efficacy as fourth- or later-line monotherapy (ClinicalTrials.gov Identifier: NCT04254939).