Immune priming and induction of tertiary lymphoid structures in a cord-blood humanized mouse model of gastrointestinal stromal tumor.

Gastrointestinal stromal tumors (GISTs) harbor diverse immune cell populations but so far immunotherapy in patients has been disappointing. Here, we established cord blood humanized mouse models of localized and disseminated GIST to explore the remodeling of the tumor environment for improved immunotherapy. Specifically, we assessed the ability of a cancer vascular targeting peptide (VTP) to bind to mouse and patient GIST angiogenic blood vessels and deliver the TNF superfamily member LIGHT (TNFS14) into tumors. LIGHT-VTP treatment of GIST in humanized mice improved vascular function and tumor oxygenation, which correlated with an overall increase in intratumoral human effector T cells. Concomitant with LIGHT-mediated vascular remodeling, we observed intratumoral high endothelial venules (HEVs) and tertiary lymphoid structures (TLS), which resemble spontaneous TLS found in GIST patients. Thus, by overcoming the limitations of immunodeficient xenograft models, we demonstrate the therapeutic feasibility of vascular targeting and immune priming in human GIST. Since TLS positively correlate with patient prognosis and improved response to immune checkpoint inhibition, vascular LIGHT targeting in GIST is a highly translatable approach to improve immunotherapeutic outcomes.

Safety, effectiveness and the optimal duration of preoperative imatinib in locally advanced gastric gastrointestinal stromal tumors: A retrospective cohort study.

BACKGROUND: The optimal duration of preoperative imatinib (IM) remains controversial. This study aimed to evaluate the safety, therapeutic effectiveness, and optimal duration of preoperative IM in patients with locally advanced gastric gastrointestinal stromal tumors (GIST). METHODS: The clinicopathologic data of 41 patients with locally advanced gastric GIST who received preoperative IM and underwent surgical resection from January 2014 and December 2021 were retrospectively analyzed. RESULTS: After a median of 7.0 (IQR: 4.5-10) months of preoperative IM treatment, 30 patients experienced adverse events (AEs), 80% of which were grade 1/2 AEs. The mean tumor size decreased from 12.71 ± 5.34 cm to 8.26 ± 4.00 cm, with a reduction rate of 35%. Setting 8 months as the cut-off value according to the results of ROC analysis. The proportion of laparoscopic surgery was higher in patients with short-term (≤8 months) versus long-term (>8 months) preoperative IM. Compared with the subtotal/total gastrectomy group, patients in the local gastrectomy group exhibited less intraoperative blood loss, shorter length of postoperative hospital stay, and fewer postoperative complications. The 3-year recurrence-free survival (RFS) and overall survival (OS) rates were 82.9% and 97.6%, and the expected 5-year RFS and OS rates were 75.6% and 90.2% respectively. RFS was better in the short-term than in the long-term preoperative IM treatment group, and it was also better in pre- plus postoperative IM treatment group than that in the preoperative IM alone group. Both univariate and multivariate COX analysis showed that a higher mitotic index and long-term preoperative IM treatment were associated with worse RFS, while postoperative IM treatment could significantly improve RFS. CONCLUSIONS: The study suggests that in patients with locally advanced gastric GIST, preoperative short-term (≤8 months) use of IM is associated with higher RFS than long-term use.

circ_SMA4 promotes gastrointestinal stromal tumors malignant progression by sponging miR-494-3p/KIT axis and activating JAK/STAT pathway.

Recent evidence has demonstrated that abnormal expression and regulation of circular RNA (circRNAs) are implicated in the development and progression of various tumors. The aim of this study was to investigate the effects of circ_SMA4 in Gastrointestinal Stromal Tumors (GISTs) malignant progression. Human circRNAs microarray analysis was conducted to identify differentially expressed (DE) circRNAs in GISTs. The effect of circ_SMA4 on cell proliferation, invasion, migration, and apoptosis was assessed in both in vitro and in vivo settings. Dual-luciferase reporter assay, RT-qPCR, Western-blot, and rescue assay were employed to confirm the interaction between circ_SMA4/miR-494-3p/ KIT axis. The results revealed that circ_SMA4 was significantly upregulated in GISTs, and exhibited high diagnostic efficiency with an AUC of 0.9824 (P < 0.01). circ_SMA4 promoted cell proliferation, invasion, migration, while inhibiting apoptosis in GISTs cells, both in vitro and in vivo. Silencing circ_SMA4 partially inhibited GISTs malignant progression. Additionally, circ_SMA4 acted as a competing endogenous RNA (ceRNA) by targeting miR-494-3p, and KIT was identified as a functional gene for miR-494-3p in GISTs. Furthermore, the results confirmed that circ_SMA4/miR-494-3p/ KIT axis plays a role in activating the JAK/STAT signaling pathway in GISTs. Therefore, for the first time, we have identified and emphasized that circ_SMA4 is significantly upregulated and plays an oncogenic role in GISTs by sponging miR-494-3p to activate the KIT/JAK/STAT pathway. These findings underscore circ_SMA4 may serve as a novel diagnostic biomarker and therapeutic target for GISTs.

Ligation-assisted endoscopic submucosal resection following unroofing technique for small esophageal subepithelial lesions originating from the muscularis propria.

BACKGROUND: The majority of esophageal subepithelial lesions originating from the muscularis propria (SEL-MPs) are benign in nature, although a subset may exhibit malignant characteristics. Conventional endoscopic resection techniques are time-consuming and lack efficacy for small SEL-MPs. AIM: To evaluate the efficacy and safety of ligation-assisted endoscopic submucosal resection (ESMR-L) following unroofing technique for small esophageal SEL-MPs. METHODS: From January 2021 to September 2023, 17 patients diagnosed with esophageal SEL-MPs underwent ESMR-L following unroofing technique at the endoscopy center of Shenzhen People's Hospital. Details of clinicopathological characteristics and clinical outcomes were collected and analyzed. RESULTS: The mean age of the patients was 50.12 ± 12.65 years. The mean size of the tumors was 7.47 ± 2.83 mm and all cases achieved en bloc resection successfully. The average operation time was 12.2 minutes without any complications. Histopathology identified 2 Lesions (11.8%) as gastrointestinal stromal tumors at very low risk, 12 Lesions (70.6%) as leiomyoma and 3 Lesions (17.6%) as smooth muscle proliferation. No recurrence was found during the mean follow-up duration of 14.18 ± 9.62 months. CONCLUSION: ESMR-L following roofing technique is an effective and safe technique for management of esophageal SEL-MPs smaller than 20 mm, but it cannot ensure en bloc resection and may require further treatment.

Successful modified CLEAN-NET with semicircular seromuscular layer incision for a gastric GIST near the cardia: a case report and video demonstration.

BACKGROUND: The combination of laparoscopic and endoscopic approaches to neoplasia with a non-exposure technique (CLEAN-NET) is a laparoscopic and endoscopic cooperative surgery (LECS). It combines laparoscopic gastric resection and endoscopic techniques for local resection of gastric tumors, such as gastrointestinal stromal tumors (GIST), with minimal surgical margins. A conventional CLEAN-NET surgical procedure is complex, requiring careful techniques to preserve the cardia, particularly in case of nearby lesions. We describe the case of a patient who underwent a modified CLEAN-NET approach with a semi-circular seromuscular layer incision surrounding the base of the tumor, different from a circular shape seromuscular layer in the conventional CLEAN-NET: around the tumor to preserve mucosal continuity, which acts as a barrier to avoid intraoperative tumor dissemination. CASE PRESENTATION: A 43-year-old woman was referred to our hospital because of a gastric submucosal tumor near the cardia, detected on medical examination. The patient was diagnosed with gastric GIST based on the results of endoscopic ultrasound-guided fine-needle aspiration. Modified CLEAN-NET was performed with a semicircular incision of the seromuscular layer on the opposite side of the cardia, making the surgical procedure simple and minimizing partial resection of the gastric wall, including the tumor, while preserving the cardia. The operative time was 147 min, preoperative blood loss volume was 3 mL, and postoperative hospital stay was 9 days. The resected specimen revealed a minimal resection of the gastric wall, including the tumor. The cardia and gastric nerves were preserved, and the postoperative food intake was good. CONCLUSIONS: The modified CLEAN-NET with semicircular seromuscular layer dissection is a simple and reliable surgical procedure for GIST near the cardia.

Anti-tumor effect of antibody-drug conjugate targeting cell adhesion molecule 1 on GIST cells representing small intestinal GIST.

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the alimentary tract. The prognosis depends on the primary site, and small intestinal GISTs have a worse prognosis than gastric GISTs. Molecularly targeted drugs to inhibit tyrosine kinase activity of KIT were used for unresectable or recurrent GISTs. However, secondary resistance to the drugs is often acquired, and treatments based on other mechanisms are needed. Previously, we reported that cell adhesion molecule 1 (CADM1) was highly expressed in most of small intestinal GISTs but not in most of gastric GISTs. In the present study, we examined whether the antibody-drug conjugate (ADC) with anti-CADM1 antibody and monomethyl auristatin E (anti-CAD-ADC) shows anti-tumor effect on CADM1-expressing human GIST cells. The ADC adhibited in this study was previously used for CADM1-expressing human mesothelioma cells and showed anti-tumor effect for them in vitro. GIST-T1 cell line of gastric origin which scarcely expresses CADM1 and GIST-T1 cells transfected with CADM1 cDNA (GIST-T1-CAD cells) which highly expresses CADM1 and represents small intestinal GIST were used. In vitro, anti-CAD-ADC showed remarkable cytotoxic activity on GIST-T1-CAD cells, but control ADC did not. Both anti-CAD-ADC and control ADC did not show anti-tumor effect on original GIST-T1 cells. When GIST-T1-CAD cells were subcutaneously injected to the nude mice, intravenous administration of anti-CAD-ADC showed inhibitory effect for tumor enlargement. Tumor of GIST-T1 cells grew even after anti-CAD-ADC injection. When GIST-T1-CAD cells were injected into peritoneal cavity of the SCID mice, intraperitoneal administration of anti-CAD-ADC showed reduction of the peritoneal tumor. On the other hand, peritoneal tumor grew after control ADC administration. Tissue and organ damage due to administration of anti-CAD-ADC was not apparent by macroscopic and histological examinations in mice. These results indicate that anti-CAD-ADC could have apparent anti-tumor effect on CADM1-expressing human GIST cells both in in vitro and in vivo mouse models.

Long-Term Efficacy of Single-Incision Laparoscopic Intragastric Resection in Treating Gastrointestinal Stromal Tumors.

Gastrointestinal stromal tumors (GISTs), the most common mesenchymal tumors in the gastrointestinal tract, are increasingly treated with minimally invasive surgeries. Developed techniques include laparoscopic, endoscopic, and hybrid methods for gastric GIST resection. Our study, focusing on single-incision laparoscopic intragastric resection for gastric GISTs, aims to evaluate its safety, efficacy, and long-term outcomes. In a retrospective study of GIST surgery involving 14 patients who underwent single-incision laparoscopic intragastric resections, we analyzed and compared their preoperative demographics, American Society of Anesthesiologists (ASA) scores, tumor size, neoadjuvant treatment, operation duration, hospital stay, mitotic and Ki-67 indexes, and histological features with those of patients who underwent open and laparoscopic wedge resections, to assess the impact on both survival and disease-free survival. Average operation time was 93.07 minutes (range 81-120 minutes). Average blood loss: 67 ± 20 mL (range 40-110 mL). Postoperative hospital stay averaged 6.79 days (range 4-16 days). Strong correlations were observed between preoperative and pathological tumor sizes (P = .001, P < .001). Survival analysis indicated a significant association with ASA scores (P = .031), but not with mitotic index, Ki-67, or tumor size. Average survival was 80.57 months, with no recurrence or metastasis during follow-up. Based on our experience, the single-incision laparoscopic intragastric resection method emerges as a highly efficient, timesaving, and gentle oncological procedure, providing a safe and minimally invasive alternative resulting in shorter hospital stays and excellent long-term outcomes with minimal recurrence. For more definitive conclusions, larger, multicenter, and prospective studies are recommended.

Discontinuation versus continuation of imatinib in patients with advanced gastrointestinal stromal tumours (BFR14): exploratory long-term follow-up of an open-label, multicentre, randomised, phase 3 trial.

BACKGROUND: The long-term impact of tyrosine kinase inhibitor (TKI) discontinuation on resistance and survival in patients with advanced gastrointestinal stromal tumours (GIST) is unclear. We report the exploratory long-term outcomes of patients with advanced GIST stopping imatinib in the BFR14 trial. METHODS: BFR14, an open-label, randomised, phase 3 trial, was done in 17 comprehensive cancer centres or hospitals across France. Patients with advanced GIST aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0-3, no previous treatment with imatinib, and no previous malignancy were eligible. Patients were treated with oral imatinib 400 mg daily. Patients with a complete or partial response, or stable disease, according to Response Evaluation Criteria in Solid Tumours (1.0) at 1 year, 3 years, and 5 years from the start of treatment were randomly assigned (1:1) to treatment discontinuation until progression (interruption group) or treatment continuation until progression (continuation group). Randomisation was done centrally with computer-generated permuted blocks of two and six patients stratified by participating centre and presence or absence of residual disease on CT scan. The primary endpoint was progression-free survival. Secondary endpoints included time to imatinib resistance and overall survival. Analyses were conducted on an intention-to-treat basis in all randomly assigned patients who were not lost to follow-up. This trial is registered with ClinicalTrial.gov, NCT00367861. FINDINGS: Between May 12, 2003, and March 16, 2004, after 1 year of imatinib, 32 patients were randomly assigned to the interruption group and 26 to the continuation group. Between June 13, 2005, and May 30, 2007, after 3 years of imatinib, 25 patients were randomly assigned to the interruption group and 25 to the continuation group. Between Nov 9, 2007, and July 12, 2010, after 5 years of imatinib, 14 patients were randomly assigned to the interruption group and 13 to the continuation group. Median follow-up was 235·2 months (IQR 128·8-236·6) after the 1-year randomisation, 200·9 months (190·2-208·4) after the 3-year randomisation, and 164·5 months (134·4-176·4) after the 5-year randomisation. Median progression-free survival in the interruption group versus the continuation group after 1 year of imatinib was 6·1 months (95% CI 2·5-10·1) versus 27·8 months (19·5-37·9; hazard ratio [HR] 0·36 [95% CI 0·20-0·64], log-rank p=0·0003), after 3 years of imatinib was 7·0 months (3·5-11·7) versus 67·0 months (48·8-85·6; 0·15 [0·07-0·32], log-rank p<0·0001), and after 5 years of imatinib was 12·0 months (9·0-16·6) versus not reached (NR; NR-NR; 0·13 [0·03-0·58], log-rank p=0·0016). The median time to imatinib resistance after 1 year of imatinib was 28·7 months (95% CI 18·1-39·1) versus 90·6 months (25·3-156·1; HR 0·93 [95% CI 0·51-1·71], log-rank p=0·82), after 3 years was 66·2 months (43·0-89·6) versus 127·3 months (15·0-239·7; 0·35 [0·17-0·72, log-rank p=0·0028), and after 5 years was 58·6 months (0·0-167·4) versus NR (NR-NR; 0·24 [0·05-1·12], log-rank p=0·049). Median overall survival after 1 year of imatinib was 56·0 months (95% CI 30·3-82·9) versus 105·0 months (20·6-189·6; HR 0·84 [95% CI 0·46-1·54], log-rank p=0·57), after 3 years was 104·0 months (90·7-118·7) versus 134·0 months (89·7-178·3; 0·40 [0·20-0·82], log-rank p=0·0096), and after 5 years was NR (NR-NR) versus 110·4 months (82·7-154·1; 1·28 [0·41-3·99]; log-rank p=0·67), INTERPRETATION: Imatinib interruption in patients with GIST without progressive disease is not recommended. Imatinib interruption in non-progressing patients with GIST was associated with rapid progression, faster resistance to imatinib, and shorter overall survival in the long-term follow-up when compared with imatinib continuation in patients after 3 years and 5 years of imatinib. FUNDING: Centre Léon Bérard, INCa, CONTICANET, Ligue Contre le Cancer, and Novartis.

Gastrointestinal stromal tumours: incidence, recurrence and mortality. A decade of patients from a New Zealand tertiary surgical centre.

BACKGROUND: Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours of the gastrointestinal tract. The New Zealand (NZ) population incidence has not previously been documented nor has the potential effect of ethnicity been reviewed. We furthermore wanted to assess the difference between those undergoing a wedge resection versus a more extensive operation which we hypothesised would correlate with recurrence and mortality. METHODS: All patients (n = 103) with a GIST diagnosed and treated at Te Whatu Ora Waitemata (Auckland, New Zealand) between 2012 and 2021 are presented. Patient demographics, method of GIST detection, management approach, index surgery, histological features, use of adjuvant and neoadjuvant imatinib, follow-up, recurrence and mortality rates were analysed. RESULTS: This paper reports the largest NZ GIST cohort to date and estimates an incidence of 17 cases per million per year. Eighty-four patients underwent surgical resection, 58 received a wedge resection and 17 received a more extensive operation. Five-year disease-free survival rates were 100% in the low/very low risk, 90% in the intermediate and 59% in the high risk groups as determined by the modified NIH criteria. Our overall 5-year GIST-specific survival rate was 83%; it was 91% in those who underwent a wedge resection and 60% in the extensive operation group. There is evidence that Maori have higher rates of GIST recurrence compared to non-Maori and are more likely to require an extensive surgical resection.

Shared germline genomic variants in two patients with double primary gastrointestinal stromal tumours (GISTs).

BACKGROUND: Gastrointestinal stromal tumours (GISTs) are prevalent mesenchymal tumours of the gastrointestinal tract, commonly exhibiting structural variations in KIT and PDGFRA genes. While the mutational profiling of somatic tumours is well described, the genes behind the susceptibility to develop GIST are not yet fully discovered. This study explores the genomic landscape of two primary GIST cases, aiming to identify shared germline pathogenic variants and shed light on potential key players in tumourigenesis. METHODS: Two patients with distinct genotypically and phenotypically GISTs underwent germline whole genome sequencing. CNV and single nucleotide variant (SNV) analyses were performed. RESULTS: Both patients harbouring low-risk GISTs with different mutations (PDGFRA and KIT) shared homozygous germline pathogenic deletions in both CFHR1 and CFHR3 genes. CNV analysis revealed additional shared pathogenic deletions in other genes such as SLC25A24. No particular pathogenic SNV shared by both patients was detected. CONCLUSION: Our study provides new insights into germline variants that can be associated with the development of GISTs, namely, CFHR1 and CFHR3 deep deletions. Further functional validation is warranted to elucidate the precise contributions of identified germline mutations in GIST development.

Follow-up analysis and research of very low-risk and low-risk gastrointestinal stromal tumors after endoscopic resection.

Currently, due to limited long-term evidence, there remains some controversy surrounding the recommended postoperative monitoring strategy for primary low-risk gastrointestinal stromal tumors (GISTs). This study recruited a total of 532 patients diagnosed with very low-risk and low-risk GISTs who underwent endoscopic resection from 2015 to 2021, including 460 very low-risk patients and 72 low-risk patients. Descriptive statistical analysis was used to evaluate the clinical and pathological characteristics of GIST patients, and Kaplan-Meier methods were employed for survival analysis. The results showed that the 5-year recurrence-free survival rates for very low-risk and low-risk patients were 98.5% and 95.9%, respectively. The 5-year disease-specific survival rates for both groups were 100%. Additionally, the 5-year overall survival rates were 99.7% for very low-risk patients and 100% for low-risk patients (P = 0.69). Therefore, it is suggested that routine follow-up monitoring, including endoscopic surveillance and imaging, may not be necessary for very low-risk and low-risk GISTs after endoscopic resection.

Intratumoral microbiome promotes liver metastasis and dampens adjuvant imatinib treatment in gastrointestinal stromal tumor.

Understanding the determinants of long-term liver metastasis (LM) outcomes in gastrointestinal stromal tumor (GIST) patients is crucial. We established the feature selection model of intratumoral microbiome at the surgery, achieving robust predictive accuracies of 0.953 and 0.897 AUCs in discovery (n = 74) and validation (n = 34) cohorts, respectively. Notably, despite the significant reduction in LM occurrence with adjuvant imatinib (AI) treatment, intratumoral microbiome exerted independently stronger effects on post-operative LM. Employing both 16S and full-length rRNA sequencing, we pinpoint intracellular Shewanella algae as a foremost LM risk factor in both AI- and non-AI-treated patients. Experimental validation confirmed S. algae's intratumoral presence in GIST, along with migration/invasion-promoting effects on GIST cells. Furthermore, S. algae promoted LM and impeded AI treatment in metastatic mouse models. Our findings advocate for incorporating intratumoral microbiome evaluation at surgery, and propose S. algae as a therapeutic target for LM suppression in GIST.

Endoscopic Characteristics of Small-Bowel Gastrointestinal Stromal Tumors Detected During Single-Balloon Enteroscopy: A Retrospective Analysis.

BACKGROUND/AIMS:  The endoscopic features of small-bowel gastrointestinal stromal tumors (GISTs) are not well defined. The objective of this study was to describe the endoscopic features of GISTs of the small intestine detected via single-balloon enteroscopy (SBE). MATERIALS AND METHODS:  Patients with surgically confirmed small intestinal GISTs from January 2014 to September 2022 were retrospectively analyzed. The hospital's electronic medical record system was used to retrieve the patients' data, including their demographics, clinical symptoms, hemoglobin on admission, endoscopic and computerized tomography findings, clinicopathological findings, and surgical management data. RESULTS:  In total, 46 GIST patients (23 men and 23 women) with overt bleeding were included, with a mean age of 52 years (23-80 years). The typical duration of the symptoms was 48 hours. Four patients (8.70%) had lesions in the duodenum, 32 (69.56%) had lesions in the jejunum, 8 (17.39%) had lesions in the ileum, and 2 (4.35%) had lesions around the junction of the jejunum and ileum. Out of the 46 patients, 27 underwent SBE, and GISTs were visualized in 25, while the lesions could not be visualized in the remaining 2. Submucosal round (n = 13), submucosal sessile (n = 8), and invasive/penetrating (n = 4) were among the endoscopic tumor features. Twenty patients exhibited submucosal protuberant lesions, with ulceration, vascular nodules/congestion, or erosion on the surface, and 5 patients presented ulcerative infiltrative lesions. The multiple logistic regression analysis indicated that the invasive/penetrating characteristics of GISTs under SBE evaluation are significantly correlated with the risk level of GIST malignancy (P < .05). CONCLUSION:  A variety of endoscopic characteristics could be observed during the preoperative SBE evaluation of small-intestine GISTs.

Application of Computer-Assisted Endoscopic Ultrasonography Based on Texture Features in Differentiating Gastrointestinal Stromal Tumors from Benign Gastric Mesenchymal Tumors.

BACKGROUND/AIMS:  Gastrointestinal stromal tumors are common gastric mesenchymal tumors that are potentially malignant. However, endoscopic ultrasonography is poor in diagnosing gastrointestinal stromal tumors. The study investigated the efficacy of texture features extracted from endoscopic ultrasonography images to differentiate gastrointestinal stromal tumors from gastric mesenchymal tumors. MATERIALS AND METHODS:  The endoscopic ultrasonography examinations of 120 patients with confirmed gastric gastrointestinal stromal tumors, leiomyoma, or schwannoma were evaluated. Histology was considered the gold standard. Three feature combinations were extracted from endoscopic ultrasonography images of each lesion: 48 gray-level co-occurrence matrix-based features, 48 gray-level co-occurrence matrix-based features plus 3 global gray features, and 15 gray-gradient co-occurrence matrix-based features. Support vector machine classifiers were constructed by using feature combinations to diagnose gastric gastrointestinal stromal tumors. The area under the receiver operating characteristic curve, accuracy, sensitivity, and specificity were used to evaluate the diagnostic performance. The support vector machine model's diagnostic performance was compared with the endoscopists. RESULTS:  The 3 feature combinations had better performance in differentiating gastrointestinal stromal tumors: gray-gradient cooccurrence matrix-based features yielded an area under the receiver operating characteristic curve of 0.90, which was significantly greater than an area under the receiver operating characteristic curve of 0.83 in gray-level co-occurrence matrix-based features and an area under the receiver operating characteristic curve of 0.84 in the texture features plus 3 global features. The support vector machine model (81.67% accuracy, 81.36% sensitivity, and 81.97% specificity) was also better than endoscopists (an average of 69.31% accuracy, 65.54% sensitivity, and 72.95% specificity) Conclusion: Texture features in computer-assisted endoscopic ultrasonography diagnosis are useful to differentiate gastrointestinal stromal tumors from benign gastric mesenchymal tumors and compare favorably with endoscopists. Support vector machine model using gray-gradient co-occurrence matrix-based texture features revealed the best diagnostic performance in diagnosing gastric gastrointestinal stromal tumors.

[Diagnostic yield and utility of boring biopsy for subepithelial lesions of the stomach and esophagus].

Herein, we aimed to examine the diagnostic yield and utility of boring biopsy for subepithelial lesions (SEL) of the stomach and esophagus. A total of 52 patients with SELs of the stomach or esophagus underwent boring biopsy. The diagnostic yield of boring biopsy for gastric and esophageal SELs was 50% (21/42) and 80% (8/10), and for SELs with a diameter of less than 10mm, the diagnostic yield was 67% (6/9) and 83% (5/6), respectively. Forty-three percent (9/21) of the gastric SELs were diagnosed with gastrointestinal stromal tumor (GIST), while all esophageal SELs (8/8) were leiomyomas. Ten percent (4/42) of boring biopsies for the stomach were accompanied by complications:two cases of perforation and two of bleeding.

Prospective evaluation of quantitative response parameter in patients with Gastrointestinal Stroma Tumor undergoing tyrosine kinase inhibitor therapy-Impact on clinical outcome.

The purpose of this study was to determine if dual-energy CT (DECT) vital iodine tumor burden (ViTB), a direct assessment of tumor vascularity, allows reliable response assessment in patients with GIST compared to established CT criteria such as RECIST1.1 and modified Choi (mChoi). From 03/2014 to 12/2019, 138 patients (64 years [32-94 years]) with biopsy proven GIST were entered in this prospective, multi-center trial. All patients were treated with tyrosine kinase inhibitors (TKI) and underwent pre-treatment and follow-up DECT examinations for a minimum of 24 months. Response assessment was performed according to RECIST1.1, mChoi, vascular tumor burden (VTB) and DECT ViTB. A change in therapy management could be because of imaging (RECIST1.1 or mChoi) and/or clinical progression. The DECT ViTB criteria had the highest discrimination ability for progression-free survival (PFS) of all criteria in both first line and second line and thereafter treatment, and was significantly superior to RECIST1.1 and mChoi (p < .034). Both, the mChoi and DECT ViTB criteria demonstrated a significantly early median time-to-progression (both delta 2.5 months; both p < .036). Multivariable analysis revealed 6 variables associated with shorter overall survival: secondary mutation (HR = 4.62), polymetastatic disease (HR = 3.02), metastatic second line and thereafter treatment (HR = 2.33), shorter PFS determined by the DECT ViTB criteria (HR = 1.72), multiple organ metastases (HR = 1.51) and lower age (HR = 1.04). DECT ViTB is a reliable response criteria and provides additional value for assessing TKI treatment in GIST patients. A significant superior response discrimination ability for median PFS was observed, including non-responders at first follow-up and patients developing resistance while on therapy.

Utilization of neoadjuvant therapy for localized gastric gastrointestinal stromal tumors and the association with survival.

BACKGROUND: For gastric gastrointestinal stromal tumors (GISTs), neoadjuvant imatinib is most often reserved for tumors near the gastroesophageal junction, multivisceral involvement, or limited metastatic disease. Whether localized gastric GISTs benefit from neoadjuvant therapy (NAT) remains unknown. We sought to examine factors associated with NAT utilization for localized gastric GISTs and evaluate implications on survival. METHODS: The National Cancer Database identified patients with localized gastric GISTs treated with NAT (2010-2020), excluding tumors extending beyond the gastric wall, located in the cardia, or with metastatic disease. Multivariable logistic regression assessed characteristics of NAT use. After 1:1 propensity score matching, Kaplan-Meier methods and multivariable Cox regression assessed overall survival (OS). RESULTS: Of 7203 patients, 762 (10.6%) received NAT followed by resection. On multivariable analysis, increasing tumor size was associated with NAT use (<2.0 cm vs 2.0-5.0 cm [odds ratio {OR}, 2.03; 95% CI, 1.19-3.47; P = .010] vs >5 cm [OR, 16.87; 95% CI, 10.02-28.40; P < .001]). After propensity score matching, 1506 patients remained. Median OS for NAT was 46.0 months vs 43.0 months for resection (P = .059), which was independently predictive of improved survival on multivariable analysis (hazard ratio [HR], 0.89; 95% CI, 0.80-0.99; P = .041). Subgroup analysis by tumor size showed no survival differences for tumors <2.0 cm or from 2.0 to 5.0 cm. Median OS was higher for tumors > 5.0 cm treated with NAT (NAT, 45.4 months [IQR, 29.5-65.9] vs upfront resection, 42.3 months [IQR 26.9-62.8]) and associated with improved survival on multivariable analysis (HR, 0.88; 95% CI, 0.78-0.99; P = .040). CONCLUSION: Although patients who received NAT had improved survival, this was primarily due to tumors >5.0 cm. Expanding NAT selection criteria to include localized gastric GISTs >5.0 cm may improve outcomes and warrants investigation through clinical trials.