Metastasis Of Gastrointestinal Stromal Tumor Research Articles

Metastatic GIST with a TWIST of RCC: A case report

Gastrointestinal Stromal Tumors (GIST) is a tumor of mesenchymal origin in the digestive tract, arising from Interstitial cells of Cajal. Majorly, they are an incidental finding in people of older age group (>60 years) with very rare bone metastasis. Our aim is to understand the role of genetic mutations in metastasis of GIST and coexistence of other malignancy in the same patient. We present an unusual case of a 75-year-old male with jejunal GIST, managed with resection of the tumor and imatinib, who 15 years later presented with subsequent liver, rare femoral head metastases and coexisting Renal Cell Carcinoma in left kidney. GIST cases can be associated with different syndromes and malignancies. This necessitates additional work up and long term follow up.

Percutaneous microcoil localization as an aid to ultrasound-guided hepatic gastrointestinal stromal tumor metastasis resection: A case report

Liver nodules that develop in children with cancer may represent primary malignancy, metastatic disease, or other conditions potentially requiring aggressive management. Laparoscopic methods have been utilized for nodule resection with perioperative ultrasonographic assistance. However, certain nodules in liver tissue can be difficult to identify on ultrasonography. Ultrasonography guided surgical resection after computer tomography (CT)-guided localization using microcoils is an innovative technique that has the potential to assist in the resection of small or deep liver nodules in children in these unique cases. A 15-year-old female presented with evidence of a hypermetabolic liver nodule on routine PET scan, 5 years following resection of a hepatic metastasis via right hepatic trisegmentectomy for primary gastrointestinal stromal tumor (GIST). Contrast-enhanced CT confirmed presence of a new suspicious liver nodule. Given the interval from initial treatment to the identification of this hepatic nodule, consent was received from patient and her family to surgically resect the nodule. However, pre-operatively the nodule could not be appreciated on ultrasonography. Interventional radiology was consulted for CT guided percutaneous microcoil localization of the hepatic nodule. CT-guided percutaneous microcoil localization with ultrasonographic guided liver resection allowed for complete resection of the liver nodule. We have successfully used an innovative technique of CT-guided microcoil placement to direct ultrasound-guided surgical resection of an otherwise ultrasound-occult liver nodule in the pediatric setting.

Clinical characteristics of gastrointestinal stromal tumors with lymph node metastasis: A retrospective single-centre case-controlled study.

e23509 Background: Lymph node metastasis of gastrointestinal stromal tumors (GISTs) rarely occurs, and lymphadenectomy is not routinely performed in GIST resection. To date, the relevant characteristics and prognosis of GIST patients with lymph node metastasis are not well known. Methods: From January 2010 to December 2021, GIST patients who underwent lymph node resection were enrolled in this study from a GIST referral centre. All patients were divided into either the LN- group (GISTs without lymph node metastasis) or the LN+ group (GISTs with lymph node metastasis). The clinicopathological features and follow-up data were analysed, and propensity score matching (PSM) was conducted to reduce bias caused by confounders. Results: Out of 1024 surgical patients, 198 patients (age, 52.23±13.54 years; 56.6% males) underwent GIST resection with lymph node dissection for lymphadenopathy, and 17 patients had lymph node metastases (17/1024, 1.66%; 17/198, 8.59%). The LN+ group had a higher mitotic count (P = 0.012) and a higher proportion of distant metastasis (P < 0.001) than the LN- group. After PSM, 28 patients were included (18 in the LN- group and 10 in the LN+ group). The LN- group had both longer postoperative progression-free survival (PFS, not reached vs. 15.0 months, P = 0.002) and overall survival (OS) than the LN+ group, but the difference in OS was not statistically significant (not reached vs. 35.0 months, P = 0.069). Conclusions: The rate of lymph node metastasis in GISTs is low. Lymph node metastasis may be a less common form of distant metastasis. Moreover, GIST with lymph node metastasis has an unfavourable prognosis. Further studies are warranted to identify GISTs with lymph node involvement and the potential involved mechanism. [Table: see text]

Unusual breast metastasis of gastrointestinal stromal tumor: A case report and literature review

Gastrointestinal stromal tumors (GISTs) are the most frequent mesenchymal tumors of gastrointestinal tract. The most common sites of metastases are the liver and the peritoneum, whereas breast metastases from GIST are extremely rare. We present a second case of GIST breast metastasis. We found a case of breast metastasis from rectum GIST. A 55-year-old female patient presented with rectum tumor with multiply liver lesions and metastasis in the right breast. Abdominal-perineal extirpation of rectum was performed, histology and immunohistochemistry study showed GIST, mixed type with CD117 and DOG-1 positive staining. The patient was taking imatinib 400 mg for 22 mo with stable disease. Because of growth of the breast metastasis the treatment was changed twice: The dose of imatinib was doubled with further progression in the breast lesion and then the patient was receiving sunitinib for 26 mo with partial response in the right breast and stable disease in the liver lesions. The breast lesion increased and right breast resection was done - surgery on local progression, the liver metastases were stable. Histology and immunohistochemistry studies revealed GIST metastasis, CD 117 and DOG 1 positive with KIT exon 11 mutation. After surgery the patient resumed imatinib. Until now the patient has been taking imatinib 400 mg for 19 mo without progression, last follow up was in November 2022. GISTs breast metastases are extremely rare, we described the second case. At the same time second primary tumors have been reported frequently in patients diagnosed with GISTs and breast cancer is one of the most common second primary tumors in patients with GISTs. That is why it is very important to distinguish primary from metastatic breast lesions. Surgery on local progression made it possible to resume less toxic treatment.

The relationship between Ki-67 expression and imaging signs and pathological features in GISTs.

To investigate the correlations between the Ki-67 index and plain-scan computerized tomography (CT) signs and pathological features of gastrointestinal stromal tumor (GIST) tissue. Data from 186 patients with GIST diagnosed by pathology and immunohistochemistry (IHC) in Peking University First Hospital from May 2016 to May 2022 were analyzed. The patients were divided into two groups: Ki-67 ≤5% and >5%. Correlation analysis, univariate and multivariate Logistic regression analysis were used to explore the correlations between CT signs, pathological features, and Ki-67 expression. Univariate indicators correlated with the Ki-67 index were mitotic count, pathological grade, tumor hemorrhage, tumor necrosis, tumor size, and tumor density. Multivariate Logistic regression indicated that the mitotic count [odds ratio (OR) 10.222, 95% confidence interval (CI) 4.312-31.039], pathological grade (OR 2.139, 95% CI 1.397-3.350), and tumor size (OR 1.096, 95% CI 1.020-1.190) were independently associated with the Ki-67 expression level. The concordance indexes (C-index) for the pathological features and CT signs models were 0.876 (95% CI 0.822-0.929) and 0.697 (95% CI 0.620-0.774), respectively, with positive predictive values of 93.62% and 58.11% and negative predictive values of 81.29% and 75.89%, respectively. After internal verification by the Bootstrap method, the fitting degree of the pathological features model was found to be better than that of the CT signs model. Mitotic count, pathological risk grading, and tumor size are independent risk factors correlating with high Ki-67 index. These results indicate that the Ki-67 index reflects tumor malignancy and can predict recurrence and metastasis of GIST.

Transcriptomic study of gastrointestinal stromal tumors with liver metastasis.

Introduction: GIST (gastrointestinal stromal tumor) is the most prominent mesenchymal neoplasms of the gastrointestinal tract, and liver is the most common metastasis site for GIST. The molecular mechanism leading to liver metastasis of GIST is currently unclear. Methods: With the goal of revealing the underlying mechanism, we performed whole-genome gene expression profiling on 18 pairs of RNA samples comprised of GIST tissues (with liver metastasis) and corresponding non-tumor tissues. After identifying differentially expressed gene, functional annotation and signal pathway analyses were conducted. GSE13861, datasets that compare GIST (without liver metastasis) with adjacent tissues, served as a comparison. Results: A total of 492 up-regulated genes and 629 down-regulated genes were identified as differentially expressed genes between liver metastasis tissues and non-tumor tissues. We characterized expression patterns of DEGs identified from our cohort and GSE13861 that show signatures of enrichment for functionality. In subsequent gene set enrichment analysis, differentially expressed genes were mainly enriched in Epithelial Mesenchymal Transition in both datasets. 493 genes were overlapped among our whole-genome gene expression profiling results and GSE13861, consisting 188 up-regulated genes and 305 down-regulated genes. By using CytoHubba plugin of Cytoscape, CDH1, CD34, KIT, PROM1, SOX9, FGF2, CD24, ALDH1A1, JAG1 and NES were identified as top ten hub genes in tumorigenesis and liver metastasis of GIST. higher expression levels of FGF2, JAG1, CD34, ALDH1A1 and the lower expression level of CDH1 were respectively associated with unfavorable overall survival. Meanwhile higher expression levels of CD34, FGF2, KIT, JAG1, ALDH1A were correlated with worse disease-free survival. Discussion: The present study may help to provide candidate pathways and targets for treatment of GIST and prevention methods to liver metastasis.

ADRB2 Regulates the Proliferation and Metastasis of Gastrointestinal Stromal Tumor Cells by Enhancing the ETV1-c-KIT Signaling.

Gastrointestinal stromal tumor (GIST) originates from a pacemaker cell, the Cajal cell. However, little is known about the cancer neuroscience in GIST. In this study, we aimed to elucidate the clinical and biological roles of adrenoceptor beta 2 (ADRB2) in GIST. Immunohistochemistry was used to evaluate the expression of ADRB2 in GIST tissues. The biological effects of ADRB2 on GIST cell proliferation, migration, invasion, and apoptosis were explored using Cell Counting Kit -8, plate colony formation assay, transwell invasion assay, and flow cytometry. We also explored the growth and metastasis of xenograft tumors in nude mice. Western blotting was used to quantify protein expression and phosphorylation. ADRB2 is generally highly expressed in GIST. High ADRB2 expression was significantly associated with risk level, tumor size, mitotic count, and metastasis. Overexpression of ADRB2 promoted GIST cell proliferation, migration, invasion, and apoptosis, while silencing ADRB2 expression showed the opposite effects. Furthermore, we found that silencing endogenous ADRB2 inhibited GIST progression and metastasis in nude mice. ADRB2-induced ETV1 upregulation enhanced the activation of c-KIT. ADRB2 plays an important role in the proliferation and metastasis of GIST and is expected to be a potential target for the treatment of GIST.

Tumor-associated macrophages mediate gastrointestinal stromal tumor cell metastasis through CXCL2/CXCR2.

Tumor-associated macrophages (TAMs) are linked with the progression and poor prognosis of multifarious solid tumors, but the regulatory mechanisms involved in gastrointestinal stromal tumors (GIST) remain indistinct. This study intended to delve into the job of TAM-derived chemokines in promoting metastasis in GIST microenvironment. Expression levels of M2-TAM markers and CXCL2 in primary and metastatic tissues of GIST were analyzed by bioinformatics methods, and we analyzed the correlation between CXCL2 and M2-TAM markers. Immunofluorescence was applied to assay CXCL2 and M2-TAM marker protein (CD68 and CD206) expression in tumor tissues. Serum CXCL2 concentration in metastatic and non-metastatic patients was assayed by ELISA. The differentiation of THP-1 cells was tested by flow cytometry. Cell function test was utilized to analyze the viability, invasion and migration of GIST cells. Western blot was used to examine the expression of epithelial-mesenchymal transition (EMT)-related proteins. The mouse liver metastasis model was established, and the effects of CXCL2 and EMT-related genes on metastasis were confirmed by hematoxylin-eosin staining and immunohistochemistry experiments. Bioinformatics analysis ascertained that M2-TAM marker proteins and chemokine CXCL2 were highly expressed in GIST metastatic tissues, and CXCL2 and TAM were co-located in tumor tissues. Results of in vitro cell function experiments displayed that CXCL2 secreted by M2-TAM promoted the invasion, migration and EMT of GIST tumor cells, and the anti-CXCL2 antibody could block the metastasis promoting effect of CXCL2. Additionally, the silencing of CXCR2 in GIST cells inhibited the metastasis promoting effect of CXCL2. Animal studies further confirmed that CXCL2 promoted liver metastasis of GIST in vivo. This study preliminarily revealed the mechanism of M2-TAM promoting tumor metastasis by secreting CXCL2 in GIST tumor microenvironment, and proffered theoretical reference for the development of immunotherapy strategies targeting M2-TAM.

Clinical characteristics and prognosis of gastrointestinal stromal tumors with rare site metastasis (Review).

Gastrointestinal stromal tumors (GIST) are the most common stromal-derived tumors of the gastrointestinal tract and have a potential metastatic capacity in almost half of all cases, with the most common sites of metastasis being the liver and peritoneum. However, there is evidence that GIST metastasizes to sites other than the liver and peritoneum, which poses challenges for clinical diagnosis and treatment. Therefore, the Cochrane and Medline databases were searched via PubMed in July 2022 using relevant keywords to acquire the literature associated with the metastasis of GIST to rare sites published since from 2000 onwards. Study data comprising age, sex, primary location, metastatic site, mean survival time, clinical signs and symptoms, imaging, pathological features immunohistochemical indices, treatment and prognosis were recorded and analyzed. The 118 metastases at rare sites reported in the literature included bone (n=31), lung (n=10), lymph nodes (n=13), intracranial sites (n=13), skin and subcutaneous tissue (n=10), heart (n=7), skeletal muscle (n=7), orbit and choroid (n=6), pancreas (n=3), spleen (n=2), bone marrow (n=1), testis (n=3), scrotum (n=1), epididymis (n=1), penis (n=1), ovary (n=2), cervix (n=1), kidney (n=1), bladder (n=1), adrenal gland (n=2) and thyroid gland (n=2). From the reviewed studies, it may be concluded that when metastases from gastrointestinal stromal tumors occur at rare sites, the initial symptoms may help in the identification of these sites. In addition, the site-dependent imaging of different metastatic locations may further define the metastases, and the findings of pathological or immunohistochemical analyses may be used to confirm the diagnosis.

18F]FAPI-42 PET/CT versus [18F]FDG PET/CT for imaging of recurrent or metastatic gastrointestinal stromal tumors.

PET has been important for monitoring recurrence and metastasis of Gastrointestinal Stromal Tumors (GISTs) and the selection of therapeutic strategies. A significant portion of GISTs lesions show negative FDG uptake and therefore calls for more tumor-specific imaging biomarkers. This study compared the imaging performance of [18F]FAPI-42 PET/CT and [18F]FDG PET/CT in recurrent or metastatic gastrointestinal stromal tumors (R/M GISTs). This study retrospectively included 35 patients with R/M GISTs who underwent both FAPI PET/CT and FDG PET/CT. The definite diagnosis was confirmed by pathology or follow-up drug treatment effects. The differences in detection rates and tumor-to-background SUVmax ratio (SUVTBR) of different locations between dual-tracer PET/CT were compared. Factors including tumor size, degree of enhancement, type of gene mutation, and targeted treatment potentially influencing the uptake of both tracers were assessed. The excised lesions (n = 3) underwent immunohistochemical staining to verify FAP expression in the tissue. A total of 106 lesions in 35 patients were identified, out of which 38/106 (35.8%) lesions (FAPI + /FDG -) were additionally detected by FAPI PET/CT as compared to that by FDG, including 26 liver metastases, ten peritoneal metastases, one gastrointestinal recurrence, and one bone metastasis. The positive detection rate of FAPI PET/CT for recurrent or metastatic GISTs was higher than that of FDG (80.2% vs. 53.8%, P< 0.001), especially in liver metastases (87.5% vs. 33.3%, P< 0.001). Moreover, the SUVTBR of liver metastases of GISTs in FAPI PET/CT was higher than that in FDG [2.4 (0.3 to 11.2) vs. 0.9 (0.3 to 6.5), P< 0.001]. The longest diameter of tumors in the FDG-positive group was higher than that of the FDG-negative group (P= 0.005); still, it did not differ between the FAPI-positive group and the FAPI-negative group. No difference in the degree of enhancement was observed between both tracers' positive and negative groups. Besides, the SUVTBR of FDG but not FAPI differed significantly among various gene mutations (P< 0.001) as well as the targeted therapy and no targeted therapy groups (P= 0.001). FAP was expressed in R/M GISTs, and the uptake of FAPI corresponded to the level of FAP expression. In conclusion, FAPI for imaging of R/M GISTs could be superior to FDG, specifically for liver metastases. The uptake of FAPI could reflect the level of FAP expression, and it was independent of tumor size, degree of enhancement, type of gene mutation, and targeted therapy as compared to FDG.

Risk Factors and Prognostic Analysis of Gastrointestinal Stromal Tumor Recurrence-Metastasis.

Objective Gastrointestinal stromal tumors (GISTs) are potential malignancies that occur in the digestive tract. This study aimed to investigate the risk factors and prognosis of recurrence and metastasis of gastrointestinal stromal tumor (GIST). Methods From January 2018 to December 2019, 422 patients with GIST who received surgery in the First Affiliated Hospital of Wenzhou Medical University were enrolled. Their clinical data were retrospectively analyzed, and their follow-ups were continued until March 31, 2022. Subsequently, univariate and multivariate Cox analyses, survival curves, and nomograms were adopted to explore the relationship between clinicopathological characteristics and recurrence or metastasis in patients with GIST. Results Univariate and multivariate Cox analysis exhibited that the prognosis of patients was affected by tumor rupture (P = 0.040), tumor location (P < 0.001), tumor diameter (P = 0.016), mitotic figures (P < 0.001), and risk grade (P < 0.009). The above variables were selected to create the nomogram for 3-year disease-free survival (DFS). The 3-year the ROC (receiver operating characteristic) curves of the nomogram were (0.878 95% confidence interval [CI]: 0.871–0.939). Conclusion Collectively, risk factors affecting postoperative recurrence or metastasis of GIST consist of primary site of tumors, tumor rupture, tumor diameter >10 cm, high-risk tumor classification, and mitotic figures ≥10 per 50 HPFs. And the application of nomogram may help physicians provide individualized diagnosis and treatment for patients with GISTs following surgical resection.

High-frame-rate contrast-enhanced ultrasound findings of liver metastasis of duodenal gastrointestinal stromal tumor: A case report and literature review

BACKGROUNDLiver metastasis of duodenal gastrointestinal stromal tumor (GIST) is rare. Most reports mainly focus on its treatment and approaches to surgical resection, while details on its contrast-enhanced ultrasound (CEUS) findings are lacking. The diagnosis and imaging modalities for this condition remain challenging.CASE SUMMARYA 53-year-old Chinese man presented with mild signs and symptoms of the digestive tract. He underwent routine examinations after GIST surgery. Magnetic resonance imaging showed a 2.3 cm hepatic space-occupying lesion. All the laboratory test results were within normal limits. For further diagnostic confirmation, we conducted high frame rate CEUS (H-CEUS) and found a malignant perfusion pattern. Heterogeneous concentric hyper-enhancement, earlier wash-in than the liver parenchyma, and two irregular vessel columns could be observed at the periphery of the lesion during the arterial phase. Ultrasound-guided puncture biopsy was used to confirm the diagnosis of the lesion as liver metastasis of duodenal GIST. Imatinib was prescribed after biopsy, and the patient’s clinical course was monitored.CONCLUSIONH-CEUS is useful for detecting microcirculation differences, wash-in patterns, and vascular morphogenesis and diagnosing liver metastasis of duodenal GIST.

Outcome and surveillance pattern in older GIST population.

e24016 Background: Recent studies of patients (pts) with gastrointestinal stromal tumor (GIST) have included an older patient population. The majority of these have focused on treatment, but little is known regarding the optimal duration of surveillance following surgery for localized disease. Methods: We conducted a retrospective study of pts age 70 years (yrs) and above (≥) at diagnosis (dx), who underwent surgery for their localized GIST. Charts were reviewed of GIST diagnosed between 1992 to 2016, to allow at least 5 yrs for surveillance, if performed. Demographics were analyzed and pts were risk stratified using modified NIH criteria. Results: We identified 42 pts with a median age of 74 yrs (70 to 89 yrs) at dx. The majority of pts were male (31, 74%) and non-Hispanic White (37, 88%). Most pts had gastric GIST (25, 60%). The median resected tumor was 47 mm (range 6 to 190). Thirty-nine of 42 pts had margin status documented R0 resection. The median overall survival for all pts was 7.9 yrs (1.1 to 17.7), with median recurrence free survival 5.6 yrs (1.1 to 13.7). Only 4 of 16 (25%) pts died from GIST recurrence, and all were detected under 5 yrs from surgery. Fourteen of 34 pts (41%) who survived over 5 yrs from resection had extended surveillance imaging. Demographics and risk stratification are shown in Table. None of the 16 low risk pts developed recurrence, including 6 (38%) whose surveillance imaging continued beyond 5 yrs. Among 7 intermediate risk pts, only 1 pt (14%) extended surveillance imaging beyond 5 yrs. Two intermediate risk pts (29%) developed recurrence and were symptomatic at dx. One intermediate risk pt died from GIST metastasis within 1 yr from surgery. Seven of 19 (37%) high risk pts had surveillance imaging beyond 5 yrs following surgical resection. Seven high risk pts (37%) developed recurrence within median 5.6 yrs (1.6 to 13.7) from surgery; five of these were detected on imaging. In the high risk pts with recurrence, 5 had received adjuvant imatinib and 2 declined any systemic therapy. Three pts (16%) in the high risk cohort died from GIST. Conclusions: In this cohort of pts age ≥ 70 yrs with resected GIST, the majority of pts were symptomatic at relapse. Older pts who undergo surgery for low risk GIST may not require extended surveillance. Fit, older pts with high risk GIST may benefit from extended surveillance imaging, even if they received adjuvant imatinib.[Table: see text]

Long-term progression-free survival achieved in the skull base metastasis of gastrointestinal stromal tumor with introduction of tyrosine kinase inhibitor: illustrative case.

BACKGROUNDGastrointestinal stromal tumors (GISTs) are common subepithelial tumors that rarely metastasize to the intracranial space. Because the standard treatment for metastatic intracranial GISTs has not been established, multimodal therapies are needed, especially in the case of skull base metastasis. However, its outcome has not always been favorable. The authors report the longest known surviving case of skull base metastasis of GIST treated with imatinib only.OBSERVATIONSA 52-year-old male with a history of GIST presented with left facial swelling and numbness. Examinations revealed a 70-mm tumor occupying the left middle cranial fossa and the orbit. The authors performed transnasal endoscopic tumor biopsy for definitive diagnosis and reintroduced imatinib treatment. The tumor significantly decreased in size early after the introduction of imatinib, and symptoms completely disappeared within several weeks. The lesion has remained shrunk radiologically for 63 months, and the patient is continuously being followed up under imatinib treatment.LESSONSThe authors reported a rare case of skull base metastasis of GIST successfully treated solely with systemic therapy with a tyrosine kinase inhibitor, achieving tumor control for over 5 years. This case suggests that tyrosine kinase inhibitors might play a key role in the multidisciplinary treatment for skull base metastases of GIST.

A Giant Posterior Mediastinal Metastatic Mass of GIST Gastric Origin

Gastrointestinal stromal tumors (GISTs) are uncommon visceral sarcomas that predominantly arise from the gastrointestinal tract, particularly from interstitial cells of Cajal. Although the liver is a common site for metastasis, rarely GISTs show extraintestinal manifestation in the bone and lungs. We report a case patient with an uncommon location and unusually large GIST metastasis as a mediastinal mass 3 years after undergoing total gastrectomy and chemotherapy with imatinib, a tyrosine kinase inhibitor.

The Diagnosis of Small Gastrointestinal Subepithelial Lesions by Endoscopic Ultrasound-Guided Fine Needle Aspiration and Biopsy.

Endoscopic ultrasonography (EUS) has been widely accepted in the diagnosis of all types of tumors, especially pancreatic tumors, lymph nodes, and subepithelial lesions (SELs). One reason is that the examination can provide a detailed observation, with tissue samples being immediately obtained by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). Many SELs are detected incidentally during endoscopic examinations without symptoms. Most SELs are mesenchymal tumors originating from the fourth layer, such as gastrointestinal stromal tumors (GISTs), leiomyomas, and schwannomas. GISTs are potentially malignant. Surgical treatment is recommended for localized GISTs of ≥20 mm. However, the indications for the diagnosis and follow-up of GISTs of <20 mm in size are controversial. There are several reports on the rapid progression or metastasis of small GISTs. Therefore, it is important to determine whether a SEL is a GIST or not. The main diagnostic method is EUS-FNA. Recently, endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) using a new biopsy needle has been reported to obtain larger tissue samples. Additionally, various biopsy methods have been reported to have a high diagnostic rate for small GISTs. In local gastric SELs, regardless of the tumor size, EUS can be performed first; then, EUS-FNA/B or various biopsy methods can be used to obtain tissue samples for decision-making in relation to therapy and the follow-up period.

Performance of the Combined Model Based on Both Clinicopathological and CT Texture Features in Predicting Liver Metastasis of High-risk Gastrointestinal Stromal Tumors

Objective To investigate the performance of the combined model based on both clinicopathological features and CT texture features in predicting liver metastasis of high-risk gastrointestinal stromal tumors(GISTs). Methods The high-risk GISTs confirmed by pathology from January 2015 to December 2020 were analyzed retrospectively,including 153 cases from the Cancer Hospital of the University of Chinese Academy of Sciences and 51 cases from the Shaoxing Central Hospital.The cases were randomly assigned into a training set(n=142)and a test set(n=62)at a ratio of 7∶3.According to the results of operation or puncture,they were classified into a liver metastasis group(76 cases)and a non-metastasis group(128 cases).ITK-SNAP was employed to delineate the volume of interest of the stromal tumors.Least absolute shrinkage and selection operator(LASSO)was employed to screen out the effective features.Multivariate logistic regression was adopted to construct the models based on clinicopathological features,texture features extracted from CT scans,and the both(combined model),respectively.Receiver operating characteristic(ROC)curve and calibration curve were established to evaluate the predictive performance of the models.The area under the curve(AUC)was compared by Delong test. Results Body mass index(BMI),tumor size,Ki-67,tumor occurrence site,abdominal mass,gastrointestinal bleeding,and CA125 level showed statistical differences between groups(all P<0.05).A total of 107 texture features were extracted from CT images,from which 13 and 7 texture features were selected by LASSO from CT plain scans and CT enhanced scans,respectively.The AUC of the prediction with the training set and the test set respectively was 0.870 and 0.855 for the model based on clinicopathological features,0.918 and 0.836 for the model based on texture features extracted from CT plain scans,0.920 and 0.846 for the model based on texture features extracted from CT enhanced scans,and 0.930 and 0.889 for the combined model based on both clinicopathological features and texture features extracted from CT plain scans.Delong test demonstrated no significant difference in AUC between the models based on the texture features extracted from CT plain scans and CT enhanced scans(P=0.762),whereas the AUC of the combined model was significantly different from that of the clinicopathological feature-based model and texture feature-based model(P=0.001 and P=0.023,respectively). Conclusion Texture features extracted from CT plain scans can predict the liver metastasis of high-risk GISTs,and the model established with clinicopathological features combined with CT texture features has best prediction performance.

Metastatic gastrointestinal stromal tumor of the greater omentum. Case report

Gastrointestinal stromal tumors (GIST) are the most common type of mesenchymal malignancies of the gastrointestinal (GI) tract. Almost 10% of them are originated outside of the GI tract (extra-GIST), while GIST of the greater omentum constitutes about 1% among stromal tumors. More than 80% of GIST have mutations in c-KIT and PDGFRA genes. Herein we demonstrate the case of successful treatment of patient with giant omental GIST with c-KIT exon 11 mutation. 64-years-old woman, was admitted to the Department of abdominal oncology with complaints of shortness of breath and abdominal enlargement in volume. CT-scan revealed a large tumor in the abdominal cavity with tumor size of 543422 cm. The patient underwent left thoraco-abdominal approach. It was found that the tumor was originated from the greater omentum with several metastases located on the peritoneum of the left lateral channel. Resection of the large omentum, splenectomy, liver resection and was done. Postoperative immunohistochemical study showed the expression of CD117, CD34 in tumor cells. Ki-67 index was 1215%. Genetic study revealed c-KIT exon 11 mutation. Treatment with imatinib 400 mg per day was started. Patient has been treated with imatinib for 12 years. On control examination we have found a metastasis in the anterior abdominal wall 3,532,5 cm in diameter. Afterwards we performed resection of anterior abdominal wall with metastasis on 9 November 2017. Immunohistochemical study confirmed metastasis of GIST. The index of tumor proliferation activity (Ki-67) was 45%. Patient prolonged imatinib treatment at the dose of 400 mg per day after operation. No signs of progression have been revealed on control examination 72 months after the operation. 12-year progression-free survival during imatinib treatment is unique in our practice. Moreover, in the case of further progression, we have second and third-line targeted therapy (sunitinib and regorafenib) and surgery treatment in local progression.

Combined model based on enhanced CT texture features in liver metastasis prediction of high-risk gastrointestinal stromal tumors.

To investigate the use of the combined model based on clinical and enhanced CT texture features for predicting the liver metastasis of high-risk gastrointestinal stromal tumors (GISTs). This retrospective study was conducted including 204 patients with pathologically confirmed high-risk GISTs from the Zhejiang Cancer Hospital from January 2015 to June 2021, and 76 cases of them were diagnosed with simultaneous liver metastasis. We randomly divided the cohort into a training cohort (n = 142) and a validation cohort (n = 62) with a ratio of 7:3. All volumes of interest (VOIs) of the high-risk GISTs were manually segmented on the portal venous phase CT images using the ITK-SNAP software. The least absolute shrinkage and selection operator (Lasso) algorithm was performed to determine the most valuable features from a total of 110 texture features extracted by the A-K software to reflect the texture information of the given VOIs. Texture-based predictive model was built from the selected texture features. Independent clinical risk factors were identified through univariate logistic analysis. Then, the texture-based model incorporated the clinical predictors to develop a combined model by multivariate logistic regression. Receiver operating characteristic curve, calibration curve, and decision curve analysis were utilized to analyze the discrimination capacity and clinical application value of the predictive models. The nine optimal texture features were remained after the reduction of dimension using Lasso method. Another four clinical parameters (BMI, location, gastrointestinal bleeding, and CA125 level) were included in the clinical-based predictive model. Finally, with the combination of remaining texture and clinical features, a multivariate logistic regression classifier was built to predict the liver metastasis potential of high-risk GISTs. The remarkable classification performance of the combined model for the prediction of liver metastasis in the subjects with high-risk GISTs was obtained with area under curve (AUC) = 0.919, sensitivity = 83.9%, specificity = 89.7%, and accuracy = 84.9% in our validation group. The texture-based radiomic signature derived from the portal venous phase CT images could predict liver metastasis of high-risk GISTs in a non-invasive way. Integrating additional clinical variables into the model further leads to an improvement of liver metastasis risk prediction.

Significance of circulating tumor cell monitoring in targeted therapy for gastrointestinal stromal tumors

Objective: To explore the significance of circulating tumor cell (CTC) monitoring in evaluating the efficacy of targeted therapy for gastrointestinal stromal tumor (GIST). Methods: A prospective cohort study was performed. The data of patients with locally advanced GIST or liver metastasis who were admitted to The Affiliated Hospital of Nantong University from August 2013 to December 2018 were collected. Inclusion criteria: (1) patients aged older than 18 years; (2) patients who were diagnosed with GIST based on pathology; (3) patients without surgery, whose preoperative imaging evaluation of GIST found the violations of the surrounding organs or partial transfer of an estimated difficulty to achieve R0 resection, or the maximum diameter of the tumor > 10 cm, or the liver metastasis, or the expectation of higher risk of surgical complications; (4) patients who were treated with the imatinib 400 mg/d for the first time; (5) Eastern Cooperative Oncology Group (ECOG) score of 0-2. Exclusion criteria: (1) genetic testing revealed a D842V mutation in exon 18 of the PDGFRA gene; (2) alanine aminotransferase and/or aspartate aminotransferase > 2.5 times the normal upper limit; (3) serum total bilirubin >1.5 times of normal upper limit; (4) neutrophil count < 1.5×10(9)/L, or platelet count < 75×10(9)/L, or hemoglobin < 60 g/L; (5) creatinine > normal upper limit; (6) patients had serious cardiovascular and cerebrovascular diseases within 12 months before enrollment; (7) female patients were pregnant or lactating; (8) patients suffered from other serious acute and chronic physical or mental problems, and were not suitable for participating in this study judged by researchers. The patients who could not tolerate treatment regimen, or developed serious adverse reactions and did not follow the medication scheme after enrollment were excluded. Before imatinib treatment and 1-month and 2-month after treatment, quantitative PCR was used to detect the DOG-1 expression of monocytes in peripheral blood, and the ratio of DOG-1/β-actin > 3×10(-5) was used as the CTC positive threshold of GIST. The positive rate of CTC, the efficacy of imatinib treatment (complete response, partial response, stable disease, progressive disease, and occurrence of adverse reactions), and the relationship between CTC positive rate and clinicopathological characteristics of patients were analyzed. Furthermore, the ratio of DOG-1 decrease/baseline DOG-1 after 1-month of treatment was used as an indicator to evaluate whether targeted therapy was effective. The receiver operating characteristic (ROC) curve was rendered, and the area under the curve (AUC) was calculated. Results: A total of 68 GIST patients were enrolled in this study, including 39 cases of locally advanced GIST and 29 cases with liver metastases, 32 males and 36 females with the mean age of (51.2±11.8) (range 31 to 74) years. After 2-month of imatinib treatment, 43 cases were evaluated as partial response, 11 cases as stable disease, and 14 cases as progressive disease, with an effective rate of 79.4% (54/68). During the treatment of imatinib, the incidence of grade 3 or higher adverse reactions was 22.1% (15/68), including 12 cases of grade 3 neutropenia and 3 of grade 4 drug eruption, which were all relieved after conservative treatment. The positive rates of CTC in 68 patients before treatment, 1-month and 2-month after treatment were 66.2% (45/68), 41.2% (28/68) and 23.5% (16/68), respectively. The positive rate of CTC was associated with tumor size, liver metastasis, mitotic count and risk level (all P<0.05). By analyzing the effective group and the ineffective group of targeted therapy, it was found that the positive rate of CTC in the effective group showed a decreasing trend, while the positive rate of CTC in the ineffective group showed an increasing trend. The AUC of predicting the efficacy of targeted therapy for GIST was 0.823 by detecting the change trend of CTC 1-month after treatment (P<0.001). When the DOG-1 content decreased by more than 57.5% 1-month after treatment, it can be used as an indicator to judge the effectiveness of the treatment, whose sensitivity was 72.2% and specificity was 100%. Conclusion: The detection of peripheral blood CTC can evaluate the efficacy of targeted therapy in GIST patients and can provide decision-making basis for further clinical treatment.