Recurrent Gastrointestinal Stromal Tumors Research Articles

The Regulation of SPRY4 Intronic Transcript 1 (SPRY4-IT1) on KIT Signaling and Imatinib Resistance of Gastrointestinal Stromal Tumor (GIST) Cells

BACKGROUND: SPRY4 intronic transcript 1 (SPRY4-IT1), is a long non-coding RNA coded by the intron of SPRY4. SPRY4 is highly expressed in gastrointestinal stromal tumor (GIST) and inhibits the tumorigenesis of GIST, but whether SPRY4-IT1 regulates the tumorigenesis of GIST or not remains unclear. Therefore, in this study, the regulation of SPRY4-IT1 expression and its role in GIST will be investigated.METHODS: GIST-T1 cells, and Ba/F3 cells which express KIT proto-oncogene (KIT) and SPRY4-IT1 were used as cell models. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to examine mRNA expression, while the protein expression and signal transduction were examined by western blot. The association between SPRY4-IT1 and KIT was examined by pull down of KIT and PCR. Cell proliferation, survival, and cell cycle progression were examined by cell counting kit-8 (CCK8) and flow cytometry.RESULTS: KIT mutants increased the expression of SPRY4-IT1 in GIST. SPRY4-IT1 bound to KIT, also enhanced the activation and expression of both wild-type KIT and primary KIT mutants, therefore increasing the activation of downstream signaling proteins AKT and ERK of KIT, GIST cell survival, and proliferation. In addition, SPRY4-IT1 reduced the sensitivity of wild-type KIT, or primary KIT mutants to the first-line targeted therapeutic drug of GIST, imatinib, which can inhibit KIT activation. Gaining drug-resistant secondary KIT mutants might be one of the main reasons of GIST recurrence after targeted therapy. Similar to wild-type KIT and primary KIT mutants, the activation and expression of secondary KIT mutants and their resistance to imatinib were also increased by SPRY4-IT1.CONCLUSION: The results indicated positive feedback between SPRY4-IT1 and wild-type KIT, primary KIT mutants or secondary KIT mutants, and the upregulation of AKT and ERK activation by SPRY4-IT1 in GIST cells, providing a new insight in the KIT signaling regulation in GIST, and the resistance of GIST to targeted therapy.KEYWORDS: SPRY4-IT1, KIT, GIST, SPRY4, signaling

Predictive performance of [18F]F-fibroblast activation protein inhibitor (FAPI)-42 positron emission tomography/computed tomography (PET/CT) in evaluating response of recurrent or metastatic gastrointestinal stromal tumors: complementary or alternative to [18F]fluorodeoxyglucose (FDG) PET/CT?

Accurately and promptly predicting the response of gastrointestinal stromal tumors (GISTs) to targeted therapy is essential for optimizing treatment strategies. However, some fractions of recurrent or metastatic GISTs present as non-FDG-avid lesions, limiting the value of [18F]fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) in treatment evaluation. This study evaluated the efficacy of [18F]F-fibroblast activation protein inhibitor (FAPI)-42 [18F]FAPI-42) PET/CT for assessing the treatment response in recurrent or metastatic GISTs, in comparison to [18F]FDG PET/CT and explores a model integrating PET/CT imaging and clinical parameters to optimize the clinical use of these diagnostic tools. Our retrospective analysis included 27 patients with recurrent or metastatic GISTs who underwent [18F]FAPI-42 PET/CT and [18F]FDG PET/CT at baseline before switching targeted therapy. Treatment response status was divided into a progression group (PG) and a non-progression group (NPG) based on the Response Criteria in Solid Tumors (RECIST) 1.1, according to the contrast-enhanced computed tomography (CT) scan at six months. [18F]FAPI-42 and [18F]FDG PET/CT parameters including the mean standardized uptake value (SUVmean), the standard uptake value corrected for lean body mass (SULpeak), the maximum standardized uptake value (SUVmax), tumor-to-blood pool SUV ratio (TBR), tumor-to-liver SUV ratio (TLR), metabolic tumor volume (MTV)/FAPI-positive tumor volume (GTV-FAPI), total lesion glycolysis (TLG)/FAPI-positive total lesion accumulation (TLF) were correlated with the response status to identify indicative of treatment response. The predictive performance of them was quantified by generating receiver operating characteristic curves (ROC), calibration curves, and cross-validation. A total of 110 lesions were identified in 27 patients. Compared with PG, NPG was associated with lower levels of TBR and SUVmean in FDG PET/CT (TBR-FDG, SUVmean-FDG; P=0.033 and P=0.038, respectively), with higher SULpeak and TLF in FAPI PET/CT (SULpeak-FAPI, TLF-FAPI; P=0.10 and P=0.049, respectively). The predictive power of a composite-parameter model, including TBR-FDG, SULpeak-FAPI, gene mutation, and type of targeted therapy [area under the curve (AUC) =0.865], was superior to the few-parameter models incorporating TBR-FDG (AUC =0.637, P<0.001), SULpeak-FAPI (AUC =0.665, P<0.001) or both (AUC =0.721, P<0.001). Both [18F]FAPI-42 PET/CT and [18F]FDG PET/CT have value in predicting the treatment response of recurrent or metastatic GISTs. And [18F]FAPI-42 PET/CT offers synergistic value when used in combination with [18F]FDG PET/CT. Notably, the nomogram generated from the model incorporating [18F]FAPI-42 PET/CT, [18F]FDG PET/CT parameters, gene mutation, and type of targeted therapy could yield more precise predictions of the response of recurrent metastatic GISTs.

Survival of advanced/recurrent gastrointestinal stromal tumors treated with tyrosine kinase inhibitors in Taiwan: a nationwide registry study

BackgroundMost gastrointestinal stromal tumors (GISTs) harbor c-KIT or PDGFRA mutations. Administration of tyrosine kinase inhibitors (TKIs) has significantly improved the survival of patients with GISTs. We aimed to evaluate the clinical outcome of advanced or recurrent GIST patients in Taiwan.MethodsPatients diagnosed between 2010 and 2020 were enrolled. The collected data included baseline characteristics, treatment pattern, treatment outcome, genetic aberrations and survival status. Progression-free survival (PFS) and overall survival (OS) were analyzed and plotted with the Kaplan–Meier method. Cox regression analysis was used to analyze the prognostic factors of survival.ResultsA total of 224 patients with advanced or recurrent GISTs treated with TKIs were enrolled. All patients received imatinib treatment. Ninety-three and 42 patients received sunitinib and regorafenib treatment, respectively. The 48-month PFS and OS rates for patients treated with imatinib were 50.5% and 79.5%, respectively. c-KIT exon 9 and PDGFRA mutations were prognostic factors for a poor PFS and PDGFRA mutation was a prognostic factor for a poor OS in patients treated with imatinib in multivariate Cox regression analysis. The median PFS of patients who received sunitinib treatment was 12.76 months (95% confidence interval (CI), 11.01–14.52). Patients with c-KIT exon 9 mutations had a longer PFS than those with other genetic aberrations. The median PFS of patients treated with regorafenib was 7.14 months (95% CI, 3.39–10.89).ConclusionsWe present real-world clinical outcomes for advanced GIST patients treated with TKIs and identify mutational status as an independent prognostic factor for patient survival.

Survival outcomes and prognostic factors of advanced gastrointestinal stromal tumors: in the era of multiple tyrosine kinase inhibitors.

Tyrosine kinase inhibitors (TKIs) have shown great efficacy in the treatment of advanced gastrointestinal stromal tumors (GISTs), significantly prolonging the survival of patients. In the era of imatinib, a few studies reported some prognostic factors for patients with advanced GISTs, such as age, sex, performance status, diameter of the largest lesions, KIT exon mutations, and some hematological examination results. However, with the advent of more TKIs, the prognostic factors for patients with advanced GISTs have not been fully understood in the era of multiple TKIs. In this study, we aimed to identify independent prognostic factors associated with the survival of patients diagnosed with advanced GISTs. Data on clinicopathologic characteristics, treatment approaches, and survival were retrospectively collected for patients with primary unresectable or recurrent GISTs treated from January 2010 to July 2023 at the First Affiliated Hospital of Chongqing Medical University, China. Univariable and multivariable Cox proportional hazards regression models were used to identify independent prognostic factors of survival. A total of 194 patients were included in the analysis. The median follow-up duration was 59.9 months (range, 2.7-141.7 months). The median overall survival (mOS) in this cohort was 76.5 months (95% confidence interval, 63.4 to 89.6 months). All patients received TKI therapy during the follow-up period, and 56.2% received two or more types of TKIs. In multivariable Cox analysis, younger age, a single lesion at enrollment, no previous use of TKIs, smaller tumor burden, good Eastern Cooperative Oncology Group performance status (ECOG PS ≤1), and lesions limited to the liver were independent prognostic factors for better survival. We found that a single lesion at enrollment, no previous use of TKIs, a smaller tumor burden, and lesions limited to the liver were associated with better survival. Drug resistance is a severe challenge for advanced GISTs, and several factors mentioned above may be correlated with the development of drug resistance, leading to the poor survival of patients.

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

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. 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. 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±0.367months. KIT exon 9 mutation was significantly associated with poorer 5-year DFS. 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 8months. Furthermore, the potential utility of mutational analysis in guiding treatment with neoadjuvant imatinib was demonstrated.

Identification and validation of protein biomarkers for predicting gastrointestinal stromal tumor recurrence

We conducted a proteomic analysis using mass spectrometry to identify and validate protein biomarkers for accurately predicting recurrence risk in gastrointestinal stromal tumors (GIST) patients, focusing on differentially expressed proteins in metastatic versus primary GIST tissues. We selected five biomarkers—GPX4, RBM4, TPM3, PFKFB2, and PGAM5—and validated their expressions in primary tumors of recurrent and non-recurrent GIST patients via immunohistochemistry. Our analysis of the association between these biomarkers with recurrence-free survival (RFS) and overall survival (OS), along with their interrelationships, revealed that immunohistochemistry confirmed significantly higher expressions of these biomarkers in primary GIST tissues of recurrent patients. Kaplan-Meier survival analysis showed that high expressions of GPX4, RBM4, TPM3, PFKFB2, and PGAM5 correlated with lower RFS, and GPX4 and RBM4 with lower OS. All biomarker pairs showed positive associations, with high expressions correlating with increased recurrence rates, and GPX4 and RBM4 with higher mortality rates. In conclusion, the biomarkers GPX4, RBM4, TPM3, PFKFB2, and PGAM5 are clinically relevant for predicting GIST recurrence, with their high expressions in primary tumors linked to poorer RFS and OS. They serve as potential prognostic indicators, enabling early treatment and improved outcomes. The observed interrelationships among these biomarkers further validate their accuracy in predicting GIST recurrence.

Cytoreductive surgery in patients with recurrent or metastatic gastrointestinal stromal tumors sensitive to imatinib: a retrospective analysis of two Russian cancer centers.

The role of cytoreductive surgery for patients with recurrent or metastatic gastrointestinal stromal tumors (mGISTs) responding to imatinib (IM) has not yet been established. We carried out a retrospective analysis of the outcomes of patients with mGISTs in two Russian cancer centers. We compared two cohorts: treated (Group S) or not treated with surgery (Group NS) after a partial response (PR) or stable disease (SD) while on IM. A total 44 patients treated by IM as first line treatment were included in our analysis. Prognostically similar patients only sensitive to IM cases with hepatic or peritoneal metastases as well as durable response to IM lasting more than 12 months were included in a control arm. Patients in Group NS received only IM until disease progression. Patients in Group S were treated additionally with metastasectomy after having response or SD on IM. The baseline characteristics were similar between the groups with several trends: a higher proportion of patients achieved a PR in Group S (87% vs. 55%, P=0.165), and greater number of patients had peritoneal metastases in Group NS (45% vs. 27%, P=0.759). The median time to surgery from the initiation of IM was 8 months. Progression-free survival (PFS) and overall survival (OS) were significantly longer in Group S than Group NS: the median PFS was 78 vs. 35 months (P=0.088); the median OS was 141 vs. 80 months (P=0.154). The surgical resection of residual lesions after disease control with IM is likely to be beneficial to patients with mGISTs.

Prediction of High-Risk Gastrointestinal Stromal Tumor Recurrence Based on Delta-CT Radiomics Modeling: A 3-Year Follow-up Study After Surgery.

Medium- to high-risk classification-gastrointestinal stromal tumors (MH-GIST) have a high recurrence rate and are difficult to treat. This study aims to predict the recurrence of MH-GIST within 3 years after surgery based on clinical data and preoperative Delta-CT Radiomics modeling. A retrospective analysis was conducted on clinical imaging data of 242 cases confirmed to have MH-GIST after surgery, including 92 cases of recurrence and 150 cases of normal. The training set and test set were established using a 7:3 ratio and time cutoff point. In the training set, multiple prediction models were established based on clinical data of MH-GIST and the changes in radiomics texture of enhanced computed tomography (CT) at different time periods (Delta-CT radiomics). The area under curve (AUC) values of each model were compared using the Delong test, and the clinical net benefit of the model was tested using decision curve analysis (DCA). Then, the model was externally validated in the test set, and a novel nomogram predicting the recurrence of MH-GIST was finally created. Univariate analysis confirmed that tumor volume, tumor location, neutrophil-lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), diabetes, spicy hot pot, CT enhancement mode, and Radscore 1/2 were predictive factors for MH-GIST recurrence (P < .05). The combined model based on these above factors had significantly higher predictive performance (AUC = 0.895, 95% confidence interval [CI] = [0.839-0.937]) than the clinical data model (AUC = 0.735, 95% CI = [0.6 62-0.800]) and radiomics model (AUC = 0.842, 95% CI = [0.779-0.894]). Decision curve analysis also confirmed the higher clinical net benefit of the combined model, and the same results were validated in the test set. The novel nomogram developed based on the combined model helps predict the recurrence of MH-GIST. The nomogram of clinical and Delta-CT radiomics has important clinical value in predicting the recurrence of MH-GIST, providing reliable data reference for its diagnosis, treatment, and clinical decision-making.

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

IntroductionContour 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 methodsA 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.ResultsOverall, 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).ConclusionContour 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.

Predicting the risk stratification of gastrointestinal stromal tumors using machine learning-based ultrasound radiomics.

This study aimed to use conventional ultrasound features, ultrasound radiomics, and machine learning algorithms to establish a predictive model to assess the risk of post-surgical recurrence of gastrointestinal stromal tumors (GISTs). This retrospective analysis included 230 patients with pathologically diagnosed GISTs. Radiomic features were extracted from manually annotated images. Radiomic features plus conventional ultrasound features were selected using the SelectKbest analysis of variance and stratified tenfold cross-validation recursive elimination methods. Finally, five different machine learning algorithms (logistic regression [LR], support vector machine [SVM], random forest [RF], extreme gradient boosting [XGBoost], and multilayer perceptron [MLP]) were established to predict risk stratification of GISTs. The predictive performance of the established model was mainly evaluated based on the area under the receiver operating characteristic (ROC) curve (AUC) and accuracy, whereas the predictive performance of the optimal machine learning algorithm and a radiologist's subjective assessment were compared using McNemar's test. Seven radiomics features and one conventional ultrasound feature were selected to construct the machine learning models for GIST risk classification. The mentioned five machine learning models were able to predict the malignant potential of GISTs. LR and SVM outperformed other classifiers on the test set, with LR achieving an accuracy of 0.852 (AUC, 0.881; sensitivity, 0.871; specificity, 0.826) and SVM achieving an accuracy of 0.852 (AUC, 0.879; sensitivity, 0.839; specificity, 0.870), and proved significantly better than the radiologist (accuracy, 0.691; sensitivity, 0.645; specificity, 0.813). Machine learning-based ultrasound radiomics features are able to noninvasively predict the biological risk of GISTs.

DDR1/2 enhance KIT activation and imatinib resistance of primary and secondary KIT mutants in gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GISTs) are predominantly initiated by KIT mutations. In this study, we observed that discoidin domain receptors 1 and 2 (DDR1 and DDR2) exhibited high expression in GISTs, were associated with KIT, and enhanced the activation of both wild-type KIT and primary KIT mutants. Inhibition of DDR1/2 led to a reduction in the activation of KIT and its downstream signaling molecules, ultimately impairing GIST cell survival and proliferation in vitro. Consequently, treatment of mice carrying germline KIT/V558A mutation with DDR1/2 inhibitor significantly impeded tumor growth, and the combined use of DDR1/2 inhibitor and imatinib, the first-line targeted therapeutic agent for GISTs, markedly enhanced tumor growth suppression. In addition, DDR1/2 inhibition resulted in decreased KIT expression, while KIT inhibition led to upregulation of DDR1/2 expression in GISTs. The presence of DDR1/2 also decreased the sensitivity of wild-type KIT or primary KIT mutants to imatinib, indicating a possible role for DDR1/2 in promoting GIST survival during KIT-targeted therapy. The development of drug-resistant secondary KIT mutations is a primary factor contributing to GIST recurrence following targeted therapy. Similar to primary KIT mutants, DDR1/2 can associate with and enhance the activation of secondary KIT mutants, further diminishing their sensitivity to imatinib. In summary, our data demonstrate that DDR1/2 contribute to KIT activation in GISTs and strengthen resistance to imatinib for both primary and secondary KIT mutants, providing a rationale for further exploration of DDR1/2 targeting in GIST treatment.

An interpretable AI model for recurrence prediction after surgery in gastrointestinal stromal tumour: an observational cohort study

There are several models that predict the risk of recurrence following resection of localised, primary gastrointestinal stromal tumour (GIST). However, assessment of calibration is not always feasible and when performed, calibration of current GIST models appears to be suboptimal. We aimed to develop a prognostic model to predict the recurrence of GIST after surgery with both good discrimination and calibration by uncovering and harnessing the non-linear relationships among variables that predict recurrence. In this observational cohort study, the data of 395 adult patients who underwent complete resection (R0 or R1) of a localised, primary GIST in the pre-imatinib era at Memorial Sloan Kettering Cancer Center (NY, USA) (recruited 1982-2001) and a European consortium (Spanish Group for Research in Sarcomas, 80 sites) (recruited 1987-2011) were used to train an interpretable Artificial Intelligence (AI)-based model called Optimal Classification Trees (OCT). The OCT predicted the probability of recurrence after surgery by capturing non-linear relationships among predictors of recurrence. The data of an additional 596 patients from another European consortium (Polish Clinical GIST Registry, 7 sites) (recruited 1981-2013) who were also treated in the pre-imatinib era were used to externally validate the OCT predictions with regard to discrimination (Harrell's C-index and Brier score) and calibration (calibration curve, Brier score, and Hosmer-Lemeshow test). The calibration of the Memorial Sloan Kettering (MSK) GIST nomogram was used as a comparative gold standard. We also evaluated the clinical utility of the OCT and the MSK nomogram by performing a Decision Curve Analysis (DCA). The internal cohort included 395 patients (median [IQR] age, 63 [54-71] years; 214 men [54.2%]) and the external cohort included 556 patients (median [IQR] age, 60 [52-68] years; 308 men [55.4%]). The Harrell's C-index of the OCT in the external validation cohort was greater than that of the MSK nomogram (0.805 (95% CI: 0.803-0.808) vs 0.788 (95% CI: 0.786-0.791), respectively). In the external validation cohort, the slope and intercept of the calibration curve of the main OCT were 1.041 and 0.038, respectively. In comparison, the slope and intercept of the calibration curve for the MSK nomogram was 0.681 and 0.032, respectively. The MSK nomogram overestimated the recurrence risk throughout the entire calibration curve. Of note, the Brier score was lower for the OCT compared to the MSK nomogram (0.147 vs 0.564, respectively), and the Hosmer-Lemeshow test was insignificant (P=0.087) for the OCT model but significant (P<0.001) for the MSK nomogram. Both results confirmed the superior discrimination and calibration of the OCT over the MSK nomogram. A decision curve analysis showed that the AI-based OCT model allowed for superior decision making compared to the MSK nomogram for both patients with 25-50% recurrence risk as well as those with >50% risk of recurrence. We present the first prognostic models of recurrence risk in GIST that demonstrate excellent discrimination, calibration, and clinical utility on external validation. Additional studies for further validation are warranted. With further validation, these tools could potentially improve patient counseling and selection for adjuvant therapy. The NCI SPORE in Soft Tissue Sarcoma and NCI Cancer Center Support Grants.

Correction: Endoscopic removal of an extraluminal gastrointestinal stromal tumor recurrence located on the surgical stapler line at gastroesophageal junction.

Correction: Endoscopic removal of an extraluminal gastrointestinal stromal tumor recurrence located on the surgical stapler line at gastroesophageal junction.

Surgical Management of Gastrointestinal Stromal Tumors.

Gastrointestinal stromal tumors (GISTs) are considered rare, but they are one of the most common malignant mesenchymal tumors within the gastrointestinal tract, affecting 4,000 to 6,000 adults in the United States each year. Because gastrointestinal bleeding is often the initial symptom, a thorough and timely diagnostic workup is imperative to accurately diagnose a potentially deadly tumor. Endoscopic ultrasound is helpful when working through a differential diagnosis of subepithelial lesions and can help identify which mucosal layer the lesion originates from, as well as the density of the lesion; however, surgical resection is the standard of care for the treatment of a resectable nonmetastatic GIST. For recurrent GISTs, metastatic disease, or GISTs not amendable to resection, tyrosine kinase inhibitors are frequently used, with imatinib being used in the first-line setting. A multimodal treatment approach is often necessary to increase the chances of a permanent cure.

A Case Report on Recurrent Gastro Intestinal Stromal Tumor (GIST)

Gastrointestinal stromal tumor (GIST) is a rare sarcoma, typically starts in the cells that line the gastrointestinal tract’s (GIT) wall. While certain GISTs may develop slowly over time, others might spread drastically. However, it will indicate recurrence for certain people. Patients with locally resectable gastro intestinal stromal tumours continue to be treated primarily with radical surgery, which, in more than 50% of instances, results in a long-term remission of this disease. The first targeted medication for the GISTs treatment was the tyrosine kinase inhibitor imatinib, and is now the preferred option for treating advanced gastro intestinal stromal tumours. This case highlights recurrence of GIST for two times even after laparotomy which provides an information, that the hazards associated with this type of tumour must be reduced by receiving appropriate therapy because it can recur.

Cytoreductive surgery for metastatic gastrointestinal stromal tumors treated with ripretinib: A single-center experience

BackgroundCytoreductive surgery (CRS) has been advocated as an additional treatment with survival benefits for advanced gastrointestinal stromal tumor (GIST), especially in patients with responsive disease or focal progression after treatment with imatinib. Ripretinib is a fourth-line therapy for advanced GIST. This single-center pilot study investigated the short-term safety and efficacy of CRS after treatment with ripretinib in selected patients with recurrent or metastatic GIST. MethodsMedical records of patients with recurrent or metastatic GIST who underwent CRS after ripretinib in the First Affiliated Hospital of Sun Yat-sen University between June 1st, 2020 and June 1st, 2022 were retrospectively reviewed. Patients’ clinicopathological characteristics, preoperative treatment and general condition, surgical information, and postoperative management were recorded. ResultsThis study included 7 patients who underwent CRS after ripretinib. Radiographic response to ripretinib included partial response (n ​= ​1), stable disease (n ​= ​5), and progressive disease (n ​= ​1). The cumulative size of targeted lesions shrank by 4.8%–45.3% in 5 patients. R0/R1 resection was achieved in 6 (85.7%) patients. Postoperative complications (IId) were reported in 2 (28.6%) patients. There were no delayed post-operative complications. Median follow-up was 11.8 months. Median time-to-progression and median post-operative progression-free survival were not reached. Four patients who did not progress before surgery had no evidence of disease. ConclusionRipretinib combined with CRS is safe and effective in select patients with advanced GIST despite extensive prior therapy.

Endoscopic removal of an extraluminal gastrointestinal stromal tumor recurrence located on the surgical stapler line at gastroesophageal junction.

Endoscopic removal of an extraluminal gastrointestinal stromal tumor recurrence located on the surgical stapler line at gastroesophageal junction.

Utilization of Neoadjuvant Therapy in Gastrointestinal Stromal Tumors of the Stomach: Analysis of the 2006–2018 National Cancer Database

BackgroundNeoadjuvant tyrosine kinase inhibitor (TKI) therapy has reduced tumor burden and improved survival in both primary and recurrent gastrointestinal stromal tumors (GISTs). However, no clear guidelines exist on optimal patient selection for neoadjuvant therapy (NAT). Our aim was to analyze factors and outcomes associated with the therapeutic sequence of TKI therapy before and/or after surgery for gastric GISTs. MethodsWe performed a retrospective study of patients surgically treated for a gastric GIST utilizing the 2006–2018 National Cancer Database. We examined demographic, clinical, and pathological characteristics associated with NAT versus adjuvant therapy (AT) using logistic regression. ResultsOf the 3732 patients, 20.4% received NAT and 79.6% had AT. Among patients receiving therapy, NAT significantly increased over our study period (12% to 30.7%). A majority of the AT group received a partial gastrectomy (77.9%) compared with the NAT group who received more near-total/total gastrectomy or gastrectomy with en bloc resection (p < 0.001). In a multivariable model, patients were more likely to receive NAT when insured (private, aOR: 2.37, 95% CI: 1.31–4.29), treated at an academic/research program (aOR: 1.83, 95% CI: 1.49–2.56), had tumors located in the proximal stomach (aOR: 1.40, 95% CI: 1.06–1.86), tumor size > 10 cm (aOR: 1.88, 95% CI: 1.41–2.51), and received near-total/total gastrectomy (aOR: 1.81, 95% CI: 1.42–2.29). There were no differences in outcomes. ConclusionNAT for gastric GIST has increased in utilization. NAT was used in patients with larger tumors and who underwent more extensive resection. Despite these factors, outcomes were similar to patients receiving only AT. More studies are required to determine the therapeutic sequence for gastric GISTs.

Racial and ethnic disparities in presentation and outcomes of patients with gastrointestinal stromal tumors (GIST) in the era of targeted therapy.

e18573 Background: GIST is the most common malignant mesenchymal tumor of the gastrointestinal tract and is a compelling model for targeted therapies. Racial and ethnic minorities are underrepresented in clinical research, and information regarding disparities in GIST is limited. Our sarcoma center is located within a large and diverse population of Hispanic, LatinX, and African American/African Caribbean patients (pts). We aimed to identify racial and ethnic disparities among pts with GIST. Methods: We retrospectively reviewed all pts with primary or recurrent GIST between January 2003 and October 2022 in our institution. All data were retrieved from electronic medical records. SPSS Statistics was utilized, Fisher exact test and log-rank test were used for analysis. A two-sided p &lt; 0.05 was considered statistically significant. Results: A total of 1150 pts had a diagnosis of GIST during the study period. Information regarding race and ethnicity was available in 711 pts. There were 42.4% White Non-Hispanic/LatinX (WN), 33.2% Hispanic/LatinX (HL), and 24.4% Black Non-Hispanic/LatinX (BN). The stomach was the most common primary site in all three groups, especially in the BN population (80.9%) vs WN (53%) and HL (61.9%), followed by the small intestine (p &lt; 0.001). The WN pts more commonly presented with metastatic disease on diagnosis (16.2%) vs BN (12.7%) and HL (8.9) (p = 0.042) and had higher grade tumors (37.7%) vs BN (24.9%) and HL (23.7%) (p &lt; 0.001). Median disease-free survival (mDFS) after radical resection was significantly lower in BN population vs WN and HL (p = 0.014). Disease-specific survival (DSS) in BN was also significantly reduced compared to the other groups (p = 0.024). A total of 445 pts had some molecular testing done, and BN were significantly less tested (38.5%) (p &lt; 0.001). The most common primary driver mutation was KIT exon 11 throughout all groups, especially in the BN group corresponding to 80% of the cases tested (p = 0.008). The median overall survival (mOS) among pts with metastatic disease was 7.1 years (95% CI = 5.6-8.6). The HL population had a trend toward the longest mOS (8.8 years), followed by the WN (7.7 years), followed by the BN population (5.8 years) (p = 0.073). A total of 75 of these patients were tested for secondary mutations, with no statistical difference among the groups. Conclusions: We found in our study the WN population was significantly more likely to present with metastatic disease and higher-grade tumors than BN or HL pts. Nonetheless, the BN population were substantially less likely to undergo mutation testing and had a trend toward a worse mOS by more than 1 year. All pts had their care within the same healthcare system, implicating access to mutation testing and socioeconomic barriers playing a role in inferior outcomes. Further studies are needed to understand molecular differences and decrease the existing gap among these populations.

Re-appraisal of the universal definition of tumor rupture among patients with high-risk gastrointestinal stromal tumors.

Tumor rupture has been indicated as a risk factor for recurrence of gastrointestinal stromal tumors (GISTs). The universal definition of tumor rupture was proposed. This study evaluated whether the universal definition was more accurate in identification of GISTs with high recurrent risk than subjective judgment. The study included 507 patients with high-risk GISTs who underwent complete resection between December 2012 and December 2015. We conducted a questionnaire survey in participating institutes to re-diagnose tumor rupture based on the universal definition according to their surgical and pathological findings. We compared the clinical outcomes of tumor rupture based on the definition to those based on the surgeon's judgment and clarified the clinical importance of the rupture. Sixty-four patients were initially registered to have tumor rupture by surgeon's judgment, and it became 90 patients who had tumor rupture after reevaluation. Although there were significant differences in recurrence-free survival (RFS) between no rupture and rupture for both initial registration and reevaluation (p = 0.002, <0.001, respectively), a significant difference in overall survival was only observed after reevaluation (p = 0.011). Tumor rupture was significantly associated with large tumor size, mixed cell type in histology, R1 resection, frequent adjuvant therapy and recurrence, but not with location, mitosis, and genotype. Adjuvant therapy more than 3 years improved RFS of patients with tumor rupture. This study suggested that tumor rupture based on the universal definition more accurately identified GISTs with poor prognostic outcomes than the subjective judgment.