Prognosis Of Gastrointestinal Stromal Tumors Research Articles

Development and interpretation of a multimodal predictive model for prognosis of gastrointestinal stromal tumor

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal original tumor in gastrointestinal (GI) tract and is considered to have varying malignant potential. With the advancement of computer science, radiomics technology and deep learning had been applied in medical researches. It’s vital to construct a more accurate and reliable multimodal predictive model for recurrence-free survival (RFS) aiding for clinical decision-making. A total of 254 patients underwent surgery and pathologically diagnosed with GIST in The First Hospital of China Medical University from 2019 to 2022 were included in the study. Preoperative contrast enhanced computerized tomography (CE-CT) and hematoxylin/eosin (H&E) stained whole slide images (WSI) were acquired for analysis. In the present study, we constructed a sum of 11 models while the multimodal model (average C-index of 0.917 on validation set in 10-fold cross validation) performed the best on external validation cohort with an average C-index of 0.864. The multimodal model also reached statistical significance when validated in the external validation cohort (n = 42) with a p-value of 0.0088 which pertained to the recurrence-free survival (RFS) comparison between the high and low groups using the optimal threshold on the predictive score. We also explored the biological significance of radiomics and pathomics features by visualization and quantitative analysis. In the present study, we constructed a multimodal model predicting RFS of GIST which was prior over unimodal models. We also proposed hypothesis on the correlation between morphology of tumor cell and prognosis.

Prognostic impact of positive microscopic margins (R1 resection) in patients with GIST (gastrointestinal stromal tumours): Results of a multicenter European study

BackgroundAlthough several prognostic factors in GIST have been well studied such as tumour size, mitotic rate, or localization, the influence of microscopic margins or R1 resection remains controversial. The aim of this study was to evaluate the influence of R1 resection on the prognosis of GIST in a large multicentre retrospective series of patients. MethodsFrom 2001 to 2013, 1413 patients who underwent surgery for any site of GIST were identified from 61 European centers. 1098 patients were included, excluding synchronous metastases, concurrent malignancies, R2 resection or GIST recurrence. Tumour rupture (TR) was reclassified according to the Oslo sarcoma classification. Cox proportional hazards ratio and Kaplan-Meier survival estimates were used to analyse 5-year recurrence-free survival (RFS). ResultsOf 1098 patients, 38 (3%) underwent R1 resection with a risk of TR of 11%. The 5-year RFS was 89.6% with a median follow-up of 81 months [range: 31.2–152 months]. On univariate analysis, lower RFS was significantly associated with R1 resection [HR = 2.13; p = 0.04], high risk score according to the modified NIH classification, administration of adjuvant therapy [HR = 2.24; p < 0.001] and intraoperative complications [HR = 2.82; p < 0.001]. Only intraoperative complications [HR = 1.79; p = 0.02] and high risk according to the modified NIH classification including the updated definition of TR [HR = 3.43; p = 0.04] remained significant on multivariate analysis. ConclusionThis study shows that positive microscopic margins are not an independent predictive factor for RFS in GIST when taking into account the up-dated classification of TR. R1 resection may be considered a reasonable alternative to avoid major functional sequelae and should not lead to reoperation.

The development of a prediction model based on deep learning for prognosis prediction of gastrointestinal stromal tumor: a SEER-based study

Accurately predicting the prognosis of Gastrointestinal stromal tumor (GIST) patients is an important task. The goal of this study was to create and assess models for GIST patients' survival patients using the Surveillance, Epidemiology, and End Results Program (SEER) database based on the three different deep learning models. Four thousand five hundred thirty-eight patients were enrolled in this study and divided into training and test cohorts with a 7:3 ratio; the training cohort was used to develop three different models, including Cox regression, RSF, and DeepSurv model. Test cohort was used to evaluate model performance using c-index, Brier scores, calibration, and the area under the curve (AUC). The net benefits at risk score stratification of GIST patients based on the optimal model was compared with the traditional AJCC staging system using decision curve analysis (DCA). The clinical usefulness of risk score stratification compared to AJCC tumor staging was further assessed using the Net Reclassification Index (NRI) and Integrated Discrimination Improvement (IDI). The DeepSurv model predicted cancer-specific survival (CSS) in GIST patients showed a higher c-index (0.825), lower Brier scores (0.142), and greater AUC of receiver operating characteristic (ROC) analysis (1-year ROC:0.898; 3-year:0.853, and 5-year ROC: 0.856). The calibration plots demonstrated good agreement between the DeepSurv model's forecast and actual results. The NRI values ( training cohort: 0.425 for 1-year, 0.329 for 3-year and 0.264 for 5-year CSS prediction; test cohort:0.552 for 1-year,0.309 for 3-year and 0.255 for 5-year CSS prediction) and IDI (training cohort: 0.130 for 1-year,0.141 for 5-year and 0.155 for 10-year CSS prediction; test cohort: 0.154 for 1-year,0.159 for 3-year and 0.159 for 5-year CSS prediction) indicated that the risk score stratification performed significantly better than the AJCC staging alone (P < 0.001). DCA demonstrated the risk score stratification as more clinically beneficial and discriminatory than AJCC staging. Finally, an interactive native web-based prediction tool was constructed for the survival prediction of GIST patients. This study established a high-performance prediction model for projecting GIST patients based on deep learning, which has advantages in predicting each person's prognosis and risk stratification.

Prognostic nomogram in patients with gastrointestinal stromal tumors: a SEER-based study.

Gastrointestinal stromal tumor (GIST) is a common mesenchymal tumor of the gastrointestinal system. They originate from the interstitial cells of Cajal located within the muscle layer and are characterized by over-expression of the tyrosine kinase receptor KIT. Data from the Surveillance Epidemiology, and End Results (SEER) database of 1,213 patients diagnosed with GIST between 2010 and 2019 were dichotomized into a modeling set and a validation set at a 2:1 ratio. For the modeling set, both univariate and multivariate Cox regression analyses were used to identify independent prognostic factors. A nomogram was then constructed based on these determinants. Model efficacy was tested using receiver operating characteristic (ROC) curves, calibration curves, clinical decision curves, and risk stratification analysis in both subsets. Identified prognostic determinants included age, sex, pathological differentiation level, tumor-node-metastasis (TNM) stage, surgical intervention, radiotherapy, and marital status. The constructed nomogram showed area under the ROC curve (AUC) values of 0.822, 0.793, and 0.779 for 1-, 3-, and 5-year overall survival (OS) in the modeling set, respectively, while in the validation set, the values were 0.796, 0.823, and 0.806, respectively. Calibration plots from both sets confirmed the concordance between predicted and observed survival. Decision curve analysis (DCA) indicated significant clinical utility for the nomogram. Risk stratification of the patient data revealed distinct survival differences between high-risk and low-risk cohorts in both sets (P<0.001). A novel and potent nomogram for the prognosis of GIST has been introduced. This model's precision offers crucial insights for clinical decisions, yet further external validation remains essential.

Is lymph node metastasis an event indicating an advanced gastrointestinal stromal tumor?

754 Background: The clinicopathological features and prognosis of gastrointestinal stromal tumors (GISTs) with lymph node metastasis remain controversial owing to their low incidence. A multicenter retrospective cohort study was conducted to compare the clinicopathological features and oncologic outcomes of GIST with and without lymph node metastases. Methods: The medical records of patients with GISTs in 16 large medical centers in China from January 2014 to December 2020 were reviewed. Patients were divided into three groups: no metastasis, lymph node metastasis without distant metastasis, and distant metastasis without lymph node metastasis. Propensity score matching (PSM) was performed to reduce confounding factors. Results: A total of 1109 cases of primary GIST were included in this study, comprising 607 males (54.7%) and 502 females (45.3%), with a mean age of 56.6±11.9 years. There were 1024 patients (92.3%) with no lymph node metastasis after surgery, and 85 patients (7.7%) had lymph node metastasis. Compared to that in GIST without lymph node metastasis, the proportion of non-gastric GIST was higher in GIST with lymph node metastasis (52.9% vs. 40.7%) with a larger tumor diameter (&gt;10 cm: 36.5% vs. 18.1%) and more patients with distant metastasis (11.8% vs. 3.5%). Tumor location not in the stomach, the largest tumor diameter, and distant metastasis were independent risk factors for GIST with lymph node metastasis (all P &lt; 0.05). After PSM, 96, 48, 24 patients comprised no metastasis, lymph node metastasis without distant metastasis, and distant metastasis without lymph node metastasis, respectively. The relapse-free survival (RFS) of the lymph node metastasis group was comparable to that of the distant metastasis group without lymph node metastasis ( P = 0.368) and significantly inferior to that of no metastases ( P = 0.042). Conclusions: The prognosis of patients with GIST with lymph node metastasis was comparable to that of patients with distant metastasis and significantly worse than that of patients without metastasis. Lymph node metastasis may be an advanced event in GIST.

Factors associated with gastrointestinal stromal tumor rupture and pathological risk: A single-center retrospective study.

Gastrointestinal stromal tumor (GIST) is a rare gastrointestinal mesenchymal tumor with potential malignancy. Once the tumor ruptures, regardless of tumor size and mitotic number, it can be identified into a high-risk group. It is of great significance for the diagnosis, treatment, and prognosis of GIST if non-invasive examination can be performed before surgery to accurately assess the risk of tumor. To identify the factors associated with GIST rupture and pathological risk. A cohort of 50 patients with GISTs, as confirmed by postoperative pathology, was selected from our hospital. Clinicopathological and computed tomography data of the patients were collected. Logistic regression analysis was used to evaluate factors associated with GIST rupture and pathological risk grade. Pathological risk grade, tumor diameter, tumor morphology, internal necrosis, gas-liquid interface, and Ki-67 index exhibited significant associations with GIST rupture (P < 0.05). Gender, tumor diameter, tumor rupture, and Ki-67 index were found to be correlated with pathological risk grade of GIST (P < 0.05). Multifactorial logistic regression analysis revealed that male gender and tumor diameter ≥ 10 cm were independent predictors of a high pathological risk grade of GIST [odds ratio (OR) = 11.12, 95% confidence interval (95%CI): 1.81-68.52, P = 0.01; OR = 22.96, 95%CI: 2.19-240.93, P = 0.01]. Tumor diameter ≥ 10 cm, irregular shape, internal necrosis, gas-liquid interface, and Ki-67 index ≥ 10 were identified as independent predictors of a high risk of GIST rupture (OR = 9.67, 95%CI: 2.15-43.56, P = 0.01; OR = 35.44, 95%CI: 4.01-313.38, P < 0.01; OR = 18.75, 95%CI: 3.40-103.34, P < 0.01; OR = 27.00, 95%CI: 3.10-235.02, P < 0.01; OR = 4.43, 95%CI: 1.10-17.92, P = 0.04). Tumor diameter, tumor morphology, internal necrosis, gas-liquid, and Ki-67 index are associated with GIST rupture, while gender and tumor diameter are linked to the pathological risk of GIST. These findings contribute to our understanding of GIST and may inform non-invasive examination strategies and risk assessment for this condition.

Imatinib induces ferroptosis in gastrointestinal stromal tumors by promoting STUB1-mediated GPX4 ubiquitination

Imatinib (IM) has significantly improved the prognosis of gastrointestinal stromal tumor (GIST) patients, but some patients still have primary resistance to IM, and approximately half of patients develop acquired drug resistance within 2 years of treatment, necessitating exploration of new treatment strategies. Targeting ferroptosis as a novel approach to tumor treatment has gained attention. Yet, there is limited research on ferroptosis in GIST, and the underlying mechanism remains unclear. In this study, we revealed that IM increased lipid reactive oxygen species and intracellular Fe2+ levels, and decreased glutathione levels in GIST. This effect could be partially inhibited by Ferrostatin-1. Additionally, knocking down STUB1 and overexpressing GPX4 reversed the IM-induced ferroptosis effect. Moreover, STUB1 was identified as a novel E3 ubiquitin ligase of GPX4, promoting the ubiquitination at site K191 of GPX4. The combination of the GPX4 inhibitor RSL3 and IM synergistically induces ferroptosis, inhibiting GIST proliferation both in vivo and in vitro. Furthermore, STUB1 and GPX4 expression serve as independent prognostic factors for GIST. In conclusion, This study is the first to demonstrate that IM induces ferroptosis by promoting STUB1-mediated GPX4 ubiquitination in GIST, and the combination of RSL3 and IM emerges as a promising therapeutic strategy for GIST.

CD117‐Targeted Intraoperative Imaging of Gastrointestinal Stromal Tumor Using a Stem‐Cell‐Factor‐Labeled Fluorophore

Complete resection without damaging the capsule is the gold‐standard surgical approach for nonmetastatic gastrointestinal stromal tumors (GIST). However, accurately locating tumors during surgery is challenging because GIST is covered by normal mucosal tissue, leading to suboptimal surgeries and increased cancer recurrence rates. To enhance surgical care for GIST, a cutting‐edge near‐infrared (NIR) fluorescent nanoprobe is presented that enables real‐time navigation of GIST by specifically targeting CD117, a protein frequently overexpressed in GIST. By attaching a zwitterionic NIR fluorophore called ZW800‐1C to a CD117 ligand, stem cell factor (SCF), precise targeting is achieved while minimizing nonspecific tissue interactions. In in vitro studies, the high affinity of nanoprobe for CD117‐positive GIST‐T1 cell lines is demonstrated, while exhibiting no binding to CD117‐negative cells or GIST‐5 R cells. In a xenograft model of GIST‐T1 in mice, the nanoprobe produces strong and persistent NIR signals that last over 72 h following a single intravenous injection. Moreover, the nanoprobe successfully detects spontaneous tumors in the cecum of heterozygous Kit K641E mice. In these findings, the promise of CD117‐targeted molecular imaging is highlighted as an intraoperative strategy for GIST. Furthermore, this imaging approach holds potential for early diagnosis, as well as monitoring GIST prognosis before and after surgical resection.

Development and validation of a prognostic nomogram for gastrointestinal stromal tumors in the postimatinib era: A study based on the SEER database and a Chinese cohort.

After the standardization, recording and follow-up of imatinib use that significantly prolongs survival of gastrointestinal stromal tumors (GISTs), a comprehensive reassessment of the prognosis of GISTs is necessary and more conductive to treatment options. A total of 2185 GISTs between 2013 and 2016 were obtained from the Surveillance, Epidemiology, and End Results database and comprised our training (n = 1456) and internal validation cohorts (n = 729). The risk factors extracted from univariate and multivariate analyses were used to establish a predictive nomogram. The model was evaluated and tested in the validation cohort internally and in 159 patients with GIST diagnosed between January 2015 and June 2017 in Xijing Hospital externally. The median OS was 49 months (range, 0-83 months) in the training cohort and 51 months (0-83 months) in the validation cohort. The concordance index (C-index) of the nomogram was 0.777 (95% CI, 0.752-0.802) and 0.7787 (0.7785, bootstrap corrected) in training and internal validation cohorts, respectively, and 0.7613 (0.7579, bootstrap corrected) in the external validation cohort. Receiver operating characteristic curves and calibration curves for 1-, 3-, and 5-year overall survival (OS) showed a high degree of discrimination and calibration. The area under the curve showed that the new model performed better than the TNM staging system. In addition, the model could be dynamically visualized on a webpage. We developed a comprehensive survival prediction model for assessing the 1-, 3- and 5-year OS of patients with GIST in the postimatinib era. This predictive model outperforms the traditional TNM staging system and sheds light on the improvement of the prognostic prediction and the selection of treatment strategies for GISTs.

Malignant diagnosis and prognostic analysis of 89 GIST patients using preoperative FDG-PET

There is no preoperative imaging accurately diagnose malignancy of gastrointestinal stromal tumor (GIST). To evaluate the usefulness of preoperative [18F]2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in the malignant diagnosis and prognostic analysis of GIST. Eighty-nine consecutive patients with GIST who underwent curative surgery were reviewed retrospectively. PET scan was performed within 2–3 weeks before surgery and maximum standardized uptake values (SUVmax) were assessed for GIST. The relationship between prognostic factors and prognosis of GIST and SUVmax were evaluated. Tumor size, mitotic count, and Ki-67 index showed significant positive correlations with the SUVmax. When the cutoff value was set as SUVmax 5.68, the accuracy was 86.5% for the high-risk group, 76.4% for the recurrence group, and 73.0% for the death group. The group with SUVmax ≥ 5.68 demonstrated a significantly lower 10-year relapse-free survival than the group with SUVmax < 5.68 (55.2% vs. 98.2%, P < 0.001), while the group with SUVmax ≥ 5.68 demonstrated a significantly lower 10-year overall survival than the group with SUVmax < 5.68 (68.0% vs. 97.6%, P < 0.001). In GISTs, FDG-PET is a very useful imaging marker for the diagnosis of malignant GISTs, such as those in high-risk and poor-prognosis groups.

Prognostic Role of Preoperative Onodera's Prognostic Nutritional Index (OPNI) in Gastrointestinal Stromal Tumors: a Systematic Review and Meta-analysis.

The inflammatory parameters of peripheral blood are related to the prognosis of various cancers. The aim of this meta-analysis is to explore the prognostic value of preoperative OPNI in gastrointestinal stromal tumors (GIST). The following search strategies were used to locate all literature published up to May 1, 2022: PubMed, Web of Science, CBM, EMBASE, and Cochrane, using the keywords "Prognosis," "survival," "Nutritional Assessment," "Nutrition Index," and "PNI," "OPNI," "Gastrointestinal stromal tumor," and "GIST." Studies that did not report an associated cumulative hazard ratio (HR) of recurrence-free survival (RFS) were excluded. The pooled hazard ratio (HR) and corresponding 95% confidence intervals (CI) were calculated by a fixed-effects model. Subgroups were analyzed for heterogeneity of studies, and Egger's test was applied to assess the risk of publication bias. Through the inclusion and exclusion criteria, 8 articles with a total of 2462 patients with gastrointestinal stromal tumors were selected for analysis. The HR summary of univariate analysis of RFS was 2.73 (95% CI: 2.17-3.43, P < 0.0001), and there was no heterogeneity, which indicated that the prognosis of gastrointestinal stromal tumors with low OPNI before operation was poor. Except for one article that did not give the HR of RFS under the condition of multi-factor analysis, the other 7 articles gave the HR of RFS and summarized it to 1.81 (95% CI: 1.40-3.83, P < 0.0001). Although there was slight heterogeneity in the multifactorial analysis, the publication bias risk and sensitivity assessment showed that the results were still reliable (p > 0.05). The results of this systematic review and meta-analysis show that decreased preoperative OPNI is closely associated with poor long-term survival (RFS) in GIST patients. Monitoring OPNI in GIST patients may help with risk stratification and individualized treatment.

Development and validation of a prognostic model to predict the prognosis of patients with colorectal gastrointestinal stromal tumor: A large international population-based cohort study.

Colorectal gastrointestinal stromal tumors (GISTs), mesenchymal malignancy, only accounts for about 6% of GISTs, but prognosis is generally poor. Given the rarity of colorectal GISTs, the prognostic values of clinicopathological features in the patients remain unclear. Nomograms can provide a visual interface to help calculate the predicted probability of a patient meeting a specific clinical endpoint and communicate it to the patient. We included a total of 448 patients with colorectal GISTs diagnosed between 2000 and 2019 from the Surveillance, Epidemiology, and End Results (SEER) database. For nomogram construction and validation, patients in the SEER database were divided randomly into the training cohort and internal validation cohort at a ratio of 7:3, while 44 patients with colorectal GISTs from our hospital patient data set between 2010 to 2016 served as the external validation cohort. The OS curves were drawn using the Kaplan-Meier method and assessed using the log-rank test. And, Fine and Gray's competing-risks regression models were conducted to assess CSS. We performed univariate and multivariate analyses to select prognostic factors for survival time and constructed a predictive nomogram based on the results of the multivariate analysis. Through univariate and multivariate analyses, it is found that age, primary site, SEER stage, surgery, and tumor size constitute significant risk factors for OS, and age, primary site, histological grade, SEER stage, American Joint Committee for Cancer (AJCC) stage, surgery, and tumor size constitute risk factors for CSS. We found that the nomogram provided a good assessment of OS and CSS at 1-, 3- and 5- year in patients with colorectal GISTs. The calibration plots for the training, internal validation and external validation cohorts at 1-, 3- and 5- year OS and CSS indicated that the predicted survival rates closely correspond to the actual survival rates. We constructed and validated an unprecedented nomogram to predict OS and CSS in patients with colorectal GISTs. The nomogram had the potential as a clinically predictive tool for colorectal GISTs prognosis, and can be used as a potential, objective and additional tool for clinicians in predicting the prognosis of colorectal GISTs patients worldwide. Clinicians could wield the nomogram to accurately evaluate patients' OS and CSS, identify high-risk patients, and provide a baseline to optimize treatment plans.

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.

Associations of CD34, Ki67, layer of invasion and clinical pathological characteristics, prognosis outcomes in gastrointestinal stromal tumors-a retrospective cohort study.

BackgroundGastrointestinal stromal tumors (GIST) is the most common interstitial tumor of the digestive tract. GIST, like other malignancies, can recur, metastasize, and even metastasize to the brain, leading to death. Therefore, the prevention and treatment of GIST is very important. The clinical features of GIST are uniquely different to those of other common malignancies. Therefore, it is of great significance to explore the relationship between the pathological features and prognosis of GIST to strengthen the prevention and treatment of GIST. The objectives of this study were to study the clinical features of Ki67, Cluster Differentiation 34 (CD34), and their correlations in the Jianghuai region of China in recent years, and to analyze their relationship with prognosis.MethodsA total of 423 cases of GIST in Northern Jiangsu People’s Hospital in Yangzhou from 2013 to 2020 were retrospectively analyzed. The data of CD34, Ki67 and layer of invasion was collected, and their associations with the clinical pathological characteristics, prognosis outcomes of GIST were studied. CD34 and Ki67 were tested by immunohistochemistry (IHC) And data was analyzed by chi-square test, t-test, Kaplan-Meier (KM) method survival curve, Log-rank test, and Cox regression.ResultsThe results showed that CD34 was associated with the clinical features of primary site, tumor size, risk, recurrence, and progression-free survival (PFS) (P<0.001, =0.01, <0.001, =0.039 and =0.018), but not with nuclear division or overall survival (OS) (P>0.05). Further, Ki67 was associated with nuclear division, tumor size, risk, recurrence, and PFS (P<0.001, <0.001, <0.001, <0.001 and <0.001), but there was no significant correlation with the primary site and CD34 (P>0.05), and Ki67 was associated with OS, but there was no statistical significance (P=0.0507). The layer of invasion was associated with the primary site, nuclear division, tumor size, risk, CD34, smooth muscle actin (SMA), recurrence, Ki67, and PFS (P<0.001, <0.001, <0.001, <0.001, <0.001, <0.001, <0.001, <0.001 and =0.0025), but not with OS (P=0.6680).ConclusionsCD34, Ki67, and layer of invasion may play important roles in the occurrence and development of GIST, affecting the prognosis of GIST.

GIST: Correlation of risk classifications and outcome.

In clinical practice, there are often discrepancies between the oncological prognosis of gastrointestinal stromal tumors (GIST) and the actual clinical course. This study aimed to check with our collective how reliably the current classifications (Miettinen, Fletcher) predict the prognosis of GIST and to evaluate whether an extension of the classifications by the parameter proliferation activity could make sense. This prospective study enrolled 58 patients who underwent surgery on GIST from 01/2006 to 12/2016. The postoperative course (curation, recurrence, progress) was correlated with the identified risk classification and the proliferative activity. Coincidences with other tumors were strikingly common in patients with GIST (43%). Based on the risk group assignment of GIST, no assessment of the probability of the occurrence of second neoplasia could be derived. Individual patients were under- or over-graduated concerning the assessment of biological behavior based on the standard risk classifications. The inclusion of proliferative activity did not allow for a more precise predictive power - neither to the risk of recurrence and metastasis nor to the development of a second neoplasia. The study showed that there is currently no parameter or logarithm that reliably predicts the biological behavior of GIST. Due to the frequency of coincidence of second neoplasia and (rare) distant metastases, for everyday clinical practice, appropriate staging diagnostic and regular follow-up care should also be used for benign GIST.

Molecular heterogeneity and analysis of the long-term survival of patients with gastrointestinal stromal tumors

Introduction. Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract the character diagnostic feature of which is CD117 (KIT) expression. GISTs are clinically diverse and have different genetic alterations that may have predictive and prognostic significance.Aim – the study of clinical, morphological and genetic features of GISTs to assess the overall survival (OS) of patients with various profiles of genetic disorders for elucidation the factors contributing to prognosis.Materials and methods. A total 244 GIST patients who received combined treatment were enrolled in the study and their clinical characteristics and mutational status of KIT, PDGFRA, BRAF were analyzed. SDH-deficient GISTs were detected using IHC-analysis of SDHB expression.Results. Stromal tumors developed in stomach (50 %), small intestine (37.7 %), colon or rectum (8.6 %), esophagus (0.4 %) and extraorganically (EGIST, 5.7 %). Overall survival correlated with gastric site (p = 0.005), tumor size &lt;10 cm (p = 0,0001) and mitotic count HPF&lt; 10 / 50 (p = 0.007). KIT mutations were found in 168 (68.9 %) and PDGFRA – in 31 (12.1 %) of GISTs, 14 novel mutations were detected. Mutations in KIT exon 11 were found in 140 (57.4 %) tumors, 10-year OS, 51 %, median 124 months. Patients with deletions had lower OS than patients with substitutions or duplications in KIT exon 11 (p = 0,023). The lowest OS was in patients with primary mutations in KIT exons 13 or 17 (median 28 months) and duplications in KIT exon 9 (median 71 months). There was a low OS of young patients with homozygous KIT mutations, mutations that begin in intron and two simultaneous KIT mutations. GISTs with PDGFRA mutations were located in stomach and had no metastases, 10-year OS, 63 %, median 175 months. KIT / PDGFRA mutations were not observed in 45 (18.4 %) patients (wild-type GIST), 10-year OS, 59 %, median 250 months. Wild-type GISTs with BRAF, NF1 mutations and SDH deficiency were detected. The better OS was demonstrated by patients with BRAFV600E (10-year ОS, 84 %, median 97 months) and SDH deficiency (10-year and 15-year OS, 82 %).Conclusion. Genetic analysis is necessary to clarify GIST prognosis and predict the effectiveness of targeted therapy. The clinical, morphological and genetic diversity of GISTs was confirmed. Wild-type GISTs with BRAF mutations and SDHdeficiency were identified in the Russian population for the first time. The long-term 10- и 15-year OS of GIST patients were evaluated.

Ki67 for evaluating the prognosis of gastrointestinal stromal tumors: A systematic review and meta-analysis.

Overexpression of Ki67 is observed in tumor cells, and it has been suggested to be a marker for cancer prognosis. However, the relationship between Ki67 expression and the risk of recurrence of gastrointestinal stromal tumors (GISTs) remains poorly defined. In the present study, a meta-analysis was used to examine the associations between Ki67 levels and GIST recurrence. Studies reporting GIST and Ki67 were found by searching Cochrane Library, PubMed and Embase until October 14, 2021. The Newcastle-Ottawa Scale (NOS) was used to verify the quality of the evidence. Totally, 1682 patient cases were included. The odds ratio (OR) estimates and 95% confidence interval (CI) for each publication were determined by a fixed-effects (Mantel-Haenszel) model. A total of 20 studies that fulfilled the inclusion criteria were finally included in the analysis. The average score of quality evaluation was 6.4 points according to NOS. It was found that Ki67 levels were significantly higher in the NIH L group compared with the NIH VL group (OR: 0.51; 95% CI: 0.26-0.99; P=0.04; P heterogeneity=0.44). There was also greater Ki67 overexpression in the NIH I group compared with the NIH L group (OR: 0.45, 95% CI: 0.31-0.65; P<0.0001; P heterogeneity=0.32), while Ki67 levels were greater in the NIH H group than in the NIH I group (OR: 0.20; 95% CI: 0.15-0.28; P<0.00001; P heterogeneity=0.56). In conclusion, Ki67 overexpression may be a useful marker of the risk of recurrent GIST transformation.

Prediction of the Ki-67 expression level and prognosis of gastrointestinal stromal tumors based on CT radiomics nomogram.

To build and validate a radiomics nomogram integrated with the radiomics signature and subjective CT characteristics to predict the Ki-67 expression level of gastrointestinal stromal tumors (GISTs). Moreover, the purpose was to compare the performance of pathological Ki-67 expression level with predicted Ki-67 expression level in estimating the prognosis of GISTs patients. According to pathological results, patients were classified into high-Ki-67 labeling index group (Ki-67 LI ≥ 5%) and low-Ki-67 LI group (Ki-67 LI < 5%). Radiomics features extracted from contrast-enhanced CT(CECT) images were selected and classified to build a radiomics signature. A combined model was built by incorporating radiomics signature and determinant subjective CT characteristics using multivariate logistic regression analysis. The diagnostic performance of the radiomics signature, subjective CT model and combined model were explored by receiver operating characteristic (ROC) curve analysis and Delong test. The model with best diagnostic performance was then set up for the prediction nomogram. Recurrence-free survival (RFS) rates were compared utilizing Kaplan-Meier curve. The generated combined model yielded the best diagnostic performance with area under the curve (AUC) values of 0.738 [95% confidence interval (CI): 0.669-0.807] and 0.772 (95% CI 0.683-0.860) in the training set and testing set respectively. The nomogram based on the combined model demonstrated good calibration in the training set and testing set (both P > 0.05). Patients of high-Ki-67 LI group predicted by our nomogram had a poorer RFS than patients of low-Ki-67 LI group (P < 0.0001). This radiomics nomogram based on CECT had a satisfactory performance in predicting both the Ki-67 expression level and prognosis noninvasively in patients with GISTs, which may serve as an effective imaging tool that can assist in guiding personalized clinical treatment.

Sarcopenia as a novel prognostic factor in the patients of primary localized gastrointestinal stromal tumor

BackgroundSarcopenia predicts poor prognosis of a variety of gastrointestinal malignancies. However, there is a lack of study on the association between skeletal muscle index (SMI) and the prognosis of gastrointestinal stromal tumor (GIST). The aim of this study is to develop a novel nomogram based on sarcopenia for GIST patients to predict overall survival (OS).MethodsSMI was measured by computed tomography scan of 107 patients who underwent resection for primary localized gastrointestinal stromal tumor (GIST). Sarcopenia was defined by cutoff values for SMI as 40.1 cm2/m2 and 39.8 cm2/m2 using optimum stratification for males and females respectively. Factors were included in the nomogram were specified by univariate and multiple Cox proportional hazard analysis. Concordance index (C-index) and calibration curves were conducted to measure the discrimination and accuracy of the nomogram. The utility of the nomogram was assessed by the decision curve analysis (DCA).ResultsTwenty-eight (26.2%) of 107 patients were sarcopenic. Sarcopenia was correlated significantly with body mass index, albumin, female sex, resection style, mitotic index, rupture status, survival. Sarcopenia was significantly related to decreased overall survival (p = 0.003).The nomogram including sarcopenia status, resection style and mitotic index had an excellent discrimination with C-index 0.794. The calibration curves represented a good accordance between the actual observation and nomogram prediction for overall survival. Decision curve analysis illustrated that the nomogram was helpful in clinic.ConclusionsWe developed a nomogram based on sarcopenia to predict overall survival after resection of GISTs which is an effective and favorable prognostication tool.

Prognostic Factors and Management of Colorectal Gastrointestinal Stromal Tumors

Abstract Introduction The gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. Even though it can be found in any location of the digestive tract, the colorectal GIST is rare. With this study, we aim to review the current knowledge regarding the prognosis and management of colorectal GIST. Methods A literature search was conducted in PubMed, and 717 articles were collected. After analyzing these studies, 60 articles were selected to use in this review. Results The mitotic index, as well as tumor size and location were identified as good discriminators of prognosis in various studies. Surgery remains the only curative therapy for potentially resectable tumors. However, even after surgical resection, some patients develop disease recurrence and metastasis, especially those with high-risk tumors. Therefore, surgical resection alone might be inadequate for the management of all colorectal GISTs. The discovery of GIST's molecular pathway led to a shift in its therapy, insofar as tyrosine kinase inhibitors became part of the treatment schemes for this tumor, revolutionizing the treatment's outcome and prognosis. Discussion/Conclusion The controversy concerning colorectal GIST prognosis and treatment can be, in part, attributed to the limited number of studies in the literature. In this review, we gathered the most recent knowledge about the prognosis and management of GIST in this rare location and propose two algorithms for its approach. Lastly, we highlight the importance of an individualized approach in the setting of a multidisciplinary team.