Survival In Gastrointestinal Stromal Tumors Research Articles

Comparing gastrointestinal stromal tumor outcomes between geriatric and non-geriatric patients: Apopulation-based analysis.

Gastrointestinal Stromal Tumors (GISTs) are the most common mesenchymal tumors of the GI tract. SEER is an extensive cancer database which proves useful in analyzing population trends. This analysis investigated GIST outcomes between geriatric & non-geriatric patients. SEER*STAT 8.4.0.1 was used to extract relevant GIST data from 2000 to 2019. Geriatric age was defined as ≥70years. Variables included age, sex, surgery, cancer-specific death, and overall survival. Statistical tests included univariate analysis using KM survival estimate (95% confidence interval) to calculate 5-year survival (5YS). Log-Rank tests determined statistical significance. Multivariable Cox's PH regression estimated the geriatric hazard death ratio adjusted for sex, stage, and surgery. The number of patients included was 13,579, yielding overall 5YS of 68.6% (95% CI 67.7-69.5). Cancer-specific death was 39.11% in 2000 & 3.33% in 2019. Non-geriatric & geriatric patient data yielded 5YS of 77.4% (76.4%-78.3%) and 53.3% (51.7%-54.8%) respectively (p<0.0001). For no surgery/surgery, younger patient data yielded 5YS of 48.7% (45.8%-51.4%) and 83.7% (82.7%-84.7%) respectively (p<0.0001); geriatric data yielded 5YS of 29.3% (26.5%-32.1%) and 62.8% (60.8%-64.6%) respectively (p<0.0001). Multivariable analysis yielded a geriatric hazard death of 2.56 (2.42-2.70) (p<0.0001). Cancer-specific death decreased since 2000, indicating an improvement in survival & treatment methods. Observed lower survival rates overall in the geriatric group. Surgery appeared to enhance survival rates in both groups, suggesting that surgery is an important factor in GIST survival regardless of age. Large prospective studies will help define clinical management for geriatric patients.

Predicting the progression-free survival of gastrointestinal stromal tumors after imatinib therapy through multi-sequence magnetic resonance imaging.

Identify radiomics features associated with progression-free survival (PFS) and develop a predictive model for accurate PFS prediction in liver metastatic gastrointestinal stromal tumor patients (GIST). This multi-center retrospective study involved a comprehensive review of clinical and imaging data pertaining to 211 patients with gastrointestinal stromal tumors (GIST) from Center A and B. A total of 147 patients with hepatic metastatic GIST were included, with 102 cases as the training set and 45 cases as the external validation set. Radiomics features were extracted from non-enhanced MR images, specifically T2WI, DWI, and ADC, and relevant features were selected through LASSO-Cox regression. A radiomics nomogram model was then constructed using multivariable Cox regression analysis to effectively predict PFS. The models performance were evaluated with the concordance index (C-index). The median age of the patients was 53 years, with 82 males and 65 females. A total of 21 radiomics features were selected to generate the radiomics signature. Radiomics signature slightly outperformed the clinical model but without significant difference (P>0.05). Integrated radiomics signature with clinical features to build a nomogram, which exhibited high predictive performance in both training (C-index 0.757, 95% CI 0.692-0.822) and validation cohorts (C-index 0.718, 95% CI 0.618-0.818). Nomogram significantly outperformed the clinical model (P=0.002 for training cohort, P<0.001 for validation cohort). Stable long-term predictions shown by time-dependent ROC analysis (AUC 0.765-0.919 in training, 0.766-0.893 in validation). Multivariable Cox regression confirmed radiomics signature as an independent prognostic factor for preoperative survival prediction in hepatic metastatic GIST patients (HR=3.973). Radiomics signature is valuable for predicting PFS in metastatic GIST patients. Integrating imaging features and clinical factors into a comprehensive nomogram improves accuracy and effectiveness of survival prognosis, guiding personalized treatment strategies.

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.

Comparing GIST outcomes between geriatric and non-geriatric patients: A population-based analysis.

e23513 Background: Gastrointestinal Stromal Tumors (GISTs) are the most common mesenchymal tumors of the GI tract, typically presenting as subepithelial neoplasms in the stomach with rarer occurrences in the small bowel, colorectum, &amp; esophagus. Standard-of-care treatment includes surgical resection followed by Imatinib. It is unclear whether differences in patient outcomes exist across age groups. The Surveillance, Epidemiology, &amp; End Results (SEER) program is an extensive cancer database which proves useful in analyzing cancer trends. This SEER analysis aims to investigate differences in GIST outcomes for patients aged &gt; 70 versus ≤70 years. Methods: SEER*STAT version 8.4.0.1 was used to extract relevant gastrointestinal stromal sarcoma (ICD-O-3 8936/3) data for the years 2000-2019. Geriatric age was defined as &gt; 70 years. Variables assessed include age, surgery, gender, cause-specific death, &amp; overall survival. Statistical methods included univariate analysis using the KM survival estimate (95% confidence interval) for five-year survival and Log-Rank tests to observe statistical significance of the survival distribution. Multivariate Cox’s PH regression model was also used to estimate hazard ratio of death for geriatric patients adjusted for gender, stage, and surgery. Results: The number of patients included in this analysis within the study period was 13579, with an overall 5-year survival of 68.6% (95% CI: 67.7–69.5). Non-geriatric and geriatric patient data yielded 5-year survival rates of 77.4% (76.4%–78.3%) and 53.3% (51.7%–54.8%) respectively ( p&lt; .0001). Cancer-specific death was 39.11% in 2000 and 3.33% in 2019. Male and female patients yielded 5-year survival rates of 73.0% (71.5%–74.4%) and 82.6% (81.2%–83.9%) in the younger group respectively ( p&lt; .0001), while geriatric data yielded rates of 49.1% (46.8%–51.3%) and 57.3% (55.1%–59.4%) respectively ( p&lt; .0001). With respect to no surgery and surgery, younger patient data yielded 5-year survival rates of 48.7% (45.8%–51.4%) and 83.7% (82.7%–84.7%) respectively ( p&lt; .0001), while geriatric data yielded rates of 29.3% (26.5%–32.1%) and 62.8% (60.8%–64.6%) respectively ( p&lt; .0001). Multivariate Cox PH regression model yielded an estimated hazard ratio of 2.56 (2.42–2.70) for geriatric patients ( p&lt; .0001). Conclusions: Cancer-specific death has decreased since 2000, indicating an overall improvement in survival &amp; treatment methods. Younger female patients had the highest 5-year survival rates, while older male patients yielded the lowest rates. We observed lower survival rates overall in the older group &amp; a hazard ratio of 2.56 for geriatric patients. Surgery appeared to enhance survival rates in both the geriatric &amp; non-geriatric groups, suggesting that surgery is an important factor in overall GIST survival regardless of age group. Large prospective studies will help define the appropriate management in geriatric patients.

Trends and outcomes of minimally invasive surgery for gastrointestinal stromal tumors (GIST).

Minimally invasive surgery (MIS) is increasingly being utilized for the resection of gastrointestinal cancers. National trends for perioperative and oncologic outcomes of MIS for gastrointestinal stromal tumors (GIST) are unknown. We hypothesized that with increased use of MIS, the perioperative outcomes and survival for GIST are preserved. The National Cancer Database (2010-2016) was utilized to assess perioperative and oncologic outcomes for GIST of the stomach and small bowel. Kaplan-Meier method and log rank test were used to compare survival outcomes. Data from 8923 gastric and 3683 small bowel resections were analyzed. Over the study period, MIS became the prevalent modality for gastrectomies (2010: robotic: 2.4%, laparoscopic: 26.1%, open: 71.5% vs. 2016: robotic: 9.6%, laparoscopic: 48.8%, open: 41.6%; p < 0.001), with a smaller increase in enterectomies (2010: robotic: 1%, laparoscopic: 17.3%, open: 81.6% vs. 2016: robotic: 3.9%, laparoscopic: 27.2%, open: 68.9%; p < 0.001). Age and Charlson comorbidity index were similar among groups. MIS approaches were associated with fewer readmissions and lower 90day mortality for gastrectomies and similar rates for enterectomies. MIS did not compromise patient survival even in patients who underwent neoadjuvant treatment or harbored tumors ≥ 10cm. Minimally invasive surgery is increasingly being utilized for resection of gastric and small bowel GIST, with improved postoperative outcomes.In this retrospective review, overall survival after minimally invasive or open surgery was comparable, even in challenging scenarios of neoadjuvant treatment or large tumors (≥ 10cm).

The tumor site of origin and its effect on survival in gastrointestinal stromal tumors(GIST)

AbstractBackground: GIST is a common mesenchymal tumor of the Gastrointestinal Tract. The stomach is the most frequently affected site. In this study, we focus on the relation between tumor site and survival.Materials and methods: our retrospective study included 47 patients diagnosed with GIST at Sohag University Hospital, Sohag Cancer Center, and Sohag Health Insurance Hospitals during the period between 2012 -2017. The collected data were extracted from patient's files. Missed data in the files were obtained via phone communication with the patients or their relatives. Results: 47 cases with gastrointestinal tumors were selected. All tumors were stained positive for c-kit. 48.9% (23/47) of the tumors were located in the stomach, 40.4% (19/47) in the small intestine, and 10.6% (5/47) in the large intestine. The mean progression-free survival (PFS) was 20.75 months ranging between 7months and 39 months. On analyzing the impact of tumor site on PFS we found that There was a significant relationship between the gastric site of the tumor and improved PFS (log-rank P = 0.010). The mean overall survival (OS) was 35.26 months ranging between 1 month and 108 months, on analyzing the impact of tumor site on OS we found no relation. Conclusion: Gastric origin of GIST is associated with more benign behavior and improved PFS in comparison with the intestinal origin.Keywords: GIST, gastric GIST, survival.

Positive microscopic surgical margins: Is there an association with survival in resected small gastrointestinal stromal tumors?

BackgroundFew studies evaluate the relationships between surgical approach, histologic margin, and overall survival in gastrointestinal stromal tumor. We test the hypothesis that margin positive resection is associated with compromised overall survival. MethodsWe queried the National Cancer Data Base to identify patients undergoing resections for gastrointestinal stromal tumors ≤3 cm in size between 2010 and 2015. Multivariable logistic regression was used to identify factors associated with positive microscopic margins on final pathology. Cox proportional hazard methods were used to evaluate factors associated with overall survival. Results2064 patients met inclusion criteria; 135 (6.5%) had a microscopically positive surgical margin. On multivariable regression, minimally invasive approach was not associated with risk of a positive margin (OR 1.06 95% CI [0.71, 1.59]). On Cox analysis, positive margin status was not associated with OS (R1: 1.03, CI [0.46–2.31], reference R0). ConclusionsPositive microscopic surgical margins are not associated with compromised overall survival in patients undergoing resection of small gastrointestinal stromal tumors. Minimally invasive surgical approaches do not compromise oncologic outcomes in these cases.

Racial Disparity in Incidence and Survival for Gastrointestinal Stromal Tumors (GISTs): an Analysis of SEER Database

Gastrointestinal tumors (GISTs) represent the most common mesenchymal tumors of the gastrointestinal tract. There has been limited data on GIST incidence and survival disparities between ethnic groups. Assess disparities in incidence and survival among race in the USA in the era of available GIST histologic codes and treatment. We queried Surveillance, Epidemiology, and End Results (SEER) database for GIST from 2002 to 2015, with diagnostic code 8936. Of the 7204 patients identified, 4928 (68.4%) were White, 1308 (18.2%) African American (AA), and 968 (13.4%) were classified as "Other" (American Indian/Alaskan Native, Asian/Pacific Islander). The overall incidence rate (IR) was 0.75 per 100,000. IR was highest among AA at 1.37/100,000, but 0.65/100,000 for Whites, 1.10/100,000 for Asians/Pacific Islanders, and 0.28/100,000 for American Indians/Alaskan Natives. The GIST incidence was twice as high for AA as for Whites (rate ratio [RR]: 2.12; 95% CI: 1.98-2.26; p < 0.001). There was higher proportion of Whites than AA, who underwent surgical extirpation. Median overall survival (OS) and GIST specific survival (GSS) were not reached for all race, which indicates more than half of the patients were still alive at end of follow-up period. In multivariate Cox model, belonging to "Other" had better OS (adjusted hazard ratio [aHR]; 0.73, 95% CI: 0.55-0.95, P = 0.021) for GIST, but no difference in prognosis and OS for AA and White [(aHR for whites; 0.84, 95% CI: 0.69-1.02, P = 0.071), AA = reference]. There was no difference in GSS among races. Significant racial disparity in incidence and overall survival for GIST exists, and efforts should be made to bridge this gap and improve outcomes for all races. The overall incidence rate for GIST was noted to be 7.5 per 1 million, and IR of GIST was twice as high for African Americans as compared to Whites. The "Other" racial group (American Indians/Alaskan Natives, Asians, and Pacific Islanders) had superior OS as compared to African Americans and Whites.

Prognostic impact of preoperative neutrophil-lymphocyte ratio for surgically resected gastrointestinal stromal tumors.

Neutrophil–lymphocyte ratio (NLR) was shown to be prognostic value in various malignancies. There are limited data about predictive or prognostic role of NLR during gastrointestinal stromal tumors (GISTs) patients. This study evaluated the prognostic significance of preoperative NLR in patients with GIST.We retrospectively enrolled 72 primary GIST patients who received initial curative surgical resection with or without adjuvant imatinib therapy. The preoperative NLR in the peripheral blood was calculated. Univariate and multivariate Cox proportional hazard regression models were used to identify potential predictors of tumor outcomes.The NLR cut-off value of 4.18 was selected. Multivariate analysis revealed that high NLR was associated with a unfavorable prognosis of GISTs (P < .05). Tumor size, tumor location, and age were significantly correlated with the NLR (P < .05).High NLR was an unfavorable prognostic factor of overall survival in GISTs and may be a useful preoperative biomarker of the prognosis of GISTs.

Efficacy and Tolerability of 5-Year Adjuvant Imatinib Treatment for Patients With Resected Intermediate- or High-Risk Primary Gastrointestinal Stromal Tumor

Three years of adjuvant imatinib mesylate therapy is associated with reduced recurrence rates and improved overall survival in patients with high-risk primary gastrointestinal stromal tumor (GIST) compared with patients who receive 1 year of treatment. The impact of a longer duration of therapy is unknown. To determine whether adjuvant treatment for primary GIST with imatinib for 5 years is tolerable and efficacious. This prospective, single-arm, phase 2 clinical trial (Postresection Evaluation of Recurrence-free Survival for Gastrointestinal Stromal Tumors With 5 Years of Adjuvant Imatinib [PERSIST-5]) included adult patients with primary GIST (expressing KIT) at 21 US institutions who underwent a macroscopically complete resection and were at intermediate or high risk of recurrence, defined as primary GIST at any site measuring 2 cm or larger with 5 or more mitoses per 50 high-power field or nongastric primary GIST measuring 5 cm or larger. Data were collected from August 5, 2009, through December 20, 2016. Imatinib, 400 mg once daily, orally for 5 years or until discontinuation of therapy because of progression or intolerance. The primary end point was recurrence-free survival (RFS). The secondary end point was overall survival. Of the 91 patients enrolled, 48 (53%) were men with a median age of 60 years (range, 30-90 years). Median tumor size was 6.5 cm (range, 2.3-30.0 cm). Median treatment duration was 55.1 months (range, 0.5-60.6 months); 46 patients (51%) completed 5 years of imatinib therapy. Estimated 5-year RFS was 90% (95% CI, 80%-95%), and overall survival was 95% (95% CI, 86%-99%). Recurrence was noted in 7 patients: 1 had disease recur while receiving imatinib (PDGFRA D842V mutation) and died; 6 had disease recur after discontinuation of imatinib therapy. Two additional deaths were unrelated to treatment or tumor progression. Forty-five patients (49%) stopped treatment early because of patient choice (10 [21%]), adverse events (15 [16%]), or other (11 [12%]). All 91 patients experienced at least 1 adverse event, and 17 (19%) experienced grade 3 or 4 adverse events. In this first adjuvant trial, to our knowledge, of patients with resected primary GIST who received 5 years of imatinib therapy, no patient with imatinib-sensitive mutations had disease recur during therapy. For patients in whom disease recurred, recurrence was within 2 years of discontinuation of imatinib therapy. Approximately half of the patients discontinued treatment early, most commonly because of patient choice, thus emphasizing the importance of close clinical monitoring to continue imatinib treatment for patients at appropriate risk. ClinicalTrials.gov identifier: NCT00867113.

The influence of marital status on the survival of patients with operable gastrointestinal stromal tumor: A SEER-based study.

Marital status has been demonstrated as a predictive factor for prognosis in diverse malignancies, but its role in the survival of gastrointestinal stromal tumor (GIST) remains unclear. This study was aimed to investigate the impact of marital status on the overall survival (OS) and cancer-specific survival (CSS) of operable GIST cases, by using data from Surveillance, Epidemiology, and End Results (SEER) database. In total, 6582 GIST patients between 1973 and 2013 were identified from SEER database. Univariate and multivariate analyses demonstrated the marital status as an independent predictive factor for survival. Married group had better 5-year OS and CSS than unmarried group (OS: 79.2% vs 71.3%, P<.001; CSS: 88.9% vs 84.8%, P<.001). And compared to married, divorced/separated, and single group, widowed group had the lowest 5-year OS and CSS (61.3% and 82.2%). Further subgroup analyses validated the relationship between marital status and survival among all SEER stages and different age groups. And additional sensitivity analyses according to other clinicopathological features confirmed that married cases had higher survival rate than unmarried cases. In conclusion, marriage could be a protective prognostic factor for survival, and widowed patients had a higher risk of death.

Prognostic factors of recurrence and survival of gastrointestinal stromal tumors: First multicentric study of Mexico.

11045 Background: Gastrointestinal stromal tumors are mesenchymal lesions arising from the interstitial cells of Cajal. In GIST the location, size, number of mitosis and risk group are accepted as prognostic factors; some factors in which there are still controversies about their value as prognostic factors include male gender, tumor cellularity, the margins of resection, the presence or absence of p16 or intraperitoneal tumor breakdown. Methods: Observational, retrospective and longitudinal study. Patients admitted to the Oncology Hospital, CMN Siglo XXI of January 1, 1991 to April 30, 2012. Results: We identified 384 patients, the mean follow-up time was 55.86 months, the mean age was 58 years, 80.3% had symptoms and only 4.54% the finding was incidental. The most common site was the stomach (66.6%), followed by small intestine (28.7%) and colon (1.54%). The 7.57% had metastases at diagnosis, 4.54% in liver and 3.03% in the peritoneum. Were expressed by abdominal pain (39.39%) and gastrointestinal bleeding (30.30%), intestinal obstruction in 1.5%. The most common site was the stomach (66.6%), followed by small intestine (28.7%) and colon (1.54%). The 7.57% had metastases at diagnosis. The average tumor size was 10.84 cm (2.2 to 38 cm). Immunohistochemical markers were studied: 94.28% positive for CD117, CD34 74.28%, 11.42% S100 protein, desmin 5.71% and 51.72% for smooth muscle actin (AML). Overall rate at 5 years and 82% rate of recurrence-free survival at 5 years and 61% survival. The location of the tumor (p = 0.0002), size (p = 0.03145), the number of mitosis (p = 0.008), risk group (p = 0.020) and adjuvant treatment with Imatinib showed a statistically significant difference for Survival Recurrence-free. For overall survival, lesion location was the only factor that showed statistical significance with p = 0.0054. Conclusions: The tumor location, size, number of mitosis, the risk group and adjuvant treatment with Imatinib were statistically significant prognostic factors for disease recurrence. The location of the lesion was the only factor that showed statistical significance as a predictor of overall survival.

Genetic polymorphisms as predictive biomarker of survival in patients with gastrointestinal stromal tumors treated with sunitinib.

This study aimed to identify single-nucleotide polymorphisms (SNPs) that are associated with outcome to treatment with sunitinib in patients with advanced gastrointestinal stromal tumors (GIST). Forty-nine SNPS involved in the pharmacokinetic and pharmacodynamic pathway of sunitinib were associated with progression-free survival (PFS) and overall survival (OS) in 127 patients with advanced GIST who have been treated with sunitinib. PFS was significantly longer in carriers of the TT genotype in POR rs1056878 (hazards ratio (HR) 4.310, 95% confidence interval (CI):1.457-12.746, P=0.008). The presence of the T-allele in SLCO1B3 rs4149117 (HR 2.024, 95% CI:1.013-4.044, P=0.046), the CCC-CCC alleles in SLC22A5 haplotype (HR 2.603, 95% CI: 1.216-5.573, P=0.014), and the GC-GC alleles in the IL4 R haplotype (HR 7.131, 95% CI:1.518-33.496, P=0.013) were predictive for OS. This shows that polymorphisms in the pharmacokinetic and pharmacodynamic pathways of sunitinib are associated with survival in GIST. This may help to identify patients that benefit more from treatment with sunitinib.

Gastrointestinal Stromal Tumours: A Review on Genetics, Pathology, Risk Stratification, Clinical Characteristics, Investigation, and Treatment

Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours of the gastrointestinal tract, arising from the interstitial cells of Cajal. They are known to occur in all parts of the gastrointestinal tract from the oesophagus to the anorectum, with the stomach being the most commonly affected organ (60%). GISTs are commonly known to occur within the fifth and sixth decades of life, carry an equal predisposition between females and males, and are associated with tyrosine-protein kinase (KIT) or platelet-derived growth factor receptor alpha (PDGFRA) mutations in 85–90% of cases. Familial syndromes associated with GISTs are neurofibromatosis Type 1, Carney’s triad (gastric GIST, pulmonary chordoma, and paraganglioma), Carney–Stratakis syndrome (GIST and paraganglioma), and familial GISTs. Lesions vary in size from a few mm to &gt;30 cm, with a median size between 5 and 8 cm. Immunohistochemical staining with KIT and DOG1 show the highest sensitivity for GISTs. While 20% of GISTs are diagnosed asymptomatically, and 10% at autopsy, 70% are symptomatic. Bleeding followed by abdominal pain and a mass growth are the most common symptoms. Forty to fifty percent of GISTs are biologically malignant. Malignant GISTs spread haematogenously to the liver and peritoneum, while lymphatic spread is rare. Risk stratification subdivides GISTs into very low, low, intermediate, and high-risk groups. Computed tomography (CT) scan is the mainstay of diagnosis, though they are often incidentally detected on endoscopy. Surgery offers the best chance of cure in resectable lesions, while tyrosine kinase inhibitors are the treatment of choice in non-resectable and metastatic GISTs. Neoadjuvant and adjuvant tyrosine kinase inhibitors increase resectability, time to recurrence, recurrence-free survival, and overall survival in GISTs.

Combined inhibition of MAP kinase and KIT signaling synergistically destabilizes ETV1 and suppresses GIST tumor growth.

Gastrointestinal stromal tumor (GIST), originating from the interstitial cells of Cajal (ICC), is characterized by frequent activating mutations of the KIT receptor tyrosine kinase. Despite the clinical success of imatinib, which targets KIT, most patients with advanced GIST develop resistance and eventually die of the disease. The ETS family transcription factor ETV1 is a master regulator of the ICC lineage. Using mouse models of Kit activation and Etv1 ablation, we demonstrate that ETV1 is required for GIST initiation and proliferation in vivo, validating it as a therapeutic target. We further uncover a positive feedback circuit where MAP kinase activation downstream of KIT stabilizes the ETV1 protein, and ETV1 positively regulates KIT expression. Combined targeting of ETV1 stability by imatinib and MEK162 resulted in increased growth suppression in vitro and complete tumor regression in vivo. The combination strategy to target ETV1 may provide an effective therapeutic strategy in GIST clinical management. ETV1 is a lineage-specific oncogenic transcription factor required for the growth and survival of GIST. We describe a novel strategy of targeting ETV1 protein stability by the combination of MEK and KIT inhibitors that synergistically suppress tumor growth. This strategy has the potential to change first-line therapy in GIST clinical management.

Significance of surgery for prognosis of gist in cohort from transitional healthcare settings

Objective: Despite significant improvement in survival of gastrointestinal stromal tumors (GIST) due to use of tyrosine kinase inhibitors, surgery still represents the important part of clinical management. The aim of our study was to retrospectively analyze prognosis of GIST depending on the success of surgical treatments and utilization of chemotherapy in transitional country with relatively limited resources. Methods: cohort of consecutive patients operated for GIST in tertiary medical center, within time frame 1999–2012. Results: 54 patients, in age range 20–85 years (63.3 ± 14.7), male to female ratio 28 (51.9%):26 (48.1%), respectively. Complete excision with clean resection margins (R0) was obtained in 44 (81.5%)of total patients i.e. 44/47 (93.6%) of localized GISTs. Mean follow up was 3.9 ± 3.3 years and 19 patients (35.2%) received imatinib. Rate of overall survival was 40 (74.1%), disease-free survival 31 (57.4%) and 20 (37.0%) experienced recidivism. Follow-up parameters showed significant difference in connection with utilization of imatinib, completeness of resection and existence of metastatic disease (all p < 0.05). ROC analyzes revealed critical value of Ki-67 > 9% as significant predictor of long-term mortality; sensitivity 64.3% [95%CI = 35.1–87.2]; specificity 75.0% [58.8–87.3]; (AUC = 0.693; p = 0.049). Conclusion: Rate of complete resections in studied sample of patients from transitional background was overall peer comparable with reports from the developed countries. On the other hand, relatively dominant prognostic position of surgical treatments might be consequence of limited utilization of adjuvant treatment with tyrosine kinase inhibitors.

An evaluation of national treatment trends and survival in GIST.

e21510 Background: Systemic therapy (ST) for gastrointestinal stromal tumors (GIST) has changed considerably. Real-world data on changing patterns of therapy, including adjuvant management, are spa...

Incidence and survival analysis of gastrointestinal stromal tumors in shanghai: a population-based study from 2001 to 2010.

Objectives. A population-based study was undertaken to investigate the epidemiological features of gastrointestinal stromal tumors (GISTs) in Shanghai, especially the incidence and the preliminary exploration of survival. Methods. A total of 1923 patients with GISTs diagnosed from 2001 to 2010 in Shanghai were reviewed. The annual incidence and overall survival of GISTs were calculated; Cox proportional hazards' regression was used to analyze several prognostic factors. Results. The average crude incidence of GISTs was 2.11 per 100,000 between 2004 and 2008, and the age-standardized incidence was 1.28 per 100,000. The incidence increased gradually from 2004 to 2008. In addition, 57% of cases had GIST in the stomach and 33% in the intestine. The 5-year overall survival of GISTs was 86.98%. The Cox regression analysis showed older age (≥65 yr versus <40 yr, HR = 5.085; (40, 65) yr versus <40 yr, HR = 1.975), male gender (HR = 1.474), and tumor locations (intestinal versus stomach, HR = 1.609) were predictors of its mortality. Conclusion. GISTs, mainly occurring in the stomach, are more common in elderly population, with an increasing incidence from 2004 to 2008. Older age, male gender, and tumor locations are risk factors for its mortality.

繰り返す再発に対し集学的治療を行い長期生存が得られた小腸GISTの1例

繰り返す再発に対し集学的治療を行い長期生存が得られた小腸GISTの1例

A Retrospective Study of the Incidence of GIST in Scotland from 1995 to 1999

Background and aims: Gastrointestinal Stromal Tumours (GIST) are mesenchymal soft tissue neoplasms which express the c-kit receptor and are exquisitely sensitivity to tyrosine kinase receptor inhibitors such as imatinib. This has significantly improved prognosis so it is important to identify retrospective cases. Methods: Patients between 1995-1999 with suspected GIST were identified via Scottish pathology departments. C-kit + and C-kit -/CD34 + tumours were included. Data were analysed according to NIH consensus and the newer AFIP criteria. Results: The incidence of GIST was 0.69/100000/year. 44.8% were originally diagnosed as GISTs. Using NIH Consensus criteria there was a statistically significant relationship between overall survival and necrosis (p=0.004), prognostic group (p<0.0001) and mitotic rate (p=<0.0001). Overall survival was correlated with AIFP criteria (p value <0.0001). Conclusion: This pan Scotland study validates the AFIP criteria for assessment of overall survival in GISTs. In addition using the established NIH consensus criteria confirms a similar incidence to other European countries. We have identified patients who are eligible for targeted therapies who would otherwise have been missed.