Long-term survival outcomes of endoscopic therapy vs. surgical resection in patients with cardia gastrointestinal stromal tumor.

The ideal surgical approach for treating cardia gastrointestinal stromal tumor (GIST) is not clearly established. This study aimed to assess the long-term survival results among patients who received endoscopic therapy (ET) or surgical resection (SR) for cardia GIST. Cardia GIST patients from 2000 to 2019 were selected from the surveillance, epidemiology, and end result (SEER) database. Multiple imputation (MI) was applied to handle missing data, and propensity score matching (PSM) was carried out to mitigate selection bias during comparisons. Demographic and clinical characteristics' effects on overall survival (OS) and cancer-specific survival (CSS) were assessed using Kaplan-Meier analyses and multivariate Cox proportional hazard models. A total of 330 patients with cardia GIST were enrolled, including 47 (14.2%) patients with ET and 283 (85.8%) patients with SR. The 5-year OS and CSS rates in the ET and SR groups were comparable [before PSM, (OS) (76.1% vs. 81.2%, P = 0.722), (CSS) (95.0% vs. 89.3%, P = 0.186); after PSM, (OS) (75.4% vs. 85.4%, P = 0.540), (CSS) (94.9% vs. 92.0%, P = 0.099)]. Moreover, there was no significant difference between ET and SR in terms of long-term OS (hazard ratio [HR] 0.735, 95% confidence interval [CI] 0.422-1.282) and CSS (HR 1.560, 95% CI 0.543-4.481). Our study found no significant disparity in long-term survival outcomes between ET and SR in cardia GIST patients, implying that ET could be a valid surgical strategy for treating cardia GIST.

The impact of gender on survival outcomes in patients with small intestinal stromal tumors: a comprehensive analysis using the SEER database.

BACKGROUND: Small intestinal stromal tumors (SISTs) are a rare type of mesenchymal tumor. Gender is known to influence the incidence and prognosis of various tumors, but its role on the survival of SISTs at the population level remains unclear. Therefore, we aim to explore the relationship between gender and the prognosis of SISTs using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: Data on SISTs patients from 2000 to 2019 were derived from the SEER database. Multiple imputation was used to address missing data. Kaplan-Meier analyses and Cox proportional hazard models were applied to evaluate the impact of demographic and clinical characteristics on overall survival (OS) and cancer-specific survival (CSS). RESULTS: A total of 3513 patients with SISTs were analyzed, including 1921 males and 1592 females. Kaplan-Meier analysis coupled with log-rank testing demonstrated a significantly higher mortality rate among male patients compared to females (P < 0.001). Notably, female patients exhibited superior OS (hazard ratio [HR] 0.808, 95% confidence interval [CI] 0.724-0.902, P < 0.001) and CSS (HR 0.801, 95% CI 0.692-0.927, P = 0.003) compared to male patients. While the mean 1-year CSS rates were comparable between genders (95.3% for males vs. 96.0% for females, P = 0.332), male patients consistently showed lower mean survival rates at 3-, 5-, and 10-year intervals. Surgical intervention significantly boosted 5-year OS and CSS rates in both male and female patients (P < 0.001). Multivariate Cox regression analysis identified age, sex, grade, TNM stage, surgery, and mitotic rate as independent risk factors for OS and CSS in patients with SISTs. CONCLUSIONS: Our findings suggest that male patients with SISTs have a higher risk of mortality compared to female patients, indicating that gender may serve as a predictive indicator for survival in this patient population.

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

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

Discontinuation of imatinib in patients with oligometastatic gastrointestinal stromal tumour who are in complete radiological remission: a prospective multicentre phase II study.

INTRODUCTION: Metastatic gastrointestinal stromal tumour (GIST) is considered incurable, and life-long treatment with tyrosine kinase inhibitors is recommended. We investigated whether selected patients with metastatic GIST may remain in durable remission despite imatinib discontinuation. PATIENTS: In this 1-group, prospective, multicentre phase II trial selected patients with oligometastatic (≤3 metastases) GIST discontinued imatinib treatment. Eligible patients had been treated with imatinib >5 years without progression and had no radiologically detectable metastases after metastasectomy, radiofrequency ablation (RFA) or complete response to imatinib. The primary endpoint was progression-free survival (PFS) 3-years after stopping imatinib. Overall survival (OS) and quality of life (QoL) were secondary endpoints. RESULTS: The trial closed prematurely due to slow accrual. Between January 5, 2017, and June 5, 2019, 13 patients were enrolled, of whom 12 discontinued imatinib. The median follow-up time was 55 months (range, 36 to 69) after study entry. Five (42%) of the 12 eligible patients remained progression free, and seven (58%) progressed with a median time to progression 10 months. Median PFS was 23 months and the estimated 3-year PFS 41%. Six of the seven patients who progressed restarted imatinib, and all six responded. Three-year OS was 100%, and all patients were alive at the time of the study analysis. QoL measured 5 and 11 months after discontinuation of imatinib demonstrated improvement compared to the baseline. INTERPRETATION: A substantial proportion of selected patients with oligometastatic GIST treated with imatinib and metastasis surgery/RFA may remain disease-free for ≥3 years with improved QoL after stopping of imatinib.

Clinical outcomes of endoscopic resection for the treatment of intermediate- or high-risk gastric small gastrointestinal stromal tumors: a multicenter retrospective study.

BACKGROUND AND AIMS: Many studies of gastric gastrointestinal stromal tumors (g-GISTs) following endoscopic resection (ER) have typically focused on tumor size, with most tumors at low risk of aggressiveness after risk stratification. There have been few systematic studies on the oncologic outcomes of intermediate- or high-risk g-GISTs after ER. METHODS: From January 2014 to January 2020, we retrospectively collected patients considered at intermediate- or high-risk of g-GISTs according to the modified NIH consensus classification system. The primary outcome was overall survival (OS). RESULTS: Six hundred and seventy nine (679) consecutive patients were diagnosed with g-GISTs and treated by ER between January 2014 and January 2020 in three hospitals in Shanghai, China. 43 patients (20 males and 23 females) were confirmed at intermediate-or high-risk. The mean size of tumors was 2.23 ± 1.01 cm. The median follow-up period was 62.02 ± 15.34 months, with a range of 28 to 105 months. There were no recurrences or metastases, even among patients having R1 resections. The 5-year OS rate was 97.4% (42/43). CONCLUSION: ER for intermediate- or high-risk gastric small GISTs is a feasible and safe method, which allows for a wait-and-see approach before determining the necessity for imatinib adjuvant or surgical treatment. This approach to g-GISTs does require that patients undergo close follow-up.

Evaluating nomogram models for predicting survival outcomes in gastric gastrointestinal stromal tumors with SEER database analysis.

Gastrointestinal stromal tumors (GISTs) predominantly develop in the stomach. While nomogram offer tremendous therapeutic promise, there is yet no ideal nomogram comparison customized specifically for handling categorical data and model selection related gastric GISTs. (1) We selected 5463 patients with gastric GISTs from the SEER Research Plus database spanning from 2000 to 2020; (2) We proposed an advanced missing data imputation algorithm specifically designed for categorical variables; (3) We constructed five Cox nomogram models, each employing distinct methods for the selection and modeling of categorical variables, including Cox (Two-Stage), Lasso-Cox, Ridge-Cox, Elastic Net-Cox, and Cox With Lasso; (4) We conducted a comprehensive comparison of both overall survival (OS) and cancer-specific survival (CSS) tasks at six different time points; (5) To ensure robustness, we performed 50 randomized splits for each task, maintaining a 7:3 ratio between the training and test cohorts with no discernible statistical differences. Among the five models, the Cox (Two-Stage) nomogram contains the fewest features. Notably, at Near-term, Mid-term, and Long-term intervals, the Cox (Two-Stage) model attains the highest Area Under the Curve (AUC), top-1 ratio, and top-3 ratio in both OS and CSS tasks. For the prediction of survival in patients with gastric GISTs, the Cox (Two-Stage) nomogram stands as a simple, stable, and accurate predictive model with substantial promise for clinical application. To enhance the clinical utility and accessibility of our findings, we have deployed the nomogram model online, allowing healthcare professionals and researchers worldwide to access and utilize this predictive tool.

The influence of lymphadenectomy on the prognosis of small intestinal stromal tumors: a study based on the SEER database.

BACKGROUND: Small intestinal stromal tumors (SISTs) typically require surgical treatment. However, the impact of lymphadenectomy (LA) on long-term prognosis in patients remains unclear. Therefore, we plan to analyze the effect of LA on the prognosis of patients with SISTs using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: Data on SISTs patients between 2000 and 2019 were obtained from the SEER database. Multiple imputation (MI) was employed to handle missing data, while propensity score matching (PSM) was conducted to mitigate selection bias in the comparative assessments between the LA group and the No-LA group. Kaplan-Meier analyses and multivariate Cox proportional hazards models were utilized to evaluate both overall survival (OS) and cancer-specific survival (CSS). RESULTS: A total of 2412 patients diagnosed with SISTs were included in the study, with 879 undergoing LA and 1533 not undergoing LA. There were no significant differences observed between the two cohorts concerning long-term OS (hazard ratio [HR] 0.97, 95% confidence interval [CI] 0.84-1.13, P = 0.720) and CSS (HR 1.05, 95% CI 0.86-1.29, P = 0.622). After PSM, 1596 patients (798 in the LA group and 789 in the No-LA group) were matched for comparison. There was also no difference in long-term OS and CSS between the two groups. Subgroup analysis revealed that in the age group > 60 years, the CSS in the No-LA group was superior to that in the LA group. Multivariate Cox regression analysis revealed that age, M stage, marital status, and mitotic rate are significant risk factors influencing OS and CSS. CONCLUSIONS: Conducting LA in patients with SISTs does not enhance long-term prognosis. For patients aged over 60 years, it may be more advisable to refrain from performing LA.

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

BACKGROUND: 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. METHODS: SEER*STAT 8.4.0.1 was used to extract relevant GIST data from 2000 to 2019. Geriatric age was defined as ≥70 years. 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. RESULTS: 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). CONCLUSIONS: 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.

Long-term outcomes of endoscopic therapy versus surgical resection for 2-5 cm gastric gastrointestinal stromal tumors: A population-based comparative study.

BACKGROUND: Endoscopic therapy (ET) of gastrointestinal stromal tumors (GIST) has become a viable treatment. We intended to compare long-term outcomes of ET versus surgical resection for 2-5 cm GIST using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: A multicenter retrospective study was conducted to compare the long-term outcomes of patients treated with ET and surgical resection for GIST. The multivariate Cox proportional hazards models were used to identify predictors for patients survival. To balance the clinicopathologic characteristics, a 1:1 propensity score matching (PSM) was utilized. RESULTS: A total of 749 patients with 2-5 cm GIST were enrolled, of whom 113 accepted ET and 636 underwent surgical resection. Before PSM, there was no significant difference in long-term outcomes between ET and surgical resection (5-year overall survival (OS): 93.5% vs. 91.6%, P=0.374; 5-year cancer-specific survival (CSS): 99.1% vs. 96.5%, P=0.546; 10-year OS: 71.1% vs. 78.2%, P=0.374; 10-year CSS: 93.6% vs. 92.7%, P=0.546). After adjusting for the relevant variables using the multivariable Cox proportional hazards models, we observed that the ET and surgical resection groups were similar in OS (HR 0.726, 95%CI 0.457-1.153, P=0.175) and CSS (HR 1.286, 95%CI 0.474-3.488, P=0.621). After PSM, the long-term OS and CSS of patients with 2-5 cm GIST after ET and surgical resection were comparable. CONCLUSIONS: We found that the long-term survival of patients with 2-5 cm gastric GIST after ET and surgical resection were comparable. Further high-quality studies are needed to confirm the role of ET in 2-5 cm GIST.

Primary Pancreatic GIST - A-Single Centre Case Series and Systematic Review of Literature.

PURPOSE: GISTs arising from organs outside GI tract are defined as extragastrointestinal GISTs (EGIST). The majority of EGISTs arise from small intestinal mesentry, mesocolon, omentum, retroperitoneum, abdominal wall, liver and pancreas with pancreas comprising less than 5% of it. Due to limited data, it is unknown if the results of GIST can be generalised for EGISTs. We thereby present the largest single-centre case series of primary pancreatic GIST so far with review of existing literature. METHODS: A total of 9 patients of primary pancreatic GIST were treated at our institute from September 2016 to February 2023. After literature search for all studies published before February 2023, 51 articles including 57 patients were identified. Their clinicopathological data and survival analysis were assessed. RESULTS: The median age of patients treated at our centre was 53 years with a female predominance. The most common epicentre was pancreatic head with abdominal pain as the most common presenting symptom. All 57 patients documented in literature belonged to a similar age group with similar gender predilection. The factors impacting DFS were histologic type, mitotic index, NIH risk category and adjuvant therapy. The median DFS was 74 months with a 5-year DFS being 71.9%, while the 5-year OS was 90.4%. CONCLUSION: Pancreatic GIST is a rare entity. Due to limited evidence and evolving literature, results cannot be generalised to a larger population. Larger case series with longer follow-up data are required to further understand the disease biology and long-term outcomes of pancreatic GIST.

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

BACKGROUND: Sarcopenia 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). METHODS: SMI 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). RESULTS: Twenty-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. CONCLUSIONS: We developed a nomogram based on sarcopenia to predict overall survival after resection of GISTs which is an effective and favorable prognostication tool.

Down-regulation of SOCS6: an unfavorable prognostic factor for gastrointestinal stromal tumor proven by survival analysis.

BACKGROUND: Many studies reporting that down-regulation of SOCS6 plays vital roles in promoting progression of malignant tumors have been published. The present study was performed to evaluate whether SOCS6 was significantly associated with prognosis of GIST patients. METHODS: Immunohistochemical staining was accomplished to evaluate the expression levels of SOCS6 among GIST patients. The impacts of SOCS6 expression on overall survival (OS) and recurrence-free survival (RFS) of GIST patients were assessed by Cox proportional hazard regression model analysis and Kaplan-Meier curve analysis. RESULTS: It was demonstrated that the expression level of SOCS6 was significantly associated with tumor size (P=0.001). Then according to Kaplan-Meier curve analysis, low expression of SOCS6 was significantly correlated with worse OS and RFS of GIST patients. Ultimately, it was revealed by Cox proportional regression model analysis that low expression of SOCS6 was an independent predictive factor for OS and RFS. CONCLUSIONS: Low expression of SOCS6 was an independent prognostic factor for GIST, suggesting its potential as a novel biomarker predicting survival of GIST patients.

Dynamic survival analysis of gastrointestinal stromal tumors (GISTs): a 10-year follow-up based on conditional survival.

BACKGROUND: The prognosis of patients with gastrointestinal stromal tumors (GISTs) is generally evaluated at the time of diagnosis but does not reflect the survival dynamics of patients in the future. Therefore, the purpose of this article was to evaluate the conditional survival (CS) of Chinese patients with GISTs after radical resection. METHODS: This retrospective study included 451 patients who underwent radical surgery for GISTs. A Cox proportional hazard model was used to evaluate the prognostic factors of disease-free survival (DFS). The 3-year conditional DFS (CDFS3) of patients who survived for x years was expressed as CDFS3=DFS(x + 3)/DFS(x). RESULTS: The traditional 3-year DFS rate decreased gradually from 94.0% at 3 years to 77.3% at 7 years, while the CDFS3 rate increased from 94.0 to 95.2% over the survival time of the patients. In addition, classic clinicopathological prognostic factors had different effects on CDFS3, with changes observed in survival time, but these effects were only slight or moderate (|d|<0.5). Although multivariate analysis showed that age, sex, mitotic index and tumor rupture were independent risk factors for DFS at baseline, all adverse prognostic factors, except for the mitotic index, lost their predictive significance at 5 years after operation. When the Modified NIH criteria were included, the risk staging was found to be an independent risk factor for recurrence or death. Time-dependent Cox regression analysis showed that the modified NIH criteria independently affected the recurrence or death of GIST patients within 2 years after operation. CONCLUSION: CS provides detailed dynamic survival information about Chinese patients with primary resected GISTs. The mitotic index is of great clinical significance for the monitoring and follow-up of patient populations with a high risk of tumor recurrence or death until 5 years after surgery.

A Retrospective Study of Postoperative Outcomes in 98 Patients Diagnosed with Gastrointestinal Stromal Tumor (GIST) of the Upper, Middle, and Lower Gastrointestinal Tract Between 2009 and 2019 at a Single Center in Poland.

BACKGROUND Gastrointestinal stromal tumors (GISTs) arise in the smooth muscle pacemaker interstitial cells of Cajal, or similar cells. The aim of this retrospective study between 2009 and 2019 from a single center in Poland was to assess the selected prognostic factors (location, tumor size, mitotic index, body mass index (BMI), length of hospital stay, age, sex, and coexistent neoplasm) and to investigate postoperative outcomes in 98 patients with GIST of the upper, middle, and lower gastrointestinal tract. MATERIAL AND METHODS Between 2009 and 2019, 98 patients (50 women and 48 men) with an average age of 63.8 years (range from 38 to 90 years) were operated on for GIST in the Department of Gastrointestinal Surgery in Katowice, Poland. Based on the intraoperative and postoperative investigations, the tumor size and mitotic index were determined in each case. RESULTS A statistically significant correlation between age and mitotic index (MI) was found (p=0.02). The higher the MI, the younger the age of the patients. However, regardless of sex, younger patients had a tendency to survive longer. A >60-year-old male patient's probability of survival was around 65% after 40 months. Higher mitotic index was also associated with larger tumor size (p<0.0001). Female patients had a tendency to survive longer than males. CONCLUSIONS The findings from this small retrospective study support the importance of preoperative evaluation and frequent postoperative follow-up for patients with GIST of the gastrointestinal tract, particularly in older male patients, and patients with malignant comorbidities, which are associated with increased mortality.

Expression of fatty acid-binding protein-4 in gastrointestinal stromal tumors and its significance for prognosis.

BACKGROUND: Fatty acid-binding proteins (FABPs) have been found to be involved in tumorigenesis and development. However, the role of FABP4, a member of the FABPs, in GISTs (Gastrointestinal stromal tumors) remains unclear. This study aimed to investigate the expression of FABP4 and its prognostic value in GISTs. METHODS: FABP4 expression in 125 patients with GISTs was evaluated by immunohistochemical analysis of tissue microarrays. The relationship between FABP4 expression and clinicopathological features and prognosis of GISTs was analyzed. RESULTS: Multiple logistic regression analysis showed that expression of FABP4 correlated with tumor size and mitotic index. Furthermore, FABP4 level, tumor size, mitotic index, and high AFIP-Miettinen risk were independent prognostic factors in GISTs. The Kaplan-Meier survival curve showed that the 5-year survival rate of patients with high-FABP4 expression GISTs was lower. CONCLUSIONS: These results suggested that high-FABP4 expression might be a marker of malignant phenotype of GISTs and poor prognosis.

Avapritinib Versus Regorafenib in Locally Advanced Unresectable or Metastatic GI Stromal Tumor: A Randomized, Open-Label Phase III Study.

PURPOSE: Primary or secondary mutations in KIT or platelet-derived growth factor receptor alpha (PDGFRA) underlie tyrosine kinase inhibitor resistance in most GI stromal tumors (GISTs). Avapritinib selectively and potently inhibits KIT- and PDGFRA-mutant kinases. In the phase I NAVIGATOR study (NCT02508532), avapritinib showed clinical activity against PDGFRA D842V-mutant and later-line KIT-mutant GIST. VOYAGER (NCT03465722), a phase III study, evaluated efficacy and safety of avapritinib versus regorafenib as third-line or later treatment in patients with unresectable or metastatic GIST. PATIENTS AND METHODS: VOYAGER randomly assigned patients 1:1 to avapritinib 300 mg once daily (4 weeks continuously) or regorafenib 160 mg once daily (3 weeks on and 1 week off). Primary end point was progression-free survival (PFS) by central radiology per RECIST version 1.1 modified for GIST. Secondary end points included objective response rate, overall survival, safety, disease control rate, and duration of response. Regorafenib to avapritinib crossover was permitted upon centrally confirmed disease progression. RESULTS: Four hundred seventy-six patients were randomly assigned (avapritinib, n = 240; regorafenib, n = 236). Median PFS was not statistically different between avapritinib and regorafenib (hazard ratio, 1.25; 95% CI, 0.99 to 1.57; 4.2 v 5.6 months; P = .055). Overall survival data were immature at cutoff. Objective response rates were 17.1% and 7.2%, with durations of responses of 7.6 and 9.4 months for avapritinib and regorafenib; disease control rates were 41.7% (95% CI, 35.4 to 48.2) and 46.2% (95% CI, 39.7 to 52.8). Treatment-related adverse events (any grade, grade ≥ 3) were similar for avapritinib (92.5% and 55.2%) and regorafenib (96.2% and 57.7%). CONCLUSION: Primary end point was not met. There was no significant difference in median PFS between avapritinib and regorafenib in patients with molecularly unselected, late-line GIST.

Ripretinib intrapatient dose escalation after disease progression provides clinically meaningful outcomes in advanced gastrointestinal stromal tumour.

PURPOSE: Ripretinib is a switch-control tyrosine kinase inhibitor that broadly inhibits KIT and platelet-derived growth factor receptor α kinase signalling. Ripretinib showed preliminary efficacy in patients with advanced gastrointestinal stromal tumour (GIST) in a phase I study across a range of doses. Results were confirmed in the phase III INVICTUS study, and ripretinib 150 mg once daily (QD) was subsequently approved as a ≥fourth-line therapy. Here, we report the phase I study results of intrapatient dose escalation (IPDE) in patients with GIST treated across second, third and later lines of therapy. METHODS: Patients with advanced GIST who experienced disease progression (PD) at ripretinib 150 mg QD could dose escalate to 150 mg twice daily (BID). Progression-free survival (PFS) 1 was calculated from the date of the first dose of ripretinib 150 mg QD to PD (as per Response Evaluation Criteria in Solid Tumours 1.1); PFS2 was from the date of IPDE (150 mg BID) to PD or death. Treatment-emergent adverse events (TEAEs) were summarised by dosing periods and compared descriptively. RESULTS: Of 142 patients with GIST receiving ripretinib 150 mg QD, 67 underwent IPDE. IPDE provided benefit across all lines of therapy; the median PFS2 was 5.6, 3.3 and 4.6 months for patients on second-, third- and ≥fourth-line therapy, respectively. A partial metabolic response after IPDE was demonstrated in 13 of 37 patients with available positron emission tomography scans. TEAEs reported at both doses were similar. CONCLUSION: Ripretinib IPDE after PD provided continued clinical benefit in advanced GIST across second, third and later lines of therapy with a similar safety profile to that observed with the QD regimen.

Clinicopathological Features and Outcomes of Gastrointestinal Stromal Tumours in Oman: A multi-centre study.

OBJECTIVES: This study aimed to report the clinicopathological features, management and long-term outcomes of patients with gastrointestinal stromal tumours (GISTs) in Oman. METHODS: This retrospective study was conducted on patients treated for GIST between January 2003 and December 2017 at three tertiary referral centres in Muscat, Oman. All patients with confirmed histopathological diagnoses of GIST and followed-up at the centres during this period were included. Relevant information was retrieved from hospital records until April 2019. RESULTS: A total of 44 patients were included in the study. The median age was 55.5 years and 56.8% were female. The most common primary site of disease was the stomach (63.6%) followed by the jejunum/ileum (18.2%). Two patients (4.5%) had c-Kit-negative, discovered on GIST-1-positive disease. A total of 24 patients (54.5%) presented with localised disease and eight (33.3%) were classified as being at high risk of relapse. Patients with metastatic disease received imatinib in a palliative setting, whereas those with completely resected disease in the intermediate and high-risk groups were treated with adjuvant imatinib. Of the six patients (13.6%) with progressive metastatic disease, of which four had mutations on exon 11 and one on exon 9, while one had wild-type disease. Overall, rates of progression-free survival and overall survival (OS) at 100 months were 77.4% and 80.4%, respectively. Rates of OS for patients with localised and metastatic disease were 89.9% and 80.2%, respectively. CONCLUSION: The presenting features and outcomes of patients with GISTs in Oman were comparable to those reported in the regional and international literature.

Prognostic Value of Bleeding in Gastrointestinal Stromal Tumors: A Meta-Analysis.

BACKGROUND: Gastrointestinal bleeding is the most common clinical manifestation of gastrointestinal stromal tumor. It is of great significance to the prognosis of patients. But the results are controversial. The purpose of this study was to evaluate the relationship between gastrointestinal bleeding and clinical prognosis in patients with GIST. METHODS: A systematic literature search was performed in Pumbed, Cochrane Library, EMBASE, ClinicalTrials.gov, CNKI, VIP and wanfang databases with the pattern of unlimited languages. 12 studies with 2781 individuals were included in the final analysis. The overall survival (OS), recurrence-free survival/disease-free survival (RFS/DFS) and related factors affecting bleeding in patients with gastrointestinal stromal tumor (GIST) were extracted. Hazard ratio (HR) and 95% confidence interval (CI) were used for in the meta-analysis. RESULTS: A total of 12 articles were included in the study, including 2781 patients with GIST, including 845 patients with gastrointestinal bleeding. The OS of GIST patients with gastrointestinal bleeding was significantly worse (HR = 2.54, 95% CI = 1.13-5.73, P = 0.025). But there was no significant difference in RFS between gastrointestinal bleeding patients and non-bleeding patients (HR = 1.35, 95% CI = 0.70-2.61, P = 0.371). Further analysis of the related factors of GI bleeding in GIST patients was observed, besides the aging factor (HR = 1.02, 95% CI = 0.69-1.50, P = 0.929), Small intestinal stromal tumor (HR = 0.56, 95% CI = 0.41-0.76, P < 0.001), tumor diameter ≥ 5 cm (HR = 2.09, 95% CI = 1.20-3.63, P = 0.009), Mitotic index ≥ 5/50 HPF (HR = 1.66, 95% CI = 1.11-2.49, P = 0.014) and tumor rupture (HR = 2.04, 95% CI = 1.0-3.82, P = 0.026) all increased the risk of GI bleeding in patients with GIST. CONCLUSIONS: The OS of GIST patients with GI bleeding was worse than non-GI bleeding, but had no significant effect on RFS. Nevertheless the aging factor, the location of GIST in the small intestine, tumor diameter ≥ 5 cm, Mitotic index ≥ 5/50 HPF and tumor rupture all increased the risk of GI bleeding in patients with GIST.

The effect of neoadjuvant imatinib therapy on outcome and survival in rectal gastrointestinal stromal tumors: A multiinstitutional study.

BACKGROUND AND OBJECTIVES: This study aimed to characterize the efficacy of neoadjuvant imatinib in rectal gastrointestinal stromal tumors (GISTs) and the prognostic characteristics of patients after surgery. METHODS: Patients with rectal GISTs who received neoadjuvant imatinib between 2000 and 2019 were selected from 11 large-scale tertiary hospitals in China. The best response to neoadjuvant imatinib was assessed. Propensity score matching (PSM) was conducted to reduce confounders. Recurrence free survival (RFS) and overall survival (OS) were estimated using Kaplan-Meier method. RESULTS: Of the 100 patients, 75, 18, and 7 had a partial response (PR), stable disease (SD), and progressive disease (PD), respectively. The median tumor size decreased from 5 cm before treatment to 4 cm after treatment (p < 0.001). A total of 31 patients underwent genetic testing after surgery; 23 of patients with exon 11 mutation had PR and 2 had SD. One of the patients with exon 9 mutation had PR, 2 had SD, and 1 had PD. Two patients with the wild type GIST had PD. A total of 86 patients underwent surgery of which 85 underwent complete resection; 72 underwent anal preservation and 40 underwent local excision (LE). After PSM, patients who received neoadjuvant therapy had higher rates of LE (p = 0.001) and anal preservation (p = 0.033) than those of patients without neoadjuvant therapy. The median follow-up time was 37 months. Nine patients experienced recurrence and one patient died. The 3-year RFS and OS rates were 95.0% and 100%, respectively. After PSM, we found that there was no significant difference in RFS between patients who received or did not receive neoadjuvant therapy (p = 0.623). Univariate analysis showed postneoadjuvant tumor size (p = 0.469) and mitotic count (p = 0.294) were not associated with the RFS in patients who received neoadjuvant imatinib. CONCLUSIONS: Neoadjuvant imatinib can shrink rectal GIST size, increasing the possibility of complete resection and anal preservation. Further studies are warranted to understand the long-term outcomes of rectal GISTs in patients receiving neoadjuvant imatinib.