El-Matbouly MA, Al-Thani H, El-Menyar A, Al-Sulaiti M, Asim M, Al Yaseen M, Suliman A, Albahrani A, Al-Bozom I, Tabeb A. Evolving patterns of gastrointestinal stromal tumor presentation, management, and outcome over three decades: A Middle Eastern retrospective study. World J Clin Oncol 2026; 17(6): 120388 [DOI: 10.5306/wjco.120388]
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Ayman El-Menyar, MD, Department of Surgery, Hamad Medical Corporation, Al-Rayyan Street, Doha 3050, Qatar. aymanco65@yahoo.com
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Oncology
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El-Matbouly MA, Al-Thani H, El-Menyar A, Al-Sulaiti M, Asim M, Al Yaseen M, Suliman A, Albahrani A, Al-Bozom I, Tabeb A. Evolving patterns of gastrointestinal stromal tumor presentation, management, and outcome over three decades: A Middle Eastern retrospective study. World J Clin Oncol 2026; 17(6): 120388 [DOI: 10.5306/wjco.120388]
Moamena Ahmed El-Matbouly, Hassan Al-Thani, Ayman El-Menyar, Maryam Al-Sulaiti, Mohammad Al Yaseen, Ahmed Suliman, Ahmed Albahrani, Abdelhakem Tabeb, Department of Surgery, Hamad Medical Corporation, Doha 3050, Qatar
Co-first authors: Moamena Ahmed El-Matbouly and Hassan Al-Thani.
Author contributions: El-Matbouly MA, Al-Thani H, and El-Menyar A contributed to conceptualization; El-Matbouly MA, Al-Thani H, Al-Sulaiti M, Asim M, Al Yaseen M, Suliman A, Albahrani A, Al-Bozom I, and Tabeb A contributed to methodology; El-Matbouly MA, Al-Thani H, Al Yaseen M, Suliman A, Albahrani A, Al-Bozom I, and Tabeb A contributed to data curation; Asim M, and El-Menyar A contributed to formal analysis; El-Matbouly MA, Al-and Thani H contributed to writing-original draft preparation; El-Matbouly MA, Al-Thani H, Al Yaseen M, Suliman A, Albahrani A, Al-Bozom I, Tabeb A, El-Menyar A, and Asim M contributed to writing review and editing. All authors have read and agreed to the published version of the manuscript. El-Matbouly MA and Al-Thani H contributed equally to this work as co-first authors.
AI contribution statement: Grammarly was used only for language polishing.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of Hamad Medical Corporation, Doha, Qatar, No. 13269/13, No. MRC-01-20-958 and No. MRC-01-25-1067.
Informed consent statement: This study was approved with a waiver of informed consent from the medical research center at Hamad Medical Corporation, Doha, Qatar IRB 13269/13; MRC-01-20-958 and MRC-01-25-1067), as data were collected anonymously, retrospectively, and without direct contact with patients.
Conflict-of-interest statement: The authors declare no conflict of interest.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Data sharing statement: All data are presented in the manuscript, figures, and tables. It will be available upon reasonable request and upon approval by the medical research center of Hamad Medical Corporation, upon signing a data-sharing agreement form.
Corresponding author: Ayman El-Menyar, MD, Department of Surgery, Hamad Medical Corporation, Al-Rayyan Street, Doha 3050, Qatar. aymanco65@yahoo.com
Received: February 25, 2026 Revised: March 11, 2026 Accepted: May 22, 2026 Published online: June 24, 2026 Processing time: 117 Days and 12.1 Hours
Abstract
BACKGROUND
Gastrointestinal stromal tumor (GIST) represent the most common mesenchymal neoplasms of the gastrointestinal tract, with evolving management driven by advances in molecular profiling, targeted therapy, and minimally invasive surgical techniques. However, longitudinal regional data describing real-world outcomes remain limited.
AIM
To evaluate trends in presentation, surgical management, risk stratification, and outcomes of GIST over three decades in a Middle Eastern tertiary referral center.
METHODS
A retrospective cohort study included patients with GIST who were managed between 1995 and 2024. We analyzed demographic, clinicopathological, radiological, and treatment-related variables. We compared clinicopathological characteristics across risk stratification groups (low-, intermediate-, and high-risk) and by surgical approach (open vs minimally invasive). Survival outcomes were evaluated using Kaplan-Meier analysis.
RESULTS
A total of 282 patients were included. The mean age was 53.4 ± 13.5 years, and 64.9% were male. Gastric tumors predominated (67.7%), followed by small-bowel GIST (21.3%). Most tumors were localized at presentation (64.5%), while 12.8% had distant metastases. The median tumor size was 5.5 cm (range 0.3-29.0). Mitotic count was ≤ 5 per 50 high-power field in 66.2%, 6-10 in 19.7%, and > 10 in 14.1%. Risk categories included low (57.1%), intermediate (14.2%), and high (28.7%). Resection was performed in 94.3% of cases (open 46.6%, laparoscopic 42.9%, robotic 10.5%), and R0 margins were achieved in 85.5% of cases. Minimally invasive surgery (MIS) made up 53.4% of resections. It was associated with smaller tumors, more localized disease, fewer positive margins, and shorter hospital stay compared with open surgery. Adjuvant or systemic therapy was given in 51.4% of patients, predominantly imatinib. Median hospital stay was 8 days (1-60). Over a median follow-up of 35.5 months, disease-free survival (DFS) was 82.3%. A total of 10.6% were alive with recurrence or metastases, and 7.1% died. Incidental GIST detection during bariatric surgery occurred in 8.9% of cases. The surgical approach, both laparoscopic [hazard ratio (HR) 2.454, 95% confidence interval (CI): 1.604-3.754, P < 0.001] and robotic resections (HR 2.936, 95%CI: 1.682-5.124, P < 0.001), were significantly associated with improved DFS compared with open surgery.
CONCLUSION
This study found that most GISTs were gastric in origin. Over three decades, the region showed a shift toward MIS, more molecularly guided and risk-adapted therapy, and improved outcomes. High rates of complete resection and favorable DFS underscore the effectiveness of multidisciplinary care. These region-specific findings provide important benchmarks to shape practice and future collaboration across centers.
Core Tip: Gastrointestinal stromal tumors (GIST) represent the most common mesenchymal neoplasms of the gastrointestinal tract, with evolving management driven by advances in molecular profiling, targeted therapy, and minimally invasive surgical techniques. However, longitudinal regional data describing real-world outcomes remain limited. This study aimed to evaluate trends in presentation, surgical management, risk stratification, and outcomes of GIST over three decades in a Middle Eastern country. Gastric primary tumors were the most common GIST. Over three decades, the management of GIST in this regional cohort has evolved toward increased adoption of minimally invasive surgery, molecularly guided therapy, and risk-adapted treatment strategies. High rates of complete resection and favorable disease-free survival highlight the effectiveness of multidisciplinary care. These findings provide region-specific benchmarks to inform clinical practices and future collaborations across multiple centers.
Citation: El-Matbouly MA, Al-Thani H, El-Menyar A, Al-Sulaiti M, Asim M, Al Yaseen M, Suliman A, Albahrani A, Al-Bozom I, Tabeb A. Evolving patterns of gastrointestinal stromal tumor presentation, management, and outcome over three decades: A Middle Eastern retrospective study. World J Clin Oncol 2026; 17(6): 120388
Gastrointestinal stromal tumors (GISTs) account for about 1%-2% of all gastrointestinal tumors. The estimated annual incidence is 10-15 cases per million population[1]. GISTs are the most common mesenchymal neoplasms of the gastrointestinal tract and are usually driven by activating KIT or PDGFRA mutations[2]. Immunohistochemically, GISTs show strong CD117 expression (80%-90%) with frequent CD34 positivity (60%-70%). These findings are key for diagnostic confirmation[3]. Current guidelines recommend contrast-enhanced computed tomography (CT) for staging, selective endoscopic ultrasound-guided tissue sampling, and comprehensive molecular profiling for prognostic and therapeutic assessment[4-6].
Anatomically, GISTs most commonly arise in the stomach (about 60%) and proximal small intestine (around 30%), though they can occur anywhere along the gastrointestinal tract[1]. Clinically, these tumors show a wide spectrum, ranging from incidental lesions detected during imaging or surgery[7] to aggressive metastatic disease, which is reported in about 15%-47% of cases[8]. To better estimate malignant potential, the modified National Institutes of Health developed a risk stratification system based on tumor size and mitotic activity, classifying tumors as very low-, low-, intermediate-, or high-risk[9]. This system has been widely validated as a reliable predictor of recurrence and metastatic progression[10].
For localized disease, complete surgical resection with negative margins (R0) is the cornerstone of treatment. Tumor rupture should be avoided. For unresectable or metastatic cases, continuous imatinib therapy is standard, with sunitinib, regorafenib, and ripretinib as next options for tumors with KIT/PDGFRA mutations[11]. Avapritinib is preferred for PDGFRA exon 18 mutations, including D842V, which are resistant to imatinib[12]. A 10-year analysis of the SSGXVIII/AIO trial showed an overall survival benefit with 3 years of adjuvant imatinib vs 1 year[13]. The IMADGIST phase III trial suggested extending adjuvant imatinib to 6 years can further reduce recurrence in select very high-risk patients[14]. Advances in surgery have allowed more minimally invasive surgery (MIS) for appropriately selected gastric GIST. Recent studies show that MIS has oncologic outcomes and perioperative advantages comparable to those of open surgery. Robotic approaches are also emerging in specialized centers[15,16]. Despite these advances, contemporary data on integrating risk stratification, evolving surgical strategies, and clinicopathological features remain limited. Therefore, this study aimed to evaluate the prevalence, characteristics, management, and outcomes of patients with GISTs. The study also examined associations between risk stratification, surgical approach, and clinicopathological features at a tertiary care hospital.
MATERIALS AND METHODS
A retrospective observational study was conducted, including all consecutive patients with primary GIST who underwent surgical resection and follow-up at Hamad General Hospital (HGH), the only tertiary center in Doha, Qatar, between January 1995 and December 2024. The diagnosis of GIST was established based on histopathological and immunohistochemical criteria, including: (1) Tumor location within or adjacent to the gastrointestinal tract, mesentery, omentum, or retroperitoneum; (2) Spindle and/or epithelioid morphological features consistent with GIST; and (3) Unequivocal immunoreactivity for CD117. Eligible cases were identified from the institutional surgical database at HGH, and clinical data were retrieved from the electronic medical record system (Cerner) at Hamad Medical Corporation in Qatar.
Data analysis included demographics (age, sex), clinical history and presentation, radiological investigations [plain radiography, ultrasonography, CT scan, magnetic resonance imaging (MRI), barium studies, and endoscopy]. Tumor-related variables comprised primary tumor location, local organ invasion, distant metastases, histological subtype (spindle cell type, epithelioid type mixed type, and unspecified), histological type (spindle cell, epithelioid, mixed, or unspecified), tumor size, mitotic index [per 50 high-power fields (HPF)], presence of tumor necrosis, and immunohistochemical expression of CD117, CD34, smooth-muscle actin, and S-100 protein. Risk stratification was performed according to established consensus criteria based on maximal tumor size and mitotic activity[17]. Management variables included chemotherapy, radiation therapy, and surgical approach (open, laparoscopic, robotic). Study outcomes included disease-free survival (DFS), recurrent or metastatic progression, and mortality.
DFS is defined as the interval from surgical resection of the tumor to the first documented evidence of disease recurrence. Assessment of recurrence in GIST patients was made based on tumor size, mitotic activity, and the anatomical location of the primary lesion.
Risk categories were defined as follows: (1) Very low risk (< 2 cm and < 5 mitoses/50 HPF) and low risk (2-5 cm and < 5 mitoses/50 HPF); (2) Intermediate risk (< 5 cm with 6-10 mitoses/50 HPF or 5-10 cm with < 5 mitoses/50 HPF); and (3) High risk (> 5 cm with > 5 mitoses/50 HPF or > 10 cm regardless of mitotic activity).
GIST mutation: Before 2009, all the patients were treated with imatinib empirically without mutation testing. Biomarker testing for GIST started at our center in 2009 with a very selective patient (high risk). Recently, more patients were tested because different mutations respond to different drugs and different dosing.
This retrospective study was approved by the Medical Research Center at Hamad Medical Corporation, Doha, Qatar (IRB 13269/13; MRC-01-20-958 and MRC-01-25-1067), with a waiver of informed consent. All data were collected anonymously, and the study adhered to the STROBE guidelines.
Statistical analysis
Data are presented as percentages, mean ± SD for normally distributed continuous variables, and median with range for non-normally distributed data, when applicable. Normality was assessed using the Shapiro-Wilk test prior to applying parametric analyses. Clinicopathological characteristics were compared across risk stratification (low-, intermediate-, and high-risk) and surgical approach (open vs minimally invasive). The χ2 test (or Fisher’s exact test) was used for categorical variables. In contrast, student’s t-test or one-way analysis of variance (ANOVA) was used for normally distributed continuous variables. Nonparametric data were analyzed using the Mann-Whitney U test or Kruskal-Wallis test. Survival outcomes were estimated using the Kaplan-Meier method and compared using the log-rank test. Additionally, multivariable Cox proportional hazards regression was performed to evaluate DFS while adjusting for potential confounders, including age, tumor size, mitotic index, risk category, tumor location, surgical approach, and chemotherapy use. Hazard ratios (HR) with 95% confidence interval (CI) are reported. A two-tailed P value < 0.05 was considered statistically significant. All analyses were performed using SPSS version 21.0 (IBM Corp., Chicago, IL, United States).
RESULTS
Study cohort and baseline characteristics
During the study period, 282 patients underwent evaluation and management for GIST. The mean age at surgery was 53.4 ± 13.5 years, and the majority were male (64.9%), with Qatari nationals comprising 18.4% of the cohort (Table 1). At presentation, 64.5% of tumors were localized to the primary organ, 22.0% demonstrated locally advanced disease involving adjacent gastrointestinal structures, and 12.8% had distant metastases. The stomach was the most common primary site (67.7%), followed by the small bowel (21.3%), duodenum (5.3%), rectum (2.8%), omentum (2.1%), and less frequent locations including the esophagus (1.1%), colon (1.4%), and retroperitoneum (0.4%).
Table 1 Demographics and clinical presentation of gastrointestinal stromal tumor patients (n = 282), n (%).
Abdominal pain was the most common presenting symptom (67.0%), followed by melena or hematemesis (39.7%), vomiting (30.1%), fatigue related to anemia (21.3%), and bowel obstruction (4.6%). The distribution of presenting symptoms is illustrated in Figure 1. CT was the most frequently performed imaging modality (81.9%), followed by endoscopy (60.3%). Ultrasonography (40.1%), MRI (31.6%), plain radiography (25.5%), and barium studies (7.1%) were used selectively based on clinical indication. Representative imaging of gastric and small-bowel GISTs is shown in Figures 2 and 3.
Figure 2 Coronal and cross-sectional computed tomography scan cuts of gastric gastrointestinal stromal tumor, showing the exophytic component of the gastric tumor with proximity to the left lobe of the liver.
Computed tomography scans showing gastric gastrointestinal stromal tumor: A large heterogeneous hypodense lobulated partly exophytic mass measuring about 10.5 cm in maximal dimension was noted at the gastric fundus, showing ulceration of its intraluminal component; superiorly, it abutted the left hemidiaphragm (probable infiltrate) and the lateral aspect of the left hepatic lobe.
Figure 3 The radiological images of the small-bowel gastrointestinal stromal tumor.
A: A large heterogeneously enhancing mass measuring approximately 18.2 cm × 10.7 cm × 2.3 cm in the mid and lower abdomen, demonstrating hypodense areas and a large central area of necrosis. The mass appeared to arise/communicate with the loop of the ileum with oral contrast and air within the necrotic region; B: Radiodense soft-tissue mass arising from the jejunal loops in the right lower quadrant and hemipelvis; C: It measures 7.2 cm × 7.2 cm × 6.2 cm (maximum AP, transverse, and CC, respectively).
Pathology and immunohistochemistry
Histopathological evaluation demonstrated spindle cell morphology in 56.4% of cases, mixed histology in 18.4%, epithelioid subtype in 6.4%, and unspecified histology in 18.8%. Among tested specimens, immunohistochemical positivity was observed for CD117 in 79.9%, CD34 in 66.7%, smooth-muscle actin in 34.2%, and S-100 protein in 7.7% (Figure 4).
Figure 4 Example of microscopic view and immunohistochemistry of gastrointestinal stromal tumor.
A: Light microscopic view of gastrointestinal stromal tumor (GIST) tumors occupying the submucosa and muscularis propria, notice normal gastric mucosa in the left upper corner [hematoxylin and eosin (H&E) staining × 20]; B: High power light microscopic appearance of GIST tumor characterized by fascicles of spindle cells (H&E × 600); C: GIST tumor cells stain strongly and diffusely positive with DOG-1 antibody (Immunohistochemistry × 200); D: GIST tumor cells stain strongly and diffusely positive with CD117 antibody (Immunohistochemistry × 200).
Tumor size, mitotic index, necrosis, and risk stratification
The median tumor size was 5.5 cm (range 0.3-29.0). Tumor size distribution was ≤ 2 cm in 13.2%, > 2-5 cm in 31.6%, > 5-10 cm in 38.2%, and > 10 cm in 16.9%. Representative intraoperative images of the gastric GIST and GIST of the small bowel are shown in Figures 5 and 6, respectively. Mitotic count was ≤ 5/50 HPF in 66.2%, 6-10/50 HPF in 19.7%, and > 10/50 HPF in 14.1%. Tumor necrosis was present in 34.7% of cases. According to consensus risk criteria, tumors were classified as low risk in 57.1%, intermediate risk in 14.2%, and high risk in 28.7%.
Figure 5 Multiple intraoperative and post-operative images of the gastric gastrointestinal stromal tumor.
Gastrointestinal stromal tumors of the stomach with umbilicated ulcers within tumors that usually bleed and present with melena.
Figure 6 Multiple intraoperative small bowel gastrointestinal stromal tumors.
Management
Most tumors were completely resectable (94.3%), whereas 5.7% were deemed unresectable and managed with partial procedures or open biopsy (Table 2). Surgical approaches included open surgery (46.6%), laparoscopic resection (42.9%), and robotic surgery (10.5%). R0 resection was achieved in 85.5%, and R1 resection at 11.7%. Chemotherapy was administered to 51.4% of patients, predominantly imatinib, with a small proportion receiving sunitinib; radiotherapy was used in 1.1%. Post-operative transfusion within 24 hours was required in 24.8% (median 1 unit, IQR 1-4). The most common postoperative complications were bleeding (3.9%), followed by infection (3.2%), deep venous thrombosis (1.8%), and anastomotic leakage (1.8%). The median length of hospital stay was 8 days (range 1-60).
Table 2 Management and outcome of gastrointestinal stromal tumor cases, n (%).
Other than GIST cancer during follow-up, 19 patients had cancer other than GIST during follow-up (4 had colon cancer, 4 had breast cancer, 2 had rectal cancer, 3 had Gastro-esophageal cancer, 2 had chronic myeloid leukemia, 1 had tongue cancer, 1 had lung cancer, 1 had renal cell carcinoma and 1 had prostate cancer). 2 patients had two cancer types than GIST during follow-up (1 had prostate and lymphoma, 1 had esophageal and lung cancer)
Over a median follow-up of 35.5 months (range 1-252), DFS was 82.3%. At the last follow-up, 10.6% of patients were alive with recurrent or metastatic disease, and 7.1% had died. Reported causes of death were primarily advanced hemorrhagic GIST (45%), followed by metastatic disease (15%), coronary artery disease (10%), intracranial hemorrhage (10%), sepsis or urinary tract infection (UTI) (5%), and unknown causes (15%). Loss to follow-up after surgery occurred in 19.1% of patients. Incidental GIST detection after sleeve gastrectomy was observed in 8.9% of cases, and 4.6% required multiple surgical procedures. Non-GIST secondary malignancies developed in 7.4% of patients, with some individuals experiencing more than one malignancy during follow-up.
The clinicopathological characteristics of risk stratification are outlined in Table 3. Demographics and clinical history were comparable among the three groups. Among presenting symptoms, vomiting was more frequently observed in high-risk tumors compared with low- and intermediate-risk groups (40.7% vs 26.7% and 22.5%, P = 0.04), while other symptoms showed no statistically significant difference. Imaging utilization also differed: High-risk tumors underwent more plain radiography (P = 0.04), whereas barium studies were more common in intermediate-risk disease (P = 0.003). Intermediate-risk tumors were more often localized to the primary organ (87.5%), while locally advanced disease and distant metastases were significantly more frequent in the high-risk group (P = 0.001 and P = 0.01, respectively). Histologically, spindle cell morphology was more prevalent in low- and intermediate-risk tumors, whereas epithelioid and mixed patterns were more common among high-risk tumors (P = 0.001). Immunohistochemical expression of CD34 increased with risk category (P = 0.01), while CD117, SMA, and S-100 expression showed no significant differences.
Table 3 Demographics and clinical presentation of gastrointestinal stromal tumor patients based on risk stratification, n (%).
Table 4 compares management and outcomes across risk strata. Tumor size distribution differed significantly among the three groups, with intermediate-risk tumors more commonly measuring 5-10 cm and high-risk tumors more frequently exceeding 10 cm (P = 0.05). Mitotic activity is also strongly associated with risk classification, with higher mitotic counts observed in high-risk tumors (P = 0.001). Tumor necrosis was more common in intermediate- and high-risk disease but did not reach statistical significance. Complete resection with negative margins was achieved in all intermediate-risk cases and in most low-risk tumors.
Table 4 Management and outcome of gastrointestinal stromal tumor cases based on risk stratification, n (%).
In contrast, high-risk tumors demonstrated lower R0 resection rates and a higher proportion of positive margins (P = 0.001). The surgical approach did not differ significantly between the groups. Chemotherapy use was significantly higher among intermediate- and high-risk patients (P = 0.001). Postoperative complications, transfusion requirements, and length of hospital stay were similar across groups. Although overall DFS did not differ significantly, the mortality rate was higher in the high-risk cohort.
Comparison by surgical approach (Table 5) showed that patients undergoing MIS were more likely to present with localized disease, whereas open surgery was more frequently performed for locally advanced tumors (P = 0.001). Tumors treated with open surgery were significantly larger (median 8 cm vs 5 cm, P = 0.001) and more commonly located in the small bowel (P = 0.001). Endoscopy was more frequently utilized in patients managed with MIS (P = 0.001).
Table 5 Comparison of clinico-pathological characteristics based on surgical approach, n (%).
R0 resection rates were significantly higher in the MIS group compared with open surgery (P = 0.03). Although chemotherapy utilization and transfusion rates were similar between approaches, open surgery was associated with longer hospital stay (P = 0.009) and higher postoperative bleeding rates (P = 0.005). Incidental GIST detection following sleeve gastrectomy was more frequent in the MIS cohort (P = 0.001). Furthermore, MIS was associated with higher DFS and lower mortality compared with open surgery (P = 0.003), although differences in risk stratification between groups were not statistically significant (P = 0.34). Kaplan-Meier survival analysis (log-rank test) showed a significant difference in mortality among the three risk-stratified groups (P = 0.001; Figure 7).
Figure 7 Kaplan Meier survival analysis based on risk stratification.
GIST mutation testing before imatinib therapy
One hundred and forty-five patients (51.4%) received imatinib; of these, 46 (31.7%) underwent mutation testing, as shown in Figure 8. Primary KIT mutations occurred in 72% of those who were tested (n = 33/46). Exon 11 mutations were found in 30 patients (91.9%), while Exon 9 mutations were found in 6 patients (18.1%). A PDFGA mutation was observed in 30% (n = 6/20), and an EGFRA mutation was observed in 1 patient (n = 1/11).
An increasing trend in the GIST incidence was observed over the three decades (Figure 9). Table 6 demonstrated significant evolution in surgical management over the three decades. Open surgery predominated during 1995-2004 (92.0%) and remained common in 2005-2014 (76.4%) but markedly declined in 2015-2024 (21.7%), coinciding with a substantial increase in laparoscopic resections (8.0%, 16.9%, and 63.8%, respectively) and adoption of robotic surgery in the most recent decade (0%, 6.7%, and 14.5%, respectively; P = 0.001). Chemotherapy utilization increased progressively over time (32.0%, 50.0%, and 55.3%) but did not reach statistical significance (P = 0.09). Radiotherapy use declined significantly over time (P = 0.04).
Regarding outcomes, DFS differed significantly across periods (92.0% in 1995-2004, 71.9% in 2005-2014, and 87.0% in 2015-2024; P = 0.01). The proportion of patients surviving with recurrent or metastatic disease was highest during 2005-2014 (17.7%) compared to other groups. Mortality rates showed a decreasing trend in the most recent decade (8.0%, 10.4%, and 5.0%, respectively), although differences were not statistically significant.
Multivariable analysis of DFS
On multivariable Cox proportional hazards regression analysis, increasing tumor size was significantly associated with disease recurrence (HR 0.915, 95%CI: 0.865-0.968, P = 0.002).
Also, surgical approach, both laparoscopic (HR 2.454, 95%CI: 1.604-3.754, P < 0.001) and robotic resections (HR 2.936, 95%CI: 1.682-5.124, P < 0.001) were significantly associated with improved DFS compared with open surgery (Figure 10 and Table 7).
This is an updated longitudinal study describing the epidemiology, clinical presentation, management strategies, and outcomes of GISTs over three decades in a Middle Eastern population. We observed a progressive increase in the annual incidence of diagnosed GIST cases in Qatar, likely reflecting advances in molecular diagnostics, improved imaging modalities, and greater clinical awareness[18]. Earlier institutional data reported a lower incidence between 1995 and 2012[19], a pattern also reflected in our temporal analysis. Key findings of the present study include the predominance of gastric primaries (67.7%), median tumor size of 5.5 cm, and a predominance of low-risk disease (57.1%). High rates of complete (R0) resection (85.5%) and favorable DFS approaching 82% at a median follow-up of 35.5 months align with contemporary international benchmarks emphasizing early detection, adherence to oncologic principles, and multidisciplinary management[4,20].
Importantly, temporal analysis revealed a marked shift in surgical strategy and in the utilization of adjuvant therapy over the three decades. Open surgery, which predominated in the earliest period, declined substantially in the most recent decade, while laparoscopic and robotic resections increased significantly. This transition reflects growing institutional expertise, improved perioperative care, and adherence to evolving international guidelines supporting minimally invasive approaches in appropriately selected patients[21]. Concurrently, chemotherapy utilization increased progressively, while radiotherapy use declined significantly, consistent with the expanding role of risk-adjusted adjuvant imatinib and the limited therapeutic value of radiotherapy in GIST. Notably, DFS improved in the most recent decade following a relative decline in the intermediate period, suggesting that advances in surgical technique, patient selection, and targeted adjuvant therapy may have collectively contributed to improved outcomes[22]. Although causal inference cannot be established, these findings highlighted the clinical impact of integrating MIS and molecular-guided therapy within a multidisciplinary framework.
The clinical presentation of GIST is heterogeneous, ranging from incidental detection to symptomatic disease associated with bleeding, obstruction, or mass effect[23,24]. In our cohort, abdominal pain, gastrointestinal bleeding, and vomiting were the most frequent presenting features, consistent with prior reports describing nonspecific gastrointestinal symptoms as common initial manifestations[25]. In most cases, endoscopy, along with endoscopic ultrasound, helps confirm the diagnosis by demonstrating tumor origin from the muscular layer[26]. In line with current practice, CT imaging was the most frequently used modality in our study, followed by endoscopy and ultrasonography. It has been reported that duodenal GISTs may closely mimic hypervascular pancreatic neuroendocrine tumors on imaging due to overlapping enhancement patterns and anatomical proximity, underscoring the critical need for precise preoperative differentiation given the markedly different surgical strategies and treatment approaches[27].
However, imaging alone is insufficient for definitive diagnosis. Accurate histopathological confirmation remains essential, particularly through immunohistochemical markers such as CD117 (KIT), DOG-1, and CD34, which are characteristic of GIST[28]. Furthermore, molecular profiling for KIT and PDGFRA mutations has become indispensable, not only for confirming diagnosis but also for prognostication and guiding targeted therapy with tyrosine kinase inhibitors such as imatinib[29].
Preoperative biopsy is generally avoided in resectable GIST due to concerns regarding bleeding or tumor dissemination[30], and only a small proportion of patients in our series underwent CT-guided biopsy. Diagnostic pathways are strengthened by endoscopic ultrasonography for subepithelial lesions and by evidence comparing fine-needle aspiration vs biopsy for tissue acquisition[26,31].
From a patient perspective, the most common presenting problems are abdominal pain, overt or occult bleeding, vomiting, and anemia, highlighting the importance of rapid diagnostic pathways from emergency and endoscopy units to multidisciplinary sarcoma boards. Enhanced recovery protocols, early mobilization, and anemia optimization are particularly impactful in this population. Our cohort’s transfusion needs highlight the importance of streamlined emergency diagnostic pathways, including rapid imaging, endoscopic evaluation, multidisciplinary decision-making, and early surgical intervention[4,5,20,32].
Tumor location remains a critical prognostic factor. Small intestinal GISTs are traditionally associated with more aggressive biological behavior and higher tumor-related mortality compared with gastric GISTs, particularly in tumors larger than 5 cm or with elevated mitotic activity[33]. In our series, small bowel tumors accounted for approximately one-fifth of cases, with a notable proportion demonstrating high-risk features. Histological heterogeneity and site-dependent prognosis remain central considerations in contemporary risk models[34-36].
High-risk tumors in our cohort demonstrated higher mitotic counts and were more likely to receive systemic therapy, reflecting guideline-concordant management. Randomized evidence supports adjuvant imatinib for high-risk disease, with improved overall survival observed with 3 years vs one year of therapy after complete resection[13], and emerging evidence suggesting additional benefit from extended treatment in selected very-high-risk patients[14]. Molecular profiling increasingly guides therapeutic decisions, including the use of avapritinib for PDGFRA exon 18 D842V mutation and ripretinib in later lines for KIT/PDGFRA-driven disease[5,12,37]. Radiotherapy played a limited role in our cohort and was primarily used for palliation, consistent with existing literature supporting selective use in symptom control[38].
Treatment depends on the tumor’s size and location, with surgical resection as the mainstay of management[39]. Advances in MIS, including laparoscopic and robotic techniques, have expanded treatment options for appropriately selected patients[40]. Table 8 summarizes the recent literature on the treatment options for GIST[41-46]. The laparoscopic approach has numerous advantages over the open technique. A recent meta-analysis comparing laparoscopic vs open resection for gastric GIST found that laparoscopic resection was associated with a higher overall success rate (93%) than open surgery (88%)[47]. Our findings agree with those of a previous meta-analysis, which showed that 92.6% were completely resected via a minimally invasive approach, compared with 78.1% via open surgery. Robotic-assisted laparoscopic resections, which offer technology and devices to enable technically challenging resections, address the shortcomings of the laparoscopic technique[48].
Table 8 Summary of recent studies on the treatment options for gastrointestinal stromal tumor.
1015 GIST cases between 2010-2019 received radical surgery
In intermediate-risk patients, the Ki-67 index and postoperative TKI treatment are closely related to prognosis however, if their primary tumor is the stomach, the value of TKI-targeted therapy after surgery seems not necessary
In some high-risk patients, the prognosis can be improved by prolonging the treatment time of TKI
105 GIST cases between 2019-2021 (LAP vs endoscopic)
LAP and endoscopic resection, have good curative result, safety, and prognosis in the treatment of GIST. Endoscopic resections have less trauma, faster recovery, shorter hospitalization time, and lower cost compared with LAP
177 cases with 2-5 cm gastric GISTs between 2007-2019 (endoscopic vs surgery)
The endoscopic group had shorter anal exhaust time and less hospital cost. The rate of complications and reoperation in the endoscopic group was relatively higher than the surgical group. No significant difference observed in recurrence-free survival or overall survival between two groups
LAP is usually recommended for GISTs of ≤ 5 cm diameter, and for the greater curvature of the stomach and the front wall of the fundus
Meta-analysis included 485 cases before April 2017 (open and LAP wedge resection)
The operation time was similar between the 2 groups LAP showed less blood loss earlier time to flatus, shorter hospital stays, and a decreased overall complication rate compared with open surgery
Long-term follow-up showed no obvious difference between the two groups
91 patients (LAP, laparoscopic and endoscopic cooperative surgery, or endoscopic submucosal dissection surgeries for gastric GISTs ≤ 5 cm)
The operative time and intraoperative blood loss in endoscopic submucosal dissection were significantly less than that in endoscopic cooperative surgery and LAP groups. No statistical difference was found in the postoperative recovery and complications among the three groups
The decision for a minimally invasive intervention should be according to the tumor size & location, pattern of tumor growth, and experience of surgeons
275 gastric submucosal tumors < 5 cm, 2013 to January 2017 (endoscopic vs LAP)
The endoscopic resection patients had shorter hospitalization time, postoperative hospital stay and diet recovery time. The LAP had shorter operation time, less cost and less blood loss
It is difficult to locate via LAP in some small endogenous GIST. LAP is inconvenient and difficult to expose lesions of the cardia or upper part of the stomach close to the fundus
In this study, MIS (laparoscopic/robotic) accounted for more than half of resections and was associated with more localized disease, smaller tumors, fewer positive margins, shorter length of stay, and improved DFS compared with open surgery. We also found that MIS, such as laparoscopic (HR 2.454) and robotic resections (HR 2.936), were independently associated with improved DFS compared with open surgery. These findings align with growing evidence demonstrating comparable oncologic outcomes, perioperative advantages of MIS, and the increasing feasibility of robotic approaches in specialized centers[15,16]. However, these findings should be interpreted with caution because baseline differences between the MIS and open surgery cohorts introduce selection bias and potential residual confounding. Therefore, the apparent DFS advantage of MIS should be viewed as hypothesis-generating rather than definitive evidence of causal superiority. Moreover, a 2025 propensity-weighted study focusing on 'unfavorable' gastric sites supports the feasibility of laparoscopic resection in carefully selected patients, reinforcing that the approach should be tailored to tumor size, location, and rupture risk, rather than defaulting to open surgery[16].
Studies have shown that the median survival of patients with unresectable GIST is approximately 12 months (range 2-20 months)[19]. In our study, eight patients had unresectable tumors, of which the majority were extra-gastric. Surgery alone or in combination with traditional chemotherapy or radiation therapy has been largely ineffective in treating most patients with malignant GIST[34]. Small gastric GISTs often form solid, submucosal, intramural, or inward bulging masses, and less commonly polypoid intraluminal masses. The use of radiation therapy is limited by its associated toxicity to adjacent structures; thus, radiation therapy is of uncertain value[49]. In our cohort, only three patients received radiation therapy because of the larger size of the tumor.
The study findings also provide important regional insights. Our previous institutional reports anticipated several trends confirmed in the present expanded cohort, including gastric predominance, increasing adoption of MIS, and favorable short-term outcomes following R0 resection[19,50,51]. Surgical approach, both laparoscopic (HR 2.454, 95%CI: 1.604-3.754, P < 0.001) and robotic (HR 2.936, 95%CI: 1.682-5.124, P < 0.001), was significantly associated with improved DFS compared with open surgery. However, these associations should be interpreted cautiously, given the retrospective design, potential selection bias, and residual confounding. In practice, we individualized the duration based on risk category, mutation status (e.g., KIT exon 11 vs exon 9), tolerance, and patient preference, recognizing that prolonged therapy may mitigate relapse but also add cumulative toxicity and cost. These considerations are increasingly salient in our region, where medication coverage and long-term follow-up can be inconsistent. Routine mutation testing is now standard because it guides neoadjuvant/adjuvant decisions and sequencing in advanced disease. Avapritinib provides a practical option for PDGFRA exon 18 (including D842V) mutation genotypes that are largely imatinib-insensitive, while ripretinib has become the fourth-line standard for KIT/PDGFRA-driven disease[5,12]. Ensuring timely access to molecular testing across the care pathway remains a priority; our cohort predates the introduction of universal testing, which likely contributed to the missing genotype data.
Incidental detection of GIST during bariatric surgery occurred in nearly 9% of cases, emphasizing the need for careful intraoperative inspection and standardized postoperative pathways for histopathology review, risk stratification, and multidisciplinary follow-up[52]. Given the observed loss to follow-up, improved patient engagement strategies and streamlined referral pathways may enhance long-term surveillance and adherence to adjuvant therapy.
Limitations
This study has several limitations. Its retrospective design introduces potential selection bias, and missing data, particularly regarding mitotic index and KIT/PDGFRA mutation status, may have influenced risk classification. Molecular genotyping was not routinely performed or consistently available during the earlier years of this three-decade cohort, and archival tissue was not uniformly stored or suitable for later sequencing; therefore, mutation data were unavailable for a substantial proportion of cases. In our cohort, mutation testing was performed in only one-third of patients, and the results were consistent with prior data[53]. Second, we acknowledge that the 30-year study period introduces heterogeneity due to evolving diagnostic imaging, surgical techniques, molecular testing, and standards for adjuvant therapy, which may confound comparisons of outcomes. Therefore, limit the findings to primarily descriptive and exploratory rather than causal interpretations. Third, the comparison between MIS and open surgery is subject to selection bias, as tumor size, stage, and localization differ between groups.
Additionally, loss to follow-up and incomplete long-term surveillance limit definitive assessment of recurrence patterns. Moreover, two patients died during follow-up due to unrelated causes (cerebral hemorrhage and septic shock after UTI). Also, we did not identify risk factors for disease remission and lacked information regarding local or distant recurrence. We noticed that the risk factors for recurrence in our study included tumor unreachability, lack of chemotherapy in earlier years, high mitotic rate, and high-risk features such as extra-gastric location of GIST tumors. Finally, we acknowledge that the observed increase in GIST cases over time was not adjusted for population growth, as the analysis was based on institutional data rather than population-level incidence rates. Despite these limitations, the large cohort size, unified healthcare system, and multi-decade observation period provide robust region-specific data.
CONCLUSION
The incidence of GIST in Qatar has increased over time, likely reflecting advances in diagnostic imaging, molecular testing, and clinical expertise. Gastric tumors predominated, and most lesions were amenable to complete surgical resection with favorable oncologic outcomes. Our experience demonstrates strong R0 resection rates and encouraging DFS within a contemporary Middle Eastern cohort. Expansion of MIS, routine molecular profiling, and risk-adapted adjuvant therapy remain key priorities for optimizing outcomes. Therefore, combination therapies that personalize GIST treatment and target chemotherapy are essential for optimizing patient outcomes and reducing GIST burden. Future studies should integrate molecular data, explore neoadjuvant strategies to enable organ-preserving resections, and strengthen regional collaborative registries to support comparative effectiveness analyses.
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