Evolving patterns of gastrointestinal stromal tumor presentation, management, and outcome over three decades: A Middle Eastern retrospective study

Table 1 Demographics and clinical presentation of gastrointestinal stromal tumor patients (n = 282), n (%)

Variable	Value	Variable	Value
Age at surgery (mean ± SD)	53.4 ± 13.5	Esophagus	3 (1.1)
Males	183 (64.9)	Colon	4 (1.4)
Females	99 (35.1)	Retroperitoneal	1 (0.4)
Qatari	52 (18.4)	Mesentery of small bowel1	3 (1.1)
Clinical history		Liver	1 (0.4)
Neurofibromatosis	7 (2.5)	Other sites	14 (5.0)
Familial GIST	6 (2.1)	Immunohistochemical analysis
A skin disorder	2 (0.7)	CD 117 (n = 259)	207 (79.9)
Familial urticaria pigmentosa	0 (0.0)	CD 34 (n = 252)	168 (66.7)
Clinical presentation		Smooth-muscle actin (n = 243)	83 (34.2)
Abdominal pain	189 (67.0)	S-100 protein (n = 246)	19 (7.7)
Melena/hematemesis	112 (39.7)	Maximum size of tumor (cm) (median, range) (n = 272)	5.5 (0.3-29.0)
Vomiting	85 (30.1)	Tumor size (cm)
Fatigue due to anemia	60 (21.3)	≤ 2	36 (13.2)
Bowel obstruction	13 (4.6)	> 2-5	86 (31.6)
Radiological investigations		> 5-10	104 (38.2)
Computed tomography scan	(81.9)	> 10	46 (16.9)
Endoscopy	170 (60.3)	Mitotic count (HPF) (n = 213)
Ultrasonography	113 (40.1)	≤ 5	141 (66.2)
MRI	89 (31.6)	6-10	42 (19.7)
X-ray	72 (25.5)	> 10	30 (14.1)
Barium study	20 (7.1)	Tumor necrosis (n = 262)	91 (34.7)
Localized to primary organ site	182 (64.5)	Risk stratification
Locally advanced to other GIT structures	62 (22.0)	Low-risk	161 (57.1)
Distant metastases at evaluation	36 (12.8)	Intermediate-risk	40 (14.2)
Primary location		High-risk	81 (28.7)
Stomach2	191 (67.7)
Small bowel	60 (21.3)
Duodenum	15 (5.3)
Rectum	8 (2.8)
Omentum	6 (2.1)

¹One had metastasis of the liver and other had multiple peritoneal metastasis.

²One had lymph node recurrence, and one had liver metastasis.

HPF: High power field; GIT: Gastro-intestinal tract; MRI: Magnetic resonance imaging.

Table 2 Management and outcome of gastrointestinal stromal tumor cases, n (%)

Management	Value
Resection	266 (94.3)
Unresectable (4 partial and 4 open biopsy)	8 (2.8)
CT guided biopsy only	8 (2.8)
Types of resections (n = 266)
Open	124 (46.6)
Laparoscopic resection	114 (42.9)
Robotic resection	28 (10.5)
Completely resectable with negative margin (R0)	241 (85.5)
Completely resectable with positive margin (R1)	33 (11.7)
Chemotherapy1	145 (51.4)
Radiation therapy	3 (1.1)
Blood transfusion (within 24 hours post-operation)	70 (24.8)
Blood transfusion units (within 24 hours post-operation)	1 (1-4)
Hemoglobin (before operation)	10.9 ± 2.9
Post-operative complications
Bleeding	11 (3.9)
Infection	9 (3.2)
Deep vein thrombosis	5 (1.8)
Anastomotic leaks	5 (1.8)
Hospital length of stay (days)	8 (1-60)
Follow-up period (months)	35.5 (1-252)
Outcome
Disease free survival	232 (82.3)
Survived with recurrent/metastatic disease	30 (10.6)
Death	20 (7.1)
Cause of death
Primary advance GIST tumor (hemorrhagic shock)	9 (45.0)
Coronary artery disease	2 (10.0)
Septic shock (UTI primary source)	1 (5.0)
Cerebro-vascular accident (intracranial hemorrhage)	2 (10.0)
Metastatic disease	3 (15.0)
Unknown	3 (15.0)
Lost to follow-up after surgery	54 (19.1)
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)	21 (7.4)
Incidental post sleeve gastrectomy	25 (8.9)
Multiple operations	13 (4.6)

¹The type of chemotherapy: 139 patients Imatinib and 1 had Sunitinib.

GIST: Gastrointestinal stromal tumor; UTI: Urinary tract infection; CT: Computed tomography.

Table 3 Demographics and clinical presentation of gastrointestinal stromal tumor patients based on risk stratification, n (%)

	Low-risk (n = 161)	Intermediate-risk (n = 40)	High-risk (n = 81)	P value
Age at surgery (mean ± SD)	55.1 ± 12.8	50.1 ± 12.5	51.4 ± 15.0	0.06
Males	101 (62.7)	28 (70.0)	54 (66.7)	0.63 for all
Females	60 (37.3)	12 (30.0)	27 (33.3)
Clinical history
Neurofibromatosis	4 (2.5)	0 (0.0)	3 (3.7)	0.46
A skin disorder	0 (0.0)	0 (0.0)	2 (2.5)	0.08
Familial GIST	2 (1.2)	0 (0.0)	4 (4.9)	0.10
Clinical presentation
Abdominal pain	106 (65.8)	24 (60.0)	59 (72.8)	0.32
Vomiting	43 (26.7)	9 (22.5)	33 (40.7)	0.04
Blood in stool/vomit	55 (34.2)	19 (47.5)	38 (46.9)	0.08
Fatigue due to anemia	37 (23.0)	11 (27.5)	12 (14.8)	0.20
Bowel obstruction	7 (4.3)	0 (0.0)	6 (7.4)	0.18
Radiological investigations
X-ray	34 (21.1)	9 (22.5)	29 (35.8)	0.04
Ultrasonography	67 (41.6)	16 (40.0)	30 (37.0)	0.79
Computed tomography	127 (78.9)	38 (95.0)	66 (81.5)	0.06
Barium study	5 (3.1)	7 (17.5)	8 (9.9)	0.003
MRI	54 (33.5)	11 (27.5)	24 (29.6)	0.69
Endoscopy	95 (59.0)	22 (55.0)	53 (65.4)	0.47
Localized to primary organ site	98 (60.9)	35 (87.5)	49 (60.5)	0.005
Locally advanced to other GIT structures	30 (18.6)	3 (7.5)	29 (35.8)	0.001
Distant metastases	15 (9.3)	3 (7.5)	18 (22.2)	0.01
Primary location
Stomach	103 (64.0)	28 (70.0)	60 (74.1)	0.26
Duodenum	10 (6.2)	1 (2.5)	4 (4.9)	0.63
Small bowel	33 (20.5)	13 (32.5)	14 (17.3)	0.14
Colon	4 (2.5)	0 (0.0)	0 (0.0)	0.21
Rectum	6 (3.7)	0 (0.0)	2 (2.5)	0.43
Esophagus	3 (1.9)	0 (0.0)	0 (0.0)	0.32
Omentum	0 (0.0)	2 (5.0)	4 (4.9)	0.08
Other sites	8 (5.0)	0 (0.0)	6 (7.4)	0.21
Histological type
Spindle cell type	102 (63.4)	27 (67.5)	30 (37.0)	0.001 for all
Epithelioid type	5 (3.1)	1 (2.5)	12 (14.8)
Mixed type	24 (14.9)	8 (20.0)	20 (24.7)
Unspecified	30 (18.6)	4 (10.0)	19 (23.5)
Immuno-histochemistry
CD 117 (n = 259)	114 (75.5)	31 (83.8)	62 (87.3)	0.10
CD 34 (n = 252)	87 (59.6)	26 (70.3)	55 (79.7)	0.01
SMA (n = 243)	39 (28.3)	14 (37.8)	30 (44.1)	0.06
S-100 protein (n = 246)	8 (5.8)	2 (5.4)	9 (12.9)	0.16

GIST: Gastrointestinal stromal tumor; GIT: Gastrointestinal tract; MRI: Magnetic resonance imaging.

Table 4 Management and outcome of gastrointestinal stromal tumor cases based on risk stratification, n (%)

	Low-risk (n = 161)	Intermediate-risk (n = 40)	High-risk (n = 81)
Maximum size of tumor (cm)	5.3 (0.3-23.0)	6.3 (2.3-14.0)	6.4 (0.4-29.0)
Tumor size (cm)
≤ 2	25 (16.0)	0 (0.0)	11 (14.5)
> 2-5	51 (32.7)	13 (32.5)	22 (28.9)
> 5-10	53 (34.0)	24 (60.0)	27 (35.5)
> 10	27 (17.3)	3 (7.5)	16 (21.1)
Mitotic count (HPF) (n = 213)
< 5	98 (79.0)	21 (61.8)	22 (40.0)
6-10	14 (11.3)	11 (32.4)	17 (30.9)
> 10	12 (9.7)	2 (5.9)	16 (29.1)
Tumor necrosis	42 (28.6)	17 (42.5)	32 (42.7)
Management
Complete resection with negative surgical margins	142 (88.2)	40 (100)	59 (72.8)
Complete resection with positive surgical margins	15 (9.3)	0 (0.0)	18 (22.2)
Unresectable	4 (2.5)	0 (0.0)	4 (4.9)
CT guided biopsy	6 (3.7)	2 (5.0)	0 (0.0)
Types of resections
Open	65 (43.0)	18 (47.4)	41 (53.2)
Laparoscopic resection	72 (47.7)	15 (39.5)	27 (35.1)
Robotic resection	14 (9.3)	5 (13.2)	9 (11.7)
Chemotherapy1	68 (42.2)	27 (67.5)	50 (61.7)
Radiation therapy	2 (1.2)	0 (0.0)	1 (1.2)
Blood transfusion (< 24 hours post-operation)	41 (25.5)	9 (22.5)	20 (24.7)
Blood units transfused	1 (1-4)	1 (1-2)	1 (1-4)
Hospital length of stay (days)	7 (1-60)	8.5 (1-32)	8 (1-44)
Follow-up period (months)	32 (1-252)	31 (1-181)	53 (1-250)
Post-operative complications
Bleeding	7 (4.3)	2 (5.0)	2 (2.5)
Infection	5 (3.1)	3 (7.5)	1 (1.2)
Deep vein thrombosis	4 (2.5)	0 (0.0)	1 (1.2)
Anastomotic leaks	2 (1.2)	0 (0.0)	3 (3.7)
Outcome
Disease-free survival	131 (81.4)	36 (90.0)	65 (80.2)
Survived with recurrent/metastatic disease	21 (13.0)	3 (7.5)	6 (7.4)
Died	9 (5.6)	1 (2.5)	10 (12.3)
Incidental post-sleeve gastrectomy	19 (11.8)	0 (0.0)	6 (7.4)
Multiple operations	6 (3.7)	0 (0.0)	7 (8.6)

¹Imatinib.

HPF: High power field; CT: Computerized tomography.

Table 5 Comparison of clinico-pathological characteristics based on surgical approach, n (%)

	Open (n = 124)	Minimally invasive surgeries1 (n = 142)	P value
Age (mean ± SD)	51.9 ± 14.8	54.3 ± 12.5	0.16
Localized to primary organ site	63 (50.8)	117 (82.4)	0.001
Locally advanced to other GIT sites	40 (32.3)	11 (7.7)	0.001
Small bowel	45 (36.3)	11 (7.7)	0.001
Endoscopy	50 (40.3)	110 (77.5)	0.001
Maximum size of tumor (cm)	8 (0.3-23)	5 (0.25-16)	0.001
Risk stratification			0.34 for all
Low-risk	65 (52.4)	86 (60.6)
Intermediate-risk	18 (14.5)	20 (14.1)
High-risk	41 (33.1)	36 (25.4)
Tumor necrosis	42 (37.5)	40 (29.0)	0.15
Management
Complete resection with negative surgical margins	103 (83.1)	130 (91.5)	0.03 for all
Complete resection with positive surgical margins	21 (16.9)	12 (8.5)
Chemotherapy	65 (52.4)	70 (49.3)	0.61
Radiation therapy	2 (1.6)	0 (0.0)	0.12
Blood transfusion (< 24 hours post-operation)	31 (25.0)	36 (25.4)	0.94
Hospital length of stay (days)	9 (1-60)	7 (1-44)	0.009
Follow-up period (months)	47.5 (1-250)	26 (1-252)	0.002
Post-operative complications
Bleeding	9 (7.3)	1 (0.7)	0.005
Infection	7 (5.6)	2 (1.4)	0.11
Deep vein thrombosis	3 (2.4)	1 (0.7)	0.25
Anastomotic leaks	2 (1.6)	3 (2.1)	0.76
Outcome
Disease free survival	95 (76.6)	130 (91.5)	0.003 for all
Survived with recurrent/metastatic disease	18 (14.5)	7 (4.9)
Died	11 (8.9)	5 (3.5)
Lost to follow-up after surgery	29 (23.4)	22 (15.5)	0.10
Incidental post-sleeve gastrectomy	2 (1.6)	23 (16.2)	0.001
Multiple operations	7 (5.6)	6 (4.2)	0.59

¹Laparoscopic and robotic.

GIT: Gastrointestinal tract.

Table 6 Management and outcome of gastrointestinal stromal tumor cases based on temporal stratification, n (%)

	1995-2004 (n = 25)	2005-2014 (n = 96)	2015-2024 (n = 161)	P value
Management
Complete resection with negative surgical margins	21 (84.0)	81 (84.4)	139 (86.3)	0.76 for all
Complete resection with positive surgical margins	4 (16.0)	11 (11.5)	18 (11.2)
Unresectable	0 (0.0)	4 (4.2)	4 (2.5)
CT guided biopsy	0 (0.0)	3 (3.1)	5 (3.1)	0.67
Types of resections
Open	23 (92.0)	68 (76.4)	33 (21.7)	0.001 for all
Laparoscopic resection	2 (8.0)	15 (16.9)	97 (63.8)
Robotic resection	0 (0.0)	6 (6.7)	22 (14.5)
Chemotherapy1	8 (32.0)	48 (50.0)	89 (55.3)	0.09
Radiation therapy	2 (8.0)	0 (0.0)	1 (0.6)	0.04
Outcome
Disease-free survival	23 (92.0)	69 (71.9)	140 (87.0)	0.01 for all
Survived with recurrent/metastatic disease	0 (0.0)	17 (17.7)	13 (8.1)
Died	2 (8.0)	10 (10.4)	8 (5.0)
Incidental post-sleeve gastrectomy	2 (8.0)	4 (4.2)	19 (11.8)	0.11
Multiple operations	2 (8.0)	2 (2.1)	9 (5.6)	0.30

¹Imatinib.

CT: Computerized tomography.

Table 7 Multivariable Cox proportional hazards regression to evaluate disease-free survival

	Hazard ratios	95%CI		P value
		Lower	Upper
Age	0.991	0.978	1.004	0.162
Tumor size	0.915	0.865	0.968	0.002
Risk-stratification				0.471
Intermediate risk	0.820	0.515	1.306	0.404
High-risk	0.780	0.499	1.220	0.276
Mitotic count (HPF)				0.870
6-10	1.047	0.673	1.630	0.837
> 10	1.205	0.602	2.414	0.598
Types of resections				0.000
Laparoscopic	2.454	1.604	3.754	0.000
Robotic	2.936	1.682	5.124	0.000
Chemotherapy	1.139	0.730	1.776	0.566

HPF: High power field; CI: Confidence interval.

Table 8 Summary of recent studies on the treatment options for gastrointestinal stromal tumor

Ref.	Patients/duration/intervention	Results	Comment
Wang et al[41]	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
Wu et al[42]	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
Lei et al[43]	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
Yang et al[44]	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
Yin et al[45]	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
Zhang et al[46]	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

GIST: Gastrointestinal stromal tumor; LAP: Laparoscopic resection; TKI: Tyrosine kinase inhibitors.