Abstract
Purpose
Multiple gastrointestinal stromal tumors (MGISTs) are relatively rare and may exhibit distinct clinical characteristics and prognosis compared to solitary GISTs (SGISTs). The objective of this study was to investigate the clinical features and prognosis of MGISTs.
Materials and methods
The Surveillance, Epidemiology, and End Results (SEER) database was used to identify all GIST patients diagnosed between 2010 and 2019. Multiple imputation (MI) was utilized to address missing data, while propensity score matching (PSM) was conducted to mitigate selection bias. The impact of demographic and clinical factors on overall survival (OS) was evaluated using Kaplan–Meier analyses and Cox proportional hazards models.
Results
A total of 6241 patients were included in the study, with 4546 having SGISTs and 1695 having MGISTs. MGISTs have a higher prevalence in males, Caucasians, and elderly patients. Compared to MGISTs, the OS of SGISTs is significantly better (hazard ratio [HR] 0.49, 95% confidence interval [CI] 0.44–0.55, P < 0.001). After PSM, 3390 patients (equally distributed between the SGISTs and MGISTs groups) were matched for comparison. The OS of SGISTs is still better than that of MGISTs (HR 0.65, 95% CI 0.56–0.75, P < 0.001). Age, sex, site, surgery, marital status, mitotic rate, and chemotherapy were independent risk factors for OS in MGISTs patients. The OS of MGISTs patients who underwent surgery was significantly better than those who did not (P < 0.001). Similarly, chemotherapy-treated MGISTs patients showed improved OS compared to those who did not receive it (P = 0.045).
Conclusions
MGISTs have unique clinical characteristics and show worse OS compared to SGISTs. Surgical intervention and chemotherapy has the potential to ameliorate the prognosis of patients with MGISTs.
Supplementary Information
The online version contains supplementary material available at 10.1007/s12672-025-02454-x.
Keywords: Multiple gastrointestinal stromal tumors, Clinical characteristics, Overall survival, SEER
Introduction
Gastrointestinal stromal tumors (GISTs), arising from Cajal cells, are the predominant mesenchymal neoplasms with an annual incidence ranging from 10 to 15 cases per million [1, 2]. They can arise from any segment of the gastrointestinal (GI) tract, with a higher prevalence in the stomach and small intestine and a lower occurrence in extragastrointestinal sites [3, 4]. Solitary GISTs (SGISTs) are the most common type, developing sporadically in adults with an average age of 65 years [4]. However, multiple gastrointestinal stromal tumors (MGISTs), characterized by the presence of two or more synchronous tumors in the gastrointestinal tract [5], are extremely rare, except in cases of familial GIST syndrome [6], neurofibromatosis type 1 (NF1) [7, 8], pediatric GISTs [9], and Carney's syndrome [10].
In a prognosis analysis by Li et al. [11], 20 cases of MGISTs were examined, and it was found that the overall prognosis of patients with MGISTs was comparable to that of patients with SGISTs. Another study by Shen et al. [12] indicated that patients with MGISTs, when treated using the same approach, did not have a worse prognosis compared to patients with a single lesion of similar risk. However, a separate study [13] showed that patients with MGISTs had a poorer prognosis compared to those with SGISTs. Despite reports on the clinical characteristics and prognosis of MGISTs, these studies have been limited by small sample sizes and inconsistent findings.
Currently, there is a lack of large-scale cohort studies that comprehensively investigate the prognosis of MGISTs. Therefore, the aim of this study was to address this knowledge gap by analyzing data from the Surveillance, Epidemiology, and End Results (SEER) database, which contains information on monitoring, epidemiology, and final outcomes. The objective was to enhance our understanding of the clinical characteristics and prognosis of MGISTs.
Materials and methods
Patient selection
The study population consisted of patients with GIST diagnosed between 2010 and 2019, which was obtained from the SEER database (http://seer.cancer.gov). The identification of GIST cases was based on the International Classification of Diseases for Oncology, 3rd Edition (ICD-O-3), utilizing a specific histological subtype code of 8936. To ensure data integrity, patients were excluded from the study if they met any of the following criteria: (1) lacked a known pathological histological diagnosis; (2) had an unknown survival time; (3) lacked known surgery-related information; (4) had developed distant metastasis (M1) or lymph node metastasis (N1), or had unclear metastatic information. The variables collected for analysis comprised age, race, sex, year of diagnosis, tumor site, T stage, surgical intervention, marital status, chemotherapy administration, mitotic count, follow-up duration, and vital status. Based on the"Total number of in situ/malignant tumors for the patient,"we can differentiate between SGISTs and MGISTs. If the patient has only one tumor, it indicates a SGISTs, whereas if there are two or more tumors, it suggests a MGISTs. Age was categorized into two groups: those aged 65 or younger (referred to as the young group) and those over 65 years old (referred to as the elderly group). Race was divided into three categories: white, black, and others (including American Indian, Alaska Native, and Asian/Pacific Islander). Marital status was classified as married or unmarried, which encompasses divorced, separated, single, and widowed individuals. The variable"CS site-specific factor 6"was utilized to evaluate the mitotic rate. The primary objective of this study was to investigate the rates of overall survival (OS) among patients diagnosed with GISTs. OS were determined by measuring the time from the date of GIST diagnosis to either death or the most recent follow-up. Since the SEER database offers publicly accessible and de-identified data, this study did not involve direct participation of human subjects. Consequently, Institutional Review Board (IRB) approval and written consent were not necessary for this study.
Multiple imputation
To address missing data in several variables, such as race (1.2% of cases), marital status (5.7% of cases), and mitotic count (40.1% of cases), a polytomous regression model was constructed using the multiple imputation (MI) function in R software (version 4.1.0). This approach was employed to improve the statistical power and robustness of the study's analyses.
Statistical analysis
Categorical variables were presented as frequencies and percentages, and statistical comparisons between groups were conducted using the Chi-square test. Continuous variables that did not follow a normal distribution, the median and interquartile range (IQR) were used to describe the data, and group comparisons were performed using the Mann–Whitney U test. One-to-one propensity score matching (PSM) was employed to equalize the SGISTs and MGISTs groups. The propensity model encompassed age, race, sex, year of diagnosis, tumor site, T stage, surgical intervention, marital status, chemotherapy administration, and mitotic count, with a caliper width set at 0.01. To estimate OS, the Kaplan–Meier method was applied, and comparisons between groups were made using the log-rank test. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using univariate and multivariate Cox proportional hazard models. All statistical analyses were conducted using R software (version 4.0). Statistical significance was set at P < 0.05 to determine significant differences between groups.
Results
Patients characteristics
Figure 1 illustrates the study enrollment process, which included a total of 6241 patients. Among them, 4546 were diagnosed with SGISTs and 1695 with MGISTs. Before PSM, there were significant differences between the SGISTs and MGISTs groups in terms of age, race, sex, year of diagnosis, T stage, surgery, and chemotherapy (P < 0.05). The post-PSM analysis encompassed 1695 pairs of matched patients, with no statistically significant variations observed in any baseline characteristics between the groups (Table 1). Table 1 provides a detailed breakdown of the demographic and clinical information of the patients, whereas Supplementary Table 1 offers a comprehensive comparison of the demographic and clinical characteristics of the two groups prior to MI.
Fig. 1.
Flow chart of the study
Table 1.
Comparison of the demographic and clinical characteristics of patients before and after PSM
| Variables | Before PSM | After PSM | |||||
|---|---|---|---|---|---|---|---|
| Total (n = 6241) |
SGISTs (n = 4546) |
MGISTs (n = 1695) |
P-value | SGISTs (n = 1695) |
MGISTs (n = 1695) |
P-value | |
| Age | < 0.001 | 0.831 | |||||
| > 65 | 3000 (48%) | 1938 (43%) | 1062 (63%) | 1068 (63%) | 1062 (63%) | ||
| ≤ 65 | 3241 (52%) | 2608 (57%) | 633 (37%) | 627 (37%) | 633 (37%) | ||
| Race | < 0.001 | 0.794 | |||||
| White | 4133 (66%) | 2975 (65%) | 1158 (68%) | 1162 (69%) | 1158 (68%) | ||
| Black | 1192 (19%) | 852 (19%) | 340 (20%) | 327 (19%) | 340 (20%) | ||
| Others | 916 (15%) | 719 (16%) | 197 (12%) | 206 (12%) | 197 (12%) | ||
| Sex | 0.003 | 0.606 | |||||
| Male | 3079 (49%) | 2190 (48%) | 889 (52%) | 874 (52%) | 889 (52%) | ||
| Female | 3162 (51%) | 2356 (52%) | 806 (48%) | 821 (48%) | 806 (48%) | ||
| Year of diagnosis | < 0.001 | 0.583 | |||||
| 2010–2014 | 2880 (46%) | 2035 (45%) | 845 (50%) | 861 (51%) | 845 (50%) | ||
| 2015–2019 | 3361 (54%) | 2511 (55%) | 850 (50%) | 834 (49%) | 850 (50%) | ||
| Site | 0.149 | 0.883 | |||||
| Esophagus | 48 (1%) | 29 (1%) | 19 (1%) | 21 (1%) | 19 (1%) | ||
| Stomach | 4128 (66%) | 3005 (66%) | 1123 (66%) | 1111 (66%) | 1123 (66%) | ||
| Small intestine | 1655 (27%) | 1225 (27%) | 430 (25%) | 448 (26%) | 430 (25%) | ||
| Colon | 312 (5%) | 220 (5%) | 92 (5%) | 82 (5%) | 92 (5%) | ||
| Extragastrointestinal tract | 98 (2%) | 67 (1%) | 31 (2%) | 33 (2%) | 31 (2%) | ||
| T stage | < 0.001 | 0.879 | |||||
| T1 | 1000 (16%) | 642 (14%) | 358 (21%) | 336 (20%) | 358 (21%) | ||
| T2 | 2119 (34%) | 1526 (34%) | 593 (35%) | 614 (36%) | 593 (35%) | ||
| T3 | 1692 (27%) | 1295 (28%) | 397 (23%) | 401 (24%) | 397 (23%) | ||
| T4 | 997 (16%) | 774 (17%) | 223 (13%) | 225 (13%) | 223 (13%) | ||
| TX | 433 (7%) | 309 (7%) | 124 (7%) | 119 (7%) | 124 (7%) | ||
| Surgery | 0.016 | 0.471 | |||||
| No | 721 (12%) | 498 (11%) | 223 (13%) | 209 (12%) | 223 (13%) | ||
| Yes | 5520 (88%) | 4048 (89%) | 1472 (87%) | 1486 (88%) | 1472 (87%) | ||
| Marital status | 0.989 | 0.340 | |||||
| Married | 3797 (61%) | 2766 (61%) | 1031 (61%) | 1058 (62%) | 1031 (61%) | ||
| Unmarried | 2444 (39%) | 1780 (39%) | 664 (39%) | 637 (38%) | 664 (39%) | ||
| Chemotherapy | < 0.001 | 0.738 | |||||
| No | 3896 (62%) | 2719 (60%) | 1177 (69%) | 1168 (69%) | 1177 (69%) | ||
| Yes | 2345 (38%) | 1827 (40%) | 518 (31%) | 527 (31%) | 518 (31%) | ||
| Mitotic rate | 0.167 | 0.863 | |||||
| < 5/50 | 4931 (79%) | 3572 (79%) | 1359 (80%) | 1355 (80%) | 1359 (80%) | ||
| ≥ 5/50 | 1310 (21%) | 974 (21%) | 336 (20%) | 340 (20%) | 336 (20%) | ||
| Survival months, median (IQR) | 41.0(16.0,73.0) | 41.0(16.8,73.0) | 41.0(16.0,74.0) | 0.814 | 39.0(11.0,75.0) | 41.0(16.0,74.0) | 0.204 |
PSM: propensity score matching; SGISTs: solitary gastrointestinal stromal tumors; MGISTs: multiple gastrointestinal stromal tumors; HPF: high power field; Others: American Indian, Alaska Native, Asian/Pacific Islander; IQR: interquartile range
Survival analysis of multiple gastrointestinal stromal tumors
The mean 1-year, 3-year, and 5-year OS rates for MGISTs patients were 90.5%, 75.6%, and 59.0%, respectively. For SGISTs patients, the mean 1-year, 3-year and 5-year OS rates were 95.4%, 87.3%, and 75.4%, respectively. The OS rate of the MGISTs group was significantly poorer than that of the SGISTs group both before and after PSM (P < 0.05) (Table 2). Compared to MGISTs, the OS of SGISTs is significantly better (HR 0.49, 95% CI 0.44–0.55, P < 0.001) (Fig. 2A). After PSM, SGISTs still have better OS compared to MGISTs (HR 0.65, 95% CI 0.56–0.75, P < 0.001) (Fig. 2B).
Table 2.
Survival rates for patients with MGISTs and SGISTs
| MGISTs | SGISTs | P-value | |
|---|---|---|---|
| Overall survival rate before PSM (%) | |||
| 1-year | 90.5 | 95.4 | < 0.001 |
| 3-year | 75.6 | 87.3 | < 0.001 |
| 5-year | 59.0 | 75.4 | < 0.001 |
| Overall survival rate after PSM (%) | |||
| 1-year | 90.5 | 92.9 | 0.021 |
| 3-year | 75.6 | 83.7 | < 0.001 |
| 5-year | 59.0 | 71.6 | < 0.001 |
SGISTs: solitary gastrointestinal stromal tumors; MGISTs: multiple gastrointestinal stromal tumors; PSM: propensity score matching
Fig. 2.
OS was compared between MGISTs group and SGISTs group before and after PSM A Before PSM; B After PSM. OS: overall survival; PSM: propensity score matching; MGISTs: multiple gastrointestinal stromal tumors; SGISTs: solitary gastrointestinal stromal tumors
Univariate and multivariate cox regression
Univariate Cox regression analysis revealed that age, sex, tumor site, T stage, surgery, marital status, chemotherapy, and mitotic rate were independent risk factors for OS in MGISTs patients. With a median (IQR) follow-up time of 41.0 (16.0,74.0) months for MGISTs, our study demonstrated that age, sex, tumor site, surgery, marital status, chemotherapy, and mitotic rate were independent risk factors for OS (Table 3).
Table 3.
Univariate and multivariate cox regression for analyzing the overall survival for MGISTs
| Variables | Univariate | Multivariate | ||||
|---|---|---|---|---|---|---|
| HR | 95% CI | P-value | HR | 95% CI | P-value | |
| Age | ||||||
| ≤ 65 | 1 | Reference | 1 | Reference | ||
| > 65 | 2.41 | 1.96–2.97 | < 0.001 | 2.28 | 1.84–2.81 | < 0.001 |
| Race | ||||||
| White | 1 | Reference | – | – | – | |
| Black | 1.10 | 0.88–1.38 | 0.388 | – | – | – |
| Others | 0.89 | 0.66–1.20 | 0.434 | – | – | – |
| Sex | ||||||
| Male | 1 | Reference | 1 | Reference | ||
| Female | 0.71 | 0.59–0.85 | < 0.001 | 0.69 | 0.57–0.83 | < 0.001 |
| Year of diagnosis | ||||||
| 2010–2014 | 1 | Reference | – | – | – | |
| 2015–2019 | 0.98 | 0.79–1.22 | 0.883 | – | – | – |
| Site | ||||||
| Stomach | 1 | Reference | 1 | Reference | ||
| Small intestine | 0.93 | 0.76–1.15 | 0.515 | 1.13 | 0.91–1.39 | 0.271 |
| Esophagus | 0.89 | 0.33–2.38 | 0.815 | 0.79 | 0.29–2.12 | 0.633 |
| Colon | 0.82 | 0.53–1.26 | 0.355 | 0.69 | 0.45–1.08 | 0.102 |
| Extragastrointestinal tract | 2.69 | 1.65–4.39 | < 0.001 | 2.12 | 1.27–3.55 | 0.004 |
| T stage | ||||||
| T1 | 1 | Reference | 1 | Reference | ||
| T2 | 0.87 | 0.67–1.13 | 0.298 | 0.84 | 0.64–1.09 | 0.186 |
| T3 | 0.90 | 0.68–1.20 | 0.475 | 0.89 | 0.66–1.20 | 0.457 |
| T4 | 1.28 | 0.95–1.73 | 0.104 | 1.14 | 0.81–1.59 | 0.462 |
| TX | 1.91 | 1.39–2.64 | < 0.001 | 1.37 | 0.97–1.94 | 0.070 |
| Surgery | ||||||
| No | 1 | Reference | 1 | Reference | ||
| Yes | 0.42 | 0.34–0.53 | < 0.001 | 0.48 | 0.37–0.61 | < 0.001 |
| Marital status | ||||||
| Married | 1 | Reference | 1 | Reference | ||
| Unmarried | 1.45 | 1.21–1.73 | < 0.001 | 1.59 | 1.32–1.91 | < 0.001 |
| Chemotherapy | ||||||
| No | 1 | Reference | 1 | Reference | ||
| Yes | 0.82 | 0.67–1.00 | 0.045 | 0.76 | 0.61–0.95 | 0.016 |
| Mitotic rate | ||||||
| < 5/50 | 1 | Reference | 1 | Reference | ||
| ≥ 5/50 | 1.25 | 1.02–1.53 | 0.030 | 1.31 | 1.06–1.63 | 0.013 |
MGISTs: multiple gastrointestinal stromal tumors; HPF: high power field; Others: American Indian, Alaska Native, Asian/Pacific Islander; HR: hazard ratios; CI: confidence interval
Discussion
MGISTs are extremely rare, with previous reports mostly consisting of isolated cases or only a few cases [11–15]. In a multicenter study conducted in China from 2001 to 2014, MGISTs comprised approximately 2% of all GIST cases [16]. Another study found a prevalence of 4.17% for MGISTs [13]. However, in our study, the incidence rate of MGISTs was found to be 27.2% (1695/6241), which is significantly higher than the rates reported in previous research. This discrepancy could be attributed to the following reasons: 1) The population data analyzed in our study primarily originated from the United States, and the incidence of MGISTs may vary among different countries and populations; 2) Previous reports on MGISTs have primarily focused on the incidence rate of multiple sporadic GISTs. However, the cases of MGISTs in the SEER database used for our study may include not only multiple sporadic GISTs but also familial GIST syndrome, neurofibromatosis type 1, pediatric GISTs, and Carney's syndrome, which could have contributed to an increase in the observed MGISTs incidence rate to some extent. To the best of our knowledge, there is currently a lack of population-based studies specifically investigating the clinical characteristics and prognosis of MGISTs. Therefore, the primary objective of our study was to address this gap and investigate the clinical characteristics and prognosis of MGISTs in comparison to SGISTs using data from the SEER database, thereby contributing valuable insights to the understanding of this rare form of gastrointestinal tumor.
Our research indicates a predisposition for MGISTs to occur among older adults and Caucasian patients. Additionally, these tumors frequently manifest at earlier T staging. These characteristics are consistent with the findings of Shen et al. [12], except for gender differences. Our study showed that MGISTs were more commonly observed in males, which aligns with the results reported by Li et al. [11], Haller et al. [17], and Agaimy et al. [18]. However, the studies conducted by Shen et al. [12] and Kang et al. [19] reported a higher incidence of MGISTs in females. This variation could be attributed to potential biases caused by differences in sample sizes. Furthermore, our study found that compared to other ethnic groups, Caucasians are more prone to developing MGISTs. This predisposition may be attributed to genetic and environmental factors, but further research is still needed to fully understand the underlying reasons.
In Shen et al.'s [12] study, they found that the Disease-free survival (DFS) of patients with MGISTs was comparable to that of patients with a single lesion at the same risk under the same treatment. However, in Wu et al.'s [13] research, they observed that the progression-free survival (PFS) of patients with MGISTs was significantly worse than that of patients with SGISTs. Nevertheless, the OS was similar between patients with SGISTs and those with MGISTs. The differences in the results between the two studies may be attributed to the variations in the sample sizes included. Currently, there have been no reports on population-based studies investigating the prognosis of MGIST patients.
Our study utilized the SEER database and found that MGISTs exhibited a significantly worse OS compared to SGISTs. The poorer OS in MGIST patients may be attributed to the following reasons: 1) MGISTs typically involve multiple tumor foci, which may contribute to a higher overall tumor burden and potentially increase the complexity of management. Although our study focused on non-metastatic MGISTs, the presence of numerous tumor foci underscores the importance of close monitoring and aggressive treatment strategies to prevent potential progression to metastatic disease; 2) Early diagnosis and treatment of MGISTs could be more challenging. Due to the presence of multiple tumor foci, it may require more extensive screening and examinations to detect all tumors. Additionally, surgical interventions for MGISTs can be more complex, as they involve dealing with multiple tumor foci and their associated structures. This complexity could increase surgical risks and potentially lower treatment efficacy, thus impacting overall survival rates.
Previous studies have shown that tumor location, tumor size, mitotic index, imatinib treatment, and MGISTs are independent risk factors influencing the prognosis of GIST patients [13]. However, our research revealed different results for MGIST patients. Age, sex, tumor site, surgery, marital status, chemotherapy, and mitotic rate were identified as independent risk factors for OS in MGIST patients (Table 3). The OS of MGISTs patients who underwent surgery was significantly better than those who did not (P < 0.001). Similarly, chemotherapy-treated MGISTs patients showed improved OS compared to those who did not receive it (P = 0.045). The differences between our research and previous studies regarding the factors influencing prognosis could be attributed to differences in sample size and characteristics of study populations. Variations in the size and characteristics of the study populations can lead to differences in the results. Our study primarily involved American individuals, whereas previous research focused on Chinese individuals. These differences in study design, patient population, and inclusion criteria may contribute to the discrepancies observed in the identified prognostic factors for MGIST patients.
Recent studies have highlighted the role of targeted therapies, such as imatinib and other tyrosine kinase inhibitors, in improving survival OS for patients with GISTs, including MGISTs [13, 20–22]. These therapies have become increasingly relevant in the treatment landscape of GISTs, offering new avenues for managing this rare and complex disease. However, the efficacy and optimal use of targeted therapies in MGISTs specifically may differ from that in SGISTs due to the distinct clinical characteristics and potential molecular heterogeneity of MGISTs. Indeed, emerging evidence suggests that MGISTs may exhibit unique molecular profiles compared to SGISTs, which could contribute to the observed differences in prognosis [23, 24]. Further research is needed to elucidate the molecular mechanisms underlying MGISTs and to investigate how targeted therapies can be tailored to improve outcomes in this patient population. Nevertheless, the available data underscore the potential of targeted therapies to ameliorate the prognosis of patients with MGISTs, alongside surgical intervention and chemotherapy, as demonstrated in our study.
It is essential to acknowledge the limitations of this study. Firstly, the study's reliance on retrospective data from the SEER database presents inherent limitations and the potential for missing data. Nonetheless, we have utilized MI techniques to handle missing data and reduce its impact on the analysis. Furthermore, the SEER database lacks certain detailed clinical information, such as specific treatment regimens and molecular characteristics, which could have provided further insights into MGISTs.
In conclusion, this study provides valuable insights into the clinical characteristics and prognosis of MGISTs compared to SGISTs. MGISTs have a higher prevalence among males, Caucasians, and elderly patients, and exhibit worse OS compared to SGISTs. Surgical intervention and chemotherapy have the potential to ameliorate the prognosis of patients with MGISTs. These findings underscore the importance of individualized treatment approaches for MGISTs and highlight the need for further research to enhance our understanding of this distinct subgroup of GISTs.
Supplementary Information
Author contributions
LC and YL conceived the study and wrote the draft. JWQ and FY revised the article. ZGQ, YMM, JQ and CFW extracted the data from the clinical charts, elaborated the data set and analyzed the data. ZGQ and YMM reviewed the article. FY supervised the study and is the guarantor. All authors approved the final version of the article.
Funding
This work was supported by the Science and Technology Development Program of Suzhou (SKYXD2022041) and Science and Technology Development Program of Suzhou Ninth People’s Hospital (YK202420, YK202428).
Data availability
Publicly available datasets were analyzed in this study. These data can be found here: https://seer.cancer.gov/. The datasets supporting the conclusions of this article are included within the article.
Declarations
Ethics approval and consent to participate
Data from the SEER database were used to extract information for institutional cohorts. The authors did not conduct any studies involving human participants, so formal consent was not necessary for this type of research.
Consent for publication
We have obtained consent from all authors for publication.
Informed consent
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Liang Chen, Ye Lu and Jiawei Qian contributed equally to this article.
Contributor Information
Zhenguo Qiao, Email: qzg66666666@163.com.
Yimin Ma, Email: kelema917@sina.com.
Feng Yu, Email: 15995575351@163.com.
References
- 1.Blay JY, Kang YK, Nishida T, et al. Gastrointestinal stromal tumours. Nat Rev Dis Primers. 2021;7(1):22. 10.1038/s41572-021-00254-5. [DOI] [PubMed] [Google Scholar]
- 2.Søreide K, Sandvik OM, Søreide JA, et al. Global epidemiology of gastrointestinal stromal tumours (GIST): a systematic review of population-based cohort studies. Cancer Epidemiol. 2016;40:39–46. 10.1016/j.canep.2015.10.031. (Epub 2015 Nov 24). [DOI] [PubMed] [Google Scholar]
- 3.Ma GL, Murphy JD, Martinez ME, et al. Epidemiology of gastrointestinal stromal tumors in the era of histology codes: results of a population-based study. Cancer Epidemiol Biomarkers Prev. 2015;24(1):298–302. 10.1158/1055-9965.EPI-14-1002. (Epub 2014 Oct 2). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Miettinen M, Lasota J. Gastrointestinal stromal tumors: pathology and prognosis at different sites. Semin Diagn Pathol. 2006;23(2):70–83. 10.1053/j.semdp.2006.09.001. [DOI] [PubMed] [Google Scholar]
- 5.Gasparotto D, Rossi S, Bearzi I, Doglioni C, et al. Multiple primary sporadic gastrointestinal stromal tumors in the adult: an underestimated entity. Clin Cancer Res. 2008;14(18):5715–21. 10.1158/1078-0432.CCR-08-0622. (Epub 2008 Sep 8). [DOI] [PubMed] [Google Scholar]
- 6.Neuhann TM, Mansmann V, Merkelbach-Bruse S, et al. A novel germline KIT mutation (p.L576P) in a family presenting with juvenile onset of multiple gastrointestinal stromal tumors, skin hyperpigmentations, and esophageal stenosis. Am J Surg Pathol. 2013;37(6):898–905. 10.1097/PAS.0b013e31827bc071. [DOI] [PubMed] [Google Scholar]
- 7.Nishida T, Tsujimoto M, Takahashi T, et al. Gastrointestinal stromal tumors in Japanese patients with neurofibromatosis type I. J Gastroenterol. 2016;51(6):571–8. 10.1007/s00535-015-1132-6. (Epub 2015 Oct 29). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Takazawa Y, Sakurai S, Sakuma Y, et al. Gastrointestinal stromal tumors of neurofibromatosis type I (von Recklinghausen’s disease). Am J Surg Pathol. 2005;29(6):755–63. 10.1097/01.pas.0000163359.32734.f9. [DOI] [PubMed] [Google Scholar]
- 9.Agaram NP, Laquaglia MP, Ustun B, et al. Molecular characterization of pediatric gastrointestinal stromal tumors. Clin Cancer Res. 2008;14(10):3204–15. 10.1158/1078-0432.CCR-07-1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Carney JA. Carney triad: a syndrome featuring paraganglionic, adrenocortical, and possibly other endocrine tumors. J Clin Endocrinol Metab. 2009;94(10):3656–62. 10.1210/jc.2009-1156. (Epub 2009 Sep 1). [DOI] [PubMed] [Google Scholar]
- 11.Li K, Tjhoi W, Shou C, et al. Multiple gastrointestinal stromal tumors: analysis of clinicopathologic characteristics and prognosis of 20 patients. Cancer Manag Res. 2019;25(11):7031–8. 10.2147/CMAR.S197560. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Shen YY, Ma XL, Yang LX, et al. Clinicopathologic characteristics, diagnostic clues, and prognoses of patients with multiple sporadic gastrointestinal stromal tumors: a case series and review of the literature. Diagn Pathol. 2020;15(1):56. 10.1186/s13000-020-00939-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Wu H, Li C, Li H, et al. Clinicopathological characteristics and longterm survival of patients with synchronous multiple primary gastrointestinal stromal tumors: a propensity score matching analysis. World J Gastroenterol. 2021;27(36):6128–41. 10.3748/wjg.v27.i36.6128. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Tokunaga M, Nanjo S, Yoshita H, et al. Multiple synchronous sporadic gastrointestinal stromal tumors in the stomach and jejunum. Intern Med. 2018;57(12):1719–23. 10.2169/internalmedicine.0229-17. (Epub 2018 Feb 9). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Arima J, Hiramatsu M, Taniguchi K, et al. Multiple gastrointestinal stromal tumors caused by a novel germline KIT gene mutation (Asp820Gly): a case report and literature review. Gastric Cancer. 2020;23(4):760–4. 10.1007/s10120-020-01055-7. (Epub 2020 Mar 7). [DOI] [PubMed] [Google Scholar]
- 16.Zhang X, Ning L, Hu Y, et al. Prognostic factors for primary localized gastrointestinal stromal tumors after radical resection: Shandong Gastrointestinal Surgery Study Group, Study 1201. Ann Surg Oncol. 2020;27(8):2812–21. 10.1245/s10434-020-08244-9. (Epub 2020 Feb 10). [DOI] [PubMed] [Google Scholar]
- 17.Haller F, Schulten HJ, Armbrust T, et al. Multicentric sporadic gastrointestinal stromal tumors (GISTs) of the stomach with distinct clonal origin: differential diagnosis to familial and syndromal GIST variants and peritoneal metastasis. Am J Surg Pathol. 2007;31(6):933–7. 10.1097/01.pas.0000213440.78407.27. [DOI] [PubMed] [Google Scholar]
- 18.Agaimy A, Märkl B, Arnholdt H, et al. Multiple sporadic gastrointestinal stromal tumours arising at different gastrointestinal sites: pattern of involvement of the muscularis propria as a clue to independent primary GISTs. Virchows Arch. 2009;455(2):101–8. 10.1007/s00428-009-0803-1. (Epub 2009 Jul 2). [DOI] [PubMed] [Google Scholar]
- 19.Kang DY, Park CK, Choi JS, et al. Multiple gastrointestinal stromal tumors: clinicopathologic and genetic analysis of 12 patients. Am J Surg Pathol. 2007;31(2):224–32. 10.1097/01.pas.0000213318.66800.94. [DOI] [PubMed] [Google Scholar]
- 20.Blay JY, Schiffler C, Bouché O, et al. A randomized study of 6 versus 3 years of adjuvant imatinib in patients with localized GIST at high risk of relapse. Ann Oncol. 2024;35(12):1157–68. 10.1016/j.annonc.2024.08.2343. (Epub 2024 Sep 4). [DOI] [PubMed] [Google Scholar]
- 21.Joensuu H, Eriksson M, Sundby Hall K, et al. Survival Outcomes associated with 3 years vs 1 year of adjuvant imatinib for patients with high-risk gastrointestinal stromal tumors: an analysis of a randomized clinical trial after 10-year follow-up. JAMA Oncol. 2020;6(8):1241–6. 10.1001/jamaoncol.2020.2091. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Tsai HJ, Shan YS, Yang CY, Taiwan Cooperative Oncology Group (TCOG) GIST Study Group, et al. Survival of advanced/recurrent gastrointestinal stromal tumors treated with tyrosine kinase inhibitors in Taiwan: a nationwide registry study. BMC Cancer. 2024;24(1):828. 10.1186/s12885-024-12567-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.GIST: Molecular Profiling Suggests 2nd Therapy. Cancer Discov. 2023;13(3):521–522. 10.1158/2159-8290.CD-NB2023-0008. [DOI] [PubMed]
- 24.Calderillo-Ruíz G, Pérez-Yepez EA, García-Gámez MA, et al. Genomic profiling in GIST: implications in clinical outcome and future challenges. Neoplasia. 2024;48: 100959. 10.1016/j.neo.2023.100959. (Epub 2024 Jan 5). [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
Publicly available datasets were analyzed in this study. These data can be found here: https://seer.cancer.gov/. The datasets supporting the conclusions of this article are included within the article.