Rising GIST Cases: Need for Research and Prevention

Unfavorable trends in the diagnosis and prevalence of gastrointestinal stromal tumors (GIST) over the past 20 years have experts calling for progress on 2 fronts: for future research to investigate potential contributions from patients’ lifestyles and environments and for prevention efforts directed to minority patient populations.

This new research was recently published in JAMA Network Open, with the authors’ primary goal being to see if there were recent changes in GIST epidemiology.¹

GIST are a rare type of soft tissue sarcoma (STS) that develop in the wall of the digestive tract; they account for 0.1% to 0.3% of all gastrointestinal malignancies, and are diagnosed in between 4000 and 6000 people each year.^2-4 For this analysis, all included patients were 20 years and older with GIST that were diagnosed between January 1, 2000, and December 31, 2019; organ sites of GIST were the esophagus (n = 84), gastric tract (n = 7799), small intestine (n = 3560), colon (n = 312), and rectum (n = 354). Their data came from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) Program, including the SEER-22 and SEER-17 registries.

The authors used SEER-22 data to calculate age-standardized incidence rates (ASRs) and annual percentage changes (APCs), and SEER-17 data for median overall survival (OS), cancer-specific survival, and 5-year relative survival rates.

Most participants in each group were male patients (50.1%-61.9%), White (50.9%-65.4%), and alive at study time (51.0%-65.8%), and most had had surgery (56.0%-88.2%). The most common year of diagnosis was between 2015 and 2019 (32.0%-44.0%); pluralities had primary malignant tumors (69.0%-85.0%), tumors that were 1 to 50 mm (32.9%-42.0%), and median annual household income of at least $70,000 (42.6%-45.4%). In most patients, pathologic grade was unspecified (81.7%-94.0%), and most lived in an area with a population of more than 1 million (59.4%-63.0%). The median patient age was 64 years.

GIST account for just 0.1% to 0.3% of all gastrointestinal malignancies, making then a rare type of soft tissue sarcoma. | Image Credit: Gemütlichkeit-stock.adobe.com

The colon was the only organ to have a drop in GIST incidence: 0.2% (95% CI, –1.3 to 0.9%). For all other sites, there were substantial increases in APC:

• Esophagus: 7.3% (95% CI, 4.4%-10.2%)
• Gastric: 5.1% (95% CI, 4.2%-6.1%)
• Small intestine: 2.7% (95% CI, 1.8%-3.7%)
• Rectum: 1.9% (95% CI, 0.1%-3.8%)

Esophageal GIST

The ASR started at 0.005 per 100,000 population in 2000 and had risen to 0.014 by 2019. However, for esophageal leiomyosarcoma, there was a decrease from 0.005 to 0. Both tumor types had a combined APC of 4.5% (95% CI, 1.5%-6.6%). White patients had the longest overall survival, at 15.3 years vs 3.6, 8.8, and 10.3, respectively, for Black, Asian or Pacific Islander (API), and Hispanic patients, but API patients (HR, 5.6; 95% CI, 1.5-20.2) and Black patients (HR, 6.4; 95% CI, 2.0-20.3) had the highest overall mortality. Patients with undifferentiated or poorly differentiated tumors also had worse OS vs patients with unspecified tumors (HR, 6.3; 95% CI, 1.2-34.7).

Gastric GIST

The ASR rose from 0.24 to 0.93 per 100,000 population over the study period, but the ASR of gastric leiomyosarcoma dropped over the same period: from 0.075 to 0.009. Their combined APC was 4.8% (95% CI, 4.0%-5.5%), and this varied by anatomic subsite: 3.5% for cardia subsites, 6.2% for noncardia subsites, and 3.9% for overlapping/unspecified tumors. American Indian or Alaska Native patients had the shortest median survival vs Black, White, Hispanic, and API patients, at 8.5 years vs 9.1, 11.8, 12.6, and 13.7 years, respectively. Compared with White patients, American Indian or Alaska Native patients (HR, 1.6; 95% CI, 0.9-3.0) and Black patients (HR, 1.4; 95% CI, 1.2-1.5) had the highest mortality rates. Factors contributing to worse OS were older age, male sex, distant stage, and poorly differentiated histology.

Small Intestine GIST

There was an almost 3-fold increase in ASR over the study period: from 0.13 to 0.36 per 100,000 population. But again, incidence of leiomyosarcoma dropped: from 0.06 to 0.01 per 100,000. Combined, the APC for both was 2.3% (95% CI, 1.6%-3.0%). The longest median survival was seen in API patients (11.4 years) vs American Indian or Alaska Native (6.2 years), White (9.9 years), and Black (10.2 years) patients. The highest mortality rates were seen among Black (HR, 1.3; 95% CI, 1.0-1.5) and API (HR, 1.5; 95% CI, 0.6-4.1) patients. Patients with small intestine GIST also were predisposed to worse outcomes from older age, male sex, poorly differentiated histology, and distant stage. However, those who had surgery did see a 50% lower mortality risk (HR, 0.50; 95% CI, 0.4-0.6).

Colon GIST

The ASR saw a small increase of 0.003 between 2000 and 2019, while the ASR for leiomyosarcoma dropped (0.014 to 0.009). The combined APC for both tumor types was –0.7% (95% CI, –1.6% to 0.2%). API patients had the shortest median survival, at 5.4 years compared with Black patients who had the longest, at 19.5 years; Hispanic patients came in at 11.3 years, and White patients, 6.3 years. Correlations were seen between worse survival and older age, poorly differentiated histology, and distant stage. But again, surgery conveyed a lower risk of dying (HR, 0.60; 95% CI, 0.4-0.9).

Rectal GIST

The ASR for patients with rectal GIST more than doubled between 2000 and 2019: 0.015 to 0.033 per 100,000 population. Unlike the 4 GIST types above, leiomyosarcoma incidence rose from 0.002 to 0006 per 100,000 population over the same period. Their combined APC was 1.7% (95% CI, –0.04% to 3.5%). The longest median survival was 15.7 years for API patients, followed by 13.8 years for Hispanic patients, 13.5 years for Black patients, and 11.9 years for White patients. Factors contributing to worse survival outcomes were older age and poorly differentiated histology, whereas surgery helped to lower the risk of death by 50% (HR, 0.5; 95% CI, 0.3-0.8)

The study authors explain that the higher numbers of GIST over their study period could be due to better diagnostic tools, but that these technologies could also mean overdiagnoses. They also point to recent research on potential links with obesity.⁵ And for the variations in outcomes by race and ethnicity, they posit that disparate health care access, inadequate insurance coverage, treatment cost, and patient care practices may be to blame.

References

1.Alvarez CS, Piazuelo MB, Fleitas-Kanonnikoff T, Ruhl J, Pérez-Fidalgo JA, Camargo C. Incidence and survival outcomes of gastrointestinal stromal tumors. JAMA Netw Open. Published online August 19, 2024. doi:10.1001/jamanetworkopen.2024.28828

2. Burch J, Ahmad I. Gastrointestinal stromal cancer. In: StatPearls. Updated September 26, 2022. Accessed August 21, 2024. https://www.ncbi.nlm.nih.gov/books/NBK554541/#:~:text=While%20only%20comprising%200.1%25%20to,tumors%20of%20the%20GI%20tract

3. Gastrointestinal stromal tumor (GIST). Cleveland Clinic. Updated April 15, 2024. Accessed August 21, 2024. https://my.clevelandclinic.org/health/diseases/17031-gist-cancer-information

4. Gastrointestinal stromal tumors (GIST). Yale Medicine. Accessed August 21, 2024. https://www.yalemedicine.org/conditions/gastrointestinal-stromal-tumors-gist#:~:text=Between%204%2C000%20to%206%2C000%20people,to%20the%20American%20Cancer%20Society

5. Dowgiałło-Gornowicz N, Sztaba K, Lech P, Botulińska A, Michalik M. The incidence of gastrointestinal stromal tumors in obese patients—a large single center experience. Medicina (Kaunas). 2021;57(11):1242. doi:10.3390/medicina57111242