Second Primary Malignancy in Gastrointestinal Stromal Tumors: Insights From a Population-Based Analysis

Introduction: Gastrointestinal stromal tumor (GIST) are the most frequent mesenchymal neoplasms in the digestive tract. Second primary malignancies (SPM) have been reported frequently, either synchronously or during follow-up, in patients diagnosed with GIST. We analyzed the incidence and location of SPM in patients with GIST. Methods: We conducted a retrospective cohort study using the Surveillance, Epidemiology, and End Results database (SEER) to filter out patients diagnosed with GISTs. Patients with GIST diagnosed between 1975 and 2019 and confirmed on histopathology were included, while those diagnosed at autopsy or lost to follow-up were excluded. SPM was defined as a second tumor diagnosed more than 60 days after the initial GIST diagnosis. Standardized incidence ratio (SIR) and absolute excess risk (AER) were calculated using SEER*Stat software (version 8.4.0.1). P-values and 95% confidence intervals (95% CI) were generated assuming Poisson distribution of observed incidence of SPM. Results: Overall, 3,202 GIST patients were included (mean age 62.36 years). SPM was reported in 328 (10.2%) patients. Patients with GIST had a significantly greater risk of developing SPM in any location as compared to the general population with SIR = 1.25 (95% CI = 1.11-1.39) and AER of 32.86 per 10,000 population. The most common site for SPM was the digestive tract, specifically the colon (SIR = 1.53, 95% CI = 1.01-2.22) and stomach (SIR = 2.50, 95% CI = 1.29-4.37). Other locations where site-specific risk was significantly increased were the lungs, bronchus and trachea (SIR 1.69), soft tissues (SIR 5.27), skin (SIR 1.71), kidney (SIR 2.34), thyroid (SIR 4.13), and chronic myeloid leukemia (SIR 4.15) (Table 1). Increased risk of SPM was reported for patients aged 50-75 years (SIR = 1.28) but not for patients younger than 50 or older than 75. There was a significantly increased risk of developing SPM in all races; the SIR for Caucasians, African-Americans, and other races (American Indian/AK Native, Asian/Pacific Islander) were 1.19, 1.45, and 1.34, respectively. Increased risk of SPM was reported for latency 2-11 months (SIR 2.31) but not for latencies 12-59 months (SIR 1.06), 60-119 months (SIR 1.05), or 120+ months (SIR 1.29). Conclusion: Patients with GIST are at a high risk of developing SPM, especially tumors of the digestive and respiratory tract, along with chronic myeloid leukemia. Data suggests a higher incidence of SPM in patients aged 50-75 years and with 2-11 months latency. Table 1. - Secondary Primary Malignancy Sites Location Observed Expected SIR 95% CI AER All Sites 328 263.3 1.25# 1.11-1.39 32.86 All Solid Tumors 287 227.57 1.26# 1.12-1.42 30.18 Stomach 12 4.8 2.50# 1.29-4.37 3.66 Colon 27 17.69 1.53# 1.01-2.22 4.46 Sigmoid Colon 10 4.34 2.30# 1.1-4.24 2.87 Lung, and bronchus 60 35.46 1.69# 1.29-2.18 12.49 Skin excluding Basal and Squamous 22 12.86 1.71# 1.07-2.59 4.64 Soft Tissue including Heart 8 1.52 5.27# 2.27-10.38 3.29 Kidney 19 8.1 2.34# 1.41-3.66 5.53 Chronic Myeloid Leukemia 4 0.96 4.15# 1.13-10.62 1.54 Thyroid 16 3.87 4.13# 2.36-6.71 6.16 #represents P< 0.05.SIR : Standardized incidence ratio, AER : Absolute excess risk, 95%CI : 95% Confidence Interval.