Increased risk of additional cancers among patients with gastrointestinal stromal tumors: A population-based study

Abstract

Background: Most gastrointestinal stromal tumors (GISTs) are considered nonhereditary or sporadic. However, single-institution studies suggest that GIST patients develop additional malignancies at increased frequencies. It was hypothesized that greater insight could be gained into possible associations between GISTs and other malignancies with a national cancer database inquiry.

Methods: Patients diagnosed with GISTs (2001-2011) in the Surveillance, Epidemiology, and End Results database were included. Standardized prevalence ratios (SPRs) and standardized incidence ratios (SIRs) were used to quantify cancer risks incurred by GIST patients before and after GIST diagnoses, respectively, in comparison with the general US population.

Results: There were 6112 GIST patients, and 1047 (17.1%) had additional cancers. There were significant increases in overall cancer rates: 44% (SPR, 1.44) before the GIST diagnosis and 66% (SIR, 1.66) after the GIST diagnosis. Malignancies with significantly increased occurrence both before and after diagnoses included other sarcomas (SPR, 5.24; SIR, 4.02), neuroendocrine-carcinoid tumors (SPR, 3.56; SIR, 4.79), non-Hodgkin lymphoma (SPR, 1.69; SIR, 1.76), and colorectal adenocarcinoma (SPR, 1.51; SIR, 2.16). Esophageal adenocarcinoma (SPR, 12.0), bladder adenocarcinoma (SPR, 7.51), melanoma (SPR, 1.46), and prostate adenocarcinoma (SPR, 1.20) were significantly more common only before the GIST diagnosis. Ovarian carcinoma (SIR, 8.72), small intestine adenocarcinoma (SIR, 5.89), papillary thyroid cancer (SIR, 5.16), renal cell carcinoma (SIR, 4.46), hepatobiliary adenocarcinoma (SIR, 3.10), gastric adenocarcinoma (SIR, 2.70), pancreatic adenocarcinoma (SIR, 2.03), uterine adenocarcinoma (SIR, 1.96), non-small cell lung cancer (SIR, 1.74), and transitional cell carcinoma of the bladder (SIR, 1.65) were significantly more common only after the GIST diagnosis.

Conclusions: This is the first population-based study to characterize the associations and temporal relations between GISTs and other cancers by both site and histological type. These associations may carry important clinical implications for future cancer screening and treatment strategies.

Keywords: Surveillance, Epidemiology, and End Results (SEER); gastrointestinal stromal tumor (GIST); multiple primary neoplasm; second primary neoplasms; synchronous neoplasms.

Figure 1. Cancer development before and after the diagnosis of GIST

Occurrence of each cancer before GIST is reported using the standardized prevalence ratio (SPR, solid squares) and that after GIST is reported as the standardized incidence ratio (SIR, white circles). Horizontal lines illustrate associated 95% CIs. Only cancers with statistically significantly elevated SPRs and SIRs (P<0.05), as well as more than one reported case within the cohort, are included. * Other female genitourinary (GU) includes vulvar cancer (N=4), vaginal cancer (N=1), fallopian tube (N=2), and not otherwise specified (N=1). ** Hepatobiliary adenocarcinoma includes liver adenocarcinoma (N=2), intrahepatic cholangiocarcinoma (N=1), extrahepatic cholangiocarcinoma (N=1), and ampullary adenocarcinoma (N=4).

Figure 2. Timeline for the occurrence of additional cancers relative to the diagnosis of GIST

Occurrence of additional cancers relative to the time of GIST diagnosis is represented. Occurrence of cancer before the diagnosis of GIST is quantified using the standardized prevalence ratio (SPR) and that after GIST is quantified using the standardized incidence ratio (SIR). Error bars represent the 95% confidence intervals, and stars (*) represent P<0.05.