May 19, 2015
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Gastrointestinal stromal tumors increase risk for additional malignancies

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Patients with gastrointestinal stromal tumors faced an increased risk for developing additional cancers before and after their diagnosis, according to results of a SEER analysis.

“Only 5% of patients with gastrointestinal stromal tumors have a hereditary disorder that predisposes them to develop multiple benign and malignant tumors,” Jason K. Sicklick, MD, of the division of surgical oncology at the UC San Diego Moores Cancer Center, said in a press release. “The research indicates that these patients may develop cancers outside of these syndromes, but the exact mechanisms are not yet known.”

Researchers used the SEER database to identify 6,112 patients diagnosed with gastrointestinal stromal tumor (GIST) between 2001 and 2011. Fifty-three percent of patients were men, and the most common age range at diagnosis was 60 to 69 years (25%). Researchers excluded patients younger than 20 years at the time of diagnosis because they had a high likelihood of having hereditary syndromes.

Researchers calculated standardized prevalence ratios (SPR) — or cancer occurrence before GIST diagnosis — and standardized incidence ratios, or the risk for cancer after GIST diagnosis, by comparing data from the patients with data from the general U.S. population in 2000.  

Seventeen percent of patients (n = 1,047) had additional cancers, which represented one in every 5.8 patients with GIST. More patients were diagnosed with other cancers before GIST vs. during the same month or after GIST diagnosis (62.2% vs. 44.6%).

Patients with a GIST had a 44% (SPR = 1.44; 95% CI, 1.33-1.55) increased prevalence of additional cancers before a GIST and a 66% (SIR = 1.66; 95% CI, 1.52-1.81) increased risk for developing cancers after a GIST compared with the general population.

Malignancies that occurred significantly more frequently among patients before and after a GIST diagnosis included other sarcomas (SPR = 5.24; SIR = 4.02), neuroendocrine-carcinoid tumors (SPR = 3.56; SIR = 4.79), non-Hodgkin’s lymphoma (SPR = 1.69; SIR = 1.76) and colorectal adenocarcinoma (SPR = 1.51; SIR = 2.16).

Malignancies with significantly increased occurrence rates only prior to a GIST diagnosis included esophageal adenocarcinoma (SPR = 12), bladder adenocarcinoma (SPR = 7.51), melanoma (SPR = 1.46) and prostate adenocarcinoma (SPR =1.2).

Occurrence rates were significantly increased only after a GIST diagnosis for 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 = 3.1), gastric adenocarcinoma (SIR = 2.7), 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).

Researchers observed a higher incidence of additional cancers before a GIST diagnosis among non-Hispanic white patients compared with Hispanic patients (P = .02).

Further, patients whose primary tumors were 10 cm or smaller displayed increased rates of second cancers, and patients whose tumors were 2 cm or smaller were at the greatest risk.

The researchers acknowledged these data may be limited by a detection bias during the evaluation for symptomatic patients or follow-up after GIST treatment, which may lead to elevated occurrences of additional cancers.

“Further investigation is necessary to link the histologically confirmed, epidemiological findings from this and other population-based studies with relevant clinical decision making,” Sicklick and colleagues concluded. “In addition, the development of a national registry is necessary to capture patients with potential syndromes, raise awareness, identify prevention strategies and elucidate the role of genetic counseling.”

These data have the potential to increase awareness and detection of GISTs, Constantine A. Stratakis, MD, DMedSci, of the Eunice Kennedy Shriver National Institute of Child Health and Human Development at the NIH, wrote in an accompanying editorial.

“Whatever the mechanism explaining the observation of the authors, the implications of their findings are significant for those of us who take care of patients with GISTs,” Stratakis wrote. “As [the researchers] suggest, counseling of these patients should include the possibility of finding another tumor, and clinicians should bear in mind that another, totally unrelated lesion may be found as they screen for possible metastasis of the primary GIST. Patients with other tumors may also be found to be carrying a GIST, and in both cases, whether the other lesion is found before or after a GIST, the possibility of genetic and/or syndromic association should be considered.” – by Cameron Kelsall

Disclosure: The researchers report no relevant financial disclosures.