Small GISTs More Deadly Than Previously Thought

Veronica Hackethal, MD

April 14, 2016

Small gastrointestinal stromal tumors (GISTs) measuring less than 2 cm, although rare, might be more aggressive than previously thought, according to a study published online March 29 in the Journal of Gastrointestinal Surgery.

"The big take-home message is not to underestimate the potential for aggressive biology in small GISTs. We were certainly surprised to see the higher-than-expected 5-year mortality rate," lead author Jason Sicklick, MD, assistant professor of surgery at UC San Diego School of Medicine and a surgical oncologist at UC San Diego Health, told Medscape Medical News.

The study is the first population-based analysis of malignant GISTs smaller than 2 cm. Current information on the epidemiology and natural history of small GISTs is sparse, and comes from pathologic analyses, autopsy studies, and small case series

Results show that 5-year mortality from GISTs in patients without any other cancers was 12.9%. Five-year mortality was about 34.0% with small regionally advanced and/or metastatic GISTs, and 5.6% with small localized GISTs.

The findings are concerning, given the dearth of clear-cut evidence-based guidelines for the management of small GISTs, according to Dr Sicklick and his colleagues. Moreover, the National Comprehensive Cancer Network recommends the surgical removal of symptomatic GISTs and, for low-risk tumors, surveillance, they point out.

Right now, doctors are using their clinical judgment to manage GISTs, and have nothing to really guide practice, according to Dr Sicklick. Many physicians opt to use surveillance for most small GISTs, unless they have concerning features like rapid growth, bleeding, or high amounts of mitoses.

The problem is that GISTs might lie on a spectrum, turning the distinction between benign or malignant into a gray area. Although size and location have traditionally been used to assess risk in GISTs, an unknown subset of small GISTs might be more aggressive and might dictate management, he explained.

It is thought that GISTs develop from the pacemaker cells of the gut, and have large ranges in size and malignant behavior. GISTs smaller than 2 cm have been found in up to 30% of people, but those data come from autopsy studies of older populations and might not represent the general population in the United States. The underlying biology of GISTs remains a mystery, although certain mutations are thought to be involved, he explained.

Study Details

Dr Sicklick and his colleagues used data from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database, which contains nationally representative data and covers about 28% of the American population.

They identified 378 patients diagnosed with GISTs smaller than 2 cm and confirmed malignant histology from 2001 to 2011. The average age at diagnosis was 64 years, and the distribution of men and women was nearly equal. Black patients were 2.1 times more likely than white patients to develop GISTs smaller than 2 cm. Black race and advanced stage were also linked to an increased risk for death.

GISTs were most commonly found in the stomach (62.2%), small intestine (23.3%), colon (5.6%), and rectum (3.4%). Localized disease predominated (79.4%), although 11.4% of patients had regional/distant metastatic disease.

For all patients with GISTs smaller than 2 cm, 5-year overall mortality was unexpectedly high, at 30.9%.

Dr Sicklick and his colleagues conducted further analyses because previous work they had been involved in suggested an increased incidence of other cancers in patients with GISTs. That brought 5-year GIST mortality in patients without any other cancers down to 12.9%, and showed an 82.0% increased risk for death in patients with additional cancers (hazard ratio, 1.82; 95% confidence interval, 1.14 - 2.90; P = .012), after adjustment for age, race, sex, and disease stage.

The SEER database did not provide information on mitotic index, which could have limited the study. Also, SEER contains data on patients with resected tumors, which might have been more aggressive, and might have led to an overestimate of GIST-specific mortality.

We still don't have enough understanding of which GISTs to resect and which need surveillance.

Dr Sicklick would like to see the creation of a nationwide GIST-specific database with more details on mitotic index, specific therapies, pathology, and mutation status. More studies are needed to uncover the underlying mechanisms related to racial differences, to develop risk-assessment tools, and to identify indications for surgical resection and medical management.

"We still don't have enough understanding of which GISTs to resect and which need surveillance," Dr Sicklick emphasized. "We need to have more granular, robust data to better understand these patients."

The study was funded in part by the National Institutes of Health. Dr Sicklick and his colleagues have disclosed no relevant financial relationships.

J Gastrointest Surg. Published online March 29, 2016. Abstract


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