Survival of gastrointestinal stromal tumor patients in the imatinib era: life raft group observational registry

Abstract

Background Gastrointestinal stromal tumors (GIST), one of the most common mesenchymal tumors of the gastrointestinal tract, prior to routine immunohistochemical staining and the introduction of tyrosine kinase inhibitors, were often mistaken for neoplasms of smooth muscle origin such as leiomyomas, leiomyosarcomas or leiomyoblastomas. Since the advent of imatinib, GIST has been further delineated into adult- (KIT or PDGFRα mutations) and pediatric- (typified by wild-type GIST/succinate dehydrogenase deficiencies) types. Using varying gender ratios at age of diagnosis we sought to elucidate prognostic factors for each sub-type and their impact on overall survival. Methods This is a long-term retrospective analysis of a large observational study of an international open cohort of patients from a GIST research and patient advocacy's lifetime registry. Demographic and disease-specific data were voluntarily supplied by its members from May 2000-October 2010; the primary outcome was overall survival. Associations between survival and prognostic factors were evaluated by univariate Cox proportional hazard analyses, with backward selection at P < 0.05 used to identify independent factors. Results Inflections in gender ratios by age at diagnosis in years delineated two distinct groups: above and below age 35 at diagnosis. Closer analysis confirmed the above 35 age group as previously reported for adult-type GIST, typified by mixed primary tumor sites and gender, KIT or PDGFRα mutations, and shorter survival times. The pediatric group (< age 18 at diagnosis) was also as previously reported with predominantly stomach tumors, females, wild-type GIST or SDH mutations, and extended survival. "Young adults" however formed a third group aged 18-35 at diagnosis, and were a clear mix of these two previously reported distinct sub-types. Conclusions Pediatric- and adult-type GIST have been previously characterized in clinical settings and these observations confirm significant prognostic factors for each from a diverse real-world cohort. Additionally, these findings suggest that extra diligence be taken with "young adults" (aged 18-35 at diagnosis) as pediatric-type GIST may present well beyond adolescence, particularly as these distinct sub-types have different causes, and consequently respond differently to treatments.

Population-Based Epidemiology and Mortality of Small Malignant Gastrointestinal Stromal Tumors in the USA

“…Consistent with this hypothesis, Call et al found that among pediatric GIST cases, patients were predominately female. 22 While our study included no pediatric cases of GIST, it is possible that GISTs <2 cm share more characteristics with pediatric GIST as opposed to adult GIST, thus shifting the sex distribution. In terms of racial differences, malignant GISTs <2 cm were more common in Blacks as compared to Whites, consistent with our earlier finding in all patients with GIST.…”

Update on Gastrointestinal Stromal Tumors for Radiologists

“…Though complete surgical resection is feasible in a substantial proportion of GISTs, relapses are common, especially with high-risk GISTs (2). Surveillance with imaging in these patients can help in timely detection of relapses.…”

“…Though initially labeled histologically as leiomyosarcomas, the identification of unique activating mutations in KIT gene enabled classification of GIST as a distinct entity (1). GIST like other soft tissue sarcomas was conventionally associated with poor prognosis with a 5-year survival of 5–20% mainly due to resistance to conventional chemotherapy and radiotherapy (23). The discovery of imatinib mesylate which is a small molecule inhibitor of receptor tyrosine kinases (RTK) notably KIT dramatically changed the outcome of patients with GIST (4).…”

Can D-Dimer Measurement Reduce the Frequency of Radiological Assessment in Patients Receiving Palliative Imatinib for Gastrointestinal Stromal Tumor (GIST)?

“…A log-rank test was used to test for significant prognostic ability of baseline D-dimer levels. Adjustment for baseline clinical characteristics previously identified as prognostic in advanced GIST was undertaken using the Cox proportional hazards model [11][12][13] . Genetic mutation analysis was not conducted in patients diagnosed early in the series therefore this was not considered.…”