Gastrointestinal Stromal Tumours (GIST) in Young Adult (18–40 Years) Patients: A Report from the Dutch GIST Registry

Abstract

Gastrointestinal stromal tumour (GIST) is a disease of older adults and is dominated by KIT/PDGFR mutations. In children, GIST is rare, predominantly occurs in girls, has a stomach location and generally lacks KIT/PDGFR mutations. For young adults (YA), aged 18 to 40 years, the typical phenotypic and genotypic patterns are unknown. We therefore aimed to describe the clinical, pathological and molecular characteristics of GIST in in YA. YA GIST patients registered in the Dutch GIST Registry (DGR) were included, and data were compared to those of older adults (OA). From 1010 patients in the DGR, 52 patients were YA (54% male). Main tumour locations were stomach (46%) and small intestine (46%). GIST genetic profiles were mutations in KIT (69%), PDGFRA (6%), SDH deficient (8%), NF1 associated (4%), ETV6-NTRK3 gene fusion (2%) or wildtype (10%). Statistically significant differences were found between the OA and YA patients (localisation, syndromic and mutational status). YA presented more often than OA in an emergency setting (18% vs. 9%). The overall five-year survival rate was 85%. In conclusion, YA GISTs are not similar to typical adult GISTs and also differ from paediatric GISTs, as described in the literature. In this series, we found a relatively high percentage of small intestine GIST, emergency presentation, 25% non-KIT/PDGFRA mutations and a relatively good survival.

Gastrointestinal Stromal Tumor: An Uncommon but Serious Cause of Gastrointestinal Bleeding

“…The incidence has been increasing; but, this may be secondary to an improved diagnostic ability rather than an actual increase in incidence [ 2 ]. GIST is a disease of older adults, and the median age at diagnosis is 65 years, with only less than 10% of patients diagnosed before the age of 40 [ 3 ].…”

Treatment of Gastrointestinal Stromal Tumors (GISTs): A Focus on Younger Patients

“…Young patients with GISTs were more often diagnosed in an emergency setting (18% vs. 9%). The overall 5-year survival rate was 85% [ 13 ].…”

High proportion of wild-type gastrointestinal stromal tumor in a cohort of Chilean patients screened by KIT and PDGFRA exome profiling

“…Studies suggest these tumors may arise or differentiate from interstitial Cajal cells or their precursor stem cells (2). The most frequent primary site is the stomach (45-59%), followed by the small intestine (30-45%) (1,3,4). In terms of survival, GIST patients usually display prolonged overall survival (OS) rates ranging from 8.9 to 13 years.…”

“…In addition to first-line imatinib and sunitinib, other TKIs, such as larotrectinib and entrectinib, are recommended for GIST patients that display NTRK fusions (15). Others, such as avapritinib, are specifically designed for PDGFRA mutations, such as D842V on exon 18 or ripretinib for KIT/PDGFRA mutations that affect exons 9, 11, 13, 14, 17 or 18, including D842V (3,16,17). Therefore, the identification of primary/secondary KIT/ PDGFRA mutations provides key therapeutic information for these treatments, and could identify alternative approaches in anticipation of the development of drug resistance in GIST patients (18)(19)(20).…”