Non-D842V platelet-derived growth factor alpha (PDGFRA) mutant gastrointestinal stromal tumours (GISTs): A distinctive and heterogeneous subgroup— Experience from regional centre in United Kingdom.

Abstract

e23517 Background: PDGFRA GISTs account for 10-15% of all gists and are almost exclusively gastric in origin. Around 50% of PDGFRA gists have mutations other than exon 18 D842V mutation. These Non D842V PDGFRA mutant gists are ultra rare and the natural history and response to kinase inhibitors is not well known. We present our 15 year experience with PDGFRA Non D842V gist from a regional centre in United Kingdom. Methods: Data from the Cambridge GIST database was analysed from 2010-2015. Non D842V gist patients demographics, tumour characteristics, mutational status and response to tyrosine kinase inhibitors (TKIs) was extracted. Response to TKIs was evaluated on imaging and/or histology. Results: N = 40. M:F 26:14, Median age 64 years (range 15-84). Primary site of gist was gastric in 39 and 1 patient had extra gastrointestinal gist (E-GIST). Anatomical location ins stomach--22/40 in prepyloric/antral/distal body and 18/40 in midbody/lesser curve/greater curve. No PDGFRA gists were noted in gastric cardia or fundus Median size 7 cm (range 1-30 cm). Histology--31/40 were epithelioid or mixed only 9/40 had spindle cell morphology. Mitotic index median 4, range 0-50. On immunohistochemistry, 17/40 had patchy CD117 staining and 6/40 had patchy desmin positivity. All gists were DOG-1 positive. Treatment outcomes: 3 patients treated with Imatinib in neoadjuvant/metastatic setting had radiological and or histological responses. 3 patients were treated with 4th line Sorafenib (PDGFRA exon 18 codon 843-847 deletion). Subjective improvement was observed in all three patients and one patient has ongoing partial response. Dose reduction was needed all three patients. Conclusions: PDGFRA Non D842V gists are a heterogenous and distinct subgroup of gists. These are sensitve to imatinib. Sorafenib is active in gists with PDGFRA exon 18 codon 843-847 deletion. Larger datasets are needed to characterise the natural history, TKI responsiveness and resistance mechanisms in PDGFRA non D842V gists. Distribution & types of PDGFRA mutations. Number of patients PDGFRA Exon Mutation Comments 11 12 Codon 561 (p.Val561Asp) Most common exon 12 mutation (50%) 5 14 Codon 659 (p.Arg659Tyr) Hot spot mutation 100% 24 18 Codon 842-847 del/ins or deletion 80%