Clinicopathological and therapeutic analysis of PDGFRA mutated gastrointestinal stromal tumor

Background: Platelet-Derived Growth Factor Receptor Alpha (PDGFRA) mutation has causes a rare subgroup of gastrointestinal stromal tumor (GIST) and not too much attention has been paid on it until the appearance of Avapritinib. This study aims to explore the clinicopathological features, therapy and prognosis of PDGFRAmutant GIST for better understanding and clinical practice. Method: 119 PDGFRA-mutant GIST patients were retrospectively collected from 2038 patients who underwent genetic testing. Kaplan-Meier method was used.Results: The incidence rate of PDGFRA-mutant GIST in our center was 5.8 %, with 79 males, 40 females, and a median age of 57 (25-80) years old. All the tumors were in the stomach, among which 60 were epithelioid type, 25 were spindle type and 34 were mixed type. There were 13 cases of exon 12 mutation and 106 cases of exon 18 mutation including 83 cases of D842V mutation (69.7 %). During a median follow-up of 49.6 (range, 1-154) months, progression could be observed in 12 patients with gene mutation at the codon 842 of exon 18, another case was V561D mutation in exon 12. The 5-year diseases-free survival (DFS) was 90.1 %, which was associated with the loss of CD34 expression (P<0.001). Patients in D842V group showed a marginal worse prognosis than those in non-D842V group (P = 0.163). According to the NIH criteria, high risk group showed a poorer prognosis than non-high risk group (P = 0.003), however, there were no significant differences among the three non-high risk groups (P = 0.495, P = 0.652). Among 13 advanced patients, 5 cases (treated with Avapritinib) achieved partial remission.Conclusion: PDGFRA-mutant GIST mostly derived from stomach, with a relative indolent behavior. D842V mutation and lose of CD34 expression were adverse prognostic factors. Avapritinib can effectively control advanced patients in a certain period of time.