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Clinicopathological and therapeutic analysis of PDGFRA mutated gastrointestinal stromal tumor
Wen Huang1, Wei Yuan1, Lei Ren1
1Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China.
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 PDGFRA-mutant 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.
Insights
Platelet-Derived Growth Factor Receptor Alpha (PDGFRA) mutations are rare in gastrointestinal stromal tumors (GIST) but are often indolent. Loss of CD34 expression and specific PDGFRA mutations like D842V indicate a poorer prognosis, while Avapritinib shows promise in advanced cases.
Area of Science:
- Oncology
- Gastroenterology
- Molecular Biology
Background:
- Platelet-Derived Growth Factor Receptor Alpha (PDGFRA) mutations define a rare subset of gastrointestinal stromal tumors (GIST).
- These mutations have historically received less attention compared to other GIST subtypes.
- The advent of targeted therapies like Avapritinib has renewed interest in understanding PDGFRA-mutant GIST.
Purpose of the Study:
- To investigate the clinicopathological characteristics of PDGFRA-mutant GIST.
- To evaluate the therapeutic responses and prognostic factors in patients with PDGFRA-mutant GIST.
- To enhance clinical understanding and management strategies for this specific GIST subgroup.
Main Methods:
- Retrospective analysis of 119 PDGFRA-mutant GIST patients identified from 2038 patients who underwent genetic testing.
- Utilized the Kaplan-Meier method for survival analysis.
- Clinicopathological data and treatment outcomes were reviewed.
Main Results:
- PDGFRA-mutant GIST occurred in 5.8% of patients, predominantly in the stomach, with epithelioid, spindle, and mixed types observed.
- Exon 18 mutations, particularly D842V (69.7% of cases), were more common than exon 12 mutations.
- The 5-year disease-free survival was 90.1%, negatively associated with CD34 expression loss (P<0.001).
- While D842V mutations showed a trend towards worse prognosis (P=0.163), high-risk GIST (NIH criteria) had significantly poorer outcomes (P=0.003).
- Five of 13 advanced patients treated with Avapritinib achieved partial remission.
Conclusions:
- PDGFRA-mutant GIST predominantly originates in the stomach and exhibits relatively indolent behavior.
- Loss of CD34 expression and the D842V mutation are identified as adverse prognostic factors.
- Avapritinib demonstrates efficacy in controlling advanced PDGFRA-mutant GIST for a period.
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