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18F-Fluorodeoxyglucose Uptake in PDGFRA-Mutant Gastrointestinal Stromal Tumors
Maria Concetta Nigro1, Andrea Marchetti1, Elena Rosa Fumagalli2
1Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
Importance:
The D842V platelet-derived growth factor receptor α (PDGFRA) mutation identifies a molecular subgroup of gastrointestinal stromal tumors (GISTs), primarily resistant to standard tyrosine kinase inhibitors and with an overall more indolent behavior. Although functional imaging with 18F-fluorodeoxyglucose-labeled positron emission tomography ([18F]FDG-PET) plays a proven role in GISTs, especially in early assessment of tumor response, less is known about [18F]FDG uptake according to the GIST molecular subtypes.
Objective:
To evaluate the degree of [18F]FDG uptake in PDGFRA-mutant GISTs and better define the role of functional imaging in this rare and peculiar subset of GISTs.
Design, Setting, And Participants:
This multi-institutional retrospective cohort study involving 7 GIST reference centers in Italy included patients with PDGFRA-mutant GIST who underwent [18F]FDG-PET from January 1, 2000, to December 31, 2023. Data on the maximum standardized uptake value (SUVmax) of primary tumor or metastatic disease were collected.
Exposure:
PDGFRA-mutant GIST and [18F]FDG-PET.
Main Outcome And Measure:
The primary outcome was the degree of [18F]FDG uptake of PDGFRA-mutant GISTs, with a focus on the D842V-mutant subgroup. Secondary objectives were to assess the association between the degree of [18F]FDG uptake and main clinicopathologic features.
Results:
A total of 71 patients with PDGFRA-mutant GISTs were included in the analysis: 37 (52.1%) in the D842V subgroup (group A) and 34 (47.9%) in the non-D842V subgroup (group B). Additionally, 70 patients with KIT exon 11-mutant GIST served as a control group (group C). For all 141 participants, the median age at diagnosis was 59 (range, 26-89) years, and 81 patients (57.4%) were male. Overall, the median SUVmax was 4.4 (IQR, 0-10.1), while the median SUVmax for group A was 0 (IQR, 0-3.2); for group B, 3.6 (IQR, 0-5.1); and for group C, 10.1 (IQR, 5.1-13.9). The median SUVmax of PDGFRA-mutant GISTs was significantly lower than the median value of KIT exon 11-mutant GISTs (0 [IQR, 0-4.3] vs 10.1 [IQR, 5.1-14.0]; P < .001). Median [18F]FDG uptake was significantly lower in the D842V subgroup compared with the non-D842V subgroup (0 [IQR, 0-3.2] vs 3.6 [IQR, 0-5.1]; P = .02). Moreover, the triad of gastric primary tumor, tumor size greater than 10 cm, and SUVmax of 5.75 or less was associated with identification of PDGFRA-mutant GISTs.
Conclusions And Relevance:
In this cohort study of patients with PDGFRA-mutant GISTs, the D842V-mutant GISTs were associated with an overall lower [18F]FDG uptake compared with other GIST subgroups. Therefore, the role of functional imaging with [18F]FDG-PET in this subset of GISTs may be limited and should be further explored for its potential prognostic and predictive value.
Insights
Gastrointestinal stromal tumors (GISTs) with PDGFRA D842V mutations show significantly lower [18F]FDG uptake than other GISTs. This suggests limited utility for [18F]FDG-PET in this specific GIST subtype, warranting further research.
Area of Science:
- Oncology
- Molecular Imaging
- Gastroenterology
Background:
- The D842V mutation in platelet-derived growth factor receptor α (PDGFRA) defines a GIST subgroup resistant to tyrosine kinase inhibitors and exhibiting indolent behavior.
- While 18F-fluorodeoxyglucose-labeled positron emission tomography ([18F]FDG-PET) is established for GIST response assessment, its utility across molecular subtypes remains unclear.
Purpose of the Study:
- To quantify [18F]FDG uptake in PDGFRA-mutant GISTs.
- To explore the role of functional imaging in this specific GIST subset.
Main Methods:
- A multi-institutional retrospective cohort study included 71 patients with PDGFRA-mutant GISTs (37 D842V, 34 non-D842V) and 70 with KIT exon 11-mutant GISTs (controls).
- Data on maximum standardized uptake value (SUVmax) from [18F]FDG-PET were collected and analyzed.
Main Results:
- PDGFRA-mutant GISTs exhibited significantly lower median SUVmax (0 [IQR, 0-4.3]) compared to KIT exon 11-mutant GISTs (10.1 [IQR, 5.1-14.0]; P < .001).
- The D842V subgroup showed lower median SUVmax (0 [IQR, 0-3.2]) than the non-D842V subgroup (3.6 [IQR, 0-5.1]; P = .02).
- Gastric primary tumor, size >10 cm, and SUVmax ≤5.75 identified PDGFRA-mutant GISTs.
Conclusions:
- D842V-mutant GISTs demonstrate markedly reduced [18F]FDG uptake compared to other GIST molecular subtypes.
- The role of [18F]FDG-PET in D842V-mutant GISTs may be limited, necessitating further investigation into its prognostic and predictive value.
