<sup>18</sup>F-Fluorodeoxyglucose Uptake in <i>PDGFRA</i>-Mutant Gastrointestinal Stromal Tumors
Authors: Maria Concetta Nigro, Andrea Marchetti, Elena Rosa Fumagalli, Ida De Luca, Alexia Francesca Bertuzzi, Maria Susanna Grimaudo, Giovanni Grignani, Lorenzo D’Ambrosio, Alessandra Merlini, Giuseppe Badalamenti, Lorena Incorvaia, Alessandra Dimino, Silvia Gasperoni, Bruno Vincenzi, Stefano Fanti, Alessandro Di Federico, Davide Campana, Maria Abbondanza Pantaleo, Margherita Nannini, Annalisa Astolfi, Alice Costa, Manuela Ianni, Massimo Del Gaudio, Dario de Biase, Maria Giulia Pirini
Journal: JAMA Network Open (2025)

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 18 F-fluorodeoxyglucose–labeled positron emission tomography ([ 18 F]FDG-PET) plays a proven role in GISTs, especially in early assessment of tumor response, less is known about [ 18 F]FDG uptake according to the GIST molecular subtypes. Objective To evaluate the degree of [ 18 F]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 [ 18 F]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 [ 18 F]FDG-PET. Main Outcome and Measure The primary outcome was the degree of [ 18 F]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 [ 18 F]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 &amp;amp;lt; .001). Median [ 18 F]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 [ 18 F]FDG uptake compared with other GIST subgroups. Therefore, the role of functional imaging with [ 18 F]FDG-PET in this subset of GISTs may be limited and should be further explored for its potential prognostic and predictive value.