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Multicenter Study
. 2025 Jan 2;8(1):e2456058.
doi: 10.1001/jamanetworkopen.2024.56058.

18F-Fluorodeoxyglucose Uptake in PDGFRA-Mutant Gastrointestinal Stromal Tumors

Maria Concetta Nigro  1 , Andrea Marchetti  1 , Elena Rosa Fumagalli  2 , Ida De Luca  2 , Alexia Francesca Bertuzzi  3 , Maria Susanna Grimaudo  3 , Giovanni Grignani  4   5 , Lorenzo D'Ambrosio  6   7 , Alessandra Merlini  5   6 , Giuseppe Badalamenti  8 , Lorena Incorvaia  8 , Alessandra Dimino  8 , Silvia Gasperoni  9 , Bruno Vincenzi  10 , Stefano Fanti  1   11 , Alessandro Di Federico  1 , Davide Campana  1   12 , Maria Abbondanza Pantaleo  1   12 , Margherita Nannini  1   12 ; Tumori Rari Bologna
Collaborators, Affiliations
Multicenter Study

18F-Fluorodeoxyglucose Uptake in PDGFRA-Mutant Gastrointestinal Stromal Tumors

Maria Concetta Nigro et al. JAMA Netw Open. .

Abstract

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Fumagalli reported serving on the advisory board of Deciphera Pharmaceuticals Inc and receiving research funding from Deciphera Pharmaceuticals Inc, IDRx, Cogent Biosciences Inc, Blueprint Medicines Corporation, Boehringer Ingelheim, PharmaMar, Karyopharm Therapeutics Inc, Eisai Co Ltd, Daiichi Sankyo Company Limited, Rain Oncology Inc, Glaxo PLC, and Epizyme Inc outside the submitted work. Dr Bertuzzi reported receiving travel funding from Istituto Gentili and PharmaMar and personal fees from Deciphera Pharmaceuticals Inc outside the submitted work. Dr Grimaudo reported receiving personal fees from Deciphera Pharmaceuticals Inc and nonfinancial support from Istituto Gentili outside the submitted work. Dr D’Ambrosio reported serving on the advisory boards of PSI CRO Italy, Boerhringer Ingelheim, GSK, Eisai Co Ltd, and AstraZeneca and meeting participation for PharmaMar and Amgen Inc outside the submitted work. Dr Merlini reported receiving grant funding from PharmaMar and participating in an expert meeting for Boehringher Ingelheim outside the submitted work. Prof Incorvaia reported receiving personal fees from Deciphera Pharmaceuticals Inc, BMS, and Ipsen outside the submitted work. Dr Di Federico reported serving on advisory boards for Hanson Wade and Novartis AG and receiving honoraria from the Society for Immunotherapy of Cancer outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Graphic Representation of Maximum Standardized Uptake Value (SUVmax) Distribution and Median SUVmax of the 3 Molecular Subgroups of Gastrointestinal Stromal Tumors
A, The median SUVmax was 0. B, The median SUVmax was 3.6. C, The median SUVmax was 10.1. The curves represent the SUVmax distribution in each molecular subgroup. PDGFRA indicates platelet-derived growth factor receptor α.
Figure 2.
Figure 2.. Association Between 18F-Fluorodeoxyglucose Uptake and Molecular Pattern of Gastrointestinal Stromal Tumors
Horizontal black bars indicate the median; error bars forming the rectangle represent the interquartile range, while the upper error bar represents the maximum standardized uptake value (SUVmax) that is not an outlier and the lower error bar represents the minimum SUVmax that is not an outlier. PDGFRA indicates platelet-derived growth factor receptor α. aThe median SUVmax of PDGFRA-mutant GISTs was significantly lower than that of KIT exon 11–mutant GISTs (0 [IQR, 0-4.3] vs 10.1 [IQR, 5.1-14.0]; P < .001). bWithin PDGFRA-mutant gastrointestinal stromal tumors (GISTs), median SUVmax was significantly lower in D842V-mutant GISTs compared with non–D842V-mutant ones (0 [IQR, 0-3.2] vs 3.6 [IQR, 0-5.1]; P = .02).
See this image and copyright information in PMC

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