Nigro Maria Concetta, Marchetti Andrea, Fumagalli Elena Rosa, De Luca Ida, Bertuzzi Alexia Francesca, Grimaudo Maria Susanna, Grignani Giovanni, D'Ambrosio Lorenzo, Merlini Alessandra, Badalamenti Giuseppe, Incorvaia Lorena, Dimino Alessandra, Gasperoni Silvia, Vincenzi Bruno, Fanti Stefano, Di Federico Alessandro, Campana Davide, Pantaleo Maria Abbondanza, Nannini Margherita
Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
Medical Oncology Unit 2, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Istituto Nazionale dei Tumori, Milano, Italy.
JAMA Netw Open. 2025 Jan 2;8(1):e2456058. doi: 10.1001/jamanetworkopen.2024.56058.
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.
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.
PDGFRA-mutant GIST and [18F]FDG-PET.
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.
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.
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.
D842V血小板衍生生长因子受体α（PDGFRA）突变确定了胃肠道间质瘤（GIST）的一个分子亚组，该亚组主要对标准酪氨酸激酶抑制剂耐药，且总体行为更为惰性。尽管18F-氟脱氧葡萄糖标记的正电子发射断层扫描（[18F]FDG-PET）功能成像在GIST中已被证明发挥作用，尤其是在肿瘤反应的早期评估中，但对于GIST分子亚型的[18F]FDG摄取情况了解较少。
评估PDGFRA突变型GIST中[18F]FDG的摄取程度，并更好地界定功能成像在这一罕见且特殊的GIST亚组中的作用。
设计、地点和参与者：这项多机构回顾性队列研究涉及意大利的7个GIST参考中心，纳入了2000年1月1日至2023年12月31日期间接受[18F]FDG-PET检查的PDGFRA突变型GIST患者。收集了原发性肿瘤或转移性疾病的最大标准化摄取值（SUVmax）数据。
PDGFRA突变型GIST和[18F]FDG-PET。
主要结局是PDGFRA突变型GIST的[18F]FDG摄取程度，重点关注D842V突变亚组。次要目标是评估[18F]FDG摄取程度与主要临床病理特征之间的关联。
分析共纳入71例PDGFRA突变型GIST患者：D842V亚组（A组）37例（52.1%），非D842V亚组（B组）34例（47.9%）。此外，70例KIT外显子11突变型GIST患者作为对照组（C组）。在所有141名参与者中，诊断时的中位年龄为59岁（范围26 - 89岁），81例患者（57.4%）为男性。总体而言，中位SUVmax为4.4（四分位间距，0 - 10.1），而A组的中位SUVmax为0（四分位间距，0 - 3.2）；B组为3.6（四分位间距，0 - 5.1）；C组为10.1（四分位间距，5.1 - 13.9）。PDGFRA突变型GIST的中位SUVmax显著低于KIT外显子11突变型GIST的中位值（0[四分位间距，0 - 4.3]对10.1[四分位间距，5.1 - 14.0]；P <.001）。与非D842V亚组相比，D842V亚组的中位[18F]FDG摄取显著更低（0[四分位间距，0 - 3.2]对3.6[四分位间距，0 - 5.1]；P = 0.02）。此外，胃原发性肿瘤、肿瘤大小大于10 cm以及SUVmax为5.75或更低这三者与PDGFRA突变型GIST的识别相关。
在这项针对PDGFRA突变型GIST患者的队列研究中，与其他GIST亚组相比，D842V突变型GIST的[18F]FDG摄取总体较低。因此，[18F]FDG-PET功能成像在这一GIST亚组中的作用可能有限，其潜在的预后和预测价值应进一步探索。
