18F-DOPA PET Improves Response Assessment in IDH-Mutant Glioma Treated With IDH Inhibitors

Clinical Summary: 

• Design/Population: This retrospective, single-center study evaluated serial MRI and ¹⁸F-DOPA PET imaging in 20 patients with IDH-mutant astrocytoma or oligodendroglioma treated with the IDH inhibitors ivosidenib or vorasidenib. MRI responses were assessed using RANO 2.0 criteria, and PET responses were evaluated using PET RANO 1.0 criteria.
• Key Outcomes: While no radiographic responses were detected by conventional MRI, ¹⁸F-DOPA PET identified metabolic responses in half of the patients, including complete and partial metabolic responses. Reductions in metabolic tumor volume were associated with longer progression-free survival and helped distinguish treatment-related imaging changes from true disease progression.
• Clinical Relevance: These findings suggest that ¹⁸F-DOPA PET may complement MRI by providing an earlier and more sensitive assessment of treatment response in patients with IDH-mutant glioma receiving IDH-targeted therapy.

Diego Prost, MD, Pitié-Salpêtrière University Hospital, Paris, France, discusses a retrospective study evaluating the role of ¹⁸F-DOPA PET in assessing response to IDH inhibitors in patients with IDH-mutant glioma. The study compared metabolic imaging with conventional MRI to determine whether PET could better characterize treatment response.

The analysis demonstrated that ¹⁸F-DOPA PET detected metabolic responses not identified by MRI and that reductions in metabolic tumor volume were associated with improved progression-free survival. These findings support further investigation of metabolic imaging as an early biomarker of response to IDH-targeted therapy in diffuse glioma.

Transcript:

My name is Diego Prost, I’m a medical oncologist at Pitié-Salpêtrière Hospital in Paris. In this video, I will present our recent work on how ¹⁸F-DOPA-PET can improve the way we assess treatment response in IDH-mutant glioma patients treated with IDH inhibitors.

Diffuse gliomas are the most common malignant primary brain tumors and about ⅓ of them have a mutation in the IDH1/2 genes. In recent years, small-molecule IDH inhibitors, such as ivosidenib or vorasidenib, have emerged as promising targeted therapies for patients with IDH-mutant gliomas. However, in daily practice, we rely on conventional MRI to evaluate response. 

Under IDH inhibitors, radiologic responses are often rare, and many patients are classified as having stable disease for long periods of time. This creates 2 main problems: First, we lack early biomarkers that tell us whether the patient is truly benefiting from treatment and second, in a population that is often clinically stable, it can be difficult to decide whether to continue or stop treatment. 

PET imaging, like ¹⁸F-DOPA-PET, is more sensitive for detecting tumor functional activity, and it is already used in many centers to help with diagnosis and follow-up. To address this gap, we performed a retrospective, single-center study of 20 patients with IDH-mutant astrocytoma or oligodendroglioma treated with ivosidenib or vorasidenib. We used RANO 2.0 criteria for MRI assessment and PET RANO 1.0 criteria for PET assessment, focusing mainly on metabolic tumor volume and tumor-to-background ratios.

Our first key finding is that we did not observe any formal radiologic response on MRI. In contrast, ¹⁸F-DOPA-PET detected a significant metabolic response in half of the patients. We observed 1 complete metabolic response and 9 partial metabolic responses based on reductions in metabolic tumor volume and tracer uptake. We also found 2 patients who showed an increase in their FLAIR lesion at the first evaluation, a phenomenon already described with IDH inhibitors during the first 6 months of treatment. In these patients, PET showed a metabolic response despite the FLAIR increase. When we looked at outcomes, the functional response on PET was not just a cosmetic change, a reduction in metabolic tumor volume was associated with longer progression-free survival. 

So what does this mean for clinical practice– First, in patients treated with IDH inhibitors, adding ¹⁸F-DOPA-PET gives us extra information about tumor dynamics that we would miss using only MRI. Second, ¹⁸F-DOPA-PET seems to be a sensitive tool to detect early metabolic changes and to distinguish true progression from treatment-related fluctuations. [Lastly], our data suggest that metabolic tumor volume on PET could serve as an early marker of benefit for IDH inhibitors.

Of course, this is a preliminary study in a small cohort, larger prospective studies and standardized imaging protocols will be needed before these approaches can be widely adopted.

Source: 

Prost D, Nichelli L, Rozenblum L, et al. 18F-DOPA-PET and advanced MRI improve treatment response assessment in IDH1/2-mutant gliomas treated with IDH inhibitors. Clin Cancer Res. Published online: February 2, 2026. doi: 10.1158/1078-0432.CCR-25-0279