To our knowledge, this is the first prospective multicenter study of the impact of 18F-FDOPA PET on the clinical management of high-grade gliomas in the setting of suspicion of recurrence after initial treatment. In the framework of effectiveness of diagnostic imaging , it corresponds to a level 3 type study of “diagnostic efficacy thinking” assessing the post-test changes induced by 18F-FDOPA PET imaging. It shows that 18F-FDOPA changed the MRI based intended management in 31 cases (22.5%) and increased the confidence in the initial decision when unchanged in 87 cases (81.3%).
In her study, Walter et al.  first studied 58 patients with high and low grade brain tumors in different settings and found that 18F-FDOPA changed the intended management in 41% and the management changes were actually implemented in 31% of the cases. Unlike in our study, the clinical situations of 18F-FDOPA PET indications were diverse and PET data were not analyzed back to back or coregistered with MRI. However, the majority of the patients were studied in the context of suspected recurrence and MRI changes; the reported impact on the intended management in this subgroup was also 41%. This study included 38% of non WHO III or IV grades. The specific impact in low versus high-grade brain tumor management or in initial versus follow-up setting is unknown. This higher impact of 18F-FDOPA is probably mostly due to the study design based on a 3 questionnaires survey sent to the referring physician in Walter’s study whereas in our case these changes were decided on multidisciplinary bases in a directly operational setting. Walter et al. reported a possible bias toward favoring 18F-FDOPA PET in their study since the referring physicians were convinced 18F-FDOPA PET users. This was not the case in our study.
Humbert et al. , addressed a similar issue using 18F-FDOPA PET. The design of the study was the same as our, however this was a prospective monocentric study which included brain metastases as well as high-grade gliomas during the follow up after initial treatment. Furthermore, within the high-grade glioma patients, only 12 were studied for the diagnosis of tumor recurrence. In that subgroup the management was changed in one third of the case. Our study found a smaller percentage of 22.5% which is likely to be more realistic since obtained on 138 studied cases studied in 5 different institutions.
Other studies addressed a similar issue using other radiopharmaceuticals. Hillner et al.  investigated a large series of 367 patients with primary brain tumors from the National Oncological PET registry who underwent 18F-FDG brain PET. They analyzed pre and post PET forms filled by the referring physician and found 38.2% of intents of management changes in light of the 18F-FDG PET findings. However, the article could not document if the planned management changes were actually completed.
Yamane et al. used 11C-methionine PET to separate recurrence from radiation necrosis in brain tumors and its clinical impact based on retrospective questionnaires to the referring physicians. Twenty PET studies were performed for initial diagnosis of brain tumors and 69 for differentiating tumor recurrence from radiation necrosis. In this last subgroup which included various grades of primary brain tumors and metastases, intended management was confirmed in 42 cases and a significant management change due to PET results was found in 18 cases (42.9%).
Brendle et al. very recently published a study that addressed a similar issue using 18Ffluoroethyl-tyrosine (18F-FET) and multiparametric simultaneous PET-MR . In their subgroup of 131 patients studied during the disease course, they demonstrated a changed in patients’ management in 53% of the cases. However, this was a monocentric retrospective study which, by design, did not separate MR form PET induced changes. Nonetheless, it brings forward the interest of PET/MR in that indication as well as the value of dynamic PET data which was not evaluated in our study.
Overall, our study performed prospectively in 5 different centers, shows a slightly inferior rate of changes of patients’ management induced by 18F-FDOPA PET than reported in the literature. However, this is more likely to be generalizable. Furthermore, our study also shows that, when the decision itself was not modified, 18F-FDOPA results increased the confidence of the decision in more than 80% of the cases.
In the literature, the performances of 18F-FDOPA are generally reported as superior to MRI for the diagnosis of HGG recurrence [12, 24, 25]. However, it should be pointed out that, in our study, we measured the performances of step 2 process. 18F-FDOPA performances were not assessed independently from those of MRI since both information were taken into consideration at this step. This correspond to daily practice in which 18F-FDOPA is usually not interpreted without the MRI findings. However, we observe a sensitivity and a specificity of 86% and 64% which are rather in the lower range of the generally reported values for 18F-FDOPA PET alone in that indication [19, 24–26] reflecting the multicenter design of our study.
One limitation of the study concerns the diagnostic performances which were evaluated on surgical confirmation in only 5 cases. Furthermore, our study did not consider the use of a semi-quantitative analysis of 18F-FDOPA images. However, the visual analysis reflects the most common daily practice and neither quantitative static analysis  nor dynamic analysis  has been shown to be superior to visual analysis in that setting. The only exception is very recent the Brendle study in which maximum Tumor to Background Ratio on static 18F-FET and the presence of a washout curve in the kinetic PET analysis appeared as an important parameter. Lastly, the study evaluated the changes in the management induced by the 18F-FDOPA PET without assessing the impact on patient survival. A prospective study comparing the prognosis and the quality of life of patients who benefited from 18F-FDOPA PET information to patients treated without this additional information is necessary to fully answer this question.