Differentiating radiation necrosis from tumor recurrence in high-grade gliomas: Assessing the efficacy of 18F-FDG PET, 11C-methionine PET and perfusion MRI

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Abstract

Purpose

The authors analyzed the characteristics of perfusion magnetic resonance imaging (MRI), 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and 11C-methionine (MET) PET to compare the efficacies of these modalities in making the distinction between radiation necrosis and tumor recurrence of high-grade glioma.

Patients and methods

Ten patients were evaluated with dynamic susceptibility contrast perfusion MRI, 11C-MET PET and 18F-FDG PET to visualize gadolinium-enhanced lesions during the post-radiation follow-up period. In the perfusion MRI, four regions of interest (ROIs) were identified and average values were calculated. A reference ROI of the same size was defined in the contralateral white matter to obtain the relative cerebral blood volume (rCBV). After coregistering the PET images with the MRI, we measured the maximum uptake values of the lesion and of the contralateral cerebral white matter as reference area to calculate the Lmax/Rmax ratio.

Results

The rCBV was higher in the recurrence group than in the necrosis group (p = 0.010). There was no difference between groups in terms of the Lmax/Rmax ratio as derived from the 18F-FDG and 11C-MET PET.

Conclusion

A quantitative rCBV as calculated from a perfusion MRI scan might be superior to the Lmax/Rmax ratio as derived from 18F-FDG and 11C-MET PET in order to distinguish a recurrence of high-grade glioma from radiation necrosis.

Introduction

Since the survival benefit of postoperative 60 Gy whole-brain radiation therapy was first proven in a randomized trial in the 1970s [1], radiotherapy has been a cornerstone in the management of high-grade gliomas. Concurrent and adjuvant temozolomide in combination with radiotherapy after surgery has been shown to improve the survival rates of patients with newly diagnosed glioblastoma. This approach represents the current gold standard treatment for this disease [2]. However, even after various multi-disciplinary approaches for the treatment of patients with high-grade gliomas, tumors often recur, visible as newly enhanced lesions on conventional MRI. Furthermore, the majority of these lesions, which are typically accompanied by surrounding edema, are located at or near the primary site of the disease and within the irradiated volume [3]. However, the distinction between radiation necrosis or treatment effects and tumor recurrence remains a diagnostic challenge that should be evaluated at precisely the right time so as not to disturb the management plan.

To overcome this confusion, the efficacies of diverse methods, including specific techniques for MRI [4], [5], [6], [7], magnetic resonance spectroscopy [8], [9], [10] and PET [11], [12], [13], have been evaluated by various research groups. However, the majority of these studies were designed to show the efficacy of a single method or to assess the same category of modalities, e.g., 11C-MET PET and 18F-FDG PET.

In this paper, we report our experience with high-grade gliomas in patients who underwent radiation therapy with or without chemotherapy following surgical resection. Our goal is to compare the results of perfusion MRI, 18F-FDG PET and 11C-MET PET in distinguishing tumor recurrence from radiation necrosis.

Section snippets

Patient enrollment

All patient data were collected in accordance with the case record form approved by the Institutional Board of Research Associates at Seoul National University Hospital, Seoul, Korea. The authors analyzed patients with pathologically conclusive high-grade glioma (World Health Organization grade III or IV) who underwent surgical resection followed by radiation therapy with or without chemotherapy between 2001 and 2007. We only included patients who satisfied the following criteria: (1) newly

rCBV in perfusion MRI

The L/R ratio of rCBV was significantly higher in the tumor recurrence group (5.72 ± 1.77, mean ± standard deviation) than in the radiation necrosis group (2.53 ± 0.81; p = 0.010). A box-and-whisker diagram for the rCBV illustrates these results in Fig. 1. Newly enhanced lesions with an rCBV of above 3.69 represent tumor recurrence, as obtained through ROC curve analysis with 100% sensitivity and 100% specificity, the area under the curve 1.0 (95% confidence interval 1.000–1.000). The quantitative data

Discussion

Patronas et al. first reported the possibility of using 18F-FDG PET data to distinguish between radiation necrosis and tumor recurrence in 1982 [16], [17]. Since then, there have been several reports concerning the use of 18F-FDG PET as a diagnostic tool to identify enhanced lesions on MRI. These studies have reported that the sensitivity and specificity of 18F-FDG PET are 65–81 and 40–94%, respectively [18], [19], [20], [21]. In addition, some researchers have reported increased diagnostic

Conclusion

There is currently no gold standard in imaging modalities for the diagnosis of newly enhanced lesions on conventional MRI after radiation therapy for high-grade gliomas. Our results reveal the superior characteristics of rCBV, as compared with 18F-FDG and 11C-MET PET, in distinguishing radiation necrosis from tumor recurrence in high-grade glioma, although the statistical significance cannot be showed due to small number of cases.

Conflicts of interest

The authors disclose no direct or indirect conflicts of interest.

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