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Glioma Recurrence Versus Radiation Necrosis?

Posted Feb 28, 2010 Updated Apr 7, 2023
By Yelda Ozsunar MD , Mark E. Mullins MD PhD , Kenneth Kwong PhD , Fred H. Hochberg MD , Christine Ament MD , Pamela W. Schaefer MD , R. Gilberto Gonzalez MD PhD , Michael H. Lev MD
14 min read

Rationale and Objectives

Distinguishing recurrent glial tumor from radiation necrosis can be challenging. The purpose of this pilot study was to preliminarily compare unenhanced arterial spin-labeled (ASL) imaging, dynamic susceptibility contrast-enhanced cerebral blood volume (DSCE-CBV) magnetic resonance imaging, and positron emission tomographic (PET) imaging in distinguishing predominant glioma recurrence or progression from predominant radiation necrosis in postoperative patients treated with proton-beam therapy.

Methods

Patients with grade II to IV glioma previously treated with surgery and proton-beam therapy were enrolled on the basis of new enhancing nodules or masses with primary differential diagnoses of predominant tumor recurrence or progression versus radiation necrosis. ASL, DSCE-CBV, and PET examinations were assessed by visual qualitative and quantitative analysis for the detection of predominant tumor recurrence. Imaging results were correlated with a clinical-pathologic reference standard.

Results

Thirty patients were studied, resulting in 33 ASL, 32 DSCE-CBV, and 26 PET examinations. On the basis of visual inspection, the sensitivities of PET, ASL, and DSCE-CBV examinations for detecting high-grade tumor foci were 81%, 88%, and 86%, respectively. The highest sensitivity values for quantitative ASL imaging were obtained using a normalized cutoff ratio of 1.3, resulting in sensitivity of 94% for ASL imaging and 71% for DSCE-CBV imaging. When predominant high-grade tumors with superimposed regions of predominant mixed radiation necrosis were excluded, DSCE-CBV sensitivity improved to 90%, but ASL sensitivity remained unchanged.

Conclusions

Compared with DSCE-CBV imaging, ASL imaging may more accurately distinguish predominant recurrent high-grade glioma from radiation necrosis, especially in regions with mixed radiation necrosis, for which DSCE-CBV imaging may underestimate true blood volume because of leakage artifacts.

Primary central nervous system neoplasia is one of the most frequent causes of death between 15 and 35 years of age . Gliomas constitute >90% of primary brain tumors diagnosed after the second decade of life . Despite treatment with chemotherapy and radiation, including proton-beam therapy (PBT) and other radiosurgery, the majority of these tumors progress and/or recur. Moreover, treatment with radiation remains associated with tissue necrosis that may also lead to clinical deterioration . When a magnetic resonance imaging (MRI) scan of the brain shows a new enhancing lesion after a patient has undergone surgery and radiation for high-grade glioma, the differentiation of predominant recurrent tumor (or progression of tumor) from predominant radiation necrosis is often crucial, because the two entities have different treatment approaches and prognoses .

Computed tomographic and conventional MRI findings are relatively nonspecific, although some findings on MRI, especially when presenting in combination, may favor a given diagnosis . Positron emission tomographic (PET) and single photon-emission computed tomographic imaging provide additional information regarding tumor metabolism . Although early results with fluorodeoxyglucose (FDG) PET imaging were encouraging, some studies have reported specificities as low as 18%, high cost, and limited availability . Glioma recurrence or progression and radiation necrosis may be frequently mixed (in terms of pathology), and residual microscopic tumor foci are often present, even in so-called pure necrosis cases, further complicating the situation .

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Materials and methods

Patient Enrollment

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Brain Tumors

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Clinical Follow-Up

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PET Examinations

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MRI Examinations

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ASL Imaging

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DSCE-CBV Imaging

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Data Analysis

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Statistical Analysis

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Results

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Table 1

Distribution of Sensitivity and Specificity Values of Predominantly Recurrent or Progressive Versus Nonrecurrent High-grade Tumor

Modality Total Nonrecurrence Recurrence Sensitivity Specificity ASL imaging 33 12 (36%) 21 (64%) 88% 89% DSCE-CBV imaging 32 10 (33%) 22 (67%) 86% 70% PET imaging 26 12 (46%) 14 (54%) 81% 90% Histopathology 35 12 (34%) 23 (66%)

ASL, arterial spin-labeled; DSCE-CBV, dynamic susceptibility contrast-enhanced cerebral blood volume; PET, positron emission tomographic.

The findings are based on grading scores on three-point scale for ASL, DSCE-CBV, and PET imaging in patients treated with proton-beam therapy (Friedman’s test, P < .01 for all three comparisons). Consensus rating scores of 0 and 1 indicated nonrecurrence, whereas a score of 2 indicated high-grade recurrence.

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Figure 1, A 45-year-old man with a history of attempted resection of grade IV glioma, chemotherapy, proton-beam therapy, and subsequent new abnormal enhancing lesion on follow-up magnetic resonance imaging. Positron emission tomographic image ( a ) shows ring-shaped hypermetabolism in the right frontal lobe (arrow). Contrast-enhanced T1-weighted axial image ( b ) illustrates a heterogeneously ring-enhancing lesion at the site of lesion. Both axial arterial spin-labeled ( c ) and dynamic susceptibility contrast-enhanced cerebral blood volume ( d ) maps show ring-shaped hyperperfusion in the contrast-enhancing lesion, suggesting predominant high-grade tumor recurrence, which was confirmed on histopathology.

Figure 2, A 47-year-old man with a history of attempted resection of grade IV glioma and proton-beam therapy with new abnormal enhancing lesion on follow-up. Positron emission tomographic imaging ( a ) shows hypermetabolism at the site of the lesion on contrast-enhanced T1 axial imaging ( b ). Arterial spin-labeled (ASL) ( c ) and dynamic susceptibility contrast-enhanced cerebral blood volume (DSCE-CBV) ( d ) images show hyperperfusion that correlates with the axial postcontrast T1-weighted image. Note that the lesion is more conspicuous on ASL than on DSCE-CBV imaging. Subsequent surgical resection confirmed predominantly tumor recurrence.

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Figure 3, Receiver-operating characteristic curves for arterial spin-labeled (ASL) and dynamic susceptibility contrast-enhanced cerebral blood volume (DSCE-CBV) images obtained using mean region-of-interest measurement (95% confidence interval for ASL imaging, 0.42–0.97; 95% confidence interval for DSCE-CBV imaging, 0.34–0.97).

Table 2

Test Characteristics for the Detection of Predominant Recurrent or Progressive High-Grade Glioma in PBT-treated Patients, Based on Quantitative ROI Analyses, Applying a Cutoff Ratio of 1.3

ASL Imaging DSCE-CBV Imaging With Mixed Histology Without Mixed Histology With Mixed Histology Without Mixed Histology Variable ( n = 23) ( n = 18) ( n = 19) ( n = 15) Sensitivity 94% 92% 71% 90% Specificity 50% 50% 40% 40% PPV 88% 85% 77% 75% NPV 12% 15% 15% 16%

ASL, arterial spin-labeled; DSCE-CBV, dynamic susceptibility contrast-enhanced cerebral blood volume, NPV, negative predictive value; PBT, proton-beam therapy; PPV, positive predictive value; ROI, region of interest.

The second and fourth columns represent patients excluding mixed high-grade tumor and radiation necrosis.

Table 3

Mean Normalized ROI Values Based on Quantitative ROI Analyses of the Perfusion Map Values, Stratified According to Clinical-pathologic Diagnoses

Normalized ROI ASL Imaging DSCE-CBV Imaging Histopathology ( n = 23) ( n = 19) Predominant radiation necrosis/low-grade tumor 2.0 ± 1.4 ( n = 5) 2 ± 1.5 ( n = 5) Predominant high-grade tumor recurrence 3.9 ± 5 ( n = 13) 2.6 ± 1.8 ( n = 10) Radiation necrosis with mixed high-grade tumor 4.3 ± 1.6 ( n = 5) 1.2 ± 0.3 ( n = 4)

The differences between the nonrecurrence and predominantly high-grade recurrence for histopathologic subgroups were not statistically significant (Student’s t test).

Figure 4, A 58-year-old man with grade IV glioma and a history of attempted resection, proton-beam therapy, and with a new enhancing lesion on follow-up magnetic resonance imaging. Positron emission tomographic imaging (not shown) shows hypometabolism at the site of the abnormally enhancing left parieto-occipital lesion on contrast-enhanced T1-weighted axial image ( a ). Whereas the arterial spin-labeled (ASL) image ( b ) shows hypoperfusion, the dynamic susceptibility contrast-enhanced cerebral blood volume (DSCE-CBV) image ( c ) shows hyperperfusion of the enhancing lesion that is surrounded with hypoperfused region due to vasogenic edema. Histopathology of this lesion confirmed radiation necrosis. This case therefore demonstrates “true-negative” ASL and “false-positive” DSCE-CBV findings.

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Discussion

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Conclusion

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Academic Radiology, Volume 17, Issue 3
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