11C-methionine-18F-FDG dual-PET-tracer–based target delineation of malignant glioma: evaluation of its geometrical and clinical features for planning radiation therapy

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OBJECTIVE

It is important to correctly and precisely define the target volume for radiotherapy (RT) of malignant glioma. 11C-methionine (MET) positron emission tomography (PET) holds promise for detecting areas of glioma cell infiltration: the authors’ previous research showed that the magnitude of disruption of MET and 18F-fluorodeoxyglucose (FDG) uptake correlation (decoupling score [DS]) precisely reflects glioma cell invasion. The purpose of the present study was to analyze volumetric and geometrical properties of RT target delineation based on DS and compare them with those based on MRI.

METHODS

Twenty-five patients with a diagnosis of malignant glioma were included in this study. Three target volumes were compared: 1) contrast-enhancing core lesions identified by contrast-enhanced T1-weighted images (T1Gd), 2) high-intensity lesions on T2-weighted images, and 3) lesions showing high DS (DS ≥ 3; hDS). The geometrical differences of these target volumes were assessed by calculating the probabilities of overlap and one encompassing the other. The correlation of geometrical features of RT planning and recurrence patterns was further analyzed.

RESULTS

The analysis revealed that T1Gd with a 2.0-cm margin was able to cover the entire high DS area only in 6 (24%) patients, which indicates that microscopic invasion of glioma cells often extended more than 2.0 cm beyond a Gd-enhanced core lesion. Insufficient coverage of high DS regions with RT target volumes was suggested to be a risk for out-of-field recurrence. Higher coverage of hDS by T1Gd with a 2-cm margin (i.e., higher values of “[T1Gd + 2 cm]/hDS”) had a trend to positively impact overall and progression-free survival. Cox regression analysis demonstrated that low coverage of hDS by T1Gd with a 2-cm margin was predictive of disease recurrence outside the Gd-enhanced core lesion, indicative of out-of-field reoccurrence.

CONCLUSIONS

The findings of this study indicate that MRI is inadequate for target delineation for RT in malignant glioma treatment. Expanding the treated margins substantially beyond the MRI-based target volume may reduce the risk of undertreatment, but it may also result in unnecessary irradiation of uninvolved regions. As MET/FDG PET-DS seems to provide more accurate information for target delineation than MRI in malignant glioma treatment, this method should be further evaluated on a larger scale.

ABBREVIATIONS DS = decoupling score; FDG = 18F-fluorodeoxyglucose; HR = hazard ratio; Met = 11C-methionine; NCC = National Cancer Center Research Institute; ONH = Osaka National Hospital; OS = overall survival; PET = positron emission tomography; PFS = progression-free survival; qPCR = quantitative polymerase chain reaction; ROI = region of interest; RT = radiotherapy; T/N = tumor to normal tissue; VOI = voxel of interest.

Article Information

Correspondence Manabu Kinoshita: Osaka International Cancer Institute, Osaka, Japan. mail@manabukinoshita.com.

INCLUDE WHEN CITING Published online September 21, 2018; DOI: 10.3171/2018.4.JNS1859.

Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

© AANS, except where prohibited by US copyright law.

Headings

Figures

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    Theoretical framework behind decoupling score (DS). A: The DS is defined by the “decoupled” uptake of 11C-methionine (Met) and 18F-FDG (FDG) at the tumor invasive area. B: The “decoupling map,” a reconstructed 3D image visualizing the DS, was achieved in a voxel-wise manner. Figure is available in color online only.

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    Case presentation for target delineation in a 71-year-old man. One can easily appreciate the geometrical difference of the tumor invasive area defined by T2-weighted MRI (pink) and by the DS (yellow). Figure is available in color online only.

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    Geometrical analyses. A: Probability of underestimating tumor volume with different margins added to the Gd-enhancing region on T1-weighted MRI (T1Gd) in comparison with the high DS region (hDS). B: Percentage of overlap between T2 (the area of high signal intensity on T2-weighted MRI) and hDS outside a Gd-enhancing lesion. C: Probability of underestimating tumor volume with different margins added to T2 with T1Gd in comparison with hDS with T1Gd. D: The absolute volumes outside hDS with T1Gd for the different margins added to T2 with T1Gd (in C). The boxes represent interquartile ranges, with medians indicated, and the whiskers indicate the full ranges (minimum to maximum values).

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    Case 7. Typical imaging findings of recurrence (rec.) outside of initial Gd-enhancing lesion. The patient was a 36-year-old woman with anaplastic astrocytoma, IDH wildtype, of the left frontal lobe. A small Gd-enhancing lesion was observed in the left frontal lobe, with most of the lesion demonstrating T2/FLAIR hyperintensity. A tumor biopsy was performed, and RT was designed based on MRI. A new Gd-enhancing lesion at the corpus callosum was identified as disease recurrence. This lesion was located at the marginal area of the boost irradiated fields, a location that already presented high DS prior to surgery, although it was outside of T2/FLAIR hyperintensity. Figure is available in color online only.

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    Four illustrative cases of disease recurrence outside of the enhancing lesion on Gd-enhanced T1-weighted images. Recurrence (arrows) was identified 34 months after surgery in proximity to the high DS lesions that were identified retrospectively (during our post hoc analysis) on the basis of preoperative studies but were not evident on the MR images and were therefore not identified at the time of the original treatment. Figure is available in color online only.

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    Kaplan-Meier curves showing estimates for OS (A) and PFS (B) of patients stratified by probability of T1Gd + 2–cm margin encompassing hDS. Progression-free survival was significantly better for the good coverage group than for the poor coverage group (p = 0.05, log-rank test).

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