Abstract
BackgroundO-(2-18 F-fluoroethyl)-L-tyrosine-(FET)-PET may be helpful to improve the definition of radiation target volumes in glioblastomas compared with MRI. We analyzed the relapse patterns in FET-PET after a FET- and MRI-based integrated-boost intensity-modulated radiotherapy (IMRT) of glioblastomas to perform an optimized target volume definition.MethodsA relapse pattern analysis was performed in 13 glioblastoma patients treated with radiochemotherapy within a prospective phase-II-study between 2008 and 2009. Radiotherapy was performed as an integrated-boost intensity-modulated radiotherapy (IB-IMRT). The prescribed dose was 72 Gy for the boost target volume, based on baseline FET-PET (FET-1) and 60 Gy for the MRI-based (MRI-1) standard target volume. The single doses were 2.4 and 2.0 Gy, respectively. Location and volume of recurrent tumors in FET-2 and MRI-2 were analyzed related to initial tumor, detected in baseline FET-1. Variable target volumes were created theoretically based on FET-1 to optimally cover recurrent tumor.ResultsThe tumor volume overlap in FET and MRI was poor both at baseline (median 12 %; range 0–32) and at time of recurrence (13 %; 0–100). Recurrent tumor volume in FET-2 was localized to 39 % (12–91) in the initial tumor volume (FET-1). Over the time a shrinking (mean 12 (5–26) ml) and shifting (mean 6 (1–10 mm) of the resection cavity was seen. A simulated target volume based on active tumor in FET-1 with an additional safety margin of 7 mm around the FET-1 volume covered recurrent FET tumor volume (FET-2) significantly better than a corresponding target volume based on contrast enhancement in MRI-1 with a same safety margin of 7 mm (100 % (54–100) versus 85 % (0–100); p < 0.01). A simulated planning target volume (PTV), based on FET-1 and additional 7 mm margin plus 5 mm margin for setup-uncertainties was significantly smaller than the conventional, MR-based PTV applied in this study (median 160 (112–297) ml versus 231 (117–386) ml, p < 0.001).ConclusionsIn this small study recurrent tumor volume in FET-PET (FET-2) overlapped only to one third with the boost target volume, based on FET-1. The shrinking and shifting of the resection cavity may have an influence considering the limited overlap of initial and relapse tumor volume. A simulated target volume, based on FET-1 with 7 mm margin covered 100 % of relapse volume in median and led to a significantly reduced PTV, compared to MRI-based PTVs. This approach may achieve similar therapeutic efficacy but lower side effects offering a broader window to intensify concomitant systemic treatment focusing distant failures.
Highlights
To date, external fractionated radiotherapy is a mainstay in the multimodal treatment strategy of glioblastomas
The median tumor volume in O-(2-18 F-fluoroethyl)-L-tyrosine (FET)-positron emission tomography (PET) (FET-1) was significantly larger than that of contrast enhancement on magnetic resonance imaging (MRI)-1 (9 ml vs. 5 (0.6–20) ml; p = 0.01) while there was no significant difference between the tumor volumes of FET-PET and MRI at the time of recurrence (FET-2 and MRI-2; 13 (4–67) ml vs. 19 (4–113) ml; p = 0.7) The intersect between increased FET uptake (TBR > 1.6) and contrast enhancement in MRI was generally poor both at baseline and at the time of relapse (12 % (0–32) and 13 % (0–100), respectively)
FET uptake and contrast enhancement on MRI is illustrated in Fig. 1b and d
Summary
External fractionated radiotherapy is a mainstay in the multimodal treatment strategy of glioblastomas. The diagnostic method of choice for radiation treatment planning is contrast-enhanced MRI owing to its higher anatomical contrast and spatial resolution compared with CT. The differentiation of glioma tissue from surrounding edema, may be difficult with MRI and CT when the tumor is not sharply delineated from normal brain tissue, and when the bloodbrain barrier (BBB) remains intact [1]. After neurosurgical resection BBB disturbances and edema can be treatment-related and cannot be differentiated from residual tumor or tumor recurrence/ progression using conventional MRI [4]. O-(2-18 F-fluoroethyl)-L-tyrosine-(FET)-PET may be helpful to improve the definition of radiation target volumes in glioblastomas compared with MRI. We analyzed the relapse patterns in FET-PET after a FET- and MRI-based integrated-boost intensity-modulated radiotherapy (IMRT) of glioblastomas to perform an optimized target volume definition
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