Date Published: July 24, 2019
Publisher: Public Library of Science
Author(s): Daniel F. Fleischmann, Marcus Unterrainer, Stefanie Corradini, Maya Rottler, Stefan Förster, Christian la Fougère, Timo Siepmann, Markus Schwaiger, Peter Bartenstein, Claus Belka, Nathalie L. Albert, Maximilian Niyazi, Russell R. Lonser.
The advantage of combined PET-MRI over sequential PET and MRI is the high spatial conformity and the absence of time delay between the examinations. The benefit of this technique for planning of re-irradiation (re-RT) treatment is unkown yet. Imaging data from a phase 1 trial of re-RT for recurrent glioma was analysed to assess whether planning target volumes and treatment margins in glioma re-RT can be adjusted by PET-MRI with rater independent PET based biological tumour volumes (BTVs).
Combined PET-MRI with the tracer O-(2-18F-fluoroethyl)-l-tyrosine (18F-FET) prior to re-RT was performed in recurrent glioma patients in a phase I trial. GTVs including all regions suspicious of tumour on contrast enhanced MRI were delineated by three experienced radiation oncologists and included into MRI based consensus GTVs (MRGTVs). BTVs were semi-automatically delineated with a fixed threshold of 1.6 x background activity. Corresponding BTVs and MRGTVs were fused into union volume PET-MRGTVs. The Sørensen–Dice coefficient and the conformity index were used to assess the geometric overlap of the BTVs with the MRGTVs. A recurrence pattern analysis was performed based on the original planning target volumes (PTVs = GTV + 10 mm margin or 5 mm in one case) and the PET-MRGTVs with margins of 10, 8, 5 and 3 mm.
Seven recurrent glioma patients, who received PET-MRI prior to re-RT, were included into the present planning study. At the time of re-RT, patients were in median 54 years old and had a median Karnofsky Performance Status (KPS) score of 80. Median post-recurrence survival after the beginning of re-RT was 13 months. Concomitant bevacizumab therapy was applied in six patients and one patient received chemoradiation with temozolomide. Median GTV volumes of the three radiation oncologists were 35.0, 37.5 and 40.5 cubic centimeters (cc) and median MRGTV volume 41.8 cc. Median BTV volume was 36.6 cc and median PET-MRGTV volume 59.3 cc. The median Sørensen–Dice coefficient for the comparison between MRGTV and BTV was 0.61 and the median conformity index 0.44. Recurrence pattern analysis revealed two central, two in-field and one distant recurrence within both, the original PTV, as well as the PET-MRGTV with a reduced margin of 3 mm.
PET-MRI provides radiation treatment planning imaging with high spatial and timely conformity for high-grade glioma patients treated with re-RT with potential advancements for target volume delineation. Prospective randomised trials are warranted to further investigate the treatment benefits of PET-MRI based re-RT planning.
Prognosis for patients suffering from high-grade glioma remains poor, with a median expected survival of 42 months for patients with anaplastic astrocytomas and 15 months for patients with histology of glioblastoma . Moreover, recurrent disease is diagnosed in the majority of glioma patients. Re-irradiation (re-RT) has been reported to be an efficient retreatment option  whereas neurosurgical re-intervention at the time of recurrence is limited to a selected patient group [3,4].
Radiation treatment planning in recurrent glioma depends on high-resolution contrast enhanced MR imaging of good quality as addition to planning CT imaging. PET imaging with amino acid tracers such as 18F-FET has a high sensitivity for the detection of high-grade glioma [20,21] and provides valuable information about the metabolic activity of the tumour reaching beyond contrast-enhancing areas on MRI . Therefore 18F-FET PET is used to complement morphologic MR imaging in radiation treatment planning of glioma . Recently a prospective clinical trial was launched to evaluate the potential benefit of target volume delineation of recurrent glioma of 18F-FET PET based versus conventional contrast enhanced MRI based radiation treatment planning .
PET-MRI with spatial and temporal conformity of metabolic 18F-FET PET and morphologic MR imaging showed promising results for the optimization of target volume delineation in radiation treatment planning for patients with recurrent glioma. Rater independent 18F-FET PET based BTVs, which differed significantly from MR based GTVs in the present study, may be used as a complementing element in target volume delineation. Prospective trials are needed to assess the treatment benefits of PET-MRI based re-RT treatment planning for patients with recurrent glioma.