Impact of 18F-FET PET on Target Volume Definition and Tumor Progression of Recurrent High Grade Glioma Treated with Carbon-Ion Radiotherapy

Abstract

High-precision radiotherapy (HPR) of recurrent high grade glioma (HGG) requires accurate spatial allocation of these infiltrative tumors. We investigated the impact of 18F-FET PET on tumor delineation and progression of recurrent HGG after HPR with carbon ions. T1 contrast enhanced MRI and 18F-FET-PET scans of 26 HGG patients were fused with radiotherapy planning volumes. PET-positive (PET+) tumor volumes using different isocontours (I%) were systematically investigated and compared with MRI-derived gross tumor volumes (GTV). Standardized uptake ratios (SUR) were further correlated with GTV and tumor progression patterns. In grade IV glioma, SUR > 2.92 significantly correlated with poor median overall survival (6.5 vs 13.1 months, p = 0.00016). We found no reliable SUR cut-off criteria for definition of PET+ volumes. Overall conformity between PET and MRI-based contours was low, with maximum conformities between 0.42–0.51 at I40%. The maximum sensitivity and specificity for PET+ volumes outside of GTV predicting tumor progression were 0.16 (I40%) and 0.52 (I50%), respectively. In 75% of cases, FLAIR hyperintense area covered over 80% of PET+ volumes. 18F-FET-PET derived SUR has a prognostic impact in grade IV glioma. The value of substantial mismatches between MRI-based GTV and PET+ volumes to improve tumor delineation in radiotherapy awaits further validation in randomized prospective trials.

Carbon irradiation overcomes glioma radioresistance by eradicating stem cells and forming an antiangiogenic and immunopermissive niche

“…Lack of induction of these compensatory and evasive mechanisms by carbon ions opens a new venue for development of novel therapy strategies for this devastating disease. However, clinical experiences (19) reported here show that despite these advantages of CIR, tumors progress and ultimately relapse after monotherapy. It is conceivable that combination therapies will be needed to translate the beneficial effects of carbon ions into an enduring In line with these observations, reduced influx of CD11b + microglia and myeloid cells, including Gr1 + MdSCs, after CIR was confirmed and correlated with decreased SDF1 levels (SMA-560 n = 3-4, Gl261 n = 6).…”

“…Despite these encouraging data in n = 1 representative patient for which serial imaging and long-term follow-up of the primary tumor, conversion to recurrent HGG and post-photon/carbon ion therapy were available, only prospective trials could confirm the value of our preclinical observations. Indeed, preliminary data on the first collectives of recurrent HGG patients reirradiated with raster scanning carbon ions are promising, indicating that progress mainly occurred outside the high-dose field, in contrast with the predominantly central progression pattern found after PIR (18,19).…”

FET PET reveals considerable spatial differences in tumour burden compared to conventional MRI in newly diagnosed glioblastoma

“…Predominantly, the impact of FET PET on radiotherapy target volume definition in patients with low-and high-grade gliomas has been investigated [39][40][41][42]. These studies provide converging evidence that the spatial correlation of MRI-and FET PETbased target volumes is low and that FET PET target volumes are considerably more extensive than MR-defined target volumes.…”

AHIF promotes glioblastoma progression and radioresistance via exosomes

“…Therefore, radiotherapy is a major adjuvant therapy for patients with GBM (4). It has long been recognized that GBM tumors are heterogeneous in their radiation response, and the degree of radiosensitivity is thought to be associated with intrinsic and extrinsic properties of the tumor cell population (5)(6)(7). The effects and underlying molecular mechanisms of GBM progression and radioresistance have yet to be clarified.…”