A Methionine PET Targeting for Gamma Knife Radiosurgery used to Treat Recurrent Malignant Gliomas at Inoperable Stage

A Methionine PET Targeting for Gamma Knife Radiosurgery used to Treat Recurrent Malignant Gliomas at Inoperable Stage. Journal of Surgery and Research 3 (2020): 457-471. Abstract Purpose: The current study investigates the usefulness of metabolic positron emission tomography (PET) imaging (in particular with 11C-methionine (MET)), Results: The median PFS after GKRS for the 24 patients with malignant gliomas was 5.5 (2-46) months and 4.5 (3-10), 4.5 (2-8) and 13.5 (2-46) months for glioblastoma, anaplastic glioma and grade II glioma patients, respectively. The median OS from the GKRS procedure for patients with recurrent glioblastomas (n=12) was 18 (6-45) months, 8 (6-184) months for anaplastic gliomas (n=6), and 22 (16-65) months for grade II gliomas (n=6). All patients with grade III and II multirecurrent gliomas (n=12) showed an early favourable local metabolic response, while this response was observed only in 6/12 of the glioblastomas. However, the majority (9/12=75%) of these grade II/III glioma patients further developed new lesions. GKRS treatment was associated with diverse chemotherapies in more than 50% (13/24) of cases. Post-GKRS radio-necrosis was observed in only one patient. Conclusion: Based on a limited series of 24 patients, our study shows, for the first time, the GKRS-induced metabolic response in focally recurrent inoperable malignant gliomas. GKRS could be part of the multidisciplinary approach for multirecurrent malignant gliomas that cannot be anymore treated by surgery.


Introduction
Malignant gliomas are infiltrating tumours, which makes complete surgical resection elusive, and tumour recurrence is more than frequent. Glioma recurrence around the resection cavity occurs in almost all patients, and the management options for evolutive malignant gliomas are limited despite advances in surgical, chemotherapeutic and radiotherapeutic techniques [1].
Moreover, the remaining glioma cells that migrate after debulking are resistant to conventional treatments [2].
SRS treatments can be refined with the use of various imaging approaches to improve tumour targeting.
Among the different approaches, metabolic imaging using positron emission tomography (PET) in addition to conventional magnetic resonance imaging (MRI) can provide relevant information on tumour metabolism, which allows for more accurate diagnoses and treatments [11,12]. Radiolabelled amino acids have been used in neuro-oncological practice since 1983 [13].
The largest experience with this class of PET tracers for brain tumour imaging has been gained with 11Cmethionine (MET), and MET is an essential amino acid labelled with the positron-emitting isotope carbon-11, which is associated with a 20-min half-life [14,15]

Demographics
The patient demographics are summarized in Table 1 and detailed in Table S1 (supplementary data). Thirteen patients (54%) received second-or third-line chemotherapy associated with GKRS (Table S1) (Table   S1).

Outcome
The PFS after GKRS and the OS from the GKRS procedure are summarized in Table 2 and detailed in  Table S1). Only one patient with local recurrence after a response of more than one year was treated by surgery (patient 22). Two patients with pluri-focal evolution were treated by radiotherapy. One patient that had been previously irradiated on the operative field developed radio-necrosis 7 months after GKRS treatment (patient 23). Figure 3 illustrates a patient with a long-term metabolic response.
Post-GKRS radio-necrosis was observed in only one patient (patient number 23 in Table S1) with a history of previous external brain radiotherapy at a dose of 50.4 Gy for an oligodendroglioma grade II 5 years earlier.

Discussion
The management of multirecurrent malignant gliomas is challenging due to their spatial and temporal

Conclusion
Our study aims to highlight the potential of using metabolically targeted GKRS in the multimodality management of inoperable malignant glioma local recurrence. Based on a limited series of 24 patients, the current study demonstrates the GKRS-induced metabolic response in multirecurrent malignant gliomas.
Because GKRS could be part of the multidisciplinary approach for multirecurrent malignant gliomas that cannot be anymore treated by surgery, we will evaluate the actual benefits of GKRS in patients with malignant glioma local recurrence in a prospective controlled clinical trial.

Declarations
Not applicable.

Funding
This study was made possible thanks to a grant from Dominique Jonckheere, Tom, a member of the Beatles' Empire. This work was supported by the Fonds Erasme