Multi-site, prospective trial evaluating FET-PET In Glioblastoma (FIG) Study (TROG 18.06): FET-PET biologic target volume delineation for radiation planning

Introduction: To provide 1) a brief recruitment update from the prospective multi-site trial evaluating O-(2-[18F]-fluoroethyl)-L-tyrosine Positron Emission Tomography (FET-PET) in Glioblastoma (FIG) study (1) (ACTRN12619001735145) and 2) assess the impact of central Nuclear Medicine physician (NMP) review of prospective FET-PET1 delineation of biological target volume (BTV) for radiation planning.

Methods: Up to 210 GBM participants across 11 Australian sites will undergo FET-PET post-surgery/pre-chemo-RT [CRT] (FET-PET1), one month post CRT (FET-PET2) and at suspected progression (FET-PET3) to determine FET-PET’s role in radiotherapy planning, pseudoprogression management and prognostication. Group 1 participants enter at timepoint 1 (FET-PET1 and MRI1), whilst Group 2 are registered and undergo timepoint 2 imaging. For timepoint 1, RT target volumes are derived per standard contrast MRI with hybrid post-hoc RT volumes created by incorporating the FET-PET1 NM-derived BTV. The FET-PET1 NM-derived BTV is derived using a standardised workflow developed in MiM version 7.0.

All trial sites and NMP have passed the credentialling phase which included three benchmarking cases involving BTV delineation (2). For the prospective recruitment phase, a minimum of three cases per site (n=10) are planned for central review of BTV delineation, with resubmission rate and reasons documented.

Results: Trial recruitment commenced in January 2021. To date, 168 (n=105 Group 1 and n=63 Group 2) participants have been enrolled, aiming for a target of 140 Group 1 participants. The IDSMC reviewed the trial on 17 October 2023 and supported that the trial continue, as planned.

During the trial credentialling phase of the study, published results demonstrated variations of FET-PET1 derived regions, including BTV in 25/72 (34.7%; 13 minor and 12 major) of cases, which were subsequently addressed following central review (2). In the prospective recruitment phase of the study, 40 participant FET-PET1 cases with BTV delineation across activated 10 sites to date have undergone central review, with 6/40 (15%) requiring resubmission. Reasons for resubmission/protocol deviations included the incorrect selection of MRI and other options within MiM workflow (n=3), overcontouring of Static GTV (n=2) related to incorrect placement of the background region of interest (ROI) and manual adjustment of the dynamic volume of interest (VOI) (n=1).

Conclusions: The FIG trial is expected to conclude in 2024 with analyses planned at one year post CRT completion. Despite improvements in case resubmission rates compared to the credentialling phase, central review of prospective FET-PET1-derived BTV delineation remains important in ensuring adherence to study workflow and quality assurance across sites with varying experience in FET-PET. To our knowledge, the FIG study is the largest prospective multi-site study of its kind addressing FET-PET’s role in management of pseudoprogression, prognostication and impact on adjuvant radiation planning.

References:

• Koh E-S, Gan HK, Senko C, Francis RJ, Ebert M, Lee ST, et al. F-fluoroethyl-L-tyrosine (FET) in glioblastoma (FIG) TROG 18.06 study: protocol for a prospective, multicentre PET/CT trial. BMJ Open. 2023;13:e071327. doi:10.1136/bmjopen-2022-071327.

• Barry N, Francis RJ, Ebert MA, Koh E-S, Rowshanfarzad P, Hassan GM, et al. Delineation and agreement of FET PET biological volumes in glioblastoma: results of the nuclear medicine credentialing program from the prospective, multi-centre trial evaluating FET PET In Glioblastoma (FIG) study—TROG 18.06. European Journal of Nuclear Medicine and Molecular Imaging. 2023. 50(13): 3970–3981. doi:10.1007/s00259-023-06371-5.