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
Authors: Barry Nathaniel , Francis Roslyn J. , Ebert Martin A. , Koh Eng-Siew , Rowshanfarzad Pejman , Hassan Ghulam Mubashar , Kendrick Jake , Gan Hui K. , Lee Sze T. , Lau Eddie , Moffat Bradford A. , Fitt Greg , Moore Alisha , Thomas Paul , Pattison David A. , Akhurst Tim , Alipour Ramin , Thomas Elizabeth L. , Hsiao Edward , Schembri Geoffrey P. , Lin Peter , Ly Tam , Yap June , Kirkwood Ian , Vallat Wilson , Khan Shahroz , Krishna Dayanethee , Ngai Stanley , Yu Chris , Beuzeville Scott , Yeow Tow C. , Bailey Dale , Cook Olivia , Whitehead Angela , Dykyj Rachael , Rossi Alana , Grose Andrew , Scott Andrew M. 
Published: August 2023

Abstract
Purpose
The O-(2-[18F]-fluoroethyl)-l-tyrosine (FET) PET in Glioblastoma (FIG) trial is an Australian prospective, multi-centre study evaluating FET PET for glioblastoma patient management. FET PET imaging timepoints are pre-chemoradiotherapy (FET1), 1-month post-chemoradiotherapy (FET2), and at suspected progression (FET3). Before participant recruitment, site nuclear medicine physicians (NMPs) underwent credentialing of FET PET delineation and image interpretation.

Methods
Sites were required to complete contouring and dynamic analysis by ≥ 2 NMPs on benchmarking cases (n = 6) assessing biological tumour volume (BTV) delineation (3 × FET1) and image interpretation (3 × FET3). Data was reviewed by experts and violations noted. BTV definition includes tumour-to-background ratio (TBR) threshold of 1.6 with crescent-shaped background contour in the contralateral normal brain. Recurrence/pseudoprogression interpretation (FET3) required assessment of maximum TBR (TBRmax), dynamic analysis (time activity curve [TAC] type, time to peak), and qualitative assessment. Intraclass correlation coefficient (ICC) assessed volume agreement, coefficient of variation (CoV) compared maximum/mean TBR (TBRmax/TBRmean) across cases, and pairwise analysis assessed spatial (Dice similarity coefficient [DSC]) and boundary agreement (Hausdorff distance [HD], mean absolute surface distance [MASD]).

Results
Data was accrued from 21 NMPs (10 centres, n ≥ 2 each) and 20 underwent review. The initial pass rate was 93/119 (78.2%) and 27/30 requested resubmissions were completed. Violations were found in 25/72 (34.7%; 13/12 minor/major) of FET1 and 22/74 (29.7%; 14/8 minor/major) of FET3 reports. The primary reasons for resubmission were as follows: BTV over-contour (15/30, 50.0%), background placement (8/30, 26.7%), TAC classification (9/30, 30.0%), and image interpretation (7/30, 23.3%). CoV median and range for BTV, TBRmax, and TBRmean were 21.53% (12.00–30.10%), 5.89% (5.01–6.68%), and 5.01% (3.37–6.34%), respectively. BTV agreement was moderate to excellent (ICC = 0.82; 95% CI, 0.63–0.97) with good spatial (DSC = 0.84 ± 0.09) and boundary (HD = 15.78 ± 8.30 mm; MASD = 1.47 ± 1.36 mm) agreement.

Conclusion
The FIG study credentialing program has increased expertise across study sites. TBRmax and TBRmean were robust, with considerable variability in BTV delineation and image interpretation observed.