Multicenter Study

. 2023 Nov;50(13):3970-3981.

doi: 10.1007/s00259-023-06371-5. Epub 2023 Aug 11.

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

Nathaniel Barry^{1

2}, Roslyn J Francis^{3

4}, Martin A Ebert^{5

6

4

7}, Eng-Siew Koh^{8

9}, Pejman Rowshanfarzad^{5

6}, Ghulam Mubashar Hassan⁵, Jake Kendrick^{5

6}, Hui K Gan^{10

11

12

13}, Sze T Lee^{11

12

13

14}, Eddie Lau^{14

15

16}, Bradford A Moffat¹⁶, Greg Fitt¹⁵, Alisha Moore¹⁷, Paul Thomas^{18

19}, David A Pattison^{18

19}, Tim Akhurst^{12

20}, Ramin Alipour^{12

20}, Elizabeth L Thomas³, Edward Hsiao²¹, Geoffrey P Schembri²¹, Peter Lin^{9

22}, Tam Ly²², June Yap²², Ian Kirkwood^{23

24}, Wilson Vallat²³, Shahroz Khan²⁵, Dayanethee Krishna²⁵, Stanley Ngai²⁶, Chris Yu²⁶, Scott Beuzeville²⁷, Tow C Yeow²⁷, Dale Bailey^{21

28}, Olivia Cook¹⁷, Angela Whitehead¹⁷, Rachael Dykyj¹⁷, Alana Rossi¹⁷, Andrew Grose¹⁷, Andrew M Scott^{11

12

13

14}

Affiliations

¹ School of Physics, Mathematics and Computing, University of Western Australia, WA, Crawley, Australia. Nathaniel.barry@research.uwa.edu.au.
² Centre for Advanced Technologies in Cancer Research (CATCR), WA, Perth, Australia. Nathaniel.barry@research.uwa.edu.au.
³ Department of Nuclear Medicine, Sir Charles Gairdner Hospital, Nedlands, WA, Australia.
⁴ Australian Centre for Quantitative Imaging, Medical School, University of Western Australia, Crawley, WA, Australia.
⁵ School of Physics, Mathematics and Computing, University of Western Australia, WA, Crawley, Australia.
⁶ Centre for Advanced Technologies in Cancer Research (CATCR), WA, Perth, Australia.
⁷ Department of Radiation Oncology, Sir Charles Gairdner Hospital, Nedlands, WA, Australia.
⁸ Department of Radiation Oncology, Liverpool and Macarthur Cancer Therapy Centres, Liverpool, NSW, Australia.
⁹ South Western Sydney Clinical School, UNSW Medicine, University of New South Wales, Liverpool, NSW, Australia.
¹⁰ Department of Medical Oncology, Austin Hospital, Melbourne, VIC, Australia.
¹¹ Olivia Newton-John Cancer Research Institute, Melbourne, VIC, Australia.
¹² Department of Medicine, University of Melbourne, Melbourne, VIC, Australia.
¹³ School of Cancer Medicine, La Trobe University, Melbourne, VIC, Australia.
¹⁴ Department of Molecular Imaging and Therapy, Austin Health, Melbourne, VIC, Australia.
¹⁵ Department of Radiology, Austin Health, Melbourne, VIC, Australia.
¹⁶ Department of Radiology, University of Melbourne, Melbourne, VIC, Australia.
¹⁷ Trans Tasman Radiation Oncology Group (TROG Cancer Research), University of Newcastle, Callaghan, NSW, Australia.
¹⁸ Department of Nuclear Medicine, Royal Brisbane and Women's Hospital, Herston, QLD, Australia.
¹⁹ Faculty of Medicine, University of Queensland, St Lucia, QLD, Australia.
²⁰ The Sir Peter MacCallum Department of Oncology, Melbourne, VIC, Australia.
²¹ Department of Nuclear Medicine, Royal North Shore Hospital, St Leonards, NSW, Australia.
²² Department of Nuclear Medicine, Liverpool Hospital, Liverpool, NSW, Australia.
²³ Department of Nuclear Medicine, Royal Adelaide Hospital, Adelaide, SA, Australia.
²⁴ Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, SA, Australia.
²⁵ Department of Nuclear Medicine, Canberra Hospital, Woden, ACT, Australia.
²⁶ Department of Nuclear Medicine, Princess Alexandra Hospital, Woolloongabba, QLD, Australia.
²⁷ Department of Nuclear Medicine, St George Hospital, Kogarah, NSW, Australia.
²⁸ Faculty of Medicine 7 Health, University of Sydney, Sydney, NSW, Australia.

PMID: 37563351
PMCID: PMC10611835
DOI: 10.1007/s00259-023-06371-5

Multicenter Study

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

Nathaniel Barry et al. Eur J Nucl Med Mol Imaging. 2023 Nov.

. 2023 Nov;50(13):3970-3981.

doi: 10.1007/s00259-023-06371-5. Epub 2023 Aug 11.

Authors

Affiliations

¹ School of Physics, Mathematics and Computing, University of Western Australia, WA, Crawley, Australia. Nathaniel.barry@research.uwa.edu.au.
² Centre for Advanced Technologies in Cancer Research (CATCR), WA, Perth, Australia. Nathaniel.barry@research.uwa.edu.au.
³ Department of Nuclear Medicine, Sir Charles Gairdner Hospital, Nedlands, WA, Australia.
⁴ Australian Centre for Quantitative Imaging, Medical School, University of Western Australia, Crawley, WA, Australia.
⁵ School of Physics, Mathematics and Computing, University of Western Australia, WA, Crawley, Australia.
⁶ Centre for Advanced Technologies in Cancer Research (CATCR), WA, Perth, Australia.
⁷ Department of Radiation Oncology, Sir Charles Gairdner Hospital, Nedlands, WA, Australia.
⁸ Department of Radiation Oncology, Liverpool and Macarthur Cancer Therapy Centres, Liverpool, NSW, Australia.
⁹ South Western Sydney Clinical School, UNSW Medicine, University of New South Wales, Liverpool, NSW, Australia.
¹⁰ Department of Medical Oncology, Austin Hospital, Melbourne, VIC, Australia.
¹¹ Olivia Newton-John Cancer Research Institute, Melbourne, VIC, Australia.
¹² Department of Medicine, University of Melbourne, Melbourne, VIC, Australia.
¹³ School of Cancer Medicine, La Trobe University, Melbourne, VIC, Australia.
¹⁴ Department of Molecular Imaging and Therapy, Austin Health, Melbourne, VIC, Australia.
¹⁵ Department of Radiology, Austin Health, Melbourne, VIC, Australia.
¹⁶ Department of Radiology, University of Melbourne, Melbourne, VIC, Australia.
¹⁷ Trans Tasman Radiation Oncology Group (TROG Cancer Research), University of Newcastle, Callaghan, NSW, Australia.
¹⁸ Department of Nuclear Medicine, Royal Brisbane and Women's Hospital, Herston, QLD, Australia.
¹⁹ Faculty of Medicine, University of Queensland, St Lucia, QLD, Australia.
²⁰ The Sir Peter MacCallum Department of Oncology, Melbourne, VIC, Australia.
²¹ Department of Nuclear Medicine, Royal North Shore Hospital, St Leonards, NSW, Australia.
²² Department of Nuclear Medicine, Liverpool Hospital, Liverpool, NSW, Australia.
²³ Department of Nuclear Medicine, Royal Adelaide Hospital, Adelaide, SA, Australia.
²⁴ Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, SA, Australia.
²⁵ Department of Nuclear Medicine, Canberra Hospital, Woden, ACT, Australia.
²⁶ Department of Nuclear Medicine, Princess Alexandra Hospital, Woolloongabba, QLD, Australia.
²⁷ Department of Nuclear Medicine, St George Hospital, Kogarah, NSW, Australia.
²⁸ Faculty of Medicine 7 Health, University of Sydney, Sydney, NSW, Australia.

PMID: 37563351
PMCID: PMC10611835
DOI: 10.1007/s00259-023-06371-5

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 (TBR_max), 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 (TBR_max/TBR_mean) 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, TBR_max, and TBR_mean 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. TBR_max and TBR_mean were robust, with considerable variability in BTV delineation and image interpretation observed.

Keywords: Clinical trials; Credentialing; FET PET; Glioblastoma; Inter-observer.

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Conflict of interest statement

The authors declare no competing interests.

Figures

**Fig. 1**
An overview of NMP credentialing by expert reviewers and their sources of violations of the two key assessments during credentialing: FET1 BTV delineation and FET3 image interpretation. The frequency of acceptable, minor, and major violations is shown for FET1 (a) and FET3 (c), with violations split into initial, first resubmission, and second resubmission. Frequency of FET1 (b) and FET3 (d) violation reasons, accrued from reviewer comments, is shown. Violation reasons are also broken down into reports that requested resubmissions to highlight NMP critical errors

**Fig. 2**
Boxplots showing the distribution of NMP BTVs (left), TBR_max (middle), and TBR_mean (right) grouped by each nuclear medicine credentialing case

**Fig. 3**
Illustration of credentialing image FET1CASE2 that exhibited the best (DSC = 0.88 ± 0.05) agreement amongst NMPs (left) and credentialing image FET3CASE2 that showed the poorest (DSC = 0.77 ± 0.09) agreement (right). Superimposed NMP contours are shown in red. Discrepancy between NMPs when including the additional area of uptake (white arrow) in FET3CASE2 is likely the main source of variability in the pairwise analysis

**Fig. 4**
Boxplots visualising the distribution of pairwise Dice similarity coefficient (DSC) of each delineated structure, grouped by case. The biological tumour volume (BTV), GTV0 (volume obtained after threshold is applied), and Static VOI are all generated as part of the delineation process. For each set of credentialing cases, spatial overlap is assessed by calculating the DSC for every pairwise combination of NMP contours

See this image and copyright information in PMC

Comment in

Boosting the acceptance of ¹⁸F-FET PET for image-guided treatment planning with a multi-centric prospective trial.
Langen KJ, Galldiks N, Lohmann P, Mottaghy FM. Langen KJ, et al. Eur J Nucl Med Mol Imaging. 2023 Nov;50(13):3817-3819. doi: 10.1007/s00259-023-06426-7. Eur J Nucl Med Mol Imaging. 2023. PMID: 37682302 Free PMC article. No abstract available.

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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

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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

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