[18]F-fluoroethyl-l-tyrosine positron emission tomography for radiotherapy target delineation: Results from a Radiation Oncology credentialing program.

Background and purpose: The [18]F-fluoroethyl-l-tyrosine (FET) PET in Glioblastoma (FIG) study is an Australian prospective, multi-centre trial evaluating FET PET for newly diagnosed glioblastoma management. The Radiation Oncology credentialing program aimed to assess the feasibility in Radiation Oncologist (RO) derivation of standard-of-care target volumes (TVMR) and hybrid target volumes (TVMR+FET) incorporating pre-defined FET PET biological tumour volumes (BTVs). Materials and methods: Central review and analysis of TVMR and TVMR+FET was undertaken across three benchmarking cases. BTVs were pre-defined by a sole nuclear medicine expert. Intraclass correlation coefficient (ICC) confidence intervals (CIs) evaluated volume agreement. RO contour spatial and boundary agreement were evaluated (Dice similarity coefficient [DSC], Jaccard index [JAC], overlap volume [OV], Hausdorff distance [HD] and mean absolute surface distance [MASD]). Dose plan generation (one case per site) was assessed. Results: Data from 19 ROs across 10 trial sites (54 initial submissions, 8 resubmissions requested, 4 conditional passes) was assessed with an initial pass rate of 77.8 %; all resubmissions passed. TVMR+FET were significantly larger than TVMR (p < 0.001) for all cases. RO gross tumour volume (GTV) agreement was moderate-to-excellent for GTVMR (ICC = 0.910; 95 % CI, 0.708-0.997) and good-to-excellent for GTVMR+FET (ICC = 0.965; 95 % CI, 0.871-0.999). GTVMR+FET showed greater spatial overlap and boundary agreement compared to GTVMR. For the clinical target volume (CTV), CTVMR+FET showed lower average boundary agreement versus CTVMR (MASD: 1.73 mm vs. 1.61 mm, p = 0.042). All sites passed the planning exercise. Conclusions: The credentialing program demonstrated feasibility in successful credentialing of 19 ROs across 10 sites, increasing national expertise in TVMR+FET delineation.

Quantitative [68Ga]Ga-PSMA-11 PET biomarkers for the analysis of lesion-level progression in biochemically recurrent prostate cancer: a multicentre study.

[68Ga]Ga-PSMA-11 PET has become the standard imaging modality for biochemically recurrent (BCR) prostate cancer (PCa). However, its prognostic value in assessing response at this stage remains uncertain. The study aimed to assess the prognostic significance of radiographic patient-level patterns of progression derived from lesion-level biomarker quantitation in metastatic disease sites. A total of 138 BCR PCa patients with both baseline and follow-up [68Ga]Ga-PSMA-11 PET scans were included in this analysis. Tumour response was quantified at the lesion level using commonly used quantitative parameters (SUVmean, SUVmax, SUVpeak, volume), and patients were classified as systemic, mixed, or no-progression based on these response classifications. A total of 328 matched lesions between baseline and follow-up scans were analysed. The results showed that systemic progressors had a significantly higher risk of death than patients with no progression with SUVmean demonstrating the highest prognostic value (HR = 5.70, 95% CI = 2.63-12.37, p < 0.001, C-Index = 0.69). Moreover, progressive disease as measured by SUVmean using the radiographic PSMA PET Progression Criteria (rPPP) was found to be significantly prognostic for patient overall survival (HR = 3.67, 95% CI = 1.82-7.39, p < 0.001, C-Index = 0.65). This work provides important evidence supporting the prognostic utility of PSMA response quantitation in the BCR setting.

Prospective inter- and intra-tracer repeatability analysis of radiomics features in [68Ga]Ga-PSMA-11 and [18F]F-PSMA-1007 PET scans in metastatic prostate cancer.

OBJECTIVE: This study aimed to quantify both the intra- and intertracer repeatability of lesion-level radiomics features in [68Ga]Ga-prostate-specific membrane antigen (PSMA)-11 and [18F]F-PSMA-1007 positron emission tomography (PET) scans. METHODS: Eighteen patients with metastatic prostate cancer (mPCa) were prospectively recruited for the study and randomised to one of three test-retest groups: (i) intratracer [68Ga]Ga-PSMA-11 PET, (ii) intratracer [18F]F-PSMA-1007 PET or (iii) intertracer between [68Ga]Ga-PSMA-11 and [18F]F-PSMA-1007 PET. Four conventional PET metrics (standardised uptake value (SUV)max, SUVmean, SUVtotal and volume) and 107 radiomics features were extracted from 75 lesions and assessed using the repeatability coefficient (RC) and the ICC. Radiomic feature repeatability was also quantified after the application of 16 filters to the PET image. RESULTS: Test-retest scans were taken a median of 5 days apart (range: 2-7 days). SUVmean demonstrated the lowest RC limits of the conventional features, with RCs of 7.9%, 14.2% and 24.7% for the [68Ga]Ga-PSMA-11 PET, [18F]F-PSMA-1007 PET, and intertracer groups, respectively. 69%, 66% and 9% of all radiomics features had good or excellent ICC values (ICC ≥ 0.75) for the same groups. Feature repeatability therefore diminished considerably for the intertracer group relative to intratracer groups. CONCLUSION: In this study, robust biomarkers for each tracer group that can be used in subsequent clinical studies were identified. Overall, the repeatability of conventional and radiomic features were found to be substantially lower for the intertracer group relative to both intratracer groups, suggesting that assessing patient response quantitatively should be done using the same radiotracer where possible. ADVANCES IN KNOWLEDGE: Intertracer biomarker repeatability limits are significantly larger than intratracer limits.

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.

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.

Repeatability of image features extracted from FET PET in application to post-surgical glioblastoma assessment.

Positron emission tomography (PET) imaging using the amino acid tracer O-[2-(18F)fluoroethyl]-L-tyrosine (FET) has gained increased popularity within the past decade in the management of glioblastoma (GBM). Radiomics features extracted from FET PET images may be sensitive to variations when imaging at multiple time points. It is therefore necessary to assess feature robustness to test-retest imaging. Eight patients with histologically confirmed GBM that had undergone post-surgical test-retest FET PET imaging were recruited. In total, 1578 radiomic features were extracted from biological tumour volumes (BTVs) delineated using a semi-automatic contouring method. Feature repeatability was assessed using the intraclass correlation coefficient (ICC). The effect of both bin width and filter choice on feature repeatability was also investigated. 59/106 (55.7%) features from the original image and 843/1472 (57.3%) features from filtered images had an ICC ≥ 0.85. Shape and first order features were most stable. Choice of bin width showed minimal impact on features defined as stable. The Laplacian of Gaussian (LoG, σ = 5 mm) and Wavelet filters (HLL and LHL) significantly improved feature repeatability (p ≪ 0.0001, p = 0.003, p = 0.002, respectively). Correlation of textural features with tumour volume was reported for transparency. FET PET radiomic features extracted from post-surgical images of GBM patients that are robust to test-retest imaging were identified. An investigation with a larger dataset is warranted to validate the findings in this study.