Article Figures & Data
Figures
- FIGURE 1.
WHO grade, diagnosis according to WHO 2016 classification of brain tumors (2), and MGMT promoter methylation status of tumors that were later examined with 18F-FET PET; N.d. = not determined or inconclusive.
- FIGURE 2.
Examples of false-negative and -positive 18F-FET PET ratings. (A–D) A 45-y-old-patient had been diagnosed with IDH-mutant, MGMT promoter methylated glioblastoma in November 2010. After gross total resection, radiotherapy, and irinotecan chemotherapy, she received bevacizumab every other week. In January 2017, follow-up MRI indicated disease progression (RANO criteria). However, in February 2017, 18F-FET PET imaging was not suggestive of tumor, and so patient continued follow-up. Subsequent MRI revealed enlargement of both contrast-enhancing and non–contrast-enhancing lesions (tumor progression, RANO criteria), but 18F-FET PET remained negative. In November 2017, biopsy revealed tumor progression. Shown are axial MRI, October 2017, T2 image (A, left) and contrast-enhanced T1 image (A, right); 18F-FET PET, November 2017 (B); and histology (hematoxylin-eosin [HE]) (C) and immunohistochemistry (IDH1_R132H, arrowheads point to IDH1_R132H-positive tumor cells) (D) of biopsy samples, November 2017. (E–H) A 39-y-old patient had undergone subtotal resection of IDH1_R132H-mutant and 1p/19q-codeleted oligodendroglioma in August 2010, temozolomide chemotherapy until January 2011, proton therapy in May and June 2015, and lomustine chemotherapy from July to December 2015. In July 2017, putative recurrent tumor was resected. Neuropathology showed sequelae of radiation but no tumor. Shown are axial MRI, May 2017, T2 image (E, left) and contrast-enhanced T1 image (E, right); 18F-FET PET indicating tumor progression, June 2017 (F); and necrosis and calcification (arrows, HE) (G) without IDH1_R132H-positive tumor cells (H) in resected samples, July 2017. (I–K) IDH-mutant, MGMT promoter methylated glioblastoma of 38-y-old patient had been treated by partial resection in April 2016, radiotherapy, and temozolomide chemotherapy from April to June 2016. Against our advice, patient decided not to continue tumor-specific therapy. However, imaging alterations regressed spontaneously. Shown are coronal MRI, February 2017, T2 image (I, left) and contrast-enhanced T1 image (I, right); 18F-FET PET indicating tumor progression, April 2017 (J); and follow-up MRI, February 2018, T2 image (K, left) and contrast-enhanced T1 image (K, right).
- FIGURE 3.
Overall survival of all 127 patients. (A) Overall survival after 18F-FET PET imaging, depending on whether TP or TRCs were present, as assessed by histology or follow-up (P [log-rank] < 0.001). (B) Overall survival after 18F-FET PET imaging, depending on 18F-FET PET results (P [log-rank] < 0.001).
Tables
Characteristic Data % Sex (n) Male 83 65 Female 44 35 Age when 18F-FET PET imaging was performed (y) Mean ± SD 50 ± 12 Range 20–78 KPS when 18F-FET PET imaging was performed (n) 100% 49 39 90% 46 36 80% 19 15 70% 11 9 60% 2 2 Interval between last therapy and 18F-FET PET scan (d) Median 103 Range 0–3,540 Therapy before 18F-FET PET imaging (n) Radiotherapy 114 90 Chemotherapy Temozolomide 106 83 Lomustine-containing regimen 29 23 Bevacizumab 9 7 Tumor treating fields 9 7 Reresection 21 17 Reirradiation 19 15 Nivolumab 7 6 Other* 6 5 ↵* This section included 3 patients treated with nivolumab or placebo in context of clinical trial, 1 patient treated with sitimagene ceradenovec/ganciclovir, 1 patient treated with brachytherapy using 125I seeds, and 1 patient treated with irinotecan.
KPS = Karnofsky performance status.
Characteristic Data % Diagnosis (n) Glioblastoma, IDH-wild-type, WHO IV 59 46 Glioblastoma, IDH-mutant, WHO IV 7 6 Glioblastoma, not otherwise specified, WHO IV 1 0.8 Astrocytoma, IDH-wild-type WHO II 2 2 WHO III 7 6 Astrocytoma, IDH-mutant WHO II 10 8 WHO III 21 17 Astrocytoma, not otherwise specified WHO II 1 0.8 WHO III 1 0.8 Oligodendroglioma, IDH-mutant and 1p/19q-codeleted WHO II 7 6 WHO III 6 5 Diffuse midline glioma, H3 K27 M-mutant, WHO IV 1 0.8 Other* WHO II 1 0.8 WHO III 1 0.8 ND 2 2 MGMT promoter methylation status (n) Methylated 57 45 Unmethylated 40 31 ND 30 24 Extent of resection at initial diagnosis (n) Gross total resection 67 53 Subtotal resection 8 6 Partial resection 20 16 Biopsy 30 24 None 2 2 ↵* This section included 1 diffuse glioma, IDH-wild-type, nuclear ATRX retained, MGMT promoter methylated; 1 anaplastic glioma, IDH-mutant, nuclear ATRX retained, MGMT promoter methylated; 1 suspected diffuse pontine glioma (treated without prior biopsy); and 1 suspected diffuse medulla oblongata glioma (treated without prior biopsy).
ND = not determined or inconclusive.
Survival analysis Patients (n) HR 95% CI P Univariate Diagnosis based on 18F-FET PET 127 4.997 2.139–11.675 <0.001 IDH status IDH-wild-type 70 1.000 IDH-mutant 51 0.181 0.091–0.363 <0.001 MGMT promoter methylation status Unmethylated 40 1.000 Methylated 57 0.493 0.278–0.877 0.016 WHO grade 125 3.859 2.230–6.678 <0.001 Age (y) 127 1.043 1.020–1.066 <0.001 KPS (%) 127 0.965 0.940–0.990 0.007 Number of glioma recurrences before 18F-FET PET scan 127 1.051 0.792–1.395 NS Interval between last therapy and 18F-FET PET scan (d) 124 0.997 0.996–0.999 0.001 Multivariate Diagnosis based on 18F-FET PET 3.424 1.446–8.109 0.005 WHO grade 2.143 1.212–3.792 0.009 IDH status 0.412 0.210–0.808 0.010 KPS (%) 0.975 0.950–1.001 0.057 HR = hazard ratio; CI = confidence interval; KPS = Karnofsky performance status; NS = not statistically significant.
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