Article Figures & Data
Figures
- FIGURE 1.
(A) Kaplan–Meier curves for PFS on basis of dual-tracer PET. (B) Kaplan–Meier curves for PFS on basis of 2017 WHO grading system. (C) Cox proportional hazards survival curves for PFS on basis of dual-tracer PET. (D) Cox proportional hazards survival curves for PFS on basis of 2017 WHO grading system. Kaplan–Meier and Cox curves showed significantly better PFS for metabolically inactive and SSTR-expressing group than for metabolically active and non–SSTR-expressing group when cohort was analyzed on basis of dual-tracer PET. Analysis based on 2017 WHO grading system did not yield any significant difference. Cum = cumulative.
- FIGURE 2.
(A) Kaplan–Meier curves for OS on basis of dual-tracer PET. (B) Kaplan–Meier curves for OS on basis of 2017 WHO grading system. (C) Cox proportional hazards survival curves for OS on basis of dual-tracer PET. (D) Cox proportional hazards survival curves for OS on basis of 2017 WHO grading system. Kaplan–Meier and Cox curves showed significantly better OS for metabolically inactive and SSTR-expressing group than for metabolically active and non–SSTR-expressing group when cohort was analyzed on basis of dual-tracer PET. Analysis based on 2017 WHO grading system did not yield any significant difference. Cum = cumulative.
- FIGURE 3.
A 61-y-old man with NET metastatic to liver, mediastinal and abdominal nodes, and multiple skeletal sites, with unknown primary. Histopathology revealed poorly differentiated NEC, positive for synaptophysin and chromogranin, and CK19-positive on IHC. Despite high proliferative index of 25%, 68Ga-DOTATATE PET/CT at baseline revealed intense SSTR expression in hepatic and skeletal lesions and in mediastinal, abdominal, and pelvic nodes, whereas 18F-FDG PET/CT showed single metabolically active pariceliac node. Follow-up 68Ga-DOTATATE PET/CT revealed partial response, with decrease in size and SSTR expression in almost all lesions, whereas 18F-FDG PET/CT did not show any abnormal uptake, suggesting complete metabolic resolution. Despite poorly differentiated G3 NEC (WHO 2017), dual-tracer PET/CT studies suggested favorable tumor biology, which was adequately clinically translated. After third PRRT, patient is doing fine, with significant symptomatic and morphologic improvement.
- FIGURE 4.
A 64-y-old woman with NET metastatic to liver and skeletal sites, with unknown primary. Patient presented with pain in abdomen and weight loss and was referred for PRRT in view of SSTR-expressing metastatic NET. Histopathology of liver lesion revealed metastatic, well-differentiated NET with MIB-1 index of 24%, positive for synaptophysin and chromogranin, and CDX2-negative on IHC. Baseline 68Ga-DOTATATE PET/CT revealed multiple areas of increased tracer uptake (SSTR expression) in both lobes of liver (bilobar hepatic metastases, which is not amenable to surgical resection) and skeletal sites, with no abnormal hypermetabolism evident on baseline 18F-FDG PET/CT. Follow-up dual-tracer PET/CT after 4 PRRTs showed decrease in number of smaller hepatic metastases, with mild interval decrease in size of larger hepatic lesion in left lobe (overall partial response). Dual-tracer PET/CT appeared to agree with histopathologic finding of well-differentiated G3 NET (WHO 2017), and findings were adequately clinically translated.
Tables
WHO classification Ki-67 index Mitoses/ 10 HPFs 2010 Well-differentiated NENs NET G1 <3 <2 NET G2 3–20 2–20 Poorly differentiated NENs NEC G3 (small cell or large cell) >20 >20 MANEC 2017 Well-differentiated NENs NET G1 <3 <2 NET G2 3–20 2–20 NET G3 >20 >20 Poorly differentiated NENs NEC G3 >20 >20 Small cell type Large cell type MiNEN HPF = high-power field.
Demographic Data Total patients 36 (100%) Sex Male 24 (67%) Female 12 (33%) Age (y) Median 50 Range 25–66 Site of primary Pancreas 12 (33.3%) Unknown 7 (19.4%) Rectum 5 (13.9%) Small bowel 4 (11.1%) Lung 3 (8.3%) Mediastinum 2 (5.6%) Stomach 1 (2.8%) Gallbladder 1 (2.8%) Skin appendages (Merkel cell carcinoma) 1 (2.8%) WHO grade (2017 classification) G1 NET 7 (19.4%) G2 NET 15 (41.7%) G3 NET 7 (19.4%) G3 NEC 7 (19.4%) Differentiation status Well-differentiated 27 (75.0%) Poorly differentiated 7 (19.4%) Not known 2 (5.6%) Data are number and percentage, except for age.
Characteristic Data Synaptophysin (IHC) Positive 30 (83.3%) Negative 6 (16.7%) Chromogranin A (IHC) Positive 26 (72.2%) Negative 3 (8.3%) Not known 7 (19.4%) Epithelial markers (AE1/AE3; IHC) Positive 11 (30.6%) Negative 2 (5.6%) Not known 23 (63.9%) Other IHC markers (ATRX, cytokeratin, CD56, CK7, CK19, CK20, and CDX2) Positive 10 (27.8%) Not known 26 (72.2%) Data are number and percentage.
Characteristic Data Baseline 18F-FDG uptake (SUVmax) <5 14 (38.9%) 5–10 5 (13.9%) 10–20 10 (27.8%) >20 7 (19.4%) Baseline DOTATATE uptake Krenning 1 2 (5.6%) Krenning 2 5 (13.9%) Krenning 3 10 (27.8%) Krenning 4 19 (52.8%) Dual-tracer PET Metabolically inactive and SSTR-expressing 14 (38.9%) Metabolically active and non–SSTR-expressing 10 (27.8%) Matched (metabolically active and SSTR-expressing) 12 (33.3%) Data are number and percentage.
