Prognostic Value of <sup>18</sup>F-FLT PET in Patients with Neuroendocrine Neoplasms: A Prospective Head-to-Head Comparison with <sup>18</sup>F-FDG PET and Ki-67 in 100 Patients

Johnbeck, Camilla Bardram; Knigge, Ulrich; Langer, Seppo W.; Loft, Annika; Berthelsen, Anne Kiil; Federspiel, Birgitte; Binderup, Tina; Kjær, Andreas

doi:10.2967/jnumed.116.174714

Cited by 30 publications

(46 citation statements)

References 36 publications

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“…FDG was positive in 39% of G1 and 50% of G2 patients. In these patients with well-differentiated NET, only FDG-positivity was a significant prognostic factor with a hazard ratio of 2.4 for PFS (P = 0.003) and 5.3 for OS (P = 0.001) 14.…”

Section: What Is the Frequency Of Fdg-positive Scans In Well-differenmentioning

confidence: 93%

“…Three prospective studies showed that FDG positivity is not rare in metastatic well-differentiated G1/G2 NET and is a stronger predictor of progression and prognosis than the existing WHO groups 10,11,14. In the study by Garin and colleagues, 30 patients with documented well-differentiated metastatic NET were offered a period of wait-and-watch before treatment 10,13.…”

Section: What Is the Frequency Of Fdg-positive Scans In Well-differenmentioning

confidence: 99%

“…Five of 47 patients in the G1 group died, four of whom had a positive FDG-PET 11. In the study recently reported by Johnbeck et al, 88 patients had well-differentiated advanced NET 14. Treatment strategies were based on standard of care.…”

Section: What Is the Frequency Of Fdg-positive Scans In Well-differenmentioning

confidence: 99%

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The NETPET Score: Combining FDG and Somatostatin Receptor Imaging for Optimal Management of Patients with Metastatic Well-Differentiated Neuroendocrine Tumors

Hindié¹

2017

Theranostics

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Neuroendocrine tumors (NET) are often metastatic at the time of diagnosis. Metastatic well-differentiated (G1/G2) NET may display a wide range of behaviors, ranging from indolent to aggressive, even within apparently homogeneous categories. Thus, selecting the optimal treatment strategy is a challenging task. Somatostatin receptor imaging (SRI) is the standard molecular imaging technique for well-differentiated NET. When performed with 68Ga-labeled somatostatin analogs (SRI-PET), it offers exquisite sensitivity for disease staging. SRI is also a prerequisite for using targeted radionuclide therapy (e.g. 177Lu-DOTATATE). 18F-FDG imaging has traditionally been reserved for staging poorly-differentiated G3 neuroendocrine carcinomas. However, recent data showed that FDG imaging has prognostic value in patients with well-differentiated NET: high uptake was associated with an increased risk of early progression while low uptake suggested an indolent tumor.In this issue of the Journal, Chan and colleagues propose a grading system where the results from the combined reading of SRI-PET and FDG-PET are reported as a single parameter, the “NETPET” score. While the scoring system still needs validation, it is clear that time has come to think about FDG and SRI in metastatic NET not as competitors but as complementary imaging modalities. Dual-tracer imaging can be viewed as a way to characterize disease phenotype in the whole-body. Moving from the prognostic value of dual-tracer imaging to a tool that allows for individualized management would require prospective trials. This editorial will argue that dual-tracer FDG-PET and SRI-PET might influence management of patients with well-differentiated metastatic NET and help selecting between different therapy options.

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Section: What Is the Frequency Of Fdg-positive Scans In Well-differenmentioning

confidence: 93%

Section: What Is the Frequency Of Fdg-positive Scans In Well-differenmentioning

confidence: 99%

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The NETPET Score: Combining FDG and Somatostatin Receptor Imaging for Optimal Management of Patients with Metastatic Well-Differentiated Neuroendocrine Tumors

Hindié¹

2017

Theranostics

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“…18 F-fluoro-2-deoxyglucose (FDG)-PET/CT demonstrates increased cellular tissue metabolism. Although the sensitivity of 18 F-FDG-PET/ CT imaging is low for NETs, positive 18 F-FDG-PET/CT predicts poor survival for NET patients [15,16]. Dualtracer functional imaging of NF-PNET has only been studied in retrospective series [17,18].…”

Section: Introductionmentioning

confidence: 99%

Prediction of the aggressiveness of non-functional pancreatic neuroendocrine tumors based on the dual-tracer PET/CT

et al. 2019

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Background: Predicting the aggressive behavior of non-functional pancreatic neuroendocrine tumors (NF-PNET) remains controversial. We wanted to explore, in a prospective setting, whether the diagnostic accuracy can be improved by dual-tracer functional imaging 68 Ga-DOTANOC and 18 F-FDG-PET/CT in patients with NF-PNETs. Methods: Thirty-one patients with NF-PNET (90% asymptomatic) underwent PET-imaging with 18 F-FDG and 68 Ga-DOTANOC, followed by surgery (n = 20), an endoscopic ultrasonography and fine-needle biopsy (n = 2) or followup (n = 9). A focal activity on PET/CT greater than the background that could not be identified as physiological activity was considered to indicate tumor tissue. The imaging results were compared to histopathology. The mean follow-up time was 31.3 months. Results: Thirty-one patients presented a total of 53 lesions (40 histologically confirmed) on PET/CT. Thirty patients had a 68 Ga-DOTANOC-positive tumor (sensitivity 97%) and 10 patients had an 18 F-FDG-positive tumor. In addition, one 68 Ga-DOTANOC-negative patient was 18 F-FDG-positive. 18 F-FDG-PET/CT was positive in 19% (3/16) of the G1 tumors, 63% (5/8) of the G2 tumors and 1/1 of the well-differentiated G3 tumor. 68 Ga-DOTANOC-PET/CT was positive in 94% of the G1 tumors, 100% of the G2 tumors and 1/1 of the well-differentiated G3 tumor. Two out of six (33%) of the patients with lymph node metastases (LN+) were 18 F-FDG-positive. The 18 F-FDG-PET/CT correlated with tumor Ki-67 (P = 0.021). Further, the Krenning score correlated with tumor Ki-67 (P = 0.013). 18 F-FDG-positive tumors were significantly larger than the 18 F-FDG-negative tumors (P = 0.012). 18 F-FDG-PET/CT showed a positive predictive value of 78% in the detection of potentially aggressive tumors (G2, G3, or LN + PNETs); the negative predictive value was 69%.Conclusions: 18 F-FDG-PET/CT is useful to predict tumor grade but not the LN+ of NF-PNETs. Patients with 18 F-FDGavid NF-PNETs should be referred for surgery. The 68 Ga-DOTANOC-PET/CT also has prognostic value since the Krenning score predicts the histopathological tumor grade.Trial registration: The study has been registered at ClinicalTrials.gov; Non-functional Pancreatic NET and PET imaging, NCT02621541.

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“…However, as underlined by the ENETS guidelines, NEN prognosis may also depend on patient age, tumor site, metastatic spread and hormonal production. Several methods have been proposed to predict overall survival (OS) and progression-free survival (PFS) of NEN patients, including clinical nomograms taking into account the number of liver metastases, tumor size and Ki67 index (Ruzzenente et al 2016) or blood neutrophilto-lymphocyte ratio, Ki67 index and lymph node ratio (Cao et al 2016), positron emission tomography results by means of new tracers, such as (18)F-fluorothymidine (Johnbeck et al 2016), or molecular markers, such as HOPX promoter methylation/gene expression (Ushiku et al 2016) or phosphorylated histone H3 assessment (Villani et al 2016). Besides tissue-based characteristics, blood-based biomarkers have been considered, also due to easy accessibility of the compartment and possibility 24:6 of multiple sampling.…”

Section: Introductionmentioning

confidence: 99%

Circulating tumor cells and miRNAs as prognostic markers in neuroendocrine neoplasms

Zatelli¹,

Grossrubatscher²,

Guadagno³

et al. 2017

Endocrine-Related Cancer

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The prognosis of neuroendocrine neoplasms (NENs) is widely variable and has been shown to associate with several tissue-and blood-based biomarkers in different settings. The identification of prognostic factors predicting NEN outcome is of paramount importance to select the best clinical management for these patients. Prognostic markers have been intensively investigated, also taking advantage of the most modern techniques, in the perspective of personalized medicine and appropriate resource utilization. This review summarizes the available data on the possible role of circulating tumor cells and microRNAs as prognostic markers in NENs.

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Prognostic Value of ¹⁸F-FLT PET in Patients with Neuroendocrine Neoplasms: A Prospective Head-to-Head Comparison with ¹⁸F-FDG PET and Ki-67 in 100 Patients

Cited by 30 publications

References 36 publications

The NETPET Score: Combining FDG and Somatostatin Receptor Imaging for Optimal Management of Patients with Metastatic Well-Differentiated Neuroendocrine Tumors

The NETPET Score: Combining FDG and Somatostatin Receptor Imaging for Optimal Management of Patients with Metastatic Well-Differentiated Neuroendocrine Tumors

Prediction of the aggressiveness of non-functional pancreatic neuroendocrine tumors based on the dual-tracer PET/CT

Circulating tumor cells and miRNAs as prognostic markers in neuroendocrine neoplasms

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Prognostic Value of 18F-FLT PET in Patients with Neuroendocrine Neoplasms: A Prospective Head-to-Head Comparison with 18F-FDG PET and Ki-67 in 100 Patients

Cited by 30 publications

References 36 publications

The NETPET Score: Combining FDG and Somatostatin Receptor Imaging for Optimal Management of Patients with Metastatic Well-Differentiated Neuroendocrine Tumors

The NETPET Score: Combining FDG and Somatostatin Receptor Imaging for Optimal Management of Patients with Metastatic Well-Differentiated Neuroendocrine Tumors

Prediction of the aggressiveness of non-functional pancreatic neuroendocrine tumors based on the dual-tracer PET/CT

Circulating tumor cells and miRNAs as prognostic markers in neuroendocrine neoplasms

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Product

Resources

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Prognostic Value of ¹⁸F-FLT PET in Patients with Neuroendocrine Neoplasms: A Prospective Head-to-Head Comparison with ¹⁸F-FDG PET and Ki-67 in 100 Patients