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

Camilla B. Johnbeck; Ulrich Knigge; Seppo W. Langer; Annika Loft; Anne Kiil Berthelsen; Birgitte Federspiel; Tina Binderup; Andreas Kjaer

doi:10.2967/jnumed.116.174714

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

Camilla B. Johnbeck, Ulrich Knigge, Seppo W. Langer, Annika Loft, Anne Kiil Berthelsen, Birgitte Federspiel, Tina Binderup, Andreas Kjaer^*

^*Corresponding author for this work

18 Citations (Scopus)

Abstract

Neuroendocrine neoplasms (NENs) constitute a heterogeneous group of tumors arising in various organs and with a large span of aggressiveness and survival rates. The Ki-67 proliferation index is presently used as the key marker of prognosis, and treatment guidelines are largely based on this index. 39-deoxy-39-¹⁸F-fluorothymidine (¹⁸F-FLT) is a proliferation tracer for PET imaging valuable in the monitoring of disease progression and treatment response in various types of cancer. However, until now only data from 10 patients with NEN were available in the literature. The aim of the present study was to investigate ¹⁸F-FLT PET as a prognostic marker for NENs in comparison with ¹⁸F-FDG PET and Ki-67 index. Methods: One hundred patients were PET-scanned with both ¹⁸F-FLT and ¹⁸F-FDG within the same week, and the prognostic value of a positive scan was examined in terms of progression-free survival (PFS) and overall survival (OS). The correlation between the Ki-67 index and ¹⁸F-FLT uptake was also investigated. Results: Thirty-seven percent of patients had a positive ¹⁸F-FLT PET scan, and 49% had ¹⁸F-FDG PET-positive foci. Patients with a high ¹⁸F-FLT uptake had a significantly shorter OS and PFS than patients with low or no ¹⁸F-FLT uptake. No correlation was found between Ki-67 index and ¹⁸F-FLT uptake. In a multivariate analysis ¹⁸F-FLT, ¹⁸F-FDG, and Ki-67 all were significant prognostic markers of PFS. For OS, only ¹⁸F-FDG and Ki-67 remained significant. Conclusion: ¹⁸F-FLT PET has prognostic value in NEN patients but when ¹⁸F-FDG PET and Ki-67 index are also available, a multivariate model revealed that ¹⁸F-FLT PET only adds information regarding PFS but not OS, whereas ¹⁸F-FDG PET remains predictive of both PFS and OS. However, a clinically robust algorithm including ¹⁸F-FLT in addition to ¹⁸F-FDG and Ki-67 could not be found. Accordingly, the exact role, if any, of ¹⁸F-FLT PET in NENs remains to be established.

Original language	English
Journal	Journal of Nuclear Medicine
Volume	57
Issue number	12
Pages (from-to)	1851-1857
Number of pages	7
ISSN	0161-5505
DOIs	https://doi.org/10.2967/jnumed.116.174714
Publication status	Published - 1 Dec 2016

Keywords

F-FDG PET
F-FLT PET
Ki67
Neuroendocrine neoplasms
Prognosis

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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. / Johnbeck, Camilla B.; Knigge, Ulrich ; Langer, Seppo W. et al.
In: Journal of Nuclear Medicine, Vol. 57, No. 12, 01.12.2016, p. 1851-1857.

Research output: Contribution to journal › Journal article › Research › peer-review

@article{1f974e56deca4181bd930792ad374e9f,

title = "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",

abstract = "Neuroendocrine neoplasms (NENs) constitute a heterogeneous group of tumors arising in various organs and with a large span of aggressiveness and survival rates. The Ki-67 proliferation index is presently used as the key marker of prognosis, and treatment guidelines are largely based on this index. 39-deoxy-39-18F-fluorothymidine (18F-FLT) is a proliferation tracer for PET imaging valuable in the monitoring of disease progression and treatment response in various types of cancer. However, until now only data from 10 patients with NEN were available in the literature. The aim of the present study was to investigate 18F-FLT PET as a prognostic marker for NENs in comparison with 18F-FDG PET and Ki-67 index. Methods: One hundred patients were PET-scanned with both 18F-FLT and 18F-FDG within the same week, and the prognostic value of a positive scan was examined in terms of progression-free survival (PFS) and overall survival (OS). The correlation between the Ki-67 index and 18F-FLT uptake was also investigated. Results: Thirty-seven percent of patients had a positive 18F-FLT PET scan, and 49% had 18F-FDG PET-positive foci. Patients with a high 18F-FLT uptake had a significantly shorter OS and PFS than patients with low or no 18F-FLT uptake. No correlation was found between Ki-67 index and 18F-FLT uptake. In a multivariate analysis 18F-FLT, 18F-FDG, and Ki-67 all were significant prognostic markers of PFS. For OS, only 18F-FDG and Ki-67 remained significant. Conclusion: 18F-FLT PET has prognostic value in NEN patients but when 18F-FDG PET and Ki-67 index are also available, a multivariate model revealed that 18F-FLT PET only adds information regarding PFS but not OS, whereas 18F-FDG PET remains predictive of both PFS and OS. However, a clinically robust algorithm including 18F-FLT in addition to 18F-FDG and Ki-67 could not be found. Accordingly, the exact role, if any, of 18F-FLT PET in NENs remains to be established.",

keywords = "F-FDG PET, F-FLT PET, Ki67, Neuroendocrine neoplasms, Prognosis",

author = "Johnbeck, {Camilla B.} and Ulrich Knigge and Langer, {Seppo W.} and Annika Loft and Berthelsen, {Anne Kiil} and Birgitte Federspiel and Tina Binderup and Andreas Kjaer",

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doi = "10.2967/jnumed.116.174714",

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T1 - Prognostic value of 18F-FLT PET in patients with neuroendocrine neoplasms

T2 - A prospective head-to-head comparison with 18F-FDG PET and Ki-67 in 100 patients

AU - Johnbeck, Camilla B.

AU - Knigge, Ulrich

AU - Langer, Seppo W.

AU - Loft, Annika

AU - Berthelsen, Anne Kiil

AU - Federspiel, Birgitte

AU - Binderup, Tina

AU - Kjaer, Andreas

PY - 2016/12/1

Y1 - 2016/12/1

N2 - Neuroendocrine neoplasms (NENs) constitute a heterogeneous group of tumors arising in various organs and with a large span of aggressiveness and survival rates. The Ki-67 proliferation index is presently used as the key marker of prognosis, and treatment guidelines are largely based on this index. 39-deoxy-39-18F-fluorothymidine (18F-FLT) is a proliferation tracer for PET imaging valuable in the monitoring of disease progression and treatment response in various types of cancer. However, until now only data from 10 patients with NEN were available in the literature. The aim of the present study was to investigate 18F-FLT PET as a prognostic marker for NENs in comparison with 18F-FDG PET and Ki-67 index. Methods: One hundred patients were PET-scanned with both 18F-FLT and 18F-FDG within the same week, and the prognostic value of a positive scan was examined in terms of progression-free survival (PFS) and overall survival (OS). The correlation between the Ki-67 index and 18F-FLT uptake was also investigated. Results: Thirty-seven percent of patients had a positive 18F-FLT PET scan, and 49% had 18F-FDG PET-positive foci. Patients with a high 18F-FLT uptake had a significantly shorter OS and PFS than patients with low or no 18F-FLT uptake. No correlation was found between Ki-67 index and 18F-FLT uptake. In a multivariate analysis 18F-FLT, 18F-FDG, and Ki-67 all were significant prognostic markers of PFS. For OS, only 18F-FDG and Ki-67 remained significant. Conclusion: 18F-FLT PET has prognostic value in NEN patients but when 18F-FDG PET and Ki-67 index are also available, a multivariate model revealed that 18F-FLT PET only adds information regarding PFS but not OS, whereas 18F-FDG PET remains predictive of both PFS and OS. However, a clinically robust algorithm including 18F-FLT in addition to 18F-FDG and Ki-67 could not be found. Accordingly, the exact role, if any, of 18F-FLT PET in NENs remains to be established.

AB - Neuroendocrine neoplasms (NENs) constitute a heterogeneous group of tumors arising in various organs and with a large span of aggressiveness and survival rates. The Ki-67 proliferation index is presently used as the key marker of prognosis, and treatment guidelines are largely based on this index. 39-deoxy-39-18F-fluorothymidine (18F-FLT) is a proliferation tracer for PET imaging valuable in the monitoring of disease progression and treatment response in various types of cancer. However, until now only data from 10 patients with NEN were available in the literature. The aim of the present study was to investigate 18F-FLT PET as a prognostic marker for NENs in comparison with 18F-FDG PET and Ki-67 index. Methods: One hundred patients were PET-scanned with both 18F-FLT and 18F-FDG within the same week, and the prognostic value of a positive scan was examined in terms of progression-free survival (PFS) and overall survival (OS). The correlation between the Ki-67 index and 18F-FLT uptake was also investigated. Results: Thirty-seven percent of patients had a positive 18F-FLT PET scan, and 49% had 18F-FDG PET-positive foci. Patients with a high 18F-FLT uptake had a significantly shorter OS and PFS than patients with low or no 18F-FLT uptake. No correlation was found between Ki-67 index and 18F-FLT uptake. In a multivariate analysis 18F-FLT, 18F-FDG, and Ki-67 all were significant prognostic markers of PFS. For OS, only 18F-FDG and Ki-67 remained significant. Conclusion: 18F-FLT PET has prognostic value in NEN patients but when 18F-FDG PET and Ki-67 index are also available, a multivariate model revealed that 18F-FLT PET only adds information regarding PFS but not OS, whereas 18F-FDG PET remains predictive of both PFS and OS. However, a clinically robust algorithm including 18F-FLT in addition to 18F-FDG and Ki-67 could not be found. Accordingly, the exact role, if any, of 18F-FLT PET in NENs remains to be established.

KW - F-FDG PET

KW - F-FLT PET

KW - Ki67

KW - Neuroendocrine neoplasms

KW - Prognosis

U2 - 10.2967/jnumed.116.174714

DO - 10.2967/jnumed.116.174714

M3 - Journal article

C2 - 27469355

AN - SCOPUS:85001125059

SN - 0161-5505

VL - 57

SP - 1851

EP - 1857

JO - Journal of Nuclear Medicine

JF - Journal of Nuclear Medicine

IS - 12

ER -