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Erschienen in: Journal of Endocrinological Investigation 4/2021

01.04.2021 | Original Article

[18F]FDG-PET/CT and long-term responses to everolimus in advanced neuroendocrine neoplasia

verfasst von: M. Rinzivillo, D. Prosperi, F. Mazzuca, L. Magi, E. Iannicelli, E. Pilozzi, G. Franchi, A. Laghi, B. Annibale, A. Signore, F. Panzuto

Erschienen in: Journal of Endocrinological Investigation | Ausgabe 4/2021

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Abstract

Purpose

This study aims to identify in patients with neuroendocrine neoplasia (NEN) the potential correlation between FDG-PET findings and responses to everolimus therapy to identify predictors of long-term efficacy.

Methods

Retrospective analysis of patients with sporadic, advanced, progressive NEN treated with everolimus was performed based on the available data on FDG-PET patients obtained before commencing therapy. Data are expressed as the median (25–75th IQR). Risk factor analysis and survival analysis were performed by logistic regression and Cox proportional hazard regression and the determination of Kaplan–Meier curves, as appropriate.

Results

Sixty-six patients were evaluated (NET G1 19.7%, NET G2 75.7%, and NET G3 4.6%), including 45.4% with positive FDG-PET findings. Overall, disease stabilization and a partial response were achieved for 71.2% and 6% of patients, respectively. A long-term response (> 24 months) was observed in 33% of patients. Ki67 was the only predictor of tumor progression (p = 0.03). No significant difference in clinical outcomes was observed between patients with positive or negative FDG-PET findings (median PFS was 24 months and 18 months, respectively, p = 0.337; the disease control rate was 83.3% and 70%, respectively, p = 0.245).

Conclusions

Everolimus is a valid therapeutic option for advanced, progressive, well-differentiated NEN, even in patients with positive FDG-PET findings.
Literatur
1.
Zurück zum Zitat Dasari A, Shen C, Halperin D et al (2017) Trends in the incidence, prevalence, and survival outcomes in patients with neuroendocrine tumors in the United States. JAMA Oncol 3(10):1335–1342CrossRef Dasari A, Shen C, Halperin D et al (2017) Trends in the incidence, prevalence, and survival outcomes in patients with neuroendocrine tumors in the United States. JAMA Oncol 3(10):1335–1342CrossRef
2.
Zurück zum Zitat Pape UF, Jann H, Müller-Nordhorn J et al (2008) Prognostic relevance of a novel TNM classification system for upper gastroenteropancreatic neuroendocrine tumors. Cancer 113(2):256–265CrossRef Pape UF, Jann H, Müller-Nordhorn J et al (2008) Prognostic relevance of a novel TNM classification system for upper gastroenteropancreatic neuroendocrine tumors. Cancer 113(2):256–265CrossRef
3.
Zurück zum Zitat Panzuto F, Merola E, Rinzivillo M et al (2014) Advanced digestive neuroendocrine tumors: metastatic pattern is an independent factor affecting clinical outcome. Pancreas 43(2):212–218CrossRef Panzuto F, Merola E, Rinzivillo M et al (2014) Advanced digestive neuroendocrine tumors: metastatic pattern is an independent factor affecting clinical outcome. Pancreas 43(2):212–218CrossRef
4.
Zurück zum Zitat Faggiano A, Ferolla P, Grimaldi F et al (2012) Natural history of gastro-entero-pancreatic and thoracic neuroendocrine tumors. Data from a large prospective and retrospective Italian epidemiological study: the NET management study. J Endocrinol Invest 35(9):817–823. https://doi.org/10.3275/8102CrossRefPubMed Faggiano A, Ferolla P, Grimaldi F et al (2012) Natural history of gastro-entero-pancreatic and thoracic neuroendocrine tumors. Data from a large prospective and retrospective Italian epidemiological study: the NET management study. J Endocrinol Invest 35(9):817–823. https://​doi.​org/​10.​3275/​8102CrossRefPubMed
5.
Zurück zum Zitat WHO classification of tumours of endocrine organs (2020) WHO classification of tumours, 4th edition, vol. 10, In: Lloyd RV, Osamura RY, Kloppel G, Rosai J (eds) https://whobluebooks.iarc.fr; 978-92-832-4493-6 WHO classification of tumours of endocrine organs (2020) WHO classification of tumours, 4th edition, vol. 10, In: Lloyd RV, Osamura RY, Kloppel G, Rosai J (eds) https://​whobluebooks.​iarc.​fr; 978-92-832-4493-6
8.
Zurück zum Zitat Cives M, Strosberg JR (2018) Gastroenteropancreatic neuroendocrine tumors. CA Cancer J Clin 68(6):471–487CrossRef Cives M, Strosberg JR (2018) Gastroenteropancreatic neuroendocrine tumors. CA Cancer J Clin 68(6):471–487CrossRef
9.
Zurück zum Zitat Bodei L, Ferone D, Grana CM et al (2009) Peptide receptor therapies in neuroendocrine tumors. J Endocrinol Invest 32:360–369CrossRef Bodei L, Ferone D, Grana CM et al (2009) Peptide receptor therapies in neuroendocrine tumors. J Endocrinol Invest 32:360–369CrossRef
10.
Zurück zum Zitat Yao JC, Fazio N, Singh S et al (2016) Everolimus for the treatment of advanced, non-functional neuroendocrine tumours of the lung or gastrointestinal tract (RADIANT-4): a randomised, placebo-controlled, phase 3 study. Lancet 387(10022):968–977CrossRef Yao JC, Fazio N, Singh S et al (2016) Everolimus for the treatment of advanced, non-functional neuroendocrine tumours of the lung or gastrointestinal tract (RADIANT-4): a randomised, placebo-controlled, phase 3 study. Lancet 387(10022):968–977CrossRef
11.
Zurück zum Zitat Yao JC, Shah MH, Ito T et al (2011) Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med 364:514–523CrossRef Yao JC, Shah MH, Ito T et al (2011) Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med 364:514–523CrossRef
12.
Zurück zum Zitat Lee L, Ito T, Jensen RT (2018) Imaging of pancreatic neuroendocrine tumors: recent advances, current status, and controversies. Expert Rev Anticancer Ther 18(9):837–860CrossRef Lee L, Ito T, Jensen RT (2018) Imaging of pancreatic neuroendocrine tumors: recent advances, current status, and controversies. Expert Rev Anticancer Ther 18(9):837–860CrossRef
13.
Zurück zum Zitat de Mestier L, Armani M, Cros J et al (2019) Lesion-by-lesion correlation between uptake at FDG PET and the Ki67 proliferation index in resected pancreatic neuroendocrine tumors. Dig Liver Dis 51:1720–1724CrossRef de Mestier L, Armani M, Cros J et al (2019) Lesion-by-lesion correlation between uptake at FDG PET and the Ki67 proliferation index in resected pancreatic neuroendocrine tumors. Dig Liver Dis 51:1720–1724CrossRef
14.
Zurück zum Zitat Bucau M, Laurent-Bellue A, Poté N et al (2018) 18F-FDG uptake in well-differentiated neuroendocrine tumors correlates with both Ki-67 and VHL pathway inactivation. Neuroendocrinology 106(3):274–282CrossRef Bucau M, Laurent-Bellue A, Poté N et al (2018) 18F-FDG uptake in well-differentiated neuroendocrine tumors correlates with both Ki-67 and VHL pathway inactivation. Neuroendocrinology 106(3):274–282CrossRef
15.
Zurück zum Zitat Pavel M, O'Toole D, Costa F et al (2016) ENETS consensus guidelines update for the management of distant metastatic disease of intestinal, pancreatic, bronchial neuroendocrine neoplasms (NEN) and NEN of unknown primary site. Neuroendocrinology 103(2):172–185CrossRef Pavel M, O'Toole D, Costa F et al (2016) ENETS consensus guidelines update for the management of distant metastatic disease of intestinal, pancreatic, bronchial neuroendocrine neoplasms (NEN) and NEN of unknown primary site. Neuroendocrinology 103(2):172–185CrossRef
17.
Zurück zum Zitat Eisenhauer EA, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45(2):228–247CrossRef Eisenhauer EA, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45(2):228–247CrossRef
18.
Zurück zum Zitat Johnbeck CB, Munk Jensen M, Haagen Nielsen C et al (2014) 18F-FDG and 18F-FLT-PET imaging for monitoring everolimus effect on tumor-growth in neuroendocrine tumors: studies in human tumor xenografts in mice. PLoS ONE 9:e91387CrossRef Johnbeck CB, Munk Jensen M, Haagen Nielsen C et al (2014) 18F-FDG and 18F-FLT-PET imaging for monitoring everolimus effect on tumor-growth in neuroendocrine tumors: studies in human tumor xenografts in mice. PLoS ONE 9:e91387CrossRef
19.
Zurück zum Zitat Cejka D, Kuntner C, Preusser M et al (2009) FDG uptake is a surrogate marker for defining the optimal biological dose of the mTOR inhibitor everolimus in vivo. Br J Cancer 100(11):1739–1745CrossRef Cejka D, Kuntner C, Preusser M et al (2009) FDG uptake is a surrogate marker for defining the optimal biological dose of the mTOR inhibitor everolimus in vivo. Br J Cancer 100(11):1739–1745CrossRef
21.
Zurück zum Zitat Ito H, Kondo K, Kawahara T et al (2017) One-month assessment of renal cell carcinoma treated by everolimus using FDG PET/CT predicts progression-free and overall survival. Cancer Chemother Pharmacol 79(5):855–861CrossRef Ito H, Kondo K, Kawahara T et al (2017) One-month assessment of renal cell carcinoma treated by everolimus using FDG PET/CT predicts progression-free and overall survival. Cancer Chemother Pharmacol 79(5):855–861CrossRef
22.
Zurück zum Zitat Chen JL, Appelbaum DE, Kocherginsky M et al (2013) FDG-PET as a predictive biomarker for therapy with everolimus in metastatic renal cell cancer. Cancer Med 2(4):545–552CrossRef Chen JL, Appelbaum DE, Kocherginsky M et al (2013) FDG-PET as a predictive biomarker for therapy with everolimus in metastatic renal cell cancer. Cancer Med 2(4):545–552CrossRef
23.
Zurück zum Zitat Nogová L, Boellaard R, Kobe C et al (2009) Downregulation of 18F-FDG uptake in PET as an early pharmacodynamic effect in treatment of non-small cell lung cancer with the mTOR inhibitor everolimus. J Nucl Med 50(11):1815–1819CrossRef Nogová L, Boellaard R, Kobe C et al (2009) Downregulation of 18F-FDG uptake in PET as an early pharmacodynamic effect in treatment of non-small cell lung cancer with the mTOR inhibitor everolimus. J Nucl Med 50(11):1815–1819CrossRef
24.
Zurück zum Zitat Sundin A, Arnold R, Baudin E et al (2017) ENETS consensus guidelines for the standards of care in neuroendocrine tumors: radiological. Nuclear Med Hybrid Imaging Neuroendocrinol 105:212–244 Sundin A, Arnold R, Baudin E et al (2017) ENETS consensus guidelines for the standards of care in neuroendocrine tumors: radiological. Nuclear Med Hybrid Imaging Neuroendocrinol 105:212–244
25.
Zurück zum Zitat Partelli S, Rinzivillo M, Maurizi A et al (2014) The role of combined Ga-DOTANOC and (18)FDG PET/CT in the management of patients with pancreatic neuroendocrine tumors. Neuroendocrinology 100(4):293–299CrossRef Partelli S, Rinzivillo M, Maurizi A et al (2014) The role of combined Ga-DOTANOC and (18)FDG PET/CT in the management of patients with pancreatic neuroendocrine tumors. Neuroendocrinology 100(4):293–299CrossRef
26.
Zurück zum Zitat Carideo L, Prosperi D, Panzuto F, et al (2019) Role of combined [68Ga]Ga-DOTA-SST analogues and [18F]FDG PET/CT in the management of GEP-NENs: a systematic review. J Clin Med 8(7). pii: E1032. Carideo L, Prosperi D, Panzuto F, et al (2019) Role of combined [68Ga]Ga-DOTA-SST analogues and [18F]FDG PET/CT in the management of GEP-NENs: a systematic review. J Clin Med 8(7). pii: E1032.
27.
Zurück zum Zitat Chan DL, Pavlakis N, Schembri GP et al (2017) Dual somatostatin receptor/FDG PET/CT imaging in metastatic neuroendocrine tumours: proposal for a novel grading scheme with prognostic significance. Theranostics 7(5):1149–1158CrossRef Chan DL, Pavlakis N, Schembri GP et al (2017) Dual somatostatin receptor/FDG PET/CT imaging in metastatic neuroendocrine tumours: proposal for a novel grading scheme with prognostic significance. Theranostics 7(5):1149–1158CrossRef
28.
Zurück zum Zitat Seregni E, Ferrari L, Stivanello M et al (2000) Laboratory tests for neuroendocrine tumours. Q J Nucl Med 44(1):22–41PubMed Seregni E, Ferrari L, Stivanello M et al (2000) Laboratory tests for neuroendocrine tumours. Q J Nucl Med 44(1):22–41PubMed
29.
Zurück zum Zitat Rinzivillo M, Partelli S, Prosperi D et al (2018) Clinical usefulness of 18F-fluorodeoxyglucose positron emission tomography in the diagnostic algorithm of advanced entero-pancreatic neuroendocrine neoplasms. Oncologist 23(2):186–192CrossRef Rinzivillo M, Partelli S, Prosperi D et al (2018) Clinical usefulness of 18F-fluorodeoxyglucose positron emission tomography in the diagnostic algorithm of advanced entero-pancreatic neuroendocrine neoplasms. Oncologist 23(2):186–192CrossRef
30.
Zurück zum Zitat Zhang J, Liu Q, Singh A, et al (2020) Prognostic value of 18F-FDG PET/CT in a large cohort of 495 patients with advanced metastatic neuroendocrine neoplasms (NEN) treated with peptide receptor radionuclide therapy (PRRT). J Nucl Med. pii: jnumed.119.241414. Zhang J, Liu Q, Singh A, et al (2020) Prognostic value of 18F-FDG PET/CT in a large cohort of 495 patients with advanced metastatic neuroendocrine neoplasms (NEN) treated with peptide receptor radionuclide therapy (PRRT). J Nucl Med. pii: jnumed.119.241414.
31.
Zurück zum Zitat Severi S, Nanni O, Bodei L et al (2013) Role of 18FDG PET/CT in patients treated with 177Lu-DOTATATE for advanced differentiated neuroendocrine tumours. Eur J Nucl Med Mol Imaging 40(6):881–888CrossRef Severi S, Nanni O, Bodei L et al (2013) Role of 18FDG PET/CT in patients treated with 177Lu-DOTATATE for advanced differentiated neuroendocrine tumours. Eur J Nucl Med Mol Imaging 40(6):881–888CrossRef
32.
Zurück zum Zitat Sansovini M, Severi S, Ianniello A et al (2017) Long-term follow-up and role of FDG PET in advanced pancreatic neuroendocrine patients treated with 177Lu-D OTATATE. Eur J Nucl Med Mol Imaging 44(3):490–499CrossRef Sansovini M, Severi S, Ianniello A et al (2017) Long-term follow-up and role of FDG PET in advanced pancreatic neuroendocrine patients treated with 177Lu-D OTATATE. Eur J Nucl Med Mol Imaging 44(3):490–499CrossRef
33.
Zurück zum Zitat Bongiovanni A, Recine F, Riva N et al (2017) Outcome analysis of first-line somatostatin analog treatment in metastatic pulmonary neuroendocrine tumors and prognostic significance of 18FDG-PET/CT. Clin Lung Cancer 18(4):415–420CrossRef Bongiovanni A, Recine F, Riva N et al (2017) Outcome analysis of first-line somatostatin analog treatment in metastatic pulmonary neuroendocrine tumors and prognostic significance of 18FDG-PET/CT. Clin Lung Cancer 18(4):415–420CrossRef
34.
Zurück zum Zitat Panzuto F, Rinzivillo M, Fazio N et al (2014) Real-world study of everolimus in advanced progressive neuroendocrine tumors. Oncologist 19(9):966–974CrossRef Panzuto F, Rinzivillo M, Fazio N et al (2014) Real-world study of everolimus in advanced progressive neuroendocrine tumors. Oncologist 19(9):966–974CrossRef
36.
Zurück zum Zitat Capdevila J, Teulé A, Barriuso J et al (2019) Phase II study of everolimus and octreotide LAR in patients with nonfunctioning gastrointestinal neuroendocrine tumors: The GETNE1003_EVERLAR study. Oncologist 24(1):38–46CrossRef Capdevila J, Teulé A, Barriuso J et al (2019) Phase II study of everolimus and octreotide LAR in patients with nonfunctioning gastrointestinal neuroendocrine tumors: The GETNE1003_EVERLAR study. Oncologist 24(1):38–46CrossRef
Metadaten
Titel
[18F]FDG-PET/CT and long-term responses to everolimus in advanced neuroendocrine neoplasia
verfasst von
M. Rinzivillo
D. Prosperi
F. Mazzuca
L. Magi
E. Iannicelli
E. Pilozzi
G. Franchi
A. Laghi
B. Annibale
A. Signore
F. Panzuto
Publikationsdatum
01.04.2021
Verlag
Springer International Publishing
Erschienen in
Journal of Endocrinological Investigation / Ausgabe 4/2021
Elektronische ISSN: 1720-8386
DOI
https://doi.org/10.1007/s40618-020-01378-3

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