Peptide receptor radionuclide therapy with (177)Lu-DOTATATE in advanced bronchial carcinoids: prognostic role of thyroid transcription factor 1 and (18)F-FDG PET

Annarita Ianniello, Maddalena Sansovini, Stefano Severi, Silvia Nicolini, Chiara Maria Grana, Katrin Massri, Alberto Bongiovanni, Lorenzo Antonuzzo, Valentina Di Iorio, Anna Sarnelli, Paola Caroli, Manuela Monti, Emanuela Scarpi, Giovanni Paganelli

Research output: Contribution to journalArticle

Abstract

PURPOSE: Typical and atypical carcinoids (TC and AC) represent 20 - 25 % of all neuroendocrine tumours. No standard therapeutic approach is available for patients with advanced disease. The aim of this phase II study was to investigate the efficacy and safety of peptide receptor radionuclide therapy with (177)Lu-DOTATATE (Lu-PRRT) and the role of thyroid transcription factor 1 (TTF-1) and (18)F-FDG PET as prognostic factors in patients with advanced TC or AC.

METHODS: A total of 34 consecutive patients with radiologically documented progressive disease were treated with Lu-PRRT at a therapeutic cumulative activity of 18.5 or 27.8 GBq in four or five cycles according to the patient's kidney function and bone marrow reserve. Information on TTF-1 was available in all patients. FDG PET studies prior to Lu-PRRT were available in 29 patients.

RESULTS: The median follow-up was 29 months (range 7 - 69 months). The disease control rate (DCR) in patients with TC was 80 %: 6 % complete response, 27 % partial response and 47 % stable disease. The median progression-free survival (mPFS) was 20.1 months (95 % CI 11.8 - 26.8 months). Stable disease was achieved in 47 % of patients with AC with a mPFS of 15.7 months (95 % CI 10.6 - 25.9 months). No major acute or delayed toxicity occurred in either group or with either cumulative activity. mPFS in patients with TTF-1-negative TC was 26.3 months (95 % CI 12.9 - 45.2 months), but in patients with TTF-1-positive TC mPFS was 7.2 months (4.2 - 14.0 months; p = 0.0009). FDG PET was negative in 13 patients (10 TC and 3 AC) and positive in 16 patients (4 TC and 12 AC). The mPFS in the FDG PET-negative group was 26.4 months (95 % CI 14.2 - 48.9 months) and 15.3 months (11.7 - 31.1 months) in the FDG PET-positive group.

CONCLUSION: Lu-PRRT showed antitumour activity in terms of DCR and PFS and proved safe, even in patients with a higher risk of side effects. TTF-1 would appear to be a prognostic factor. FDG PET positivity in bronchial carcinoids is a hallmark of aggressive tumour and is more frequent in patients with AC than in those with TC.

Original languageEnglish
Pages (from-to)1040-6
Number of pages7
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Volume43
Issue number6
DOIs
Publication statusPublished - Jun 2016

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Peptide Receptors
Carcinoid Tumor
Radioisotopes
Disease-Free Survival
Therapeutics
thyroid nuclear factor 1
Neuroendocrine Tumors

Keywords

  • Adult
  • Aged
  • Disease-Free Survival
  • Female
  • Fluorodeoxyglucose F18
  • Humans
  • Male
  • Middle Aged
  • Neuroendocrine Tumors
  • Nuclear Proteins
  • Octreotide
  • Organometallic Compounds
  • Positron-Emission Tomography
  • Receptors, Peptide
  • Safety
  • Transcription Factors
  • Clinical Trial, Phase II
  • Journal Article

Cite this

@article{15b203030914453c98ca176e39666892,
title = "Peptide receptor radionuclide therapy with (177)Lu-DOTATATE in advanced bronchial carcinoids: prognostic role of thyroid transcription factor 1 and (18)F-FDG PET",
abstract = "PURPOSE: Typical and atypical carcinoids (TC and AC) represent 20 - 25 {\%} of all neuroendocrine tumours. No standard therapeutic approach is available for patients with advanced disease. The aim of this phase II study was to investigate the efficacy and safety of peptide receptor radionuclide therapy with (177)Lu-DOTATATE (Lu-PRRT) and the role of thyroid transcription factor 1 (TTF-1) and (18)F-FDG PET as prognostic factors in patients with advanced TC or AC.METHODS: A total of 34 consecutive patients with radiologically documented progressive disease were treated with Lu-PRRT at a therapeutic cumulative activity of 18.5 or 27.8 GBq in four or five cycles according to the patient's kidney function and bone marrow reserve. Information on TTF-1 was available in all patients. FDG PET studies prior to Lu-PRRT were available in 29 patients.RESULTS: The median follow-up was 29 months (range 7 - 69 months). The disease control rate (DCR) in patients with TC was 80 {\%}: 6 {\%} complete response, 27 {\%} partial response and 47 {\%} stable disease. The median progression-free survival (mPFS) was 20.1 months (95 {\%} CI 11.8 - 26.8 months). Stable disease was achieved in 47 {\%} of patients with AC with a mPFS of 15.7 months (95 {\%} CI 10.6 - 25.9 months). No major acute or delayed toxicity occurred in either group or with either cumulative activity. mPFS in patients with TTF-1-negative TC was 26.3 months (95 {\%} CI 12.9 - 45.2 months), but in patients with TTF-1-positive TC mPFS was 7.2 months (4.2 - 14.0 months; p = 0.0009). FDG PET was negative in 13 patients (10 TC and 3 AC) and positive in 16 patients (4 TC and 12 AC). The mPFS in the FDG PET-negative group was 26.4 months (95 {\%} CI 14.2 - 48.9 months) and 15.3 months (11.7 - 31.1 months) in the FDG PET-positive group.CONCLUSION: Lu-PRRT showed antitumour activity in terms of DCR and PFS and proved safe, even in patients with a higher risk of side effects. TTF-1 would appear to be a prognostic factor. FDG PET positivity in bronchial carcinoids is a hallmark of aggressive tumour and is more frequent in patients with AC than in those with TC.",
keywords = "Adult, Aged, Disease-Free Survival, Female, Fluorodeoxyglucose F18, Humans, Male, Middle Aged, Neuroendocrine Tumors, Nuclear Proteins, Octreotide, Organometallic Compounds, Positron-Emission Tomography, Receptors, Peptide, Safety, Transcription Factors, Clinical Trial, Phase II, Journal Article",
author = "Annarita Ianniello and Maddalena Sansovini and Stefano Severi and Silvia Nicolini and Grana, {Chiara Maria} and Katrin Massri and Alberto Bongiovanni and Lorenzo Antonuzzo and {Di Iorio}, Valentina and Anna Sarnelli and Paola Caroli and Manuela Monti and Emanuela Scarpi and Giovanni Paganelli",
year = "2016",
month = "6",
doi = "10.1007/s00259-015-3262-8",
language = "English",
volume = "43",
pages = "1040--6",
journal = "European Journal of Nuclear Medicine and Molecular Imaging",
issn = "1619-7070",
publisher = "Springer Verlag",
number = "6",

}

TY - JOUR

T1 - Peptide receptor radionuclide therapy with (177)Lu-DOTATATE in advanced bronchial carcinoids

T2 - prognostic role of thyroid transcription factor 1 and (18)F-FDG PET

AU - Ianniello, Annarita

AU - Sansovini, Maddalena

AU - Severi, Stefano

AU - Nicolini, Silvia

AU - Grana, Chiara Maria

AU - Massri, Katrin

AU - Bongiovanni, Alberto

AU - Antonuzzo, Lorenzo

AU - Di Iorio, Valentina

AU - Sarnelli, Anna

AU - Caroli, Paola

AU - Monti, Manuela

AU - Scarpi, Emanuela

AU - Paganelli, Giovanni

PY - 2016/6

Y1 - 2016/6

N2 - PURPOSE: Typical and atypical carcinoids (TC and AC) represent 20 - 25 % of all neuroendocrine tumours. No standard therapeutic approach is available for patients with advanced disease. The aim of this phase II study was to investigate the efficacy and safety of peptide receptor radionuclide therapy with (177)Lu-DOTATATE (Lu-PRRT) and the role of thyroid transcription factor 1 (TTF-1) and (18)F-FDG PET as prognostic factors in patients with advanced TC or AC.METHODS: A total of 34 consecutive patients with radiologically documented progressive disease were treated with Lu-PRRT at a therapeutic cumulative activity of 18.5 or 27.8 GBq in four or five cycles according to the patient's kidney function and bone marrow reserve. Information on TTF-1 was available in all patients. FDG PET studies prior to Lu-PRRT were available in 29 patients.RESULTS: The median follow-up was 29 months (range 7 - 69 months). The disease control rate (DCR) in patients with TC was 80 %: 6 % complete response, 27 % partial response and 47 % stable disease. The median progression-free survival (mPFS) was 20.1 months (95 % CI 11.8 - 26.8 months). Stable disease was achieved in 47 % of patients with AC with a mPFS of 15.7 months (95 % CI 10.6 - 25.9 months). No major acute or delayed toxicity occurred in either group or with either cumulative activity. mPFS in patients with TTF-1-negative TC was 26.3 months (95 % CI 12.9 - 45.2 months), but in patients with TTF-1-positive TC mPFS was 7.2 months (4.2 - 14.0 months; p = 0.0009). FDG PET was negative in 13 patients (10 TC and 3 AC) and positive in 16 patients (4 TC and 12 AC). The mPFS in the FDG PET-negative group was 26.4 months (95 % CI 14.2 - 48.9 months) and 15.3 months (11.7 - 31.1 months) in the FDG PET-positive group.CONCLUSION: Lu-PRRT showed antitumour activity in terms of DCR and PFS and proved safe, even in patients with a higher risk of side effects. TTF-1 would appear to be a prognostic factor. FDG PET positivity in bronchial carcinoids is a hallmark of aggressive tumour and is more frequent in patients with AC than in those with TC.

AB - PURPOSE: Typical and atypical carcinoids (TC and AC) represent 20 - 25 % of all neuroendocrine tumours. No standard therapeutic approach is available for patients with advanced disease. The aim of this phase II study was to investigate the efficacy and safety of peptide receptor radionuclide therapy with (177)Lu-DOTATATE (Lu-PRRT) and the role of thyroid transcription factor 1 (TTF-1) and (18)F-FDG PET as prognostic factors in patients with advanced TC or AC.METHODS: A total of 34 consecutive patients with radiologically documented progressive disease were treated with Lu-PRRT at a therapeutic cumulative activity of 18.5 or 27.8 GBq in four or five cycles according to the patient's kidney function and bone marrow reserve. Information on TTF-1 was available in all patients. FDG PET studies prior to Lu-PRRT were available in 29 patients.RESULTS: The median follow-up was 29 months (range 7 - 69 months). The disease control rate (DCR) in patients with TC was 80 %: 6 % complete response, 27 % partial response and 47 % stable disease. The median progression-free survival (mPFS) was 20.1 months (95 % CI 11.8 - 26.8 months). Stable disease was achieved in 47 % of patients with AC with a mPFS of 15.7 months (95 % CI 10.6 - 25.9 months). No major acute or delayed toxicity occurred in either group or with either cumulative activity. mPFS in patients with TTF-1-negative TC was 26.3 months (95 % CI 12.9 - 45.2 months), but in patients with TTF-1-positive TC mPFS was 7.2 months (4.2 - 14.0 months; p = 0.0009). FDG PET was negative in 13 patients (10 TC and 3 AC) and positive in 16 patients (4 TC and 12 AC). The mPFS in the FDG PET-negative group was 26.4 months (95 % CI 14.2 - 48.9 months) and 15.3 months (11.7 - 31.1 months) in the FDG PET-positive group.CONCLUSION: Lu-PRRT showed antitumour activity in terms of DCR and PFS and proved safe, even in patients with a higher risk of side effects. TTF-1 would appear to be a prognostic factor. FDG PET positivity in bronchial carcinoids is a hallmark of aggressive tumour and is more frequent in patients with AC than in those with TC.

KW - Adult

KW - Aged

KW - Disease-Free Survival

KW - Female

KW - Fluorodeoxyglucose F18

KW - Humans

KW - Male

KW - Middle Aged

KW - Neuroendocrine Tumors

KW - Nuclear Proteins

KW - Octreotide

KW - Organometallic Compounds

KW - Positron-Emission Tomography

KW - Receptors, Peptide

KW - Safety

KW - Transcription Factors

KW - Clinical Trial, Phase II

KW - Journal Article

U2 - 10.1007/s00259-015-3262-8

DO - 10.1007/s00259-015-3262-8

M3 - Article

C2 - 26611427

VL - 43

SP - 1040

EP - 1046

JO - European Journal of Nuclear Medicine and Molecular Imaging

JF - European Journal of Nuclear Medicine and Molecular Imaging

SN - 1619-7070

IS - 6

ER -