Peptide receptor radionuclide therapy with 177Lu-DOTATATE in advanced bronchial carcinoids: prognostic role of thyroid transcription factor 1 and 18F-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 177Lu-DOTATATE (Lu-PRRT) and the role of thyroid transcription factor 1 (TTF-1) and 18F-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)1-7
Number of pages7
JournalEuropean Journal Of Nuclear Medicine
DOIs
Publication statusAccepted/In press - Nov 27 2015

Fingerprint

Peptide Receptors
Fluorodeoxyglucose F18
Carcinoid Tumor
Radioisotopes
Disease-Free Survival
Therapeutics
(177lutetium-DOTA(O)Tyr3)octreotate
thyroid nuclear factor 1
Neuroendocrine Tumors

Keywords

  • F-FDG PET
  • Bronchial carcinoids
  • Peptide receptor radionuclide therapy with Lu-DOTATATE
  • Thyroid transcription factor 1

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

@article{c3501be363b4433e9af75a731bfcaf4c,
title = "Peptide receptor radionuclide therapy with 177Lu-DOTATATE in advanced bronchial carcinoids: prognostic role of thyroid transcription factor 1 and 18F-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 177Lu-DOTATATE (Lu-PRRT) and the role of thyroid transcription factor 1 (TTF-1) and 18F-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 = "F-FDG PET, Bronchial carcinoids, Peptide receptor radionuclide therapy with Lu-DOTATATE, Thyroid transcription factor 1",
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 = "2015",
month = "11",
day = "27",
doi = "10.1007/s00259-015-3262-8",
language = "English",
pages = "1--7",
journal = "European Journal of Pediatrics",
issn = "0340-6199",
publisher = "Springer Berlin Heidelberg",

}

TY - JOUR

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

T2 - prognostic role of thyroid transcription factor 1 and 18F-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 - 2015/11/27

Y1 - 2015/11/27

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 177Lu-DOTATATE (Lu-PRRT) and the role of thyroid transcription factor 1 (TTF-1) and 18F-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 177Lu-DOTATATE (Lu-PRRT) and the role of thyroid transcription factor 1 (TTF-1) and 18F-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 - F-FDG PET

KW - Bronchial carcinoids

KW - Peptide receptor radionuclide therapy with Lu-DOTATATE

KW - Thyroid transcription factor 1

UR - http://www.scopus.com/inward/record.url?scp=84948436436&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84948436436&partnerID=8YFLogxK

U2 - 10.1007/s00259-015-3262-8

DO - 10.1007/s00259-015-3262-8

M3 - Article

AN - SCOPUS:84948436436

SP - 1

EP - 7

JO - European Journal of Pediatrics

JF - European Journal of Pediatrics

SN - 0340-6199

ER -