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: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Nuclear Medicine and Radiometabolic Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via Maroncelli 40, 47014, Meldola, Italy.
authors.forename: Annarita
authors.initials: A
authors.lastname: Ianniello
authors.affiliation: Nuclear Medicine and Radiometabolic Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via Maroncelli 40, 47014, Meldola, Italy.
authors.forename: Maddalena
authors.initials: M
authors.lastname: Sansovini
authors.affiliation: Nuclear Medicine and Radiometabolic Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via Maroncelli 40, 47014, Meldola, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Severi
authors.affiliation: Nuclear Medicine and Radiometabolic Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via Maroncelli 40, 47014, Meldola, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Nicolini
authors.affiliation: Division of Nuclear Medicine, European Institute of Oncology Milan (IEO), Milan, Italy.
authors.forename: Chiara Maria
authors.initials: CM
authors.lastname: Grana
authors.affiliation: Nuclear Medicine, Department of Radiology, Ospedale San Luca, Lucca, Italy.
authors.forename: Katrin
authors.initials: K
authors.lastname: Massri
authors.affiliation: Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Bongiovanni
authors.affiliation: SC Oncologia Medica 1, AOU Careggi, Firenze, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Antonuzzo
authors.affiliation: Oncology Pharmacy Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Di Iorio
authors.affiliation: Medical Physics Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Sarnelli
authors.affiliation: Nuclear Medicine and Radiometabolic Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via Maroncelli 40, 47014, Meldola, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Caroli
authors.affiliation: Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Monti
authors.affiliation: Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Scarpi
authors.affiliation: Nuclear Medicine and Radiometabolic Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via Maroncelli 40, 47014, Meldola, Italy. giovanni.paganelli@irst.emr.it.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Paganelli
mesh_terms: D000328:Adult; D000368:Aged; D018572:Disease-Free Survival; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000000981:diagnostic imaging / Q000378:metabolism / Q000532:radiotherapy*; D009687:Nuclear Proteins / Q000378:metabolism*; D015282:Octreotide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009942:Organometallic Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D049268:Positron-Emission Tomography; D018000:Receptors, Peptide / Q000378:metabolism*; D012449:Safety; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: C000614412:NKX2-1 protein, human; D009687:Nuclear Proteins; D009942:Organometallic Compounds; D018000:Receptors, Peptide; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D019788:Fluorodeoxyglucose F18; C447941:lutetium Lu 177 dotatate; D015282:Octreotide
keywords: 18F-FDG PET; Bronchial carcinoids; Peptide receptor radionuclide therapy with 177Lu-DOTATATE; Thyroid transcription factor 1