title: Long-term results of PRRT in advanced bronchopulmonary carcinoid.
abstract: OBJECTIVE
  Peptide receptor radionuclide therapy (PRRT) for the treatment of neuroendocrine tumours (NET) has been explored for almost two decades, but there are still few trials that have exclusively investigated well-differentiated and moderately differentiated NET arising from the respiratory tree. Thus, the aim of this study was to explore the outcome in patients affected by bronchopulmonary carcinoid (BPC) following PRRT.
  
  
  METHODS
  We retrospectively analysed 114 patients with advanced stage BPC consecutively treated with PRRT at the European Institute of Oncology, Milan, from 1997 to 2012 and followed until October 2014. The objective responses, overall survival (OS) and progression-free survival (PFS) were rated, and three different PRRT protocols ((90)Y-DOTATOC vs. (177)Lu-DOTATATE vs. (90)Y-DOTATOC + (177)Lu-DOTATATE) were compared with regard to their efficacy and tolerability.
  
  
  RESULTS
  The median OS (evaluated in 94 of the 114 patients) was 58.8 months. The median PFS was 28.0 months. The (177)Lu-DOTATATE protocol resulted in the highest 5-year OS (61.4%). Morphological responses (partial responses + minor responses) were obtained in 26.5% of the cohort and were associated with longer OS and PFS. The (90)Y-DOTATOC + (177)Lu-DOTATATE protocol provided the highest response rate (38.1%). Adverse events were mild in the majority of patients. However, haematological toxicity negatively affected survival. No severe (grade 3/4) serum creatinine increase was observed. Patients treated with (90)Y-DOTATOC alone more frequently showed a mild/moderate decrease in renal function. In patients treated with chemotherapy before PRRT had a shorter OS and PFS, and a higher risk of developing nephrotoxicity.
  
  
  CONCLUSIONS
  In a large cohort of patients with advanced BPC treated in a "real-world" scenario and followed up for a median of 45.1 months (range 2-191 months), PRRT proved to be promising in prolonging survival and delaying disease progression. Despite the potential selection biases, considering the risk-benefit ratio, (177)Lu-DOTATATE monotherapy seems the best option for PRRT. Our results indicate that the use of PRRT in earlier stages of the disease could provide a more favorable outcome.
authors.affiliation: Division of Nuclear Medicine, European Institute of Oncology, via Ripamonti 435, 20141, Milan, Italy. annap_mar@hotmail.it.
authors.forename: Annapaola
authors.initials: A
authors.lastname: Mariniello
authors.affiliation: Division of Nuclear Medicine, European Institute of Oncology, via Ripamonti 435, 20141, Milan, Italy.
authors.forename: Lisa
authors.initials: L
authors.lastname: Bodei
authors.affiliation: Epidemiology and Biometric Unit, IRCCS Foundation Policlinico San Matteo, Pavia, Italy.
authors.forename: Carmine
authors.initials: C
authors.lastname: Tinelli
authors.affiliation: Division of Nuclear Medicine, European Institute of Oncology, via Ripamonti 435, 20141, Milan, Italy.
authors.forename: Silvia Melania
authors.initials: SM
authors.lastname: Baio
authors.affiliation: Division of Nuclear Medicine, European Institute of Oncology, via Ripamonti 435, 20141, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Gilardi
authors.affiliation: Division of Nuclear Medicine, European Institute of Oncology, via Ripamonti 435, 20141, Milan, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Colandrea
authors.affiliation: Division of Nuclear Medicine, European Institute of Oncology, via Ripamonti 435, 20141, Milan, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Papi
authors.affiliation: Presidio Ospedaliero E. Morelli AOVV, Sondalo, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Valmadre
authors.affiliation: Unit of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, Milan, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Fazio
authors.affiliation: Thoracic Surgery Division, European Institute of Oncology, Milan, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Galetta
authors.affiliation: Nuclear Medicine and Radiometabolic Units, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Paganelli
authors.affiliation: Division of Nuclear Medicine, European Institute of Oncology, via Ripamonti 435, 20141, Milan, Italy.
authors.forename: Chiara Maria
authors.initials: CM
authors.lastname: Grana
mesh_terms: D000368:Aged; D002276:Carcinoid Tumor / Q000532:radiotherapy*; D018278:Carcinoma, Neuroendocrine / Q000532:radiotherapy; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood; D003625:Data Collection; D018450:Disease Progression; D018572:Disease-Free Survival; D005060:Europe; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008187:Lutetium / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D018358:Neuroendocrine Tumors / Q000532:radiotherapy*; D015282:Octreotide / Q000031:analogs & derivatives / Q000737:chemistry; D016017:Odds Ratio; D009942:Organometallic Compounds / Q000737:chemistry; D016499:Radioimmunotherapy; D011868:Radioisotopes / Q000737:chemistry; D019275:Radiopharmaceuticals / Q000627:therapeutic use*; D018000:Receptors, Peptide / Q000737:chemistry*; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D009942:Organometallic Compounds; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D018000:Receptors, Peptide; D008187:Lutetium; C447941:lutetium Lu 177 dotatate; D003404:Creatinine; D015282:Octreotide; C106246:Edotreotide
keywords: Bronchopulmonary carcinoid; Neuroendocrine tumours; Peptide receptor radionuclide therapy