Annapaola Mariniello1, Lisa Bodei2, Carmine Tinelli3, Silvia Melania Baio2, Laura Gilardi2, Marzia Colandrea2, Stefano Papi2, Giuseppe Valmadre4, Nicola Fazio5, Domenico Galetta6, Giovanni Paganelli7, Chiara Maria Grana2. 1. Division of Nuclear Medicine, European Institute of Oncology, via Ripamonti 435, 20141, Milan, Italy. annap_mar@hotmail.it. 2. Division of Nuclear Medicine, European Institute of Oncology, via Ripamonti 435, 20141, Milan, Italy. 3. Epidemiology and Biometric Unit, IRCCS Foundation Policlinico San Matteo, Pavia, Italy. 4. Presidio Ospedaliero E. Morelli AOVV, Sondalo, Italy. 5. Unit of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, Milan, Italy. 6. Thoracic Surgery Division, European Institute of Oncology, Milan, Italy. 7. Nuclear Medicine and Radiometabolic Units, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
Abstract
PURPOSE: 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. CONCLUSION: 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.
PURPOSE: 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. CONCLUSION: 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: Martijn van Essen; Eric P Krenning; Willem H Bakker; Wouter W de Herder; Maarten O van Aken; Dik J Kwekkeboom Journal: Eur J Nucl Med Mol Imaging Date: 2007-01-27 Impact factor: 9.236
Authors: Lisa Bodei; Marta Cremonesi; Stefania Zoboli; Chiara Grana; Mirco Bartolomei; Paola Rocca; Maurizio Caracciolo; Helmut R Mäcke; Marco Chinol; Giovanni Paganelli Journal: Eur J Nucl Med Mol Imaging Date: 2002-11-16 Impact factor: 9.236
Authors: Dik J Kwekkeboom; Wouter W de Herder; Boen L Kam; Casper H van Eijck; Martijn van Essen; Peter P Kooij; Richard A Feelders; Maarten O van Aken; Eric P Krenning Journal: J Clin Oncol Date: 2008-05-01 Impact factor: 44.544
Authors: Roelf Valkema; Stanislas Pauwels; Larry K Kvols; Raffaella Barone; Francois Jamar; Willem H Bakker; Dik J Kwekkeboom; Hakim Bouterfa; Eric P Krenning Journal: Semin Nucl Med Date: 2006-04 Impact factor: 4.446
Authors: Amir Sabet; Alexander R Haug; Collin Eiden; Christoph J Auernhammer; Birgit Simon; Peter Bartenstein; Hans J Biersack; Samer Ezziddin Journal: Am J Nucl Med Mol Imaging Date: 2017-04-15
Authors: Robert A Ramirez; Aman Chauhan; Juan Gimenez; Katharine E H Thomas; Ioni Kokodis; Brianne A Voros Journal: Rev Endocr Metab Disord Date: 2017-12 Impact factor: 6.514
Authors: Giuseppe Lo Russo; Sara Pusceddu; Natalie Prinzi; Martina Imbimbo; Claudia Proto; Diego Signorelli; Milena Vitali; Monica Ganzinelli; Marco Maccauro; Roberto Buzzoni; Ettore Seregni; Filippo de Braud; Marina Chiara Garassino Journal: Tumour Biol Date: 2016-07-27
Authors: Lisa Bodei; Mark S Kidd; Aviral Singh; Wouter A van der Zwan; Stefano Severi; Ignat A Drozdov; Jaroslaw Cwikla; Richard P Baum; Dik J Kwekkeboom; Giovanni Paganelli; Eric P Krenning; Irvin M Modlin Journal: Eur J Nucl Med Mol Imaging Date: 2018-02-26 Impact factor: 9.236