Antongiulio Faggiano1, Silvana Di Maio2, Carmela Mocerino3, Margaret Ottaviano4, Chiara De Divitiis5, Valentina Guarnotta6, Pasquale Dolce7, Roberta Modica2, Ivana Puliafito8, Lucia Tozzi9, Antonella Di Sarno10, Silvana Leo11, Ferdinando Riccardi3, Giovannella Palmieri4, Salvatore Tafuto5, Antonella Bianco10, Giuseppe Badalamenti12, Annamaria Colao2. 1. Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy. antongiulio.faggiano@uniroma1.it. 2. Division of Endocrinology, Department of Clinical Medicine and Surgery, Federico II University of Naples, Naples, Italy. 3. Oncology Unit, Azienda Ospedaliera Antonio Cardarelli, Naples, Italy. 4. Oncology Unit, Department of Clinical Medicine and Surgery, Federico II University of Naples, Naples, Italy. 5. Medical Oncology Unit, Istituto Nazionale per lo studio e la cura dei tumori "Fondazione G. Pascale"-IRCCS, Naples, Italy. 6. Division of Endocrinology, Diabetology and Metabolism, DIBIMIS, University of Palermo, Palermo, Italy. 7. Department of Public Health, Federico II University of Naples, Naples, Italy. 8. Oncology Unit, Department of Medical Oncology, IOM-Istituto Oncologico del Mediterraneo, Catania, Italy. 9. Fondazione IRCCS Casa Sollievo della Sofferenza, UO di Oncologia, San Giovanni Rotondo, FG, Italy. 10. Oncology Unit, AO dei Colli, Monaldi Unit, Naples, Italy. 11. Oncology Unit, Ospedale Civico, Lecce, Italy. 12. Division of Oncology, Department of Surgical and Oncological Sciences, University of Palermo, Palermo, Italy.
Abstract
PURPOSE: Many different treatments are suggested by guidelines to treat grade 1-2 (G1-G2) neuroendocrine tumors (NET). However, a precise therapeutic algorithm has not yet been established. This study aims at identifying and comparing the main therapeutic sequences in G1-G2 NET. METHODS: A retrospective observational Italian multicenter study was designed to collect data on therapeutic sequences in NET. Median progression-free survival (PFS) was compared between therapeutic sequences, as well as the number and grade of side effects and the rate of dose reduction/treatment discontinuation. RESULTS: Among 1182 patients with neuroendocrine neoplasia included in the ELIOS database, 131 G1-G2 gastroenteropancreatic, lung and unknown primary NET, unresectable or persistent/relapsing after surgery, treated with ≥2 systemic treatments, were included. Four main therapeutic sequences were identified in 99 patients: (A) somatostatin analogs (SSA) standard dose to SSA high dose (n = 36), (B) SSA to everolimus (n = 31), (C) SSA to chemotherapy (n = 17), (D) SSA to peptide receptor radionuclide therapy (PRRT) (n = 15). Median PFS of the second-line treatment was not reached in sequence A, 33 months in sequence B, 20 months in sequence C, 30 months in sequence D (p = 0.16). Both total number and severity of side effects were significantly higher in sequences B and C than A and D (p = 0.04), as well as the rate of dose reduction/discontinuation (p = 0.03). CONCLUSIONS: SSA followed by SSA high dose, everolimus, chemotherapy or PRRT represent the main therapeutic sequences in G1-G2 NET. Median PFS was not significantly different between sequences. However, the sequences with SSA high dose or PRRT seem to be better tolerated than sequences with everolimus or chemotherapy.
PURPOSE: Many different treatments are suggested by guidelines to treat grade 1-2 (G1-G2) neuroendocrine tumors (NET). However, a precise therapeutic algorithm has not yet been established. This study aims at identifying and comparing the main therapeutic sequences in G1-G2 NET. METHODS: A retrospective observational Italian multicenter study was designed to collect data on therapeutic sequences in NET. Median progression-free survival (PFS) was compared between therapeutic sequences, as well as the number and grade of side effects and the rate of dose reduction/treatment discontinuation. RESULTS: Among 1182 patients with neuroendocrine neoplasia included in the ELIOS database, 131 G1-G2 gastroenteropancreatic, lung and unknown primary NET, unresectable or persistent/relapsing after surgery, treated with ≥2 systemic treatments, were included. Four main therapeutic sequences were identified in 99 patients: (A) somatostatin analogs (SSA) standard dose to SSA high dose (n = 36), (B) SSA to everolimus (n = 31), (C) SSA to chemotherapy (n = 17), (D) SSA to peptide receptor radionuclide therapy (PRRT) (n = 15). Median PFS of the second-line treatment was not reached in sequence A, 33 months in sequence B, 20 months in sequence C, 30 months in sequence D (p = 0.16). Both total number and severity of side effects were significantly higher in sequences B and C than A and D (p = 0.04), as well as the rate of dose reduction/discontinuation (p = 0.03). CONCLUSIONS:SSA followed by SSA high dose, everolimus, chemotherapy or PRRT represent the main therapeutic sequences in G1-G2 NET. Median PFS was not significantly different between sequences. However, the sequences with SSA high dose or PRRT seem to be better tolerated than sequences with everolimus or chemotherapy.
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