title: Somatostatin analogues according to Ki67 index in neuroendocrine tumours: an observational retrospective-prospective analysis from real life.
abstract: Somatostatin analogues (SSAs) have shown limited and variable antiproliferative effects in neuroendocrine tumours (NETs). Whether tumour control by SSAs depends on grading based on the 2010 WHO NET classification is still unclear. The aim of this study is to evaluate the efficacy of long-acting SSAs in NETs according to Ki67 index. An observational Italian multicentre study was designed to collect data in patients with gastro-entero-pancreatic or thoracic NETs under SSA treatment. Both retrospective and prospective data were included and they were analysed in line with Ki67 index, immunohistochemically evaluated in tumour samples and graded according to WHO classification (G1 = Ki67 index 0-2%, G2 = Ki67 index 3-20%, G3 = Ki67 index > 20%). Among 601 patients with NET, 140 with a histologically confirmed gastro-entero-pancreatic or thoracic NET or NET with unknown primary were treated with lanreotide autogel or octreotide LAR. An objective tumour response was observed in 11%, stability in 58% and progression in 31%. Objective response and tumour stability were not significantly different between G1 and G2 NETs. Progression free survival was longer but not significantly different in G1 than G2 NETs (median: 89 vs 43 months, p = 0.15). The median PFS was significantly longer in NETs showing Ki67 < 5% than in those showing Ki67 ≥ 5% (89 vs 35 months, p = 0.005). SSA therapy shows significant antiproliferative effects in well differentiated low/intermediate-proliferating NETs, not only G1 but also in G2 type. A Ki67 index of 5% seems to work better than 3% to select the best candidates for SSA therapy.
authors.affiliation: Thyroid and Parathyroid Surgery Unit, Istituto Nazionale per lo Studio e la Cura dei Tumouri "Fondazione G. Pascale" IRCCS, Napoli, Italy.
authors.forename: Antongiulio
authors.initials: A
authors.lastname: Faggiano
authors.affiliation: Endocrinology Unit, Department of Clinical Medicine and Surgery, Università di Napoli Federico II, Napoli, Italy.
authors.forename: Anna Chiara
authors.initials: AC
authors.lastname: Carratù
authors.affiliation: Pathology Unit, Department of Advanced Biomedical Sciences, Università di Napoli Federico II, Napoli, Italy.
authors.forename: Elia
authors.initials: E
authors.lastname: Guadagno
authors.affiliation: Medical Oncology Unit, Istituto Nazionale per lo studio e la cura dei tumouri "Fondazione G. Pascale" IRCCS, Napoli, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Tafuto
authors.affiliation: Pathology Unit, Istituto Nazionale per lo Studio e la Cura dei Tumouri "Fondazione G. Pascale" IRCCS, Napoli, Italy.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Tatangelo
authors.affiliation: Oncology Unit, AORN Cardarelli, Napoli, Italy.
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Riccardi
authors.affiliation: Oncology Unit, AORN Cardarelli, Napoli, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Mocerino
authors.affiliation: Oncology Unit, Department of Clinical Medicine and Surgery, Università di Napoli Federico II, Napoli, Italy.
authors.forename: Giovannella
authors.initials: G
authors.lastname: Palmieri
authors.affiliation: Oncology Unit, Department of Clinical Medicine and Surgery, Università di Napoli Federico II, Napoli, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Damiano
authors.affiliation: Department of Industrial Engeenering, Università di Napoli Federico II, Napoli, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Siciliano
authors.affiliation: Oncology Unit, Ospedale Civico, Lecce, Italy.
authors.forename: Silvana
authors.initials: S
authors.lastname: Leo
authors.affiliation: Oncology Unit, Ospedale Civico, Lecce, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Mauro
authors.affiliation: Oncology Unit, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
authors.forename: Lucia Franca
authors.initials: LF
authors.lastname: Tozzi
authors.affiliation: Endocrinology Unit, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Battista
authors.affiliation: Pathology Unit, Department of Advanced Biomedical Sciences, Università di Napoli Federico II, Napoli, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: De Rosa
authors.affiliation: Endocrinology Unit, Department of Clinical Medicine and Surgery, Università di Napoli Federico II, Napoli, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Colao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D002454:Cell Differentiation / Q000187:drug effects; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D018358:Neuroendocrine Tumors / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015282:Octreotide / Q000627:therapeutic use*; D011379:Prognosis; D011446:Prospective Studies; D012189:Retrospective Studies; D015996:Survival Rate; D055815:Young Adult
chemical_list: D018931:Antineoplastic Agents, Hormonal; D019394:Ki-67 Antigen; D015282:Octreotide
keywords: Ki67 index; lanreotide; neuroendocrine tumours; octreotide; somatostatin analogues