RT Journal Article
SR Electronic
T1 Utility of KI-67 as a prognostic biomarker in pulmonary neuroendocrine neoplasms: a systematic review and meta-analysis
JF BMJ Open
JO BMJ Open
FD British Medical Journal Publishing Group
SP e041961
DO 10.1136/bmjopen-2020-041961
VO 12
IS 3
A1 Naheed, Salma
A1 Holden, Chloe
A1 Tanno, Lulu
A1 Pattini, Linda
A1 Pearce, Neil W
A1 Green, Bryan
A1 Jaynes, Eleanor
A1 Cave, Judith
A1 Ottensmeier, Christian H.
A1 Pelosi, Giuseppe
YR 2022
UL http://bmjopen.bmj.com/content/12/3/e041961.abstract
AB Objectives Ki-67, a marker of cellular proliferation, is associated with prognosis across a wide range of tumours, including gastroenteropancreatic neuroendocrine neoplasms (NENs), lymphoma, urothelial tumours and breast carcinomas. Its omission from the classification system of pulmonary NENs is controversial. This systematic review sought to assess whether Ki-67 is a prognostic biomarker in lung NENs and, if feasible, proceed to a meta-analysis.Research design and methods Medline (Ovid), Embase, Scopus and the Cochrane library were searched for studies published prior to 28 February 2019 and investigating the role of Ki-67 in lung NENs. Eligible studies were those that included more than 20 patients and provided details of survival outcomes, namely, HRs with CIs according to Ki-67 percentage. Studies not available as a full text or without an English manuscript were excluded. This study was prospectively registered with PROSPERO.Results Of 11 814 records identified, seven studies met the inclusion criteria. These retrospective studies provided data for 1268 patients (693 TC, 281 AC, 94 large cell neuroendocrine carcinomas and 190 small cell lung carcinomas) and a meta-analysis was carried out to estimate a pooled effect. Random effects analyses demonstrated an association between a high Ki-67 index and poorer overall survival (HR of 2.02, 95% CI 1.16 to 3.52) and recurrence-free survival (HR 1.42; 95% CI 1.01 to 2.00).Conclusion This meta-analysis provides evidence that high Ki-67 labelling indices are associated with poor clinical outcomes for patients diagnosed with pulmonary NENs. This study is subject to inherent limitations, but it does provide valuable insights regarding the use of the biomarker Ki-67, in a rare tumour.Prospero registration number CRD42018093389.All data relevant to the study are included in the article or uploaded as supplementary information.