title: Ki-67 index and response to chemotherapy in patients with neuroendocrine tumours.
abstract: Chemotherapy (CT) is widely used for neuroendocrine tumours (NETs), but there are no validated biomarkers to predict response. The Ki-67 proliferation index has been proposed as a means of selecting patients for CT, but robust data are lacking. The aim of this study was to investigate the relationship between response to chemotherapy and Ki-67 in NET. We reviewed data from 222 NET patients treated with CT. Tumours were graded according to Ki-67 index: G1 ≤2%, G2 3-20% and G3 >20%. Response was assessed according to RECIST and survival calculated from start of chemotherapy to death. To explore Ki-67 as a marker of response, we calculated the likelihood ratio and performed receiver operating characteristic analysis. Overall, 193 patients had a documented Ki-67 index, of which 173 were also evaluable for radiological response: 10% were G1, 46% G2 and 43% G3; 46% were pancreatic NET (PNET). Median overall survival was 22.1 months. Overall response rate was 30% (39% in PNET vs 22% in non-PNET) and 43% of patients had stable disease. Response rate increased with grade: 6% in G1 tumours, 24% in G2 and 43% in G3. However, maximum likelihood ratio was 2.3 at Ki-67=35%, and the area under the ROC curve was 0.60. As reported previously, a high Ki-67 was an adverse prognostic factor for overall survival. In conclusion, response to CT increases with Ki-67 index, but Ki-67 alone is an unreliable means to select patients for CT. Improved methods to stratify patients for systemic therapy are required.
authors.affiliation: Department of OncologyRoyal Free London NHS Foundation Trust, London, UK.
authors.forename: Alexa
authors.initials: A
authors.lastname: Childs
authors.affiliation: Cancer Research UK & UCL Cancer Trials CentreLondon, UK.
authors.forename: Amy
authors.initials: A
authors.lastname: Kirkwood
authors.affiliation: UCL Cancer InstituteUCL, London, UK.
authors.forename: Julien
authors.initials: J
authors.lastname: Edeline
authors.affiliation: Department of PathologyRoyal Free London NHS Foundation Trust, London, UK.
authors.forename: Tu Vinh
authors.initials: TV
authors.lastname: Luong
authors.affiliation: Department of PathologyRoyal Free London NHS Foundation Trust, London, UK.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Watkins
authors.affiliation: Institute of Cancer SciencesUniversity of Manchester/The Christie NHS Foundation Trust, Manchester, UK.
authors.forename: Angela
authors.initials: A
authors.lastname: Lamarca
authors.affiliation: King's College Hospital NHS Foundation TrustLondon, UK.
authors.forename: Doraid
authors.initials: D
authors.lastname: Alrifai
authors.affiliation: Department of RadiologyRoyal Free London NHS Foundation Trust, London, UK.
authors.forename: Phyllis
authors.initials: P
authors.lastname: Nsiah-Sarbeng
authors.affiliation: Department of OncologyRoyal Free London NHS Foundation Trust, London, UK.
authors.forename: Roopinder
authors.initials: R
authors.lastname: Gillmore
authors.affiliation: Department of OncologyRoyal Free London NHS Foundation Trust, London, UK.
authors.forename: Astrid
authors.initials: A
authors.lastname: Mayer
authors.affiliation: Department of OncologyRoyal Free London NHS Foundation Trust, London, UK UCL Cancer InstituteUCL, London, UK.
authors.forename: Christina
authors.initials: C
authors.lastname: Thirlwell
authors.affiliation: King's College Hospital NHS Foundation TrustLondon, UK.
authors.forename: Debashis
authors.initials: D
authors.lastname: Sarker
authors.affiliation: Institute of Cancer SciencesUniversity of Manchester/The Christie NHS Foundation Trust, Manchester, UK.
authors.forename: Juan W
authors.initials: JW
authors.lastname: Valle
authors.affiliation: Department of OncologyRoyal Free London NHS Foundation Trust, London, UK UCL Cancer InstituteUCL, London, UK t.meyer@ucl.ac.uk.
authors.forename: Tim
authors.initials: T
authors.lastname: Meyer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D005047:Etoposide / Q000627:therapeutic use; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D018358:Neuroendocrine Tumors / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D017671:Platinum Compounds / Q000627:therapeutic use; D011379:Prognosis; D011743:Pyrimidines / Q000627:therapeutic use; D013311:Streptozocin / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D019394:Ki-67 Antigen; D017671:Platinum Compounds; D011743:Pyrimidines; D013311:Streptozocin; D005047:Etoposide
keywords: Ki-67; chemotherapy; neuroendocrine tumour; response