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Ki-67 index and response to chemotherapy in patients with neuroendocrine tumours

Childs, A; Kirkwood, A; Edeline, J; Tu, VL; Watkins, J; Lamarca, A; Alrifai, D; ... Meyer, T; + view all (2016) Ki-67 index and response to chemotherapy in patients with neuroendocrine tumours. Endocrine-Related Cancer , 23 (7) pp. 563-570. 10.1530/ERC-16-0099. Green open access

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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.

Type: Article
Title: Ki-67 index and response to chemotherapy in patients with neuroendocrine tumours
Open access status: An open access version is available from UCL Discovery
DOI: 10.1530/ERC-16-0099
Publisher version: https://doi.org/10.1530/ERC-16-0099
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Science & Technology, Life Sciences & Biomedicine, Oncology, Endocrinology & Metabolism, neuroendocrine tumour, chemotherapy, Ki-67, response, RADIOLABELED SOMATOSTATIN ANALOG, PANCREATIC ENDOCRINE CARCINOMAS, STREPTOZOCIN PLUS FLUOROURACIL, ISLET-CELL CARCINOMA, PROGNOSTIC-FACTORS, GRADING SYSTEM, DOXORUBICIN, THERAPY, SURVIVAL, TEMOZOLOMIDE
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > CRUK Cancer Trials Centre
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10049170
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