Dalvinder Mandair1,2, Mohid S Khan1,2,3, Andre Lopes4, Luke Furtado O'Mahony5, Leah Ensell2, Helen Lowe2, John A Hartley2, Christos Toumpanakis1, Martyn Caplin1, Tim Meyer2,6. 1. Neuroendocrine Tumour Unit, Royal Free Hospital, London. 2. Department of Oncology, UCL Cancer Institute, University College London, London. 3. Department of Gastroenterology, University Hospital of Wales, Cardiff, Wales. 4. Cancer Research UK & UCL Cancer Trials Centre, University College London, London. 5. University College London Medical School, University College London, London. 6. Department of Oncology, Royal Free Hospital, London.
Abstract
BACKGROUND: Circulating tumour cells (CTCs) are detectable in patients with NET and are accurate prognostic markers although the optimum threshold has not been defined. OBJECTIVE: To define optimal prognostic CTC threshold in pancreatic and midgut NET. PATIENTS AND METHODS: CellSearch was used to enumerate CTCs in 199 patients with metastatic pancreatic (PanNET) (90) or midgut NET (109). Patients were followed for progression free survival (PFS) and overall survival (OS) for a minimum of 3 years or until death. RESULTS: AUROC for progression at 12 months in PanNET and midgut NET identified the optimal CTC threshold as ≥1 and ≥2 respectively. In multivariate logistic regression analysis, these thresholds were predictive for 12 month progression with OR of 6.69 (p< 0.01) for PanNET and 5.88 (p<0.003) for midgut. The same thresholds were found to be optimal for predicting death at 36 months with an OR of 2.87 (p< 0.03) and 5.09 (p<0.005) for PanNET and midgut NET respectively. In multivariate Cox hazard regression analysis for PFS in PanNET, ≥ 1 CTC had HR 2.6 (p <0.01) whilst ≥ 2 CTCs had HR 2.25 (p < 0.01) in midgut NET. In multivariate analysis OS in PanNET, ≥ 1 CTC had HR 3.16 (p < 0.01) and in midgut NET, ≥ 2 CTCs had HR of 1.73 (p < 0.06). CONCLUSIONS: The optimal CTC threshold to predict PFS and OS in metastatic PanNET and midgut NET is 1 and 2, respectively. These thresholds can be used to stratify patients in clinical practice and clinical trials.
BACKGROUND: Circulating tumour cells (CTCs) are detectable in patients with NET and are accurate prognostic markers although the optimum threshold has not been defined. OBJECTIVE: To define optimal prognostic CTC threshold in pancreatic and midgut NET. PATIENTS AND METHODS: CellSearch was used to enumerate CTCs in 199 patients with metastatic pancreatic (PanNET) (90) or midgut NET (109). Patients were followed for progression free survival (PFS) and overall survival (OS) for a minimum of 3 years or until death. RESULTS: AUROC for progression at 12 months in PanNET and midgut NET identified the optimal CTC threshold as ≥1 and ≥2 respectively. In multivariate logistic regression analysis, these thresholds were predictive for 12 month progression with OR of 6.69 (p< 0.01) for PanNET and 5.88 (p<0.003) for midgut. The same thresholds were found to be optimal for predicting death at 36 months with an OR of 2.87 (p< 0.03) and 5.09 (p<0.005) for PanNET and midgut NET respectively. In multivariate Cox hazard regression analysis for PFS in PanNET, ≥ 1 CTC had HR 2.6 (p <0.01) whilst ≥ 2 CTCs had HR 2.25 (p < 0.01) in midgut NET. In multivariate analysis OS in PanNET, ≥ 1 CTC had HR 3.16 (p < 0.01) and in midgut NET, ≥ 2 CTCs had HR of 1.73 (p < 0.06). CONCLUSIONS: The optimal CTC threshold to predict PFS and OS in metastatic PanNET and midgut NET is 1 and 2, respectively. These thresholds can be used to stratify patients in clinical practice and clinical trials.
Authors: Tim Meyer; Martyn Caplin; Mohid S Khan; Christos Toumpanakis; Shishir Shetty; John K Ramage; Aude Houchard; Kate Higgs; Tahir Shah Journal: J Neuroendocrinol Date: 2022-02-07 Impact factor: 3.870
Authors: Alexa Childs; Christopher D Steele; Clare Vesely; Francesca M Rizzo; Leah Ensell; Helen Lowe; Pawan Dhami; Heli Vaikkinen; Tu Vinh Luong; Lucia Conde; Javier Herrero; Martyn Caplin; Christos Toumpanakis; Christina Thirlwell; John A Hartley; Nischalan Pillay; Tim Meyer Journal: Endocr Relat Cancer Date: 2021-08-11 Impact factor: 5.678