Background: Bone metastases have been described in up to 15% of patients with NETs and are associated with a worse clinical outcome. Here we investigate the role of CTCs as a marker of bone metastases in a large cohort of patients with gastroenteropancreatic NETs.
Methods: To be eligible for the study, patients were required to be ≥ 18 years old, have histologically confirmed midgut or pancreatic NET (pNET) and metastatic disease measurable by RECIST. Data were collected on age, gender, primary site, grade, metastatic sites and previous treatments. Patients provided 7.5 ml blood samples which were collected into CellSave tubes, maintained at room temperature and processed within 96 hours of collection. The CellSearch platform was used for detection and enumeration of CTCs by two independent operators, as previously described.
Results: Between 2009 and 2017, 251 patients with metastatic NETs were recruited from the Royal Free Hospital including 128 patients with pNET and 123 with midgut NET. Of patients with pNETs, 38% had CTCs detected with a mean of 11 CTCs per 7.5 ml of blood (range 0430). Bone metastases were reported in 29 pNET patients (23%) and were significantly associated with CTC presence (P<0.0001). There was no association between lung, peritoneal or lymph node metastases and CTC presence. Of patients with midgut tumours, 52% had detectable CTCs with a mean number of 15 (range 0636). Bone metastases were reported in 36 midgut patients (29%) and were significantly associated with CTC presence (P=0.02). There was no association between grade, lung, peritoneal or lymph node metastases and CTC presence. In both midgut and pNETs, the association between bone metastases and CTC presence was confirmed by logistic regression analysis and was independent from grade as well as from other sites of metastases.
Conclusion: Presence of CTCs measured by CellSearch is associated with bone metastases in NET patients. CTCs will be further analyzed for expression of markers involved in the molecular mechanisms underlying skeletal metastasis.
04 Dec 2017
UK and Ireland Neuroendocrine Tumour Society