Carcinoid syndrome (CS), characterised by flushing, diarrhoea, wheeze and fibrotic valvulopathy, arises in patients (pts) with advanced NETs due to serotonin and kallikrein secretion.
Sequential pts with advanced well-differentiated gastroenteropancreatic NETs (GEP-NETs) treated at The Christie (1998-2017) with ≥1 carcinoid symptom(s) and raised serum/urinary 5-hydroxyindoleacetic acid (5-HIAA) were identified. Ratio of 5-HIAA/upper limit normal (ULN) was calculated. Progression-free (PFS) and overall survival (OS) were estimated (Kaplan-Meier method) and prognostic factors identified (Cox proportional hazards model).
Of 882 pts, 139 (16%) had CS: median (med) age 64 yrs, 55% male, 80% performance status (PS) 0-1, 13% PS 2; 65% had small bowel primary, 10% large bowel, 4% pancreas, 0.7% gastric, 21% unknown primary (consistent with GEP-NET origin). Tumour grade (G) was 1 in 45%; G2 in 29%; symptoms included diarrhoea (91%), flushing (89%), wheeze (22%), and carcinoid heart disease (CHD; 35%). Fifty-seven (41%) had primary resection, and 121 (87%) had liver metastases. In first line, 66% received a somatostatin analogue (SSA), 20% debulking surgery, 14% other. Med baseline 5-HIAA levels were 8.45 x ULN (urinary: 10.56 x ULN, serum: 6.07 x ULN). Med follow-up was 45.7 months (mo). Med PFS and OS were 27.0 (95%CI 17.2-33.9) and 65.4 (95%CI 50.4-76.4) mo. On univariate analysis, small bowel primary (P = 0.045), liver metastases (P = 0.03), Ki-67 (P
Baseline 5-HIAA ratio, but not change from baseline to 6 months, was prognostic for PFS and OS. Treatment optimisation is pivotal.
Clinical trial identification
Legal entity responsible for the study
Audit Department - The Christie NHS Foundation Trust, Manchester
All authors have declared no conflicts of interest.