Personalised Medicine Strategies For Patients With Neuroendocrine Tumours

Student thesis: Doctoral ThesisDoctor of Medicine by Research

Abstract

dissection are used to resect localised rectal NENs. The treatment of advanced disease is multimodal. Data from the English bowel cancer-screening programme (BCSP), a double screening programme of faecal occult blood testing (FOBT) and colonoscopy, were analysed for NEN diagnoses. The incidence rates per 100,000 colonoscopies of NENs by anatomical site was 29 for rectal, 18 for colonic and 11 for ileal. The majority of rectal NENs had grade 1 (80%) and stage T1 (85%) disease. Over half of ileal NENs (54%) in this study had T3/4 invasive disease, with 85% having nodal and 36% having metastastatic disease. Putative carcinoid heart disease (CHD) markers were studied in comparison to the recommended NT-proBNP in cohorts of patients with CHD, functional and non- iii functional sbNENs. Calprotectin was elevated across all three groups while the remaining markers ST2, GAL3 and adrenomedullin were not elevated. NT-proBNP was significantly different in the CHD cohort when compared to the functional and non-functional groups. This supports the consensus guidance for NT-proBNP in assessing advanced CHD. Quantitative proteomic studies of fresh frozen G1 pancreatic NEN (pNEN) tissue were performed. 187 significant proteins mapped to cancer pathways, in particular RAS and PI3K-Akt signalling pathways. Ten proteins of interest were identified that may be involved in cancer development; Neudesin, Tenascin-X, Actin-related protein 3, Fibulin-1, Moesin, Secretogranin-2, CD63 antigen, tropomyosin 3, 14-3-3 protein beta/alpha and Calnexin. These results have added to our knowledge of symptoms that differentiate NEN patients from functional conditions, individualising rectal NEN patient care, NENs identified through BCSPs, NT-proBNP for screening for CHD and proteins of interest for future study in pNENs. These span the domains of personalised medicine from symptom onset through to diagnostic and biomarker strategies.
Date of Award2019
Original languageEnglish
Awarding Institution
  • King's College London
SupervisorRaj Srirajaskanthan (Supervisor), Alberto Quaglia (Supervisor) & John K. Ramage (Supervisor)

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