A combination of surgery, theranostics, and liquid biopsy - a personalised oncologic approach to treatment of patients with advanced metastatic neuroendocrine neoplasms.

Rationale: Neuroendocrine neoplasia (NEN) of small bowel (SBNEN) frequently present with metastatic disease. Theranostics (molecular imaging followed by targeting therapy) allow for personalised medicine. Liquid biopsies enable precise identification of residual disease and real-time monitoring of therapeutic response. Our aim was to determine the clinical utility of a combination of surgery, theranostics, and a multigene blood measurement in metastasised SBNEN. Methods: Inclusion criteria were SBNEN, G1/G2 NEN, initial tumour diagnosis, stage IV NEN, positivity on 68Ga somatostatin analogue PET/CT, eligible for surgery, and 177Lu peptide receptor radionuclide therapy (PRRT). Blood samples for NETest were collected longitudinally. Progression-free survival (PFS) and overall survival (OS) were calculated. NETest results were assessed prior to surgery and during clinical follow-up. Results: A surgical cohort of 39 SBNEN patients met eligibility criteria. Thirty-two patients underwent ileal resection and 7 right hemicolectomy. The mean number of 177Lu PRRT cycles was 4. Mortality was nil. Surgical morbidity was 10.3%. Transient grade 1/2 toxicity occurred in 41% (PRRT). NETest scores (n=9 patients) decreased in 100% following treatment and correlated with diminished tumour volume and disease stabilization following surgery and PRRT. Median follow-up: 78 months. Median PFS and OS: 42.7 and 110 months, respectively. Progression-free survival at 1-, 3-, and 5-years was 79.4%, 57.1% and 40.5%, respectively. Overall survival at 1-, 3-, and 5-years was 97.4%, 97.4%, and 94.1%, respectively. Conclusions: Surgery combined with 177Lu PRRT is safe and provides favourable PFS and OS in selected patients with advanced SBNEN. Liquid biopsy (NETest) has the potential to accurately delineate disease status.