Int J Med Sci 2021; 18(10):2166-2175. doi:10.7150/ijms.51740 This issue

Research Paper

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

Andrea Frilling1✉, Ashley K. Clift1, Adam E. Frampton1, Jamshed Bomanji2, Daniel Kaemmerer3, Adil Al-Nahhas4, Ali Alsafi4, Mark Kidd5, Irvin M. Modlin6, Dieter Hoersch7, Richard P. Baum8

1. Department of Surgery and Cancer, Imperial College London, London, UK.
2. Department of Nuclear Medicine, University College London Hospitals, London, UK.
3. Department of General and Visceral Surgery, Zentralklinik Bad Berka, Bad Berka, Germany.
4. Department of Imaging and Nuclear Medicine, Imperial College London, London, UK.
5. WREN Laboratories, Branford, USA.
6. Gastroenterological and Endoscopic Surgery, Yale University School of Medicine, New Haven, USA.
7. Department of Gastroenterology/Endocrinology, Zentralklinik Bad Berka, Bad Berka, Germany.
8. CURANOSTICUM Wiesbaden-Frankfurt at DKD Helios Klinik, Wiesbaden, Germany.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
Frilling A, Clift AK, Frampton AE, Bomanji J, Kaemmerer D, Al-Nahhas A, Alsafi A, Kidd M, Modlin IM, Hoersch D, Baum RP. A combination of surgery, theranostics, and liquid biopsy - a personalised oncologic approach to treatment of patients with advanced metastatic neuroendocrine neoplasms. Int J Med Sci 2021; 18(10):2166-2175. doi:10.7150/ijms.51740. Available from https://www.medsci.org/v18p2166.htm

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Abstract

Graphic abstract

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.

Keywords: Neuroendocrine neoplasia, small bowel, surgery, peptide receptor radionuclide therapy, NETest, mRNA, multianalyte gene biomarker.