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

Published on Mar 19, 2021in International Journal of Medical Sciences2.523
· DOI :10.7150/IJMS.51740
Andrea Frilling19
Estimated H-index: 19
(Imperial College London),
Ashley K. Clift13
Estimated H-index: 13
(Imperial College London)
+ 8 AuthorsRichard P. Baum63
Estimated H-index: 63
Sources
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.
References63
Newest
#2Matthias TwrznikH-Index: 1
#3Harshad R. KulkarniH-Index: 26
Last. Merten HommannH-Index: 20
view all 7 authors...
MINI: The role of resection of primary tumors in patients with advanced neuroendocrine neoplasms is still unclear. We investigated 2 groups of patients treated using peptide receptor radionuclide therapy (PRRT; mean of 4 cycles PRRT) with and without a prior primary tumors resection. Surgical resection resulted in a significantly prolonged overall- and progression-free survival.This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Deriva...
7 CitationsSource
#1Stefano Partelli (UniSR: Vita-Salute San Raffaele University)H-Index: 43
#2Valentina Andreasi (UniSR: Vita-Salute San Raffaele University)H-Index: 8
Last. Massimo Falconi (UniSR: Vita-Salute San Raffaele University)H-Index: 105
view all 5 authors...
BACKGROUND: Surgery remains the only treatment for the cure of pancreatic neuroendocrine tumors (PanNETs). Biomarkers to identify the completeness of resection and predict recurrence are lacking. OBJECTIVE: The aims of this study were to evaluate if the blood measurement of neuroendocrine gene transcripts (NETest) was diagnostic of PanNETs, and whether NETest blood levels could identify complete resection. We compared transcript analysis with the biomarker chromogranin A (CgA). METHODS: This was...
10 CitationsSource
#1Angelena Crown (Virginia Mason Medical Center)H-Index: 10
#2Flavio G. Rocha (Virginia Mason Medical Center)H-Index: 22
Last. Hagen F. Kennecke (Virginia Mason Medical Center)H-Index: 9
view all 10 authors...
BACKGROUND: Somatostatin analog functional imaging with gallium-68 (Ga-68) dotatate positron emission tomography/computed tomography (PET/CT) has demonstrated superiority in lesion detection in patients with neuroendocrine tumors (NETs). The clinical impact of this imaging modality on US surgical and medical oncology practices has not been established. METHODS: Consecutive patients with NET at our institution who received an initial Ga-68 dotatate PET/CT between July 2017 and September 2018 were...
16 CitationsSource
#1Kjell ÖbergH-Index: 116
#2Andrea Califano (Columbia University)H-Index: 76
Last. S. Paulson (Baylor University)H-Index: 1
view all 11 authors...
Background The lack of an accurate blood biomarker in neuroendocrine tumor (NET) disease has hindered management. The advance of genomic medicine and the development of molecular biomarkers has provided a strategy—liquid biopsy—to facilitate real-time management. We reviewed the role of a blood mRNA-based NET biomarker, the NETest, as an in vitro diagnostic (IVD). Patients and methods A systematic review of the literature using the Preferred Reporting Items for Systematic Reviews and Meta-Analys...
29 CitationsSource
OBJECTIVE: The purpose of this study was to assess the efficacy of Lu-labeled peptide receptor radionuclide therapy (PRRT) induction treatments for patients with unresectable metastatic neuroendocrine tumors. METHODS: MEDLINE, EMBASE, and Ovid were systematically searched with keywords "lutetium," "Lu-177," "PRRT," "neuroendocrine," and "prognosis." Studies evaluating treatment with Lu-labeled PRRT were assessed for disease response and/or disease control rate by Response Evaluation Criteria in ...
11 CitationsSource
Liquid biopsy has been introduced as a new diagnostic concept predicated on the analysis of circulating tumour cells (CTCs) or circulating tumour-derived factors, in particular, cell-free tumour DNA (ctDNA). Highly sensitive liquid biopsy assays have been developed that can now be applied to detect and characterize minimal residual disease (MRD), which reflects the presence of tumour cells disseminated from the primary lesion to distant organs in patients who lack any clinical or radiological si...
298 CitationsSource
#1Eric LiuH-Index: 1
#2Scott Paulson (Texas Oncology)H-Index: 1
Last. Lisa Bodei (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 25
view all 9 authors...
BACKGROUND: The clinical relevance of molecular biomarkers in oncology management has been recognized in breast and lung cancers. We evaluated a blood-based multigene assay for management of neuroendocrine tumors (NETs) in a real-world study (U.S. registry NCT02270567). Diagnostic accuracy and relationship to clinical disease status in two cohorts (treated and watch-and-wait) were evaluated. MATERIALS AND METHODS: Patients with NETs (n = 100) were followed for 6-12 months. Patients' primary tumo...
25 CitationsSource
#1Diamantis I. Tsilimigras (The Ohio State University Wexner Medical Center)H-Index: 21
#2Ioannis Ntanasis-Stathopoulos (UoA: National and Kapodistrian University of Athens)H-Index: 19
Last. Timothy M. Pawlik (The Ohio State University Wexner Medical Center)H-Index: 118
view all 7 authors...
Introduction Patients with midgut neuroendocrine tumors (MNETs) frequently present with metastatic disease at the time of diagnosis. Although combined resection of the primary MNET and liver metastases (NELM) is usually recommended for appropriate surgical candidates, primary tumor resection (PTR) in the setting of extensive, inoperable metastatic disease remains controversial.
22 CitationsSource
#1Mustapha El LakisH-Index: 8
#2Andreas GianakouH-Index: 1
Last. Electron Kebebew (Stanford University)H-Index: 85
view all 11 authors...
Importance Neuroendocrine tumors (NETs) express somatostatin receptors, which can be targeted with radiolabeled peptides. In a variety of solid tumors, radioguided surgery (RGS) has been used to guide surgical resection. Gallium 68 ( 68 Ga) dota peptides have been shown to be more accurate than other radioisotopes for detecting NETs. A pilot study previously demonstrated the feasibility and safety of 68 Ga-dotatate RGS for patients with NETs. Objective To evaluate what intraoperative techniques ...
21 CitationsSource
#1Mark J C van Treijen (UU: Utrecht University)H-Index: 4
#2Catharina M. Korse (UU: Utrecht University)H-Index: 2
Last. Gerlof D. Valk (UU: Utrecht University)H-Index: 40
view all 8 authors...
Background: Available neuroendocrine biomarkers are considered to have insufficient accuracy to discriminate patients with gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) from healthy controls. Recent studies have demonstrated a potential role for circulating neuroendocrine specific transcripts analysis - the NETest - as a more accurate biomarker for NETs compared to available biomarkers. This study was initiated to independently validate the discriminative value of the NETest as well ...
29 CitationsSource
Cited By1
Newest
#1Ariadni Spyroglou (UoA: National and Kapodistrian University of Athens)H-Index: 11
#2Konstantinos Bramis (UoA: National and Kapodistrian University of Athens)H-Index: 13
Last. Krystallenia I. Alexandraki (UoA: National and Kapodistrian University of Athens)H-Index: 29
view all 3 authors...
Abstract Neuroendocrine neoplasms (NENs) are relatively rare neoplasms. Most NENs are slowly-progressing malignancies with prolonged survival even in the presence of advanced metastatic disease implying an increased need for additional therapies upon failure of those initially administered. However, a subset of NENs may display truly aggressive behavior, often refractory to current chemotherapeutic regimens, underlining the need for more appropriate schemes. Following these unmet needs, new ther...
Source