Radioguided Surgery for Gastroenteropancreatic Neuroendocrine Tumours: a Systematic Literature Review

Background Radioguided surgery (RGS) for gastroenteropancreatic neuroendocrine tumours (GEP-NETs) has been suggested as a way to improve intraoperative lesion detection. This systematic literature review of reports of the use of RGS for GEP-NETs was performed to determine if there is a benefit. Methods A literature search was conducted using Google Scholar and PubMed, and snowballing from any relevant literature. Full-text studies were included if they were published in the English language and reported outcomes of RGS on human subjects with GEP-NETs. Qualitative data synthesis was performed. Results Twenty-six papers including a total of 209 patients were included. The tracers used were predominantly indium-111 pentetreotide, gallium-68 DOTA-peptides, and technetium-99m EDDA/HYNIC-peptides. Heterogeneous protocols make comparisons difficult, but most papers reported a benefit from the use of RGS in tumours in the gastrointestinal tract; utility in localisation of pancreatic tumours was less clear. Time between tracer administration and operation varied: from 16 h to 8 days with indium-111, 0–24 h with technetium-99m, and 19–193 min with gallium-68. Eight teams reported the thresholding technique used for discrimination—four used a ratio, four statistical methods, and one looked at the sensitivity and specificity of different cut-offs. Six teams performed follow-up of 24 patients (three pancreas, eight gastrinoma, 13 gastrointestinal tract) for between 3 months and 3 years. Two patients relapsed (one pancreas, one gastrinoma) between 6 and 12 months post-surgery. Conclusions RGS appears to aid in localisation of gastrointestinal NETs, but the benefit is more equivocal in pancreatic NETs. Further work into outcomes is warranted.

Radioguided Surgery for Gastroenteropancreatic Neuroendocrine Tumours; a Systematic Literature Review

Background:Radioguided surgery (RGS) for gastroenteropancreatic neuroendocrine tumours (GEP-NETs) has been suggested as a way to improve intraoperative lesion detection. This systematic literature review of reports of the use of RGS for GEP-NETs was performed to determine if there is a benefit.Methods: A literature search was conducted using Google Scholar and PubMed, and snowballing from any relevant literature. Full-text studies were included if they were published in the English Language and reported outcomes of RGS on human subjects with GEP-NETs. Qualitative data synthesis was performed. Results: 26 papers including a total of 209 patients were included. The tracers used were predominantly indium-111 pentetreotide, gallium-68 DOTA-Peptides, and technetium-99m EDDA/HYNIC-Peptides. Heterogeneous protocols make comparisons difficult, but most papers reported a benefit from the use of RGS in tumours in the gastrointestinal tract; utility in localisation of pancreatic tumours was less clear. Time between tracer administration and operation varied; from 16 hours to 8 days with indium-111, 0-24 hours with technetium-99m and 19-193 minutes with gallium-68. Eight teams reported the thresholding technique used for discrimination – four used a ratio, four statistical methods, and one looked at the sensitivity and specificity of different cut-offs. Six teams performed follow-up of 24 patients (three pancreas, eight gastrinoma, 13 gastrointestinal tract) for between 3 months and 3 years. Two patients relapsed (one pancreas, one gastrinoma) between six and 12 months post-surgery. Conclusions:RGS appears to aid in localisation of gastrointestinal NETs, but the benefit is more equivocal in pancreatic NETs. Further work into outcomes is warranted.

A novel read methodology to evaluate the optimal dose of 68Ga-satoreotide trizoxetan as a PET imaging agent in patients with gastroenteropancreatic neuroendocrine tumours: a phase II clinical trial

Background 68Ga-satoreotide trizoxetan is a novel somatostatin receptor antagonist exhibiting higher tumour-to-background ratios and sensitivity compared to 68Ga-DOTATOC. This randomised, 2 × 3 factorial, phase II study aimed to confirm the optimal peptide mass and radioactivity ranges for 68Ga-satoreotide trizoxetan, using binary visual reading. To that end, 24 patients with metastatic gastroenteropancreatic neuroendocrine tumours received 5–20 µg of 68Ga-satoreotide trizoxetan on day 1 of the study and 30–45 µg on day 16–22, with one of three gallium-68 radioactivity ranges (40–80, 100–140, or 160–200 MBq) per visit. Two 68Ga-satoreotide trizoxetan PET/CT scans were acquired from each patient post-injection, and were scored by experienced independent blinded readers using a binary system (0 for non-optimal image quality and 1 for optimal image quality). For each patient pair of 68Ga-satoreotide trizoxetan scans, one or both images could score 1. Results Total image quality score for 68Ga-satoreotide trizoxetan PET scans was lower in the 40–80 MBq radioactivity range (56.3%) compared to 100–140 MBq (90.6%) and 160–200 MBq (81.3%). Both qualitative and semi-quantitative analysis showed that peptide mass (5–20 or 30–45 µg) did not influence 68Ga-satoreotide trizoxetan imaging. There was only one reading where readers diverged on scoring; one reader preferred one image because of higher lesion conspicuity, and the other reader preferred the alternative image because of the ability to identify more lesions. Conclusions Binary visual reading, which was associated with a low inter-reader variability, has further supported that the optimal administered radioactivity of 68Ga-satoreotide trizoxetan was 100–200 MBq with a peptide mass up to 50 µg. Trial registration ClinicalTrials.gov, NCT03220217. Registered 18 July 2017, https://clinicaltrials.gov/ct2/show/NCT03220217

Marked improvement in hyperammonaemic encephalopathy from multimodal treatment of metastatic neuroendocrine tumour

Gastroenteropancreatic neuroendocrine tumours (GEPNETs) are a heterogenous group of tumours which are rising in incidence. Morbidity and mortality related to these tumours is dependent on the location of metastatic spread. Hyperammonaemia and subsequent encephalopathy has previously been described in GEPNET and is typically associated with a poor prognosis. We describe a case of a 55-year-old woman with hyperammonaemic encephalopathy and a new diagnosis of GEPNET. Given the poor prognosis and the outcomes in this patient group we feel this case highlights the benefit of a multimodality treatment approach including peptide receptor radionucleotide therapy and transarterial chemoembolisation.

Satisfaction and quality of life in patients with symptomatic gastroenteropancreatic neuroendocrine tumours treated with lanreotide Autogel in South Africa

Background: Neuroendocrine tumours are known to impact patients’ quality of life because of the symptoms caused by hypersecretion of serotonin and other peptides, in particular diarrhoea and flushing.Aim: The Q-SYMTU study was a prospective, observational registry that included 24 symptomatic patients with gastroenteropancreatic neuroendocrine tumours.Setting: Multiple oncology practices in South Africa.Method: Patients’ level of satisfaction was evaluated for a 6-month period from initiation of treatment with lanreotide Autogel.Results: The number of patients who had greater than 50% self-reported reduction in daily episodes of diarrhoea and flushing were 67% and 80%, respectively, over a 6-month period.Conclusion: Treatment with lanreotide Autogel was generally well tolerated, as demonstrated by low occurrence of Grade 3 and Grade 4 adverse events (AEs). None of the Grade 4 AEs were related to the study treatment. No Grade 5 AEs were reported.