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Predictors of antiproliferative effect of lanreotide autogel in advanced gastroenteropancreatic neuroendocrine neoplasms.

ABSTRACT: PURPOSE:The antiproliferative properties of lanreotide autogel (LAN) in gastroenteropancreatic neuroendocrine neoplasms (GEP NENs) were demonstrated in the CLARINET study. However, there is limited literature regarding factors that affect progression-free survival (PFS) in patients with GEP NENs treated with LAN. METHODS:We identified a total of 191 treatment-naive patients with advanced GEP NENs and positive SSTR uptake on imaging (Octreoscan or 68Gallium DOTATATE Positron Emission Tomography [68GaPET]) who received first-line LAN monotherapy, albeit at various starting doses (60, 90 or 120 mg/month). A group of 102 patients who initiated treatment at the standard dose of 120 mg/month were included in the study and further evaluated by univariate and multivariate analyses to identify predictors of PFS. RESULTS:The location of tumour primary was in the small bowel in 63 (62%), pancreas in 31 (30%) and colon/rectum in 8 patients (8%). The tumours were well-differentiated, and the majority were grade 1 (52%), or 2 (38%). About 60% of cases had progressive disease at the time of treatment initiation. Most patients with available pretreatment nuclear medicine imaging (Octreoscan or 68Ga PET) had a Krenning score of 3 (44%) or 4 (50%). The median PFS for the entire cohort was 19 months (95% CI 12, 26 months). The univariate analysis demonstrated that grade 2 tumours, progressive disease at baseline and metastatic liver disease were associated with a significantly shorter PFS, while other evaluated variables did not affect PFS at a statistically significant level. However, at multivariate analysis only the tumour grade remained statistically significant. CONCLUSIONS:The current study showed that, of many evaluated variables, only the tumour grade was predictive of PFS duration and this should be considered during patient selection for treatment.

SUBMITTER: Laskaratos FM

PROVIDER: S-EPMC6968981 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Our understanding about the epidemiological aspects, pathogenesis, molecular diagnosis, and targeted therapies of neuroendocrine neoplasms (NENs) have drastically advanced in the past decade. Gastroenteropancreatic (GEP) NENs originate from the enteroendocrine cells of the embryonic gut which share common endocrine and neural differentiation factors. Most NENs are well-differentiated, and slow growing. Specific neuroendocrine biomarkers that are used in the diagnosis of functional NENs include insulin, glucagon, vasoactive intestinal polypeptide, gastrin, somatostatin, adrenocorticotropin, growth hormone releasing hormone, parathyroid hormone-related peptide, serotonin, histamine, and 5-hydroxy indole acetic acid (5-HIAA). Biomarkers such as pancreatic polypeptide, human chorionic gonadotrophin subunits, neurotensin, ghrelin, and calcitonin are used in the diagnosis of non-functional NENs. 5-HIAA levels correlate with tumour burden, prognosis and development of carcinoid heart disease and mesenteric fibrosis, however several diseases, medications and edible products can falsely elevate the 5-HIAA levels. Organ-specific transcription factors are useful in the differential diagnosis of metastasis from an unknown primary of well-differentiated NENs. Emerging novel biomarkers include circulating tumour cells, circulating tumour DNA, circulating micro-RNAs, and neuroendocrine neoplasms test (NETest) (simultaneous measurement of 51 neuroendocrine-specific marker genes in the peripheral blood). NETest has high sensitivity (85%-98%) and specificity (93%-97%) for the detection of gastrointestinal NENs, and is useful for monitoring treatment response, recurrence, and prognosis. In terms of management, surgery, radiofrequency ablation, symptom control with medications, chemotherapy and molecular targeted therapies are all considered as options. Surgery is the mainstay of treatment, but depends on factors including age of the individual, location, stage, grade, functional status, and the heredity of the tumour (sporadic vs inherited). Medical management is helpful to alleviate the symptoms, manage inoperable lesions, suppress postoperative tumour growth, and manage recurrences. Several molecular-targeted therapies are considered second line to somatostatin analogues. This review is a clinical update on the pathophysiological aspects, diagnostic algorithm, and management of GEP NENs.

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Predictors of antiproliferative effect of lanreotide autogel in advanced gastroenteropancreatic neuroendocrine neoplasms.

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