Antiproliferative effect of somatostatin analogs in gastroenteropancreatic neuroendocrine tumors

Somatostatin analogs were initially developed for the control of hormonal syndromes associated with neuro-endocrine tumors (NETs). In recent years, accumul ating data has supported their role as antiproliferative agents, capable of stabilizing tumor growth in patients with metastatic neuroendocrine malignancies, including carci-noid and pancreatic endocrine tumors. A phase Ⅲ, ran-domized, placebo-controlled trial has now demonstrated that octreotide long-acting repeatable (LAR) 30 mg can significantly prolong time to tumor progression among patients with metastatic midgut NETs regardless of functional status, chromogranin A level or age. In addition to signif icantly lengthening time to tumor pro-gression in the overall study population, subset analysis suggests that patients with low tumor burden are most likely to experience disease stabilization with octreotide LAR 30 mg, supporting the early use of octreotide LAR in patients with metastatic disease. Further research efforts are underway to evaluate the use of somatostatin analogs as antiproliferative agents in other types of gastroenteropancreatic-NETs. Ongoing studies are also evaluating novel somatostatin analogs and somatostatin analogs in combination with other anti-tumor therapies.

Acquired hepatocerebral degeneration in a metastatic neuroendocrine tumor long-term survivor——an update on neuroendocrine neoplasm’s treatment:A case report

BACKGROUND Metastatic small bowel low-grade neuroendocrine tumors(NETs)have a good prognosis.Surgery is the only curative treatment;however,this may induce advanced liver disease,particularly in long-term survivor patients.Acquired hepatocerebral degeneration or Parkinsonism in cirrhosis is characterized by rapidly progressive extrapyramidal symptoms in patients with advanced liver disease.CASE SUMMARY A 70-year-old man presented to the emergency department with diminished consciousness and disorientation,and was diagnosed with hepatic encephalopathy.The patient was diagnosed in 1993 with a metastatic small bowel NET,for which he twice underwent hepatic surgery,with metastatic resection in 1993 and a right hepatectomy in 2002 to remove two hepatic metastases.In 2003,the patient started first-line chemotherapy and in 2004 started the first of three consecutive biological treatments,followed by radio-molecular therapy,achieving stable disease for 14 years.Disease progression was identified and he underwent an endoscopic retrograde cholangiopancreatography.However,in 2019 advanced liver disease was identified.We diagnosed the development of acquired hepatocerebral degeneration,an unusual long-term side effect after multiple hepatic procedures.CONCLUSION The importance of regular and ongoing surveillance in long-term NET survivors who undergo hepatic procedures should be integrated into the therapeutic management plan,as some of these negative outcomes could be prevented.

Real-world treatment patterns of gastrointestinal neuroendocrine tumors: A claims database analysis

AIM To describe real-world treatment patterns of gastrointestinal neuroendocrine tumors(GI NET).METHODS In this retrospective cohort study,we used 2009-2014 data from 2 United States commercial claims databases to examine newly pharmacologically treated patients using tabular and graphical techniques. Treatments included somatostatin analogues(SSA),cytotoxic chemotherapy(CC),targeted therapy(TT),interferon(IF) and combinations. We identified patients at least 18 years of age,with ≥ 1 inpatient or ≥ 2 outpatient claims for GI NET who initiated pharmacologic treatment from 7/1/09-6/30/14. A 6 mo clean period prior to first treatment ensured patients were newly treated. Patients were followed until end of enrollment or the study end date,whichever was first.RESULTS We identified 2258 newly treated GI NET patients: mean(SD) age was 55.6 years(SD = 9.7),47.2% of the patients were between 55 and 64 years,and 48.8% were female. All regions of the United States were represented. 59.6% started first-line therapy with SSA monotherapy(964 with octreotide LAR,380 with octreotide SA,and 1 with lanreotide),33.3% CC,3.6% TT,and 0.5% IF. The remainder received combinations. Mean follow up was 576 d. Overall mean first-line therapy duration was 361 d(449 d for SSA,215 for CC,267 for TT). 58.9% of patients had no pharmacological treatment beyond first line. The most common secondline was combination therapy with SSA. In graphical pattern analysis,there was no clear pattern visible after first line therapy.CONCLUSION In this study,60% of patients initiated treatment with SSA alone or in combination. The relatively long time to discontinuation suggests possible sustained effectiveness and tolerability.

Orbital lesions,an exceedingly rare site of neuroendocrine tumor metastasis

Neuroendocrine tumors are rare neoplasms arising primarily in the gastrointestinal tract and lung.The liver is the most common site of metastases,but these tumors can rarely metastasize to atypical sites.Surgery is the only curative approach while the optimal medical treatment is debated.From this perspective,a multidisciplinary approach for each single case becomes very important.In this report we describe the case of a male affected by a single intraorbital metastasis from a midgut well differentiated neuroendocrine tumor.The patient refused surgical removal and therefore he was at first treated with stereotactic radiotherapy and systemic treatment with a somatostatin analog(SSA).After achieving a stable disease for four months he underwent primary tumor resection.Six years after the initial diagnosis,the patient is currently stable and receiving SSA at standard dose.