The Management and Outcomes of Patients with Extra-Pulmonary Neuroendocrine Neoplasms and Brain Metastases.

BACKGROUND: Brain metastases (BMs) in patients with extra-pulmonary neuroendocrine neoplasms (EP-NENs) are rare, and limited clinical information is available. The aim of this study was to detail the clinicopathological features, management and outcomes in patients with EP-NENs who developed BMs. METHODS: A retrospective single-centre analysis of consecutive patients with EP-NENs (August 2004-February 2020) was conducted. Median overall survival (OS)/survival from BMs diagnosis was estimated (Kaplan-Meier). RESULTS: Of 730 patients, 17 (1.9%) had BMs, median age 61 years (range 15-77); 8 (53%) male, unknown primary NEN site: 40%. Patients with BMs had grade 3 (G3) EP-NENs 11 (73%), G2: 3 (20%), G1: 1 (7%). Eight (53%) had poorly differentiated NENs, 6 were well-differentiated and 1 was not recorded. Additionally, 2 (13%) patients had synchronous BMs at diagnosis, whilst 13 (87%) developed BMs metachronously. The relative risk of developing BMs was 7.48 in patients with G3 disease vs. G1 + G2 disease (p = 0.0001). Median time to the development of BMs after NEN diagnosis: 15.9 months (range 2.5-139.5). Five patients had a solitary BM, 12 had multiple BMs. Treatment of BMs were surgery (n = 3); radiotherapy (n = 5); 4: whole brain radiotherapy, 1: conformal radiotherapy (orbit). Nine (53%) had best supportive care. Median OS from NEN diagnosis was 23.6 months [95% CI 15.2-31.3]; median time to death from BMs diagnosis was 3.0 months [95% CI 0.0-8.3]. CONCLUSION: BMs in patients with EP-NENs are rare and of increased risk in G3 vs. G1 + G2 EP-NENs. Survival outcomes are poor, and a greater understanding is needed to improve therapeutic outcomes.

Pancreaticobiliary Malignancies in the Emergency Room: Management of Acute Complications and Oncological Emergencies.

BACKGROUND: Management of pancreaticobiliary (PB) malignancies remains a clinical challenge. In this review, we focus on the management of oncological emergencies in PB malignancies and the potential complication of associated therapeutic interventions. METHODS: Biobliographic review of current evidence on the management of oncological emergencies, their potential complications, as well as synthesis of recommendations was performed. The pathogenesis, frequency, related symptoms as well as appropriate investigations are presented. RESULTS: The oncologic emergencies in PB patients were summarised in six categories: (1) hematological (including febrile neutropaenia, thrombocytopenia, coagulopathies), (2) gastrointestinal (gastric outlet and biliary obstruction, gastrointestinal bleeding), (3) thromboembolic events, (4) ascites, (5) metabolic disorders and (6) neurologic complications. The pathogenesis, frequency, related symptoms as well as appropriate investigations are also presented. CONCLUSION: Patients with PB malignancies are at increased risk of a wide variation of medical emergencies. Clinical knowledge, early recognition and collaboration with the relevant specialties are critical to manage these complications effectively, tailoring overall management around the actual prognosis and individuals' expectations.

Antiproliferative Systemic Therapies for Metastatic Small Bowel Neuroendocrine Tumours.

OPINION STATEMENT: Neuroendocrine neoplasms (NENs) are a heterogeneous group of malignancies with rising incidence and prevalence. Outcome and therapy of small bowel neuroendocrine tumours (SBNETs) is variable, depending on the grade, differentiation, tumour burden, as well as the site of the tumour origin. Because of this, multidisciplinary approach is essential. Large randomized clinical trials, with somatostatin analogues (PROMID, CLARINET) or with peptide receptor radionuclide therapy (PRRT) with 177-lutetium (NETTER-1 trial) as well as the mammalian target of rapamycin inhibitor (mTOR) everolimus (RADIANT trials), represent milestones for the medical management of unresectable grade 1 and 2 SBNETS over the last decade. Novel therapies, such as tyrosine kinase inhibitors (TKI), are on the cutting edge. However, multiple unsolved questions remain. This review provides a comprehensive review of the main systemic therapeutic options for advanced SBNETs and discusses the latest guideline recommendations for palliative treatment.

Targeted Therapy For RET-Rearranged Non-Small Cell Lung Cancer: Clinical Development And Future Directions.

Approximately 1-2% of unselected patients with Non-small Cell Lung Cancer (NSCLC) harbor RET rearrangements resulting in enhanced cell survival and proliferation. The initial treatment strategy for RET rearranged NSCLC has been multi-target tyrosine kinase inhibition. With overall response rates (ORR) of 16-53% and a median progression-free survival (PFS) of 4.5-7.3 months these outcomes are clearly inferior to the efficacy outcomes of selective tyrosine kinase inhibitors (TKI) in other oncogene-addicted NSCLC. Additionally, multi-kinase inhibition in RET-driven NSCLC patients showed concerning rates of high-grade toxicity, mainly induced by anti-VEGFR-kinase activity. Novel selective RET inhibitors like BLU-667, LOXO-292 and RXDX-105 have been recently investigated in early phase clinical trials showing promising efficacy with a manageable toxicity profile.