Efficacy and Safety of First-Line Everolimus Therapy Alone or in Combination with Octreotide in Gastroenteropancreatic Neuroendocrine Tumors. A Hellenic Cooperative Oncology Group (HeCOG) Study.

The purpose of this study was to explore the efficacy and safety of everolimus administered as a first-line treatment in newly diagnosed patients with metastatic or inoperable gastroenteropancreatic neuroendocrine tumors (GEP NETs). This phase II, multicenter, single-arm study included patients with well-differentiated GEP NETs and a Ki67 < 20%. Everolimus, at 10 mg/day, was administered until disease progression; 18 patients (72%) concomitantly received octreotide long-acting release (LAR), at 30 mg/month. The primary endpoint was the 15-month progression-free survival (PFS) rate. Twenty-five patients (grade 1: 11 patients, grade 2: 14 patients) were enrolled between August 2012 and October 2015. At a median follow-up of 58.1 months, the median PFS was 14.6 months, while the 15-month PFS rate was 48%; median overall survival had not been reached yet. Normal baseline chromogranin A (<4 nmol/l) confirmed a longer PFS (HR = 0.25, 95% CI 0.08-0.77, p = 0.016). Seven patients (28%) achieved an objective response (one complete response and six partial responses) in a median of 2.6 months. Twenty-three grade 3-4 events were recorded (14 patients). No fatal reactions occurred. This prospective phase II study unravels the notable activity of everolimus as a first-line treatment in patients with GEP NETS and contributes valuable information about the high activity of the combination of everolimus and octreotide LAR in this setting. Clinical trial information: NCT01648465.

Current best practice in the management of neuroendocrine tumors.

Neuroendocrine neoplasms are rare tumors that display marked heterogeneity with varying natural history, biological behavior, response to therapy and prognosis. Their management is complex, particularly as a number of them may be associated with a secretory syndrome and involve a variety of options. A number of factors such as proliferation rate, degree of differentiation, functionality and extent of the disease are mostly utilized to tailor treatment accordingly, ideally in the context of a multidisciplinary team. In addition, a number of relevant scientific societies have published therapeutic guidelines in an attempt to direct and promote evidence-based treatment. Surgery remains the treatment of choice with an intention to cure while it may also be recommended in some cases of metastatic disease and difficult to control secretory syndromes. Long-acting somatostatin analogs constitute the main treatment for the majority of functioning tumors, whereas specific evolving agents such as telotristat may be used for the control of carcinoid syndrome and related sequelae. In patients with advanced disease not amenable to surgical resection, treatment options include locoregional therapies, long-acting somatostatin analogs, molecular targeted agents, radionuclides, chemotherapy and recently immunotherapy, alone or in combination. However, the ideal time of treatment initiation, sequence of administration of different therapies and identification of robust prognostic markers to select the most appropriate treatment for each individual patient still need to be defined.

Nonneuroendocrine Neoplasms of the Pituitary Region.

CONTEXT: Although most sellar lesions are related to pituitary adenomas, the region gives rise to a variety of neoplasms that can be associated with substantial morbidity and/or mortality. DESIGN: Information from reviews and guidelines of relevant societies dealing with such neoplasms, as well as articles that have provided new developments that made important contributions to their pathogenesis and treatment up to 2018, were obtained: public indexes such as PubMed/MEDLINE were used with the relevant search items. RESULTS: Sellar neoplasms have a worse outcome than pituitary adenomas that is related not only to their natural history but also to side effects of therapies and evolving endocrine and/or hypothalamic deficiencies. Recent imaging advances have established the radiological fingerprint of some of these neoplasms, and several chromosomal aberrations have also been identified. Although established approaches along with new surgical and radiotherapeutic approaches remain the main treatment modalities, recent evidence has provided insight into their molecular pathogenesis involving, other than chemotherapy, treatments with targeted agents as in gliomas and craniopharyngiomas bearing BRAF mutations. Development of predictive markers of recurrences may also identify high-risk patients, including proliferative markers and expression of the progesterone receptor in meningiomas, and lead to less aggressive surgery. Owing to the rarity and complexity of these neoplasms, patients should be managed in dedicated centers. CONCLUSIONS: The diagnosis and management of sellar neoplasms necessitate a multidisciplinary approach. Following evolving recent advances in their diagnosis and therapy, such a multidisciplinary approach needs to be extended to establish evidence-based diagnostic and management plans.

Evaluation of bone involvement in patients with Gaucher disease: a semi-quantitative magnetic resonance imaging method (using ROI estimation of bone lesion) as an alternative method to semi-quantitative methods used so far.

OBJECTIVE: The aim of this study was to evaluate bone involvement in patients with Gaucher disease (GD) and to propose a novel semi-quantitative magnetic resonance imaging (MRI) staging. METHODS: MRI of the lumbar spine, femur, and tibia was performed in 24 patients with GD and 24 healthy controls. We also measured circulating levels of C-C motif ligand-3 (CCL-3) chemokine, C-telopeptide of collagen type-1 (CTX), and tartrate-resistant acid phosphatase isoform type-b (TRACP-5b). RESULTS: We used the following staging based on MRI data: stage I: region of interest (ROI) 1/2 of normal values and bone infiltration up to 30%; stage II: ROI 1/3 of normal values and bone infiltration from 30 to 60%; stage III: ROI 1/4 of normal values and bone infiltration from 60% to 80%; and stage IV: detection of epiphyseal infiltration, osteonecrosis and deformity regardless of the ROI's values. All but two patients had abnormal MRI findings: 9 (37.5%), 6 (25%), 3 (12.5%), and 4 (16.7%) had stages I-IV, respectively. Patients with GD had elevated chitotriosidase, serum TRACP-5b, and CCL-3 levels (P < 0.001). CONCLUSIONS: We propose an easily reproducible semi-quantitative scoring system and confirm that patients with GD have abnormal MRI bone findings and enhanced osteoclast activity possibly due to elevated CCL-3.