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Background: Long-acting somatostatin analogs (SSAs) are the primary first-line treatment of well-differentiated advanced gastroenteropancreatic neuroendocrine tumors (NETs), but data about their efficacy in pancreatic NETs (panNETs) with Ki-67 ≥10% are still limited., Materials and Methods: To assess the clinical outcomes of advanced, nonfunctioning, well-differentiated panNETs with Ki-67 ≥10% receiving first-line long-acting SSAs in a real-world setting, we carried out a retrospective, multicenter study including patients treated between 2014-2018 across 10 centers of the NET CONNECT Network. The primary endpoints were time to next treatment (TNT) and progression-free survival (PFS), whereas overall survival (OS) and treatment safety were secondary endpoints., Results: A total of 73 patients were included (68 grade [G]2, 5 G3), with liver metastases in 61 cases (84%). After a median follow-up of 36.4 months (range, 6-173), the median TNT and PFS were 14.2 months (95% confidence interval [CI], 11.6-16.2) and 11.9 months (95% CI, 8.6-14.1) respectively. No statistically significant difference was observed according to the somatostatin analog used (octreotide vs. lanreotide), whereas increased tumor grade (hazard ratio [HR], 4.4; 95% CI, 1.2-16.6; p = .04) and hepatic tumor load (HR, 2; 95% CI, 1-4; p = .03) were independently associated with shortened PFS. The median OS recorded was 86 months (95% CI, 56.8-86 months), with poor outcomes observed when the hepatic tumor burden was >25% (HR, 3.4; 95% CI, 1.2-10; p = .01). Treatment-related adverse events were reported in 14 patients, most frequently diarrhea., Conclusion: SSAs exert antiproliferative activity in panNETs with Ki-67 ≥10%, particularly in G2 tumors, as well as when hepatic tumor load is ≤25%., Implications for Practice: The results of the study call into question the antiproliferative activity of somatostatin analogs (SSAs) in pancreatic neuroendocrine tumors with Ki-67 ≥10%. Patients with grade 2 tumors and with hepatic tumor load ≤25% appear to derive higher benefit from SSAs. Prospective studies are needed to validate these results to optimize tailored therapeutic strategies for this specific patient population., (© 2020 AlphaMed Press.)

Background: Surgery represents the only curative treatment for stage I-III midgut neuroendocrine tumors (NETs). At present, there are very limited data on the risk of postoperative recurrence. The optimal modality, duration and frequency of surveillance have not been well established. In this work, we investigated the long-term risk of recurrence, peak timing of recurrence, and potential predictors of relapse in patients with stage I-III midgut NETs., Methods: We retrospectively evaluated 129 patients with stage I-III midgut NETs who were seen at the Moffitt Cancer Center between 2000 and 2010 following an R0/R1 resection. Disease-free survival (DFS) was estimated using the Kaplan-Meier method. Demographic, clinical, and pathological features were assessed as potential predictors of recurrence. All statistical tests were two-sided., Results: After a median postoperative follow-up of 81 months (range = 1-295 months), recurrence was diagnosed in 40 out of 129 patients (31.0%, 95% confidence interval [CI] = 23.0% to 39.0%). Liver, mesentery, and pelvic lymph nodes were the main sites of relapse. The median DFS was 138 months (95% CI = 117 to 223 months). Resection of 17 or fewer lymph nodes predicted relapse (P = .01) and shorter DFS (P = .04). Among patients who relapsed, the cumulative risks of recurrence at one, five, and 10 years were 15.0% (95% CI = 3.9% to 26.1%), 50.0% (95% CI = 34.5% to 65.5%), and 85.0% (95% CI = 73.9% to 96.0%). No recurrence was observed among patients (n = 6) with stage I tumors, whereas similar rates of relapse were noted in patients with stage II or III NETs (n = 118)., Conclusions: An annual surveillance interval may allow early detection of recurrence. Given the apparent decline in recurrence after eight years from surgery, a decade-long duration of active surveillance may be proposed.

Langerhans cell histiocytosis (LCH) is a rare proliferative disorder characterized by an accumulation of cells sharing the major phenotypic features of cutaneous Langerhans cells. Given its variable clinical evolution, ranging from self-limiting lesions to multisystemic forms with a poor prognosis, in the last decades it has been debated whether LCH might not have a neoplastic rather than an inflammatory nature. However, although the fundamental events underlying the pathogenesis of LCH are still elusive, recent advances have strikingly improved our understanding of the disease. In particular, the identification of multiple interplays between LCH cells and their tumor microenvironment, along with the recognition of the lesional cytokine storm as a key determinant of LCH progression, has substantiated new opportunities for devising targeted therapeutic approaches. Strikingly, the detection of the rapidly accelerated fibrosarcoma isoform B(V600E) gain-of-function mutation as a genetic alteration recurring in more than 50% of patients has fueled the paradoxical picture of LCH as a tumor of the antigen-presenting cells that can evade rejection by the immune system. Thus, new evidence regarding the ontogeny of LCH cells, as well as a better understanding of the putative immune system frustrating strategy in LCH, may help to define the precise pathogenesis.