Immunotherapy, so promising in many neoplasms, still does not have a precise role in the treatment of neuroendocrine neoplasms (NENs). In this article, we provide an overview on the current knowledge about immunotherapy with immune checkpoint inhibitors (ICIs) applied to NENs, evaluating future perspectives in this setting of tumors.Evidence so far available for ICIs in gastroenteropancreatic (GEP)-NENs is definitively not as robust as for other tumors such as Small Cell Lung Cancer or Merkel Cell Carcinoma. In fact, with regard to the well-differentiated forms of NENs (NETs), the results obtained nowadays have been disappointing. However, the near future, might reserve interesting results for ICIs in GEP-NEN from a total of nine different ICI drugs, used throughout 19 randomised controlled trials. Such numbers highlight the growing attention gathering around NENs and ICIs, in response to the need of stronger evidences supporting such therapy.For the future, the most important aspect will be to study strategies that can make NETs more susceptible to response to ICI and, thus, enhance the effectiveness of these treatments. Therefore, the combination of conventional therapy, target therapy and immunotherapy deserve attention and warrant to be explored. A sequential chemotherapy, possibly inducing an increase in tumor mutational burden and tested before immunotherapy, could be a hypothesis deserving more consideration. A radiation treatment that increases tumor-infiltrating lymphocytes, could be another approach to explore before ICIs in NENs. Equally essential will be the identification of biomarkers useful for selecting patients potentially responsive to this type of treatment.

The pre-surgical selection of thyroid nodules with indeterminate cytology (Thy 3 according to British Thyroid Association) after fine-needle aspiration biopsy (FNAB) is currently required in order to reduce unnecessary total thyroidectomy. The objective of our study was to use a surgical series of Thy 3 nodules to evaluate the predictive role of ultrasound elastosonography (USE) and contrast-enhanced ultrasonography (CEUS) in pre-surgical diagnoses of malignancy. We enrolled 63 patients with Thy 3 nodules in which cytological–histological correlation was available. The ELX 2/1 strain index was obtained by means of semi-quantitative USE, which was performed before surgery in addition to conventional ultrasonography (US) and contrast-enhanced US (CEUS) on the Thy 3 nodules. The ELX 2/1 strain index, a five-item US score and both peak (P) index and time to peak (TTP) index from CEUS were correlated with the histological results. After surgical diagnosis, the data were analysed by using a receiver-operating characteristic (ROC) curve. Histology was benign in 50 and malignant in 13 Thy 3 nodules. No difference in maximal diameter was noted between benign (22.8 ± 1.6 mm) and malignant (18.9 ± 2.9 mm) nodules. Significant correlations were found between histology and cumulative US findings (p=0.005), ELX 2/1 index (p=0.002), P index (p=0.01) and TTP index (p=0.02). On analysing data from US, USE and CEUS, significant ROC areas under the curve were observed (p2), ELX 2/1 (>0.95), P index (0.98) scores. The diagnostic power of the cumulative pre-surgical analysis of Thy 3 nodules with US, USE and CEUS, considering the experimental cut-off points obtained from the ROC curves was: sensitivity 64%, specificity 92%, PPV 75% and accuracy 84%. The ELX 2/1 index in conjunction with the US score can be useful in orienting surgical strategies in Thy 3 nodules. The information added by CEUS is less sensitive than that provided by US and USE. The use of a cut-off based on histology can reduce thyroidectomy. Observation should be the first choice when not all instrumental results are suspect.

BACKGROUND:In thyroid nodules with indeterminate cytology, further clinical assessment aimed at ruling out malignancy is often mandatory. Ancillary imaging techniques and genetic mutation analysis can improve the risk stratification of such lesions, ...

Background: The role of radioiodine (RAI) therapy for differentiated thyroid cancers (DTCs) is still a matter of debate. Low-dose RAI (LDRAI) therapy is a possible treatment for patients at low–intermediate risk of recurrence. The aim of this study was to evaluate the occurrence of post-RAI therapy clinical and biochemical side effects with respect to its dosage. Methods: We retrospectively examined 142 patients who had been administered RAI therapy for DTCs and carried out at least a 12-month follow-up. The incidence of clinical adverse events (CAEs: xerophthalmia, xerostomia, and dysgeusia) and values for hemoglobin (Hb), red blood cells (RBCs), white blood cells (WBCs) and platelets (PLTs) during the first year of follow-up were compared between patients who underwent standard-dose RAI (SDRAI) therapy and LDRAI therapy. Results: Of the 142 patients, 66 were treated with LDRAI and 76 with SDRAI. A higher incidence of CAEs was found in the SDRAI group than in the LDRAI group (p = 0.002). An administered dose above 2849 MBq was associated with CAEs (sensitivity 88.89%, specificity 54.03%, p < 0.001). We found a slight decrease in Hb (p = 0.008), RBCs (p = 0.013), WBCs (p = 0.004) and PLTs (p < 0.001) in the SDRAI group, while in the LDRAI group only WBCs showed a minimal decrease (p = 0.027) with any occurrence of overt bone-marrow disease. Conclusions: According to our data, LDRAI therapy seemed to be associated with a lower incidence of CAEs than SDRAI therapy. Both methods showed an excellent safety profile in terms of hematopoietic effects. However, the effect of SDRAI therapy in this setting might have been more positive than that of LDRAI therapy.