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The aim of the present study was to evaluate the safety and efficacy of radionuclide therapy with [177Lu]Lu-DOTA-TATE according to our single center experience at the University of Naples Federico II. For the present analysis, we considered 21 patients with progressive, advanced, well-differentiated G1 and G2 in patients with gastro-entero-pancreatic (GEP) neuroendocrine tumors (NETs) treated with [177Lu]Lu-DOTA-TATE according to the decisions of a multidisciplinary team. All patients underwent four cycles of 7–8 GBq of [177Lu]Lu-DOTA-TATE every 8 weeks. A whole-body scan (WBS) was performed 4, 48, and 168 h after each treatment. The dosimetry towards the organ at risk and target lesions was calculated. For each patient, renal and bone marrow parameters were evaluated before, during, and 3 months after the end of the treatment. Follow-up data were obtained and RECIST criteria were considered as the endpoint. Among 21 patients enrolled (mean age 65 ± 9 years); 17 (81%) were men and the small intestine was the most frequent location of disease (n = 12). A mild albeit significant variation (p < 0.05) in both platelets and white blood cell counts among all time points was observed, despite it disappearing 3 months after the end of the therapy. According to the RECIST criteria, 11 (55%) patients had a partial response to therapy and 8 (40%) had stable disease. Only one (5%) patient had disease progression 4 months after treatment. Our data confirm that [177Lu]Lu-DOTA is safe and effective in controlling the burden disease of G1/G2 GEP-NETs patients.

Background: Differentiated thyroid cancer (DTC) patients have an outstanding overall long-term survival rate, and certain subsets of DTC patients have a very high likelihood of disease recurrence. Radioactive iodine (RAI) therapy is a cornerstone in DTC management, but cancer cells can eventually develop resistance to RAI. Radioactive iodine-refractory DTC (RAIR-DTC) is a condition defined by ATA 2015 guidelines when DTC cannot concentrate RAI ab initio or loses RAI uptake ability after the initial therapy. The RAIR condition implies that RAI cannot reveal new met-astatic foci, so RAIR-DTC metabolic imaging needs new tracers. 18F-FDG PET/CT has been widely used and has demonstrated prognostic value, but 18F-FDG DTC avidity may remain low. Fibroblast activation protein inhibitors (FA-Pi)s, prostatic-specific membrane antigen (PSMA), and somatostatin receptor (SSTR) tracers have been proposed as theragnostic agents in experimental settings and Arg-Gly-Asp (RGD) peptides in the diagnostic trial field. Multi-targeted tyrosine kinase inhibitors are relatively new drugs approved in RAIR-DTC therapy. Despite the promising targeted setting, they relate to frequent adverse-event onset. Sorafenib and trametinib have been included in re-differentiation protocols aimed at re-inducing RAI accumulation in DTC cells. Results appear promising, but not excellent. Conclusions: RAIR-DTC remains a challenging nosological entity. There are still controversies on RAIR-DTC definition and post-RAI therapy evaluation, with post-therapy whole-body scan (PT-WBS) the only validated criterion of response. The recent introduction of multiple diagnostic and therapeutic agents obliges physicians to pursue a multidisciplinary approach aiming to correct drug introduction and timing choice.

Second primary malignancies (SPM) are described as any primary, not synchronous, malignancy arising in a different anatomical district, with confirmed histological diagnosis. Age at diagnosis, previous non-thyroidal primary malignancy, and radioactive iodine (RAI) therapy have been proposed as independent risk factors for SPM. RAI therapy is a standard treatment for moderate-high risk differentiated thyroid cancer (DTC), and its effect on the development of SPM has become a critical topic in DTC treatment. The purpose of this retrospective single-center study was to investigate the occurrence and the possible association of non-thyroidal SPM diagnosed after DTC and RAI therapy in a cohort of 1326 consecutive DTC patients referred at our Institution for RAI treatment from 1993 to 2009. Eighty-nine patients with ages ≤ 18 years at the time of DTC diagnosis or with a follow-up of ≤12 months were excluded from the final analysis. All patients underwent a complete clinical and hematological follow-up every 6 months for a minimum of 12 months. During follow-up (mean 89 ± 73 months), 25 patients (2%) had an SPM diagnosis (mean 133 ± 73 months). The most common site of the second malignancy was the breast, accounting for 32% of all SPM, followed by colon-rectal cancer (16%), leukemia, and gynecological and kidney cancer (4%). At Cox univariable regression analysis, age at DTC diagnosis (p < 0.001), age ≥55 years (p < 0.001) and follow-up duration (p < 0.004) were associated with SPM onset, while no significant association was observed with the administered activity of radioiodine. In conclusion, our data suggest that the older a person gets, the more sharply the likelihood of developing additional diseases, such as PMS, increases. Similarly, for follow-up, the more a patient is followed up clinically over time, the higher the risk of new diagnoses increases.