Cabozantinib for different endocrine tumours: killing two birds with one stone. A systematic review of the literature.

PURPOSE: Cabozantinib is an oral multi-tyrosine kinase inhibitor (TKI) that has been approved in Europe for advanced renal cell carcinoma, hepatocellular carcinoma, locally advanced and metastatic medullary thyroid carcinoma (MTC) and radioiodine-refractory differentiated thyroid cancer. Merkel cell carcinoma (MCC) is a rare and highly aggressive cutaneous malignant neuroendocrine tumour that usually presents in sun-exposed skin areas of immunosuppressed patients. Conflicting data exist about cabozantinib for MCC and this TKI is currently under investigation in several onco-endocrine frameworks. METHODS: We herein report a case of an 83-year-old man who was diagnosed with MCC during the treatment of an advanced metastatic MTC. The diagnosis of MCC was established based on clinical, histopathologic evaluation and immunohistochemistry. A systematic review of the literature on cabozantinib use for advanced endocrine and neuroendocrine tumours has been performed. RESULTS: The patient was initially treated with surgery and adjuvant radiotherapy. Cabozantinib was therefore started to control both MTC and MCC. After 24 months, no sign of local or metastatic MCC relapse was evidenced. CONCLUSION: Promising data on cabozantinib treatment for endocrine and neuroendocrine neoplasms is recently emerging in the literature. In our clinical case, we reported that, besides the good response for the MTC, cabozantinib also seems to effectively control metastatic MCC, along with efficient surgery and adjuvant radiotherapy. Further investigations are needed to determine the efficacy and safety of cabozantinib in MCC patients and in off-label endocrine tumours.

Early calcitonin levels in medullary thyroid carcinoma: Prognostic role in patients without distant metastases at diagnosis.

Introduction: Calcitonin is the most specific marker for medullary thyroid carcinoma, thus, low detectable calcitonin values after surgery can conceal persistent disease. The present study aimed to explore the prognostic role of pre-operative and early calcitonin levels in patients without distant metastases at diagnosis. Methods: A retrospective cohort of patients suffering from medullary thyroid carcinoma was considered (N=55). The final disease status, i.e. complete response (undetectable calcitonin levels and negative radiological assessments) or persistent disease (detectable calcitonin levels and/or positive radiological assessments), was deduced from the last available follow-up. Pre-operative and early calcitonin levels (i.e. six months after surgery) have been correlated to several clinical and histological features, according to the final disease status. Results: Persistent disease patients showed higher pre-operative and early calcitonin values (p=0.028 and p<0.001, respectively), compared to complete response sub-cohort. Cox-regression models show that early detectable calcitonin increases up to 18-fold the risk of persistent disease, independently from tumour size and pre-operative calcitonin levels (p=0.006). Of note, when considering only patients who finally developed distant metastasis, ROC curve analysis shows that an early calcitonin level ≥16 pg/ml predicts the final disease status with a sensitivity of 89% and a specificity of 82% (AUC=0.911, CI95%: 0.819-1000, p<0.001). Conclusion: Calcitonin levels six months after surgery represents an easy and effective predictor of persistent disease for medullary thyroid carcinoma without distant metastasis at diagnosis.

Education degree predicts cardiovascular outcomes in men suffering from erectile dysfunction.

BACKGROUND: The level of education has been recognized as a cardiovascular risk factor; nevertheless, it is often neglected in cardiovascular risk prediction. OBJECTIVES: To evaluate the psychobiological correlates of the level of education and if it could predict incident major adverse cardiovascular events in men consulting for erectile dysfunction. METHODS: Total 3733 men (49.8 ± 13.7 years old) attending an andrology outpatient clinic for erectile dysfunction were studied. Sexual and psychological symptoms, hormonal and metabolic, as well as instrumental (penile color Doppler ultrasound) parameters were evaluated according to the education level (university, upper secondary, lower secondary, and primary degree). For a subset of 956 patients, data on incident major adverse cardiovascular events were retrospectively collected for 3.9 ± 2.4 years. RESULTS: As compared with men with university degree, those with a lower education had an increased frequency of moderate-severe erectile dysfunction (odds ratio = 1.21 [0.99;1.48], 1.41 [1.14;1.73], 1.70 [1.26;2.30] for upper secondary, lower secondary, and primary school, respectively) and reduced flaccid peak systolic velocity at penile color Doppler ultrasound. Men with a lower level of education tend to suffer from metabolic syndrome (odds ratio = 1.38 [1.06;1.79], 1.73 [1.34;2.24], 1.72 [1.24;2.37] for upper secondary, lower secondary, and primary school, respectively) and were more likely to have history of previous cardiovascular events. In the longitudinal study, men with a higher level of education had a significantly lower incidence of major adverse cardiovascular events. The role of higher education as an independent predictor of major adverse cardiovascular events was established by multivariable Cox regressions (hazard ratio = 2.14 [1.24-3.69]). DISCUSSION: In erectile dysfunction subjects, lower level of education is associated with a more severely impaired erectile function with atherogenic pathogenesis and with a worse cardio-metabolic profile. In addition, a lower level of education predicts forthcoming major adverse cardiovascular events. Therefore, education level should be considered as a costless but valuable information in the assessment of cardiovascular risk in patients with erectile dysfunction.