Major adverse cardiovascular events associated with VEGF-targeted anticancer tyrosine kinase inhibitors: a real-life study and proposed algorithm for proactive management.

BACKGROUND: Vascular endothelial growth factor receptor (VEGFR)-targeted tyrosine kinase inhibitors (TKIs) are widely used in cancer treatment and burdened by cardiovascular toxicity. The majority of data come from clinical trials, thus in selected populations. The aim of our study is to evaluate the cardiotoxicity profile of VEGFR-targeted TKIs and the impact of cardiovascular risk factors in a real-life population. PATIENTS AND METHODS: In this cohort, population-based study, patients treated with VEGFR-targeted TKIs, bevacizumab and trastuzumab between 2009 and 2014 were analyzed. A multi-source strategy for data retrieval through hospital, pharmaceutical and administrative databases of the Lombardy region, Italy, has been adopted. The primary endpoint was to determine the incidence and type of major adverse cardiovascular events (MACEs) along with their temporal trend. The secondary endpoint was to define the impact of cardiovascular risk factors in the occurrence of MACEs. RESULTS: A total of 829 patients were treated with VEGFR-targeted TKIs. Eighty-one MACEs occurred in the first year of follow-up [crude cumulative incidence (CCI): 9.79%] mainly consisting of arterial thrombotic events (ATEs, 31 events, CCI: 3.99%), followed by rhythm disorders (22 events, CCI: 2.66%), pulmonary embolisms and heart failures (13 events each, CCI: 1.57%). While the incidence of most MACEs showed a plateau after 6 months, ATEs kept increasing along the year of follow-up. Hypertension and dyslipidemia were associated with an increase in risk of ATEs [relative risk difference (RRD) +209.8% and +156.2%, respectively], while the presence of previous MACEs correlated with a higher risk of all MACEs in multivariate analysis (RRD 151.1%, 95% confidence interval 53.6% to 310.3%, P < 0.001). CONCLUSIONS: MACEs occur in a clinically significant proportion of patients treated with VEGFR-targeted TKIs, with ATEs being predominant, mainly associated with hypertension and dyslipidemia. A clinical algorithm for effective proactive management of these patients is warranted.

Intensa retención de 99mTc-MIBI en la fase tardía como causa de error diagnóstico en la gammagrafía combinada paratiroides-tiroides / High retention of 99mTc-MIBI in delayed phase as a pitfall in the combined parathyroid-thyroid scintigraphy

La gammagrafía de paratiroides con 99mTc-sestaMIBI es muy sensible en el diagnóstico y localización del adenoma de paratiroides. Sin embargo, se pueden producir errores diagnósticos debido a la coexistencia de lesiones tiroideas captantes de MIBI o en pacientes con cirugía tiroidea previa. Para intentar detectar dichas alteraciones tiroideas se realiza una gammagrafía con 99mTc-pertecnetato comparativa el mismo día. Ocasionalmente, como en nuestro caso, la lesión paratiroidea puede presentar una captación inicial y retención tardía de MIBI lo suficientemente importantes como para ser visualizadas en la gammagrafía tiroidea realizada a continuación, dando la falsa apariencia de una lesión captante también de pertecnetato. Este hecho ha sido llamado «shine through». Para evitarlo se pueden realizar las gammagrafías paratiroidea y tiroidea en días distintos. A nosotros nos resultó también de gran utilidad la comparación con ecografía y la PAAF de la lesión con determinación de PTH y tiroglobulina en el líquido aspirado(AU)

Dual phase parathyroid scintigraphy with 99mTc-sestaMIBI is a very sensitive technique in the preoperative localization and diagnosis of parathyroid adenoma. However, pitfalls have been reported in patients with thyroid nodules with MIBI uptake or with previous thyroid surgery. To solve this problem, a thyroid scintigraphy with 99mTc-pertechnetate is usually performed following the parathyroid study. Occasionally, as in our patient the parathyroid lesion may show high MIBI uptake and delayed washout that interfere with the subsequent thyroid scintigraphy giving the false appearance of a pertechnetate avid lesion. This has been called the «shine through» effect. To avoid it, the parathyroid and thyroid scintigraphies can be performed on separate days. We have also found it useful to compare our results with that of ultrasound and fine needle aspiration puncture with measurement of the parathyroid hormone (PTH) and thyroglobulin in the aspirated material(AU)

[High retention of (99m)Tc-MIBI in delayed phase as a pitfall in the combined parathyroid-thyroid scintigraphy]. / Intensa retención de (99m)Tc-MIBI en la fase tardía como causa de error diagnóstico en la gammagrafía combinada paratiroides-tiroides.

Dual phase parathyroid scintigraphy with (99m)Tc-sestaMIBI is a very sensitive technique in the preoperative localization and diagnosis of parathyroid adenoma. However, pitfalls have been reported in patients with thyroid nodules with MIBI uptake or with previous thyroid surgery. To solve this problem, a thyroid scintigraphy with (99m)Tc-pertechnetate is usually performed following the parathyroid study. Occasionally, as in our patient the parathyroid lesion may show high MIBI uptake and delayed washout that interfere with the subsequent thyroid scintigraphy giving the false appearance of a pertechnetate avid lesion. This has been called the «shine through¼ effect. To avoid it, the parathyroid and thyroid scintigraphies can be performed on separate days. We have also found it useful to compare our results with that of ultrasound and fine needle aspiration puncture with measurement of the parathyroid hormone (PTH) and thyroglobulin in the aspirated material.