Cardiac arrhythmia considerations of hormone cancer therapies

International audienceBreast and prostate cancers are among the most prevalent cancers worldwide. Oestradiol and progesterone are major drivers for breast cancer proliferation, and androgens for prostate cancer. Endocrine therapies are drugs that interfere with hormone-activated pathways to slow cancer progression. Multiple new breakthrough drugs improving overall survival have recently been developed within this class. As the use of these latter drugs grows, incidence of cardiac arrhythmias has emerged as an unappreciated complication. These changes are not surprising given that sex hormones alter ventricular repolarization. Testosterone shortens action potential duration and QT interval duration, while oestradiol has an opposite effect. In patients with breast cancer, selective oestrogen receptor modulators are associated with more reports for long QT and torsade de pointes (TdP) than aromatase inhibitors, likely through an oestradiol-like effect on the heart. Cyclin-dependent kinase 4/6 inhibitors, a new class of anticancer drugs used in combination with endocrine therapies in hormone receptor positive breast cancer, are also variably associated with drug-induced long QT, particularly with ribociclib. In prostate cancer, androgen deprivation therapy is associated with long QT and TdP, and possibly atrial fibrillation for abiraterone. In this review, we have summarized the clinical and preclinical data focusing on cardiac arrhythmia considerations of hormone cancer therapies

Impact of age on survival in radioiodine refractory differentiated thyroid cancer patients

International audienceObjective The objectives of our study were to analyze the influence of age on the survival of patients with RAIR-DTC and to determine their prognostic factors according to age. Methods This single-center, retrospective study enrolled 155 patients diagnosed with RAIR-DTC. The primary end point was overall survival (OS) according to different cutoff (45, 55, 65, 75 years). Secondary endpoints were progression free survival (PFS) and prognostic factors in patients under and over 65 years. Results Median OS after RAIR diagnosis was 8.2 years (95% IC: 5.3–9.6). There was no difference according to age with a 65 ( P = 0.47) and 55 years old cutoff ( P = 0.28). Median OS improved significantly before 45 years old ( P = 0.0043). After 75 years old, median OS significantly decreased ( P = 0.0008). Median PFS was 2.1 years (95% CI: 0.8–3) in patients 65 years old, the presence of a mediastinum metastasis was a significant factor for mortality (HR: 4.55, 95% CI: 2.27–9.09). Conclusion In RAIR-DTC patients, a cut-off age of 65 years old was not a significant predictive factor of survival. Forty-five and 75-years-old cutoff were predictive for OS but not PFS

Outcomes and Prognostic Factors in Radioiodine Refractory Differentiated Thyroid Carcinomas

International audienceBackground.Outcomes vary among patients with radioiodine refractory (RR) differentiated thyroid cancer (DTC). The prognostic factors for survival are not well-known, resulting in difficulty in selecting patients for new targeted therapies. We assessed overall survival (OS) and cancer-specific survival (CSS) from RR-DTC to identify prognostic factors associated with survival.Patients and Methods.The data on all cases of metastatic RR-DTC treated in our center from 1990 to 2011 were retrospectively reviewed. Survival was estimated using the Kaplan-Meier method; associated prognostic factors were assessed using Cox’s model.Results.Of 153 cases of metastatic DTC, 59% (n = 91) met a criterion for RR: that is, 60% (n = 55) had at least 1 metastasis without 131I uptake; 21% (n = 19) had progressive disease (PD) despite 131I; 19% (n = 17) had persistent disease despite a cumulative activity of 131I of ≥600 mCi. After the diagnosis of RR, median OS was 8.9 years (95% confidence interval [CI]: 5.4-NR); median CSS was 9.6 years (95% CI: 6.01-NR). In multivariate analyses, PD despite 131I as a criterion for RR disease and the time from initial diagnosis of DTC to diagnosis of RR 1 year or negative Tg-DT.Conclusion.The identification of prognostic factors for decreased survival in RR-DTC may improve the selection of patients for targeted agents