Efficacy and safety of oral sirolimus for high-flow vascular malformations in real clinical practice.

BACKGROUND: Vascular malformations are a complex pathology with few treatment options. In previously published studies, oral sirolimus (rapamycin) has shown promising results in the treatment of low-flow vascular malformations, but its usefulness in high-flow vascular malformations is controversial. AIM: To evaluate the efficacy and safety of sirolimus for the treatment of high-flow vascular malformations in real-life practice. METHODS: In a unit specializing in vascular anomalies, patients treated with oral sirolimus for high-flow vascular malformations were located by consulting the drug dispensations. Reviewing the electronic medical records, data on patient demographics, vascular malformation characteristics, treatments, toxicity and clinical course were collected and statistically analysed. RESULTS: Nine patients with vascular malformations were included: eight had arteriovenous malformation and one had arteriovenous fistula. Six of these malformations were isolated while three were part of a syndrome. Sirolimus was initiated at a dosage of 1-4 mg/day to be taken as a single dose. Partial response was observed in eight of the nine patients (88.9%) with high-flow vascular malformation, while worsening was observed in the remaining patient. The treatment was well tolerated and at the most recent follow-up, five patients remained on treatment with oral sirolimus. CONCLUSION: Our results show that oral sirolimus is a well-tolerated therapeutic option, with an excellent safety profile, which can be useful in the long-term stabilization of patients with high-flow vascular malformations. Single-daily dosage may improve long-term adherence to treatment without worsening its effectiveness.

Cutaneous malignant melanoma mortality in Spain from 1979 to 2018. Trends and new perspectives in the immunotherapy era.

BACKGROUND: Recent studies suggest that cutaneous melanoma mortality rates in Spain are stabilizing and even decreasing in younger cohorts. OBJECTIVES: To analyse mortality rates of melanoma from the last 40 years, focusing on changes related with the development of new therapeutic approaches. METHODS: Death records and mid-year population data were collected from the National Statistics Institute. By using the direct method, age-standardized mortality rates were calculated for overall population and for each sex and age group. Significant changes in mortality trends were identified by Joinpoint regressions. The independent effects of age, period and cohort (APC) and potential years of life lost (PYLL) due to melanoma were also analysed. RESULTS: Age-standardized melanoma mortality rates rose in Spain from 0.78 to 2.13 deaths per 100 000 from the first to the last quinquennium of the study (1979-1983 to 2014-2018) for the overall population. After a marked increase until 1995, mortality rates levelled off. Following this stabilization, from 2015 to 2018 there was a decrease in mortality rates for the overall population (average annual per cent change (AAPC): -4.3, not significant), more accused in males over 64 years old (yo). A period effect was observed from the beginning of 21st century, with mortality rates dropping to date. CONCLUSIONS: There is a decrease in melanoma mortality rates from 2015 in all age groups that confirms previous trends in mortality in younger cohorts. Improvement in diagnosis and development of new therapies for advanced melanoma may have a crucial role in this event. Close monitoring of melanoma mortality rates is necessary to confirm these trends.